ALBERT

Description: Secreted phosphoprotein 24 kDa (Spp24) is an apatite- and BMP/TGF-β cytokine-binding phosphoprotein found in serum and many tissues, including bone. N-terminally intact degradation products ranging in size from 14 kDa to 23 kDa have been found in bone. The cleavage sites in Spp24 that produce these short forms have not been definitively identified, and the biological activities and mechanisms of action of Spp24 and its degradation products have not been fully elucidated. We found that the C-terminus of Spp24 is labile to proteolysis by furin, kallikrein, lactoferrin, and trypsin, indicating that both extracellular and intracellular proteolytic events could account for the generation of biologically-active Spp18, Spp16, and Spp14. We determined the effects of these truncation products on kinase-mediated signal transduction, gene expression, and osteoblastic differentiation in W-20-17 bone marrow stromal cells cultured in basal or pro-osteogenic media. After culturing for five days, all forms inhibited BMP-2-stimulated osteoblastic differentiation, assessed as induction of alkaline phosphatase activity, in basal, but not pro-osteogenic media. After 10 days, they also inhibited BMP-2-stimulated mineral deposition in pro-osteogenic media. Spp24 had no effect on Erk1/2 phosphorylation, but Spp18 stimulated short-term Erk1/2, MEK 1/2, and p38 phosphorylation. Pertussis toxin and a MEK1/2 inhibitor ablated Spp18-stimulated Erk 1/2 phosphorylation, indicating a role for G i proteins and MEK1/2 in the Spp18-stimulated Erk1/2 phosphorylation cascade. Truncation products, but not full-length Spp24, stimulated RUNX2, ATF4, and CSF1 transcription. This suggests that Spp24 truncation products have effects on osteoblastic differentiation mediated by kinase pathways that are independent of exogenous BMP/TGF-β cytokines. This article is protected by copyright. All rights reserved

Description: Similar to phosphorylation, transient conjugation of ubiquitin to target proteins (ubiquitination) mediated by the concerted action of ubiquitin ligases and de-ubiquitinating enzymes (DUBs) can affect substrate function. As obligate intracellular parasites, viruses rely on different cellular pathways for their own replication and the well conserved ubiquitin conjugating/de-conjugating system is not an exception. Viruses not only usurp the host proteins involved in the ubiquitination/de-ubiquitination process, but they also encode their own ubiquitin ligases and DUBs. Here we report that an N-terminal variant of the herpes simplex virus (HSV) type-1 large tegument protein VP1/2 (VP1/2 1–767 ), encompassing an active DUB domain (herpesvirus tegument ubiquitin specific protease, htUSP), and TSG101, a component of the endosomal sorting complex required for transport (ESCRT)-I, functionally interact. In particular, VP1/2 1–767 modulates TSG101 ubiquitination and influences its intracellular distribution. Given the role played by the ESCRT machinery in crucial steps of both cellular pathways and viral life cycle, the identification of TSG101 as a cellular target for the HSV-1 specific de-ubiquitinating enzyme contributes to the clarification of the still under debate function of viral encoded DUBs highly conserved throughout the Herpesviridae family. This article is protected by copyright. All rights reserved

Description: Sarcopenia and osteoporosis have recently been noted for their relationship with locomotive syndrome and increased number of older people. Sarcopenia is defined by decreased muscle mass and impaired muscle function, which may be associated with frailty. Several clinical data have indicated that increased muscle mass is related to increased bone mass and reduced fracture risk. Genetic, endocrine and mechanical factors as well as inflammatory and nutritional states concurrently affect muscle tissues and bone metabolism. Several genes, including myostatin and α-actinin 3, have been shown in a genome-wide association study (GWAS) to be associated with both sarcopenia and osteoporosis. Vitamin D, growth hormone and testosterone as well as pathological disorders, such as an excess in glucocorticoid and diabetes, affect both muscle and bone. Basic and clinical research of bone metabolism and muscle biology suggests that bone interacts with skeletal muscle via signaling from local and humoral factors in addition to their musculoskeletal function. However, the physiological and pathological mechanisms related to muscle and bone interactions remain unclear. We found that Tmem119 may play a critical role in the commitment of myoprogenitor cells to the osteoblast lineage. We also reported that osteoglycin and FAM5C might be muscle-derived humoral osteogenic factors. Other factors, including myostatin, osteonectin, insulin-like growth factor I, irisin and osteocalcin, may be associated with the interactions between muscle tissues and bone metabolism. This article is protected by copyright. All rights reserved

Description: The transition to a pathological phenotype such as Barrett's esophagus occurs via induction of resistance upon repeated contact with gastric refluxate in esophagus. This study examined the molecular changes within normal esophageal epithelial cells (EECs) under short-term acid loading and the role of these changes in defensive resistance against acidic cytotoxicity. After primary cultured EECs were exposed to pH 4-acidified medium (AM4), cell viability was determined by the MTT assay. Reactive oxygen species (ROS) and NAD(P)H oxidase (NOX) activity were measured. Activation of the mitogen-activated protein kinases (MAPKs) MEK/ERK1/2, p38 and JNK; phosphoinositol-3-kinase (PI3K)/Akt, and nuclear factor-kappa B (NF-κB) were detected by Western blot analysis or immunofluorescence staining. AM4 incubation induced intracellular ROS generation accompanied by increase in NOX activity, which was further increased by Na + /H + exchange-1 (NHE1)-dependent inhibition but was prevented by inhibition of NOX or mitochondria complex I. AM4 also induced phosphorylation of MEK/ERK1/2, p38 MAPK, PI3K/Akt, and nuclear translocation of NF-κB, and all these effects, except for p38 MAPK phosphorylation, were abolished by inhibition of ROS. ROS-dependent PI3K/Akt activation, which mediates NF-κB nuclear translocation, was inhibited by protein tyrosine kinase (PTK) inhibitors and NHE1-specific inhibitor. All inhibitors of NHE, ROS, PTK, PI3K or NF-κB further decreased AM4-induced cell viability. Acid loading in the presence of NHE1-dependent protection induced ROS generation by activating NOX and mitochondria complex I, which stimulated PTK/PI3K/Akt/NF-κB-dependent survival in EEC. Our data indicate that normal EEC initially respond to acid loading through intrinsic survival activation. This article is protected by copyright. All rights reserved

Description: Key Points Net COS production in wheat field soil and roots scaled linearly by temperature Sterilized wheat field soil demonstrated abiotic COS production mechanism Lab observations of COS fluxes from soil confirmed previous field measurements

Description: The CRIPSR-Cas9 system consists of a site-specific, targetable DNA nuclease that holds great potential in gene editing and genome-wide screening applications. In order to apply the CRISPR-Cas9 system to these assays successfully, the rate at which Cas9 induces DNA breaks at undesired loci must be understood. We characterised the rate of Cas9 off-target activity in typical Cas9 experiments in two human and one mouse cell lines. We analysed the Cas9 cutting activity of 12 gRNAs in both their targeted sites and ∼90 predicted off-target sites per gRNA. In a Cas9-based knock-out experiment, gRNAs induced detectable Cas9 cutting activity in all on-target sites and in only a few off-target sites genome-wide in human 293FT, human iPS cells and mouse ES cells. Both the cutting rates and DNA repair patterns were highly correlated between the two human cell lines in both on-target and off-target sites. In clonal Cas9 cutting analysis in mouse ES cells, bi-allelic Cas9 cutting was observed with low off-target activity. Our results show that off-target activity of Cas9 is low and predictable by the degree of sequence identity between the gRNA and a potential off-target site. Off-target Cas9 activity can be minimized by selecting gRNAs with few off-target sites of near-complementarity. genesis 00:00–00, 2014. © 2014 Wiley Periodicals, Inc.

Description: In this study we first present updated riverine total alkalinity (TA) loads to the various Baltic Sea sub-basins, based on monthly measurements in 82 of the major rivers that represent 85% of the total runoff. Simulations in the coupled physical-biogeochemical BALTSEM model show that these river loads together with North Sea water inflows are not sufficient to reproduce observed TA concentrations in the system, demonstrating the large influence from internal sources. Budget calculations indicate that the required internal TA generation must be similar to river loads in magnitude. The non-riverine source in the system amounts to about 2.4 mmol m -2 d -1 on average. We argue here that the majority of this source is related to denitrification together with unresolved sediment processes such as burial of reduced sulfur and/or silicate weathering. This hypothesis is supported by studies on sediment processes on a global scale, and also by data from sediment cores in the Baltic Sea. In a model simulation with all internal TA sources and sinks switched on, the net absorption of atmospheric CO 2 increased by 0.78 mol C m -2 y -1 compared to a simulation where TA was treated as a passive tracer. Our results clearly illustrate how pelagic TA sources together with anaerobic mineralization in coastal sediments generate a significant carbon sink along the aquatic continuum, mitigating CO 2 evasions from coastal and estuarine systems.

Description: ABSTRACT The recent advances on ascidian pigment sensory organ development and function represent a fascinating platform to get insight on the basic programs of chordate eye formation. This review aims to summarize current knowledge, at the structural and molecular levels, on the two main building blocks of ascidian light sensory organs, i.e . pigment cells and photoreceptor cells. The unique features of these structures (e.g. simplicity and well characterized cell lineage) are indeed making it possible to dissect the developmental programs at single cell resolution and will soon provide a panel of molecular tools to be exploited for a deep developmental and comparative-evolutionary analysis. © 2014 Wiley Periodicals, Inc.

Description: Dynamic interactions with DNA allow replication protein A to direct single-stranded DNA-intermediates into different pathways for synthesis or repair. On pages 1156–1161 , Chen and Wold review recent discoveries that show that replication protein A (RPA), the major eukaryotic single-stranded DNA-binding protein, binds DNA dynamically and that this is important for correct processing of DNA intermediates. The cover shows a model of human RPA interacting with ssDNA based on the known structures of the domains of human RPA and the structure of Ustalago RPA bound to DNA. The three subunits of RPA are shown in blue (RPA1), red (RPA2), and green (RPA3) with ssDNA shown in black.

Description: The aim of this study was to investigate the involvement of exchange proteins directly activated by cyclic adenosine (ADO) monophosphate (EPAC) in 4-mer hyaluronan (HA) oligosaccharide-induced inflammatory response in mouse normal synovial fibroblasts (NSF). Treatment of NSF with 4-mer HA increased Toll-like receptor-4, TNF-alpha and IL-1beta mRNA expression and of the related proteins, as well as nuclear factor kappaB (NF-kB) activation. Addition to NSF, previously stimulated with 4-mer HA oligosaccharides, of ADO significantly reduced NF-kB activation, TNF-alpha and IL-1beta expression. The pre-treatment of NSF with cyclic ADO monophosphate and/or PKA and/or EPAC-specific inhibitors significantly inhibited the anti-inflammatory effect exerted by ADO. In particular, the EPAC inhibitor reduced the ADO effect to a major extent than the PKA inhibitor. These results mean that both PKA and EPAC pathways are involved in ADO-induced NF-kB inhibition although EPAC seems to be more involved than PKA. Copyright © 2014 John Wiley & Sons, Ltd.

Description: Temporally controlled induction of gene expression is a useful technique for analyzing gene function. To make such a technique possible in Ciona intestinalis embryos, we employed the cis -regulatory region of the heat-shock protein 70 (HSP70) gene Ci-HSPA1/6/7-like for heat-inducible gene expression in C. intestinalis embryos. We showed that Ci-HSPA1/6/7-like becomes heat shock-inducible by the 32-cell stage during embryogenesis. The 5'-upstream region of Ci-HSPA1/6/7-like , which contains heat-shock elements indispensable for heat-inducible gene expression, induces the heat shock-dependent expression of a reporter gene in the whole embryo from the 32-cell to the middle gastrula stages and in progressively restricted areas of embryos in subsequent stages. We assessed the effects of heat-shock treatments in different conditions on the normality of embryos and induction of transgene expression. We evaluated the usefulness of this technique through overexpression experiments on the well-characterized, developmentally relevant gene, Ci-Bra , and showed that this technique is applicable for inferring the gene function in C. intestinalis . © 2014 Wiley Periodicals, Inc.

Description: Osteolytic bone diseases are characterized by excessive osteoclast formation and activation. Protein kinase C (PKC)-dependent pathways regulate cell growth, differentiation and apoptosis in many cellular systems, and have been implicated in cancer development and osteoclast formation. A number of PKC inhibitors with anti-cancer properties have been developed, but whether they might also influence osteolysis (a common complication of bone invading cancers) is unclear. We studied the effects of the PKC inhibitor compound, GF109203X on osteoclast formation and activity, processes driven by receptor activator of NFκB ligand (RANKL). We found that GF109203X strongly and dose dependently suppresses osteoclastogenesis and osteoclast activity in RANKL-treated primary mouse bone marrow cells. Consistent with this GF109203X reduced expression of key osteoclastic genes, including cathepsin K, calcitonin receptor, tartrate resistant acid phosphatase (TRAP) and the proton pump subunit V-ATPase-d2 in RANKL-treated primary mouse bone marrow cells. Expression of these proteins is dependent upon RANKL-induced NF-κB and NFAT transcription factor actions; both were reduced in osteoclast progenitor populations by GF109203X treatment, notably NFATc1 levels. Furthermore, we showed that GF109203X inhibits RANKL-induced calcium oscillation. Together, this study shows GF109203X may block osteoclast functions, suggesting that pharmacological blockade of PKC-dependent pathways has therapeutic potential in osteolytic diseases. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.

Description: The sesquiterpene lactone Parthenolide (PN) exerted a cytotoxic effect on MDA-MB231 cells, a triple-negative breast cancer (TNBC) cell line, but its effectiveness was scarce when employed at low doses. This represents an obstacle for a therapeutic utilization of PN. In order to overcome this difficulty we associated to PN the suberoylanilide hydroxamic acid (SAHA), an histone deacetylase inhibitor. Our results show that SAHA synergistically sensitized MDA-MB231 cells to the cytotoxic effect of PN. It is noteworthy that treatment with PN alone stimulated the survival pathway Akt/mTOR and the consequent nuclear translocation of Nrf2, while treatment with SAHA alone induced autophagic activity. However when the cells were treated with SAHA/PN combination, SAHA suppressed PN effect on Akt/mTOR/Nrf2 pathway, while PN reduced the prosurvival autophagic activity of SAHA. In addition SAHA/PN combination induced GSH depletion, fall in Δψm, release of cytochrome c, activation of caspase 3 and apoptosis. Finally we demonstrated that combined treatment maintained both hyperacetylation of histones H3 and H4 induced by SAHA and down-regulation of DNMT1 expression induced by PN. Inhibition of the DNA-binding activity of NF-kB, which is determined by PN, was also observed after combined treatment. In conclusion, combination of PN to SAHA inhibits the cytoprotective responses induced by the single compounds, but does not alter the mechanisms leading to the cytotoxic effects. Taken together our results suggest that this combination could be a candidate for TNBC therapy. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.

Description: The tenet that ecological opportunity drives adaptive diversification has been central to theories of speciation since Darwin, yet no widely accepted definition or mechanistic framework for the concept currently exists. We propose a definition for ecological opportunity that provides an explicit mechanism for its action. In our formulation, ecological opportunity refers to environmental conditions that both permit the persistence of a lineage within a community, as well as generate divergent natural selection within that lineage. Thus, ecological opportunity arises from two fundamental elements: (1) niche availability, the ability of a population with a phenotype previously absent from a community to persist within that community and (2) niche discordance, the diversifying selection generated by the adaptive mismatch between a population's niche-related traits and the newly encountered ecological conditions. Evolutionary response to ecological opportunity is primarily governed by (1) spatiotemporal structure of ecological opportunity, which influences dynamics of selection and development of reproductive isolation and (2) diversification potential, the biological properties of a lineage that determine its capacity to diversify. Diversification under ecological opportunity proceeds as an increase in niche breadth, development of intraspecific ecotypes, speciation, and additional cycles of diversification that may themselves be triggered by speciation. Extensive ecological opportunity may exist in depauperate communities, but it is unclear whether ecological opportunity abates in species-rich communities. Because ecological opportunity should generally increase during times of rapid and multifarious environmental change, human activities may currently be generating elevated ecological opportunity – but so far little work has directly addressed this topic. Our framework highlights the need for greater synthesis of community ecology and evolutionary biology, unifying the four major components of the concept of ecological opportunity. The tenet that ecological opportunity drives adaptive diversification has been central to theories of speciation since Darwin, yet there is currently no widely accepted definition or mechanistic framework for the concept. We propose an explicit definition and mechanism for ecological opportunity that includes its two fundamental elements: (1) niche availability, the opportunity for initial persistence of a new phenotype within a community, and (2) niche discordance, the rearrangement of ecological constraints that generates diversifying selection.

Description: Santín et al. (2014) report the conversion of different boreal forest biomass pools to pyrogenic organic matter (PyOM) during a forest fire, and suggest that ~100 Tg C y −1 may be converted to PyOM in boreal forests globally. They further suggest that PyOM formation represents a missing C sink. The phrase ‘missing C sink’ derives from a lack of closure in the atmospheric C budget. Approximately ⅓ of the CO 2 emitted to the atmosphere via burning of fossil fuels and land use change cannot be accounted for after oceanic uptake and atmospheric accumulations are tallied (Schlesinger and Bernhardt 2013). This article is protected by copyright. All rights reserved.

Description: A significant part of the soil organic carbon that is eroded in uplands is deposited and buried in colluvial settings. Understanding the fate of this deposited soil organic carbon (SOC) is of key importance for the understanding of the role of (accelerated) erosion in the global C cycle: the residence time of the deposited carbon will determine if, and for how long, accelerated erosion due to human disturbance will induce sequestration of SOC from the atmosphere to the soil. Experimental studies may provide useful information, but, given the time scale under consideration, the response of the colluvial SOC can only be simulated using numerical models which need careful calibration using field data. In this study, we present a depth explicit SOC model (ICBM-DE) including soil profile evolution due to sedimentation to simulate the long-term C dynamics in colluvial soils. The SOC profile predicted by our model is in good agreement with field observations. The C burial efficiency (the ratio of current C content of the buried sediments to the original C content at the time of sedimentation) of deposited sediments exponentially decreases with time and gradually reached an equilibrium value. This equilibrium C burial efficiency is positively correlated with the sedimentation rate. The sedimentation rate is crucial for the long-term dynamics of the deposited SOC as it controls the time that buried sediments spend at a given soil depth, thereby determining its temporal evolution of C input and decomposition rate during the burial process: C input and decomposition rate vary with depth due to the vertical variation of root distribution and soil environmental factors such as (but not limited to) humidity, temperature and aeration. The model demonstrates that, for the profiles studied, it takes ca. 300 yr for the buried SOC to lose half of its C load. It would also take centuries for the SOC accumulated in colluvial soils over the past decades due to soil redistribution under mechanized agriculture to be released to the atmosphere after the application of soil conservation measures such as conservation tillage.

Description: Massive DNA sequencing has significantly increased the amount of data available for population genetics and molecular ecology studies. However, the parallel computation of simple statistics within and between populations from large panels of polymorphic sites is not yet available, making the exploratory analyses of a set or subset of data a very laborious task. Here, we present 4P (parallel processing of polymorphism panels), a stand-alone software program for the rapid computation of genetic variation statistics (including the joint frequency spectrum) from millions of DNA variants in multiple individuals and multiple populations. It handles a standard input file format commonly used to store DNA variation from empirical or simulation experiments. The computational performance of 4P was evaluated using large SNP (single nucleotide polymorphism) datasets from human genomes or obtained by simulations. 4P was faster or much faster than other comparable programs, and the impact of parallel computing using multicore computers or servers was evident. 4P is a useful tool for biologists who need a simple and rapid computer program to run exploratory population genetics analyses in large panels of genomic data. It is also particularly suitable to analyze multiple data sets produced in simulation studies. Unix, Windows, and MacOs versions are provided, as well as the source code for easier pipeline implementations. 4P is a new computer program for parallel computation of basic population genetics statistics (including the joint allele frequency spectrum) from large panel of SNPs. 4P is fast and simple to use, read files with genomic data saved in classical formats, do not require ad hoc scripts, and it very fast with servers but also when multi-core stand-alone computers are used. It is particularly suitable to analyse multiple data sets produced in simulation studies.

Description: Tumor cells display different bioenergetic profiles when compared to normal cells. In the present work we showed metabolic reprogramming by means of inhibitors of histone deacetylase (HDACis), sodium butyrate and trichostatin A in breast cancer cells representing different stages of aggressiveness and metabolic profile. When testing the effect of NaB and TSA on viability of cells, it was shown that non-tumorigenic MCF-10A cells were less affected by increasing doses of the drugs than the tumorigenic, hormone dependent, tightly cohesive MCF-7, T-47D and the highly metastatic triple-negative MDA-MB 231 cells. T-47D cells were the most sensitive to treatment with both, NaB and TSA. Experiments measuring anchorage- independent growth of tumor cells showed that MCF-7, T-47D, and MDA-MB-231 cells were equally sensitive to the treatment with NaB. The NaB induced an attenuation of glycolysis, reflected by a decrease in lactate release in MCF-7 and T47D lines. Pyruvate kinase activity was significantly enhanced by NaB in MDA-MB-231 cells only. In contrast, the inhibitor enhanced lactate dehydrogenase activity specifically in T-47 D cells. Glucose-6-phosphate dehydrogenase activity was shown to be differentially modulated by NaB in the cell lines investigated: the enzyme was inhibited in MCF-7 cells, whereas in T-47D and MDA-MB-231 cells, G6PDH was activated. NaB and TSA were able to significantly increase the oxygen consumption by MDA-MB-231 and T-47D cells. Collectively the results show that epigenetic changes associated to acetylation of proteins in general affect the energy metabolism in all cancer cell lines and that mitochondria may occupy a central role in metastasis. This article is protected by copyright. All rights reserved

Description: Genomic and trascriptomic profiling has recently contributed details to the characterization of luminal B breast cancer. We explored the contribution of anthropometric, metabolic and molecular determinants to the multifaceted heterogeneity of this breast cancer subtype, with a specific focus on the association between body mass index (BMI), pre-treatment fasting glucose, hormone receptors and expression of human epidermal growth factor receptor 2 (HER2). Extensively annotated specimens were obtained from 154 women with luminal B breast cancer diagnosed at two Italian comprehensive cancer centres. Participants' characteristics were descriptively analyzed overall and by HER2 status (positive vs negative). BMI (〈25 vs ≥25), pre-treatment fasting glucose (〈median value of 94 mg/dl vs ≥94) and percentage of hormone receptors were tested for association with HER2 expression in regression models. In univariate models, BMI, fasting glucose and, at a lesser extent, percentage of estrogen receptors (ER) were significantly and inversely associated with HER2 expression (OR: 0.32, 95%CI: 0.16-0.66; 0.43, 0.23-0.0.82; 0.96, 0.94-0.97, respectively). The multivariate models confirmed the protective role of BMI and ER on HER2 expression, with luminal B HER2 positive patients being significantly less frequent among women within the highest category of BMI and percentage expression of ER compared with their counterparts (OR: 0.22, 95%CI: 0.09-0.53; 0.95, 0.93-0.97). In conclusions, BMI and percentage of ER representation are inversely associated with HER2 expression in luminal B breast cancers. Upon confirmatory findings, this might help identify patient subgroups who may best benefit from the use of interventions targeting insulin resistance in well depicted breast cancer scenarios. This article is protected by copyright. All rights reserved

Description: Citations published in online supplementary material (OSM) are invisible to search engines used to calculate citation counts, potentially negatively impacting popular performance indices and journal rankings that rely on citation counts for quantification. To quantify the number of citations that are “lost” in OSM, we conducted a systematic survey of supplementary citation practices in four high-ranking, society-run journals from two geographical locations (Europe and North America). In 2012, 6% of all citations were only included in the OSM and were therefore not included in citation counts. We found a significant increase in the number of references invisible to citation counting services over the last two decades. A solution to this problem is urgently required and could include journal indexing of citations in OSM or the inclusion of all references in the main text. Citations published in online supplementary material (OSM) are invisible to search engines used to calculate citation counts, potentially negatively impacting popular performance indices and journal rankings that rely on citation counts for quantification. We conducted a systematic survey of historical supplementary citation practices in four journals from two geographical locations (Europe and North America) and found a significant increase in the number of references invisible to citation counting services over the last two decades. A solution to this problem is urgently required and could include journal indexing of citations in OSM or the inclusion of all references in the main text.

Description: Histone deacetylases (HDACs) play a crucial role in the regulation of gene expression through remodeling of chromatin structures. However, the molecular mechanisms involved in this event remain unknown. In this study, we sought to examine whether HDAC inhibition-mediated protective effects involved HDAC4 sumoylation, degradation, and the proteasome pathway. Isolated neonatal mouse ventricular myocytes (NMVM) and H9c2 cardiomyoblasts were subjected to 48 hours of hypoxia (H) (1% O 2 ) and 2 hours of reoxygenation (R). Treatment of cardiomyocytes with trichostatin A (TSA) attenuated H/R-elicited injury, as indicated by a reduction of lactate dehydrogenase (LDH) leakage, an increase in cell viability, and decrease in apoptotic positive cardiomyocytes. MG132, a potent proteasome pathway inhibitor, abrogated TSA-induced protective effects, which was associated with the accumulation of ubiquitinated HDAC4. NMVM transduced with adenoviral HDAC4 led to an exaggeration of H/R-induced injury. TSA treatment resulted in a decrease in HDAC4 in cardiomyocytes infected with adenoviral HDAC4, and HDAC4-induced injury was attenuated by TSA. HDAC inhibition resulted in a significant reduction in reactive oxygen species (ROS) in cardiomyoblasts exposed to H/R, which was attenuated by blockade of the proteasome pathway. Cardiomyoblasts carrying wild type and sumoylation mutation (K559R) were established to examine effects of HDAC4 sumoylation and ubiquitination on H/R injury. Disruption of HDAC4 sumoylation brought about HDAC4 accumulation and impairment of HDAC4 ubiquitination in association with enhanced susceptibility of cardiomyoblasts to H/R. Taken together, these results demonstrated that HDAC inhibition stimulates proteasome dependent degradation of HDAC4, which is associated with HDAC4 sumoylation to induce these protective effects. This article is protected by copyright. All rights reserved

Description: Tree-ring analysis is often used to assess long-term trends in tree growth. A variety of growth-trend detection methods (GDMs) exist to disentangle age/size trends in growth from long-term growth changes. However, these detrending methods strongly differ in approach, with possible implications for their output. Here we critically evaluate the consistency, sensitivity, reliability and accuracy of four most widely used GDMs: Conservative Detrending applies mathematical functions to correct for decreasing ring-widths with age; Basal Area Correction transforms diameter into basal-area growth; Regional Curve Standardization detrends individual tree-ring series using average age/size trends; and Size Class Isolation calculates growth trends within separate size classes. First, we evaluated whether these GDMs produce consistent results applied to an empirical tree-ring dataset of Melia azedarach , a tropical tree species from Thailand. Three GDMs yielded similar results – a growth decline over time – but the widely used Conservative Detrending method did not detect any change. Second, we assessed the sensitivity (probability of correct growth trend detection), reliability (1- probability of detecting false trends), and accuracy (whether the strength of imposed trends is correctly detected) of these GDMs, by applying them to simulated growth trajectories with different imposed trends: no trend, strong trends (-6% and +6% change per decade), and weak trends (-2%, +2%). All methods except Conservative Detrending, showed high sensitivity, reliability and accuracy to detect strong imposed trends. However, these were considerably lower in the weak or no-trend scenarios. Basal Area Correction showed good sensitivity and accuracy, but low reliability, indicating uncertainty of trend-detection using this method. Our study reveals that the choice of GDM influences results of growth-trend studies. We recommend applying multiple methods when analysing trends and encourage performing sensitivity and reliability analysis. Finally, we recommend Size Class Isolation and Regional Curve Standardization, as these methods showed highest reliability to detect long-term growth trends. This article is protected by copyright. All rights reserved.

Description: Surface-to-atmosphere emissions of dimethyl sulfide (DMS) may impact global climate through the formation of gaseous sulfuric acid, which can yield secondary sulfate aerosols and contribute to new particle formation. While oceans are generally considered the dominant source of DMS, a shortage of ecosystem observations prevents an accurate analysis of terrestrial DMS sources. Using mass spectrometry, we quantified ambient DMS mixing ratios within and above a primary rainforest ecosystem in the central Amazon Basin in real-time (2010–2011) and at high vertical resolution (2013–2014). Elevated but highly variable DMS mixing ratios were observed within the canopy, showing clear evidence of a net ecosystem source to the atmosphere during both day and night in both the dry and wet seasons. Periods of high DMS mixing ratios lasting up to 8 hours (up to 160 ppt) often occurred within the canopy and near the surface during many evenings and nights. Daytime gradients showed mixing ratios (up to 80 ppt) peaking near the top of the canopy as well as near the ground following a rain event. The spatial and temporal distribution of DMS suggests that ambient levels and their potential climatic impacts are dominated by local soil and plant emissions. A soil source was confirmed by measurements of DMS emission fluxes from Amazon soils as a function of temperature and soil moisture. Furthermore, light and temperature dependent DMS emissions were measured from seven tropical tree species. Our study has important implications for understanding terrestrial DMS sources and their role in coupled land-atmosphere climate feedbacks.

Description: Question Hemiparasitic plants can profoundly affect the structure of the community in which they occur, mainly due to parasitic suppression of hosts. As a consequence, non-host species have the opportunity to colonize resulting gaps. In contrast to most grassland species, hemiparasites are generally short-lived and can reach high densities; as a consequence, vegetation gaps are left after their death. These gaps form microsites more suitable for seed germination and therefore might increase recruitment of other species. Which species suffer or profit from parasitism and is there a positive effect on seedling establishment? Location Semi-natural grasslands in northern Belgium. Methods We selected two hemiparasitic plant species from contrasting vegetation types: Rhinanthus angustifolius growing in mesotrophic grassland and Pedicularis sylvatica growing in oligotrophic heath-grassland. A weeding experiment was set up at six sites in which the hemiparasite was repeatedly removed in half of the plots during three growing seasons. The abundance change of individual species was compared between weeded and control plots. After the second growing season, seeds of up to ten species were added. The number of seedlings in the third year was then compared between weeded and control plots. Results Rhinanthus removal significantly affected the abundance of species relative to control plots, both positively and negatively, and decreased the species evenness. Pedicularis removal only increased the abundance of some species. Only Juncaceae (but no other graminoid families) increased after Rhinanthus and Pedicularis weeding, and there was considerable variation within functional groups. Moreover, based on our observations, we propose as a new hypothesis that species with persistent clonal spread are more vulnerable to parasitism. Once attached, resources are potentially drawn from a whole network of interconnected ramets. Finally, only half of the sown species successfully established seedlings; hemiparasite removal had a significantly negative effect on seedling number for two of these species. Conclusions Effects of hemiparasites on species differ considerably, also within functional groups. Persistent clonal spread emerges as an important plant trait determining vulnerability to hemiparasites. Finally, our results suggest that hemiparasitic plants might have a limited positive effect on seedling establishment in these semi-natural grasslands where chances for successful establishment were shown to be low. We studied the effect of 2 grassland hemiparasites on individual species in the established phase and in the establishment phase. Based on our observations, we propose an exciting new hypothesis: that species with persistent clonal spread are more vulnerable to parasitism because once attached, resources are potentially drawn from a whole network of interconnected ramets.

Description: (http://onlinelibrary.wiley.com/doi/10.1111/gcb.12697/full) The above article, published online on 18 August 2014 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, Dr Melanie Harsch and Associate Professor Janneke Hille Ris Lambers, journal Editor‐in‐Chief, Professor Stephen Long, and John Wiley & Sons Ltd. The retraction has been agreed for the following reasons: a coding error affected the results and therefore invalidated the broad‐scale conclusions presented in the article. The article presented broad‐scale patterns of species distribution shifts in response to recent climate change. Unfortunately, it has since been found that one approach used to account for sampling bias, the null model approach, was affected by the coding error. Following the identification of the coding error, we are therefore retracting the article. We thank Drs Adam Wolf and William Anderegg for bringing this issue to our attention. Reference Harsch MA, Hille Ris Lambers J (2014) Species distributions shift downward across western North America. Global Change Biology. doi: 10.1111/gcb.12697.

Description: Serine protease inhibitors (PIs) have been described in many plant species and are universal throughout the plant kingdom, where trypsin inhibitors is the most common type. In the present study, trypsin and chymotrypsin inhibitory activity was detected in the seed flour extracts of 13 selected cultivars/accessions of cowpea. Two cowpea cultivars, Cream7 and Buff, were found to have higher trypsin and chymotrypsin inhibitory potential compared to other tested cultivars for which they have been selected for further purification studies using ammonium sulfate fractionation and DEAE-Sephadex A-25 column. Cream7-purified proteins showed two bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) corresponding to molecular mass of 17.10 and 14.90 kDa, while the purified protein from Buff cultivar showed a single band corresponding mass of 16.50 kDa. The purified inhibitors were stable at temperature below 60°C and were active at wide range of pH from 2 to 12. The kinetic analysis revealed noncompetitive type of inhibition for both inhibitors against both enzymes. The inhibitor constant ( K i ) values suggested high affinity between inhibitors and enzymes. Purified inhibitors were found to have deep and negative effects on the mean larval weight, larval mortality, pupation, and mean pupal weight of Spodoptera littoralis , where Buff PI was more effective than Cream7 PI. It may be concluded that cowpea PI gene(s) could be potential insect control protein for future studies in developing insect-resistant transgenic plants.

Description: The vitamin A-redox hypothesis provides an explanation for honest signaling of phenotypic quality by carotenoid-dependent traits. A key aspect of the vitamin A-redox hypothesis, applicable to both yellow and red coloration, is the hypothesized negative feedback of tightly regulated Vitamin A plasma levels on the enzyme responsible for sequestering both Vitamin A and carotenoids from the gut. We performed a meta-analysis and find that vitamin A levels are positively related to carotenoid plasma levels ( r  =   0.50, P  = 0.0002). On the basis of this finding and further theoretical considerations, we propose that the vitamin A-redox hypothesis is unlikely to explain carotenoid-dependent honest signaling. The vitamin A-redox hypothesis provides an explanation for honest signaling of phenotypic quality by carotenoid-dependent traits. We performed a meta-analysis and find that vitamin A levels are positively related to carotenoid plasma levels ( r  = 0.50, P  = 0.0002). On the basis of this finding and further theoretical considerations we propose that the vitamin A-redox hypothesis is unlikely to explain carotenoid-dependent honest signaling.

Description: Seaweed beds play a key role in providing essential habitats and energy to coastal areas, with enhancements in productivity and biodiversity and benefits to human societies. However, the spatial extent of seaweed beds around Japan has decreased due to coastal reclamation, water quality changes, rising water temperatures, and heavy grazing by herbivores. Using monthly mean sea surface temperature (SST) data from 1960 to 2099 and SST-based indices, we quantitatively evaluated the effects of warming seawater on the spatial extent of suitable versus unsuitable habitats for temperate seaweed Ecklonia cava, which is predominantly found in southern Japanese waters. SST data were generated using the most recent multiple climate projection models and emission scenarios (the Representative Concentration Pathways or RCPs) used in the Coupled Model Intercomparison Project phase 5 (CMIP5). In addition, grazing by Siganus fuscescens, an herbivorous fish, was evaluated under the four RCP simulations. Our results suggest that continued warming may drive a poleward shift in the distribution of E. cava, with large differences depending on the climate scenario. For the lowest emission scenario (RCP2.6), most existing E. cava populations would not be impacted by seawater warming directly but would be adversely affected by intensified year-round grazing. For the highest emission scenario (RCP8.5), previously suitable habitats throughout coastal Japan would become untenable for E. cava by the 2090s, due to both high-temperature stress and intensified grazing. Our projections highlight the importance of not only mitigating regional warming due to climate change, but also protecting E. cava from herbivores to conserve suitable habitats on the Japanese coast. In this study, we quantitatively evaluated the effects of warming seawater on the spatial extent of suitable versus unsuitable habitats for temperate seaweed using the most recent multiple climate projection models and emission scenarios. Our results suggest that continued warming may drive a poleward shift of temperate seaweeds, with large differences depending on the severity of warming, and most of seaweeds' populations would be exposed to intensified grazing by herbivores, even if it were possible to mitigate regional warming.

Description: Endothelial cells play a major role in the initiation and perpetuation of the inflammatory process in health and disease, including their pivotal role in leukocyte recruitment. The role of pro-inflammatory transcription factors in this process has been well-described, including NF-κB. However, much less is known regarding transcription factors that play an anti-inflammatory role in endothelial cells. Myocyte enhancer factor 2 C (MEF2C) is a transcription factor known to regulate angiogenesis in endothelial cells. Here, we report that MEF2C plays a critical function as an inhibitor of endothelial cell inflammation. Tumor necrosis factor (TNF)-α inhibited MEF2C expression in endothelial cells. Knockdown of MEF2C in endothelial cells resulted in the upregulation of pro-inflammatory molecules and stimulated leukocyte adhesion to endothelial cells. MEF2C knockdown also resulted in NF-κB activation in endothelial cells. Conversely, MEF2C overexpression by adenovirus significantly repressed TNF-α induction of pro-inflammatory molecules, activation of NF-κB, and leukocyte adhesion to endothelial cells. This inhibition of leukocyte adhesion by MEF2C was partially mediated by induction of KLF2. In mice, lipopolysaccharide (LPS)-induced leukocyte adhesion to the retinal vasculature was significantly increased by endothelial cell-specific ablation of MEF2C. Taken together, these results demonstrate that MEF2C is a novel negative regulator of inflammation in endothelial cells and may represent a therapeutic target for vascular inflammation. This article is protected by copyright. All rights reserved

Description: Capture–mark–recapture (CMR) approaches are the backbone of many studies in population ecology to gain insight on the life cycle, migration, habitat use, and demography of target species. The reliable and repeatable recognition of an individual throughout its lifetime is the basic requirement of a CMR study. Although invasive techniques are available to mark individuals permanently, noninvasive methods for individual recognition mainly rest on photographic identification of external body markings, which are unique at the individual level. The re-identification of an individual based on comparing shape patterns of photographs by eye is commonly used. Automated processes for photographic re-identification have been recently established, but their performance in large datasets (i.e., 〉 1000 individuals) has rarely been tested thoroughly. Here, we evaluated the performance of the program AMPHIDENT, an automatic algorithm to identify individuals on the basis of ventral spot patterns in the great crested newt ( Triturus cristatus ) versus the genotypic fingerprint of individuals based on highly polymorphic microsatellite loci using GENECAP. Between 2008 and 2010, we captured, sampled and photographed adult newts and calculated for 1648 samples/photographs recapture rates for both approaches. Recapture rates differed slightly with 8.34% for GENECAP and 9.83% for AMPHIDENT. With an estimated rate of 2% false rejections (FRR) and 0.00% false acceptances (FAR), AMPHIDENT proved to be a highly reliable algorithm for CMR studies of large datasets. We conclude that the application of automatic recognition software of individual photographs can be a rather powerful and reliable tool in noninvasive CMR studies for a large number of individuals. Because the cross-correlation of standardized shape patterns is generally applicable to any pattern that provides enough information, this algorithm is capable of becoming a single application with broad use in CMR studies for many species. Capture-mark-recapture (CMR) of individuals is the backbone of many studies in population ecology. Automated processes for photographic re-identification of individuals have been recently established but their performance in large datasets have rarely been tested thoroughly. By applying genetic fingerprinting we show that cross-correlated automatic photo-identification of individuals is highly efficient in large capture-mark–recapture studies.

Description: Predator community composition can alter habitat quality for prey by changing the strength and direction of consumptive effects. Whether predator community composition also alters prey density via nonconsumptive effects during habitat selection is not well known, but is important for understanding how changes to predator communities will alter prey populations. We tested the hypothesis that predator community composition (presence of caged trout, caged dragonflies, or caged trout + dragonflies) alters colonization of aquatic mesocosms by ovipositing aquatic insects. In a previous experiment in this system, we found a spatial contagion effect, in which insects avoided pools with predators, but only when predator-free pools were isolated (~5 m away from predator pools). Here, we removed the isolated predator-free pools, allowing us to test whether insects would make fine-scale (~1 m) oviposition decisions in the absence of preferred isolated pools. We also estimated consumptive effects by allowing predators to feed on colonists for 5 days following colonization. All insects collected after 21 days were dipterans, dominated by Chironomidae. Total colonization, measured as the number of developing larvae after 21 days, was not affected by either predator presence or composition. Consumption was significant in the trout only treatment, reducing larval insect density by 46 ± 37% (mean ± SE). No other predator treatment significantly reduced prey density, although the proportion of chironomid larvae in protective cases increased in response to direct predation from dragonflies, indicating an antipredatory behavioral response. Taken together, these results reveal that predator community composition altered larval survival and behavior, but colonizing females either did not or could not assess these risks across small scales during oviposition. We found no evidence that predatory trout or dragonflies altered colonization of adjacent mesocosms by aquatic dipterans (i.e., larvae of the adult Chironomid pictured above). However, both trout and dragonflies (but not trout + dragonflies) had consumptive effects on the colonized larval community. We interpret our results in light of previous studies as a function of (1) a failure of colonizing insects to differentiate predator risk at small scales; and (2) possible spatial contagion effects that override colonization decisions at small scales.

Description: Identification of units within species worthy of separate management consideration is an important area within conservation. Mitochondrial DNA (mtDNA) surveys can potentially contribute to this by identifying phylogenetic and population structure below the species level. The American crocodile ( Crocodylus acutus ) is broadly distributed throughout the Neotropics. Its numbers have been reduced severely with the species threatened throughout much of its distribution. In Colombia, the release of individuals from commercial captive populations has emerged as a possible conservation strategy that could contribute to species recovery. However, no studies have addressed levels of genetic differentiation or diversity within C. acutus in Colombia, thus complicating conservation and management decisions. Here, sequence variation was studied in mtDNA cytochrome b and cytochrome oxidase I gene sequences in three Colombian captive populations of C. acutus . Two distinct lineages were identified: C. acutus -I, corresponding to haplotypes from Colombia and closely related Central American haplotypes; and C. acutus -II, corresponding to all remaining haplotypes from Colombia. Comparison with findings from other studies indicates the presence of a single “northern” lineage (corresponding to C. acutus -I) distributed from North America (southern Florida), through Central America and into northern South America. The absence of C. acutus -II haplotypes from North and Central America indicates that the C. acutus -II lineage probably represents a separate South American lineage. There appears to be sufficient divergence between lineages to suggest that they could represent two distinct evolutionary units. We suggest that this differentiation needs to be recognized for conservation purposes because it clearly contributes to the overall genetic diversity of the species. All Colombian captive populations included in this study contained a mixture of representatives of both lineages. As such, we recommend against the use of captive-bred individuals for conservation strategies until further genetic information is available.

Description: Marine organisms are simultaneously exposed to anthropogenic stressors with likely interactive effects, including synergisms in which the combined effects of multiple stressors are greater than the sum of individual effects. Early life stages of marine organisms are potentially vulnerable to the stressors associated with global change, but identifying general patterns across studies, species and response variables is challenging. This review represents the first meta-analysis of multi-stressor studies to target early marine life stages (embryo to larvae), particularly between temperature, salinity and pH as these are the best studied. Knowledge gaps in research on multiple abiotic stressors and early life stages are also identified. The meta-analysis yielded several key results: 1) Synergistic interactions (65% of individual tests) are more common than additive (17%) or antagonistic (17%) interactions. 2) Larvae are generally more vulnerable than embryos to thermal and pH stress. 3) Survival is more likely than sub-lethal responses to be affected by thermal, salinity, and pH stress. 4) Interaction types vary among stressors, ontogenetic stages, and biological responses, but they are more consistent among phyla. 5) Ocean acidification is a greater stressor for calcifying than non-calcifying larvae. Although more ecologically realistic than single-factor studies, multifactorial studies may still oversimplify complex systems, and so meta-analyses of the data from them must be cautiously interpreted with regard to extrapolation to field conditions. Nonetheless our results identify taxa with early life stages that may be particularly vulnerable (e.g. molluscs, echinoderms) or robust (e.g. arthropods, cnidarians) to abiotic stress. We provide a list of recommendations for future multiple stressor studies, particularly those focussed on early marine life stages. This article is protected by copyright. All rights reserved.

Description: Questions What are the driving factors for the species richness of understorey herbs of isolated forest patches? How can the relative direct and indirect effects of patch area, site quality, habitat isolation and continuity be disentangled? What are the effects on different species groups? Location Eutrophic hardwood forest patches in northwestern Germany. The isolation of these patches results from extensive agricultural land use and prevailing poor soil conditions in the surrounding landscape. Thus, the patches are embedded within a matrix of both open habitats and species-poor acidic forests. Methods We surveyed 76 eutrophic forest patches and recorded all understorey herb species. Several measured site variables were divided into soil and structural components, and into variables describing mean site conditions and site heterogeneity. Partial least squares structural equation modelling (PLS-SEM) was employed to determine the direct and indirect effects of patch area, site heterogeneity, mean site conditions, isolation and habitat continuity on species richness of several species groups. Results The most important factor determining species richness was patch area, which showed the strongest direct effect on eutrophic forest specialist species. Richness of forest matrix species, which also occur in the surrounding forest areas, was not directly influenced by area. Soil heterogeneity as well as structural heterogeneity increased with area, but only soil heterogeneity was relevant for species richness. Soil heterogeneity was more important for forest species in general and stress tolerators than for generalist species, open habitat species, competitors and ruderals. Mean site conditions influenced species richness of generalists, open habitat species, competitors and nutrient-demanding species. Isolation had a (negative) effect only on habitat specialists. Conclusions The relative effects of driving factors varied considerably between species groups. From our results for eutrophic forest specialists, we conclude that large and well-connected habitat patches are especially important for the successful conservation of the unique and partly endangered flora of eutrophic hardwood forests. We determined the relative effects of driving factors on species richness of eutrophic forest patches and found considerable differences between different species groups. Richness of specialists was driven by soil heterogeneity, direct area effects and isolation whereas these factors hardly affected generalists and open habitat species. We conclude that large, well-connected habitat patches play an important role with respect to conservation.

Description: Ramathal et al. have employed an elegant xenotransplantation technique to study the fate of human induced pluripotent stem cells (hiPSCs) from fertile males and from males carrying Y chromosome deletions of the azoospermia factor ( AZF ) region. When placed in a mouse testis niche, hiPSCs from fertile males differentiate into germ cell-like cells (GCLCs). Highlighting the crucial role of cell autonomous factors in male sterility, hiPSCs derived from azoospermic males prove to be less successful under similar circumstances. Their studies argue that the agametic “Sertoli cell only” phenotype of two of the AZF deletions likely arises from a defect in the maintenance of germline stem cells (GSCs) rather than from a defect in their specification. These observations underscore the importance of the dialogue between the somatic niche and its inhabitant stem cells, and open up interesting questions concerning the functioning of the somatic niche and how it communicates to the GSCs. In Ramathal et al., human induced pluripotent stem cells (hiPSCs) from wild type and azoospermic men adopt germ cell fate in vitro. Upon xenotransplantation into mouse seminiferous tubules, these hiPSCs acquired germ cell-like (GCL) fate. Remarkably, samples from azoospermic males were less efficient in both contexts.

Description: Human adult stem cells, which are capable of self-renewal and differentiation into other cell types, can be isolated from various tissues. There are no ethical and rejection problems as in the case of embryonic stem cells, so they are a promising source for cell therapy. The human body contains a great amount of adipose tissue that contains high numbers of mesenchymal stem cells. Human adipose-derived stem cells (hADSCs) could be easily induced to form neuron-like cells, and because of its availability and abundance, we can use it for clinical cell therapy. On the other hand, T 3 hormone as a known neurotropic factor has important impressions on the nervous system. The aim of this study was to explore the effects of T 3 treatment on neural differentiation of hADSCs. ADSCs were harvested from human adipose tissue, after neurosphere formation, and during final differentiation, treatment with T 3 was performed. Immunocytochemistry, real-time RT-PCR, Western blotting techniques were used for detection of nestin, MAP2, and GFAP markers in order to confirm the effects of T 3 on neural differentiation of hADSCs. Our results showed an increase in the number of glial cells but reduction in neuronal cells number fallowing T 3 treatment. Copyright © 2014 John Wiley & Sons, Ltd.

Description: Palmitate induces insulin resistance and apoptosis in insulin target tissues. Rosiglitazone (RSG), a peroxisome proliferator-activated receptor γ (PPAR γ ) agonist, can activate both pro-apoptotic and anti-apoptotic pathways in different cells; however, its effect on palmitate-induced apoptosis in skeletal muscle cells remains to be elucidated. After differentiation of C2C12 cells, myotubes were treated with palmitate, RSG and GW9662 (PPAR γ antagonist). MTT and terminal deoxynucleotide transferase dUTP nick end labelling (TUNEL) assays and caspase-3 activity were used to investigate the apoptosis. To study the underlying mechanism, glucose uptake, gene expression and protein levels were evaluated. A total of 0.75 mM palmitate reduced cell viability by 43% and increased TUNEL-positive cells and caspase-3 activity by 15-fold and 6.6-fold, respectively. RSG (10 μM) could markedly decrease the level of TUNEL-positive cells and caspase-3 activity in palmitate-treated cells. The protective effect of RSG on apoptosis was abrogated by GW9662. To investigate the molecular mechanism of this effect, gene expression and protein level of protein tyrosine phosphatase 1B (PTP1B) were evaluated. Palmitate and RSG individually increased the expression and protein level of PTP1B, whereas combined treatment (palmitate and RSG) were able to further increase the expression of PTP1B in C2C12 cells. We also evaluated the effect of RSG on palmitate-induced insulin resistance in muscle cells. RSG could significantly improve glucose uptake by 0.4-fold in myotubes treated with palmitate. Moreover, RSG could restore the phosphorylation of Akt in palmitate-treated cells. These data suggest that RSG protects skeletal muscle cells against palmitate-induced apoptosis and this effect appears to be mediated via the PPAR γ -dependent and PTP1B-independent mechanisms. Copyright © 2014 John Wiley & Sons, Ltd. SIGNIFICANCE OF THE STUDY Saturated free fatty acids (FFAs), such as palmitate, have been shown to induce cellular apoptosis. Strategies for preventing the cytotoxic effect of palmitate are useful in reduction of diabetes complications. In this study, we introduced RSG as an agent that protects skeletal muscle cells against palmitate-induced apoptosis and insulin resistance. It appears that RSG protects skeletal muscle cells against palmitate-induced apoptosis via the PPARγ-dependent and PTP1B-independent mechanisms. Given the role of FFAs in skeletal muscle apoptosis, these findings support the idea that RSG can ameliorate diabetes complications such as skeletal muscle loss.

Description: The expression of Hes1 is increased following myocardial infarct and other ischemic cardiomyopathies, but the role of Hes1 in cardioprotection provided by ischemic postconditioning (IPost) remains unclear. In this study, we used gain and loss of function approaches to investigate the role of Hes1 in cardioprotection during IPost. Primary cardiac myocytes exposed to ischemia reperfusion injury (IRI) and IPost were used as the experimental model. The results showed that Hes1 expression was increased during myocardial IPost, and Hes1 promoted the viability while inhibited the apoptosis of cardiomyocytes. Moreover, Hes1 inhibited the opening of mitochondrial permeability transition pore (mPTP) and the generation of reactive oxygen species in primary cardiac myocytes exposed to IRI. Mechanistically, we found that Hes1-mediated cardioprotection was related to the downregulation of phosphatase and tensin homolog and the activation of phosphatidylinositol 3-kinase/Akt and signal transducer and activator of transcription 3 signalling. These data demonstrate that Hes1 is upregulated and mediates cardioprotection provided by IPost and suggest that Hes1 is a potential new target for the treatment of ischemic cardiomyopathy. Copyright © 2014 John Wiley & Sons, Ltd.

Description: The aim of this study was to study RAS-siRNA blocking RAS pathway and suppressing cell growth in human oesophageal squamous cell carcinoma in nude mice. The methods in this study was to construct RAS-siRNA expression vector, establish 40 oesophageal squamous cell carcinoma xenograft animal models and divided them into five groups: control group, siRNA control group, RAS-siRNA group, paclitaxel group and RAS-siRNA and paclitaxel group. We observed tumour growth in nude mice, studied histology by HE staining, tumour growth inhibition by TUNEL assay and detected the RAS, MAPK and cyclin D1 protein expression by immunohistochemistry and western blot. We have obtained the following results: (i) successfully established animal models; (ii) nude mice in each group after treatment inhibited tumour volume was significantly reduced compared with the control group ( p  〈 0.05); (iii) compared with the control group, the number of apoptotic cells were significantly increased in the siRNA control group and the RAS-siRNA group, and the number of apoptosis cells in the paclitaxel and RAS-siRNA group is significantly most than the paclitaxel group and RAS-siRNA group ( p  〈 0.05); and (iv) after treatment, RAS, MAPK and cyclin D1 expression in five groups was decreasing gradually. After adding paclitaxel, the protein expression in the paclitaxel and RAS-siRNA group was significantly lower than that of paclitaxel group, negative control and paclitaxel group ( p  〈 0.05). We therefore conclude that RAS-siRNA can block the RAS signal transduction pathway, reduce the activity of tumour cells, arrest tumour cell cycle, promote apoptosis, inhibit cell proliferation and increase tumour cell sensitivity to chemotherapeutic drugs. Copyright © 2014 John Wiley & Sons, Ltd.

Description: There is increasing evidence suggesting that oxidative stress plays an important role in the development of many chronic and degenerative conditions such as diabetic encephalopathy and depression. Considering that diabetic rats and mice present higher depressive-like behaviour when submitted to the forced swimming test and that treatment with insulin and/or clonazepam is able to reverse the behavioural changes of the diabetic rats, the present work investigated the antioxidant status, specifically total antioxidant reactivity and antioxidant potential of insulin and clonazepam, as well as the effect of this drugs upon protein oxidative damage and reactive species formation in cortex, hippocampus and striatum from diabetic rats submitted to forced swimming test. It was verified that longer immobility time in diabetic rats and insulin plus clonazepam treatment reversed this depressive-like behaviour. Moreover, data obtained in this study allowed to demonstrate through different parameters such as protein carbonyl content, 2′7′-dichlorofluorescein oxidation, catalase, superoxide dismutase, glutathione peroxidase assay, total radical-trapping antioxidant potential and total antioxidant reactivity that there is oxidative stress in cortex, hippocampus and striatum from diabetic rats under depressive-like behaviour and highlight the insulin and/or clonazepam effect in these different brain areas, restoring antioxidant status and protein damage. Copyright © 2014 John Wiley & Sons, Ltd.

Description: Propofol is widely used in paediatric anaesthesia and intensive care unit because of its essentially short-acting anaesthetic effect. Recent data have shown that propofol induced neurotoxicity in developing brain. However, the mechanisms are not extremely clear. To gain a better insight into the toxic effects of propofol on hippocampal neurons, we treated cells at the days in vitro 7 (DIV 7), which were prepared from Sprague–Dawley embryos at the 18th day of gestation, with propofol (0.1–1000 μM) for 3 h. A significant decrease in neuronal proliferation and a remarkable increase in neuroapoptosis were observed in DIV 7 hippocampal neurons as measured by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis assay respectively. Moreover, propofol treatment decreased the nuclear factor kappaB (NF-κB) p65 expression, which was accompanied by a reduction in B-cell lymphoma 2 (Bcl-2) mRNA and protein levels, increased caspase-3 mRNA and activation of caspase-3 protein. These results indicated that downregulation of NF-κB p65 and Bcl-2 were involved in the potential mechanisms of propofol-induced neurotoxicity. This likely led to the caspase-3 activation, triggered apoptosis and inhibited the neuronal growth and proliferation that we have observed in our in vitro systems. Copyright © 2014 John Wiley & Sons, Ltd.

Description: Understanding the evolution of dispersal is essential for understanding and predicting the dynamics of natural populations. Two main factors are known to influence dispersal evolution: spatio-temporal variation in the environment and relatedness between individuals. However, the relation between these factors is still poorly understood, and they are usually treated separately. In this article, I present a theoretical framework that contains and connects effects of both environmental variation and relatedness, and reproduces and extends their known features. Spatial habitat variation selects for balanced dispersal strategies, whereby the population is kept at an ideal free distribution. Within this class of dispersal strategies, I explain how increased dispersal is promoted by perturbations to the dispersal type frequencies. An explicit formula shows the magnitude of the selective advantage of increased dispersal in terms of the spatial variability in the frequencies of the different dispersal strategies present. These variances are capable of capturing various sources of stochasticity and hence establish a common scale for their effects on the evolution of dispersal. The results furthermore indicate an alternative approach to identifying effects of relatedness on dispersal evolution. This article presents a theoretical framework that brings together spatial habitat heterogeneities and kin selection models for the evolution of dispersal in a conceptually illuminative way. The impact of the former is measured in terms of spatial fluxes of individuals, while the effect of relatedness is expressed via type frequency variances, which provides striking insight: any force that induces variation into the dispersal type frequencies causes selection for increased dispersal. Consequently, a common scale for different factors of dispersal evolution is established, indicating that future studies should focus on the type frequency variability as a force promoting dispersal.

Description: Checkerspot butterflies in the genera Euphydryas and Chlosyne exhibit phenotypic polymorphisms along a well-defined latitudinal and elevational gradient in California. The patterns of phenotypic variation in Euphydryas chalcedona, Chlosyne palla, and Chlosyne hoffmanni suggest a mimetic relationship; in addition, the specific patterns of variation in C. palla suggest a female-limited polymorphic mimicry system (FPM). However, the existence of polymorphic models runs counter to predictions of mimicry theory. Palatability trials were undertaken to assess whether or not the different color morphs of each species were distasteful or toxic to a generalized avian predator, the European starling ( Sturnus vulgaris ). Results indicate that the black morph of E. chalcedona is distasteful, but not toxic, to predators, while the red morph is palatable. C . hoffmanni and both color morphs of C. palla are palatable to predators. Predators that learn to reject black E. chalcedona also reject black C. palla , suggesting that the latter is a FPM of the former. C. hoffmanni does not appear to be involved in this mimetic relationship. The Variable Checkerspot, Euphydryas chalcedona , occurs in a palatable red form and an unpalatable black form (shown). The Northern Checkerspot is a palatable Female-limited Batesian mimic of the Variable Checkerspot. Only females of the Northern Checkerspot occur in the black form.

Description: Trophic interactions play a critical role in the structure and function of ecosystems. Given the widespread loss of biodiversity due to anthropogenic activities, understanding how trophic interactions respond to natural gradients (e.g., abiotic conditions, species richness) through large-scale comparisons can provide a broader understanding of their importance in changing ecosystems and support informed conservation actions. We explored large-scale variation in reef fish trophic interactions, encompassing tropical and subtropical reefs with different abiotic conditions and trophic structure of reef fish community. Reef fish feeding pressure on the benthos was determined combining bite rates on the substrate and the individual biomass per unit of time and area, using video recordings in three sites between latitudes 17°S and 27°S on the Brazilian Coast. Total feeding pressure decreased 10-fold and the composition of functional groups and species shifted from the northern to the southernmost sites. Both patterns were driven by the decline in the feeding pressure of roving herbivores, particularly scrapers, while the feeding pressure of invertebrate feeders and omnivores remained similar. The differential contribution to the feeding pressure across trophic categories, with roving herbivores being more important in the northernmost and southeastern reefs, determined changes in the intensity and composition of fish feeding pressure on the benthos among sites. It also determined the distribution of trophic interactions across different trophic categories, altering the evenness of interactions. Feeding pressure was more evenly distributed at the southernmost than in the southeastern and northernmost sites, where it was dominated by few herbivores. Species and functional groups that performed higher feeding pressure than predicted by their biomass were identified as critical for their potential to remove benthic biomass. Fishing pressure unlikely drove the large-scale pattern; however, it affected the contribution of some groups on a local scale (e.g., large-bodied parrotfish) highlighting the need to incorporate critical functions into conservation strategies. We explored large-scale variation in reef fish trophic interactions, encompassing tropical and subtropical reefs with different abiotic conditions and trophic structure of reef fish community. There were remarkable changes in the intensity and composition of fish feeding pressure on the benthos across the studied sites, driven by the decline in the feeding pressure of roving herbivores from the northernmost to the southernmost site. Comparing how species with different feeding ecology affect the strength and distribution of trophic interactions across large spatial scales can shed light to new interaction-based approaches to functional redundancy and conservation of reef ecosystems.

Description: Compared with non-invasive species, invasive plant species may benefit from certain advantageous traits, for example, higher photosynthesis capacity and resource/energy-use efficiency. These traits can be preadapted prior to introduction, but can also be acquired through evolution following introduction to the new range. Disentangling the origins of these advantageous traits is a fundamental and emerging question in invasion ecology. We conducted a multiple comparative experiment under identical environmental condition with the invasive haplotype M lineage of the wetland grass Phragmites australis and compared the ecophysiological traits of this invasive haplotype M in North America with those of the European ancestor and the conspecific North American native haplotype E lineage, P. australis ssp.  americanus . The invasive haplotype M differed significantly from the native North American conspecific haplotype E in several ecophysiological and morphological traits, and the European haplotype M had a more efficient photosynthetic apparatus than the native North American P. australis ssp.  americanus . Within the haplotype M lineage, the introduced North American P. australis exhibited different biomass allocation patterns and resource/energy-use strategies compared to its European ancestor group. A discriminant analysis of principal components separated the haplotype M and the haplotype E lineages completely along the first canonical axis, highly related to photosynthetic gas-exchange parameters, photosynthetic energy-use efficiency and payback time. The second canonical axis, highly related to photosynthetic nitrogen use efficiency and construction costs, significantly separated the introduced P. australis in North America from its European ancestor. Synthesis . We conclude that the European P. australis lineage was preadapted to be invasive prior to its introduction, and that the invasion in North America is further stimulated by rapid post-introduction evolution in several advantageous traits. The multicomparison approach used in this study could be an effective approach for distinguishing preadaptation and post-introduction evolution of invasive species. Further research is needed to link the observed changes in invasive traits to the genetic variation and the interaction with the environment. Disentangling the origins of the advantageous traits is a fundamental and emerging question in invasion ecology. We compared the ecophysiological traits of the invasive haplotype M of Phragmites australis in North America with those in Europe and the conspecific North American native haplotype E lineage, P. australis ssp.  americanus . The invasive haplotype M differed significantly from the native North American conspecific haplotype E in several ecophysiological and morphological traits, and the European haplotype M had a more efficient photosynthetic apparatus than the native North American P. australis ssp.  americanus . Within the haplotype M lineage, the introduced North American P. australis exhibited different biomass allocation patterns and resource/energy-use strategies compared to its European ancestor group. A discriminant analysis of principal components (DAPC) significantly separated the three groups. We conclude that the European P. australis lineage was preadapted to be invasive prior to its introduction, and that the invasion in North America is further stimulated by rapid post-introduction evolution in several advantageous traits.

Description: Understanding the behavioral decisions behind animal movement and space use patterns is a key challenge for behavioral ecology. Tools to quantify these patterns from movement and animal–habitat interactions are vital for transforming ecology into a predictive science. This is particularly important in environments undergoing rapid anthropogenic changes, such as the Amazon rainforest, where animals face novel landscapes. Insectivorous bird flocks are key elements of avian biodiversity in the Amazonian ecosystem. Therefore, disentangling and quantifying the drivers behind their movement and space use patterns is of great importance for Amazonian conservation. We use a step selection function (SSF) approach to uncover environmental drivers behind movement choices. This is used to construct a mechanistic model, from which we derive predicted utilization distributions (home ranges) of flocks. We show that movement decisions are significantly influenced by canopy height and topography, but depletion and renewal of resources do not appear to affect movement significantly. We quantify the magnitude of these effects and demonstrate that they are helpful for understanding various heterogeneous aspects of space use. We compare our results to recent analytic derivations of space use, demonstrating that the analytic approximation is only accurate when assuming that there is no persistence in the animals' movement. Our model can be translated into other environments or hypothetical scenarios, such as those given by proposed future anthropogenic actions, to make predictions of spatial patterns in bird flocks. Furthermore, our approach is quite general, so could potentially be used to understand the drivers of movement and spatial patterns for a wide variety of animal communities. Movement of multi-species bird flocks in Amazonia is driven by both canopy height and topography, both of which have large effects on the resources present there. Higher canopies and lower ground tend to be preferable.

Description: Vegetation phenology is a sensitive indicator of the dynamic response of terrestrial ecosystems to climate change. In this study, the spatiotemporal pattern of vegetation dormancy onset date (DOD) and its climate controls over temperate China were examined by analysing the satellite-derived normalized difference vegetation index and concurrent climate data from 1982 to 2010. Results show that preseason (May through October) air temperature is the primary climatic control of the DOD spatial pattern across temperate China, whereas preseason cumulative precipitation is dominantly associated with the DOD spatial pattern in relatively cold regions. Temporally, the average DOD over China's temperate ecosystems has delayed by 0.13 days per year during the past three decades. However, the delay trends are not continuous throughout the 29-year period. The DOD experienced the largest delay during the 1980s, but the delay trend slowed down or even reversed during the 1990s and 2000s. Our results also show that interannual variations in DOD are most significantly related with preseason mean temperature in most ecosystems, except for the desert ecosystem for which the variations in DOD are mainly regulated by preseason cumulative precipitation. Moreover, temperature also determines the spatial pattern of temperature sensitivity of DOD, which became significantly lower as temperature increased. On the other hand, the temperature sensitivity of DOD increases with increasing precipitation, especially in relatively dry areas (e.g. temperate grassland). This finding stresses the importance of hydrological control on the response of autumn phenology to changes in temperature, which must be accounted in current temperature-driven phenological models.

Description: While it is widely recognized that peatlands are important in the global carbon cycle, there is limited information on belowground gas production in tropical peatlands. We measured porewater methane (CH 4 ) and carbon dioxide (CO 2 ) concentrations and δ 13 C isotopic composition and CH 4 and CO 2 production rates in peat incubations from the Changuinola wetland in Panama. Our most striking finding was that CH 4 was depleted in 13 C (-94‰ in porewater and produced at -107‰ in incubated peat) relative to CH 4 found in most temperate and northern wetlands, potentially impacting the accuracy of approaches that use carbon isotopes to constrain global mass balance estimates. Fractionation factors between CH 4 and CO 2 showed that hydrogenotrophic methanogenesis was the dominant CH 4 production pathway, with up to 100% of the CH 4 produced via this route. Far more CO 2 than CH 4 (7 to 100 X) was measured in porewater, due in part to loss of CH 4 through ebullition or oxidation and to the production of CO 2 from pathways other than methanogenesis. We analyzed data on 58 wetlands from the literature to determine the dominant factors influencing the relative proportions of CH 4 produced by hydrogenotrophic and acetoclastic methanogenesis and found that a combination of environmental parameters including pH, vegetation type, nutrient status and latitude are correlated to the dominant methanogenic pathway. Methane production pathways in tropical peatlands do not correlate with these variables in the same way as their more northerly counterparts and thus may be differently affected by climate change.

Description: Gene transcription is strictly controlled by the interplay of regulatory events at gene promoters and gene-distal regulatory elements called enhancers. Despite extensive studies of enhancers, we still have a very limited understanding of their mechanisms of action and their restricted spatio-temporal activities. A better understanding would ultimately lead to fundamental insights into the control of gene transcription and the action of regulatory genetic variants involved in disease. Here, I review and discuss pros and cons of state-of-the-art genomics methods to localize and infer the activity of enhancers. Among the different approaches, profiling of enhancer RNAs yields the highest specificity and may be superior in detecting in vivo activity. I discuss their apparent similarities to promoters, which challenge the established view of enhancers and promoters as distinct entities, and present a unifying model of regulatory elements in transcriptional regulation, in which activity, transcriptional output and regulatory function is context specific. Profiling of enhancer RNAs (eRNAs) likely represents a paradigm shift in enhancer genomics, yielding high specificity in the localization of active enhancers. The similarities between enhancers and promoters are discussed and their established distinctions are deconstructed. Based on this, a unified model of regulatory elements in transcriptional regulation is presented.

Description: Investigations on the functional niche of organisms have primarily focused on differences among species and tended to neglect the potential effects of intraspecific variability despite the fact that its potential ecological and evolutionary importance is now widely recognized. In this study, we measured the distribution of functional traits in an entire population of largemouth bass ( Micropterus salmoides ) to quantify the magnitude of intraspecific variability in functional traits and niche (size, position, and overlap) between age classes. Stable isotope analyses ( δ 13 C and δ 15 N) were also used to determine the association between individual trophic ecology and intraspecific functional trait variability. We observed that functional traits were highly variable within the population (mean coefficient variation: 15.62% ± 1.78% SE) and predominantly different between age classes. In addition, functional and trophic niche overlap between age classes was extremely low. Differences in functional niche between age classes were associated with strong changes in trophic niche occurring during ontogeny while, within age classes, differences among individuals were likely driven by trophic specialization. Each age class filled only a small portion of the total functional niche of the population and age classes occupied distinct portions in the functional space, indicating the existence of ontogenetic specialists with different functional roles within the population. The high amplitude of intraspecific variability in functional traits and differences in functional niche position among individuals reported here supports the recent claims for an individual-based approach in functional ecology. This study investigated the importance of intraspecific variations in the functional niche of a freshwater predator species. We demonstrated the existence of “ontogenetic specialists” in the population that displayed distinct functional and trophic niches driven by ontogenetic shifts (differences between age classes) and trophic specialization (differences within age classes), revealing the importance of accounting for intraspecific trait variability when quantifying the functional diversity of animal communities.

Description: Understanding how invasive species establish and spread is vital for developing effective management strategies for invaded areas and identifying new areas where the risk of invasion is highest. We investigated the explanatory power of dispersal histories reconstructed based on local-scale wind data and a regional-scale wind-dispersed particle trajectory model for the invasive seed chalcid wasp Megastigmus schimitscheki (Hymenoptera: Torymidae) in France. The explanatory power was tested by: (1) survival analysis of empirical data on M. schimitscheki presence, absence and year of arrival at 52 stands of the wasp's obligate hosts, Cedrus (true cedar trees); and (2) Approximate Bayesian analysis of M. schimitscheki genetic data using a coalescence model. The Bayesian demographic modeling and traditional population genetic analysis suggested that initial invasion across the range was the result of long-distance dispersal from the longest established sites. The survival analyses of the windborne expansion patterns derived from a particle dispersal model indicated that there was an informative correlation between the M. schimitscheki presence/absence data from the annual surveys and the scenarios based on regional-scale wind data. These three very different analyses produced highly congruent results supporting our proposal that wind is the most probable vector for passive long-distance dispersal of this invasive seed wasp. This result confirms that long-distance dispersal from introduction areas is a likely driver of secondary expansion of alien invasive species. Based on our results, management programs for this and other windborne invasive species may consider (1) focusing effort at the longest established sites and (2) monitoring outlying populations remains critically important due to their influence on rates of spread. We also suggest that there is a distinct need for new analysis methods that have the capacity to combine empirical spatiotemporal field data, genetic data, and environmental data to investigate dispersal and invasion. We investigated the explanatory power of dispersal histories reconstructed based on local-scale wind data and a regional-scale wind-dispersed particle trajectory model for an invasive habitat-specialist insect species. We showed that prevailing winds can favour the spread of invasive species facing habitat fragmentation through increased frequencies of long-distance dispersal events.

Description: Biogeochemical rate processes in the Arctic are not currently well constrained and there is very limited information on how rates may change as the region warms. Here we present data on the sensitivity of ammonium (NH 4 + ) uptake and nitrification rates to short-term warming. Samples were collected from the Chukchi Sea off the coast of Barrow, Alaska during winter, spring, and summer and incubated for 24 hours in the dark with additions of 15 NH 4 + at -1.5, 6, 13, and 20 °C. Rates of NH 4 + uptake and nitrification were measured in conjunction with bacterial production. In all seasons, NH 4 + uptake rates were highest at temperatures similar to current summertime conditions, but dropped off with increased warming, indicative of psychrophilic (i.e. cold-loving) microbial communities. In contrast, nitrification rates were less sensitive to temperature and were higher in winter and spring compared to summer. These findings suggest that as the Arctic coastal ecosystem continues to warm, NH 4 + assimilation may become increasingly important, relative to nitrification, although the magnitude of NH 4 + assimilation would be still be lower than nitrification.

Description: Urban green spaces provide ecosystem services to city residents, but their management is hindered by a poor understanding of their ecology. We examined a novel ecosystem service relevant to urban public health and esthetics: the consumption of littered food waste by arthropods. Theory and data from natural systems suggest that the magnitude and resilience of this service should increase with biological diversity. We measured food removal by presenting known quantities of cookies, potato chips, and hot dogs in street medians (24 sites) and parks (21 sites) in New York City, USA. At the same sites, we assessed ground-arthropod diversity and abiotic conditions, including history of flooding during Hurricane Sandy 7 months prior to the study. Arthropod diversity was greater in parks (on average 11 hexapod families and 4.7 ant species per site), than in medians (nine hexapod families and 2.7 ant species per site). However, counter to our diversity-based prediction, arthropods in medians removed 2–3 times more food per day than did those in parks. We detected no effect of flooding (at 19 sites) on this service. Instead, greater food removal was associated with the presence of the introduced pavement ant ( Tetramorium sp. E) and with hotter, drier conditions that may have increased arthropod metabolism. When vertebrates also had access to food, more was removed, indicating that arthropods and vertebrates compete for littered food. We estimate that arthropods alone could remove 4–6.5 kg of food per year in a single street median, reducing its availability to less desirable fauna such as rats. Our results suggest that species identity and habitat may be more relevant than diversity for predicting urban ecosystem services. Even small green spaces such as street medians provide ecosystem services that may complement those of larger habitat patches across the urban landscape.

Description: Environmental variation often induces shifts in functional traits, yet we know little about whether plasticity will reduce extinction risks under climate change. As climate change proceeds, phenotypic plasticity could enable species with limited dispersal capacity to persist in situ , and migrating populations of other species to establish in new sites at higher elevations or latitudes. Alternatively, climate change could induce maladaptive plasticity, reducing fitness, and potentially stalling adaptation and migration. Here, we quantified plasticity in life history, foliar morphology, and ecophysiology in Boechera stricta (Brassicaceae), a perennial forb native to the Rocky Mountains. In this region, warming winters are reducing snowpack and warming springs are advancing the timing of snow melt. We hypothesized that traits that were historically advantageous in hot and dry, low-elevation locations will be favored at higher elevation sites due to climate change. To test this hypothesis, we quantified trait variation in natural populations across an elevational gradient. We then estimated plasticity and genetic variation in common gardens at two elevations. Finally, we tested whether climatic manipulations induce plasticity, with the prediction that plants exposed to early snow removal would resemble individuals from lower elevation populations. In natural populations, foliar morphology and ecophysiology varied with elevation in the predicted directions. In the common gardens, trait plasticity was generally concordant with phenotypic clines from the natural populations. Experimental snow removal advanced flowering phenology by 7 days, which is similar in magnitude to flowering time shifts over 2–3 decades of climate change. Therefore, snow manipulations in this system can be used to predict eco-evolutionary responses to global change. Snow removal also altered foliar morphology, but in unexpected ways. Extensive plasticity could buffer against immediate fitness declines due to changing climates.

Description: Compensatory growth (CG) may be an adaptive mechanism that helps to restore an organisms’ growth trajectory and adult size from deviations caused by early life resource limitation. Yet, few studies have investigated the genetic basis of CG potential and existence of genetically based population differentiation in CG potential. We studied population differentiation, genetic basis, and costs of CG potential in nine-spined sticklebacks ( Pungitius pungitius ) differing in their normal growth patterns. As selection favors large body size in pond and small body size in marine populations, we expected CG to occur in the pond but not in the marine population. By manipulating feeding conditions ( viz . high, low and recovery feeding treatments), we found clear evidence for CG in the pond but not in the marine population, as well as evidence for catch-up growth (i.e., size compensation without growth acceleration) in both populations. In the marine population, overcompensation occurred individuals from the recovery treatment grew eventually larger than those from the high feeding treatment. In both populations, the recovery feeding treatment reduced maturation probability. The recovery feeding treatment also reduced survival probability in the marine but not in the pond population. Analysis of interpopulation hybrids further suggested that both genetic and maternal effects contributed to the population differences in CG. Hence, apart from demonstrating intrinsic costs for recovery growth, both genetic and maternal effects were identified to be important modulators of CG responses. The results provide an evidence for adaptive differentiation in recovery growth potential. Compensatory growth (CG) may be an adaptive mechanism that helps to restore an organisms’ growth trajectory and adult size from deviations caused by early life resource limitation. Here, we show that nine-spined sticklebacks show clear evidence for true compensatory growth, but these responses differ between two phenotypically and genetically divergent populations. Evidence is also provided for costs of compensatory growth.

Description: Recent studies indicate that lianas are increasing in size and abundance relative to trees in neotropical forests. As a result, forest dynamics and carbon balance may be altered through liana-induced suppression of tree growth and increases in tree mortality. Increasing atmospheric CO 2 is hypothesized to be responsible for the increase in neotropical lianas, yet no study has directly compared the relative response of tropical lianas and trees to elevated CO 2 . We explicitly tested whether tropical lianas had a larger response to elevated CO 2 than co-occurring tropical trees, and whether seasonal drought alters the response of either growth form. In two experiments conducted in central Panama, one spanning both wet and dry seasons and one restricted to the dry season, we grew liana (n=12) and tree (n=10) species in open-top growth chambers maintained at ambient or twice-ambient CO 2 levels. Seedlings of eight individuals (four lianas, four trees) were grown in the ground in each chamber for at least three months during each season. We found that both liana and tree seedlings had a significant and positive response to elevated CO 2 (in biomass, leaf area, leaf mass per area, and photosynthesis), but that the relative response to elevated CO 2 for all variables was not significantly greater for lianas than trees regardless of the season. The lack of differences in the relative response between growth forms does not support the hypothesis that elevated CO 2 is responsible for increasing liana size and abundance across the neotropics. This article is protected by copyright. All rights reserved.

Description: Inland waters are hotspots for carbon (C) cycling and therefore important for landscape C budgets. Small streams and lakes are particularly important, however quantifying C fluxes is difficult and has rarely been done for the entire aquatic continuum, comprised of connected streams and lakes within the same catchment. We investigated carbon dioxide (CO 2 ) evasion and fluvial fluxes of dissolved inorganic and organic carbon (DIC and DOC) in stream and lake systems within the 2.3 km 2 catchment of a small boreal lake. Our results show pronounced spatial and temporal variability in C fluxes even at a small spatial scale. C loss from the catchment through CO 2 evasion from headwaters for the total open water-sampling period was 9.7 g C m -2 catchment, dominating the total catchment C loss (including CO 2 evasion, DIC and DOC export from the lake, which were 2.7, 0.2 and 5.2 g C m -2 catchment, respectively). Aquatic CO 2 evasion was dominated by headwater streams that occupy ~0.1% of the catchment, but contributed 65% to the total aquatic CO 2 evasion from the catchment. The importance of streams was mainly an effect of the higher gas transfer velocities than compared to lakes (median, 67 and 2.2 cm h -1 , respectively). Accurately estimating the contribution of C fluxes from headwater streams, particularly the temporal and spatial dynamics in their gas transfer velocity, is key to landscape-scale C budgets. This study demonstrates that CO 2 evasion from headwaters can be the major pathway of C loss from boreal catchments, even at a small spatial scale.

Description: Worldwide dam building in large river basins has substantially altered the carbon cycle by trapping much of the riverine transported particulate organic carbon (POC) in terrestrial reservoirs. Here we take the Changjiang (Yangtze) River basin, in which ~50,000 dams were built over the past 50 years, as an example to evaluate the effect of dam building on POC sequestration. We report the characteristics (elemental composition, radiocarbon and stable carbon isotopic compositions, and Raman spectra) of bulk POC in the lower Changjiang from October 2007 to September 2008, and we estimate the POC sequestration induced by dam building since the 1950s for the Changjiang Basin. Using radiocarbon measurements, we quantify the fraction of biospheric POC (POC bio ) and petrogenic POC (POC petro ) in Changjiang POC. Over the study period, around 25% of the Changjiang POC is radiocarbon-dead POC petro ; the remaining is POC bio with a mean radiocarbon age of ~3.5 kyr. Studies on the East China Sea (ECS) shelf, along with an oxidation experiment, suggest that, prior to dam building, the Changjiang POC bio was significantly oxidized in the ECS margin. In contrast, high preservation of POC is observed in Changjiang reservoirs. Combining our POC data with hydrometric datasets, our study indicates that, over the past five decades, dam building may have largely shifted the Changjiang POC burial site from the ECS margin to terrestrial reservoirs. This shift in burial site preserved labile POC bio that would have been oxidized, suggesting a new temporary carbon sink. We estimate that dam building in the Changjiang has sequestered ~4.9 ± 1.9 Mt POC bio every year since 2003, approximately 10% of the global riverine POC burial flux to the oceans.

Description: Analyses of the international human genome sequencing results in 2004 converged to a consensual number of ~20 000 protein-coding genes, spanning over 〈2% of the total genomic sequence. Therefore, the developmental and physiological complexity of human beings remains unaccounted if viewed only in terms of the number of protein-coding genes; the epigenetic influences involving chromatin remodelling and RNA interference and alternative precursor messenger RNA splicing of functional protein-coding transcripts as well as post-translational modifications of proteins increase the diversity and the functionality of the proteome and likely explain the increased complexity. In addition, there has been an explosion of research addressing possible functional roles for the other 98% of the human genome that does not encode proteins. In fact, 〉90% of the human genome is likely to be transcribed yielding a complex network of overlapping transcripts that include tens of thousands of long RNAs with little or no protein forming capacity; they are collectively called non-coding RNA. This review highlights the fundamental concepts of biological roles of non-coding RNA and their importance in regulation of cellular physiology under disease conditions like cancer. Copyright © 2014 John Wiley & Sons, Ltd.

Description: Despite benefits for precision, ecologists rarely use informative priors. One reason that ecologists may prefer vague priors is the perception that informative priors reduce accuracy. To date, no ecological study has empirically evaluated data-derived informative priors' effects on precision and accuracy. To determine the impacts of priors, we evaluated mortality models for tree species using data from a forest dynamics plot in Thailand. Half the models used vague priors, and the remaining half had informative priors. We found precision was greater when using informative priors, but effects on accuracy were more variable. In some cases, prior information improved accuracy, while in others, it was reduced. On average, models with informative priors were no more or less accurate than models without. Our analyses provide a detailed case study on the simultaneous effect of prior information on precision and accuracy and demonstrate that when priors are specified appropriately, they lead to greater precision without systematically reducing model accuracy. Despite benefits for precision, ecologists rarely use informative priors. One reason ecologists prefer vague priors is the perception that informative priors reduce accuracy. To date no ecological study has evaluated informative priors' effects on precision and accuracy. To determine impacts of priors, we evaluated mortality models for tree species using data from a forest dynamics plot in Thailand.

Description: Despite strong interest in understanding how habitat spatial structure shapes the genetics of populations, the relative importance of habitat amount and configuration for patterns of genetic differentiation remains largely unexplored in empirical systems. In this study, we evaluate the relative influence of, and interactions among, the amount of habitat and aspects of its spatial configuration on genetic differentiation in the pitcher plant midge, Metriocnemus knabi . Larvae of this species are found exclusively within the water-filled leaves of pitcher plants ( Sarracenia purpurea ) in a system that is naturally patchy at multiple spatial scales (i.e., leaf, plant, cluster, peatland). Using generalized linear mixed models and multimodel inference, we estimated effects of the amount of habitat, patch size, interpatch distance, and patch isolation, measured at different spatial scales, on genetic differentiation ( F ST ) among larval samples from leaves within plants, plants within clusters, and clusters within peatlands. Among leaves and plants, genetic differentiation appears to be driven by female oviposition behaviors and is influenced by habitat isolation at a broad (peatland) scale. Among clusters, gene flow is spatially restricted and aspects of both the amount of habitat and configuration at the focal scale are important, as is their interaction. Our results suggest that both habitat amount and configuration can be important determinants of genetic structure and that their relative influence is scale dependent. We explore a long-standing question in landscape ecology on the relative importance of habitat amount and configuration on spatial patterns of genetic differentiation. Using a spatially nested empirical system, we show that the importance of habitat amount and configuration depends on spatial scale and that they can interact to drive spatial genetic patterns.

Description: Studying the population history and demography of organisms with important ecological roles can aid understanding of evolutionary processes at the community level and inform conservation. We screened genetic variation (mtDNA and microsatellite) across the populations of the southern grey shrike ( Lanius meridionalis koenigi ) in the Canary Islands, where it is an endemic subspecies and an important secondary seed disperser. We show that the Canarian subspecies is polyphyletic with L. meridionalis elegans from North Africa and that shrikes have colonized the Canary Islands from North Africa multiple times. Substantial differences in genetic diversity exist across islands, which are most likely the product of a combination of historical colonization events and recent bottlenecks. The Eastern Canary Islands had the highest overall levels of genetic diversity and have probably been most recently and/or frequently colonized from Africa. Recent or ongoing bottlenecks were detected in three of the islands and are consistent with anecdotal evidence of population declines due to human disturbance. These findings are troubling given the shrike's key ecological role in the Canary Islands, and further research is needed to understand the community-level consequences of declines in shrike populations. Finally, we found moderate genetic differentiation among populations, which largely reflected the shrike's bottleneck history; however, a significant pattern of isolation-by-distance indicated that some gene flow occurs between islands. This study is a useful first step toward understanding how secondary seed dispersal operates over broad spatial scales. We used molecular markers to determine the population history of the southern grey shrike ( Lanius meridionalis koenigi ) in the Canary Islands, where it is an endemic subspecies and an important secondary seed disperser. We show close relationships between Canarian populations and North African subspecies, and that three of the Canarian populations have undergone recent population declines, probably due to human disturbance. The implications for the ecology and conservation of shrikes are discussed.

Description: Since the discovery of brain asymmetry in a wide range of vertebrate species, it has become possible to study development and expression of lateralized behavior accurately in well-controlled experiments. Several species have emerged as useful models for investigating aspects of lateralization. Discussed here are: (1) the influence of exposure to light during embryonic development on lateralization, (2) effects of steroid hormones on lateralization, (3) developmental changes in which hemisphere is controlling behavior, and (4) asymmetry in memory formation and recall. The findings have bearing on understanding the development of hemispheric specialization in humans and are likely to provide insight into dysfunctional behavior associated with weak or absent lateralization and impaired interhemispheric communication (e.g., autism, schizophrenia, dyslexia). This review features research on chicks, pigeons and zebrafish, with the addition of some recent evidence of lateralization in bees. Discoveries made using these species have highlighted the interaction between experience, hormones and genetic factors during development, and have provided some of the first clear evidence of the advantage of having a lateralized brain. © 2014 Wiley Periodicals, Inc.

Description: Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome, which spontaneously resolves within several weeks or months after birth, may represent a very special form of leukemia arising in the fetal liver (FL). To explore the role of the fetal hematopoietic microenvironment in the pathogenesis of TAM, we examined the in vitro influences of stromal cells of human FL and fetal bone marrow (FBM) on the growth of TAM blasts. Both FL and FBM stromal cells expressed mesenchymal cell antigens (vimentin, α-smooth muscle actin, CD146 and nestin), being consistent with perivascular cells/mesenchymal stem cells that support hematopoietic stem cells. In addition, a small fraction of the FL stromal cells expressed an epithelial marker, cytokeratin 8, indicating that they could be cells in epithelial-mesenchymal transition (EMT). In the coculture system, stromal cells of the FL, but not FBM, potently supported the growth of TAM blast progenitors, mainly through humoral factors. High concentrations of hematopoietic growth factors were detected in culture supernatants of the FL stromal cells and a neutralizing antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) almost completely inhibited the growth-supportive activity of the culture supernatants. These results indicate that FL stromal cells with unique characteristics of EMT cells provide a pivotal hematopoietic microenvironment for TAM blasts and that GM-CSF produced by FL stromal cells may play an important role in the pathogenesis of TAM.

Description: Because of the biological relevance of thiols and sulfides such as cysteine, homocysteine, glutathione and hydrogen sulfide, their detection has attracted a great deal of research interest. Fluorescent probes are emerging as a new strategy for thiol and hydrogen sulfide analysis due to their high sensitivity, low cost, and ability to detect and image thiols in biological samples. In this short review we have summarized recent advances in the development of thiol and hydrogen sulfide reactive fluorescent probes. These probes are compared and contrasted with regard to their designing strategies, mechanisms, photophysical properties, and/or reaction kinetics. Biological applications of these probes are also discussed. J. Cell. Biochem. 9999: XX–XX, 2014. © 2013 Wiley Periodicals, Inc.

Description: Liraglutide, a modified form of glucagon-like peptide-1 (GLP-1), has been found to improve beta cell function in type 2 diabetes (T2DM). However, the effect of liraglutide on beta cell function under lipotoxic stress and the underlying molecular mechanisms remain unclear. In the present study, we investigated the role of PI3K/Akt/FoxO1 signaling in liraglutide-involved beta cell protection in high free fatty acids (FFAs) condition. The apoptosis, proliferation, and insulin secretion capability of MIN6 cells and islets from C57BL/6J mice were evaluated when exposed to FFAs with/without liraglutide. The expression of effectors involved in PI3K/Akt/FoxO1signalling pathway was detected by real-time PCR and western blotting in MIN6 cells and islets from C57BL/6J mice. Liraglutide substantially inhibited the lipoapoptosis and improved the proliferation and insulin secretion of beta cells in high FFAs condition. Western blot revealed that the phosphorylation of Akt and FoxO1 was markedly decreased under lipid stress but was elevated when treated with liraglutide. Moreover, FFAs could up-regulate the expression levels of p27, Bax, Cidea but down-regulate the expression levels of Pdx-1, MafA, and NeuroD in beta cells, which was canceled by the addition of liraglutide. Moreover, LY294002, a PI3K inhibitor, could significantly abrogate all the protective actions of liraglutide against lipotoxicity. We concluded that liraglutide markedly improved beta cell function under lipid stress and that the protective action of liraglutide was mediated by activation of PI3K/Akt, which resulted in inactivation of FoxO1 along with the down-regulation of p27, Bax, Cidea and up-regulation of Pdx-1, MafA, and NeuroD expressions.

Description: The protective potential of chelators, i.e. N-acetyl cysteine (0.6 mg /kg, intraperitoneally) and dithiothreitol (15.4 mg kg −1 , intraperitoneally) with selenium (0.5 mg kg −1 , pre-oral) were evaluated individually and in combination against methylmercury-induced biochemical alterations and oxidative stress consequences. Forty-two male Sprague–Dawley rats were exposed with methylmercury (1.5 mg kg −1 , pre-oral) daily for 21 days followed by different treatments for five consecutive days. Administration of methylmercury caused significant enhancement in the release of transaminases, alkaline phosphatases and lactate dehydrogenases in serum. A significant increased was observed in lipid peroxidation level with a concomitant decreased in glutathione content after methylmercury exposure in liver, kidney and brain. Hepatic microsomal drug metabolizing enzymes (aniline hydroxylase and amidopyrine N-demethylase) of cytochrome p4502E 1 showed sharp depletion after methylmercury exposure. Alterations in histological changes in liver, kidney and brain were also noted in methylmercury administered group. All treated groups showed recovery pattern, but the combined treatments with N-acetyl cysteine and dithiothreitol in combination with selenium were more effective than that with either alone treatments in recovering blood biochemical changes after methylmercury toxicity. In conclusion, the results demonstrated that combination therapy may recover all blood biochemical alterations and offer maximum protection against methylmercury-induced toxicity. Copyright © 2014 John Wiley & Sons, Ltd.

Description: Comparing structural and evolutionary dynamics of proteins . On pages 209–218 Marsh and Teichmann discuss parallels between protein dynamics and evolution, and how we can gain insights into function from these studies. Buried residues, for example, are usually more evolutionarily conserved and evolve less quickly than exposed residues. These residues generally form more intramolecular contacts, and mutating them would therefore more likely lead to a destabilization of the protein. Having more intramolecular contacts on the other hand also means that these residues are less flexible to move around. In contrast, dynamic parts of a protein in real time are also dynamic over evolutionary time and evolve more quickly. The cover shows the buried (blue) and surface (red) residues for the receiver domain of sensor histidine kinase CKI1 from Arabidopsis .

Description: [1]  Shrublands in semi-arid regions are heterogeneous landscapes consisting of infertile bare areas separated by nutrient rich vegetated areas known as resource islands. Spatial patterns in these landscapes are structured by feedbacks driven by the transport of water and nutrient resources from the intershrub space to areas below shrubs, and the retention of these resources to locally drive productivity and tight biogeochemical cycles. Most understanding of plant-soil feedbacks is based predominantly on studies of low topographic gradient landscapes, and it is unclear whether the patterns of association between soils and vegetation, and the autogenic processes that create them, also occur on more steeply sloping terrain. Here we analyze the spatial patterns of soils, vegetation and micro-topography on hillslopes of contrasting lithology (one granite at 16 ∘ , one schist at 27 ∘ ) in the Sonoran desert foothills of the Catalina Mountains. We also describe a method of extracting vegetation density from terrestrial laser scanning point-cloud data at 5 cm × 5 cm scales, and find that it correlates well with soil organic carbon measurements. Vegetation was associated with microtopographic mounds (relative to the mean slope) extending 0.3 m downslope and 1.8 m (schist) and 0.9 m (granite) upslope on the study hillslopes. Soils below the shrub canopies exhibited 2-3 times more soil organic matter and 2-4 times higher hydraulic conductivity than the interspaces. Soils enriched with organic matter were found to extend at least two canopy radii downslope of woody shrubs, but not upslope. These plumes were clearest in the lower-gradient granite site where vegetation mounds created distinct patterns of microtopographic convergence and divergence. At the steeper schist site microtopography appeared to have a weaker control on topographic flow accumulation. Collectively our findings suggest that the spatial structure of association between soils and microtopography and vegetation on these slopes exhibit many of the features observed in lower-gradient areas. However microtopography and soils are more asymmetric along the downslope axis of the hillslopes than lower-gradient areas, and vary with lithology. Alluvial and colluvial processes are likely more important in shaping vegetation and soil dynamics on hillslopes, and these factors need further consideration in scaling results to the landscape level.

Description: [1]  Plant phenology, a sensitive indicator of climate change, influences vegetation-atmosphere interactions by changing the carbon and water cycles from local to global scales. Camera-based phenological observations of the color changes of the vegetation canopy with throughout the growing season have become popular in recent years. However, the linkages between camera phenological metrics and leaf biochemical, biophysical and spectral properties are elusive. We measured key leaf properties including chlorophyll and carotenoids concentrations and leaf reflectance on a weekly basis from June to November, 2011 in a white oak forest on the island of Martha's Vineyard, Massachusetts, USA. Concurrently, we used a digital camera to automatically acquire daily pictures of the tree canopies. We found that there was a mismatch between the camera-based phenological metric for the canopy greenness (green chromatic coordinate, g cc ) and the total chlorophyll and carotenoids concentration and leaf mass per area during late spring/early summer. The seasonal peak of g cc is approximately 20 days earlier than the peak of the total chlorophyll concentration. During the summer we observed a gradual decline of g cc and leaf-level vegetation index in a period of insignificant change in total chlorophyll concentration. During the fall, both canopy and leaf redness (red chromatic coordinate, r cc ) were significantly correlated with the vegetation index for anthocyanin concentration, opening a new window to quantify vegetation senescence remotely. Satellite and camera-based vegetation indices agreed well, suggesting that camera-based observations can be used as the ground validation for satellites. Using the high temporal resolution dataset of leaf biochemical, biophysical and spectral properties, our results show the strengths and potential uncertainties to use canopy color as the proxy of ecosystem functioning. Our results suggest an urgent need for additional research that bridges the gap between leaf physiological properties and camera-based phenological metrics.

Description: Ecological Applications, Volume 24, Issue 1, Page 3, January 2014.

Description: Ecological Applications, Volume 24, Issue 1, Page 23-24, January 2014.

Description: Ecological Applications, Volume 24, Issue 1, Page 227-228, January 2014.

Description: Ecology, Volume 95, Issue 1, Page 68-77, January 2014. Delayed life history effects (DLHEs) occur when fitness in one life stage affects fitness in subsequent life stages. Given their biphasic life cycle, pond-breeding amphibians provide a natural system for studying DLHEs, although these effects are not restricted to species with biphasic life histories. In this study, we used multiple mark–recapture techniques enabled by a large trapping array to monitor components of fitness and resulting DLHEs in a population of the endangered California tiger salamander (Ambystoma californiense). We found that DLHEs are prominent across all life stage transitions and that there is variation in whether selection acts primarily at the individual or cohort level. We also demonstrated that there is more than an order of magnitude variation in mean cohort fitness, providing tremendous variation for DLHEs to act upon. We documented an evolutionary trade-off between mass at emergence and date of emergence, which may play a role in maintaining the variation in mass (fitness) at emergence. A literature review revealed that such high levels of intercohort variation occur in many other pond-breeding amphibians, and that appropriately documenting the magnitude of intercohort variation requires long-term studies (roughly two population turnovers). Given the profound effect that DLHEs can have on population dynamics, quantifying intercohort variation in mean fitness and the level(s) at which selection acts will be very important for developing accurate models of population dynamics. In general, when developing models of population dynamics, more attention should be paid to variation in mean fitness and not just variation in total numbers.

Description: Ecological Applications, Volume 24, Issue 1, Page 71-83, January 2014. Concerns about bycatch of protected species have become a dominant factor shaping fisheries management. However, efforts to mitigate bycatch are often hindered by a lack of data on the distributions of fishing effort and protected species. One approach to overcoming this problem has been to overlay the distribution of past fishing effort with known locations of protected species, often obtained through satellite telemetry and occurrence data, to identify potential bycatch hotspots. This approach, however, generates static bycatch risk maps, calling into question their ability to forecast into the future, particularly when dealing with spatiotemporally dynamic fisheries and highly migratory bycatch species. In this study, we use boosted regression trees to model the spatiotemporal distribution of fishing effort for two distinct fisheries in the North Pacific Ocean, the albacore (Thunnus alalunga) troll fishery and the California drift gillnet fishery that targets swordfish (Xiphias gladius). Our results suggest that it is possible to accurately predict fishing effort using

Description: Ecology, Volume 95, Issue 1, Page 30-36, January 2014. Competition plays an important role in structuring the community dynamics of phytophagous insects. As the number and impact of biological invasions increase, it has become increasingly important to determine whether competitive differences exist between native and exotic insects. We conducted a meta-analysis to test the hypothesis that native/exotic status affects the outcome of herbivore competition. Specifically, we used data from 160 published studies to assess plant-mediated competition in phytophagous insects. For each pair of competing herbivores, we determined the native range and coevolutionary history of each herbivore and host plant. Plant-mediated competition occurred frequently, but neither native nor exotic insects were consistently better competitors. Spatial separation reduced competition in native insects but showed little effect on exotics. Temporal separation negatively impacted native insects but did not affect competition in exotics. Insects that coevolved with their host plant were more affected by interspecific competition than herbivores that lacked a coevolutionary history. Insects that have not coevolved with their host plant may be at a competitive advantage if they overcome plant defenses. As native/exotic status does not consistently predict outcomes of competitive interactions, plant–insect coevolutionary history should be considered in studies of competition.

Description: Trehalose-6-phosphate phosphatase (TPP) catalyzes the final step in the biosynthesis of the anti-stress sugar trehalose. An 82 kDa TPP enzyme was isolated from Candida utilis with 61% yield and 43-fold purification. The protein sequence, determined by N-terminal sequencing and MALDI-TOF analysis, showed significant homology with known TPP sequences from related organisms. The full length gene sequence of TPP of Candida utilis was identified using rapid amplification of cDNA ends - PCR reaction (RACE-PCR). The gene was cloned and expressed in E. coli BL21. Recombinant TPP enzyme was isolated using affinity chromatography. CD spectroscopy and steady state fluorescence revealed that the structural and conformational aspects were identical in both native and recombinant forms. The biochemical properties of the two forms were also similar. K m was determined to be ∼0.8 mM. Optimum temperature and pH was found to be 30 °C and 8.5 respectively. Activity was dependent on the presence of divalent cations and inhibited by metal chelators. Methylation mediated regulation of TPP enzyme and its effect on the overall survival of the organism under stress were investigated. The results indicated that enhancement of TPP activity by methylation at the Cysteine residues increased resistance of Candida cells against thermal stress. This work involves extensive investigations towards understanding the physico-chemical properties of the first TPP enzyme from any yeast strain. The mechanism by which methylation regulates its activity has also been studied. A correlation between regulation of trehalose synthesis and survivability of the organism under thermal stress was established. J. Cell. Physiol. 9999: XX–XX, 2014. © 2014 Wiley Periodicals, Inc.

Description: The microvascular network of the microcirculation works in tight communication with surrounding tissues to control blood supply and exchange of solutes. In cerebral circulation, microvascular endothelial cells constitute a selective permeability barrier that controls the environment of parenchymal brain tissue, which is known as the blood-brain barrier (BBB). Connexin- and pannexin-formed channels (gap junctions and hemichannels) play a central role in the coordination of endothelial and smooth muscle cell function and connexin-mediated signaling in endothelial cells is essential in the regulation of BBB permeability. Likewise, gap junction communication between astrocyte-end feet also contributes to maintain the BBB integrity, but the participation of hemichannels in this process cannot be discarded. Sympathetic and sensory perivascular nerves are also involved in the control and coordination of vascular function through the release of vasoconstrictor or vasodilator signals and by the regulation of gap junction communication in the vessel wall. Conversely, ATP release through pannexin-1-formed channels mediates the α1-adrenergic signaling. Furthermore, here we show that capsaicin-induced CGRP release from mesenteric perivascular sensory nerves induces pannexin-1-formed channel opening, which in turn leads to reduction of pannexin-1 and endothelial nitric oxide synthase (eNOS) expression along the time. Interestingly, blockade of CGRP receptors with CGRP 8–37 increased eNOS expression by ∼5 fold, suggesting that capsaicin-sensitive sensory nerves are involved in the control of key signaling proteins for vascular function. In this review, we discuss the importance of connexin-based channels in the control of BBB integrity and the functional interaction of vascular connexins and pannexins with the peripheral nervous system.

Description: [1]  The equatorial Pacific is a dynamic region that plays an important role in the global carbon cycle. This region is the largest oceanic source of carbon dioxide (CO 2 ) to the atmosphere, which varies interannually dependent on the El Niño-Southern Oscillation (ENSO) and other climatic and oceanic drivers. We present high-resolution observations of surface ocean CO 2 partial pressure ( p CO 2 ) at four fixed locations in the Niño 3.4 area with datasets encompassing 10 ENSO warm and cold events from 1997 to 2011. The mooring observations confirm that ENSO controls much of the interannual variability in surface seawater p CO 2 with values ranging from 315 to 578 µatm. The mooring time series also capture the temporal variability necessary to make the first estimates of long-term pH trends in the equatorial Pacific, which suggest the combination of ocean acidification and decadal variability create conditions for high rates of pH change since the beginning of the mooring record. Anthropogenic CO 2 increases play a dominant role in significant observed seawater p CO 2 trends of +2.3 to +3.3 µatm yr -1 and pH trends of -0.0018 to -0.0026 yr -1 across the full time series in this region. However, increased upwelling driven by increased trade winds, a shallower thermocline, and increased frequency of La Niña events also contribute an average of 40% of the observed trends since 1998. These trends are higher than previous estimates based on underway observations and suggest that the equatorial Pacific is contributing a greater amount of CO 2 to the atmospheric CO 2 inventory over the last decade.

Description: Ecology, Volume 0, Issue 0, Ahead of Print. Predicting the future trend and viability of populations is an essential task in ecology. Because many populations respond to changing environments, uncertainty surrounding environmental responses must be incorporated into population assessments. However, understanding the effects of environmental variation on population dynamics requires information on several important demographic parameters which are often difficult to estimate. Integrated population models facilitate the integration of time-series data on population size and all existing demographic information from a species, allowing the estimation of demographic parameters for which limited or no empirical data exist. Although these models are ideal for assessments of population viability, they have so far not included environmental uncertainty. We incorporated environmental variation in an integrated population model to account for both demographic and environmental uncertainty in an assessment of population viability. In addition, we used this model to estimate true juvenile survival, an important demographic parameter for population dynamics that is difficult to estimate empirically. We applied this model to assess the past and future population trend of a rare island endemic songbird, the Montserrat Oriole Icterus oberi, which is threatened by volcanic activity. Montserrat Orioles experienced lower survival in years with volcanic ash-fall, causing periodic population declines that were compensated by higher seasonal fecundity in years with high pre-breeding season rainfall. Due to the inclusion of both demographic and environmental uncertainty in the model, the estimated population growth rate in the immediate future was highly imprecise (95% credible interval 0.844 - 1.105), and the probability of extinction after three generations (in the year 2028) was low (2.1%). This projection demonstrates that accounting for both demographic and environmental sources of uncertainty provides a more realistic assessment of the viability of populations under unknown future environmental conditions.

Description: Ecology, Volume 0, Issue 0, Ahead of Print. Evidence of age-dependent changes in foraging behavior of free-ranging individuals is scarce, especially at older stages. Using the isotopic niche as a proxy of the trophic niche during both the breeding (blood) and inter-nesting (feather) periods, we report here empirical evidence for age-, gender- and breeding status-dependent foraging ecology and examine its potential consequences on subsequent reproduction and survival in an extremely long-lived species, the wandering albatross. Immature wandering albatrosses of both sexes forage in the subtropics (δ13C) and feed at the same trophic position (δ15N) than the adults. In contrast to immature birds, adult females forage on average at northern latitudes than males, with both sexes feeding in the subtropics during the inter-nesting period, and males, not females, favouring subantartic waters during incubation. In contrast to adult females, males showed a unique pattern among birds and mammals of a continuous change with age in their main feeding habitat by foraging progressively further south in colder waters during both the breeding and inter-nesting periods. In males, foraging at higher latitudes (lower feather δ13C values) is associated with a lower probability to breed during the following years compared to other birds, but with no effect on their probability to survive. Foraging in cold and windy waters may be linked to foraging impairment that might explain different life history trade-offs and lower investment in reproduction with age. This key point requires further longitudinal investigations and/or studies examining foraging success and energy budget of birds feeding in different water masses.

Description: Ecology, Volume 0, Issue 0, Ahead of Print. Interactions between plants and scatterhoarding animals may shift from mutualism to predation as a function of resources available to those animals. Because seed species differ in their nutrient content and defenses to predation, resource selection and cache management by scatterhoarders, and thus seed fate, may also depend on the relative availability of different seed types. We tracked the fates of tagged Castanea dentata, Quercus alba, and Q. rubra seeds presented to rodents in pairwise combinations and found that C. dentata, which has moderate dormancy prior to germination, survived better in the presence of Q. alba (no dormancy) than with Q. rubra (longer dormancy). Decisions made by scatterhoarders in response to the composition of available seed resources can alter the relationship between masting and seed dispersal effectiveness in individual tree species and may have influenced the evolution of asynchrony among species-specific masting patterns in temperate forests. In theory, preferential allocation of certain seed species to storage or consumption may also result in indirect apparent predation by one seed species on another.

Description: Potter et al., (2013) highlight the challenges and provide recommendations for progress in representing microclimate in Species Distribution Models (SDMs), which are widely used to predict distributions by establishing relationships between climatic variables and species presence. They show that the grid lengths of published SDMs are typically four orders of magnitude larger than the length of animals under study, and three orders of magnitude larger than plants. They conclude that the mismatch between the length scales of climate data and the species themselves is a major barrier for progress, and that the ideal spatial resolution for climate data in SDMs, notwithstanding practical constraints, is between 1 and 10 times the length of the organism. This article is protected by copyright. All rights reserved.

Description: We previously established a role for cancer-associated fibroblasts (CAFs) in enhancing the self-renewal and differentiation potentials of putative prostate cancer stem cells (CSCs). Our published work focused on androgen-dependent prostate cancer (ADPC) using the conditional Pten deletion mouse model. Employing the same model, we now describe the interaction of CAF and CSC in castration-resistant prostate cancer (CRPC). CAF isolated from ADPC (ADPCAF) and from CRPC (CRPCAF) were compared in terms of their ability to support organoid formation and tumor initiation by CSC from CRPC (CRPCSC) in vitro and in vivo. CRPCSC formed spheroids in vitro and well-differentiated glandular structures under the renal capsules of recipient mice in vivo more effectively in the presence of CRPCAF compared to ADPCAF. Furthermore, whereas CSC with CAF from ADPC formed mostly well-differentiated tumors in our previous study, we now show that CRPCSC, when combined with CRPCAF (but not ADPCAF) can form aggressive, poorly differentiated tumors. The potential of CRPCAF to support organoid/tumor formation by CRPCSC remained greater even when compared to 10-fold more ADPCAF, suggesting that paracrine factors produced specifically by CRPCAF preferentially potentiate the stemness and tumorigenic properties of the corresponding CSC. This apparently unique property of CRPCAF was notable when the CAF and CSC were grafted in either intact or castrated recipient mice. In both environments, CRPCAF induced in the epithelial compartment higher proliferative activity compared to ADPCAF, indicated by a higher Ki67 index. Factors released by CRPCAF to regulate CRPCSC may be targeted to develop novel therapeutic approaches to manage prostate cancer. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.

Description: Tat transactivating activity regulated by NAD + -dependent histone deacetylase sirtuin1 (SIRT1) connects HIV transcription with the metabolic state of the cell. Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the mammalian NAD + biosynthesis. Nampt, SIRT1 and AMPK were involved in inhibiting HIV-1 transactivation through redox-regulated pathway. Tanshinone IIA is a main lipid-soluble monomer derivative from the root of Salvia miltiorrhiza (Danshen) and tanshinone ⅡA possess a variety of biological activities through redox signaling pathway. Here we investigated the effect of tanshinone ⅡA on Tat-induced HIV-1 transactivation and the redox signaling pathway involved in it. As the results were shown, tanshinone ⅡA reversed Tat-induced reactive oxygen species (ROS) production and down-regulation of glutathione (GSH) levels in TZM-bl cells through up-regulation of Nrf2 expression. Tanshinone ⅡA reversed Tat-induced inhibition of SIRT1 activity but not SIRT1 protein expression. Tanshinone ⅡA reversed Tat-induced inhibition of Nampt protein expression and depletion of NAD + levels in TZM-bl cells in a dose-dependent manner. Tanshinone ⅡA-evoked Nampt expression was mediated by AMPK signaling pathway. Tanshinone ⅡA inhibited Tat-induced HIV-1 LTR transactivation dependent on AMPK-Nampt pathway. Collectively, our data provide new insights into understanding of the molecular mechanisms of tanshinone ⅡA inhibited Tat-regulated transcription, suggesting that targeting AMPK/Nampt/SIRT1 pathway could serve as new anti-HIV-1 agents.

Description: Osteoblast differentiation is tightly regulated by several factors including microRNAs (miRNAs). In this paper we report that pre-mir-15b is highly expressed in differentiated osteoblasts. The functional role of miR-15b in osteoblast differentiation was determined using miR-15b mimic/inhibitor and the expression of osteoblast differentiation marker genes such as alkaline phosphatase (ALP), type I collagen genes was decreased by miR-15b inhibitor. Runx2, a bone specific transcription factor is generally required for expression of osteoblast differentiation marker genes and in response to miR-15b inhibitor treatment, Runx2 mRNA expression was not changed; whereas its protein expression was decreased. Even though Smurf1 (SMAD specific E3 ubiquitin protein ligase 1), HDAC4 (histone deacetylase 4), Smad7, and Crim1 were found to be few of miR-15b's putative target genes, there was increased expression of only Smurf1 gene at mRNA and protein levels by miR-15b inhibitor. miR-15b mimic treatment significantly increased and decreased expressions of Runx2 and Smurf1 proteins, respectively. We further identified that the Smurf1 3’UTR is directly targeted by miR-15b using the luciferase reporter gene system. This is well documented that Smurf1 interacts with Runx2 and degrades it by proteasomal pathway. Hence, based on our results we suggest that miR-15b promotes osteoblast differentiation by indirectly protecting Runx2 protein from Smurf1 mediated degradation. Thus, this study identified that miR-15b can act as a positive regulator for osteoblast differentiation.

Description: The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R) on a pancreatic cancer patient-derived orthotopic xenografts (PDOX). The PDOX model was originally established from a pancreatic cancer patient in SCID-NOD mice. The pancreatic cancer PDOX was subsequently transplanted by surgical orthotopic implantation (SOI) in transgenic nude red fluorescent protein (RFP) mice in order that the PDOX stably acquired red fluorescent protein (RFP)-expressing stroma for the purposes of imaging the tumor after passage to non-transgenic nude mice in order to visualize tumor growth and drug efficacy. The nude mice with human pancreatic PDOX were treated with A1-R or standard chemotherapy, including gemcitabine (GEM), which is first-line therapy for pancreatic cancer, for comparison of efficacy. A1-R treatment significantly reduced tumor weight, as well as tumor fluorescence area, compared to untreated control ( P  = 0.011), with comparable efficacy of GEM, CDDP, and 5-FU. Histopathological response to treatment was defined according to Evans’s criteria and A1-R had increased efficacy compared to standard chemotherapy. The present report is the first to show that A1-R is effective against a very low-passage patient tumor, in this case, pancreatic cancer. The data of the present report suggest A1-1 will have clinical activity in pancreatic cancer, a highly lethal and treatment-resistant disease and may be most effectively used in combination with other agents.