bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of correlation between number of neurons and behavioral performance in Swiss mice
Authors: Kleber Neves , Duarte Guercio Gerson , Yuri Anjos-Travassos , Stella Costa , Ananda Perozzo , Karine Montezuma , Suzana Herculano-Houzel , Rogério Panizzutti 
Published: September 2018

AbstractNeuronal number varies by several orders of magnitude across species, and has been proposed to predict cognitive capability across species. Remarkably, numbers of neurons vary across individual mice by a factor of 2 or more. We directly addressed the question of whether there is a relationship between performance in behavioral tests and the number of neurons in functionally relevant structures in the mouse brain. Naïve Swiss mice went through a battery of behavioral tasks designed to measure cognitive, motor and olfactory skills. We estimated the number of neurons in different brain regions (cerebral cortex, hippocampus, olfactory bulb, cerebellum and remaining areas) and crossed the two datasets to test the a priori hypothesis of correlation between cognitive abilities and numbers of neurons. As previous evidence indicates that environmental enrichment may increase neurogenesis and improve neuronal survival, we added a control group that did not undergo cognitive testing to rule out the possibility that our test battery could alter the neuronal number. We found that behavioral testing did not change numbers of neurons in the cerebral cortex and in the hippocampus. Surprisingly, performance in the behavioral tasks did not correlate strongly with number of neurons in any of the brain regions studied. Our results show that whereas neuronal number is a good predictor of cognitive skills across species, it is not a predictor of cognitive, sensory or motor ability across individuals within a species, which suggests that other factors are more relevant for explaining cognitive differences between individuals of the same species.
Geochemical and metagenomic characterization of Jinata Onsen, a Proterozoic-analog hot spring, reveals novel microbial diversity including iron-tolerant phototrophs and thermophilic lithotrophs
Authors: Ward Lewis M. , Idei Airi , Nakagawa Mayuko , Ueno Yuichiro , Fischer Woodward W. , McGlynn Shawn E. 
Published: September 2018

AbstractHydrothermal systems, including terrestrial hot springs, contain diverse geochemical conditions that vary over short spatial scales due to progressive interaction between the reducing hydrothermal fluids, the oxygenated atmosphere, and in some cases seawater. At Jinata Onsen, on Shikinejima Island, Japan, an intertidal, anoxic, iron-rich hot spring mixes with the oxygenated atmosphere and seawater over short spatial scales, creating a diversity of chemical potentials and redox pairs over a distance ~10 m. We characterized the geochemical conditions along the outflow of Jinata Onsen as well as the microbial communities present in biofilms, mats, and mineral crusts along its traverse via 16S rDNA amplicon and genome-resolved shotgun metagenomic sequencing. The microbial community changed significantly downstream as temperatures and dissolved iron concentrations decreased and dissolved oxygen increased. Near the spring source, biomass is limited relative to downstream, and primary productivity may be fueled by oxidation of ferrous iron and molecular hydrogen by members of the Zetaproteobacteria and Aquificae. Downstream, the microbial community is dominated by oxygenic Cyanobacteria. Cyanobacteria are abundant and active even at ferrous iron concentrations of ~150 μM, which challenges the idea that iron toxicity limited cyanobacterial expansion in Precambrian oceans. Several novel lineages of Bacteria are also present at Jinata Onsen, including previously uncharacterized members of the Chloroflexi and Caldithrichaeota phyla, positioning Jinata Onsen as a valuable site for future characterization of these clades.ImportanceHigh temperatures and reducing conditions allow hot springs to support microbial communities that are very different from those found elsewhere on the surface of the Earth today; in some ways, these environments and the communities they support can be similar to environments that existed on the early Earth and that may exist on other planets. Here, we describe a novel hot spring system where hot, iron-rich but oxygen-poor water flows into the ocean, supporting a range of unique microbial communities. Metagenomic sequencing recovered many novel microbial lineages, including deep-branching and uniquely thermotolerant members of known groups. Comparison of the biological communities in the upstream part of the hot spring, potentially supported by biological iron and hydrogen oxidizing metabolisms, to downstream microbial mats, supported by oxygenic photosynthesis, provides insight into the potential productivity of life during Proterozoic time and on other planets where oxygenic photosynthesis is not possible.
DNA co-methylation networks outline the structure and remodeling dynamics of colorectal cancer epigenome
Authors: Mallona Izaskun , Aussó Susanna , Díez-Villanueva Anna , Moreno Víctor , Peinado Miguel A. 
Published: September 2018

AbstractEpigenomic plasticity is interconnected with chromatin structure and gene regulation. In tumor progression, orchestrated remodeling of genome organization accompanies the acquisition of malignant properties. DNA methylation, a key epigenetic mark extensively altered in cancer, is also linked to genome architecture and function. Based on this association, we postulate that the dissection of long-range co-methylation structure unveils cancer cell’s genome architecture remodeling.We applied network-modeling of DNA methylation co-variation in two colon cancer cohorts and found abundant and consistent transchromosomal structures in both normal and tumor tissue. Normal-tumor comparison indicated substantial remodeling of the epigenome covariation and revealed novel genomic compartments with a unique signature of DNA methylation rank inversion.
Determination of sex of sacrum in adult Macaca mulatta1
Authors: Wang Yan-Mei , Han Xiao-Fan , Zhao Xiao-Jin 
Published: September 2018

[Abstract]BackgroundSacrum being a part of pelvis is an important bone for identification of sex in both living primates and fossil ones.AimAim of this work was to examine the sex differences of sacral parameters in rhesus macaques and to compare with those of the other primates.Materials and MethodsFifty-six adult scara of macaques (17 males and 39 females) have been investigated. Measurement of various parameters was done using sliding vernier calliper; and statistical analysis was done using SPSS 23.0 package.ResultsThe present study showed that the cranial breadth of the sacrum, the sacral length, transverse diameter and sagittal diameter of the cranial articular surface, and two indices of relative sacral breadth were highly significant for sex determination in Macaca mulatta. Comparison of the present data with other studies suggest that sex determination of sacrum can be very different in various types of primates.ConclusionThe results suggest that these measures may be functionally integrated in response to locomotion, obstetric adequacy and cephalopelvic proportions in primates. Sacral index is more reliable and should be applied for sex determination of sacrum in various anatomical and anthropological investigations.
Enhancedin vivo-imaging in fish by optimized anaesthesia, fluorescent protein selection and removal of pigmentation
Authors: Lischik Colin Q. , Adelmann Leonie , Wittbrodt Joachim 
Published: September 2018

AbstractFish are ideally suited forin vivo-imaging due to their transparency at early stages combined with a large genetic toolbox. Key challenges to further advance imaging are fluorophore selection, immobilization of the specimen and approaches to eliminate pigmentation.We addressed all three and identified the fluorophores and anaesthesia of choice by high throughput time-lapse imaging. Our results indicate that eGFP and mCherry are the best conservative choices forin vivo-fluorescence experiments, when availability of well-established antibodies and nanobodies matters. Still, mVenusNB and mGFPmut2 delivered highest absolute fluorescence intensitiesin vivo. Immobilization is of key importance during extendedin vivoimaging. Here, traditional approaches are outperformed by mRNA injection of α-Bungarotoxin which allows a complete and reversible, transient immobilization. In combination with fully transparent juvenile and adult fish established by the targeted inactivation of both,oca2andpnp4avia CRISPR/Cas9-mediated gene editing in medaka we could dramatically improve the state-of-the art imaging conditions in post-embryonic fish, now enabling light-sheet microscopy of the growing retina, brain, gills and inner organs in the absence of side effects caused by anaesthetic drugs or pigmentation.
On the optimal design of metabolic RNA labeling experiments
Authors: Uvarovskii Alexey , Naarmann-de Vries Isabel S. , Dieterich Christoph 
Published: September 2018

SummaryMassively parallel RNA sequencing (RNA-seq) in combination with metabolic labeling has become thede factostandard approach to study alterations in RNA transcription, processing or decay. Regardless of advances in the experimental protocols and techniques, every experimentalist needs to specify the key aspects of experimental design: For example, which protocol should be used (biochemical separation vs. nucleotide conversion) and what is the optimal labeling time? In this work, we provide approximate answers to these questions using asymptotic theory of optimal design. Specifically, we derive the optimal labeling time for any given degradation rate and show that sub-optimal time points yield better rate estimates if they precede the optimal time point. Subsequently, we show that an increase in sample numbers should be preferred over an increase in sequencing depth. Lastly, we provide some guidance on use cases when laborious biochemical separation outcompetes recent nucleotide conversion based methods (such as SLAMseq).
Origin and evolution of papillomavirus (onco)genes and genomes
Authors: Willemsen Anouk , Bravo Ignacio G. 
Published: September 2018

ABSTRACTPapillomaviruses (PVs) are ancient viruses infecting vertebrates, from fish to mammals. Although the genomes of PVs are small and show conserved synteny, PVs display large genotypic diversity and ample variation in the phenotypic presentation of the infection. Most PVs genomes contain two small early genes E6 and E7. In a bunch of closely related human PVs, the E6 and E7 proteins provide the viruses with oncogenic potential.The recent discoveries of PVs without E6 and E7 in different fish species place a new root on the PV tree, and suggest that the ancestral PV consisted of the minimal PV backbone E1-E2-L2-L1.Bayesian phylogenetic analyses date the most recent common ancestor of the PV backbone to 424 million years ago (Ma). Common ancestry tests on extant E6 and E7 genes indicate that they share respectively a common ancestor dating back to at least 184 Ma. In AlphaPVs infecting primates, the appearance of the E5 oncogene 53-58 Ma concurred with i) a significant increase in substitution rate, ii) a basal radiation, and iii) key gain of functions in E6 and E7. This series of events was instrumental to build the extant phenotype of oncogenic human PVs.Our results assemble the current knowledge on PV diversity and present an ancient evolutionary timeline punctuated by evolutionary innovations in the history of this successful viral family.
Social relationships, social isolation, and the human gut microbiota
Authors: Dill-McFarland Kimberly A. , Tang Zheng-Zheng , Kemis Julia H. , Kerby Robert L. , Chen Guanhua , Palloni Alberto , Sorenson Thomas , Rey Federico E. , Herd Pamela 
Published: September 2018

ABSTRACTSocial relationships shape human health and mortality via behavioral, psychosocial, and physiological mechanisms, including inflammatory and immune responses. Though not tested in human studies, recent primate studies indicate that the gut microbiome may also be a biological mechanism linking relationships to health. Integrating microbiota data into the 60-year-old Wisconsin Longitudinal Study, we found that socialness with family and friends is associated with differences in the human fecal microbiota. Analysis of spouse (N = 94) and sibling pairs (N = 83) further revealed that spouses have more similar microbiota and more bacterial taxa in common than siblings, with no observed differences between sibling and unrelated pairs. These differences held even after accounting for dietary factors. The differences between unrelated individuals and married couples was driven entirely by couples who reported close relationships; there were no differences in similarity between couples reporting somewhat close relationships and unrelated individuals. Moreover, the microbiota of married individuals, compared to those living alone, has greater diversity and richness, with the greatest diversity among couples reporting close relationships, which is notable given decades of research documenting the health benefits of marriage. These results suggest that human interactions, especially sustained, close marital relationships, influence the gut microbiota.
WNT vampirization by glioblastoma leads to tumor growth and neurodegeneration
Authors: Portela Marta , Venkataramani Varun , Fahey-Lozano Natasha , Seco Esther , Losada-Perez Maria , Winkler Frank , Casas-Tintó Sergio 
Published: September 2018

SummaryGlioblastoma (GB) is the most lethal brain tumor due to its high proliferation, aggressiveness, infiltration capacity and resilience to current treatments. Activation of the Wingless-related-integration-site (WNT) pathway is associated with a bad prognosis. UsingDrosophilaand primary xenograft models of human GB, we describe a mechanism that leads to the activation of WNT signaling [Wingless (Wg) inDrosophila] in tumor cells. GB cells display a network of tumor microtubes (TMs) which enwraps neurons, accumulates Wg receptor Frizzled1 (Fz1), and, thereby, actively depletes Wg from the neurons. Consequently, GB cells proliferate due to β-catenin activation, and neurons degenerate due to Wg signaling extinction. This novel view explains both neuron-dependent tumor progression, and also the neural decay associated with GB.
Relief from nitrogen starvation entails quick unexpected down-regulation of glycolytic/lipid metabolism genes in enologicalSaccharomyces cerevisiae
Authors: Catherine Tesnière , Chloé Bessière , Martine Pradal , Isabelle Sanchez , Bruno Blondin , Frédéric Bigey 
Published: September 2018

AbstractNitrogen composition of the grape must has an impact on yeast growth and fermentation kinetics as well as on the organoleptic properties of the final product. In some technological processes, such as white wine/rosé winemaking, the yeast-assimilable nitrogen content is sometimes insufficient to cover yeast requirements, which can lead to slow or sluggish fermentations. Growth is nevertheless quickly restored upon relief from nutrient starvation, e.g. through the addition of ammonium nitrogen, allowing fermentation completion. The aim of this study was to determine how nitrogen repletion affected the transcriptional response of aSaccharomyces cerevisiaewine yeast strain, in particular within the first hour after nitrogen addition. We found almost 4800 genes induced or repressed, sometimes within minutes after nutrient changes. Some of these responses to nitrogen depended on the TOR pathway, which controls positively ribosomal protein genes, amino acid and purine biosynthesis or amino acid permease genes and negatively stress-response genes, and genes related to the retrograde response (RTG) specific to the tricarboxylic acid (TCA) cycle and nitrogen catabolite repression (NCR). Some unexpected transcriptional responses concerned all the glycolytic genes, carbohydrate metabolism and TCA cycle-related genes that were down-regulated, as well as genes from the lipid metabolism.
Invasive aliens threatened with native extinction: examining best practice for species translocations under climate change
Authors: Egan Paul A. , Bourke David , Thuiller Wilfried , Baudraz Maude E.A. , Georges Damien , Renaud Julien , Stout Jane C. 
Published: September 2018

AbstractAimTranslocation remains a controversial strategy in species conservation. Here, we utilise the unusual scenario of invasive alien species (IAS) threatened with extinction in their native range to address key challenges in deciding ‘whether’, ‘where’, and ‘when’ to implement translocation, and how best to approach conservation under seemingly contradictory circumstances.LocationIberian Peninsula, NW EuropeMethodsRhododendron ponticumssp.baeticumwas selected as a model IAS for case study analysis. We used species distribution models (SDMs) coupled with dynamic simulations of migration to assess: 1. the extinction risk posed to this species in its native Iberian range under climate change; 2. whether SDMs calibrated on the native range (replicating typical translocation planning) could predict invasive capacity in NW Europe; and 3. the extent to which recommended biogeographical constrains on translocations may limit available options. Insights gained on the above were used to build and test a generic decision framework for translocation, based on robust identification of microrefugia.ResultsOur findings suggest a high likelihood of climate-induced extinction forR.p. ssp.baeticumin its native range. Notably, SDMs completely failed to predict invasive capacity in NW Europe. However, application of our framework was successful in identifying sites more proximate to the native range – albeit outside this species’ current biogeographic region – potentially suited to translocation.Main conclusionsThe framework here developed can be used to guide translocation of climate-endangered species in a spatially and temporally precise manner. However, we caution that use of SDMs can possess short-comings in failing to capture a full picture of sites suited to translation, and in risk assessment of the capacity of translocated taxa to form invasive species. Strict biogeographic constraints to the selection of translocation sites can evidently help to safeguard against invasions, but may also severely hinder the options available to avert climate-induced extinctions.
Residual Structure of Unfolded Ubiquitin as Revealed by Hydrogen/Deuterium-Exchange 2D NMR
Authors: Chandak M. S. , Nakamura T. , Yagi-Utsumi M. , Yamaguchi T. , Kato K. , Kuwajima K. 
Published: September 2018

AbstractThe characterization of residual structures persistent in unfolded proteins in concentrated denaturant solution is currently an important issue in studies of protein folding, because the residual structure present, if any, in the unfolded state may form a folding initiation site and guide the subsequent folding reactions. Here, we thus studied the hydrogen/deuterium (H/D)-exchange behavior of unfolded ubiquitin in 6.0 M guanidinium chloride at pH 2.6 and 20°C. We employed a dimethylsulfoxide (DMSO)-quenched H/D-exchange NMR technique with the use of spin desalting columns, which allowed us to make a quick medium exchange from 6.0 M guanidinium chloride to a quenching DMSO solution. The technique is particularly effective for studies of the H/D-exchange kinetics of unfolded proteins in concentrated denaturant. By the backbone resonance assignment of the hetero-nuclear single quantum coherence spectrum of 15N-labeled ubiquitin in the DMSO solution, we successfully investigated the H/D-exchange kinetics of 27 identified peptide amide groups in the ubiquitin sequence. Although most of these amide groups were not protected, the four amide groups of Ile3, Val5, Ile13 and Leu73 were weakly but significantly protected with a protection factor of 2.5–3.0, indicating that there were residual structures in unfolded ubiquitin and that these amide groups were 60–67% hydrogen-bonded by the residual structures. We show that the first native β-hairpin, composed of residues 2–16 in the native ubiquitin structure, is partially structured even in 6.0 M guanidinium chloride and that the amide group of Leu73 is protected by a nonnative hydrogen-bonding interaction. From comparison with the previous folding studies of ubiquitin, it is concluded that the residual native β-hairpin in unfolded ubiquitin forms a folding initiation site and guides the subsequent folding reactions of the protein.
Alternative splicing of bicistronic MOCS1 defines a novel mitochondrial protein maturation mechanism
Authors: Mayr Simon Julius , Röper Juliane , Schwarz Geunter 
Published: September 2018

AbstractMolybdenum cofactor biosynthesis is a conserved multistep pathway. The first step, the conversion of GTP to cyclic pyranopterin monophosphate (cPMP), requires bicsistronic MOCS1. Alternative splicing of MOCS1 in exons 1 and 9 produces four different N-terminal and three different C-terminal products (type I-III). Type I splicing results in bicistronic transcripts with two open reading frames, of which only the first, MOCS1A, is translated, whereas type II/III splicing produces two-domain MOCS1AB proteins. Here, we report and characterize the mitochondrial translocation of alternatively spliced MOCS1 proteins. While MOCS1A requires exon 1a for mitochondrial translocation, MOCS1AB variants target to mitochondria via an internal motif overriding the N-terminal targeting signal. Within mitochondria, MOCS1AB undergoes proteolytic cleavage resulting in mitochondrial matrix localization of the MOCS1B domain. In conclusion we found that MOCS1 produces two functional proteins, MOCS1A and MOCS1B, which follow different translocation routes before mitochondrial matrix import, where both proteins collectively catalyze cPMP biosynthesis. MOCS1 protein maturation provides a novel mechanism of alternative splicing ensuring the coordinated targeting of two functionally related mitochondrial proteins encoded by a single gene.
A heterochromatic histone methyltransferase lowers nucleosome occupancy at euchromatic promoters
Authors: Chen H.M. , Sackton T.B. , Mutlu B. , Wang J. , Keppler-Ross S. , Levine E. , Liu T. , Mango S.E. 
Published: September 2018

AbstractH3K9me3 (histone H3 modified with tri-methylation at lysine 9) is a hallmark of transcriptional silencing and heterochromatin. However, its global effects on the genome, including euchromatin, are less well understood. Here we develop Formaldehyde-Assisted Identification of Regulatory Elements (FAIRE) forC. elegansto examine the chromatin configuration of mutants that lack virtually all H3K9me3, while leaving H3K9me1 and H3K9me2 intact. We find that nucleosomes are mildly disrupted, and levels of H3K9me2 and H3K27me3 rise in mutant embryos. In addition to these expected changes, the most dramatic change occurs in euchromatin: many regions encompassing transcription start sites (TSSs) gain an average of two nucleosomes in mutants. The affected regions normally lack H3K9me3, revealing a locus non-autonomous role for H3K9me3. Affected TSSs are associated with genes that are active in epithelia and muscles, and implicated in development, locomotion, morphogenesis and transcription. Mutant embryos develop normally under ideal laboratory conditions but die when challenged, with defects in morphogenesis and development. Our findings reveal that H3K9me3 protects transcription start sites within euchromatin from nucleosome deposition. These results may be relevant to mammals, where diseases that disrupt the nuclear lamina and heterochromatin can alter epithelial and muscle gene expression.