ALBERT

Description: Publication date: Available online 7 September 2013 Source: FEBS Open Bio Author(s): Veronika Temml , Susanne Kuehnl , Daniela Schuster , Stefan Schwaiger , Hermann Stuppner , Dietmar Fuchs Mediterranean Carthamus tinctorius (Safflower) is used for treatment of inflammatory conditions and neuropsychiatric disorders. Recently C. tinctorius lignans arctigenin and trachelogenin but not matairesinol were described to interfere with the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in peripheral blood mononuclear cells in vitro . We examined a potential direct influence of compounds on IDO enzyme activity applying computational calculations based on 3D geometry of the compounds. The interaction pattern analysis and force field-based minimization was performed within LigandScout 3.03, the docking simulation with MOE 2011.10 using the X-ray crystal structure of IDO. Results confirm the possibility of an intense interaction of arctigenin and trachelogenin with the binding site of the enzyme, while matairesinol had no such effect.

Description: Publication date: Available online 7 September 2013 Source: FEBS Open Bio Author(s): Mitsuru Ishikawa , Jun Shiota , Yuta Ishibashi , Tomoyuki Hakamata , Shizuku Shoji , Mamoru Fukuchi , Masaaki Tsuda , Tomoaki Shirao , Yuko Sekino , Toshihisa Ohtsuka , Jay M. Baraban , Akiko Tabuchi Megakaryoblastic leukemia 1 (MKL1) is a member of the MKL family of serum response factor (SRF) coactivators. Here we have identified three rat MKL1 transcripts: two are homologues of mouse MKL1 transcripts, full-length MKL1 (FLMKL1) and basic, SAP, and coiled-coil domains (BSAC), the third is a novel transcript, M KL1- elo ngated d erivative of y ield (MELODY). These rat MKL1 transcripts are differentially expressed in a wide variety of tissues with highest levels in testis and brain. During brain development, these transcripts display differential patterns of expression. The FLMKL1 transcript encodes two isoforms that utilize distinct translation start sites. The longer form possesses three actin-binding RPXXXEL (RPEL) motifs and the shorter form, MKL1met only has two RPEL motifs. All four rat MKL1 isoforms, FLMKL1, BSAC, MKL1met and MELODY increased SRF-mediated transcription, but not CREB-mediated transcription. Accordingly, the differential expression of MKL1 isoforms may help fine-tune gene expression during brain development.

Description: Not all calcite ballast is created equal: differing effects of foraminiferan and coccolith calcite on the formation and sinking of aggregates Biogeosciences Discussions, 10, 14861-14885, 2013 Author(s): K. Schmidt, C. L. De La Rocha, M. Gallinari, and G. Cortese Correlation between particulate organic carbon (POC) and calcium carbonate sinking through the deep ocean has led to the idea that ballast provided by calcium carbonate is important for the export of POC from the surface ocean. While this idea is certainly to some extent true, it is worth considering in more nuance, for example, examining the different effects on the aggregation and sinking of POC of small, non-sinking calcite particles like coccoliths and large, rapidly sinking calcite like planktonic foraminiferan tests. We have done that here in a simple experiment carried out in roller tanks that allow particles to sink continuously without being impeded by container walls. Coccoliths were efficiently incorporated into aggregates that formed during the experiment, increasing their sinking speed compared to similarly sized aggregates lacking added calcite ballast. The foraminiferan tests, which sank as fast as 700 m d −1 , became associated with only very minor amounts of POC. In addition, when they collided with other, larger, foraminferan-less aggregates, they fragmented them into two smaller, more slowly sinking aggregates. While these effects were certainly exaggerated within the confines of the roller tanks, they clearly demonstrate that calcium carbonate ballast is not just calcium carbonate ballast- different forms of calcium carbonate ballast have notably different effects on POC aggregation, sinking, and export.

Description: Publication date: Available online 11 September 2013 Source: FEBS Open Bio Author(s): Gisele Castro , Maria Fernanda C. Areias , Lais Weissmann , Paula G.F. Quaresma , Carlos K. Katashima , Mario J.A. Saad , Patricia O. Prada Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala.

Description: Phenology as a strategy for carbon optimality: a global model Biogeosciences Discussions, 10, 15107-15152, 2013 Author(s): S. Caldararu, D. W. Purves, and P. I. Palmer Phenology is essential to our understanding of biogeochemical cycles and the climate system. We develop a global mechanistic model of leaf phenology based on the hypothesis that phenology is a strategy for optimal carbon gain at the canopy level so that trees adjust leaf gains and losses in response to environmental factors such as light, temperature and soil moisture, to achieve maximum carbon assimilation. We fit this model to five years of satellite observations of leaf area index (LAI) using a Bayesian fitting algorithm. We show that our model is able to reproduce phenological patterns for all vegetation types and use it to explore variations in growing season length and the climate factors that limit leaf growth for different biomes. Phenology in wet tropical areas is limited by leaf age physiological constraints while at higher latitude leaf seasonality is limited by low temperature and light availability. Leaf growth in grassland regions is limited by water availability but often in combination with other factors. This model will advance the current understanding of phenology for ecosystem carbon models and our ability to predict future phenological behaviour.

Description: Publication date: Available online 12 September 2013 Source: Cell Reports Author(s): Debra A. Mayes , Tilat A. Rizvi , Haley Titus-Mitchell , Rachel Oberst , Georgianne M. Ciraolo , Charles V. Vorhees , Andrew P. Robinson , Stephen D. Miller , Jose A. Cancelas , Anat O. Stemmer-Rachamimov , Nancy Ratner Patients with neurofibromatosis type 1 (NF1) and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB) developed, implicating a soluble mediator. Nitric oxide (NO) can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1–NOS3) were upregulated in mutant white matter. Treating mice with the NOS inhibitor NG-nitro-L-arginine methyl ester or the antioxidant N-acetyl cysteine corrected cellular phenotypes. CNP-HRasG12V mice also displayed locomotor hyperactivity, which could be rescued by antioxidant treatment. We conclude that Nf1/Ras regulates oligodendrocyte NOS and that dysregulated NO signaling in oligodendrocytes can alter the surrounding vasculature. The data suggest that antioxidants may improve some behavioral deficits in Rasopathy patients. Graphical abstract Teaser In this study, Ratner and colleagues show that altering intracellular signaling in oligodendrocytes affects brain astrocytes and blood vessels that together make up the blood-brain barrier. Increasing oligodendrocyte Ras-GTP, mimicking neurofibromatosis type 1 and Costello syndrome, disrupted astrocyte and endothelial cell tight junctions and gap junctions and caused a leaky blood-brain barrier. Exposure to a nitric oxide synthase inhibitor or an antioxidant reversed cellular phenotypes and behavioral hyperactivity. Thus, oligodendrocytes contribute to brain homeostasis, and antioxidant therapy may be beneficial when homeostasis is disrupted.

Description: Publication date: Available online 12 September 2013 Source: Cell Reports Author(s): Dalit Ben-Yosef , Francesca S. Boscolo , Hadar Amir , Mira Malcov , Ami Amit , Louise C. Laurent Given the association between mutational load and cancer, the observation that genetic aberrations are frequently found in human pluripotent stem cells (hPSCs) is of concern. Prior studies in human induced pluripotent stem cells (hiPSCs) have shown that deletions and regions of loss of heterozygosity (LOH) tend to arise during reprogramming and early culture, whereas duplications more frequently occur during long-term culture. For the corresponding experiments in human embryonic stem cells (hESCs), we studied two sets of hESC lines: one including the corresponding parental DNA and the other generated from single blastomeres from four sibling embryos. Here, we show that genetic aberrations observed in hESCs can originate during preimplantation embryo development and/or early derivation. These early aberrations are mainly deletions and LOH, whereas aberrations arising during long-term culture of hESCs are more frequently duplications. Our results highlight the importance of close monitoring of genomic integrity and the development of improved methods for derivation and culture of hPSCs. Graphical abstract Teaser Human embryonic stem cells (hESCs) are potential sources of cells for transplantation therapy. However, given the association between mutations and cancer, the frequency of genetic aberrations observed in hESCs is concerning. Using unique pedigrees of hESC lines, Laurent and colleagues now find that aberrations that occur during cell-line derivation are mainly deletions and loss of heterozygosity, whereas duplications arise more commonly during long-term culture. These results highlight the need for improved methods for derivation and culture that preserve the genetic integrity of hESCs.

Description: Publication date: Available online 12 September 2013 Source: Cell Reports Author(s): Jason Karpac , Benoit Biteau , Heinrich Jasper Loss of metabolic homeostasis is a hallmark of aging and is commonly characterized by the deregulation of adaptive signaling interactions that coordinate energy metabolism with dietary changes. The mechanisms driving age-related changes in these adaptive responses remain unclear. Here, we characterize the deregulation of an adaptive metabolic response and the development of metabolic dysfunction in the aging intestine of Drosophila . We find that activation of the insulin-responsive transcription factor Foxo in intestinal enterocytes is required to inhibit the expression of evolutionarily conserved lipases as part of a metabolic response to dietary changes. This adaptive mechanism becomes chronically activated in the aging intestine, mediated by changes in Jun-N-terminal kinase (JNK) signaling. Age-related chronic JNK/Foxo activation in enterocytes is deleterious, leading to sustained repression of intestinal lipase expression and the disruption of lipid homeostasis. Changes in the regulation of Foxo-mediated adaptive responses thus contribute to the age-associated breakdown of metabolic homeostasis. Graphical abstract Teaser Aging is associated with a loss of metabolic homeostasis, which is a risk factor for various human pathologies. Using Drosophila , Karpac, Biteau, and Jasper show that the transcription factor Foxo regulates intestinal lipid homeostasis as part of an adaptive response to dietary changes and that chronic intestinal activation of Foxo with age leads to the disruption of lipid metabolism. These results demonstrate that changes in the regulation of adaptive signaling mechanisms can contribute to the age-associated breakdown of metabolic homeostasis.

Description: Timing of sea ice retreat can alter phytoplankton community structure in the western Arctic Ocean Biogeosciences Discussions, 10, 15153-15180, 2013 Author(s): given_name prefix surname suffix, A. Fujiwara, T. Hirawake, K. Suzuki, I. Imai, and S.-I. Saitoh This study assesses the response of phytoplankton assemblages to recent climate change, especially with regard to the shrinking of sea ice in the northern Chukchi Sea of the western Arctic Ocean. Distribution patterns of phytoplankton groups in the late summers of 2008–2010 were analyzed based on HPLC pigment signatures and, the following four major algal groups were inferred via multiple regression and cluster analyses: prasinophytes, diatoms, haptophytes and dinoflagellates. A remarkable interannual difference in the distribution pattern of the groups was found in the northern basin area. Haptophytes dominated and dispersed widely in warm surface waters in 2008, whereas prasinophytes dominated in cold water in 2009 and 2010. A difference in the onset date of sea ice retreat was evident among years – the sea ice retreat in 2008 was 1–2 months earlier than in 2009 and 2010. The spatial distribution of early sea ice retreat matched the areas in which a shift in algal community composition was observed. Steel-Dwass's multiple comparison tests were used to assess the physical, chemical and biological parameters of the four clusters. We found a statistically significant difference in temperature between the haptophyte-dominated cluster and the other clusters, suggesting that the change in the phytoplankton communities was related to the earlier sea ice retreat in 2008 and the corollary increase in sea surface temperatures. Longer periods of open water during the summer, which are expected in the future, may affect food webs and biogeochemical cycles in the western Arctic due to shifts in phytoplankton community structure.

Description: Publication date: Available online 17 September 2013 Source: FEBS Open Bio Author(s): Rasheda Sultana , Maria A. Theodoraki , Avrom J. Caplan The UBR1 ubiquitin ligase promotes degradation of proteins via the N-end rule and by another mechanism that detects a misfolded conformation. Although UBR1 was shown recently to act on protein kinases whose misfolding was promoted by inhibition of Hsp90, it was unknown whether this ubiquitin ligase targeted other client types of the chaperone. We analyzed the role of UBR1 in the degradation of nuclear receptors that are classical clients of Hsp90. Our results showed that UBR1 deletion results in impaired degradation of the glucocorticoid receptor and the androgen receptor but not the estrogen receptor α. These findings demonstrate specificity in the actions of the UBR1 ubiquitin ligase in the degradation of Hsp90 clients in the presence of small molecule inhibitors that promote client misfolding. Graphical abstract

Description: Publication date: Available online 19 September 2013 Source: Cell Reports Author(s): George E. Gentsch , Nick D.L. Owens , Stephen R. Martin , Paul Piccinelli , Tiago Faial , Matthew W.B. Trotter , Michael J. Gilchrist , James C. Smith The design of effective cell replacement therapies requires detailed knowledge of how embryonic stem cells form primary tissues, such as mesoderm or neurectoderm that later become skeletal muscle or nervous system. Members of the T-box transcription factor family are key in the formation of these primary tissues, but their underlying molecular activities are poorly understood. Here, we define in vivo genome-wide regulatory inputs of the T-box proteins Brachyury, Eomesodermin, and VegT, which together maintain neuromesodermal stem cells and determine their bipotential fates in frog embryos. These T-box proteins are all recruited to the same genomic recognition sites, from where they activate genes involved in stem cell maintenance and mesoderm formation while repressing neurogenic genes. Consequently, their loss causes embryos to form an oversized neural tube with no mesodermal derivatives. This collaboration between T-box family members thus ensures the continuous formation of correctly proportioned neural and mesodermal tissues in vertebrate embryos during axial elongation. Graphical abstract Teaser The development of effective cell replacement therapies requires detailed knowledge of how embryonic stem cells form primary tissues, such as mesoderm or neurectoderm that later become skeletal muscle or spinal cord. Gentsch, Smith, and colleagues now provide mechanistic insight into how T-box transcription factors regulate stem cells to form neural or mesodermal tissues. The authors show how this ensures the harmonious formation of spinal cord, muscle, and notochord as the vertebrate embryo elongates along its anteroposterior axis.

Description: Publication date: Available online 19 September 2013 Source: Cell Reports Author(s): Ivan Zanoni , Roberto Spreafico , Caterina Bodio , Marco Di Gioia , Clara Cigni , Achille Broggi , Tatiana Gorletta , Michele Caccia , Giuseppe Chirico , Laura Sironi , Maddalena Collini , Mario P. Colombo , Natalio Garbi , Francesca Granucci Natural killer (NK) cells have antitumor, antiviral, and antibacterial functions, and efforts are being made to manipulate them in immunotherapeutic approaches. However, their activation mechanisms remain poorly defined, particularly during bacterial infections. Here, we show that upon lipopolysaccharide or E. coli exposure, dendritic cells (DCs) produce three cytokines—interleukin 2 (IL-2), IL-18, and interferon β (IFN-β)—necessary and sufficient for NK cell activation. IFN-β enhances NK cell activation by inducing IL-15 and IL-15 receptor α not only in DCs but, surprisingly, also in NK cells. This process allows the transfer of IL-15 on NK cell surface and its cis presentation. cis -presented NK cell-derived and trans -presented DC-derived IL-15 contribute equally to optimal NK cell activation. Graphical abstract Teaser NK cells depend on IL-15 provided by accessory cells for their survival under steady-state conditions. It has long been believed that a similar requirement is applied to NK cell activation as well. Zanoni, Granucci, and colleagues now show that NK cells express IL-15 and IL-15Rα when stimulated by type I interferons. NK cells cis -present self-produced IL-15, and this is as important to NK cell activation as trans presentation of IL-15 by dendritic cells.

Description: Publication date: Available online 19 September 2013 Source: Cell Reports Author(s): Oren Ben-Ami , Dan Friedman , Dena Leshkowitz , Dalia Goldenberg , Kira Orlovsky , Niv Pencovich , Joseph Lotem , Amos Tanay , Yoram Groner The t(8;21) and inv(16) chromosomal aberrations generate the oncoproteins AML1-ETO (A-E) and CBFβ-SMMHC (C-S). The role of these oncoproteins in acute myeloid leukemia (AML) etiology has been well studied. Conversely, the function of native RUNX1 in promoting A-E- and C-S-mediated leukemias has remained elusive. We show that wild-type RUNX1 is required for the survival of t(8;21)-Kasumi-1 and inv(16)-ME-1 leukemic cells. RUNX1 knockdown in Kasumi-1 cells (Kasumi-1 RX1-KD ) attenuates the cell-cycle mitotic checkpoint, leading to apoptosis, whereas knockdown of A-E in Kasumi-1 RX1-KD rescues these cells. Mechanistically, a delicate RUNX1/A-E balance involving competition for common genomic sites that regulate RUNX1/A-E targets sustains the malignant cell phenotype. The broad medical significance of this leukemic cell addiction to native RUNX1 is underscored by clinical data showing that an active RUNX1 allele is usually preserved in both t(8;21) or inv(16) AML patients, whereas RUNX1 is frequently inactivated in other forms of leukemia. Thus, RUNX1 and its mitotic control targets are potential candidates for new therapeutic approaches. Graphical abstract Teaser The t(8;21) and inv(16) chimeric oncogenes are major etiological drivers of human acute myeloid leukemia. However, the function of native RUNX1 in these leukemias has remained unknown. Groner and colleagues demonstrate that expression of wild-type RUNX1 is essential for t(8;21) and inv(16) leukemogenesis. Reducing RUNX1 activity destines the leukemic cells for apoptosis. Importantly, an active RUNX1 allele is usually preserved in t(8;21) or inv(16) patients, whereas, in other leukemias, it is frequently inactivated, underscoring the significance of this leukemic cell addiction to RUNX1.

Description: Publication date: Available online 19 September 2013 Source: Cell Reports Author(s): Markus Reschke , John G. Clohessy , Nina Seitzer , Daniel P. Goldstein , Susanne B. Breitkopf , Daniel B. Schmolze , Ugo Ala , John M. Asara , Andrew H. Beck , Pier Paolo Pandolfi Increasing evidence points to an important role for the ribosome in the regulation of biological processes and as a target for deregulation in disease. Here, we describe a SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry approach to probing mammalian riboproteomes. Using a panel of cell lines, as well as genetic and pharmacological perturbations, we obtained a comparative characterization of the cellular riboproteome. This analysis identified a set of riboproteome components, consisting of a diverse array of proteins with a strong enrichment for RNA-binding proteins. Importantly, this global analysis uncovers a high incidence of genetic alterations to riboproteome components in cancer, with a distinct bias toward genetic amplification. We further validated association with polyribosomes for several riboproteome components and demonstrate that enrichment at the riboproteome can depend on cell type, genetics, or cellular stimulus. Our results have important implications for the understanding of how ribosomes function and provide a platform for uncovering regulators of translation. Graphical abstract Teaser Increasing evidence points to an important role for the ribosome in regulating biological processes and as a target in disease. Now, Pandolfi and colleagues use mass spectrometry to probe the mammalian riboproteome. They show that the riboproteome displays differential composition in cancer cells and contains an array of proteins, many of which are frequently amplified in cancer. These results have important implications for the understanding of how ribosomes function and provide a platform to broaden our understanding of translational regulation.

Description: Publication date: Available online 19 September 2013 Source: Cell Reports Author(s): Shunqiang Li , Dong Shen , Jieya Shao , Robert Crowder , Wenbin Liu , Aleix Prat , Xiaping He , Shuying Liu , Jeremy Hoog , Charles Lu , Li Ding , Obi L. Griffith , Christopher Miller , Dave Larson , Robert S. Fulton , Michelle Harrison , Tom Mooney , Joshua F. McMichael , Jingqin Luo , Yu Tao , Rodrigo Goncalves , Christopher Schlosberg , Jeffrey F. Hiken , Laila Saied , Cesar Sanchez , Therese Giuntoli , Caroline Bumb , Crystal Cooper , Robert T. Kitchens , Austin Lin , Chanpheng Phommaly , Sherri R. Davies , Jin Zhang , Megha Shyam Kavuri , Donna McEachern , Yi Yu Dong , Cynthia Ma , Timothy Pluard , Michael Naughton , Ron Bose , Rama Suresh , Reida McDowell , Loren Michel , Rebecca Aft , William Gillanders , Katherine DeSchryver , Richard K. Wilson , Shaomeng Wang , Gordon B. Mills , Ana Gonzalez-Angulo , John R. Edwards , Christopher Maher , Charles M. Perou , Elaine R. Mardis , Matthew J. Ellis To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation. Graphical abstract Teaser In this study, Ellis and colleagues compare whole-tumor genomes from drug-resistant breast cancers with paired xenografts. Genomic fidelity upon transplantation was high for structural variants but variable at the single-nucleotide level. Therefore, tumor and xenograft whole-genome comparisons critically assess genetic drift and clonal representation. Additional analysis revealed ESR1 mutations, amplification, and translocations associated with endocrine resistance in lumenal xenografts. Sequenced patient-derived xenografts are an important resource for functional genomics and capture treatment-resistance etiologies that are not observed in standard cell lines.

Description: Uptake of phytodetritus by benthic foraminifera under oxygen depletion at the Indian Margin (Arabian Sea) Biogeosciences Discussions, 10, 15305-15335, 2013 Author(s): A. J. Enge, U. Witte, M. Kucera, and P. Heinz Benthic foraminifera in sediments on the Indian margin of the Arabian Sea where the oxygen minimum zone (OMZ) impinges on the continental slope are exposed to particularly severe levels of oxygen depletion. Food supply for the benthic community is high but delivered in distinct pulses during upwelling and water mixing events associated with summer and winter monsoon periods. In order to investigate the response by benthic foraminifera to such pulsed food delivery under oxygen concentrations of less than 0.1 mL L −1 (4.5 μmol L −1 ), an in situ isotope labeling experiment ( 13 C, 15 N) was performed at the western continental slope of India at 540 m water depth (OMZ core region). The assemblage of living foraminifera (〉125 μm) in the uppermost centimeter at this depth is characterized by an unexpectedly high population density of 3982 ind. 10 cm −2 and a strong dominance by few calcareous species. For the experiment, we concentrated on the nine most abundant taxa, which constitute 93% of the entire foraminifera population at 0–1 cm sediment depth. Increased concentrations of 13 C and 15 N in the cytoplasm indicate that all investigated taxa took up the labeled phytodetritus during the 4 day experimental phase. In total, these nine species had assimilated 113.8 mg C m −2 (17.5% of the total added carbon). The uptake of nitrogen by the three most abundant taxa ( Bolivina aff. B. dilatata , Cassidulina sp., Bulimina gibba ) was 2.7 mg N m −2 (2% of the total added nitrogen) and showed the successful application of 15 N as tracer in foraminiferal studies. The short-term response to the offered phytodetritus varied largely among foraminiferal species with Uvigerina schwageri being by far the most important species in short-term processing whereas the most abundant taxa Bolivina aff. B. dilatata and Cassidulina sp. showed comparably low uptake of the offered food. We suggest that the observed species-specific differences are related to individual biomass of species and to specific feeding preferences. The high numbers of living foraminifera and their rapid response to deposited fresh phytodetritus demonstrate the importance of foraminifera in short-term carbon cycling under oxygen-depleted conditions. We propose that foraminifera at the studied site benefit from unique adaptations in their metabolisms to nearly anoxic conditions as well as from the exclusion of macrofauna and the resulting relaxation of competition for food and low predation pressure.

Description: Summertime canopy albedo is sensitive to forest thinning Biogeosciences Discussions, 10, 15373-15414, 2013 Author(s): J. Otto, D. Berveiller, F.-M. Bréon, N. Delpierre, G. Geppert, A. Granier, W. Jans, A. Knohl, A. Kuusk, B. Longdoz, E. Moors, M. Mund, B. Pinty, M.-J. Schelhaas, and S. Luyssaert Despite an emerging body of literature linking canopy albedo to forest management, understanding of the process is still fragmented. We combined a stand-level forest gap model with a canopy radiation transfer model and satellite-derived model parameters to quantify the effects of forest thinning, that is removing trees at a certain time during the forest rotation, on summertime canopy albedo. The effects of different forest species (pine, beech, oak) and four thinning strategies (light to intense thinning regimes) were examined. During stand establishment, summertime canopy albedo is driven by tree species. In the later stages of stand development, the effect of tree species on summertime canopy albedo decreases in favour of an increasing influence of forest thinning on summertime canopy albedo. These trends continue until the end of the rotation where thinning explains up to 50% of the variance in near-infrared canopy albedo and up to 70% of the variance in visible canopy albedo. More intense thinning lowers the summertime shortwave albedo in the canopy by as much as 0.02 compared to unthinned forest. The structural changes associated with forest thinning can be described by the change in LAI in combination with crown volume. However, forests with identical canopy structure can have different summertime albedo values due to their location: the further north a forest is situated, the more the solar zenith angle increases and thus the higher is the summertime canopy albedo, independent of the wavelength. Despite the increase of absolute summertime canopy albedo values with latitude, the difference in canopy albedo between managed and unmanaged forest decreases with increasing latitude. Forest management thus strongly altered summertime forest albedo.

Description: Publication date: Available online 26 September 2013 Source: Cell Reports Author(s): Jun Ding , Ursula Loizides-Mangold , Gianpaolo Rando , Vincent Zoete , Olivier Michielin , Janardan K. Reddy , Walter Wahli , Howard Riezman , Bernard Thorens Specific metabolic pathways are activated by different nutrients to adapt the organism to available resources. Although essential, these mechanisms are incompletely defined. Here, we report that medium-chain fatty acids contained in coconut oil, a major source of dietary fat, induce the liver ω-oxidation genes Cyp4a10 and Cyp4a14 to increase the production of dicarboxylic fatty acids. Furthermore, these activate all ω- and β-oxidation pathways through peroxisome proliferator activated receptor (PPAR) α and PPARγ, an activation loop normally kept under control by dicarboxylic fatty acid degradation by the peroxisomal enzyme L-PBE. Indeed, L-pbe −/− mice fed coconut oil overaccumulate dicarboxylic fatty acids, which activate all fatty acid oxidation pathways and lead to liver inflammation, fibrosis, and death. Thus, the correct homeostasis of dicarboxylic fatty acids is a means to regulate the efficient utilization of ingested medium-chain fatty acids, and its deregulation exemplifies the intricate relationship between impaired metabolism and inflammation. Graphical abstract Teaser Specific metabolic pathways are activated by different nutrients to adapt the organism to available resources. Riezman, Thorens, and colleagues find that mice lacking the peroxisomal L-bifunctional enzyme (L-pbe) die of liver failure when fed coconut oil but not lard. Medium-chain fatty acids in coconut oil induce the liver ω-oxidation to increase the production of dicarboxylic fatty acids (DCAs). Furthermore, these activate all ω- and β-oxidation pathways through peroxisome proliferator activated receptors, an activation loop normally fine tuned by L-PBE degrading DCAs. Their work demonstrates the physiological role of mouse L-PBE in hepatic adaptation to medium-chain fatty acids.

Description: Publication date: Available online 26 September 2013 Source: Cell Reports Author(s): Tae Kyung Kim , Jai-Yoon Sul , Henrik Helmfors , Ulo Langel , Junhyong Kim , James Eberwine Protein synthesis in neuronal dendrites underlies long-term memory formation in the brain. Local translation of reporter mRNAs has demonstrated translation in dendrites at focal points called translational hotspots. Various reports have shown that hundreds to thousands of mRNAs are localized to dendrites, yet the dynamics of translation of multiple dendritic mRNAs has remained elusive. Here, we show that the protein translational activities of two dendritically localized mRNAs are spatiotemporally complex but constrained by the translational hotspots in which they are colocalized. Cotransfection of glutamate receptor 2 (GluR2) and GluR4 mRNAs (engineered to encode different fluorescent proteins) into rat hippocampal neurons demonstrates a heterogeneous distribution of translational hotspots for the two mRNAs along dendrites. Stimulation with s -3,5-dihydroxy-phenylglycine modifies the translational dynamics of both of these RNAs in a complex saturable manner. These results suggest that the translational hotspot is a primary structural regulator of the simultaneous yet differential translation of multiple mRNAs in the neuronal dendrite. Graphical abstract Teaser Local translation of dendritic mRNAs plays a crucial role in synaptic plasticity and formation of long-term memory. However, the dynamics of simultaneous translation of multiple dendritic mRNAs has remained elusive. In this study, Eberwine and colleagues show that the translational activities of two dendritically localized mRNAs are spatiotemporally complex but constrained by the translational hotspots in which they are colocalized. The results suggest structural constraints and stochastic regulation of synaptic plasticity.

Description: Publication date: Available online 26 September 2013 Source: Cell Reports Author(s): Sara Ribeiro , Ilaria Napoli , Ian J. White , Simona Parrinello , Adrienne M. Flanagan , Ueli Suter , Luis F. Parada , Alison C. Lloyd Schwann cells are highly plastic cells that dedifferentiate to a progenitor-like state following injury. However, deregulation of this plasticity, may be involved in the formation of neurofibromas, mixed-cell tumors of Schwann cell (SC) origin that arise upon loss of NF1. Here, we show that adult myelinating SCs (mSCs) are refractory to Nf1 loss. However, in the context of injury, Nf1-deficient cells display opposing behaviors along the wounded nerve; distal to the injury, Nf1 −/− mSCs redifferentiate normally, whereas at the wound site Nf1 −/− mSCs give rise to neurofibromas in both Nf1 +/+ and Nf1 +/− backgrounds. Tracing experiments showed that distinct cell types within the tumor derive from Nf1-deficient SCs. This model of neurofibroma formation demonstrates that neurofibromas can originate from adult SCs and that the nerve environment can switch from tumor suppressive to tumor promoting at a site of injury. These findings have implications for both the characterization and treatment of neurofibromas. Graphical abstract Teaser Neurofibromas are mixed-cell tumors of Schwann cell (SC) origin that arise upon loss of NF1. Here, Lloyd and colleagues show that adult myelinating SCs (mSCs) are insensitive to NF1 loss. However, when nerves are injured, NF1-deficient mSCs display opposing behavior along the wounded nerve, forming tumors at the injury site while redifferentiating normally along the rest of the nerve. This demonstrates that the nerve environment can switch from tumor suppressive to tumor promoting at a site of injury.

Description: Publication date: Available online 26 September 2013 Source: Cell Reports Author(s): Hui Zheng , Vibhor Gupta , Jeffrey Patterson-Fortin , Sabyasachi Bhattacharya , Kanstantsin Katlinski , Junmin Wu , Bentley Varghese , Christopher J. Carbone , Bernadette Aressy , Serge Y. Fuchs , Roger A. Greenberg Lysine63-linked ubiquitin (K63-Ub) chains represent a particular ubiquitin topology that mediates proteasome-independent signaling events. The deubiquitinating enzyme (DUB) BRCC36 segregates into distinct nuclear and cytoplasmic complexes that are specific for K63-Ub hydrolysis. RAP80 targets the five-member nuclear BRCC36 complex to K63-Ub chains at DNA double-strand breaks. The alternative four-member BRCC36 containing complex (BRISC) lacks a known targeting moiety. Here, we identify serine hydroxymethyltransferase (SHMT) as a previously unappreciated component that fulfills this function. SHMT directs BRISC activity at K63-Ub chains conjugated to the type 1 interferon (IFN) receptor chain 1 (IFNAR1). BRISC-SHMT2 complexes localize to and deubiquitinate actively engaged IFNAR1, thus limiting its K63-Ub-mediated internalization and lysosomal degradation. BRISC-deficient cells and mice exhibit attenuated responses to IFN and are protected from IFN-associated immunopathology. These studies reveal a mechanism of DUB regulation and suggest a therapeutic use of BRISC inhibitors for treating pathophysiological processes driven by elevated IFN responses. Graphical abstract Teaser Fuchs, Greenberg, and colleagues describe a deubiquitinating (DUB) enzyme complex consisting of an interaction between BRISC and SHMT enzymes. This lysine63-ubiquitin-specific DUB complex deubiquitinates the actively engaged type I interferon receptor, resulting in receptor stabilization and activation of interferon signaling pathways. BRISC-deficient cells and mice have attenuated interferon responses and are resistant to bacterial lipopolysaccharide. These findings suggest strategies for treating disease states that arise from elevated interferon signals.

Description: Oxygen minimum zone of the open Arabian Sea: variability of oxygen and nitrite from daily to decadal time scales Biogeosciences Discussions, 10, 15455-15517, 2013 Author(s): K. Banse, S. W. A. Naqvi, P. V. Narvekar, J. R. Postel, and D. A. Jayakumar The oxygen minimum zone (OMZ) of the Arabian Sea is the thickest of the three oceanic OMZs, which is of global biogeochemical significance because of denitrification in the upper part leading to N 2 and N 2 O production. The residence time of the OMZ water is believed to be less than a decade. The upper few hundred meters of this zone are nearly anoxic but non-sulfidic and still support animal (metazoan) pelagic life, possibly as a result of episodic injections of O 2 by physical processes. The very low O 2 values obtained with the new STOX sensor in the eastern tropical South Pacific probably also characterize the Arabian Sea OMZ, but there is no apparent reason as to why the temporal trends of the historic data should not hold. We report on discrete measurements of dissolved O 2 and NO 2 - , besides temperature and salinity, made between 1959 and 2004 well below the tops of the sharp pycno- and oxyclines near 150, 200, 300, 400, and 500 m depth. We assemble nearly all O 2 determinations (originally, 849 values, 695 in the OMZ) by the visual endpoint detection of the iodometric Winkler procedure, which in our data base yields about 0.04 mL L −1 (∼2 μM) O 2 above the endpoint from modern automated titration methods. We find 632 values acceptable (480 from 150 stations in the OMZ). The data are grouped in zonally-paired boxes of 1° lat. and 2° long. centered at 8°, 10°, 12°, 15°, 18°, 20°, and 21° N along 65° E and 67° E. The latitudes of 8–12° N, outside the OMZ, are only treated in passing. The principal results are as follows: (1) an O 2 climatology for the upper OMZ reveals a marked seasonality at 200 to 500 m depth with O 2 levels during the northeast monsoon and spring intermonsoon season elevated over those during the southwest monsoon season (median difference, 0.08 mL L −1 [3.5 μM]). The medians of the slopes of the seasonal regressions of O 2 on year for the NE and SW monsoon seasons are −0.0043 and −0.0019 mL L −1 a −1 , respectively (−0.19 and −0.08 μM a −1 ; n = 10 and 12, differing at p = 0.01); (2) four decades of statistically significant decreases of O 2 between 15° and 20° N but a trend to a similar increase near 21° N are observed. The balance of the mechanisms that more or less annually maintain the O 2 levels are still uncertain. At least between 300 and 500 m the annual reconstitution of the decrease is inferred to be due to lateral, isopycnal re-supply of O 2 , while at 200 (250?) m it is diapycnal, most likely by eddies. Similarly, recent models show large vertical advection of O 2 well below the pycno- cum -oxycline. The spatial (within drift stations) and temporal (daily) variability in hydrography and chemistry is large also below the principal pycnocline. The seasonal change of hydrography is considerable even at 500 m. There is no trend in the redox environment for a quarter of a century at a GEOSECS station near 20° N. In the entire OMZ the slopes on year within seasons for the quite variable NO 2 - (taken as an indicator of active denitrification) do not show a clear pattern. Also, future O 2 or nutrient budgets for the OMZ should not be based on single cruises or sections obtained during one season only. Steady state cannot be assumed any longer for the intermediate layers of the central Arabian Sea.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Tamás Schauer , Petra C. Schwalie , Ava Handley , Carla E. Margulies , Paul Flicek , Andreas G. Ladurner Chromatin organization and gene activity are responsive to developmental and environmental cues. Although many genes are transcribed throughout development and across cell types, much of gene regulation is highly cell-type specific. To readily track chromatin features at the resolution of cell types within complex tissues, we developed and validated chromatin affinity purification from specific cell types by chromatin immunoprecipitation (CAST-ChIP), a broadly applicable biochemical procedure. RNA polymerase II (Pol II) CAST-ChIP identifies ∼1,500 neuronal and glia-specific genes in differentiated cells within the adult Drosophila brain. In contrast, the histone H2A.Z is distributed similarly across cell types and throughout development, marking cell-type-invariant Pol II-bound regions. Our study identifies H2A.Z as an active chromatin signature that is refractory to changes across cell fates. Thus, CAST-ChIP powerfully identifies cell-type-specific as well as cell-type-invariant chromatin states, enabling the systematic dissection of chromatin structure and gene regulation within complex tissues such as the brain. Graphical abstract Teaser Much gene regulation is cell-type specific, but there are few tools that allow the genome-wide tracking of chromatin features and transcriptional states at the resolution of cell types within complex tissues. Margulies, Flicek, Ladurner, and colleagues developed and validated CAST-ChIP, a biochemical procedure that profiles chromatin-associated proteins in cell types of the Drosophila brain. CAST-ChIP identified 1,500 neuron- and glia-specific genes and revealed that histone H2A.Z marks cell-type-invariant domains. CAST-ChIP enables the systematic dissection of gene regulation in cell types.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Per Nilsson , Krishnapriya Loganathan , Misaki Sekiguchi , Yukio Matsuba , Kelvin Hui , Satoshi Tsubuki , Motomasa Tanaka , Nobuhisa Iwata , Takashi Saito , Takaomi C. Saido Alzheimer’s disease (AD) is a neurodegenerative disease biochemically characterized by aberrant protein aggregation, including amyloid beta (Aβ) peptide accumulation. Protein aggregates in the cell are cleared by autophagy, a mechanism impaired in AD. To investigate the role of autophagy in Aβ pathology in vivo, we crossed amyloid precursor protein (APP) transgenic mice with mice lacking autophagy in excitatory forebrain neurons obtained by conditional knockout of autophagy-related protein 7. Remarkably, autophagy deficiency drastically reduced extracellular Aβ plaque burden. This reduction of Aβ plaque load was due to inhibition of Aβ secretion, which led to aberrant intraneuronal Aβ accumulation in the perinuclear region. Moreover, autophagy-deficiency-induced neurodegeneration was exacerbated by amyloidosis, which together severely impaired memory. Our results establish a function for autophagy in Aβ metabolism: autophagy influences secretion of Aβ to the extracellular space and thereby directly affects Aβ plaque formation, a pathological hallmark of AD. Graphical abstract Teaser In this study, Nilsson, Saido, and colleagues show that autophagy influences secretion of Alzheimer’s disease (AD) amyloid beta (Aβ) peptide. Autophagy deficiency, achieved by genetic deletion of autophagy-related gene 7 in excitatory neurons in mouse brain, reduced Aβ plaque load and caused intracellular Aβ accumulation. In addition, amyloidosis exacerbated autophagy-deficiency-induced neurodegeneration and caused severe memory impairment. Thus, autophagy has a key role in the two main characteristics of AD: intracellular Aβ accumulation and extracellular Aβ plaque formation.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Antonia Borovina , Brian Ciruna The role for cilia in establishing planar cell polarity (PCP) is contentious. Although knockdown of genes known to function in ciliogenesis has been reported to cause PCP-related morphogenesis defects in zebrafish, genetic mutations affecting intraflagellar transport (IFT) do not show PCP phenotypes despite the requirement for IFT in cilia formation. This discrepancy has been attributed to off-target effects of antisense morpholino oligonucleotide (MO) injection, confounding maternal effects in zygotic mutant embryos, or an inability to distinguish between cilia-dependent versus cilia-independent protein functions. To determine the role of cilia in PCP, we generated maternal + zygotic IFT88 (MZ ift88 ) mutant zebrafish embryos, which never form cilia. We clearly demonstrate that cilia are not required to establish PCP. Rather, IFT88 plays a cilia-independent role in controlling oriented cell divisions at gastrulation and neurulation. Our results have important implications for the interpretation of cilia gene function in normal development and in disease. Graphical abstract Teaser The role of cilia in establishing planar cell polarity (PCP) remains contentious, confounded by off-target effects of antisense morpholino oligonucleotide use, maternal effects in zygotic mutant backgrounds, and difficulties distinguishing between cilia-dependent versus cilia-independent protein function. Here, Borovina and Ciruna clearly demonstrate that PCP is established normally in cilia-deficient maternal-zygotic IFT88 mutant zebrafish. Furthermore, by analyzing morphogenic events that occur prior to cilia formation, they identify a cilia- and PCP-independent role for IFT88 in controlling polarized cell divisions.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Tian Xie , Wei Peng , Chuangye Yan , Jianping Wu , Xinqi Gong , Yigong Shi RIP3 is an essential upstream kinase in necroptosis. The pseudokinase MLKL functions as a substrate of RIP3 to mediate downstream signaling. The molecular mechanism by which RIP3 recognizes and phosphorylates MLKL remains unknown. Here, we report the crystal structures of the mouse RIP3 kinase domain, the MLKL kinase-like domain, and a binary complex between the two. Both RIP3 and MLKL adopt the canonical kinase fold. Free RIP3 exists in an active conformation, whereas MLKL-bound RIP3 is stabilized by AMP-PNP to adopt an inactive conformation. The formation of the RIP3-MLKL complex, involving their respective N- and C-lobes, is accompanied by pronounced conformational changes of the αC helix and activation loop in RIP3 and the corresponding structural elements in MLKL. RIP3-mediated MLKL phosphorylation, though important for downstream signaling, is dispensable for stable complex formation between RIP3 and MLKL. Our study serves as a framework for mechanistic understanding of RIP3-mediated necroptotic signaling. Graphical abstract Teaser RIP3 is an essential upstream kinase in necroptosis. The pseudokinase MLKL functions as a substrate of RIP3 to mediate downstream signaling. In this study, Shi and colleagues report the crystal structures of the mouse RIP3 kinase domain, the MLKL kinase-like domain, and a binary complex between the two, which reveals the structural basis of MLKL recognition by RIP3 and gives structural insights into RIP3-mediated necroptotic signaling. Their structural analysis serves as a framework for understanding RIP3-mediated necroptosis.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Albert Ribes-Zamora , Sandra M. Indiviglio , Ivana Mihalek , Christopher L. Williams , Alison A. Bertuch Telomeres are protected from nonhomologous end-joining (NHEJ) to avoid deleterious chromosome fusions, yet they associate with the Ku heterodimer that is principal in the classical NHEJ (c-NHEJ) pathway. T-loops have been proposed to inhibit Ku’s association with telomeric ends, thus inhibiting c-NHEJ; however, deficiencies in the t-loop model suggest additional mechanisms are in effect. We demonstrate that TRF2 interacts with Ku at telomeres and via residues in Ku70 helix 5 (α5), which are vital for NHEJ. We show that Ku’s interaction with a TRF2 mutant that induces telomeric fusions is significantly impaired. Additionally, we demonstrate that Ku70 α5 is required for Ku self-association in live cells, which can bridge DNA ends. Together, these findings lead us to propose a model in which telomeres are directly protected from c-NHEJ via TRF2 impeding Ku’s ability to synapse telomere ends. Graphical abstract Teaser The protection of chromosomal termini from fusions is an essential function of telomeres. Nonetheless, the Ku heterodimer, a factor required for nonhomologous end-joining (NHEJ), is associated with functional telomeres. In this study, Bertuch and colleagues show that the telomere end protection factor TRF2 interacts with a region of Ku required for NHEJ. They further show that this region promotes Ku-Ku interactions. These data lead the authors to propose a model for the protection of telomeres from NHEJ.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Hong Wu , Nikolas Mathioudakis , Boubou Diagouraga , Aiping Dong , Ludmila Dombrovski , Frédéric Baudat , Stephen Cusack , Bernard de Massy , Jan Kadlec PRDM9, a histone lysine methyltransferase, is a key determinant of the localization of meiotic recombination hot spots in humans and mice and the only vertebrate protein known to be involved in hybrid sterility. Here, we report the crystal structure of the PRDM9 methyltransferase domain in complex with a histone H3 peptide dimethylated on lysine 4 (H3K4me2) and S-adenosylhomocysteine (AdoHcy), which provides insights into the methyltransferase activity of PRDM proteins. We show that the genuine substrate of PRDM9 is histone H3 lysine 4 (H3K4) and that the enzyme possesses mono-, di-, and trimethylation activities. We also determined the crystal structure of PRDM9 in its autoinhibited state, which revealed a rearrangement of the substrate and cofactor binding sites by a concerted action of the pre-SET and post-SET domains, providing important insights into the regulatory mechanisms of histone lysine methyltransferase activity. Graphical abstract Teaser The histone methyltransferase PRDM9 is a key determinant of meiotic recombination hot spots in humans and mice and the only vertebrate protein known to be involved in hybrid sterility. In this study, de Massy, Kadlec, and colleagues analyzed PRDM9 substrate specificity and report the crystal structures of its methyltransferase domain in an autoinhibited state and in complex with an H3K4me2 peptide and AdoHcy. These data provide important insights into the regulatory mechanisms of histone lysine methyltransferase activity.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Gwynneth Thomas , Jenna L. Betters , Caleb C. Lord , Amanda L. Brown , Stephanie Marshall , Daniel Ferguson , Janet Sawyer , Matthew A. Davis , John T. Melchior , Lawrence C. Blume , Allyn C. Howlett , Pavlina T. Ivanova , Stephen B. Milne , David S. Myers , Irina Mrak , Vera Leber , Christoph Heier , Ulrike Taschler , Jacqueline L. Blankman , Benjamin F. Cravatt , Richard G. Lee , Rosanne M. Crooke , Mark J. Graham , Robert Zimmermann , H. Alex Brown , J. Mark Brown The serine hydrolase α/β hydrolase domain 6 (ABHD6) has recently been implicated as a key lipase for the endocannabinoid 2-arachidonylglycerol (2-AG) in the brain. However, the biochemical and physiological function for ABHD6 outside of the central nervous system has not been established. To address this, we utilized targeted antisense oligonucleotides (ASOs) to selectively knock down ABHD6 in peripheral tissues in order to identify in vivo substrates and understand ABHD6’s role in energy metabolism. Here, we show that selective knockdown of ABHD6 in metabolic tissues protects mice from high-fat-diet-induced obesity, hepatic steatosis, and systemic insulin resistance. Using combined in vivo lipidomic identification and in vitro enzymology approaches, we show that ABHD6 can hydrolyze several lipid substrates, positioning ABHD6 at the interface of glycerophospholipid metabolism and lipid signal transduction. Collectively, these data suggest that ABHD6 inhibitors may serve as therapeutics for obesity, nonalcoholic fatty liver disease, and type II diabetes. Graphical abstract Teaser Metabolic syndrome has become a leading health concern. Now, Brown and colleagues show that that serine hydrolase ABHD6 is a key driver of the metabolic syndrome and that inhibition of ABHD6 protects mice from high-fat-diet-induced obesity, hepatic steatosis, and systemic insulin resistance. Using combined in vivo lipidomic and in vitro enzymology approaches, the authors show that ABHD6 is a promiscuous lipase that hydrolyzes monoacylglycerols and lysophospholipids and argue that ABHD6 inhibitors may hold therapeutic promise.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Kinyui Alice Lo , Adam Labadorf , Norman J. Kennedy , Myoung Sook Han , Yoon Sing Yap , Bryan Matthews , Xiaofeng Xin , Lei Sun , Roger J. Davis , Harvey F. Lodish , Ernest Fraenkel Diet-induced obesity (DIO) predisposes individuals to insulin resistance, and adipose tissue has a major role in the disease. Insulin resistance can be induced in cultured adipocytes by a variety of treatments, but what aspects of the in vivo responses are captured by these models remains unknown. We use global RNA sequencing to investigate changes induced by TNF-α, hypoxia, dexamethasone, high insulin, and a combination of TNF-α and hypoxia, comparing the results to the changes in white adipose tissue from DIO mice. We found that different in vitro models capture distinct features of DIO adipose insulin resistance, and a combined treatment of TNF-α and hypoxia is most able to mimic the in vivo changes. Using genome-wide DNase I hypersensitivity followed by sequencing, we further examined the transcriptional regulation of TNF-α-induced insulin resistance, and we found that C/EPBβ is a potential key regulator of adipose insulin resistance. Graphical abstract Teaser Obesity-related insulin resistance is an increasingly common medical problem. Lodish, Fraenkel, and colleagues examine in vitro models for adipose insulin resistance using next-generation sequencing to analyze mRNA levels and chromatin states. They demonstrate that common models capture dramatically different aspects of the in vivo changes, with a combined TNF-α-hypoxia treatment most able to mimic diet-induced obesity. Their approach reveals C/EPBβ as a potential regulator of adipose insulin resistance. AdipoSight, a web portal, provides access to their data and algorithms.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Ricardo Weinlich , Andrew Oberst , Christopher P. Dillon , Laura J. Janke , Sandra Milasta , John R. Lukens , Diego A. Rodriguez , Prajwal Gurung , Chandra Savage , Thirumala D. Kanneganti , Douglas R. Green Caspase-8 or cellular FLICE-like inhibitor protein (cFLIP) deficiency leads to embryonic lethality in mice due to defects in endothelial tissues. Caspase-8 −/− and receptor-interacting protein kinase-3 (RIPK3) −/− , but not cFLIP −/− and RIPK3 −/− , double-knockout animals develop normally, indicating that caspase-8 antagonizes the lethal effects of RIPK3 during development. Here, we show that the acute deletion of caspase-8 in the gut of adult mice induces enterocyte death, disruption of tissue homeostasis, and inflammation, resulting in sepsis and mortality. Likewise, acute deletion of caspase-8 in a focal region of the skin induces local keratinocyte death, tissue disruption, and inflammation. Strikingly, RIPK3 ablation rescues both phenotypes. However, acute loss of cFLIP in the skin produces a similar phenotype that is not rescued by RIPK3 ablation. TNF neutralization protects from either acute loss of caspase-8 or cFLIP. These results demonstrate that caspase-8-mediated suppression of RIPK3-induced death is required not only during development but also for adult homeostasis. Furthermore, RIPK3-dependent inflammation is dispensable for the skin phenotype. Graphical abstract Teaser In this study, Green and colleagues show that acute loss of caspase-8 in the gut or the skin can induce a TNF-dependent, RIPK3-mediated loss of tissue homeostasis and inflammation, demonstrating that RIPK3 function is tightly regulated in adult tissues. Strikingly, the authors show that loss of cFLIP in RIPK3-deficient background induces a similar phenotype, suggesting that loss of tissue barrier function, rather than the type of cell death (necroptosis or apoptosis), defines the onset of disease.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Todd C. Metzger , Imran S. Khan , James M. Gardner , Maria L. Mouchess , Kellsey P. Johannes , Anna K. Krawisz , Katarzyna M. Skrzypczynska , Mark S. Anderson Thymic epithelial cells in the medulla (mTECs) play a critical role in enforcing central tolerance through expression and presentation of tissue-specific antigens (TSAs) and deletion of autoreactive thymocytes. TSA expression requires autoimmune regulator (Aire), a transcriptional activator present in a subset of mTECs characterized by high CD80 and major histocompatibility complex II expression and a lack of potential for differentiation or proliferation. Here, using an Aire-DTR transgenic line, we show that short-term ablation specifically targets Aire + mTECs, which quickly undergo RANK-dependent recovery. Repeated ablation also affects Aire − mTECs, and using an inducible Aire-Cre fate-mapping system, we find that this results from the loss of a subset of mTECs that showed prior expression of Aire, maintains intermediate TSA expression, and preferentially migrates toward the center of the medulla. These results clearly identify a distinct stage of mTEC development and underscore the diversity of mTECs that play a key role in maintaining tolerance. Graphical abstract Teaser In this study, Anderson and colleagues investigate the recovery and developmental potential of Aire + thymic epithelial cells (TECs), a cell population with unique roles in limiting self-reactivity of developing T cells. The authors find that this population is capable of rapid recovery following targeted ablation and that such ablation leads to loss of tolerance to self. The authors also find that Aire + TECs progress to a terminal Aire − stage, which may have a unique role in driving central tolerance.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Anastazja Grabarz , Josée Guirouilh-Barbat , Aurélia Barascu , Gaëlle Pennarun , Diane Genet , Emilie Rass , Susanne M. Germann , Pascale Bertrand , Ian D. Hickson , Bernard S. Lopez The choice of the appropriate double-strand break (DSB) repair pathway is essential for the maintenance of genomic stability. Here, we show that the Bloom syndrome gene product, BLM, counteracts CtIP/MRE11-dependent long-range deletions (>200 bp) generated by alternative end-joining (A-EJ). BLM represses A-EJ in an epistatic manner with 53BP1 and RIF1 and is required for ionizing-radiation-induced 53BP1 focus assembly. Conversely, in the absence of 53BP1 or RIF1, BLM promotes formation of A-EJ long deletions, consistent with a role for BLM in DSB end resection. These data highlight a dual role for BLM that influences the DSB repair pathway choi (1) protection against CtIP/MRE11 long-range deletions associated with A-EJ and (2) promotion of DNA resection. These antagonist roles can be regulated, according to cell-cycle stage, by interacting partners such as 53BP1 and TopIII, to avoid unscheduled resection that might jeopardize genome integrity. Graphical abstract Teaser The choice of the appropriate double-strand break (DSB) repair pathway is essential for the maintenance of genomic stability. Here, Lopez and colleagues show a dual role for the Bloom syndrome gene product, BLM, that influences the DSB repair pathway choice in two ways: (1) protection against long-range deletions associated with DSB end-joining and (2) promotion of DNA resection. These antagonistic roles can be regulated, according to cell-cycle stage, by interacting partners, to avoid unscheduled resection that might jeopardize genome integrity.

Description: Publication date: Available online 3 October 2013 Source: Cell Reports Author(s): Samantha B. Foley , Zacariah L. Hildenbrand , Abigail A. Soyombo , Jeffery A. Magee , Yipin Wu , Katherine I. Oravecz-Wilson , Theodora S. Ross Chronic myeloid leukemia (CML) and some acute lymphoblastic leukemias are characterized by the t(9;22) chromosome, which encodes the BCR/ABL oncogene. Multiple mouse models of CML express BCR/ABL at high levels from non- Bcr promoters, resulting in the development of leukemias. In contrast, a significant fraction of healthy humans have been found to have BCR/ABL-positive hematopoietic cells. To bridge the gap between the information derived from current mouse models and nonleukemic humans with the BCR/ABL oncogene, we generated a knockin model with BCR/ABL p210 expressed from the Bcr locus. Unlike previous models, expression of BCR/ABL from the knockin allele did not induce leukemia. BCR/ABL mutant cells did exhibit favorable bone marrow engraftment compared to control cells. These data suggest that BCR/ABL expression alone is insufficient to induce disease. This model allows for inducible spatial and temporal control of BCR/ABL expression for analysis of early steps in the pathogenesis of BCR/ABL-expressing leukemias. Graphical abstract Teaser In this study, Ross and colleagues show that when the BCR/ABL oncogene is placed in the mouse genome as a single-copy knockin mutation, the mice, like some humans with the BCR/ABL mutation, are leukemia free. The combination of this BCR/ABL allele with an AML1/ETO knockin allele led to myeloid neoplasia. This mouse mutation will aid in understanding BCR/ABL-associated predisease, which many predict is the precursor to florid chronic myeloid leukemia.

Description: Stable isotopes dissect food webs from top to the bottom Biogeosciences Discussions, 10, 14923-14952, 2013 Author(s): J. J. Middelburg Stable isotopes have been used extensively to study food web functioning, i.e. the flow of energy and matter among organisms. Traditional food-web studies are based on the natural variability of carbon and nitrogen isotopes and are limited to larger organisms that can be physically separated from their environment. Recent developments allow isotope ratio measurements of microbes and this in turn allows then measurement of entire food webs, i.e. from small producers at the bottom to large consumers at the top. Here, I provide a concise review on the use and potential of stable isotope to reconstruct end-to-end food webs. I will first discuss food web reconstruction based on natural abundances isotope data and will then show that the use of stable isotopes as deliberately added tracers provides complementary information. Finally, challenges and opportunities for end-to-end food web reconstructions in a changing world are discussed.

Description: Responses of carbon dioxide flux and plant biomass to drought in a treed peatland in northern Alberta: a climate change perspective Biogeosciences Discussions, 10, 14999-15031, 2013 Author(s): T. M. Munir, B. Xu, M. Perkins, and M. Strack Northern peatland ecosystems represent large carbon stocks that are susceptible to changes such as accelerated mineralization due to water table lowering expected under a climate change scenario. During the growing seasons of 2011 and 2012 we monitored CO 2 fluxes and plant biomass along a microtopographic gradient (hummocks-hollows) in an undisturbed dry continental boreal treed bog (control) and a nearby site that was drained (drained) in 2001. Ten years of drainage in the bog significantly increased coverage of shrubs at hummocks and lichens at hollows. Considering measured hummock coverage and including tree incremental growth, we estimate that the control site was a larger sink in 2011 of −40 than that of −13 g C m −2 in 2012 while the drained site was a source of 144 and 140 g C m −2 over the same years. We infer that, drainage induced changes in vegetation growth led to increased biomass to counteract a portion of soil carbon losses. These results suggest that spatial variability (microtopography) and changes in vegetation community in boreal peatlands will affect how these ecosystems respond to lowered water table potentially induced by climate change.

Description: The coccolithophores Emiliania huxleyi and Coccolithus pelagicus : extant populations from the Norwegian-Iceland Sea and Fram Strait Biogeosciences Discussions, 10, 15077-15106, 2013 Author(s): C. V. Dylmer, J. Giraudeau, V. Hanquiez, and K. Husum Extant coccolithophores and their relation to the governing oceanographic features in the northern North Atlantic were investigated along two zonal transects of surface water sampling, both conducted during summer 2011 and fall 2007. The northern transects crossed Fram Strait and its two opposing boundary currents (West Spitsbergen Current and East Greenland Current), while the southern transects sampled the Norwegian and Iceland Seas (passing the island Jan Mayen) from the Lofoten Islands to the continental margin off Eastern Greenland. The distribution of the dominant coccolithophore species Emiliania huxleyi and Coccolithus pelagicus is discussed in view of both the surface hydrology at the time of sampling and the structure of the surface mixed layer. Remote-sensing images as well as CTD and ARGO profiles are used to constrain the physico-chemical state of the surface water at the time of sampling. Both transects were characterized by strong seasonal differences in bulk coccolithophore standing stocks with maximum values of 53 × 10 3 cells L −1 for the northern transect and 72 × 10 3 cells L −1 for the southern transect in fall and summer, respectively. The highest recorded bulk cell densities are essentially explained by E. huxleyi . This species shows a zonal shift in peak abundance in the Norwegian-Iceland Seas from a summer maximum in the Lofoten gyre to peak cell densities around the island Jan Mayen in fall. Vertical mixing of Atlantic waters west of Lofoten Island, a phenomenom related to pervasive summer large scale atmospheric changes in the eastern Nordic Seas, on one hand, and strengthened influence of melt-water and related surface water stratification around the island Jan Mayen during fall, on the other hand, explains the observed seasonal migration of the E. huxleyi peak production area, as well as the seasonal change in dominating species within the Iceland Sea. In addition our datasets are indicative of a well-defined maximum boundary temperature of 6 °C for the production of C. pelagicus in the northern North Atlantic. The Fram Strait transects provides, to our knowledge, a first view of the zonal distribution of extant coccolithophores in this remote setting during summer and fall. Our datasets are indicative of a seasonal change in the species community from an E. huxleyi -dominated assemblage during summer to a C. pelagicus -rich population during fall. Here, higher irradiance and increased Atlantic water influence during summer favored the production of the opportunistic species E. huxleyi close to the Arctic Front, whereas the peak production area during fall, with high concentrations of C. pelagicus , lays in true Arctic/Polar waters.

Description: Publication date: Available online 12 September 2013 Source: Cell Reports Author(s): Ke Zhao , Juan Du , Xue Han , John L. Goodier , Peng Li , Xiaohong Zhou , Wei Wei , Sean L. Evans , Linzhang Li , Wenyan Zhang , Ling E. Cheung , Guanjun Wang , Haig H. Kazazian Jr. , Xiao-Fang Yu Long interspersed elements 1 (LINE-1) occupy at least 17% of the human genome and are its only active autonomous retrotransposons. However, the host factors that regulate LINE-1 retrotransposition are not fully understood. Here, we demonstrate that the Aicardi-Goutières syndrome gene product SAMHD1, recently revealed to be an inhibitor of HIV/simian immunodeficiency virus (SIV) infectivity and neutralized by the viral Vpx protein, is also a potent regulator of LINE-1 and LINE-1-mediated Alu/SVA retrotransposition. We also found that mutant SAMHD1s of Aicardi-Goutières syndrome patients are defective in LINE-1 inhibition. Several domains of SAMHD1 are critical for LINE-1 regulation. SAMHD1 inhibits LINE-1 retrotransposition in dividing cells. An enzymatic active site mutant SAMHD1 maintained substantial anti-LINE-1 activity. SAMHD1 inhibits ORF2p-mediated LINE-1 reverse transcription in isolated LINE-1 ribonucleoproteins by reducing ORF2p level. Thus, SAMHD1 may be a cellular regulator of LINE-1 activity that is conserved in mammals. Graphical abstract Teaser Long interspersed elements 1 (LINE-1) are active autonomous retrotransposons that occupy 17% of the human genome. The host factors that regulate LINE-1 retrotransposition are not fully understood. In this study, Yu and colleagues show that the Aicardi-Goutières syndrome (AGS) gene product, SAMHD1, is a potent regulator of LINE-1 retrotransposition. SAMHD1 mutants linked to AGS are defective in LINE-1 inhibition. Although SAMHD1 has also recently been shown to suppress HIV-1, the authors find that suppression of LINE-1 occurs through a distinct mechanism.

Description: Publication date: Available online 12 September 2013 Source: Cell Reports Author(s): Runsheng He , Ning Huang , Yitian Bao , Haining Zhou , Junlin Teng , Jianguo Chen During interphase, centrosomes are connected by a proteinaceous linker between the proximal ends of the centrioles, which is important for the centrosomes to function as a single microtubule-organizing center. However, the composition and regulation of centrosomal linker remain largely unknown. Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. Moreover, LRRC45 interacts with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber-like structures are significantly reduced, which subsequently leads to centrosome separation. Thus, LRRC45 is a critical component of the proteinaceous linker between two centrioles and is required for centrosome cohesion. Graphical abstract Teaser During interphase, the centrosomes are connected by a loose proteinaceous linker. Here, Teng, Chen, and colleagues identify LRRC45 as a centrosome linker required for centrosome cohesion. It is recruited by C-Nap1 at the proximal ends of the centrioles and forms fiber-like structures, together with rootletin. Also, LRRC45 is phosphorylated by Nek2A, which induces centrosome separation during mitosis. These findings facilitate a better understanding of the composition and regulation of centrosome linkers.

Description: Publication date: Available online 12 September 2013 Source: Cell Reports Author(s): Ying Tan , Dinghui Yu , Germain U. Busto , Curtis Wilson , Ronald L. Davis Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNAi approach. Interfering with β-catenin expression in adult mushroom body neurons specifically impaired long-term memory (LTM) without altering short-term memory. The impairment was reversible, being rescued by expression of a wild-type β-catenin transgene, and correlated with disruption of a cellular LTM trace. Inhibition of wingless , a Wnt ligand, and arrow , a Wnt coreceptor, also impaired LTM. Wingless expression in wild-type flies was transiently elevated in the brain after LTM conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in adult mushroom bodies impairs LTM, indicating that this pathway mechanistically underlies this specific form of memory. Graphical abstract Teaser Wnt signaling is crucial for many aspects of embryonic development, including cell proliferation, cell movement, and cell-fate decisions. In this report, Davis and colleagues show that Wnt signaling is required for the formation of protein-synthesis-dependent, long-term memory. Using RNAi approaches that target Wnt signaling components in the adult fly mushroom body, they show that knockdown of the Wnt ligand wingless , the Wnt coreceptor arrow , and the effector molecule β-catenin all impair the formation of long-term behavioral memory as well as a cellular memory trace representing this form of memory.

Description: Anthropogenic and natural methane fluxes in Switzerland synthesized within a spatially-explicit inventory Biogeosciences Discussions, 10, 15181-15224, 2013 Author(s): R. V. Hiller, D. Bretscher, T. DelSontro, T. Diem, W. Eugster, R. Henneberger, S. Hobi, E. Hodson, D. Imer, M. Kreuzer, T. Künzle, L. Merbold, P. A. Niklaus, B. Rihm, A. Schellenberger, M. H. Schroth, C. J. Schubert, H. Siegrist, J. Stieger, N. Buchmann, and D. Brunner We present the first high-resolution (500 m × 500 m) gridded methane (CH 4 ) emission inventory for Switzerland, which integrates the national emission totals reported to the United Nations Framework Convention on Climate Change (UNFCCC) and recent CH 4 flux studies conducted by research groups across Switzerland. In addition to anthropogenic emissions, we also include natural and semi-natural CH 4 fluxes, i.e., emissions from lakes and reservoirs, wetlands, wild animals as well as uptake by forest soils. National CH 4 emissions were disaggregated using detailed geostatistical information on source locations and their spatial extent and process- or area-specific emission factors. In Switzerland, the highest CH 4 emissions in 2011 originated from the agricultural sector (150 Gg CH 4 yr −1 ), mainly produced by ruminants and manure management, followed by emissions from waste management (15 Gg CH 4 yr −1 ) mainly from landfills and the energy sector (12 Gg CH 4 yr −1 ), which was dominated by emissions from natural gas distribution. Compared to the anthropogenic sources, emissions from natural and semi-natural sources were relatively small (6 Gg CH 4 yr −1 ), making up only 3 % of the total emissions in Switzerland. CH 4 fluxes from agricultural soils were estimated to be not significantly different from zero (between −1.5 and 0 Gg CH 4 yr −1 ), while forest soils are a CH 4 sink (approx. −2.8 Gg CH 4 yr −1 ), partially offsetting other natural emissions. Estimates of uncertainties are provided for the different sources, including an estimate of spatial disaggregation errors deduced from a comparison with a global (EDGAR v4.2) and a European CH 4 inventory (TNO/MACC). This new spatially-explicit emission inventory for Switzerland will provide valuable input for regional scale atmospheric modeling and inverse source estimation.

Description: Seasonal trends of dry and bulk concentration of nitrogen compounds over a rain forest in Ghana Biogeosciences Discussions, 10, 15225-15255, 2013 Author(s): F. Fattore, T. Bertolini, S. Materia, S. Gualdi, A. Thongo M'Bou, G. Nicolini, R. Valentini, A. De Grandcourt, D. Tedesco, and S. Castaldi African tropical forests of the equatorial belt might receive significant input of extra nitrogen derived from biomass burning occurring in the north savanna belt and transported equator wards by NE winds. In order to test this hypothesis an experiment was set up in a tropical rain forest in the National park of Ankasa (Ghana) aiming at: quantifying magnitude and seasonal variability of concentrations of N compounds, present as gas and aerosol (dry nitrogen) or in the rainfall (bulk nitrogen), over the studied forest; relating their seasonal variability to trends of local and regional winds and rainfall and to variations of fire events in the region. Three Delta systems, implemented for monthly measurements of NO 2 , were mounted over a tower at 45 m height, 20 m above forest canopy to sample gas (NH 3 , NO 2 , HNO 3 , HCl, SO 2 ) and aerosol (NH 4 + , NO 3 − , and several ions), together with three tanks for bulk rainfall collection (to analyze NH 4 + , NO 3 − and ion concentration). The tower was provided with a sonic anemometer to estimate local wind data. The experiment started in October 2011 and data up to October 2012 are presented. To interpret the observed seasonal trends of measured compounds, local and regional meteo data and regional satellite fire data were analyzed. The concentration of N compounds significantly increased from December to April, during the drier period, peaking in December-February when North Eastern winds (Harmattan) were moving dry air masses over the West central African region and the inter tropical convergence zone (ITCZ) was at its minimum latitude over the equator. This period also coincided with peaks of fire in the whole region. On the contrary, N concentration in gas, aerosol and rain decreased from May to October when prevalent winds arrived from the sea (South-East), during the Monsoon period. Both ionic compositions of rain and analysis of local wind direction showed a significant and continuous presence of see-breeze at site. The ionic composition of rain water resulted much closer to see water and poorer in N compounds from May to October.

Description: Publication date: Available online 19 September 2013 Source: FEBS Open Bio Author(s): Wei Chi , Xiaoni Gan , Wuhan Xiao , Wen Wang , Shunping He Hypoxia-inducible factor (HIF) is a crucial regulator of cellular and systemic responses to low oxygen levels. Here we firstly cloned three HIF-α isoforms from the basal branches of Osteichthyes and used computational tools to characterize the molecular change underlying the functional divergence of HIF-α isoforms in different lineages. Only the HIF-1α and HIF-2α in African lungfish and amphibians were found under positive selection. HIF-1α and -2α were less functionally divergent in basal ray-finned fish than in teleosts, and showed conserved but different transcriptional activity toward specific target genes.

Description: Publication date: Available online 19 September 2013 Source: Cell Reports Author(s): Hongxia Zhao , Alphée Michelot , Essi V. Koskela , Vadym Tkach , Dimitrios Stamou , David G. Drubin , Pekka Lappalainen Bin-Amphiphysin-Rvs (BAR) domain proteins are central regulators of many cellular processes involving membrane dynamics. BAR domains sculpt phosphoinositide-rich membranes to generate membrane protrusions or invaginations. Here, we report that, in addition to regulating membrane geometry, BAR domains can generate extremely stable lipid microdomains by “freezing” phosphoinositide dynamics. This is a general feature of BAR domains, because the yeast endocytic BAR and Fes/CIP4 homology BAR (F-BAR) domains, the inverse BAR domain of Pinkbar, and the eisosomal BAR protein Lsp1 induced phosphoinositide clustering and halted lipid diffusion, despite differences in mechanisms of membrane interactions. Lsp1 displays comparable low diffusion rates in vitro and in vivo, suggesting that BAR domain proteins also generate stable phosphoinositide microdomains in cells. These results uncover a conserved role for BAR superfamily proteins in regulating lipid dynamics within membranes. Stable microdomains induced by BAR domain scaffolds and specific lipids can generate phase boundaries and diffusion barriers, which may have profound impacts on diverse cellular processes. Graphical abstract Teaser Bin-Amphiphysin-Rvs (BAR) domain superfamily proteins are central membrane-sculpting proteins in all eukaryote cells. Here, Lappalainen and colleagues demonstrate that BAR domain scaffolds not only bend membranes but also affect lipid distribution and dynamics by dramatically inhibiting the lateral diffusion of phosphoinositides. The extremely stable BAR domain-induced phosphoinositide microdomains can generate lipid phase boundaries and diffusion barriers, which are likely to have profound impacts on a wide variety of cellular processes, including endocytosis.

Description: Inferences from CO 2 and CH 4 concentration profiles at the Zotino Tall Tower Observatory (ZOTTO) on local summer-time ecosystem fluxes Biogeosciences Discussions, 10, 15337-15372, 2013 Author(s): J. Winderlich, C. Gerbig, O. Kolle, and M. Heimann The Siberian region is still sparsely covered by ecosystem observatories, which motivates to exploit existing datasets to gain spatially and temporally better-resolved carbon fluxes. The Zotino Tall Tower Observatory (ZOTTO, 60°48' N, 89°21' E) observations of CO 2 and CH 4 mole fractions as well as meteorological parameters from six different heights up to 301 m allow for an additional estimate of surface-atmosphere fluxes of CO 2 and CH 4 for the Middle-Siberian region since 2009. The total carbon flux is calculated from the storage and the turbulent flux component. The gradients between the different tower levels determine the storage flux component, which dominates the local fluxes, especially during night. As a correction term, the turbulent flux component was estimated by the modified Bowen ratio method based on the sensible heat flux measurements at the top of the tower. The gained average night time fluxes (23:00 to 04:00 local time) are 2.7 ± 1.1 μmol (m 2 s) −1 for CO 2 and 5.6 ± 4.5 nmol (m 2 s) −1 for CH 4 during the summer months June-September in 2009 and 2011. During day, the method is limited due to numeric instabilities from vanishing vertical gradients; however, the derived CO 2 fluxes exhibit reasonable diurnal shape and magnitude compared to the eddy covariance technique, which become available at the site in 2012. Therefore, the tall tower data facilitates the extension of the new eddy covariance flux dataset back in time. The diurnal signal of the CH 4 flux is predominantly characterized by a strong morning transition, which is explained by local topographic effects.

Description: Live foraminiferal faunas (Rose Bengal stained) from the northern Arabian Sea: links with bottom-water oxygenation Biogeosciences Discussions, 10, 15257-15304, 2013 Author(s): C. Caulle, K. A. Koho, M. Mojtahid, G. J. Reichart, and F. J. Jorissen Live (Rose Bengal stained) benthic foraminifera from the Murray Ridge, within and below the northern Arabian Sea Oxygen Minimum Zone (OMZ), were studied in order to determine the relationship between faunal composition, bottom-water oxygenation (BWO), pore-water chemistry and organic matter (organic carbon and phytopigment) distribution. A series of multicores were recovered from a ten-station oxygen (BWO: 2–78 μM) and bathymetric (885–3010 m depth) transect during the winter monsoon in January 2009. Foraminifera were investigated from three different size fractions (63–125 μm, 125–150 μm and 〉 150 μm). The larger foraminifera (〉 125 μm) were strongly dominated by agglutinated species (e.g. Reophax spp.). In contrast, in the 63–125 μm fraction, calcareous taxa were more abundant, especially in the core of the OMZ, suggesting an opportunistic behaviour. On the basis of a Principal Component Analysis, three foraminiferal groups were identified, reflecting the environmental parameters along the study transect. The faunas from the shallowest stations, in the core of the OMZ (BWO: 2 μM), were composed of "low oxygen" species, typical of the Arabian Sea OMZ (e.g., Rotaliatinopsis semiinvoluta , Praeglobobulimina spp. , Bulimina exilis, Uvigerina peregrina type parva ). These taxa are adapted to the very low BWO conditions and to high phytodetritus supplies. The transitional group, typical for the lower part of the OMZ (BWO: 5–16 μM), is composed of more cosmopolitan taxa tolerant to low-oxygen concentrations ( Globocassidulina subglobosa , Ehrenbergina trigona ). Below the OMZ (BWO: 26–78 μM), where food availability is more limited and becomes increasingly restricted to surficial sediments, more cosmopolitan calcareous taxa were present, such as Bulimina aculeata, Melonis barleeanus, Uvigerina peregrina and Epistominella exigua . Miliolids were uniquely observed in this last group, reflecting the higher BWO. At these deeper sites, the faunas exhibit a clear depth succession of superficial, intermediate and deep-infaunal microhabitats, because of the deeper oxygen and nitrate penetration into the sediment.

Description: Publication date: Available online 25 September 2013 Source: FEBS Open Bio Author(s): Michal Slutzki , Maroor K. Jobby , Seth Chitayat , Alon Karpol , Bareket Dassa , Yoav Barak , Raphael Lamed , Steven P. Smith , Edward A. Bayer The cellulosome is a large extracellular multi-enzyme complex that facilitates the efficient hydrolysis and degradation of crystalline cellulosic substrates. During the course of our studies on the cellulosome of the rumen bacterium Ruminococcus flavefaciens, we focused on the critical ScaA dockerin (ScaADoc), the unique dockerin that incorporates the primary enzyme-integrating ScaA scaffoldin into the cohesin-bearing ScaB adaptor scaffoldin. In the absence of a high-resolution structure of the ScaADoc module, we generated a computational model, and, upon its analysis, we were surprised to discover a putative stacking interaction between an N-terminal Trp and a C-terminal Pro, which we termed intramolecular clasp. In order to verify the existence of such an interaction, these residues were mutated to alanine. Circular dichroism spectroscopy, intrinsic tryptophan and ANS fluorescence, and NMR spectroscopy indicated that mutation of these residues has a destabilizing effect on the functional integrity of the Ca 2+ -bound form of ScaADoc. Analysis of recently determined dockerin structures from other species revealed the presence of other well-defined intramolecular clasps, which consist of different types of interactions between selected residues at the dockerin termini. We propose that this thematic interaction may represent a major distinctive structural feature of the dockerin module. Graphical abstract

Description: Landscape-scale changes in forest structure and functional traits along an Andes-to-Amazon elevation gradient Biogeosciences Discussions, 10, 15415-15454, 2013 Author(s): G. P. Asner, C. Anderson, R. E. Martin, D. E. Knapp, R. Tupayachi, T. Kennedy-Bowdoin, F. Sinca, and Y. Malhi Elevation gradients provide opportunities to explore environmental controls on forest structure and functioning, but plot-based studies have proven highly variable due to limited geographic scope. We used airborne imaging spectroscopy and LiDAR (light detection and ranging) to quantify changes in three-dimensional forest structure and canopy functional traits in a series of 25 ha landscapes distributed along a 3300 m elevation gradient from lowland Amazonia to treeline in the Peruvian Andes. Canopy greenness, photosynthetic fractional cover and exposed non-photosynthetic vegetation varied as much across lowland forests (100–200 m) as they did from the lowlands to the Andean treeline (3400 m). Elevation was positively correlated with canopy gap density and understory vegetation cover, and negatively related to canopy height and vertical profile. Increases in gap density were tightly linked to increases in understory plant cover, and larger gaps (20–200 m 2 produced 25–30 times the response in understory cover than did smaller gaps ( 〈 5 m 2 . Scaling of gap size to gap frequency was, however, relatively constant along the elevation gradient, which when combined with other canopy structural information, indicates equilibrium turnover patterns from the lowlands to treeline. Our results provide a first landscape-scale quantification of forest structure and canopy functional traits with changing elevation, thereby improving our understanding of disturbance, demography and ecosystem processes in the Andes-to-Amazon corridor.

Description: Publication date: 26 September 2013 Source: Cell Reports, Volume 4, Issue 6 Author(s): Steffi Oesterreich , Adam M. Brufsky , Nancy E. Davidson In this issue of Cell Reports , Li et al. show that the analysis of genetic changes in patient-derived xenografts can reveal crucial details of tumor evolution, such as the emergence of functional estrogen receptor mutations in endocrine-resistant breast cancer.

Description: Publication date: Available online 26 September 2013 Source: Cell Reports Author(s): Lingjie Li , Bo Liu , Orly L. Wapinski , Miao-Chih Tsai , Kun Qu , Jiajing Zhang , Jeff C. Carlson , Meihong Lin , Fengqin Fang , Rajnish A. Gupta , Jill A. Helms , Howard Y. Chang Long noncoding RNAs (lncRNAs) are thought to be prevalent regulators of gene expression, but the consequences of lncRNA inactivation in vivo are mostly unknown. Here, we show that targeted deletion of mouse Hotair lncRNA leads to derepression of hundreds of genes, resulting in homeotic transformation of the spine and malformation of metacarpal-carpal bones. RNA sequencing and conditional inactivation reveal an ongoing requirement of Hotair to repress HoxD genes and several imprinted loci such as Dlk1-Meg3 and Igf2-H19 without affecting imprinting choice. Hotair binds to both Polycomb repressive complex 2, which methylates histone H3 at lysine 27 (H3K27), and Lsd1 complex, which demethylates histone H3 at lysine 4 (H3K4) in vivo. Hotair inactivation causes H3K4me3 gain and, to a lesser extent, H3K27me3 loss at target genes. These results reveal the function and mechanisms of Hotair lncRNA in enforcing a silent chromatin state at Hox and additional genes. Graphical abstract Teaser A targeted and conditional knockout of the lncRNA, Hotair , is now presented by Chang and colleagues. The authors find that Hotair disruption causes homeotic transformation and skeletal malformation during mouse development. Hotair knockout leads to derepression of multiple genes, including HoxD and several imprinted genes. Furthermore, Hotair interacts with PRC2 and LSD1, and Hotair deletion altered chromatin states at specific targets.

Description: Publication date: Available online 26 September 2013 Source: Cell Reports Author(s): Saskia Delpretti , Thomas Montavon , Marion Leleu , Elisabeth Joye , Athanasia Tzika , Michel Milinkovitch , Denis Duboule Hox genes are required for the development of the intestinal cecum, a major organ of plant-eating species. We have analyzed the transcriptional regulation of Hoxd genes in cecal buds and show that they are controlled by a series of enhancers located in a gene desert flanking the HoxD cluster. The start site of two opposite long noncoding RNAs (lncRNAs), Hotdog and Twin of Hotdog , selectively contacts the expressed Hoxd genes in the framework of a topological domain, coinciding with robust transcription of these genes during cecum budding. Both lncRNAs are specifically transcribed in the cecum, albeit bearing no detectable function in trans . Hedgehogs have kept this regulatory potential despite the absence of the cecum, suggesting that these mechanisms are used in other developmental situations. In this context, we discuss the implementation of a common “budding toolkit” between the cecum and the limbs. Graphical abstract Teaser The intestinal cecum is a major organ for plant-eating species. Duboule and colleagues report that a series of enhancers, along with the Hotdog lncRNA, selectively contact a subset of HoxD genes and form a 3D regulatory structure, which coincides with a topological domain and elicits robust transcription. Hedgehogs have kept this regulatory potential despite absence of the cecum, suggesting that these mechanisms are part of a common “budding toolkit” also used during limb bud development.

Description: Publication date: Available online 26 September 2013 Source: Cell Reports Author(s): Inna Shcherbakova , Aaron A. Hoskins , Larry J. Friedman , Victor Serebrov , Ivan R. Corrêa Jr. , Ming-Qun Xu , Jeff Gelles , Melissa J. Moore Removal of introns from nascent transcripts (pre-mRNAs) by the spliceosome is an essential step in eukaryotic gene expression. Previous studies have suggested that the earliest steps in spliceosome assembly in yeast are highly ordered and the stable recruitment of U1 small nuclear ribonucleoprotein particle (snRNP) to the 5′ splice site necessarily precedes recruitment of U2 snRNP to the branch site to form the “prespliceosome.” Here, using colocalization single-molecule spectroscopy to follow initial spliceosome assembly on eight different S. cerevisiae pre-mRNAs, we demonstrate that active yeast spliceosomes can form by both U1-first and U2-first pathways. Both assembly pathways yield prespliceosomes functionally equivalent for subsequent U5⋅U4/U6 tri-snRNP recruitment and for intron excision. Although fractional flux through the two pathways varies on different introns, both are operational on all introns studied. Thus, multiple pathways exist for assembling functional spliceosomes. These observations provide insight into the mechanisms of cross-intron coordination of initial spliceosome assembly. Graphical abstract Teaser Intron excision by the spliceosome is an essential process in eukaryotic gene expression. Gelles, Moore, and colleagues use single-molecule colocalization to monitor early spliceosome assembly events in yeast whole-cell extract. They demonstrate that pre-mRNAs can initiate the formation of functional spliceosomes by first binding either U1 or U2 snRNP. This branched pathway has important implications for mechanisms of cross-intron coordination during early spliceosome assembly.

Description: Publication date: Available online 26 September 2013 Source: Cell Reports Author(s): Naif Zaman , Lei Li , Maria Luz Jaramillo , Zhanpeng Sun , Chabane Tibiche , Myriam Banville , Catherine Collins , Mark Trifiro , Miltiadis Paliouras , Andre Nantel , Maureen O’Connor-McCourt , Edwin Wang Individual cancer cells carry a bewildering number of distinct genomic alterations (e.g., copy number variations and mutations), making it a challenge to uncover genomic-driven mechanisms governing tumorigenesis. Here, we performed exome sequencing on several breast cancer cell lines that represent two subtypes, luminal and basal. We integrated these sequencing data and functional RNAi screening data (for the identification of genes that are essential for cell proliferation and survival) onto a human signaling network. Two subtype-specific networks that potentially represent core-signaling mechanisms underlying tumorigenesis were identified. Within both networks, we found that genes were differentially affected in different cell lines; i.e., in some cell lines a gene was identified through RNAi screening, whereas in others it was genomically altered. Interestingly, we found that highly connected network genes could be used to correctly classify breast tumors into subtypes on the basis of genomic alterations. Further, the networks effectively predicted subtype-specific drug targets, which were experimentally validated. Graphical abstract Teaser In this study, Wang and colleagues examine cancer genome sequencing data in a framework of a signaling network integrated with genome-wide RNAi knockdown information. They show that cancer cell survival network genes recurrently switch roles, between essential and cancer driving, among cancer subtypes. Mutations and copy number variations driving tumorigenesis are selected to be convergent onto cell survival networks. Genomic alterations of cancer cell survival subtype-specific network genes successfully predicted cancer subtype-specific drug targets and accurately classified cancer subtypes.

Description: Publication date: Available online 27 September 2013 Source: Cell Reports Author(s): Elizabeth Garner , Yonghwan Kim , Francis P. Lach , Molly C. Kottemann , Agata Smogorzewska Holliday junctions (HJs), the DNA intermediates of homologous recombination, need to be faithfully processed in order to preserve genome integrity. In human cells, the BLM helicase complex promotes nonnucleolytic dissolution of double HJs. In vitro, HJs may be nucleolytically processed by MUS81-EME1, GEN1, and SLX4-SLX1. Here, we exploit human SLX4 -null cells to examine the requirements for HJ resolution in vivo. Lack of BLM and SLX4 or GEN1 and SLX4 is synthetically lethal in the absence of exogenous DNA damage, and lethality is a consequence of dysfunctional mitosis proceeding in the presence of unprocessed HJs. Thus, GEN1 activity cannot be substituted for the SLX4-associated nucleases, and one of the HJ resolvase activities, either of those associated with SLX4 or with GEN1, is required for cell viability, even in the presence of BLM. In vivo HJ resolution depends on both SLX4-associated MUS81-EME1 and SLX1, suggesting that they are acting in concert in the context of SLX4. Graphical abstract Teaser The requirements for Holliday junction (HJ) processing in human mitotic cells are now dissected by Smogorzewska and colleagues. The authors demonstrate that nuclease-mediated resolution of HJs, provided by SLX4-associated nucleases and GEN1, is a requirement for cell viability rather than a backup pathway for nonnucleolytic dissolution. When HJs do not get processed, dramatic chromosomal abnormalities appear and cells cannot complete division. The study also finds that two SLX4-associated nucleases, MUS81-EME1 and SLX1, are necessary for HJ resolution.

Description: Publication date: Available online 29 September 2013 Source: FEBS Open Bio Author(s): Chantel N. Jensen , Sohail T. Ali , Michael J. Allen , Gideon Grogan The flavoprotein monooxygenase (FPMO) from Stenotrophomonas maltophilia (SMFMO, Uniprot: B2FLR2) catalyses the asymmetric oxidation of thioethers and is unusual amongst FPMOs in its ability to use the non-phosphorylated cofactor NADH, as well as NADPH, for the reduction of the FAD coenzyme. In order to explore the basis for cofactor promiscuity, structure-guided mutation of two residues in the cofactor binding site, Gln193 and His194, in SMFMO were performed in an attempt to imitate the cofactor binding site of the NADPH-dependent FMO from Methylophaga aminisulfidivorans sp. SK1 (mFMO), in which structurally homologous residues Arg234 and Thr235 bind the NADPH 2’-ribose phosphate. Mutation of His194 to threonine proved most significant, with a switch in specificity from NADH to NADPH [( k cat / K m NADH)/ k cat / K m NADPH) from 1.5:1 to 1:3.5, mostly as a result of a reduced K m for NADPH of approximately seven-fold in the His194Thr mutant. The structure of the Gln193Arg/His194Thr mutant revealed no substantial changes in the backbone of the enzyme or orientation of side chains resulting from mutation. Mutation of Phe52, in the vicinity of FAD, and which in mFMO is an asparagine thought to be responsible for flavin hydroperoxide stabilisation, is, in SMFMO, a determinant of enantioselectivity in sulfoxidation. Mutation of Phe52 to valine resulted in a mutant that transformed para -tolyl methyl sulfide into the ( S )-sulfoxide with 32% e.e., compared to 25% ( R )- for the wild type. These results shed further light both on the cofactor specificity of FPMOs, and their determinants of enantioselectivity, with a view to informing engineering studies of FPMOs in the future.

Description: Publication date: Available online 30 September 2013 Source: FEBS Open Bio Author(s): Yoshichika Taira , Yuki Okegawa , Kazuhiko Sugimoto , Masato Abe , Hideto Miyoshi , Toshiharu Shikanai Antimycin A 3 (AA) is used as an inhibitor of cyclic electron transport around photosystem I. However, the high concentrations of AA that are needed for inhibition have secondary effects, even in chloroplasts. Here, we screened for chemicals that inhibited ferredoxin-dependent plastoquinone reduction in ruptured chloroplasts at lower concentrations than those required for AA. We identified two AA-like compounds: AAL1 and AAL2. AAL1 likely shares an inhibitory site with AA, most probably in the PGR5–PGRL1 protein complex, and enhances O 2 evolution in photosystem II, most likely via an uncoupler-like effect. AAL1 and AAL2 are unlikely to penetrate intact leaves. In ruptured chloroplasts, AALs are superior to AA as inhibitors of cyclic electron transport.

Description: Springtime phytoplankton dynamics in the Arctic Krossfjorden and Kongsfjorden (Spitsbergen) as a function of glacier proximity Biogeosciences Discussions, 10, 15519-15557, 2013 Author(s): A. M.-T. Piquet, W. H. van de Poll, R. J. W. Visser, C. Wiencke, H. Bolhuis, and A. G. J. Buma The hydrographic properties of the Kongsfjorden – Krossfjorden system (79° N, Spitsbergen) are affected by Atlantic water incursions as well as glacier meltwater runoff. This results in strong physical gradients (temperature, salinity and irradiance) within the fjords. Here, we tested the hypothesis that glaciers affect phytoplankton dynamics as early as the productive spring bloom period. During two campaigns in 2007 (late spring) and 2008 (early spring) we studied hydrographic characteristics and phytoplankton variability along 2 transects in both fjords, using HPLC-CHEMTAX pigment fingerprinting, molecular fingerprinting (DGGE) and sequencing of 18S rRNA genes. The sheltered inner fjord locations remained colder during spring as opposed to the outer locations. Vertical light attenuation coefficients increased from early spring onwards, at all locations, but in particular at the inner locations. During the end of spring, meltwater input had stratified surface waters throughout the fjords. The inner fjord locations were characterized by overall lower phytoplankton biomass. Furthermore HPLC-CHEMTAX data revealed that diatoms and Phaeocystis sp. were replaced by small nano- and picophytoplankton during late spring, coinciding with low nutrient availability. The innermost stations showed higher relative abundances of nano- and picophytoplankton throughout, notably of cyanophytes and cryptophytes. Molecular fingerprinting revealed a high similarity between inner fjord samples from early spring and late spring samples from all locations, while outer samples from early spring clustered separately. We conclude that glacier influence, mediated by early meltwater input, modifies phytoplankton biomass and composition already during the spring bloom period, in favor of low biomass and small cell size communities. This may affect higher trophic levels especially when regional warming further increases the period and volume of meltwater.

Description: Simulating microbial degradation of organic matter in a simple porous system using the 3-D diffusion based model MOSAIC Biogeosciences Discussions, 10, 15613-15640, 2013 Author(s): O. Monga, P. Garnier, V. Pot, E. Coucheney, N. Nunan, W. Otten, and C. Chenu This paper deals with the simulation of microbial degradation in soil within pore space at microscopic scale. Pore space was described using sphere network coming from a geometrical modeling algorithm. The biological model was improved regarding previous work in order to include transformation of dissolved organic compounds and diffusion processes. Our model was tested using experimental results of a simple substrate decomposition (Fructose) within a simple media (the sand). Diverse microbial communities were inoculated. Separated incubations in microcosms were carried out using 5 different bacterial communities at 2 different water potentials of −10 cm and −100 cm of water. We calibrated the biological parameters by means of experimental data obtained at high water content and we tested the model without any parameters change at low water content. Same as for experimental data, our simulation results showed the decrease in water content involved the decrease of mineralisation. The model was able to simulate the decrease of connectivity between substrate and microorganism due the decrease of water content.

Description: Influence of temperature and CO 2 on the strontium and magnesium composition of coccolithophore calcite Biogeosciences Discussions, 10, 15559-15586, 2013 Author(s): M. N. Müller, M. Lebrato, U. Riebesell, J. Barcelos e Ramos, K. G. Schulz, S. Blanco-Ameijeiras, S. Sett, A. Eisenhauer, and H. M. Stoll Marine calcareous sediments provide a fundamental basis for paleoceanographic studies aiming to reconstruct past oceanic conditions and understand key biogeochemical element cycles. Calcifying unicellular phytoplankton (coccolithophores) are a major contributor to both carbon and calcium cycling by photosynthesis and the production of calcite (coccoliths) in the euphotic zone and the subsequent long-term deposition and burial into marine sediments. Here we present data from controlled laboratory experiments on four coccolithophore species and elucidate the relation between the divalent cation (Sr, Mg and Ca) partitioning in coccoliths and cellular physiology (growth, calcification and photosynthesis). Coccolithophores were cultured under different seawater temperature and carbonate chemistry conditions. The partition coefficient of strontium ( D Sr ) was positively correlated with both carbon dioxide ( p CO 2 ) and temperature but displayed no coherent relation to particulate organic and inorganic carbon production rates. Furthermore, D Sr correlated positively with cellular growth rates when driven by temperature but no correlation was present when changes in growth rates were p CO 2 -induced. The results demonstrate the complex interaction between environmental forcing and physiological control on the strontium partitioning in coccolithophore calcite. The partition coefficient of magnesium ( D Mg ) displayed species-specific differences and elevated values under nutrient limitation. No conclusive correlation between coccolith D Mg and temperature was observed but p CO 2 induced a rising trend in coccolith D Mg . Interestingly, the best correlation was found between coccolith D Mg and chlorophyll a production suggesting that chlorophyll a and calcite associated Mg originate from the same intracellular pool. These results give an extended insight into the driving factors that lead to variations in the coccolith Mg / Ca ratio and can be used for Sr / Ca and Mg / Ca paleoproxy calibration.

Description: Forest NEP is significantly driven by previous year's weather Biogeosciences Discussions, 10, 15587-15611, 2013 Author(s): S. Zielis, S. Etzold, R. Zweifel, W. Eugster, M. Haeni, and N. Buchmann Understanding the response of forest net ecosystem productivity (NEP) to environmental drivers under climate change is highly relevant for predictions of annual forest carbon (C) flux budgets. Modeling annual forest NEP with soil–vegetation–atmosphere transfer models (SVATs), however, remains challenging due to unknown responses of forests to weather of the previous year. In this study, we addressed the influence of previous year's weather on the inter-annual variability of NEP for a subalpine spruce forest in Switzerland. Analysis of long-term (1997–2011) eddy covariance measurements showed that the Norway spruce forest Davos Seehornwald was a consistent sink for atmospheric CO 2 , sequestering 210 ± 88 g C m −2 per year on average. Previous year's weather strongly affected inter-annual variability of NEP, increasing the explained variance in linear models to 53% compared to 20% without previous year's weather. Thus, our results highlight the need to consider previous year's weather in modeling annual C budgets of forests. Furthermore, soil temperature in the current year's spring played a major role controlling annual NEP, mainly by influencing gross primary productivity early in the year, with spring NEP accounting for 56% of annual NEP. Consequently, we expect an increase in net CO 2 uptake with future climate warming, as long as no other resources become limiting.

Description: Synoptic evaluation of carbon cycling in Beaufort Sea during summer: contrasting river inputs, ecosystem metabolism and air–sea CO 2 fluxes Biogeosciences Discussions, 10, 15641-15710, 2013 Author(s): A. Forest, P. Coupel, B. Else, S. Nahavandian, B. Lansard, P. Raimbault, T. Papakyriakou, Y. Gratton, L. Fortier, J.-É. Tremblay, and M. Babin The accelerated decline in Arctic sea ice combined with an ongoing trend toward a more dynamic atmosphere is modifying carbon cycling in the Arctic Ocean. A critical issue is to understand how net community production (NCP; the balance between gross primary production and community respiration) responds to changes and modulates air–sea CO 2 fluxes. Using data collected as part of the ArcticNet-Malina 2009 expedition in southeastern Beaufort Sea (Arctic Ocean), we synthesize information on sea ice, wind, river, water column properties, metabolism of the planktonic food web, organic carbon fluxes and pools, as well as air–sea CO 2 exchange, with the aim of identifying indices of ecosystem response to environmental changes. Data were analyzed to develop a non-steady-state carbon budget and an assessment of NCP against air–sea CO 2 fluxes. The mean atmospheric forcing was a mild upwelling-favorable wind (~5 km h −1 ) blowing from the N-E and a decaying ice cover ( 600 mg C m −2 d −1 ) over the shelf prior to our survey, (2) freshwater dilution by river runoff and ice melt, and (3) the presence of cold surface waters offshore. Only the Mackenzie River delta and localized shelf areas directly affected by upwelling were identified as substantial sources of CO 2 to the atmosphere (〉10mmol C m −2 d −1 ). Although generally

Description: Publication date: Available online 6 June 2013 Source: Cell Reports Author(s): Guillaume Diss , Alexandre K. Dubé , Joël Boutin , Isabelle Gagnon-Arsenault , Christian R. Landry Cells contain many important protein complexes involved in performing and regulating structural, metabolic, and signaling functions. One major challenge in cell biology is to elucidate the organization and mechanisms of robustness of these complexes in vivo. We developed a systematic approach to study structural dependencies within complexes in living cells by deleting subunits and measuring pairwise interactions among other components. We used our methodology to perturb two conserved eukaryotic complexes: the retromer and the nuclear pore complex. Our results identify subunits that are critical for the assembly of these complexes, reveal their structural architecture and uncover…, and uncover mechanisms by which protein interactions are modulated. Our results also show that paralogous proteins play a key role in the robustness of protein complexes and shape their assembly landscape. Our approach paves the way for studying the response of protein interactomes to mutations and enhances our understanding of genotype-phenotype maps. Graphical abstract

Description: Publication date: Available online 6 June 2013 Source: Cell Reports Author(s): Christopher R. Faehnle , Elad Elkayam , Astrid D. Haase , Gregory J. Hannon , Leemor Joshua-Tor Argonautes are the central protein component in small RNA silencing pathways. Of the four human Argonautes (hAgo1–hAgo4) only hAgo2 is an active slicer. We determined the structure of hAgo1 bound to endogenous copurified RNAs to 1.75 Å resolution and hAgo1 loaded with let-7 microRNA to 2.1 Å. Both structures are strikingly similar to the structures of hAgo2. A conserved catalytic tetrad within the PIWI domain of hAgo2 is required for its slicing activity. Completion of the tetrad, combined with a mutation on a loop adjacent to the active site of hAgo1, results in slicer activity that is substantially enhanced by swapping in the N domain of hAgo2. hAgo3, with an intact tetrad, becomes an active slicer by swapping the N domain of hAgo2 without additional mutations. Intriguingly, the elements that make Argonaute an active slicer involve a sophisticated interplay between the active site and more distant regions of the enzyme. Graphical abstract

Description: Foraminiferal survival after long term experimentally induced anoxia Biogeosciences Discussions, 10, 9243-9284, 2013 Author(s): D. Langlet, E. Geslin, C. Baal, E. Metzger, F. Lejzerowicz, B. Riedel, M. Zuschin, J. Pawlowski, M. Stachowitsch, and F. J. Jorissen Anoxia has been successfully induced in four benthic chambers installed on the Northern Adriatic seafloor from 1 week to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerGreen method has been applied. Numerous individuals have been found living at all sampling times and at all sampling depths, showing that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulphides. However, foraminiferal standing stocks decrease with sampling time in an irregular way. A large difference in standing stock between two cores samples in initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after 1 month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in a core sampled after 2 months of anoxia, to attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulphides, but rather due to a continuous diminution of labile organic matter.

Description: Environmental controls on the Emiliania huxleyi calcite mass Biogeosciences Discussions, 10, 9285-9313, 2013 Author(s): M. T. Horigome, P. Ziveri, M. Grelaud, K.-H. Baumann, G. Marino, and P. G. Mortyn Although ocean acidification is expected to impact (bio)calcification by decreasing the seawater carbonate ion concentration, [CO 3 2− ], there exists evidence of non-uniform response of marine calcifying plankton to low seawater [CO 3 2− ]. This raises questions on the role of environmental factors other than acidification and on the complex physiological responses behind calcification. Here we investigate the synergistic effect of multiple environmental parameters, including temperature, nutrient (nitrate and phosphate) availability, and seawater carbonate chemistry on the coccolith calcite mass of the cosmopolitan coccolithophore Emiliania huxleyi , the most abundant species in the world ocean. We use a suite of surface (late Holocene) sediment samples from the South Atlantic and southwestern Indian Ocean taken from depths lying well above the modern lysocline. The coccolith calcite mass in our results presents a latitudinal distribution pattern that mimics the main oceanographic features, thereby pointing to the potential importance of phosphorus and temperature in determining coccolith mass by affecting primary calcification and possibly driving the E. huxleyi morphotype distribution. This evidence does not necessarily argue against the potentially important role of the rapidly changing seawater carbonate chemistry in the future, when unabated fossil fuel burning will likely perturb ocean chemistry beyond a critical point. Rather our study highlights the importance of evaluating the combined effect of several environmental stressors on calcifying organisms to project their physiological response(s) in a high CO 2 world and improve interpretation of paleorecords.