ALBERT

Description: 〈p〉Publication date: 1 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 449〈/p〉 〈p〉Author(s): Yili Guo, Han Y.H. Chen, Azim U. Mallik, Bin Wang, Dongxing Li, Wusheng Xiang, Xiankun Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Litterfall production is a major contributor to ecosystem net primary productivity and biogeochemical cycles. However, how various abiotic and biotic drivers influence litterfall production in heterogeneous natural forests is still debated. We used structural equation models (SEM) to test the direct and indirect effects of tree species diversity, tree diameter variation, stand basal area, and abiotic drivers (canopy exposure, elevation, slope, convexity, aspect, topographic wetness index and altitude above channel) on annual litterfall production in a heterogeneous tropical karst seasonal rainforest in Southern China. The SEM with tree species diversity, tree diameter variation, stand basal area, and abiotic drivers accounted for 43.4% of the variation in annual litterfall production. Tree species diversity and stand basal area had positive direct effects, while tree diameter variation had a negative direct effect on annual litterfall production. Tree species diversity had no significant effect on tree diameter variation nor stand basal area. Both annual litterfall production and tree species diversity decreased directly with water availability, while canopy exposure positively affected annual litterfall production but not tree species diversity. Our results indicate that the positive relationship between tree species diversity and litterfall production did not result from the effects of species diversity on canopy packing; instead, it appears that increasing soil water availability simultaneously reduce tree species diversity and annual litterfall production in the tropical karst seasonal rainforest.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 449〈/p〉 〈p〉Author(s): Paulo Cañete-Salinas, Francisco Zamudio, Marco Yáñez, Javier Gyenge, Héctor Valdés, Cristian Espinosa, Francisco Jara-Rojas, Jaime Venegas, Luis Retamal, César Acevedo-Opazo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Water is the main limiting factor for poplar plantations in the Mediterranean zone of central Chile. Overall, water requirements in these plantations may be estimated using climatic and soil moisture data. However, irrigation strategies can be improved if growth and plant water status are considered. The aim of this study was to assess the growth (diameter increments) and leaf-level physiology (xylem water potential (Ψ〈sub〉x〈/sub〉) and stomatal conductance (g〈sub〉s〈/sub〉)) responses of two 〈em〉Populus × canadensis〈/em〉 clones (‘I-214’ and ‘I-488’) to different irrigation frequencies. The study was carried out during three growing seasons in commercial plantations located in the Maule Region, central Chile. Three irrigation frequencies were evaluated: an over-irrigation frequency (21 days) (T1); a standard irrigation frequency used operationally in the area (28 days) (T2) and a deficit irrigation frequency (35 days) (T3), while the watering time was held constant for all treatments. Although both clones belong to the same interspecific cross, they differed in their growth and physiological responses to water deficit. Compared with ‘I-214’, ‘I-488’ was more sensitive to lower irrigation frequencies (higher water restriction), which decreased the diameter increments, the water potential and stomatal conductance. The results suggest that the use of physiological and climatic information may improve water management on commercial poplar plantations.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 1〈/p〉 〈p〉Author(s): Jade D. Bailey, Marina Diotallevi, Thomas Nicol, Eileen McNeill, Andrew Shaw, Surawee Chuaiphichai, Ashley Hale, Anna Starr, Manasi Nandi, Elena Stylianou, Helen McShane, Simon Davis, Roman Fischer, Benedikt M. Kessler, James McCullagh, Keith M. Channon, Mark J. Crabtree〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Classical activation of macrophages (M(LPS+IFNγ)) elicits the expression of inducible nitric oxide synthase (iNOS), generating large amounts of NO and inhibiting mitochondrial respiration. Upregulation of glycolysis and a disrupted tricarboxylic acid (TCA) cycle underpin this switch to a pro-inflammatory phenotype. We show that the NOS cofactor tetrahydrobiopterin (BH〈sub〉4〈/sub〉) modulates IL-1β production and key aspects of metabolic remodeling in activated murine macrophages via NO production. Using two complementary genetic models, we reveal that NO modulates levels of the essential TCA cycle metabolites citrate and succinate, as well as the inflammatory mediator itaconate. Furthermore, NO regulates macrophage respiratory function via changes in the abundance of critical N-module subunits in Complex I. However, NO-deficient cells can still upregulate glycolysis despite changes in the abundance of glycolytic intermediates and proteins involved in glucose metabolism. Our findings reveal a fundamental role for iNOS-derived NO in regulating metabolic remodeling and cytokine production in the pro-inflammatory macrophage.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719307843-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 2 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 1〈/p〉 〈p〉Author(s): Marie-Kristin Raulf, Timo Johannssen, Svea Matthiesen, Konstantin Neumann, Severin Hachenberg, Sabine Mayer-Lambertz, Fridolin Steinbeis, Jan Hegermann, Peter H. Seeberger, Wolfgang Baumgärtner, Christina Strube, Jürgen Ruland, Bernd Lepenies〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Malaria represents a major cause of death from infectious disease. Hemozoin is a 〈em〉Plasmodium〈/em〉-derived product that contributes to progression of cerebral malaria. However, there is a gap of knowledge regarding how hemozoin is recognized by innate immunity. Myeloid C-type lectin receptors (CLRs) encompass a family of carbohydrate-binding receptors that act as pattern recognition receptors in innate immunity. In the present study, we identify the CLR CLEC12A as a receptor for hemozoin. Dendritic cell-T cell co-culture assays indicate that the CLEC12A/hemozoin interaction enhances CD8〈sup〉+〈/sup〉 T cell cross-priming. Using the 〈em〉Plasmodium berghei〈/em〉 Antwerpen-Kasapa (ANKA) mouse model of experimental cerebral malaria (ECM), we find that CLEC12A deficiency protects mice from ECM, illustrated by reduced ECM incidence and ameliorated clinical symptoms. In conclusion, we identify CLEC12A as an innate sensor of plasmodial hemozoin.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719307818-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 2 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 1〈/p〉 〈p〉Author(s): Xuezhou Hou, Guobao Chen, William Bracamonte-Baran, Hee Sun Choi, Nicola L. Diny, Jungeun Sung, David Hughes, Taejoon Won, Megan Kay Wood, Monica V. Talor, David Joel Hackam, Karin Klingel, Giovanni Davogustto, Heinrich Taegtmeyer, Isabelle Coppens, Jobert G. Barin, Daniela Čiháková〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Two types of monocytes, Ly6C〈sup〉hi〈/sup〉 and Ly6C〈sup〉lo〈/sup〉, infiltrate the heart in murine experimental autoimmune myocarditis (EAM). We discovered a role for cardiac fibroblasts in facilitating monocyte-to-macrophage differentiation of both Ly6C〈sup〉hi〈/sup〉 and Ly6C〈sup〉lo〈/sup〉 cells, allowing these macrophages to perform divergent functions in myocarditis progression. During the acute phase of EAM, IL-17A is highly abundant. It signals through cardiac fibroblasts to attenuate efferocytosis of Ly6C〈sup〉hi〈/sup〉 monocyte-derived macrophages (MDMs) and simultaneously prevents Ly6C〈sup〉lo〈/sup〉 monocyte-to-macrophage differentiation. We demonstrated an inverse clinical correlation between heart IL-17A levels and efferocytic receptor expressions in humans with heart failure (HF). In the absence of IL-17A signaling, Ly6C〈sup〉hi〈/sup〉 MDMs act as robust phagocytes and are less pro-inflammatory, whereas Ly6C〈sup〉lo〈/sup〉 monocytes resume their differentiation into MHCII〈sup〉+〈/sup〉 macrophages. We propose that MHCII〈sup〉+〈/sup〉Ly6C〈sup〉lo〈/sup〉 MDMs are associated with the reduction of cardiac fibrosis and prevention of the myocarditis sequalae.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S221112471930765X-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 15 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 448〈/p〉 〈p〉Author(s): Miaomiao Zhao, Jilin Yang, Na Zhao, Yu Liu, Yifu Wang, John P. Wilson, Tianxiang Yue〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Forests are a major contributor of terrestrial ecosystem carbon pools. Accurate estimates of forest biomass carbon sinks can improve our understanding of carbon cycles and help in developing sustainable forest management policies in the face of climate change. In this study, we update estimates of the biomass carbon stocks of China’s forests based on seven forest inventory datasets from 1977 to 2013 and carbon fraction coefficients of 46 tree species in the continuous biomass expansion factor (CBEF) model. Our findings suggest that: (1) China’s forest stands acted as an average biomass carbon sink of 99.07 Tg C year〈sup〉−1〈/sup〉; and (2) biomass carbon stocks increased by 72.62% from 1977 to 2013 and recently reached 7.27 Pg C, driven by forest area expansion and forest growth. The biomass carbon density of forest stands (canopy coverage 〉20%) increased from 38.18 to 44.52 Mg C ha〈sup〉−1〈/sup〉 during the study period, with higher carbon densities in natural compared to planted forests, and the gap increasing with forest age. The largest increases in the biomass of carbon stocks of forest stands occurred in the eastern and northern regions. Our results suggest that biomass carbon stocks of natural forests account for about 85% in the most recent inventory and that the total biomass carbon stocks of forest stands in China will keep increasing in the future because of the large area of planted forests with young and middle-aged forest growth. The results from this study can help with comprehensive investigations of forest carbon budgets and the calibration and validation of simulation model results.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 448〈/p〉 〈p〉Author(s): Steffen Herrmann, Markus O. Huber, Zoe Bont, Andreas Rigling, Jan Wunder〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Wood decay limits the function of Norway spruce (〈em〉Picea abies〈/em〉 (L.) H.Karst.) for wood production and in protection forests (i.e. forests protecting against natural hazards). Therefore, more detailed knowledge about the presence and extent of decay in living trees is highly relevant for both the timber industry and risk management strategies. However, decay detection in living Norway spruce trees is not sufficiently possible by visual methods. One possibility to overcome this problem are indirect, non- or least-destructive measurement devices such as the decay detector Rotfinder. Yet, the influence of climatic variables on the reliability of decay detection determined with the Rotfinder is not sufficiently known. Therefore, we assessed the influences of several climatic variables on the Rotfinder values continuously over one year at the same measuring position. Additionally, we determined a threshold value for decay detection in single Norway spruce trees in Central Europe. Regardless of the temperature, Rotfinder values measured over one year were mainly influenced by internal decay status, i.e. damage degree, which explained about 85% of the variation based on a generalized linear mixed effects model in this temperature range (about 6–27 °C). Together with fluctuations in air temperature, about 87% of the variation in Rotfinder values could be accounted for. For decay detection in single Norway spruce trees, a maximum threshold value of about 11,000 Rotfinder units (RU) was identified, equivalent to about 36% of the Rotfinder values measured for intact trees. Our results indicate that the Rotfinder can be used successfully for decay detection in single Norway spruce trees under Central European conditions.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 448〈/p〉 〈p〉Author(s): Raul Rosenvald, Piret Lõhmus, Riinu Rannap, Liina Remm, Katrin Rosenvald, Kadri Runnel, Asko Lõhmus〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Retention forestry is a silvicultural approach that can achieve both ecological and economic objectives in various forest ecosystems. It builds largely on the assumption that the live trees left unharvested (the main timber cost) effectively support ecological functioning of post-harvest forest. Such effectiveness can be understood as a combination of the initial ecological value of the tree (that may persist after tree death) and its survival, i.e., the prospect to develop into a high-quality veteran tree in the next forest generation. We assessed those aspects among 〉3000 live trees actually retained in 103 Estonian harvested sites and monitored over 16 years. We analysed how their survival and habitat value (estimated from tree morphology, confirmed by epiphyte surveys) translate to the veteran-tree perspectives. Only 48% of the trees were still alive after 16 years, and this final survival at the stand-scale was poorly predictable from a few years of monitoring. Only 12% retention trees had both high habitat value and high survival. Most trees (75%) were of low initial habitat value and, combined with low survival, almost 40% of all trees never provided quality habitat for tree-dwelling species. Nevertheless, we found considerable potential for post-harvest development of habitat value; notably in European nemoral hardwood species (such as 〈em〉Fraxinus, Quercus, Ulmus, Acer〈/em〉), which survived well but were usually in subcanopies at the time of the harvest. These findings indicate that retention forestry can improve also highly impoverished (e.g. short-rotation) forests, if analytical tools have been developed and applied to predict tree survival and future habitat quality.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 448〈/p〉 〈p〉Author(s): Quanzhi Zhang, Chuankuan Wang, Zhenghu Zhou〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Quantifying net primary production (NPP) and its allocation is essential for understanding and modeling the carbon (C) cycling in forest ecosystems. We used biometry-based measurements to examine the NPP allocation for six temperate forest types with similar stand age and climate but diverse stand characteristics and site conditions in northeastern China. The forest types included four naturally-regenerated stands and two planted stands. Our objectives were to (1) compare the NPP and its allocation among the six forest types, and (2) explore the factors driving the inter-stand variability of the NPP allocation patterns. We found that the total NPP (TNPP) and NPP of short-lived biomass tissues (NPP〈sub〉SL〈/sub〉) differed significantly among the forest types, varying from 709 to 927 gC m〈sup〉−2〈/sup〉 yr〈sup〉−1〈/sup〉 and from 364 to 594 gC m〈sup〉−2〈/sup〉 yr〈sup〉−1〈/sup〉, respectively. However, the NPP of long-lived tissues (NPP〈sub〉LL〈/sub〉) did not differ significantly among the forest types, varying from 305 to 364 gC m〈sup〉−2〈/sup〉 yr〈sup〉−1〈/sup〉. These results suggested that the production of structural tissues be relatively stable under the same climate, and the inter-stand difference in TNPP be mainly attributed to the difference in NPP〈sub〉SL〈/sub〉. Within the four natural stands, the foliage production was significantly and positively correlated with soil nitrogen (N) (〈em〉R〈/em〉〈sup〉2〈/sup〉 = 0.50) and phosphorus (P) stock (〈em〉R〈/em〉〈sup〉2〈/sup〉 = 0.37), whereas the fine root production was significantly and negatively correlated with soil C:P (〈em〉R〈/em〉〈sup〉2〈/sup〉 = 0.54) and N:P ratio (〈em〉R〈/em〉〈sup〉2〈/sup〉 = 0.47), implying that foliage and root production may be driven by different mechanisms. The convergence of NPP〈sub〉LL〈/sub〉 across forest types with different stand characteristics, site conditions and management practices but under the same climate has important implication in managing forest ecosystems for C sequestration, while the divergence of NPP〈sub〉SL〈/sub〉 implies that vegetation can adapt to the site conditions by changing resource-absorbing tissues production and its allocation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 452〈/p〉 〈p〉Author(s): Alicia Calle, Karen D. Holl〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉To meet their large-scale forest and landscape restoration targets, countries must find ways to accommodate areas for conservation alongside agricultural production. In some pasture-dominated regions of Latin America, intensive silvopastoral systems (SPS) are being promoted to increase cattle productivity on certain lands while facilitating the removal of cattle from marginal areas for forest restoration. However, the recovery of these forests and their contribution to the overall conservation value of the landscape has not been assessed rigorously. We evaluated forest structure and composition in 20 sites in a region of the Colombian Andes where a decade ago farmers transitioned to SPS and fenced off riparian areas to enable forest recovery. We compared these restored forests to a reference model based on the remaining riparian forest across the region, all of which has been subjected to human management. We found that woody species richness was higher in restored than in reference forests, and the proportion of large-seeded, later successional, animal-dispersed species were similar in both forest types. Whereas we found a similar suite of dominant tree species in restored and reference forest, 〈em〉Guadua angustifolia〈/em〉, a native giant bamboo was more abundant in the reference forests due to human management. Total tree basal area was higher in restored forests due to a small number of very large trees likely present in the pastures at the time of site protection. These findings highlight (1) the potential for recovery of diverse forests in riparian sites despite previous grazing use and (2) the role of remnant trees in facilitating natural succession. Overall, rapid forest recovery with minimal intervention in previously farmed lands is good news for conservation in a region that still harbors significant biodiversity despite high levels of fragmentation and the influence of human management.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 448〈/p〉 〈p〉Author(s): Joseph Langridge, Benoît Pisanu, Sébastien Laguet, Frédéric Archaux, Laurent Tillon〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Forests constitute one of the most important feeding and foraging habitats for bats. Because bat populations are declining, most likely due to habitat loss or fragmentation, it is imperative to understand the issues concerned with timber exploitation on bat conservation. We investigated the foraging activity of edge- and open-space foragers in relation to stand and vegetation structure, characteristics that are commonly affected by forestry. Acoustic surveys, culminating to 713 point count sites were undertaken covering 46 different forest massifs across mainland France over 6 years. We used generalized linear mixed models to analyse the activity of ten species: 6 edge-habitat and 4 open-habitat foragers. 〈em〉Pipistrellus pipistrellus〈/em〉 was the most detected edge-habitat forager, while 〈em〉Nyctalus leisleri〈/em〉 was the most recorded of the open-habitat foragers. 〈em〉Eptesicus serotinus〈/em〉 and 〈em〉P. pipistrellus〈/em〉 responded positively to heterogeneous vertical vegetation volume. In addition, 〈em〉P. kuhlii〈/em〉 and 〈em〉P. nathusii〈/em〉 responded negatively to tree basal area. 〈em〉Barbastella barbastellus〈/em〉, 〈em〉Hypsugo savii〈/em〉, and 〈em〉P. nathusii〈/em〉 were associated with either ground deadwood and/or logging tracks and minor-traffic roads, confirming the importance of edge space. Finally, 〈em〉B. barbastellus, E. serotinus,〈/em〉 and 〈em〉P. nathusii〈/em〉 were positively linked to the presence of tree microhabitats. This study demonstrates that bat use in forests is complex and multifaceted. Maintaining ground deadwood and heterogeneity of vegetation, at the forest plot scale, should ensure the ecological functioning of exploited forest systems and the conservation of edge- and open-habitat foraging bats.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Thomas P. Sullivan, Druscilla S. Sullivan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉Restoration practices are much needed on clearcut openings in commercial forest landscapes where some mammal species have declined in abundance from a loss of preferred food, cover, and other components of stand structure. Retention of excess woody debris in piles and windrows provides habitat for forest-floor small mammals and some of their predators such as small mustelids. However, it is unknown if these retention habitats are used over longer periods (〉10 years) as new forests grow and develop on harvested sites, or do they become unoccupied? We tested the hypotheses (H) that (H〈sub〉1〈/sub〉) abundance, species richness, and diversity of the forest-floor small mammal community, and (H〈sub〉2〈/sub〉) reproduction and survival of the southern red-backed vole (〈em〉Myodes gapperi〈/em〉), long-tailed vole (〈em〉Microtus longicaudus〈/em〉), and deer mouse (〈em〉Peromyscus maniculatus〈/em〉) would decline on sites with woody debris structures, compared with sites of dispersed woody debris or uncut forest, up to 12 years post-construction in south-central British Columbia, Canada.〈/p〉 〈p〉Woody debris structures provided habitat on new clearcuts for 〈em〉M. gapperi〈/em〉 at comparable or higher abundance than in uncut forest and 5.0 to 7.6 times higher than on dispersed sites in the first 5-year period. Although numbers declined after the initial three years, populations of 〈em〉M. gapperi〈/em〉 in debris structures recovered to earlier abundance levels at 11–12 years post-construction. Mean abundance of 〈em〉M. longicaudus〈/em〉 was consistently higher (2.8 to 3.5 times) in piles and windrows than in sites with dispersed woody debris over the first 5-year period. Populations of 〈em〉M. longicaudus〈/em〉 were high in all three treatment sites at 11 years post-construction reaching mean annual peak numbers of 24, 42, and 36 voles per ha in the dispersed, piles, and windrow sites, respectively. Mean abundance of 〈em〉P. maniculatus〈/em〉 was similar among treatment sites and consistent over time. Mean abundance of total small mammals was consistently higher (1.8 to 2.4 times) in piles and windrows than dispersed or forest sites in the first 5-year period and this pattern was continued at 11–12 years post-construction. At 11 years post-construction, all treatment sites had the highest peak numbers per ha in the study: dispersed (40.3), piles (64.1), windrows (56.1), and forest (29.0). Our results did not support H〈sub〉1〈/sub〉 as abundance, species richness, and diversity were increased or maintained in the debris structures over the 12-year period. Reproduction and survival followed the pattern of abundance for the major species, and hence H〈sub〉2〈/sub〉 was not supported. Our study is the first to measure long-term (up to 12 years) responses of forest-floor small mammals to constructed piles and windrows of woody debris as a means of habitat retention on clearcuts. These mammalian species, particularly voles, may then serve as prey for marten and other mustelids. This relationship provides further support for piles and windrows to act as baseline trophic structures in ecological restoration of cutover forest land.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Halina Smal, Sławomir Ligęza, Jacek Pranagal, Danuta Urban, Dorota Pietruczyk-Popławska〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The objective of this study was to investigate the effect of afforestation of post-arable sandy soils (Dystric Arenosols) with Scots pine (〈em〉Pinus sylvestris〈/em〉 L.) on the amount and distribution of C〈sub〉org〈/sub〉, N〈sub〉tot〈/sub〉 and P〈sub〉tot〈/sub〉 stocks between genetic soil horizons. The study was performed at three locations with five classes of afforestation each: 10-, 20-, 30-, 40-, 50-year-old stands, which additionally included the arable and the continuous forest soils as reference. The soil was sampled by genetic horizon, including the organic one, down to 100 cm, from its whole thickness, and from A horizon of the afforested soils from: 0–5, 5–10 and 10–20 cm. In the organic horizon of the afforested soils, the stock of C〈sub〉org〈/sub〉, N〈sub〉tot〈/sub〉 and P〈sub〉tot〈/sub〉 increased significantly with stand age, and an average rate of accumulation was 33.6, 1.30 and 0.04 g m〈sup〉−2〈/sup〉 year〈sup〉−1〈/sup〉 respectively. C〈sub〉org〈/sub〉 stocks in the former plough layer were found to decrease within the first decade of afforestation, and subsequently, the values gradually increased. With organic horizon included the respective stocks reached the level comparable with the related horizon of the arable soil after approx. 20–30 years. Subsoil B, BC and C horizons together accounted for approx. 35% of the C〈sub〉org〈/sub〉 stocks in the entire profile. N〈sub〉tot〈/sub〉 stocks in mineral soil horizons initially dropped in the first decade after afforestation, which was subsequently followed by an increase; however, after 50 years, still the observed values were lower in comparison with both the respective arable and continuous forest soils. P〈sub〉tot〈/sub〉 stocks in the mineral soil horizon declined over the chronosequence, and in the profile at 50-year-old stands, they were lower in comparison with both the arable and the continuous forest soils. Stand age and sampling by genetic horizons, including the organic horizon, from the entire soil profile should be considered for estimation of changes in C〈sub〉org〈/sub〉, N〈sub〉tot〈/sub〉 and P〈sub〉tot〈/sub〉 stocks following afforestation of agricultural soils.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Diletta Di Mitri, Michela Mirenda, Jelena Vasilevska, Arianna Calcinotto, Nicolas Delaleu, Ajinkya Revandkar, Veronica Gil, Gunther Boysen, Marco Losa, Simone Mosole, Emiliano Pasquini, Rocco D’Antuono, Michela Masetti, Elena Zagato, Giovanna Chiorino, Paola Ostano, Andrea Rinaldi, Letizia Gnetti, Mariona Graupera, Ana Raquel Martins Figueiredo Fonseca〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Tumor-associated macrophages (TAMs) represent a major component of the tumor microenvironment supporting tumorigenesis. TAMs re-education has been proposed as a strategy to promote tumor inhibition. However, whether this approach may work in prostate cancer is unknown. Here we find that 〈em〉Pten〈/em〉-null prostate tumors are strongly infiltrated by TAMs expressing C-X-C chemokine receptor type 2 (CXCR2), and activation of this receptor through CXCL2 polarizes macrophages toward an anti-inflammatory phenotype. Notably, pharmacological blockade of CXCR2 receptor by a selective antagonist promoted the re-education of TAMs toward a pro-inflammatory phenotype. Strikingly, CXCR2 knockout monocytes infused in 〈em〉Pten〈/em〉〈sup〉pc−/−〈/sup〉; 〈em〉Trp53〈/em〉〈sup〉pc−/−〈/sup〉 mice differentiated in tumor necrosis factor alpha (TNF-α)-releasing pro-inflammatory macrophages, leading to senescence and tumor inhibition. Mechanistically, 〈em〉PTEN〈/em〉-deficient tumor cells are vulnerable to TNF-α-induced senescence, because of an increase of 〈em〉TNFR1〈/em〉. Our results identify TAMs as targets in prostate cancer and describe a therapeutic strategy based on CXCR2 blockade to harness anti-tumorigenic potential of macrophages against this disease.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309726-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): John D. Gagnon, Robin Kageyama, Hesham M. Shehata, Marlys S. Fassett, Darryl J. Mar, Eric J. Wigton, Kristina Johansson, Adam J. Litterman, Pamela Odorizzi, Dimitre Simeonov, Brian J. Laidlaw, Marisella Panduro, Sana Patel, Lukas T. Jeker, Margaret E. Feeney, Michael T. McManus, Alexander Marson, Mehrdad Matloubian, Shomyseh Sanjabi, K. Mark Ansel〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Coordinate control of T cell proliferation, survival, and differentiation are essential for host protection from pathogens and cancer. Long-lived memory cells, whose precursors are formed during the initial immunological insult, provide protection from future encounters, and their generation is the goal of many vaccination strategies. microRNAs (miRNAs) are key nodes in regulatory networks that shape effective T cell responses through the fine-tuning of thousands of genes. Here, using compound conditional mutant mice to eliminate miR-15/16 family miRNAs in T cells, we show that miR-15/16 restrict T cell cycle, survival, and memory T cell differentiation. High throughput sequencing of RNA isolated by cross-linking immunoprecipitation of AGO2 combined with gene expression analysis in miR-15/16-deficient T cells indicates that these effects are mediated through the direct inhibition of an extensive network of target genes within pathways critical to cell cycle, survival, and memory.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309684-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Shawn P. Brown, Allison M. Veach, Jonathan L. Horton, Emerald Ford, Ari Jumpponen, Richard Baird〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Decades of fire suppression coupled with changing climatic conditions have increased the frequency and intensity of wildfires. The Southern Appalachia region of the United States is predicted to be particularly susceptible to climatic changes, with predicted increases in fire severity and occurrence. Following the record breaking fire season in 2016 in Southern Appalachia, we examined wildfire impacts on soil chemistry and below ground communities (fungi and bacteria – Illumina MiSeq) within two substrates (duff and soil) at two adjacent locations with similar plant communities (Great Smoky Mountains National Park – ‘Chimney Top 2’ Fire (GRSM) and Nantahala National Forest – ‘Cliffside’ Fire (NNF)) from replicate plots representing a range of fire severities (unburned, low severity, moderate severity, severe). Differing fire severities changed community composition, and fire severity played a stronger role in structuring bacterial communities than in structuring fungal communities. Further, fire impacts on soil communities and functional guilds responses were location- and substrate-specific with NNF responding more strongly to fire than GRSM. Additionally, using a novel analysis tool (Axis Weighted Ordination Distance – AWOrD), domain and location specific responses to wildfire severity are demonstrated. Taken together, our results suggest context-dependency in microbial responses to fire that must be accounted for to generate ecosystem-wide recovery predictions.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Alissa J. Freeman, William M. Hammond, Justin R. Dee, Richard C. Cobb, Stephen M. Marek, Henry D. Adams〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Incidents of 〈em〉Quercus〈/em〉 decline have been driven by complicated interactions among factors, such as temperature, drought, pathogenic fungi, insect pests, and stand structure, which operate at multiple time scales. Past incidents of elevated tree mortality during drought in the upland forests of Oklahoma were associated with biotic factors; specifically, the infection of 〈em〉Quercus〈/em〉 species by canker-causing fungi in the genus 〈em〉Biscogniauxia〈/em〉. Biscogniauxia canker and dieback have been previously associated with water stress but little is known about the interactions between forest densification, prescribed fire, water stress, and canker incidence. We investigated the effects of prescribed fire and reduced basal area on Biscogniauxia canker incidence in 〈em〉Quercus〈/em〉 species at the Pushmataha Wildlife Management Area (PWMA) in southeastern Oklahoma. The PWMA is an ongoing forest management experiment established in 1984 with stands maintained to the present day with prescribed fire return intervals of 34+yr, 4-yr, and 1-yr. Through field surveys we found that the incidence of Biscogniauxia canker was lowest among units with a fire return interval of 1–4 years (p 〈 0.002). Additionally, greater canopy dieback was associated with greater frequency of stem cankers. Management of these forests reduces basal area, alters water stress, and may reduce pathogen incidence due to both greater host resilience and reduction of sporulation sources. To evaluate associations among these factors, we assessed Biscogniauxia canker incidence and leaf stable C isotope composition (δ〈sup〉13〈/sup〉C)—an indicator of stomatal closure from drought stress—from 〈em〉Quercus marilandica〈/em〉 (blackjack oak) and 〈em〉Quercus stellata〈/em〉 (post oak) trees in units experiencing 34+yr, 4-yr, and 1-yr fire return intervals. We found that leaf δ〈sup〉13〈/sup〉C was highest in units experiencing 4-yr and 1-yr fire return intervals, indicating that these trees more frequently had closed stomata, counter to our expectation that the reduced basal area associated with frequent fire would decrease δ〈sup〉13〈/sup〉C due to decreased water stress. Instead, our results suggest that trees in units experiencing reduced basal area encounter additional stressors (e.g., wind, vapor pressure deficit, and high soil evaporation) that lead to stomatal closure. Additionally, higher δ〈sup〉13〈/sup〉C in units receiving prescribed fire applications may be a response to frequent disturbance via direct effects of fire on tree water relations. Further investigation is needed to understand the interactions of fire regimes with water stress in these ecosystems. Although, we did not find a clear link to tree water status, basal area reduction decreased the incidence of Biscogniauxia canker, demonstrating that prescribed fire can be used to promote forest health.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Débora Cristina Rother, Ana Paula Liboni, Luiz Fernando Silva Magnago, Anne Chao, Robin L. Chazdon, Ricardo Ribeiro Rodrigues〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Ecological restoration can re-establish plant species populations, enhance forested habitats extension, improve landscape connectivity, and enable biodiversity persistence within a landscape. However, the potential benefits of ecological restoration on beta diversity have never been explored. Here we use field data to investigate, for the first time, if restoration plantings enhance the taxonomic and functional plant beta diversity in a fragmented landscape of the threatened Atlantic forest. Woody species were evaluated for 320 plots established in 18 forest fragments and 14 restoration plantings within a sugarcane production landscape with low forest cover, in southeastern Brazil. Diversity metrics were assessed using the multiple incidence-data version of Hill numbers and were compared among three sets of study sites: fragments, restoration plantings and the two combined. Fragments showed higher levels of alpha diversity and proportional abundance of non-pioneer and animal-dispersed species than restoration plantings. Exotic, pioneer and non-zoochoric species were more abundant in restoration plantings, an expected result considering sites still be in the early or mid-successional stages of development. Taxonomic and functional beta diversity of trees was greatest when both areas were combined. For regenerating plants, however, beta diversity results varied according to species incidence-based frequencies. Although restoration plantings do not result in full recovery of alpha diversity, they can all together complement diversity of forest fragments at the landscape level. The findings indicate two key ecological implications for biodiversity conservation: the critical importance of forest fragments as biodiversity repositories and the positive effect of restoration efforts on landscape-scale diversity in degraded regions. These novel results highlight the importance of species selection for restoration initiatives toward species and functional attributes recognized as significantly reduced or locally rare. Overall, forest fragments and restoration plantings can act synergistically to promote recovery of plant diversity in heavily deforested agricultural landscapes.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Lisa J. Samuelson, Tom A. Stokes, Michael R. Ramirez, Caren C. Mendonca〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Longleaf pine (〈em〉Pinus palustris〈/em〉 Mill.) forests are thought to be drought tolerant and if so, planting longleaf pine presents a forest management strategy for climate change adaptation in the southeastern United States (U.S.). To better understand how longleaf pine copes with drought, leaf water relations, sap flow, canopy stomatal conductance (G〈sub〉S〈/sub〉), and growth were studied over three growing seasons in response to ambient throughfall (ambient treatment) versus an approximate 40% reduction in throughfall (drought treatment) in a 13-year-old plantation. An exceptional drought occurred the first year of the study and decreased mean predawn (Ψ〈sub〉PD〈/sub〉) and midday (Ψ〈sub〉MD〈/sub〉) leaf water potential to −2.9 MPa and −3.6 MPa, respectively, and decreased average monthly midday Gs to near zero for at least one month in both treatments. Stomatal closure occurred at a Ψ〈sub〉MD〈/sub〉 of −3.0 MPa in both treatments. Leaf water potentials and transpiration recovered quickly following significant rain events that terminated the drought and mortality was similar among years and treatments (2.8%). Longleaf pine responded to drought treatment with greater stomatal control of plant water loss rather than adjustments in leaf area, the sapwood to leaf area ratio, or leaf water potential at the turgor loss point (Ψ〈sub〉TLP〈/sub〉). Annual transpiration per unit leaf area was reduced 16% by drought treatment, but greater stomatal control of water loss in response to drought treatment was associated with decreases in growth efficiency and volume, and no improvement in water use efficiency.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Joshua J. Gruber, Justin Chen, Benjamin Geller, Natalie Jäger, Andrew M. Lipchik, Guangwen Wang, Allison W. Kurian, James M. Ford, Michael P. Snyder〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Individuals with a single functional copy of the 〈em〉BRCA2〈/em〉 tumor suppressor have elevated risks for breast, ovarian, and other solid tumor malignancies. The exact mechanisms of carcinogenesis due to 〈em〉BRCA2〈/em〉 haploinsufficiency remain unclear, but one possibility is that at-risk cells are subject to acute periods of decreased BRCA2 availability and function (“BRCA2-crisis”), which may contribute to disease. Here, we establish an 〈em〉in vitro〈/em〉 model for BRCA2-crisis that demonstrates chromatin remodeling and activation of an NF-κB survival pathway in response to transient BRCA2 depletion. Mechanistically, we identify BRCA2 chromatin binding, histone acetylation, and associated transcriptional activity as critical determinants of the epigenetic response to BRCA2-crisis. These chromatin alterations are reflected in transcriptional profiles of pre-malignant tissues from 〈em〉BRCA2〈/em〉 carriers and, therefore, may reflect natural steps in human disease. By modeling BRCA2-crisis 〈em〉in vitro〈/em〉, we have derived insights into pre-neoplastic molecular alterations that may enhance the development of preventative therapies.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309611-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Adam J. Vogrin, Neil I. Bower, Menachem J. Gunzburg, Sally Roufail, Kazuhide S. Okuda, Scott Paterson, Stephen J. Headey, Steven A. Stacker, Benjamin M. Hogan, Marc G. Achen〈/p〉 〈div〉 〈h6〉Summary〈/h6〉 〈p〉Lymphatic vascular development establishes embryonic and adult tissue fluid balance and is integral in disease. In diverse vertebrate organs, lymphatic vessels display organotypic function and develop in an organ-specific manner. In all settings, developmental lymphangiogenesis is considered driven by vascular endothelial growth factor (VEGF) receptor-3 (VEGFR3), whereas a role for VEGFR2 remains to be fully explored. Here, we define the zebrafish Vegf/Vegfr code in receptor binding studies. We find that while Vegfd directs craniofacial lymphangiogenesis, it binds Kdr (a VEGFR2 homolog) but surprisingly, unlike in mammals, does not bind Flt4 (VEGFR3). Epistatic analyses and characterization of a 〈em〉kdr〈/em〉 mutant confirm receptor-binding analyses, demonstrating that Kdr is indispensible for rostral craniofacial lymphangiogenesis, but not caudal trunk lymphangiogenesis, in which Flt4 is central. We further demonstrate an unexpected yet essential role for Kdr in inducing lymphatic endothelial cell fate. This work reveals evolutionary divergence in the Vegf/Vegfr code that uncovers spatially restricted mechanisms of developmental lymphangiogenesis.〈/p〉 〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309593-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Susan Lindtner, Rinaldo Catta-Preta, Hua Tian, Linda Su-Feher, James D. Price, Diane E. Dickel, Vanille Greiner, Shanni N. Silberberg, Gabriel L. McKinsey, Michael T. McManus, Len A. Pennacchio, Axel Visel, Alex S. Nord, John L.R. Rubenstein〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉DLX transcription factors (TFs) are master regulators of the developing vertebrate brain, driving forebrain GABAergic neuronal differentiation. Ablation of 〈em〉Dlx1&2〈/em〉 alters expression of genes that are critical for forebrain GABAergic development. We integrated epigenomic and transcriptomic analyses, complemented with 〈em〉in situ〈/em〉 hybridization (ISH), and 〈em〉in vivo〈/em〉 and 〈em〉in vitro〈/em〉 studies of regulatory element (RE) function. This revealed the DLX-organized gene regulatory network at genomic, cellular, and spatial levels in mouse embryonic basal ganglia. DLX TFs perform dual activating and repressing functions; the consequences of their binding were determined by the sequence and genomic context of target loci. Our results reveal and, in part, explain the paradox of widespread DLX binding contrasted with a limited subset of target loci that are sensitive at the epigenomic and transcriptomic level to 〈em〉Dlx1&2〈/em〉 ablation. The regulatory properties identified here for DLX TFs suggest general mechanisms by which TFs orchestrate dynamic expression programs underlying neurodevelopment.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S221112471930912X-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): 〈/p〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Lan Wu, Tomomichi Kato, Hisashi Sato, Takashi Hirano, Tomotsugu Yazaki〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Large storms are a major source of natural disturbance in forest ecosystems in coastal regions of the world. With the changing climate, some climate projection models predict that storms will become stronger in the future, especially in the Northwest Pacific. Although the destruction of typhoons has a strong impact on the structure and carbon balance of forest ecosystems, leading to local climate change feedback, the long-term effect of typhoon frequency and intensity on forest and carbon dynamics has not been investigated from the perspective of future climate change. To elucidate these long-term effects, we adapted a dynamic vegetation model to a deciduous-coniferous mixed forest in southern Hokkaido, Japan, to represent the development of a larch plantation established in 1954 after typhoon Toyamaru struck a natural forest and the natural regeneration from 2004 when the plantation suffered windthrow by typhoon Songda. The model was validated using eddy flux and biomass data. The adapted model was then forced with various combinations of typhoon frequency, typhoon intensity, and projected climatic conditions for 2017–2100 under RCP2.6 and RCP8.5. These future projections suggest that increasing typhoon frequency and intensity has a significant effect on forest and carbon dynamics under both RCP2.6 and RCP8.5. As the frequency and intensity of typhoons increase, aboveground biomass (AGB) and net primary production (NPP) decrease. However, increasing typhoon frequency and intensity had a greater influence on AGB than NPP. The values of AGB and NPP are much higher under RCP8.5 than under RCP2.6 and at baseline. As the frequency and intensity of typhoons increase, net ecosystem production first increases and then decreases. Our projection indicates that the forest at the Tomakomai site will become a carbon sink under different typhoon scenarios at the end of the 21st century. Our result also predicts that if typhoon frequency is ≤2 (i.e., a typhoon occurs up to two times between 2017 and 2100) and intensity is ≤40% (i.e., up to 40% of trees damaged), then forest AGB can recover to that before typhoon Songda by the end of the 21st century. Simulation results also showed strong linear relationships among forest structural traits (AGB, tree height, tree density, and woody plant and grass leaf area indexes), carbon fluxes, and typhoon frequency and intensity.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 452〈/p〉 〈p〉Author(s): Eduarda Martiniano de Oliveira Silveira, Marcela de Castro Nunes Santos Terra, Hans ter Steege, Eduardo Eiji Maeda, Fausto Weimar Acerbi Júnior, Jose Roberto Soares Scolforo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉Tropical vegetation provides a myriad of ecosystem services and at the same time is highly threatened. This creates a demand for more efficient conservation strategies that focus on multiple benefits at once. For instance, conservation actions that deliver returns for both aboveground carbon (AGC) and tree species diversity (TSD) would be an advance when compared to carbon-focused initiatives. Here we address this issue by identifying AGC-TSD hotspots in Savanna, Atlantic Forest and Semi-Arid Woodland vegetation domains in southeast Brazil. We modelled Fisher’s alpha as an indicator of TSD, using remote sensing, climate and terrain-related data to train the random forests algorithm. We thus defined, mapped and characterized the areas that deliver returns for both AGC and TSD (“hotspots”), identifying the hotspots owners (whether within public or private lands). Our results suggest that among the group of predictor variables, precipitation, valley depth, Normalized Difference Vegetation Index (NDVI) and tree cover percent, are the main indicators of diversity across the state. The spatial patterns of carbon and diversity roughly coincide and indicate that Atlantic Forest has higher values for both indicators. AGC and TSD are weak related, so there is a potential risk for biodiversity if only a carbon-focused conservation approaches are considered across the studied domains. We estimate that 61% of the hotspots are located in unprotected areas within private properties making them highly susceptible to loss. Together, these hotspots account for 6,131,453 Mg of AGC and show mean values of Fisheŕs alpha of approximately 26. Our study reinforces the need to select natural areas on private lands to be considered as priority areas for protection.〈/p〉 〈p〉.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 449〈/p〉 〈p〉Author(s): Gabriel Dehon Sampaio Peçanha Rezende, José Luis Lima, Donizete da Costa Dias, Bruno Marco de Lima, Aurélio Mendes Aguiar, Fernando de Lellis Garcia Bertolucci, Magno Antônio Patto Ramalho〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The use of eucalypt clonal composites framed by improved, phenotypically similar and unrelated clones may be an important strategy to help breeders prevent commercial eucalypt plantations from unpredictable future adverse events, as well as to promote sustainable productivity gains. The present study was conducted to test this hypothesis by comparing the growth (MAI) at ages three to four years of a significant number of clones in clonal composite (CC) and monoclonal (MC) typologies under distinct environmental conditions, both at experimental and commercial scales. The CC presented MAI performance superior to MC in both experimental (9.8%) and commercial (6.3%) conditions. In each region, different clones respond differently to allo (CC) and auto-competition (MC), but most of them (73%) performed better in CC. Furthermore, CC commercial plantations presented growth uniformity, at different ages, similar to MC plantations, as well as lower genetic vulnerability given by the proportion of replanting before the end of the rotation age due to biotic or abiotic damage agents.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Patrícia M. Silva, Charles Puerner, Agnese Seminara, Martine Bassilana, Robert A. Arkowitz〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉During symmetry breaking, the highly conserved Rho GTPase Cdc42 becomes stabilized at a defined site via an amplification process. However, little is known about how a new polarity site is established in an already asymmetric cell—a critical process in a changing environment. The human fungal pathogen 〈em〉Candida albicans〈/em〉 switches from budding to filamentous growth in response to external cues, a transition controlled by Cdc42. Here, we have used optogenetic manipulation of cell polarity to reset growth in asymmetric filamentous 〈em〉C. albicans〈/em〉 cells. We show that increasing the level of active Cdc42 on the plasma membrane results in disruption of the exocyst subunit Sec3 localization and a striking 〈em〉de novo〈/em〉 clustering of secretory vesicles. This new cluster of secretory vesicles is highly dynamic, moving by hops and jumps, until a new growth site is established. Our results reveal that secretory vesicle clustering can occur in the absence of directional growth.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309660-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Xiao Yu, Bo Li, Geng-Jen Jang, Shan Jiang, Daohong Jiang, Jyan-Chyun Jang, Shu-Hsing Wu, Libo Shan, Ping He〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Proper transcriptome reprogramming is critical for hosts to launch an effective defense response upon pathogen attack. How immune-related genes are regulated at the posttranscriptional level remains elusive. We demonstrate here that P-bodies, the non-membranous cytoplasmic ribonucleoprotein foci related to 5′-to-3′ mRNA decay, are dynamically modulated in plant immunity triggered by microbe-associated molecular patterns (MAMPs). The DCP1-DCP2 mRNA decapping complex, a hallmark of P-bodies, positively regulates plant MAMP-triggered responses and immunity against pathogenic bacteria. MAMP-activated MAP kinases directly phosphorylate DCP1 at the serine〈sup〉237〈/sup〉 residue, which further stimulates its interaction with XRN4, an exonuclease executing 5′-to-3′ degradation of decapped mRNA. Consequently, MAMP treatment potentiates DCP1-dependent mRNA decay on a specific group of MAMP-downregulated genes. Thus, the conserved 5′-to-3′ mRNA decay elicited by the MAMP-activated MAP kinase cascade is an integral part of plant immunity. This mechanism ensures a rapid posttranscriptional downregulation of certain immune-related genes that may otherwise negatively impact immunity.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309581-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Guanming Wang, Takahisa Kouwaki, Masaaki Okamoto, Hiroyuki Oshiumi〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Excessive innate immune response is harmful to the host, and aberrant activation of the cytoplasmic viral RNA sensors RIG-I and MDA5 leads to autoimmune disorders. ZNF598 is an E3 ubiquitin ligase involved in the ribosome quality control pathway. It is also involved in the suppression of interferon (IFN)-stimulated gene (ISG) expression; however, its underlying mechanism is unclear. In this study, we show that ZNF598 is a negative regulator of the RIG-I-mediated signaling pathway, and endogenous ZNF598 protein binds to RIG-I. ZNF598 ubiquitin ligase activity is dispensable for the suppression of RIG-I signaling. Instead, ZNF598 delivers a ubiquitin-like protein FAT10 to the RIG-I protein, resulting in the inhibition of RIG-I polyubiquitination, which is required for triggering downstream signaling to produce type I IFN. Moreover, ZNF598-mediated suppression is abrogated by FAT10 knockout. Our data elucidate the mechanism by which ZNF598 inhibits RIG-I-mediated innate immune response.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309854-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Amber Tariq, JiaBei Lin, Meredith E. Jackrel, Christina D. Hesketh, Peter J. Carman, Korrie L. Mack, Rachel Weitzman, Craig Gambogi, Oscar A. Hernandez Murillo, Elizabeth A. Sweeny, Esin Gurpinar, Adam L. Yokom, Stephanie N. Gates, Keolamau Yee, Saurabh Sudesh, Jacob Stillman, Alexandra N. Rizo, Daniel R. Southworth, James Shorter〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Hsp104 is an AAA+ protein disaggregase, which can be potentiated via diverse mutations in its autoregulatory middle domain (MD) to mitigate toxic misfolding of TDP-43, FUS, and α-synuclein implicated in fatal neurodegenerative disorders. Problematically, potentiated MD variants can exhibit off-target toxicity. Here, we mine disaggregase sequence space to safely enhance Hsp104 activity via single mutations in nucleotide-binding domain 1 (NBD1) or NBD2. Like MD variants, NBD variants counter TDP-43, FUS, and α-synuclein toxicity and exhibit elevated ATPase and disaggregase activity. Unlike MD variants, non-toxic NBD1 and NBD2 variants emerge that rescue TDP-43, FUS, and α-synuclein toxicity. Potentiating substitutions alter NBD1 residues that contact ATP, ATP-binding residues, or the MD. Mutating the NBD2 protomer interface can also safely ameliorate Hsp104. Thus, we disambiguate allosteric regulation of Hsp104 by several tunable structural contacts, which can be engineered to spawn enhanced therapeutic disaggregases with minimal off-target toxicity.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309738-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Roberto Costa, Roberta Peruzzo, Magdalena Bachmann, Giulia Dalla Montà, Mattia Vicario, Giulia Santinon, Andrea Mattarei, Enrico Moro, Rubén Quintana-Cabrera, Luca Scorrano, Massimo Zeviani, Francesca Vallese, Mario Zoratti, Cristina Paradisi, Francesco Argenton, Marisa Brini, Tito Calì, Sirio Dupont, Ildikò Szabò, Luigi Leanza〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Wnt signaling affects fundamental development pathways and, if aberrantly activated, promotes the development of cancers. Wnt signaling is modulated by different factors, but whether the mitochondrial energetic state affects Wnt signaling is unknown. Here, we show that sublethal concentrations of different compounds that decrease mitochondrial ATP production specifically downregulate Wnt/β-catenin signaling 〈em〉in vitro〈/em〉 in colon cancer cells and 〈em〉in vivo〈/em〉 in zebrafish reporter lines. Accordingly, fibroblasts from a GRACILE syndrome patient and a generated zebrafish model lead to reduced Wnt signaling. We identify a mitochondria-Wnt signaling axis whereby a decrease in mitochondrial ATP reduces calcium uptake into the endoplasmic reticulum (ER), leading to endoplasmic reticulum stress and to impaired Wnt signaling. In turn, the recovery of the ATP level or the inhibition of endoplasmic reticulum stress restores Wnt activity. These findings reveal a mechanism that links mitochondrial energetic metabolism to the control of the Wnt pathway that may be beneficial against several pathologies.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309544-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Roja Babazadeh, Doryaneh Ahmadpour, Song Jia, Xinxin Hao, Per Widlund, Kara Schneider, Frederik Eisele, Laura Dolz Edo, Gertien J. Smits, Beidong Liu, Thomas Nystrom〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Spatial sorting to discrete quality control sites in the cell is a process harnessing the toxicity of aberrant proteins. We show that the yeast t-snare phosphoprotein syntaxin5 (Sed5) acts as a key factor in mitigating proteotoxicity and the spatial deposition and clearance of IPOD (insoluble protein deposit) inclusions associates with the disaggregase Hsp104. Sed5 phosphorylation promotes dynamic movement of COPII-associated Hsp104 and boosts disaggregation by favoring anterograde ER-to-Golgi trafficking. Hsp104-associated aggregates co-localize with Sed5 as well as components of the ER, 〈em〉trans〈/em〉 Golgi network, and endocytic vesicles, transiently during proteostatic stress, explaining mechanistically how misfolded and aggregated proteins formed at the vicinity of the ER can hitchhike toward vacuolar IPOD sites. Many inclusions become associated with mitochondria in a HOPS/vCLAMP-dependent manner and co-localize with Vps39 (HOPS/vCLAMP) and Vps13, which are proteins providing contacts between vacuole and mitochondria. Both Vps39 and Vps13 are required also for efficient Sed5-dependent clearance of aggregates.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S221112471930957X-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Tiffany Wu, Borislav Dejanovic, Vineela D. Gandham, Alvin Gogineni, Rose Edmonds, Stephen Schauer, Karpagam Srinivasan, Melanie A. Huntley, Yuanyuan Wang, Tzu-Ming Wang, Maj Hedehus, Kai H. Barck, Maya Stark, Hai Ngu, Oded Foreman, William J. Meilandt, Justin Elstrott, Michael C. Chang, David V. Hansen, Richard A.D. Carano〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Complement pathway overactivation can lead to neuronal damage in various neurological diseases. Although Alzheimer’s disease (AD) is characterized by β-amyloid plaques and tau tangles, previous work examining complement has largely focused on amyloidosis models. We find that glial cells show increased expression of classical complement components and the central component C3 in mouse models of amyloidosis (PS2APP) and more extensively tauopathy (TauP301S). Blocking complement function by deleting C3 rescues plaque-associated synapse loss in PS2APP mice and ameliorates neuron loss and brain atrophy in TauP301S mice, improving neurophysiological and behavioral measurements. In addition, C3 protein is elevated in AD patient brains, including at synapses, and levels and processing of C3 are increased in AD patient CSF and correlate with tau. These results demonstrate that complement activation contributes to neurodegeneration caused by tau pathology and suggest that blocking C3 function might be protective in AD and other tauopathies.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309647-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 15 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 452〈/p〉 〈p〉Author(s): Xueshuang Zhang, Guangze Jin, Zhili Liu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Variability in leaf mass per area (LMA) is largely explained by leaf anatomical traits. However, few studies have been conducted to explore the anatomical characteristics and the contribution of leaf anatomical traits to LMA for coexisting broadleaf species with different shade tolerances in same forests at a regional scale. Here, we analyzed variations in LMA and three leaf anatomical traits and the bivariate relationships among four leaf traits within three canopy layers for five major coexisting broadleaf species with different shade tolerances in four mixed broadleaved-Korean pine (〈em〉Pinus koraiensis〈/em〉) forests along a latitude gradient in Northeast China. We focused on assessing the relative weight of the leaf anatomical traits to predict LMA and on exploring the correlations among leaf anatomical traits, shade tolerance and LMA by using structural equation modeling (SEM). In comparison to shade-tolerant species, relative shade-intolerant species had higher LMA and length of minor veins per unit area (VLA〈sub〉min〈/sub〉). LMA, palisade tissue thickness (PT) and VLA〈sub〉min〈/sub〉 increased with the height of the canopy. The bivariate relationships among the three anatomical traits and LMA were significantly different among the five species, but there were no significant differences among the three canopy layers. LMA was directly enhanced by PT, epidermis thickness (ET) and VLA〈sub〉min〈/sub〉 and directly decreased by shade tolerance as well as indirectly decreased by shade tolerance via leaf anatomical traits. Our results clearly suggest that shade tolerance is important for driving variations in key leaf traits, which will provide a better understanding of the drivers of trait variation as well as the application of functional traits in outlining mechanisms of forest dynamics and management.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Adam L. Burrack, Ellen J. Spartz, Jackson F. Raynor, Iris Wang, Margaret Olson, Ingunn M. Stromnes〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Pancreatic ductal adenocarcinoma (PDA) is a lethal cancer resistant to immunotherapy. We create a PDA mouse model and show that neoantigen expression is required for intratumoral T cell accumulation and response to immune checkpoint blockade. By generating a peptide:MHC tetramer, we identify that PDA induces rapid intratumoral, and progressive systemic, tumor-specific T cell exhaustion. Monotherapy PD-1 or PD-L1 blockade enhances systemic T cell expansion and induces objective responses that require systemic T cells. However, tumor escape variants defective in IFNγ-inducible 〈em〉Tap1〈/em〉 and MHC class I cell surface expression ultimately emerge. Combination PD-1 + PD-L1 blockade synergizes therapeutically by increasing intratumoral KLRG1+Lag3−TNFα+ tumor-specific T cells and generating memory T cells capable of expanding to spontaneous tumor recurrence, thereby prolonging animal survival. Our studies support that PD-1 and PD-L1 are relevant immune checkpoints in PDA and identify a combination for clinical testing in those patients with neoantigen-specific T cells.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309635-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Raquel Buj, Chi-Wei Chen, Erika S. Dahl, Kelly E. Leon, Rostislav Kuskovsky, Natella Maglakelidze, Maithili Navaratnarajah, Gao Zhang, Mary T. Doan, Helen Jiang, Michael Zaleski, Lydia Kutzler, Holly Lacko, Yiling Lu, Gordon B. Mills, Raghavendra Gowda, Gavin P. Robertson, Joshua I. Warrick, Meenhard Herlyn, Yuka Imamura〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Reprogrammed metabolism and cell cycle dysregulation are two cancer hallmarks. p16 is a cell cycle inhibitor and tumor suppressor that is upregulated during oncogene-induced senescence (OIS). Loss of p16 allows for uninhibited cell cycle progression, bypass of OIS, and tumorigenesis. Whether p16 loss affects pro-tumorigenic metabolism is unclear. We report that suppression of p16 plays a central role in reprogramming metabolism by increasing nucleotide synthesis. This occurs by activation of mTORC1 signaling, which directly mediates increased translation of the mRNA encoding ribose-5-phosphate isomerase A (〈em〉RPIA〈/em〉), a pentose phosphate pathway enzyme. p16 loss correlates with activation of the mTORC1-RPIA axis in multiple cancer types. Suppression of RPIA inhibits proliferation only in p16-low cells by inducing senescence both 〈em〉in vitro〈/em〉 and 〈em〉in vivo〈/em〉. These data reveal the molecular basis whereby p16 loss modulates pro-tumorigenic metabolism through mTORC1-mediated upregulation of nucleotide synthesis and reveals a metabolic vulnerability of p16-null cancer cells.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719310009-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Mirunalini Ravichandran, Run Lei, Qin Tang, Yilin Zhao, Joun Lee, Liyang Ma, Stephanie Chrysanthou, Benjamin M. Lorton, Ales Cvekl, David Shechter, Deyou Zheng, Meelad M. Dawlaty〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉The Retinoid inducible nuclear factor (Rinf), also known as CXXC5, is a nuclear protein, but its functions in the context of the chromatin are poorly defined. We find that in mouse embryonic stem cells (mESCs), Rinf binds to the chromatin and is enriched at promoters and enhancers of 〈em〉Tet1〈/em〉, 〈em〉Tet2〈/em〉, and pluripotency genes. The Rinf-bound regions show significant overlapping occupancy of pluripotency factors Nanog, Oct4, and Sox2, as well as Tet1 and Tet2. We found that Rinf forms a complex with Nanog, Oct4, Tet1, and Tet2 and facilitates their proper recruitment to regulatory regions of pluripotency and 〈em〉Tet〈/em〉 genes in ESCs to positively regulate their transcription. Rinf deficiency in ESCs reduces expression of Rinf target genes, including several pluripotency factors and Tet enzymes, and causes aberrant differentiation. Together, our findings establish Rinf as a regulator of the pluripotency network genes and Tet enzymes in ESCs.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309842-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Richard J. Smith, Marilia H. Cordeiro, Norman E. Davey, Giulia Vallardi, Andrea Ciliberto, Fridolin Gross, Adrian T. Saurin〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉PP1 and PP2A-B56 are major serine/threonine phosphatase families that achieve specificity by colocalizing with substrates. At the kinetochore, however, both phosphatases localize to an almost identical molecular space and yet they still manage to regulate unique pathways and processes. By switching or modulating the positions of PP1/PP2A-B56 at kinetochores, we show that their unique downstream effects are not due to either the identity of the phosphatase or its precise location. Instead, these phosphatases signal differently because their kinetochore recruitment can be either inhibited (PP1) or enhanced (PP2A) by phosphorylation inputs. Mathematical modeling explains how these inverse phospho-dependencies elicit unique forms of cross-regulation and feedback, which allows otherwise indistinguishable phosphatases to produce distinct network behaviors and control different mitotic processes. Furthermore, our genome-wide analysis suggests that these major phosphatase families may have evolved to respond to phosphorylation inputs in opposite ways because many other PP1 and PP2A-B56-binding motifs are also phospho-regulated.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309714-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Qiuli Liang, Quan Zheng, Yong Zuo, Yalan Chen, Jiao Ma, Peihua Ni, Jinke Cheng〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Brown adipose tissue (BAT) is a thermogenic organ that maintains body temperature and energy homeostasis. Transcriptional regulation plays an important role in the program of brown adipogenesis. However, it remains unclear how the transcriptional events are controlled in this program. In this study, we analyze an SENP2 BAT conditional knockout mouse model and find that SENP2-mediated de-SUMOylation is essential for BAT development. SENP2 catalyzes de-SUMOylation of cAMP response element-binding protein (CREB) to suppress Necdin expression, which induces brown adipocyte differentiation and brown adipogenesis. Mechanistically, we find that SUMOylation enhances CREB interaction with serine/threonine protein phosphatase 2A (PP2A) to de-phosphorylate CREB, which activates Necdin transcription. SENP2 deficiency enhances the expression of Necdin to inhibit brown adipocyte differentiation. Therefore, we reveal a crucial role of SENP2-mediated de-SUMOylation of CREB in suppression of Necdin expression during brown adipose development and brown adipogenesis.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309878-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Nergis Kara, Matthew R. Kent, Dominic Didiano, Kamya Rajaram, Anna Zhao, Emily R. Summerbell, James G. Patton〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Unlike the adult mammalian retina, Müller glia (MG) in the adult zebrafish retina are able to dedifferentiate into a “stem cell”-like state and give rise to multipotent progenitor cells upon retinal damage. We show that 〈em〉miR-216a〈/em〉 is downregulated in MG after constant intense light lesioning and that 〈em〉miR-216a〈/em〉 suppression is necessary and sufficient for MG dedifferentiation and proliferation during retina regeneration. 〈em〉miR-216a〈/em〉 targets the H3K79 methyltransferase Dot1l, which is upregulated in proliferating MG after retinal damage. Loss-of-function experiments show that Dot1l is necessary for MG reprogramming and mediates MG proliferation downstream of 〈em〉miR-216a〈/em〉. We further demonstrate that 〈em〉miR-216a〈/em〉 and Dot1l regulate MG-mediated retina regeneration through canonical Wnt signaling. This article reports a regulatory mechanism upstream of Wnt signaling during retina regeneration and provides potential targets for enhancing regeneration in the adult mammalian retina.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309659-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Hanna Sabelström, Rebecca Petri, Ksenya Shchors, Rahul Jandial, Christin Schmidt, Rohit Sacheva, Selma Masic, Edith Yuan, Trenten Fenster, Michael Martinez, Supna Saxena, Theodore P. Nicolaides, Shirin Ilkhanizadeh, Mitchel S. Berger, Evan Y. Snyder, William A. Weiss, Johan Jakobsson, Anders I. Persson〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Identifying cellular programs that drive cancers to be stem-like and treatment resistant is critical to improving outcomes in patients. Here, we demonstrate that constitutive extracellular signal-regulated kinase 1/2 (ERK1/2) activation sustains a stem-like state in glioblastoma (GBM), the most common primary malignant brain tumor. Pharmacological inhibition of ERK1/2 activation restores neurogenesis during murine astrocytoma formation, inducing neuronal differentiation in tumorspheres. Constitutive ERK1/2 activation globally regulates miRNA expression in murine and human GBMs, while neuronal differentiation of GBM tumorspheres following the inhibition of ERK1/2 activation requires the functional expression of miR-124 and the depletion of its target gene SOX9. Overexpression of miR124 depletes SOX9 〈em〉in vivo〈/em〉 and promotes a stem-like-to-neuronal transition, with reduced tumorigenicity and increased radiation sensitivity. Providing a rationale for reports demonstrating miR-124-induced abrogation of GBM aggressiveness, we conclude that reversal of an ERK1/2-miR-124-SOX9 axis induces a neuronal phenotype and that enforcing neuronal differentiation represents a therapeutic strategy to improve outcomes in GBM.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309751-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Carles Solà-Riera, Shawon Gupta, Kimia T. Maleki, Patricia González-Rodriguez, Dalel Saidi, Christine L. Zimmer, Sindhu Vangeti, Laura Rivino, Yee-Sin Leo, David Chien Lye, Paul A. MacAry, Clas Ahlm, Anna Smed-Sörensen, Bertrand Joseph, Niklas K. Björkström, Hans-Gustaf Ljunggren, Jonas Klingström〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Cytotoxic lymphocytes normally kill virus-infected cells by apoptosis induction. Cytotoxic granule-dependent apoptosis induction engages the intrinsic apoptosis pathway, whereas death receptor (DR)-dependent apoptosis triggers the extrinsic apoptosis pathway. Hantaviruses, single-stranded RNA viruses of the order 〈em〉Bunyavirales〈/em〉, induce strong cytotoxic lymphocyte responses in infected humans. Cytotoxic lymphocytes, however, are largely incapable of eradicating hantavirus-infected cells. Here, we show that the prototypic hantavirus, Hantaan virus (HTNV), induces TRAIL production but strongly inhibits TRAIL-mediated extrinsic apoptosis induction in infected cells by downregulating DR5 cell surface expression. Mechanistic analyses revealed that HTNV triggers both 26S proteasome-dependent degradation of DR5 through direct ubiquitination of DR5 and hampers DR5 transport to the cell surface. These results corroborate earlier findings, demonstrating that hantavirus also inhibits cytotoxic cell granule-dependent apoptosis induction. Together, these findings show that HTNV counteracts intrinsic and extrinsic apoptosis induction pathways, providing a defense mechanism utilized by hantaviruses to inhibit cytotoxic cell-mediated eradication of infected cells.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309702-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Shaun Egolf, Yann Aubert, Miriam Doepner, Amy Anderson, Alexandra Maldonado-Lopez, Gina Pacella, Jessica Lee, Eun Kyung Ko, Jonathan Zou, Yemin Lan, Cory L. Simpson, Todd Ridky, Brian C. Capell〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Self-renewing somatic tissues depend upon the proper balance of chromatin-modifying enzymes to coordinate progenitor cell maintenance and differentiation, disruption of which can promote carcinogenesis. As a result, drugs targeting the epigenome hold significant therapeutic potential. The histone demethylase, LSD1 (KDM1A), is overexpressed in numerous cancers, including epithelial cancers; however, its role in the skin is virtually unknown. Here we show that LSD1 directly represses master epithelial transcription factors that promote differentiation. LSD1 inhibitors block both LSD1 binding to chromatin and its catalytic activity, driving significant increases in H3K4 methylation and gene transcription of these fate-determining transcription factors. This leads to both premature epidermal differentiation and the repression of squamous cell carcinoma. Together these data highlight both LSD1’s role in maintaining the epidermal progenitor state and the potential of LSD1 inhibitors for the treatment of keratinocyte cancers, which collectively outnumber all other cancers combined.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309623-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Khadar Abdi, Gabriel Neves, Joon Pyun, Emre Kiziltug, Angelica Ahrens, Chay T. Kuo〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Specialized microenvironments, called niches, control adult stem cell proliferation and differentiation. The brain lateral ventricular (LV) neurogenic niche is generated from distinct postnatal radial glial progenitors (pRGPs), giving rise to adult neural stem cells (NSCs) and niche ependymal cells (ECs). Cellular-intrinsic programs govern stem versus supporting cell maturation during adult niche assembly, but how they are differentially initiated within a similar microenvironment remains unknown. Using chemical approaches, we discovered that EGFR signaling powerfully inhibits EC differentiation by suppressing multiciliogenesis. We found that EC pRGPs actively terminated EGF activation through receptor redistribution away from CSF-contacting apical domains and that randomized EGFR membrane targeting blocked EC differentiation. Mechanistically, we uncovered spatiotemporal interactions between EGFR and endocytic adaptor protein Numb. Ca〈sup〉2+〈/sup〉-dependent basolateral targeting of Numb is necessary and sufficient for proper EGFR redistribution. These results reveal a previously unknown cellular mechanism for neighboring progenitors to differentially engage environmental signals, initiating adult stem cell niche assembly.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S221112471930960X-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Thomas Z. Young, Ping Liu, Guste Urbonaite, Murat Acar〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Although double-strand break (DSB) repair is essential for a cell’s survival, little is known about how DSB repair mechanisms are affected by age. Here we characterize the impact of cellular aging on the efficiency of single-strand annealing (SSA), a DSB repair mechanism. We measure SSA repair efficiency in young and old yeast cells and report a 23.4% decline in repair efficiency. This decline is not due to increased use of non-homologous end joining. Instead, we identify increased G1 phase duration in old cells as a factor responsible for the decreased SSA repair efficiency. Expression of 3x〈em〉CLN2〈/em〉 leads to higher SSA repair efficiency in old cells compared with expression of 1x〈em〉CLN2〈/em〉, confirming the involvement of cell-cycle regulation in age-associated repair inefficiency. Examining how SSA repair efficiency is affected by sequence heterology, we find that heteroduplex rejection remains high in old cells. Our work provides insights into the links between single-cell aging and DSB repair efficiency.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309866-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Kate Parkins, Amy Scott, Julian Di Stefano, Matthew Swan, Holly Sitters, Alan York〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Edges are ecologically important environmental features that have been well researched in agricultural and urban landscapes. However, little work has been conducted in flammable ecosystems where spatially and temporally dynamic fire edges are expected to influence animal activity patterns, particularly for animals reliant on vegetation for cover, foraging or nesting. We quantified the response of ground-dwelling mammals to fire edges and sought to determine whether animal activity mirrored temporal changes in regenerating understorey vegetation. We used a space-for-time substitution sampling design and selected a series of 26 treatment sites burnt by prescribed fire, where time since fire ranged from 0 to 7 years. Ten long-unburnt sites acted as controls. At each treatment site we identified a burnt/unburnt edge and used camera traps and Elliott traps to survey ground-dwelling mammals on either side. Habitat structure was measured at all 36 sites. We used general and generalised linear mixed models to determine the response of both habitat and animals to time since fire on both burnt and unburnt sides of edges. In addition, we used a resource selection index to assess the congruence between changes in understorey complexity and animal activity identified in the first set of analyses. On the unburnt side of the edge understorey complexity remained constant over time. On the burnt side understorey complexity followed a hump-shaped trend, peaking at 3 years post-fire where it exceeded the level of complexity on the unburnt edge. Larger animals with general resource requirements were more active at burnt compared to unburnt edges immediately after fire, but similarly active on both sides of fire edges from three years post-fire. Despite some activity on the burnt side of edges immediately after fire, small mammals were generally less active on burnt edges compared to unburnt edges for up to three years. Native species’ activity did not follow patterns of temporal change in structurally complex understorey vegetation. For all species, selection was strongest at recently burnt edges with little vegetation and substantially lower at 3–7 year old regenerating edges where understorey complexity was higher. In general, patterns of selection on the unburnt side of edges were similar over time. Our findings suggest that vegetation change on the burnt side of fire edges may not be a good predictor of native mammal use. Foxes and cats, exotic predators in our system, were also using the burnt edge more than expected immediately after fire. Immediate post-fire predation may be higher at fire edges than elsewhere, and recently burnt edge zones could be suitable locations for integrated predator and fire management.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Sarbajeet Nagdas, Jennifer A. Kashatus, Aldo Nascimento, Syed S. Hussain, Riley E. Trainor, Sarah R. Pollock, Sara J. Adair, Alex D. Michaels, Hiromi Sesaki, Edward B. Stelow, Todd W. Bauer, David F. Kashatus〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Mitochondria undergo fission and fusion to maintain homeostasis, and tumors exhibit the dysregulation of mitochondrial dynamics. We recently demonstrated that ectopic HRas〈sup〉G12V〈/sup〉 promotes mitochondrial fragmentation and tumor growth through Erk phosphorylation of the mitochondrial fission GTPase Dynamin-related protein 1 (Drp1). However, the role of Drp1 in the setting of endogenous oncogenic KRas remains unknown. Here, we show that Drp1 is required for KRas-driven anchorage-independent growth in fibroblasts and patient-derived pancreatic cancer cell lines, and it promotes glycolytic flux, in part through the regulation of hexokinase 2 (HK2). Furthermore, Drp1 deletion imparts a significant survival advantage in a model of KRas-driven pancreatic cancer, and tumors exhibit a strong selective pressure against complete Drp1 deletion. Rare tumors that arise in the absence of Drp1 have restored glycolysis but exhibit defective mitochondrial metabolism. This work demonstrates that Drp1 plays dual roles in KRas-driven tumor growth: supporting both glycolysis and mitochondrial function through independent mechanisms.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309283-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Shamsideen A. Ojelade, Tom V. Lee, Nikolaos Giagtzoglou, Lei Yu, Berrak Ugur, Yarong Li, Lita Duraine, Zhongyuan Zuo, Vlad Petyuk, Philip L. De Jager, David A. Bennett, Benjamin R. Arenkiel, Hugo J. Bellen, Joshua M. Shulman〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉The Alzheimer’s disease (AD) susceptibility gene, CD2-associated protein (〈em〉CD2AP〈/em〉), encodes an actin binding adaptor protein, but its function in the nervous system is largely unknown. Loss of the 〈em〉Drosophila〈/em〉 ortholog 〈em〉cindr〈/em〉 enhances neurotoxicity of human Tau, which forms neurofibrillary tangle pathology in AD. We show that Cindr is expressed in neurons and present at synaptic terminals. 〈em〉cindr〈/em〉 mutants show impairments in synapse maturation and both synaptic vesicle recycling and release. Cindr associates and genetically interacts with 14-3-3ζ, regulates the ubiquitin-proteasome system, and affects turnover of Synapsin and the plasma membrane calcium ATPase (PMCA). Loss of 〈em〉cindr〈/em〉 elevates PMCA levels and reduces cytosolic calcium. Studies of 〈em〉Cd2ap〈/em〉 null mice support a conserved role in synaptic proteostasis, and CD2AP protein levels are inversely related to Synapsin abundance in human postmortem brains. Our results reveal CD2AP neuronal requirements with relevance to AD susceptibility, including for proteostasis, calcium handling, and synaptic structure and function.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309386-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Cornelia N. Stacher Hörndli, Eleanor Wong, Elliott Ferris, Kathleen Bennett, Susan Steinwand, Alexis Nikole Rhodes, P. Thomas Fletcher, Christopher Gregg〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Complex ethological behaviors could be constructed from finite modules that are reproducible functional units of behavior. Here, we test this idea for foraging and develop methods to dissect rich behavior patterns in mice. We uncover discrete modules of foraging behavior reproducible across different strains and ages, as well as nonmodular behavioral sequences. Modules differ in terms of form, expression frequency, and expression timing and are expressed in a probabilistically determined order. Modules shape economic patterns of feeding, exposure, activity, and perseveration responses. The modular architecture of foraging changes developmentally, and different developmental, genetic, and parental effects are found to shape the expression of specific modules. Dissecting modules from complex patterns is powerful for phenotype analysis. We discover that both parental alleles of the imprinted Prader-Willi syndrome gene 〈em〉Magel2〈/em〉 are functional in mice but regulate different modules. Our study found that complex economic patterns are built from finite, genetically controlled modules.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309350-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Matthew A. Huggins, Frances V. Sjaastad, Mark Pierson, Tamara A. Kucaba, Whitney Swanson, Christopher Staley, Alexa R. Weingarden, Isaac J. Jensen, Derek B. Danahy, Vladimir P. Badovinac, Stephen C. Jameson, Vaiva Vezys, David Masopust, Alexander Khoruts, Thomas S. Griffith, Sara E. Hamilton〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Microbial exposures can define an individual’s basal immune state. Cohousing specific pathogen-free (SPF) mice with pet store mice, which harbor numerous infectious microbes, results in global changes to the immune system, including increased circulating phagocytes and elevated inflammatory cytokines. How these differences in the basal immune state influence the acute response to systemic infection is unclear. Cohoused mice exhibit enhanced protection from virulent 〈em〉Listeria monocytogenes〈/em〉 (LM) infection, but increased morbidity and mortality to polymicrobial sepsis. Cohoused mice have more TLR2〈sup〉+〈/sup〉 and TLR4〈sup〉+〈/sup〉 phagocytes, enhancing recognition of microbes through pattern-recognition receptors. However, the response to a TLR2 ligand is muted in cohoused mice, whereas the response to a TLR4 ligand is greatly amplified, suggesting a basis for the distinct response to 〈em〉Listeria monocytogenes〈/em〉 and sepsis. Our data illustrate how microbial exposure can enhance the immune response to unrelated challenges but also increase the risk of immunopathology from a severe cytokine storm.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309258-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Yasir S. Elhassan, Katarina Kluckova, Rachel S. Fletcher, Mark S. Schmidt, Antje Garten, Craig L. Doig, David M. Cartwright, Lucy Oakey, Claire V. Burley, Ned Jenkinson, Martin Wilson, Samuel J.E. Lucas, Ildem Akerman, Alex Seabright, Yu-Chiang Lai, Daniel A. Tennant, Peter Nightingale, Gareth A. Wallis, Konstantinos N. Manolopoulos, Charles Brenner〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Nicotinamide adenine dinucleotide (NAD〈sup〉+〈/sup〉) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD〈sup〉+〈/sup〉 metabolome and if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR per day for 21 days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD〈sup〉+〈/sup〉 metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309404-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Alexander J. Baker-Williams, Fiza Hashmi, Marek A. Budzyński, Mark R. Woodford, Stephanie Gleicher, Samu V. Himanen, Alan M. Makedon, Derek Friedman, Stephanie Cortes, Sara Namek, William G. Stetler-Stevenson, Gennady Bratslavsky, Alaji Bah, Mehdi Mollapour, Lea Sistonen, Dimitra Bourboulia〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉The extracellular molecular chaperone heat shock protein 90 (eHSP90) stabilizes protease client the matrix metalloproteinase 2 (MMP2), leading to tumor cell invasion. Although co-chaperones are critical modulators of intracellular HSP90:client function, how the eHSP90:MMP2 complex is regulated remains speculative. Here, we report that the tissue inhibitor of metalloproteinases-2 (TIMP2) is a stress-inducible extracellular co-chaperone that binds to eHSP90, increases eHSP90 binding to ATP, and inhibits its ATPase activity. In addition to disrupting the eHSP90:MMP2 complex and terminally inactivating MMP2, TIMP2 loads the client to eHSP90, keeping the protease in a transient inhibitory state. Secreted activating co-chaperone AHA1 displaces TIMP2 from the complex, providing a “reactivating” mechanism for MMP2. Gene knockout or blocking antibodies targeting TIMP2 and AHA1 released by HT1080 cancer cells modify their gelatinolytic activity. Our data suggest that TIMP2 and AHA1 co-chaperones function as a molecular switch that determines the inhibition and reactivation of the eHSP90 client protein MMP2.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309490-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Jakob Neuser, Caroline C. Metzen, Bernd H. Dreyer, Claudio Feulner, Joost T. van Dongen, Romy R. Schmidt, Jos H.M. Schippers〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Plants continuously need to adapt to their environment and prioritize either growth or defense responses to secure survival and reproduction. Trade-offs between growth and defense are often attributed to the allocation of energy for growth to adaptation responses. Still, the exact mechanisms underlying growth and defense trade-offs are poorly understood. Here, we demonstrate that the growth-related transcription factor HOMOLOG OF BEE2 INTERACTING WITH IBH 1 (HBI1) regulates apoplastic reactive oxygen species (ROS) homeostasis by differentially controlling the expression of NADPH oxidases (NOXs) and peroxidases (POXs). The HBI1 target genes 〈em〉RESPIRATORY BURST OXIDASE HOMOLOG A〈/em〉 (〈em〉RbohA〈/em〉) and 〈em〉RbohC〈/em〉 have contrasting effects on the regulation of cell size. In addition, the HBI1-controlled 〈em〉NOX〈/em〉s and 〈em〉POX〈/em〉s oppositely regulate susceptibility toward 〈em〉Pseudomonas syringae〈/em〉. Our findings reveal that the incompatibility between growth and defense programs can be attributed to the way apoplastic ROS homeostasis is modulated during both processes.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S221112471930926X-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Melanie Korbelius, Nemanja Vujic, Vinay Sachdev, Sascha Obrowsky, Silvia Rainer, Benjamin Gottschalk, Wolfgang F. Graier, Dagmar Kratky〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉As circulating lipid levels are balanced by the rate of lipoprotein release and clearance from the plasma, lipid absorption in the small intestine critically contributes to the maintenance of whole-body lipid homeostasis. Within enterocytes, excessive triglycerides are transiently stored as cytosolic lipid droplets (cLDs), and their mobilization sustains lipid supply during interprandial periods. Using mice lacking adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) exclusively in the intestine (intestine-specific double KO [iDKO]), we show that ATGL/CGI-58 are not involved in providing substrates for chylomicron synthesis. Massive intestinal cLD accumulation in iDKO mice independent of dietary lipids together with inefficient lipid incorporation into cLDs in the early absorption phase demonstrate the existence of a secretion/re-uptake cycle, corroborating the availability of two diverse cLD pools. This study identified ATGL/CGI-58 as critical players in the catabolism of basolaterally (blood) derived lipids and highlights the necessity to modify the current model of intestinal lipid metabolism.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309271-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Penelope Kroustallaki, Lisa Lirussi, Sergio Carracedo, Panpan You, Q. Ying Esbensen, Alexandra Götz, Laure Jobert, Lene Alsøe, Pål Sætrom, Sarantis Gagos, Hilde Nilsen〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Telomerase biogenesis is a complex process where several steps remain poorly understood. Single-strand-selective uracil-DNA glycosylase (SMUG1) associates with the DKC1-containing H/ACA ribonucleoprotein complex, which is essential for telomerase biogenesis. Herein, we show that SMUG1 interacts with the telomeric RNA component (〈em〉hTERC〈/em〉) and is required for co-transcriptional processing of the nascent transcript into mature 〈em〉hTERC〈/em〉. We demonstrate that SMUG1 regulates the presence of base modifications in 〈em〉hTERC〈/em〉, in a region between the CR4/CR5 domain and the H box. Increased levels of 〈em〉hTERC〈/em〉 base modifications are accompanied by reduced DKC1 binding. Loss of SMUG1 leads to an imbalance between mature 〈em〉hTERC〈/em〉 and its processing intermediates, leading to the accumulation of 3′-polyadenylated and 3′-extended intermediates that are degraded in an EXOSC10-independent RNA degradation pathway. Consequently, SMUG1-deprived cells exhibit telomerase deficiency, leading to impaired bone marrow proliferation in 〈em〉Smug1〈/em〉-knockout mice.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309374-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Yuanming Cheng, Hanzhi Luo, Franco Izzo, Brian F. Pickering, Diu Nguyen, Robert Myers, Alexandra Schurer, Saroj Gourkanti, Jens C. Brüning, Ly P. Vu, Samie R. Jaffrey, Dan A. Landau, Michael G. Kharas〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Stem cells balance cellular fates through asymmetric and symmetric divisions in order to self-renew or to generate downstream progenitors. Symmetric commitment divisions in stem cells are required for rapid regeneration during tissue damage and stress. The control of symmetric commitment remains poorly defined. Using single-cell RNA sequencing (scRNA-seq) in combination with transcriptomic profiling of HSPCs (hematopoietic stem and progenitor cells) from control and m〈sup〉6〈/sup〉A methyltransferase 〈em〉Mettl3〈/em〉 conditional knockout mice, we found that m〈sup〉6〈/sup〉A-deficient hematopoietic stem cells (HSCs) fail to symmetrically differentiate. Dividing HSCs are expanded and are blocked in an intermediate state that molecularly and functionally resembles multipotent progenitors. Mechanistically, RNA methylation controls 〈em〉Myc〈/em〉 mRNA abundance in differentiating HSCs. We identified MYC as a marker for HSC asymmetric and symmetric commitment. Overall, our results indicate that RNA methylation controls symmetric commitment and cell identity of HSCs and may provide a general mechanism for how stem cells regulate differentiation fate choice.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309295-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Suzanne T.S. van Beeck Calkoen, Kieran Leigh-Moy, Joris P.G.M. Cromsigt, Göran Spong, Leo C. Lebeau, Marco Heurich〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Increasing deer populations in many temperate regions can affect tree regeneration, resulting in severe long-term impacts on forest structure, composition and diversity. Of the most common deer species in Europe — red deer (〈em〉Cervus elaphus〈/em〉) and roe deer (〈em〉Capreolus capreolus〈/em〉) — roe deer are generally thought to have the highest impact on palatable tree species owing to their feeding niche. Although browsing and its potential consequences are well researched, less is known about the influence of specific deer species within multi-species ungulate communities on specific tree species. Environmental DNA (eDNA) allows the determination of species-specific browsing habits without the need for direct observations, facilitating effective targeting of management interventions. In this study eDNA was used to elucidate the browsing patterns of these two deer species in the temperate forest of the Bavarian Forest National Park, Germany and analysed the influence of tree species, management type and height of browsing, on the success rate of the method. Samples were collected from twigs used in feeding trials from enclosures containing red deer or roe deer and from naturally browsed twigs in three different management types within the national park. eDNA was successfully amplified from 98% of the feeding trial samples, and the correct deer species was identified for all samples. eDNA was successfully amplified from approximately 50% of the naturally browsed samples. Neither management type, tree species, nor height of browsing had any significant influence on the success of the method. For silver fir and rowan, no significant difference was found in the proportion of browsing events attributable to roe or red deer, when the two deer species occur at similar densities. These results indicate that roe deer might not always be disproportionately responsible for the browsing of palatable tree species as expected from its food niche. Roe deer were significantly more responsible for browsing at lower heights than red deer. Although not statistically significant, roe deer were more responsible for browsing in intact forest compared to bark-beetle-impact forest, with the opposite relationship for red deer.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Alwin A. Hardenbol, Timo Pakkala, Jari Kouki〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Tree cavities are microhabitats used by multiple taxa and are considered indicators of forest biodiversity. The factors that affect cavity occurrence and its dynamics are poorly known. We studied tree- and stand-level factors that affect cavity persistence in boreal forests. Cavities of Eurasian Three-toed Woodpeckers (〈em〉Picoides tridactylus〈/em〉) (n = 654) were surveyed in a 170 km〈sup〉2〈/sup〉 area in southern Finland for 31 years during 1987–2017. In total, 447 cavities were lost during the study period: 329 to tree fall or breakage, 72 to cavity damage, and 46 to logging. With the Kaplan-Meier method and Cox proportional hazards models, we analysed which tree- and stand-level factors affected the risk of a cavity to be damaged or lost due to tree fall. The median lifespan of cavities was 10 years, and both tree- and stand-level factors affected the persistence of cavities. Cavities in managed forest areas with low territory occupancy rates were more at risk of tree fall and cavity damage than in other types of forest areas. In all nest tree species, with the exception of European aspen (〈em〉Populus tremula〈/em〉), the risk of cavity loss to tree fall declined with increasing tree diameter. Moreover, the risk of cavity loss to tree fall was higher in dead trees than in healthy and weakened trees. Cavities in deciduous tree species other than aspen were more at risk of damage than in other tree species. Furthermore, the risk of cavity damage was greater in cavities located lower in a tree. This study showed that factors like the tree species, and size and condition of a tree modify the persistence of woodpecker-made cavities. Consequently, it is likely that these factors influence the value of cavities as microhabitats and how these cavities can be used as indicators of forest biodiversity. Understanding the dynamics of cavities in forest habitats appears critical for the use of cavities as general biodiversity indicators.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Ishmail Abdus-Saboor, Nathan T. Fried, Mark Lay, Justin Burdge, Kathryn Swanson, Roman Fischer, Jessica Jones, Peter Dong, Weihua Cai, Xinying Guo, Yuan-Xiang Tao, John Bethea, Minghong Ma, Xinzhong Dong, Long Ding, Wenqin Luo〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Rodents are the main model systems for pain research, but determining their pain state is challenging. To develop an objective method to assess pain sensation in mice, we adopt high-speed videography to capture sub-second behavioral features following hind paw stimulation with both noxious and innocuous stimuli and identify several differentiating parameters indicating the affective and reflexive aspects of nociception. Using statistical modeling and machine learning, we integrate these parameters into a single index and create a “mouse pain scale,” which allows us to assess pain sensation in a graded manner for each withdrawal. We demonstrate the utility of this method by determining sensations triggered by three different von Frey hairs and optogenetic activation of two different nociceptor populations. Our behavior-based “pain scale” approach will help improve the rigor and reproducibility of using withdrawal reflex assays to assess pain sensation in mice.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309076-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Miyuki Suzawa, Nigel M. Muhammad, Bradley S. Joseph, Michelle L. Bland〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Chronic enteropathogen infection in early childhood reduces circulating insulin-like growth factor 1 (IGF1) levels and restricts growth. Pathogen-derived molecules activate host Toll-like receptors to initiate the immune response, but whether this pathway contributes to growth inhibition is unclear. In 〈em〉Drosophila〈/em〉, activation of Toll receptors in larval fat body suppresses whole-animal growth. Here, using a transcriptomic approach, we identify 〈em〉Drosophila insulin-like peptide 6〈/em〉 (〈em〉Dilp6〈/em〉), a fat-body-derived IGF1 ortholog, as a selective target of Toll signaling induced by infection or genetic activation of the pathway. Using a tagged allele that we generated to measure endogenous Dilp6, we find a marked reduction in circulating hormone levels. Restoring Dilp6 expression in fat body rescues growth in animals with active Toll signaling. Our results establish that Toll signaling reduces growth by inducing hormone insufficiency, implying a mechanistic link between innate immune signaling and endocrine regulation of growth.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309052-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Chi-Jung Liang, Zih-Wun Wang, Yi-Wen Chang, Ko-Chuan Lee, Wei-Hsin Lin, Jia-Lin Lee〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Secreted frizzled-related proteins (SFRPs) are mainly known for their role as extracellular modulators and tumor suppressors that downregulate Wnt signaling. Using the established (CRISPR/Cas9 targeting promoters of SFRPs and targeting SFRPs transcript) system, we find that nuclear SFRPs interact with β-catenin and either promote or suppress TCF4 recruitment. SFRPs bind with β-catenin on both their N and C termini, which the repressive effects caused by SFRP-β-catenin-N-terminus binding overpower the promoting effects of their binding at the C terminus. By high Wnt activity, β-catenin and SFRPs only bind with their C termini, which results in the upregulation of β-catenin transcriptional activity and cancer stem cell (CSC)-related genes. Furthermore, we identify disulfide bonds of the cysteine-rich domain (CRD) and two threonine phosphorylation events of the netrin-related motif (NTR) domain of SFRPs that are essential for their role as biphasic modulators, suggesting that SFRPs are biphasic modulators of Wnt signaling-elicited CSC properties beyond extracellular control.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309131-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Aditya Mojumdar, Kyle Sorenson, Marcel Hohl, Mathias Toulouze, Susan P. Lees-Miller, Karine Dubrana, John H.J. Petrini, Jennifer A. Cobb〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Non-homologous end joining (NHEJ) and homologous recombination (HR) are the two major pathways of DNA double-strand break (DSB) repair and both are highly conserved from yeast to mammals. Nej1 has a role in DNA end-tethering at a DSB, and the Mre11/Rad50/Xrs2 (MRX) complex is important for its recruitment to the break. Nej1 and Dna2-Sgs1 interact with the C-terminal end of Mre11, which also includes the region where Rad50 binds. By characterizing the functionality of Nej1 in two 〈em〉rad50〈/em〉 mutants, which alter the structural features of MRX, we demonstrate that Nej1 inhibits the binding of Dna2 to Mre11 and Sgs1. Nej1 interactions with Mre11 promote tethering and inhibit hyper-resection, and when these events are compromised, large deletions develop at a DSB. The work indicates that Nej1 provides a layer of regulation to repair pathway choice and is consistent with its role in NHEJ.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309088-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Grit Bornschein, Jens Eilers, Hartmut Schmidt〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Coupling distances between Ca〈sup〉2+〈/sup〉 channels and release sensors regulate vesicular release probability (〈em〉p〈/em〉〈sub〉v〈/sub〉). Tight coupling is thought to provide a framework for high 〈em〉p〈/em〉〈sub〉v〈/sub〉 and loose coupling for high plasticity at low 〈em〉p〈/em〉〈sub〉v〈/sub〉. At synapses investigated during development, coupling distances decrease, thereby increasing 〈em〉p〈/em〉〈sub〉v〈/sub〉 and transmission fidelity. We find that neocortical high-fidelity synapses deviate from these rules. Paired recordings from pyramidal neurons with “slow” and “fast” Ca〈sup〉2+〈/sup〉 chelators combined with experimentally constrained simulations suggest that coupling tightens significantly during development. However, fluctuation analysis revealed that neither 〈em〉p〈/em〉〈sub〉v〈/sub〉 (∼0.63) nor the number of release sites (∼8) changes concomitantly. Moreover, the amplitude and time course of presynaptic Ca〈sup〉2+〈/sup〉 transients are not different between age groups. These results are explained by high-〈em〉p〈/em〉〈sub〉v〈/sub〉 release sites with Ca〈sup〉2+〈/sup〉 microdomains in young synapses and nanodomains in mature synapses. Thus, at neocortical synapses, a developmental reorganization of the active zone leaves 〈em〉p〈/em〉〈sub〉v〈/sub〉 unaffected, emphasizing developmental and functional synaptic diversity.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719308988-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Erin E. Talbert, Maria C. Cuitiño, Katherine J. Ladner, Priyani V. Rajasekerea, Melissa Siebert, Reena Shakya, Gustavo W. Leone, Michael C. Ostrowski, Brian Paleo, Noah Weisleder, Peter J. Reiser, Amy Webb, Cynthia D. Timmers, Daniel S. Eiferman, David C. Evans, Mary E. Dillhoff, Carl R. Schmidt, Denis C. Guttridge〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia is associated with increased morbidity and mortality and decreased treatment tolerance. Although advances have been made in understanding the mechanisms of cachexia, translating these advances to the clinic has been challenging. One reason for this shortcoming may be the current animal models, which fail to fully recapitulate the etiology of human cancer-induced tissue wasting. Because pancreatic ductal adenocarcinoma (PDA) presents with a high incidence of cachexia, we engineered a mouse model of PDA that we named KPP. KPP mice, similar to PDA patients, progressively lose skeletal and adipose mass as a consequence of their tumors. In addition, KPP muscles exhibit a similar gene ontology as cachectic patients. We envision that the KPP model will be a useful resource for advancing our mechanistic understanding and ability to treat cancer cachexia.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309064-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Runrui Zhang, Marcelo Boareto, Anna Engler, Angeliki Louvi, Claudio Giachino, Dagmar Iber, Verdon Taylor〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Neural stem cells (NSCs) in the adult mouse hippocampal dentate gyrus (DG) are mostly quiescent, and only a few are in cell cycle at any point in time. DG NSCs become increasingly dormant with age and enter mitosis less frequently, which impinges on neurogenesis. How NSC inactivity is maintained is largely unknown. Here, we found that 〈em〉Id4〈/em〉 is a downstream target of Notch2 signaling and maintains DG NSC quiescence by blocking cell-cycle entry. Id4 expression is sufficient to promote DG NSC quiescence and Id4 knockdown rescues Notch2-induced inhibition of NSC proliferation. 〈em〉Id4〈/em〉 deletion activates NSC proliferation in the DG without evoking neuron generation, and overexpression increases NSC maintenance while promoting astrogliogenesis at the expense of neurogenesis. Together, our findings indicate that Id4 is a major effector of Notch2 signaling in NSCs and a Notch2-Id4 axis promotes NSC quiescence in the adult DG, uncoupling NSC activation from neuronal differentiation.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309040-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Katie M. Campbell, Kathleen A. O’Leary, Debra E. Rugowski, William A. Mulligan, Erica K. Barnell, Zachary L. Skidmore, Kilannin Krysiak, Malachi Griffith, Linda A. Schuler, Obi L. Griffith〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉The NRL-PRL murine model, defined by mammary-selective transgenic rat prolactin ligand 〈em〉rPrl〈/em〉 expression, establishes spontaneous ER+ mammary tumors in nulliparous females, mimicking the association between elevated prolactin (PRL) and risk for development of ER+ breast cancer in postmenopausal women. Whole-genome and exome sequencing in a discovery cohort (n = 5) of end-stage tumors revealed canonical activating mutations and copy number amplifications of 〈em〉Kras〈/em〉. The frequent mutations in this pathway were validated in an extension cohort, identifying activating 〈em〉Ras〈/em〉 alterations in 79% of tumors (23 of 29). Transcriptome analyses over the course of oncogenesis revealed marked alterations associated with Ras activity in established tumors compared with preneoplastic tissues; in cell-intrinsic processes associated with mitosis, cell adhesion, and invasion; as well as in the surrounding tumor environment. These genomic analyses suggest that PRL induces a selective bottleneck for spontaneous Ras-driven tumors that may model a subset of aggressive clinical ER+ breast cancers.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719308848-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Tony Marks-Block, Frank K. Lake, Lisa M. Curran〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Before widespread fire exclusion policies, American Indians used broadcast understory fires or cultural burns to enhance resources integral for their livelihood and cultural practices. To restore ecocultural resources depleted from decades of fire exclusion and to reduce wildfire risks, the Karuk and the Yurok Tribes of Northwest California are leading regional collaborative efforts to expand broadcast fires and fuel reduction treatments on public, private, and Tribal lands in their ancestral territories. Through collaboration with Karuk and Yurok Tribal members and basketweavers, we evaluated the effects of broadcast fires and three fire proxy treatments on California hazelnut shrubs (〈em〉Corylus cornuta〈/em〉 var. 〈em〉californica〈/em〉) that produce highly valued ecocultural resources for basketry materials. Across a 10 ha Douglas-fir and mixed hardwood forest (500 m a.s.l.) in the Klamath mountains, we established 27 stratified blocks (16 m〈sup〉2〈/sup〉) and within each block applied three fire proxy treatments designed and used by Tribal members with an untreated control. These treatments involved manual hazelnut stem cutting, directly blistering hazelnut stems via propane torch, and igniting surface fuels piled within hazelnut shrubs to top-kill stems. Broadcast fire was applied to 12 separate blocks. After a full growing season (12–18 months post-treatment/burn), shrubs were re-measured. We then harvested these stems (〈em〉n〈/em〉 = 604; 50 shrubs) across treatments and compared results with stems gathered independently by two experienced Karuk/Yurok basketweavers (〈em〉n〈/em〉 = 396 and 〈em〉n〈/em〉 = 73) from an adjacent broadcast burned site. Compared to the untreated shrubs, pile burning, propane torching, and broadcast burning increased basketry stem production by 7–10 fold (p 〈 0.001), while the cutting treatment increased production by 4-fold (p = 0.006). Shrubs with relatively greater access to sunlight (southern aspect, ≥51% and 〈70% canopy cover) produced fewer quality stems when compared to shrubs with an eastern aspect (〈em〉p〈/em〉 〈 0.01) and ≥70% canopy cover (〈em〉p〈/em〉 〈 0.05). Harvested stems across all treatments displayed similar stem length distributions to those gathered by one of the two basketweavers (〈em〉p〈/em〉 〉 0.05). Our results demonstrate that these fire-proxy methods are an effective means to increase the production and quality of basketry materials. Expanding the area and frequency of targeted understory fire-based forest treatments on private, public and Tribal lands in California and the Pacific Northwest would substantially increase the availability of these fire-enhanced ecocultural resources that are currently limited in supply and in high demand.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Javier Castaño-Santamaría, Carlos A. López-Sánchez, José Ramón Obeso, Marcos Barrio-Anta〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The beech forests in the Cantabrian Range occur at the southwestern limit of the distribution of the species and are very important for wildlife and biodiversity in the region. Climate change is expected to increase the frequency and severity of drought events over the next few decades in southwestern Europe, and establishing how this will alter the distribution, abundance and productivity of beech is fundamental for biodiversity conservation and management. In this study, we used spatially continuous environmental variables to develop spatial distribution and site-productivity models for beech forests in the Cantabrian Range and to project these models to different climate change scenarios. Two raster-based models of resolution 250 m were constructed to identify suitable habitat (species distribution model) and to estimate site index (productivity model) for beech in the Cantabrian Range. Of the 23 variables retained in the spatial distribution model, climate, soil and terrain were the most important (explaining respectively 51.2%, 34.2% and 10.1% of the variation). The productivity model retained only three variables (percentage of silt in soil, mean diurnal range of temperature and plan curvature of the terrain) but was able to explain 54% of the total variation. Future projections based on two emission scenarios suggest that suitable habitat will be drastically reduced by 2070 (loss of 40–90% of the area for the moderate and pessimistic scenarios, respectively). However, the projections do not imply current population removal rather it can be probably interpreted in less favorable conditions for seedling establishment, higher mortality rates and a reduction in local density of populations. Productivity projections for suitable habitat suggest a large increase in the average site index (from current 15.19 to 18.18 m) in the moderate scenario and an increase of only 34 cm in the pessimistic scenario. The study findings provide basic information for conservation biology and could be used by decision-makers to develop and implement actions for mitigating the impact of climate change on beech forests.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Baorong Wang, Xiaodan Zhao, Yang Liu, Ying Fang, Rentian Ma, Qiang Yu, Shaoshan An〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Revegetation in fragile ecosystems is an efficient means to increase aggregate stability and thus reduce soil erosion. However, the influence of large-scale afforestation on soil aggregate stability and erodibility in the Loess Plateau is not well understood. To assess the sustainability and suitability of widespread, long-term planting of plantations in terms of soil aggregate stability (mean weighted diameter (MWD) and geometric mean diameter (GMD)) and erodibility (K), we performed a large-scale investigation of soil aggregate stability and soil erodibility of 〈em〉Robinia pseudoacacia〈/em〉 (RP) and 〈em〉Caragana korshinskii〈/em〉 (CK) plantations on the Loess Plateau. The results showed that the soil macroaggregate fraction (〉0.25 mm) content under RP and CK plantations had a decreasing trend with increasing latitude. Moreover, soil aggregate stability and soil organic carbon (SOC) and total nitrogen (TN) contents in RP and CK plantations decreased with increasing latitude. RP and CK plantations did not always result in improvement of soil aggregate stability and the accumulation of SOC and TN, which depended on the latitude and precipitation conditions. Specifically, RP planting in the south warm temperate forest subzone (STFZ) and north warm temperate forest subzone (NTFZ) could enhance the macroaggregate content (〉5 mm), soil aggregate stability and soil nutrients, while CK planting for the improvement of the soil macroaggregate content, soil aggregate stability and soil nutrients in the temperate forest steppe subzone (TFSZ) was more effective than was RP planting. Correlation analysis showed that the latitude, longitude and mean annual precipitation (MAP) were significantly correlated with soil MWD, GMD, K values, SOC and TN across the RP and CK plantations, and soil MWD, GMD, and K values were significantly correlated with SOC and TN in RP and CK plantations. The changing trends of SOC and TN with latitude and longitude were consistent with that of soil aggregate stability with latitude and longitude under RP and CK plantations, indicating that changes in the SOC and TN concentrations will cause changes in soil aggregate stability and erodibility. Additionally, the effects of RP and CK plantations on the soil aggregate stability, erodibility, SOC and TN content were different and distinguished by latitude and MAP. RP plantation resulted in more SOC and TN accumulation, enhanced the soil aggregate stability and decreased erodibility compared with CK plantation in areas with MAP 〉500 mm or latitude 〈36° N; in contrast, in sites with MAP 〈500 mm or latitude 〉36° N, CK plantation had slight advantages over RP plantation. This study indicated that the changes in soil aggregate stability, erodibility, SOC and TN accumulation following RP and CK plantations had different patterns along latitude and precipitation gradients. Therefore, the 36° N or 500 mm precipitation threshold may be the dividing line for planting RP and CK plantations. Overall, our study produces unique insights into the relative significance of environmental factors that influence aggregate stability at large scales and is useful for selecting suitable afforestation species and locations to optimize forest management with sustainable production.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Marcin K. Dyderski, Andrzej M. Jagodziński〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Although invasive trees species spread effectively across different habitats, data on survival of their seedlings are scarce. We compared seedling survival after the first year from germination for the three most invasive tree species in temperate Europe. We also assessed the impact of light availability, parental tree stands and intra- and inter-specific competition. We studied seedlings of three invasive species: 〈em〉Prunus serotina〈/em〉 Ehrh., 〈em〉Quercus rubra〈/em〉 L. and 〈em〉Robinia pseudoacacia〈/em〉 L., in a set of 186 study plots in W Poland over three years (2015–2018). In total, we labelled 11,135 seedlings. We assessed importance of variables using machine learning techniques. Mean seedling survival was 3.9 ± 1.2%, 12.5 ± 2.2% and 0.1 ± 0.1% for 〈em〉P. serotina〈/em〉, 〈em〉Q. rubra〈/em〉 and 〈em〉R. pseudoacacia〈/em〉 respectively, and was higher than for native species. Survival of 〈em〉Q. rubra〈/em〉 seedlings depended mostly on intraspecific competition in understory, light availability and parental trees availability. Survival of 〈em〉P. serotina〈/em〉 seedlings depended mostly on intra- and inter-specific competition, germination year (precipitation seasonality) and light availability. Our study explained that despite the high seedling densities of invasive species beneath parental tree canopies, their survival was lower than in surrounding forests. These two aspects of the establishment process (seedling abundance and survival) contribute to the dynamic equilibrium between limiting (low survival beneath maternal tree canopies) and facilitating (high seedling densities beneath maternal trees canopies) the growth of young generations of invasive tree species.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Mateus C. Silva, Grazielle S. Teodoro, Evelyn F.A. Bragion, Eduardo van den Berg〈/p〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Anna C. Talucci, Ken P. Lertzman, Meg A. Krawchuk〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Seedbanks are essential for forest resilience, and disturbance interactions could potentially modify seedbank availability, subsequent forest regeneration patterns, and successional trajectories. Regional mountain pine beetle outbreaks have altered forest structure and seedbanks in fire prone-landscapes across western North America and could influence forest regeneration. We examined the drivers of lodgepole pine recruitment across a gradient of fire severity from fire that burned through gray-phase outbreak conditions in central interior British Columbia, Canada. We considered ten potential drivers of lodgepole pine recruitment including: fire severity, mountain pine beetle outbreak severity, cone abundance, branch retention, open cones, exposed soil, snag fall, snow accumulation, climate moisture deficit, and frost events, as well as the contribution of unburned fire refugia to lodgepole pine recruitment. In 2016, we inventoried 83 plots that spanned gradients of outbreak severity, burning conditions, and fire severity across three fires that burned through lodgepole pine dominated forests with gray-phase conditions that had moderate to high mortality. We used generalized linear models to evaluate drivers of variability in seedling recruitment. Our analyses affirm that wildfire is a critical mechanism for lodgepole pine seedling recruitment. For plots that burned as crown and surface fire, recruitment densities were two or six times greater compared plots that experienced light surface or were fire refugia, respectively. Recruitment was driven by cone abundance indicating the importance of an available seed source. In fire refugia, recruitment was three times greater during the post-outbreak period compared to before outbreaks, suggesting cone senescence from mortality and/or xeriscent-cueing of cones. The unevenness in recruitment across gradients of outbreak and fire severity contribute to the heterogeneity of stand initiation across these landscapes that may be important for mediation of subsequent outbreaks.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Julie P. Thomas, Mary L. Reid, Thomas S. Jung, Robert M.R. Barclay〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉As a consequence of warmer winters, the frequency and severity of bark beetle infestations has increased in western North America, creating controversy over how to manage beetle-killed forests. Post-infestation salvage logging is increasingly used to reduce wildfire risk and recover the value of beetle-killed trees; however, the ecological consequences of this practice are poorly understood. We investigated the effects of post-infestation salvage logging in the boreal forest (Yukon, Canada) on habitat use by the little brown bat (〈em〉Myotis lucifugus〈/em〉), a forest-dwelling species that is relatively tolerant of vegetative clutter and numerically dominant in boreal bat communities. We hypothesized that little brown bats would select closed-canopied sites, particularly at high latitudes where bats may be vulnerable to predators during midsummer when daylight is nearly continuous. Thus, we expected low occupancy rates in salvage-logged stands, particularly those with low tree retention. Because night length increases drastically after summer solstice, we also predicted that bat preference for closed canopies would decline by late summer. We monitored for bat presence with ultrasound detectors in 30 unlogged, beetle-affected stands and 60 small (〈30 ha) salvage-logged stands of variable retention. We used occupancy models to test predictions regarding bat response to logging and associated changes in forest structure at local and landscape scales. Contrary to our predictions, occupancy by little brown bats was generally higher in salvage-logged stands, although differences were not statistically significant. Bat occupancy declined with increasing tree basal area, particularly during the second half of the summer when bats avoided forest stands with basal area 〉40 m〈sup〉2〈/sup〉/ha. Our results suggest that vegetative clutter was a primary constraint for little brown bats. The observed clutter avoidance in late summer may have been caused by the presence of newly volant juveniles, which are not yet proficient at flying in clutter. In addition, bats may have shifted their preference to open habitats during late summer when nights were longer and darker, and perceived predation risk was likely reduced. Our study suggests that small patches of salvage-logged boreal forest may improve foraging habitat for little brown bats through clutter reduction; however, we caution that interpretation of our results should be limited to the tree retention levels and scale of logging at our sites. Additionally, the potential importance of unlogged areas as roosting habitat requires consideration before prescriptions are made on the proportion of the landscape to be salvage-logged.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 451〈/p〉 〈p〉Author(s): Chun Han, Ning Chen, Cankun Zhang, Yongjing Liu, Salman Khan, Kanglong Lu, Yage Li, Xiaoxue Dong, Changming Zhao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The transpiration of trees plays a decisive role in the water balance of forest stands and in water yields from forested catchments, especially an artificial forest planted for the purpose of soil and water conservation in semiarid mountain ecosystem regions. For proper management of watershed ecosystems, quantification of water use, sensitivity and adaptation for artificial forest is needed. This study were monitored the sap flow for 〈em〉Larix principis-rupprechtii〈/em〉 plantation by thermal dissipation probes (TDP), analyzed the correlation between the sap flow and the meteorological factors on daily and seasonal scale, and upscaled stand transpiration from individual sap flow measurements. Within a daily timescale, the net radiation (〈em〉Ra〈/em〉), air temperature (〈em〉AT〈/em〉), air humidity (〈em〉AH〈/em〉), vapor pressure deficit (〈em〉VPD〈/em〉) and wind speed (〈em〉WS〈/em〉) showed a significantly positive correlation with sap flow velocity in day-time, but in the night-time sap flow had no significant correlation. Within a monthly timescale, the 〈em〉Ra〈/em〉, 〈em〉AT〈/em〉, 〈em〉WS〈/em〉, and 〈em〉VPD〈/em〉 showed a significantly positive correlation with stand water use, whereas precipitation (〈em〉Pr〈/em〉) showed a significantly negative correlation with stand water use. Our results also showed that the daily transpiration of 〈em〉L. principis-rupprechtii〈/em〉 continued to increase with the increase of net radiation (〈em〉Ra〈/em〉), until the late stages of growth season (except rainy and cloudy days), and the sap flow velocity showed an obvious hysteresis response to meteorological factors to alleviate plant water stress from June to October, while there was no significant correlation between day-time and night-time water use during the stage of germination and rapid growth in May. Besides, due to the relatively low temperature, the water consumption of forest stands was only about 151.05 mm during the whole growing season, and there was no obvious ‘noon break’ phenomenon in the whole growing season. These results indicated that 〈em〉L. principis-rupprechtii〈/em〉 could manage the water consumption conservatively, and were appropriate for afforestation in the mountains ecosystem with high altitude and low temperature.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Hui-Ying Lim, Hong Bao, Ying Liu, Weidong Wang〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Septate junction (SJ) complex proteins act in unison to provide a paracellular barrier and maintain structural integrity. Here, we identify a non-barrier role of two individual SJ proteins, Coracle (Cora) and Kune-kune (Kune). Reactive oxygen species (ROS)-p38 MAPK signaling in non-myocytic pericardial cells (PCs) is important for maintaining normal cardiac physiology in 〈em〉Drosophila〈/em〉. However, the underlying mechanisms remain unknown. We find that in PCs, Cora and Kune are altered in abundance in response to manipulations of ROS-p38 signaling. Genetic analyses establish Cora and Kune as key effectors of ROS-p38 signaling in PCs on proper heart function. We further determine that Cora regulates normal Kune levels in PCs, which in turn modulates normal Kune levels in the cardiomyocytes essential for proper heart function. Our results thereby reveal select SJ proteins Cora and Kune as signaling mediators of the PC-derived ROS regulation of cardiac physiology.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719308885-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Irene Salas-Armenteros, Sonia I. Barroso, Ana G. Rondón, Mónica Pérez, Eloisa Andújar, Rosa Luna, Andrés Aguilera〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉THO/TREX is a conserved complex with a role in messenger ribonucleoprotein biogenesis that links gene expression and genome instability. Here, we show that human THO interacts with MFAP1 (microfibrillar-associated protein 1), a spliceosome-associated factor. Interestingly, MFAP1 depletion impairs cell proliferation and genome integrity, increasing γH2AX foci and DNA breaks. This phenotype is not dependent on either transcription or RNA-DNA hybrids. Mutations in the yeast orthologous gene 〈em〉SPP381〈/em〉 cause similar transcription-independent genome instability, supporting a conserved role. MFAP1 depletion has a wide effect on splicing and gene expression in human cells, determined by transcriptome analyses. MFAP1 depletion affects a number of DNA damage response (DDR) genes, which supports an indirect role of MFAP1 on genome integrity. Our work defines a functional interaction between THO and RNA processing and argues that splicing factors may contribute to genome integrity indirectly by regulating the expression of DDR genes rather than by a direct role.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309003-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Preston D. Crowell, Jonathan J. Fox, Takao Hashimoto, Johnny A. Diaz, Héctor I. Navarro, Gervaise H. Henry, Blake A. Feldmar, Matthew G. Lowe, Alejandro J. Garcia, Ye E. Wu, Dipti P. Sajed, Douglas W. Strand, Andrew S. Goldstein〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Aging is associated with loss of tissue mass and a decline in adult stem cell function in many tissues. In contrast, aging in the prostate is associated with growth-related diseases including benign prostatic hyperplasia (BPH). Surprisingly, the effects of aging on prostate epithelial cells have not been established. Here we find that organoid-forming progenitor activity of mouse prostate basal and luminal cells is maintained with age. This is caused by an age-related expansion of progenitor-like luminal cells that share features with human prostate luminal progenitor cells. The increase in luminal progenitor cells may contribute to greater risk for growth-related disease in the aging prostate. Importantly, we demonstrate expansion of human luminal progenitor cells in BPH. In summary, we define a Trop2〈sup〉+〈/sup〉 luminal progenitor subset and identify an age-related shift in the luminal compartment of the mouse and human prostate epithelium.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719308976-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Elvis Felipe Elli, Paulo Cesar Sentelhas, Cleverson Henrique de Freitas, Rafaela Lorenzato Carneiro, Clayton Alcarde Alvares〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Eucalyptus〈/em〉 process-based models are the most promising tools available for assisting foresters and companies in the pursuit of appropriate planning, long-term management and for assessing the impact of climate variability and change on the forest sector. Reducing errors of 〈em〉Eucalyptus〈/em〉 yield simulations is of high importance since it increases the accuracy and credibility of decision making in forest systems. Furthermore, information on ensemble approach for 〈em〉Eucalyptus〈/em〉 yield estimations is still scarce. The aims of this study were: to calibrate and evaluate the performance (goodness-of-fit) of the FAO, APSIM and 3PG models for different major Brazilian 〈em〉Eucalyptus〈/em〉 clones; to perform an intercomparison of the structural features of 〈em〉Eucalyptus〈/em〉 simulation models; and to assess the performance of an ensemble approach of these models. To these ends, experimental yield data from 2012 to 2017 from eight 〈em〉Eucalyptus〈/em〉 clones distributed over 23 locations with several and contrasting environmental conditions in Brazil were used. During the evaluation phase, the R〈sup〉2〈/sup〉 ranged from 0.81 to 0.88, the modelling efficiency index (E) ranged from 0.75 to 0.81 and the root mean square error (RMSE) ranged from 37.1 to 42.3 m〈sup〉3〈/sup〉 ha〈sup〉−1〈/sup〉, when the models were individually assessed. The multimodel ensemble approach improved the performance of 〈em〉Eucalyptus〈/em〉 yield estimations, with higher R〈sup〉2〈/sup〉 (0.89), E (0.85) and lower RMSE (33.1 m〈sup〉3〈/sup〉 ha〈sup〉−1〈/sup〉), compared to the individual performance of the models. Forest simulation models were able to estimate 〈em〉Eucalyptus〈/em〉 yield across a wide range of climates and soil types when properly calibrated. The use of a multimodel ensemble reduced the errors of 〈em〉Eucalyptus〈/em〉 yield estimations.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Maite Lascurain-Rangel, Guillermo Rodríguez-Rivas, Jorge Antonio Gómez-Díaz, José Luis Alvarez-Palacios, Griselda Benitez-Badillo, Citlalli López-Binnquist, Raymundo Dávalos-Sotelo, Juan Carlos López-Acosta〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The use of non-timber forest products forms part of the strategy contributing to the well-being of populations near forest areas. 〈em〉Chamaedorea〈/em〉 is one of the most important palm genera that is globally commercialized profitably for its attractive foliage used in floral decorations. In our study area located in the central region of Veracruz, Mexico we identified changes in tree cover between 1973 and 2017 using the normalized difference vegetation index (NDVI). We conducted plant surveys to identify tree species richness associated with the cultivation of 〈em〉C. elegans.〈/em〉 We conducted semi-structured interviews with local palm producers to understand their perceptions regarding changes in tree cover in the study area and its association with the presence of the camedor palm. Soil cover patterns and vegetation index signatures indicated an increase in the forested area from 1973 to 2017 (after more than 43 years), with a 69% gain in secondary vegetation coverage with low NDVI values. This increase is associated with the cultivation of palm, since arboreal cover had previously been dominated by species traditionally used as shade for camedor cultivation. Tree diameters at breast height (DBH) were low, indicating young secondary forests with low recruitment and diversity in the understory suggestive of simplified species assemblages; most of the associated species were long-living pioneers and typical of the secondary forest favored by the palm producers. Producers mentioned they did not remove coffee because it is their main means of subsistence, and in combination with the palm, there is greater economic benefit. They also confirmed an increase in forest cover owing to the introduction of palm cultivars in the areas north and south of the study area. This was confirmed with the NDVI results, which detected the same spatial pattern. These changes resulted in the interruption of the processes of succession without the transition of secondary to old-growth forests. However, the canopy of the study area provides better environmental services than did the previously existing vegetation cover. This study showed the need for the assessment of non-timber forest products as key indicators of land use change and alterations in associated plant cover.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Martin Beland, Geoffrey Parker, Ben Sparrow, David Harding, Laura Chasmer, Stuart Phinn, Alexander Antonarakis, Alan Strahler〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Forest structure is an important driver of ecosystem dynamics, including the exchange of carbon, water and energy between canopies and the atmosphere. Structural descriptors are also used in numerous studies of ecological processes and ecosystem services. Over the last 20+ years, lidar technology has fundamentally changed the way we observe and describe forest structure, and it will continue to impact the ways in which we investigate and monitor the relations between forest structure and functions. Here we present the currently available lidar system types (ground, air, and space-based), we highlight opportunities and challenges associated with each system, as well as challenges associated with a wider use of lidar technology and wider availability of lidar derived products. We also suggest pathways for lidar to further contribute to addressing questions in forest ecosystem science and increase benefits to a wider community of researchers.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Jose M. Iniguez, James F. Fowler, W. Keith Moser, Carolyn H. Sieg, L. Scott Baggett, Patrick Shin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Forest spatial patterns influence many ecological processes in dry conifer forests. Thus, understanding and replicating spatial patterns is critically important in order to make these forests sustainable and more resilient to fire and other disturbances. The labor and time required to stem-map trees and the large plot size (〉0.5 ha) needed to study tree spatial patterns have limited our examination of how these patterns change as a function of site conditions and tree densities. We stem-mapped all trees 〉40 cm DBH within two large relict (minimally logged) pure ponderosa pine study sites on experimental forests at Long Valley (73 ha) on sedimentary soils and Fort Valley (32 ha) on basalt soils in northern Arizona, USA. We also simulated 1,000 4-ha plots from models of each study site incorporating field data parameters. Using cluster analysis and field data, we found that an inter-tree distance (ITD) of 9–11 m best separated single trees and groups within our study sites. Using a fixed 10-m ITD, the more productive Long Valley (LV) site had 62 trees ha〈sup〉−1〈/sup〉 and groups of up to 113 trees, compared to the Fort Valley (FV) site, which averaged 41 trees ha〈sup〉−1〈/sup〉 and had 22 trees in the largest group. However, the sites differed only slightly in terms of single trees ha〈sup〉−1〈/sup〉 (LV 7.3; FV 5.6) and group of tree ha〈sup〉−1〈/sup〉 (LV 7.2; FV 8.1). Simulation results indicated that when tree densities are equal, the spatial patterns were very similar between the two sites, suggesting that tree spatial pattern variability is a function of tree densities and only indirectly related to site productivity. As the number of trees increased, the additional trees integrated into existing groups rather than creating new groups. In addition to tree spatial patterns, we quantified gaps (defined as 〉30 m wide stem-to-stem) and openings (defined as ≥30 m wide stem-to-stem) within the two study sites. Although both sites were dominated by small openings most of the open area was found within a few large openings. Our large plots allowed us to incorporate variability and capture a larger range of tree and openings spatial patterns than have been captured in previous studies to provide insights on spatial heterogeneity that can inform management of this important forest type in North America.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Caroline C. Nóbrega, Paulo M. Brando, Divino V. Silvério, Leandro Maracahipes, Paulo de Marco〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Although tropical forest fires are naturally rare, they have become more frequent and intense in response to recent changes in land use and climate. This shift in fire regime may drive widespread forest degradation in Amazonia, with important consequences not only for species richness but also for functional and phylogenetic diversity. Here, we test the overall hypothesis that fire-induced tree mortality causes more losses in phylogenetic and functional diversity than in taxonomic diversity, because fire kills trees non-randomly. To test this hypothesis, we established a large-scale, long-term (nine-year) fire experiment in southeast Amazonia in three 50-ha plots, with unburned Control and two different fire regimes (burned annually and burned every three years), between 2004 and 2010. Overall, tree assemblages exposed to experimental fires lost more phylogenetic and functional diversity compared to unburned areas, especially where the experimental fires were more intense (in areas burned every three years). The rate of loss of phylogenetic and functional diversity per species-unit was higher for larger trees than for small ones, which indicates that fire-induced mortality is more random for small trees. Our results indicate that fire acts as a selective pressure, filtering species with similar phylogenetic and functional traits. Given that forest fires are likely to become more common and frequent in the region, it is essential to understand their impact above and beyond taxonomic diversity.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Yu Zhu, Zhili Liu, Guangze Jin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In forests, tree mortality strongly determines forest dynamics, creates gaps for recruitment and contributes to the coexistence of tree species. Individual-based models (IBMs) of tree mortality are key submodels in forest gap models and have been shown to drive simulated long-term forest dynamics. However, tree mortality IBMs remain poorly evaluated at the stand scale, particularly quantitatively, due to the lack of adequate tree mortality demographic data. Tree mortality dynamic data have often been absent from previous mortality IBMs, resulting in difficulty during model evaluation at the stand scale. The goals of this study were (1) to develop a spatially-explicit tree mortality IBM derived from the FORSKA forest gap model and (2) to evaluate its performance by both qualitative and quantitative fits based on a 10-year interval of tree mortality demographic data under a 9-ha forest dynamics plot (FDP) in an old-growth temperate forest in Northeast China. The results showed that, for model qualitative evaluation, the observed dead trees were mainly distributed in the southwest and northeast parts, but the predicted dead trees were centrally clustered only in the southwest part of the FDP. For model quantitative evaluation, the overall model error (〈em〉Error〈/em〉 (%)) for all trees was −10.5%. However, the absolute values of model error for some species (i.e., 〈em〉Acer〈/em〉 spp., 〈em〉Betula〈/em〉 spp., 〈em〉Tilia〈/em〉 spp., 〈em〉Fraxinus mandschurica〈/em〉, and 〈em〉Ulmus〈/em〉 spp.) and some diameter at breast height (DBH) classes (i.e., 30–40, 40–50, 50–60, 60–70, and ≥70 cm) were greater than or equal to 20%. Our study highlights that the tree mortality IBM at the stand scale still requires further improvement to enhance the model performance and that the FDPs could provide crucial data support for initialization, parameterization and evaluation in the tree mortality IBM at the stand scale in forest dynamic modeling.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 9〈/p〉 〈p〉Author(s): Pei-Tzu Huang, Brady James Summers, Chaoyi Xu, Juan R. Perilla, Viacheslav Malikov, Mojgan H. Naghavi, Yong Xiong〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉HIV-1 uses the microtubule network to traffic the viral capsid core toward the nucleus. Viral nuclear trafficking and infectivity require the kinesin-1 adaptor protein FEZ1. Here, we demonstrate that FEZ1 directly interacts with the HIV-1 capsid and specifically binds capsid protein (CA) hexamers. FEZ1 contains multiple acidic, poly-glutamate stretches that interact with the positively charged central pore of CA hexamers. The FEZ1-capsid interaction directly competes with nucleotides and inositol hexaphosphate (IP6) that bind at the same location. In addition, all-atom molecular dynamic (MD) simulations establish the molecular details of FEZ1-capsid interactions. Functionally, mutation of the FEZ1 capsid-interacting residues significantly reduces trafficking of HIV-1 particles toward the nucleus and early infection. These findings support a model in which the central capsid hexamer pore is a general HIV-1 cofactor-binding hub and FEZ1 serves as a unique CA hexamer pattern sensor to recognize this site and promote capsid trafficking in the cell.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309830-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Amania A. Sheikh, Lucy Cooper, Meiqi Feng, Fernando Souza-Fonseca-Guimaraes, Fanny Lafouresse, Brigette C. Duckworth, Nicholas D. Huntington, James J. Moon, Marc Pellegrini, Stephen L. Nutt, Gabrielle T. Belz, Kim L. Good-Jacobson, Joanna R. Groom〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Following infection, inflammatory cues upregulate core transcriptional programs to establish pathogen-specific protection. In viral infections, T follicular helper (TFH) cells express the prototypical T helper 1 transcription factor T-bet. Several studies have demonstrated essential but conflicting roles for T-bet in TFH biology. Understanding the basis of this controversy is crucial, as modulation of T-bet expression instructs TFH differentiation and ultimately protective antibody responses. Comparing influenza and LCMV viral infections, we demonstrate that the role of T-bet is contingent on the environmental setting of TFH differentiation, IL-2 signaling, and T cell competition. Furthermore, we demonstrate that T-bet expression by either TFH or GC B cells independently drives antibody isotype class switching. Specifically, T cell-specific loss of T-bet promotes IgG1, whereas B cell-specific loss of T-bet inhibits IgG2a/c switching. Combined, this work highlights that the context-dependent induction of T-bet instructs the development of protective, neutralizing antibodies following viral infection or vaccination.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309313-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Lucio M. Schiapparelli, Sahil H. Shah, Yuanhui Ma, Daniel B. McClatchy, Pranav Sharma, Jianli Li, John R. Yates, Jeffrey L. Goldberg, Hollis T. Cline〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉The brain processes information and generates cognitive and motor outputs through functions of spatially organized proteins in different types of neurons. More complete knowledge of proteins and their distributions within neuronal compartments in intact circuits would help in the understanding of brain function. We used unbiased 〈em〉in vivo〈/em〉 protein labeling with intravitreal NHS-biotin for discovery and analysis of endogenous axonally transported proteins in the visual system using tandem mass spectrometric proteomics, biochemistry, and both light and electron microscopy. Purification and proteomic analysis of biotinylated peptides identified ∼1,000 proteins transported from retinal ganglion cells into the optic nerve and ∼575 biotinylated proteins recovered from presynaptic compartments of lateral geniculate nucleus and superior colliculus. Approximately 360 biotinylated proteins were differentially detected in the two retinal targets. This study characterizes axonally transported proteins in the healthy adult visual system by analyzing proteomes from multiple compartments of retinal ganglion cell projections in the intact brain.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309349-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Paramita Chakraborty, Silvia G. Vaena, Krishnamurthy Thyagarajan, Shilpak Chatterjee, Amir Al-Khami, Shanmugam Panneer Selvam, Hung Nguyen, Inhong Kang, Megan W. Wyatt, Uday Baliga, Zachariah Hedley, Rose N. Ngang, Beichu Guo, Gyda C. Beeson, Shahid Husain, Chrystal M. Paulos, Craig C. Beeson, Michael J. Zilliox, Elizabeth G. Hill, Meenal Mehrotra〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Sphingosine 1-phosphate (S1P), a bioactive lysophospholipid generated by sphingosine kinase 1 (SphK1), regulates lymphocyte egress into circulation via S1P receptor 1 (S1PR1) signaling, and it controls the differentiation of regulatory T cells (Tregs) and T helper-17 cells. However, the mechanisms by which receptor-independent SphK1-mediated intracellular S1P levels modulate T cell functionality remains unknown. We show here that SphK1-deficient T cells maintain central memory phenotype and exhibit higher mitochondrial respiration and reduced differentiation to Tregs. Mechanistically, we discovered a direct correlation between SphK1-generated S1P and lipid transcription factor PPARγ (peroxisome proliferator-activated receptor gamma) activity, which in turn regulates lipolysis in T cells. Genetic and pharmacologic inhibition of SphK1 improved metabolic fitness and anti-tumor activity of T cells against murine melanoma. Further, inhibition of SphK1 and PD1 together led to improved control of melanoma. Overall, these data highlight the clinical potential of limiting SphK1/S1P signaling for enhancing anti-tumor-adoptive T cell therapy.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309416-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Stéphane G. Rolland, Sandra Schneid, Melanie Schwarz, Elisabeth Rackles, Christian Fischer, Simon Haeussler, Saroj G. Regmi, Assa Yeroslaviz, Bianca Habermann, Dejana Mokranjac, Eric Lambie, Barbara Conradt〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉The induction of the mitochondrial unfolded protein response (UPR〈sup〉mt〈/sup〉) results in increased transcription of the gene encoding the mitochondrial chaperone HSP70. We systematically screened the 〈em〉C. elegans〈/em〉 genome and identified 171 genes that, when knocked down, induce the expression of an 〈em〉hsp-6〈/em〉 HSP70 reporter and encode mitochondrial proteins. These genes represent many, but not all, mitochondrial processes (e.g., mitochondrial calcium homeostasis and mitophagy are not represented). Knockdown of these genes leads to reduced mitochondrial membrane potential and, hence, decreased protein import into mitochondria. In addition, it induces UPR〈sup〉mt〈/sup〉 in a manner that is dependent on ATFS-1 but that is not antagonized by the kinase GCN-2. We propose that compromised mitochondrial protein import signals the induction of UPR〈sup〉mt〈/sup〉 and that the mitochondrial targeting sequence of ATFS-1 functions as a sensor for this signal.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309532-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Maria Vono, Christiane Sigrid Eberhardt, Floriane Auderset, Beatris Mastelic-Gavillet, Sylvain Lemeille, Dennis Christensen, Peter Andersen, Paul-Henri Lambert, Claire-Anne Siegrist〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Maternal antibodies (MatAbs) protect offspring from infections but limit their responses to vaccination. The mechanisms of this inhibition are still debated. Using murine early-life immunization models mimicking the condition prevailing in humans, we observed the induction of CD4-T, T follicular helper, and germinal center (GC) B cell responses even when early-life antibody responses were abrogated by MatAbs. GC B cells induced in the presence of MatAbs form GC structures and exhibit canonical GC changes in gene expression but fail to differentiate into plasma cells and/or memory B cells in a MatAb titer-dependent manner. Furthermore, GC B cells elicited in the presence or absence of MatAbs use different V〈sub〉H〈/sub〉 and V〈sub〉k〈/sub〉 genes and show differences in genes associated with B cell differentiation and isotype switching. Thus, MatAbs do not prevent B cell activation but control the output of the GC reaction both quantitatively and qualitatively, shaping the antigen-specific B cell repertoire.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309519-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Stephanie A. Campbell, Cassandra L. McDonald, Nicole A.J. Krentz, Francis C. Lynn, Brad G. Hoffman〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Appropriate regulation of genes that coordinate pancreas progenitor proliferation and differentiation is required for pancreas development. Here, we explore the role of H3K4 methylation and the Trithorax group (TrxG) complexes in mediating gene expression during pancreas development. Disruption of TrxG complex assembly, but not catalytic activity, prevented endocrine cell differentiation in pancreas progenitor spheroids. 〈em〉In vivo〈/em〉 loss of TrxG catalytic activity in PDX1〈sup〉+〈/sup〉 cells increased apoptosis and the fraction of progenitors in the G1 phase of the cell cycle. Pancreas progenitors were reallocated to the acinar lineage, primarily at the expense of NEUROG3〈sup〉+〈/sup〉 endocrine progenitors. Later in development, acinar and endocrine cell numbers were decreased, and increased gene expression variance and reduced terminal marker activation in acinar cells led to their incomplete differentiation. These findings demonstrate that TrxG co-activator activity is required for gene induction, whereas TrxG catalytic activity and H3K4 methylation help maintain transcriptional stability.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309325-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 7〈/p〉 〈p〉Author(s): Kari-Anne M. Frikstad, Elisa Molinari, Marianne Thoresen, Simon A. Ramsbottom, Frances Hughes, Stef J.F. Letteboer, Sania Gilani, Kay O. Schink, Trond Stokke, Stefan Geimer, Lotte B. Pedersen, Rachel H. Giles, Anna Akhmanova, Ronald Roepman, John A. Sayer, Sebastian Patzke〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉CEP104 is an evolutionarily conserved centrosomal and ciliary tip protein. 〈em〉CEP104〈/em〉 loss-of-function mutations are reported in patients with Joubert syndrome, but their function in the etiology of ciliopathies is poorly understood. Here, we show that 〈em〉cep104〈/em〉 silencing in zebrafish causes cilia-related manifestations: shortened cilia in Kupffer’s vesicle, heart laterality, and cranial nerve development defects. We show that another Joubert syndrome-associated cilia tip protein, CSPP1, interacts with CEP104 at microtubules for the regulation of axoneme length. We demonstrate in human telomerase reverse transcriptase-immortalized retinal pigmented epithelium (hTERT-RPE1) cells that ciliary translocation of Smoothened in response to Hedgehog pathway stimulation is both CEP104 and CSPP1 dependent. However, CEP104 is not required for the ciliary recruitment of CSPP1, indicating that an intra-ciliary CEP104-CSPP1 complex controls axoneme length and Hedgehog signaling competence. Our 〈em〉in vivo〈/em〉 and 〈em〉in vitro〈/em〉 analyses of CEP104 define its interaction with CSPP1 as a requirement for the formation of Hedgehog signaling-competent cilia, defects that underlie Joubert syndrome.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309222-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Forest Ecology and Management, Volume 450〈/p〉 〈p〉Author(s): Dehai Zhao, Bronson P. Bullock, Cristian R. Montes, Mingliang Wang, Dale Greene, Lori Sutter〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Loblolly pine (〈em〉Pinus taeda〈/em〉 L.) and slash pine (〈em〉Pinus elliottii〈/em〉 Engelm.) are the two most important commercial timber species in the southeastern U.S. A long-term experimental comparison study, in which loblolly and slash pine plots were paired for combinations of planting density (741, 2224, 3706 trees ha〈sup〉−1〈/sup〉) and cultural intensity (operational versus intensive), was established in the lower Coastal Plain to investigate species differences in growth dynamics. Using age 2–21-year inventory plot data and destructive biomass/nutrient sampling data, species comparisons were conducted comprehensively, and the reasons of the species differences and management implications were discussed. When compared to slash pine, loblolly pine had higher stand basal area carrying capacity and maximum stand density index, lower fusiform rust infection rate and less wind damage, leading to its lower mortality. With no species difference in average DBH, loblolly pine consistently had greater average height and live crown length and higher level of tree size inequality. Loblolly pine had lower foliar biomass and lower foliar density, and higher crown length/width ratios due primarily to its longer crowns, suggesting perhaps a slightly greater shade tolerance or less dense canopy. As a result, loblolly pine outperformed slash pine in terms of stand basal area, total volume, aboveground biomass and carbon accumulation. Loblolly pine consistently accumulated more potassium, and this species difference increased with increasing stand age; while slash pine had slightly higher nitrogen and phosphorus contents before age 12. Species differences in mortality patterns and in nutrient accumulations in aboveground biomass emphasized the need to develop species-specific management strategies including different thinning and fertilization regimes.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Hugues Petitjean, Farin B. Bourojeni, Deborah Tsao, Albena Davidova, Susana G. Sotocinal, Jeffrey S. Mogil, Artur Kania, Reza Sharif-Naeini〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉The dorsal horn of the spinal cord is the first integration site of somatosensory inputs from the periphery. In the superficial layers of the dorsal horn, nociceptive inputs are processed by a complex network of excitatory and inhibitory interneurons whose function and connectivity remain poorly understood. We examined the role of calretinin-expressing interneurons (CR neurons) in such processing and show that they receive direct inputs from nociceptive fibers and polysynaptic inputs from touch-sensitive Aβ fibers. Their activation by chemogenetic or optogenetic stimulation produces mechanical allodynia and nocifensive responses. Furthermore, they monosynaptically engage spinoparabrachial (SPb) neurons in lamina I, suggesting CR neurons modulate one of the major ascending pain pathways of the dorsal horn. In conclusion, we propose a neuronal pathway in which CR neurons are positioned at the junction between nociceptive and innocuous circuits and directly control SPb neurons in lamina I.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309520-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Yoshimasa Oyama, Colleen M. Bartman, Stephanie Bonney, J. Scott Lee, Lori A. Walker, Jun Han, Christoph H. Borchers, Peter M. Buttrick, Carol M. Aherne, Nathan Clendenen, Sean P. Colgan, Tobias Eckle〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Consistent daylight oscillations and abundant oxygen availability are fundamental to human health. Here, we investigate the intersection between light-sensing (Period 2 [PER2]) and oxygen-sensing (hypoxia-inducible factor [HIF1A]) pathways in cellular adaptation to myocardial ischemia. We demonstrate that intense light is cardioprotective via circadian PER2 amplitude enhancement, mimicking hypoxia-elicited adenosine- and HIF1A-metabolic adaptation to myocardial ischemia under normoxic conditions. Whole-genome array from intense light-exposed wild-type or 〈em〉Per2〈/em〉〈sup〉−/−〈/sup〉 mice and myocardial ischemia in endothelial-specific PER2-deficient mice uncover a critical role for intense light in maintaining endothelial barrier function via light-enhanced HIF1A transcription. A proteomics screen in human endothelia reveals a dominant role for PER2 in metabolic reprogramming to hypoxia via mitochondrial translocation, tricarboxylic acid (TCA) cycle enzyme activity regulation, and HIF1A transcriptional adaption to hypoxia. Translational investigation of intense light in human subjects identifies similar PER2 mechanisms, implicating the use of intense light for the treatment of cardiovascular disease.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309106-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Chiara Saponaro, Valéry Gmyr, Julien Thévenet, Ericka Moerman, Nathalie Delalleau, Gianni Pasquetti, Anais Coddeville, Audrey Quenon, Mehdi Daoudi, Thomas Hubert, Marie-Christine Vantyghem, Corinne Bousquet, Yvan Martineau, Julie Kerr-Conte, Bart Staels, François Pattou, Caroline Bonner〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉The newest classes of anti-diabetic agents include sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor (GLP1R) agonists. The SGLT2 inhibitor dapagliflozin reduces glucotoxicity by glycosuria but elevates glucagon secretion. The GLP1R agonist liraglutide inhibits glucagon; therefore, we hypothesize that the cotreatment of dapagliflozin with liraglutide could reduce hyperglucagonemia and hyperglycemia. Here we use five complementary models: human islet cultures, healthy mice, 〈em〉db/db〈/em〉 mice, diet-induced obese (DIO) mice, and somatostatin receptor-2 (SSTR2) KO mice. A single administration of liraglutide and dapagliflozin in combination improves glycemia and reduces dapagliflozin-induced glucagon secretion in diabetic mice. Chronic treatment with liraglutide and dapagliflozin produces a sustainable reduction of glycemia compared with each drug alone. Moreover, liraglutide reduces dapagliflozin-induced glucagon secretion by enhancing somatostatin release, as demonstrated by SSTR2 inhibition in human islets and in mice. Collectively, these data provide mechanistic insights into how intra-islet GLP1R activation is critical for the regulation of glucose homeostasis.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S221112471930899X-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Jie Su, Dandan Zhu, Zijun Huo, Julian A. Gingold, Yen-Sin Ang, Jian Tu, Ruoji Zhou, Yu Lin, Haidan Luo, Huiling Yang, Ruiying Zhao, Christoph Schaniel, Kateri A. Moore, Ihor R. Lemischka, Dung-Fang Lee〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉A multitude of signals are coordinated to maintain self-renewal in embryonic stem cells (ESCs). To unravel the essential internal and external signals required for sustaining the ESC state, we expand upon a set of ESC pluripotency-associated phosphoregulators (PRs) identified previously by short hairpin RNA (shRNA) screening. In addition to the previously described Aurka, we identify 4 additional PRs (Bub1b, Chek1, Ppm1g, and Ppp2r1b) whose depletion compromises self-renewal and leads to consequent differentiation. Global gene expression profiling and computational analyses reveal that knockdown of the 5 PRs leads to DNA damage/genome instability, activating p53 and culminating in ESC differentiation. Similarly, depletion of genome integrity-associated genes involved in DNA replication and checkpoint, mRNA processing, and Charcot-Marie-Tooth disease lead to compromise of ESC self-renewal via an increase in p53 activity. Our studies demonstrate an essential link between genomic integrity and developmental cell fate regulation in ESCs.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309015-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Ana Uzquiano, Carmen Cifuentes-Diaz, Ammar Jabali, Delfina M. Romero, Anne Houllier, Florent Dingli, Camille Maillard, Anne Boland, Jean-François Deleuze, Damarys Loew, Grazia M.S. Mancini, Nadia Bahi-Buisson, Julia Ladewig, Fiona Francis〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Apical radial glia (aRGs) are predominant progenitors during corticogenesis. Perturbing their function leads to cortical malformations, including subcortical heterotopia (SH), characterized by the presence of neurons below the cortex. 〈em〉EML1〈/em〉/〈em〉Eml1〈/em〉 mutations lead to SH in patients, as well as to heterotopic cortex (〈em〉HeCo〈/em〉) mutant mice. In 〈em〉HeCo〈/em〉 mice, some aRGs are abnormally positioned away from the ventricular zone (VZ). Thus, unraveling EML1/Eml1 function will clarify mechanisms maintaining aRGs in the VZ. We pinpoint an unknown EML1/Eml1 function in primary cilium formation. In 〈em〉HeCo〈/em〉 aRGs, cilia are shorter, less numerous, and often found aberrantly oriented within vesicles. Patient fibroblasts and human cortical progenitors show similar defects. EML1 interacts with RPGRIP1L, a ciliary protein, and 〈em〉RPGRIP1L〈/em〉 mutations were revealed in a heterotopia patient. We also identify Golgi apparatus abnormalities in 〈em〉EML1〈/em〉/〈em〉Eml1〈/em〉 mutant cells, potentially upstream of the cilia phenotype. We thus reveal primary cilia mechanisms impacting aRG dynamics in physiological and pathological conditions.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719308824-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Keith Conrad Fernandez, Jayanta Chaudhuri〈/p〉 〈div〉〈p〉Sundaravinayagam et al. (2019) uncovered a critical role of 53BP1 in class switch recombination in B cells beyond its role in limiting end resection.〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Jaichandar Subramanian, Katrin Michel, Marc Benoit, Elly Nedivi〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉A key feature of brain plasticity is the experience-dependent selection of optimal connections, implemented by a set of activity-regulated genes that dynamically adjust synapse strength and number. The activity-regulated gene 〈em〉cpg15/neuritin〈/em〉 has been previously implicated in stabilization and maturation of excitatory synapses. Here, we combine two-photon microscopy with genetic and sensory manipulations to dissect excitatory synapse formation 〈em〉in vivo〈/em〉 and examine the role of activity and CPG15 in dendritic spine formation, PSD95 recruitment, and synapse stabilization. We find that neither visual experience nor CPG15 is required for spine formation. However, PSD95 recruitment to nascent spines and their subsequent stabilization requires both. Further, cell-autonomous CPG15 expression is sufficient to replace experience in facilitating PSD95 recruitment and spine stabilization. CPG15 directly interacts with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on immature dendritic spines, suggesting a signaling mode for this small extracellular molecule acting as an experience-dependent “selector” for spine stabilization and synapse maturation.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309027-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 6 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 6〈/p〉 〈p〉Author(s): Charles Hillier, Mercedes Pardo, Lu Yu, Ellen Bushell, Theo Sanderson, Tom Metcalf, Colin Herd, Burcu Anar, Julian C. Rayner, Oliver Billker, Jyoti S. Choudhary〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Malaria represents a major global health issue, and the identification of new intervention targets remains an urgent priority. This search is hampered by more than one-third of the genes of malaria-causing 〈em〉Plasmodium〈/em〉 parasites being uncharacterized. We report a large-scale protein interaction network in 〈em〉Plasmodium〈/em〉 schizonts, generated by combining blue native-polyacrylamide electrophoresis with quantitative mass spectrometry and machine learning. This integrative approach, spanning 3 species, identifies 〉20,000 putative protein interactions, organized into 600 protein clusters. We validate selected interactions, assigning functions in chromatin regulation to previously unannotated proteins and suggesting a role for an EELM2 domain-containing protein and a putative microrchidia protein as mechanistic links between AP2-domain transcription factors and epigenetic regulation. Our interactome represents a high-confidence map of the native organization of core cellular processes in 〈em〉Plasmodium〈/em〉 parasites. The network reveals putative functions for uncharacterized proteins, provides mechanistic and structural insight, and uncovers potential alternative therapeutic targets.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S221112471930909X-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉