bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx
Authors: Broertjes Jorrit , Klarenbeek Jeffrey , Habani Yasmin , Langeslag Michiel , Jalink Kees 
Published: February 2018

AbstractThe nonspecific divalent cation channel TRPM7 (transient receptor potential-melastatin-like 7) is involved in many Ca2+ and Mg2+-dependent cellular processes, including survival, proliferation and migration. TRPM7 expression predicts metastasis and recurrence in breast cancer and several other cancers. In cultured cells, it can induce an invasive phenotype by promoting Ca2+-mediated epithelial-mesenchymal transition. We previously showed that in neuroblastoma cells that overexpress TRPM7 moderately, stimulation with Ca2+-mobilizing agonists leads to a characteristic sustained influx of Ca2+. Here we report that sustained influx through TRPM7 is abruptly abrogated by elevating intracellular levels of cAMP. Using pharmacological inhibitors and overexpression studies we show that this blockage is mediated by the cAMP effector Protein Kinase A (PKA). Mutational analysis demonstrates that the Serine residue S1269, which is present proximal to the coiled-coil domain within the protein c-terminus, is responsible for sensitivity to cAMP.
The dynamic tumor ecosystem: how cell turnover and trade-offs affect cancer evolution
Authors: Gallaher Jill A. , Brown Joel , Anderson Alexander R. A. 
Published: February 2018

ABSTRACTTumors are not static masses of cells but rather dynamic ecosystems where cancer cells experience constant turnover and evolve fitness-enhancing phenotypes. Selection for different phenotypes may vary with 1) the tumor niche (edge or core), 2) cell turnover rates, 3) the nature of the tradeoff between traits (proliferation vs migration), and 4) whether deaths occur in response to demographic or environmental stochasticity. In an agent based, spatially-explicit model, we observe how two traits (proliferation rate and migration speed) evolve under different trade-off conditions with different turnover rates. Migration rate is favored over proliferation at the tumor’s edge and vice-versa for the interior. Increasing cell turnover rates only slightly slows the growth of the tumor, but accelerates the rate of evolution for both proliferation and migration. The absence of a tradeoff favors ever higher values for proliferation and migration. A convex tradeoff tends to favor proliferation over migration while often promoting the coexistence of a generalist and specialist phenotype. A concave tradeoff slows the rate of evolution, and favors migration at low death rates and proliferation at higher death rates. Mortality via demographic stochasticity favors proliferation at the expense of migration; and vice-versa for environmental stochasticity. All of these factors and their interactions contribute to the ecology of the tumor, tumor heterogeneity, trait evolution, and phenotypic variation. While diverse, these effects may be predictable and empirically accessible.
Insulation of gene expression by CTCF and cohesin-based subTAD (ubiquitous intra-TAD) loop structures in mouse liver
Authors: Matthews Bryan J. , Waxman David J. 
Published: February 2018

ABSTRACTCTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present a computational method to identify cohesin-and-CTCF binding sites that form intra-TAD DNA loops (subTADs). We show that predicted subTAD anchors are structurally indistinguishable from those of TADs regarding their binding partners, sequence conservation, and resistance to cohesin knockdown; further, the subTAD loops retain key functional features of TADs, including insulation of chromatin contacts, blockage of repressive histone mark spread, and ubiquity across tissues. We propose that subTADs form by the same loop extrusion mechanism as larger loops, and that their shorter length enables finer regulatory control over gene expression. 4C-seq analysis using an Alb promoter viewpoint illustrates the role of subTADs in restricting enhancer-promoter interactions. These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization, and demonstrate that distal enhancer insulation by subTADs is widespread.
Distinct impacts of air and root-zone temperatures on leaf and root features of cucumber seedlings: resource acquisition capacity, organ size and carbon-nitrogen balance
Authors: Wang Xiaozhuo , Gao Lihong , Tian Yongqiang 
Published: February 2018

ABSTRACTBoth low air (Tair) and root-zone (Troot) temperatures can inhibit resource (e.g. carbon and nutrients) acquisition by leaves and roots through various aspects, such as morphology, biomass allocation and assimilation/absorption capacity. However, it is still ambiguous whetherTairandTrootinfluence carbon (C) and nutrient acquisition via the same approach. To this end, in this study, cucumber (Cucumis sativusL.) seedlings were hydroponically grown under treatments arranged in complete factorial combination of two levels ofTair(26/18°C and 20/12°C, day/night) and two levels ofTroot(19°C and 13°C, constant). In general, bothTairandTrootaffected leaf and root sizes mainly by regulating their morphology rather than biomass investment. Under lowTairconditions (20/18°C), elevatedTroot(compare 19°C versus 13°C) did not influence C acquisition, but increased nitrogen (N) acquisition mainly due to an increase in relative root length, resulting in decreased C : N acquisition ratio. However, under lowTrootconditions (13°C), elevatedTair(compare 26/18°C versus 20/12°C) enhanced both C and N acquisition mainly because of an increase of both C assimilation in leaves and N absorption by roots, resulting in relatively constant C : N acquisition ratio. In addition, theTairandTrootinteraction was mainly observed in relative growth rate and root growth-related variables. Our results infer thatTairandTroothave distinct impacts on resource acquisition and carbon-nitrogen balance in plants.
Early Holocene morphological variation in hunter-gatherer hands and feet
Authors: Hoover Kara C. , Berbesque J. Colette 
Published: February 2018

AbstractBackgroundThe Windover mortuary pond dates to the Early Archaic period (6,800-5,200 years ago) and constitutes one of the earliest archaeological sites with intact and well-preserved human remains in North America. Unlike many prehistoric egalitarian hunter-gatherers, the Windover people may not have practiced a sex-based division of labor, rather they may have shared the load. We explore how mobility and subsistence, as reconstructed from archaeological data, influenced hand and foot bone morphology at Windover.MethodsWe took length and width measurements on four carpal bones, four tarsal bones, and load- bearing tarsal areas (calcaneus load arm, trochlea of the talus). We analyzed lateralization using side differences in raw length and width measurements. For other hypothesis testing, we used log transformed length-width ratios to mitigate the confounding effects of sexual dimorphism and trait size variation; we tested between-sex differences in weight-bearing (rear foot) and shock-absorbing (mid foot) tarsal bones and between-sex differences in carpal bones.ResultsWe identified no significant between-sex differences in rear and midfoot areas, suggesting similar biomechanical stresses. We identified no significant between-sex differences in carpal bones but the test was under-powered due to small sample sizes. Finally, despite widespread behavioral evidence on contemporary populations for human hand and foot lateralization, we found no evidence of either handedness or footedness.DiscussionThe lack evidence for footedness was expected due its minimal impact on walking gait but the lack of evidence for handedness was surprising given that ethnographic studies have shown strong handedness in hunter-gatherers during tool and goods manufacture. The reconstructed activity patterns suggested both sexes engaged in heavy load carrying and a shared division of labor. Our results support previous findings—both sexes had stronger weight-bearing bones. While male shock-absorbing bones exhibited a trend towards greater relative width (suggesting greater comparative biomechanical stress), this may simply some lingering hunting behavior with males walking greater distances at higher speeds than females. While there were no significant between-sex differences in carpal bones (supporting a shared work load model), females exhibited greater variation in index values, which may reflect a greater variety of and specialization in tasks compared to males. Because carpals and tarsals are so well- preserved at archaeological sites, we had surmised they might be useful proxies for activity in the absence of well-preserved long bones. Tarsals provide a stronger signal of past activity and may be useful in the absence or, or in addition to, preferred bones. Carpals, however, may not be useful as the effect size of biomechanical stress (in this study at least) is low and would require larger samples than may be possible at archaeological sites.
Genomic Signatures of Fine-Scale Local Adaptation in Atlantic Salmon Suggest Involvement of Sexual Maturation, Energy Homeostasis, Behaviour, and Immune Defence-Related Genes
Authors: Pritchard Victoria L. , Mäkinen Hannu , Vähä Juha-Pekka , Erkinaro Jaakko , Orell Panu , Primmer Craig R. 
Published: February 2018

ABSTRACTElucidating the genetic basis of adaptation to the local environment can improve our understanding of how the diversity of life has evolved. In this study we used a dense SNP array to identify candidate loci underlying fine-scale local adaptation within a large Atlantic salmon (Salmo salar) population. By combining outlier, gene-environment association, and haplotype homozygosity analyses, we identified multiple regions of the genome with strong evidence for diversifying selection. Several of these candidate regions had previously been identified in other studies, demonstrating that the same loci be adaptively important in Atlantic salmon at sub-drainage, regional and continental scales. Notably, we identified signals consistent with local selection around genes associated with variation in sexual maturation, energy homeostasis, behaviour, and immune defence. These included the large-effect age-at-matunty genevgll3, the known obesity genemc4r, and major histocompatibility complex II. Most strikingly, we confirmed a genomic region on Ssa09 that was extremely differentiated among subpopulations, and that is also a candidate for local selection over the global range of Atlantic salmon. This region co-localized with a genomic region strongly associated with spawning ecotype in sockeye salmon (Oncorhynchus nerka), with circumstantial evidence that the same gene (six6) may be the selective target in both cases. The phenotypic effect of this region in Atlantic salmon remains cryptic, although allelic variation is related to river flow volume and co-vanes with timing of the return spawning migration. Our results further inform management of Atlantic salmon and open multiple avenues for future research.
Microzooplankton distribution in the Amundsen Sea Polynya (Antarctica) during an extensivePhaeocystis antarcticabloom
Authors: Swalethorp Rasmus , Dinasquet Julie , Logares Ramiro , Bertilsson Stefan , Kjellerup Sanne , Krabberød Anders K. , Moksnes Per-Olav , Nielsen Torkel G. , Riemann Lasse 
Published: February 2018

AbstractIn Antarctica, summer is a time of extreme environmental shifts resulting in large coastal phytoplankton blooms fueling the food web. Despite the importance of the microbial loop in remineralizing biomass from primary production, studies of how microzooplankton communities respond to such blooms in the Southern Ocean are rather scarce. Microzooplankton (ciliates and dinoflagellates) communities were investigated combining microscopy and 18S rRNA sequencing analyses in the Amundsen Sea Polynya during an extensive summer bloom ofPhaeocystis antarctica. The succession of microzooplankton was further assessed during a 15-day induced bloom microcosm experiment. Dinoflagellates accounted for up to 58% the microzooplankton biomassin situwithGymnodiniumspp.,Protoperidiumspp. andGyrodiniumspp. constituting 87% of the dinoflagellate biomass.Strombilidiumspp.,Strombidiumspp. and tintinids represented 90% of the ciliates biomass.Gymnodinium,Gyrodiniumand tintinnids are known grazers ofPhaeocystis,suggesting that this prymnesiophyte selected for the key microzooplankton taxa. Availability of other potential prey, such as diatoms, heterotrophic nanoflagellates and bacteria, also correlated to changes in microzooplankton community structure. Overall, both heterotrophy and mixotrophy appeared to be key trophic strategies of the dominant microzooplankton observed, suggesting that they influence carbon flow in the microbial food web through top-down control on the phytoplankton community.
Long-term live imaging of theDrosophilaadult midgut reveals real-time dynamics of cell division, differentiation, and loss
Authors: Martin Judy , Sanders Erin Nicole , Moreno-Roman Paola , Balachandra Shruthi , Du XinXin , Jaramillo Koyama Leslie Ann , O’Brien Lucy Erin 
Published: February 2018

ABSTRACTOrgan renewal is governed by the dynamics of cell division, differentiation, and loss. To study these dynamics in real time, here we present a platform for extended live imaging of the adultDrosophilamidgut, a premier genetic model for stem cell-based organs. A window cut into a living animal allows the midgut to be imaged while intact and physiologically functioning. This approach prolongs imaging sessions to 12-16 hours and yields movies that document cell and tissue dynamics at vivid spatiotemporal resolution. Applying a pipeline for movie processing and analysis, we uncover new, intriguing cell behaviors: that mitotic stem cells dynamically re-orient, that daughter cells delay fate-determining Notch activation for many hours after birth, and that enterocytes extrude via constriction of a pulsatile cadherin ring. By enabling real-time study of cellular phenomena that were previously inaccessible, our platform opens a new realm for dynamic understanding of midgut organ renewal.
Delegating sex: differential gene expression in stolonizing syllids uncovers the hormonal control of reproduction in Annelida
Authors: Álvarez-Campos Patricia , Kenny Nathan J. , Verdes Aida , Fernández Rosa , Novo Marta , Giribet Gonzalo , Riesgo Ana 
Published: February 2018

AbstractStolonization in syllid annelids is a unique mode of reproduction among animals. During the breeding season, a structure resembling the adult but containing only gametes, called stolon, is formed at the posterior end of the animal. When the stolons mature, they detach from the adult and the gametes are released into the water column. The process is synchronized within each species, and it has been reported to be under environmental and endogenous control, probably via endocrine regulation. To further understand the reproduction in syllids and to elucidate the molecular toolkit underlying stolonization, we generated Illumina RNA-seq data from different tissues of reproductive and non-reproductive individuals ofSyllis magdalena, and characterized gene expression during the stolonization process. Several genes involved in gametogenesis (ovochymase,vitellogenin,testis-specific serine/threonine-kinase), immune response (complement receptor 2), neuronal development (tyrosine-protein kinase Src42A), cell proliferation (alpha-1D adrenergic receptor), and steroid metabolism (hydroxysteroid dehydrogenase2) were found differentially expressed in the different tissues and conditions analyzed. In addition, our findings suggest that several neurohormones, such as methyl farnesoate, dopamine and serotonin, might trigger the stolon formation, the correct maturation of gametes and the detachment of stolons when gametogenesis is complete. The process seems to be under circadian control, as indicated by the expression patterns ofr-opsins. Overall, our results shed light into the genes that orchestrate the onset of gamete formation, and improve our understanding of how some hormones, previously reported to be involved in reproduction and metamorphosis processes in other invertebrates, seem to also regulate reproduction via stolonization.
Worldwide cross-ecosystem carbon subsidies and their contribution to ecosystem functioning
Authors: Gounand Isabelle , Little Chelsea J. , Harvey Eric , Altermatt Florian 
Published: February 2018

AbstractEcosystems are widely inter-connected by spatial flows of resources1,2, yet primarily studied in a local context. Meta-ecosystem models suggest that cross-ecosystem subsidies can play an essential role in ecosystem functioning, notably by controlling local availability of resources for biological communities3–6. The general contribution of these resource connections to ecosystem functioning, however, remains unclear in natural systems, due to the heterogeneity and dispersion of data across the ecological literature. Here we provide the first quantitative synthesis on spatial flows of carbon connecting ecosystems worldwide. These cross-ecosystem subsidies range over eight orders of magnitude, between 10−3 and 105 gC m−2 yr−1, and are highly diverse in their provenance. We found that spatial carbon flows and local carbon fluxes are of the same order of magnitudes in freshwater and benthic ecosystems, suggesting an underlying dependency of these systems on resources provided by connected terrestrial and pelagic ecosystems respectively. By contrast, in terrestrial systems, cross-ecosystem subsidies were two to three orders of magnitude lower than local production (grasslands and forests), indicating a weaker quantitative influence on functioning. Those subsidies may still be qualitatively important, however, as some have high nutrient content7,8. We also find important gaps in carbon flow quantification, notably of cross-ecosystem subsidies driven by animal movements, which likely leads to general underestimations of the magnitude and direction of cross-ecosystem linkages9. Overall, we demonstrate strong ecosystem couplings, suggesting that ecosystems can be vulnerable to alterations of these flows and pointing to an urgent need to re-think ecosystem functioning in a spatial perspective.
Epigenetic aging of human hematopoietic cells is not accelerated upon transplantation into mice
Authors: Frobel Joana , Rahmig Susann , Franzen Julia , Waskow Claudia , Wagner Wolfgang 
Published: February 2018

AbstractTransplantation of human hematopoietic stem cells into immunodeficient mice provides a powerful in vivo model system to gain functional insights into hematopoietic differentiation. So far, it remains unclear if epigenetic changes of normal human hematopoiesis are recapitulated upon engraftment into such “humanized mice”. Mice have a much shorter life expectancy than men, and therefore we hypothesized that the xenogeneic environment might greatly accelerate the epigenetic clock. We demonstrate that genome-wide DNA methylation patterns of normal human hematopoietic development are indeed recapitulated upon engraftment in mice – particularly those of normal early B cell progenitor cells. Furthermore, we tested three epigenetic aging signatures and none of them indicated that the murine environment accelerated age-associated DNA methylation changes. These results demonstrate that the murine transplantation model overall recapitulates epigenetic changes of human hematopoietic development, whereas epigenetic aging seems to occur cell intrinsically.
babette: BEAUti 2, BEAST2 and Tracer for R
Authors: Bilderbeek Richèl J.C. , Etienne Rampal S. 
Published: February 2018

SummaryIn the field of phylogenetics, BEAST2 is one of the most widely used software tools. It comes with the graphical user interfaces BEAUti 2, DensiTree and Tracer, to create BEAST2 configuration files and to interpret BEAST2’s output files. However, when many different alignments or model setups are required, a workflow of graphical user interfaces is cumbersome.Here, we present a free, libre and open-source package,babette: ‘BEAUti 2, BEAST2 and Tracer for R’, for the R programming language.babettecreates BEAST2 input files, runs BEAST2 and parses its results, all from an R function call.We describebabette’s usage and the novel functionality it provides compared to the original tools and we give some examples.Asbabetteis designed to be of high quality and extendable, we conclude by describing the further development of the package.
A prostaglandin alpha F2 analog protects from statin-induced myopathic changes in primary human muscle cells
Authors: Grunwald Stefanie Anke , Popp Oliver , Haafke Stefanie , Jedraszczak Nicole , Grieben Ulrike , Saar Kathrin , Patone Giannino , Kress Wolfram , Steinhagen-Thiessen Elisabeth , Dittmar Gunnar , Spuler Simone 
Published: February 2018

AbstractStatin-related muscle side effects are a constant healthcare problem since patient compliance is dependent on side effects. Statins reduce plasma cholesterol levels and can prevent secondary cardiovascular disease. Although statin-induced muscle damage has been studied, preventive or curative therapies are yet to be reported.We exposed primary human muscle cell populations (n=25) to a lipophilic (simvastatin) and a hydrophilic (rosuvastatin) statin and analyzed their expressome. Data and pathway analyses included GOrilla, Reactome and DAVID. We measured mevalonate intracellularly and analyzed eicosanoid profiles secreted by human muscle cells. Functional assays included proliferation and differentiation quantification.More than 1800 transcripts and 900 proteins were differentially expressed after exposure to statins. Simvastatin had a stronger effect on the expressome than rosuvastatin, but both statins influenced cholesterol biosynthesis, fatty acid metabolism, eicosanoid synthesis, proliferation, and differentiation of human muscle cells. Cultured human muscle cells secreted ω-3 and ω-6 derived eicosanoids and prostaglandins. The ω-6 derived metabolites were found at higher levels secreted from simvastatin-treated primary human muscle cells. Eicosanoids rescued muscle cell differentiation.Our data suggest a new aspect on the role of skeletal muscle in cholesterol metabolism. For clinical practice, the addition of omega-n fatty acids could be suitable to prevent or treat statin-myopathy.