bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic identification of human SNPs affecting regulatory element activity
Authors: van Arensbergen Joris , Pagie Ludo , FitzPatrick Vincent , de Haas Marcel , Baltissen Marijke , Comoglio Federico , van der Weide Robin , Teunissen Hans , Võsa Urmo , Franke Lude , de Wit Elzo , Vermeulen Michiel , Bussemaker Harmen , van Steensel Bas 
Published: November 2018

AbstractMost of the millions of single-nucleotide polymorphisms (SNPs) in the human genome are non-coding, and many overlap with putative regulatory elements. Genome-wide association studies have linked many of these SNPs to human traits or to gene expression levels, but rarely with sufficient resolution to identify the causal SNPs. Functional screens based on reporter assays have previously been of insufficient throughput to test the vast space of SNPs for possible effects on enhancer and promoter activity. Here, we have leveraged the throughput of the SuRE reporter technology to survey a total of 5.9 million SNPs, including 57% of the known common SNPs. We identified more than 30 thousand SNPs that alter the activity of putative regulatory elements, often in a cell-type specific manner. These data indicate that a large proportion of human non-coding SNPs may affect gene regulation. Integration of these SuRE data with genome-wide association studies may help pinpoint SNPs that underlie human traits.
Co-culture and biogeography of Prochlorococcus and SAR11
Authors: Becker Jamie W. , Hogle Shane L. , Rosendo Kali , Chisholm Sallie W. 
Published: November 2018

AbstractProchlorococcus and SAR11 are among the smallest and most abundant organisms on Earth. With a combined global population of about 2.7 x 1028 cells, they numerically dominate bacterioplankton communities in oligotrophic ocean gyres and yet they have never been grown together in vitro. Here we describe co-cultures of Prochlorococcus and SAR11 isolates representing both high- and low-light adapted clades. We examined: (1) the influence of Prochlorococcus on the growth of SAR11 and vice-versa, (2) whether Prochlorococcus can meet specific nutrient requirements of SAR11, and (3) how co-culture dynamics vary when Prochlorococcus is grown with SAR11 compared with sympatric copiotrophic bacteria. SAR11 grew as much as 70% faster in the presence of Prochlorococcus, while the growth of the latter was unaffected. When Prochlorococcus populations entered stationary phase, SAR11 abundances decreased dramatically. In parallel experiments with copiotrophic bacteria however, the heterotrophic partner increased in abundance as Prochlorococcus densities leveled off. The presence of Prochlorococcus was able to meet SAR11’s central requirement for organic carbon, but not reduced sulfur. Prochlorococcus strain MIT9313, but not MED4, could meet the unique glycine requirement of SAR11, likely due to production and release of glycine betaine by MIT9313. Evidence suggests that Prochlorococcus MIT9313 may also compete with SAR11 for the uptake of 3-dimethylsulfoniopropionate (DMSP). To place our results in context, we assessed the relative contribution of Prochlorococcus and SAR11 genome equivalents to those of identifiable bacteria and archaea in over 800 marine metagenomes. At many locations, more than half of the identifiable genome equivalents in the euphotic zone belonged to Prochlorococcus and SAR11 – highlighting the biogeochemical potential of these two groups.
Convergent recruitment of life cycle regulators to direct sporophyte development in two eukaryotic supergroups
Authors: Arun Alok , Coelho Susana M. , Peters Akira F. , Bourdareau Simon , Peres Laurent , Scornet Delphine , Strittmatter Martina , Lipinska Agnieszka P. , Yao Haiqin , Godfroy Olivier , Montecinos Gabriel J. , Avia Komlan , Macaisne Nicolas , Troadec Christelle , Bendahmane Abdelhafid , Cock J. Mark 
Published: November 2018

AbstractThree amino acid loop extension homeodomain transcription factors (TALE HD TFs) act as life cycle regulators in green algae and land plants. In mosses these regulators are required for the deployment of the sporophyte developmental program. We demonstrate that mutations in either of two TALE HD TF genes,OUROBOROSorSAMSARA, in the brown algaEctocarpusresult in conversion of the sporophyte generation into a gametophyte. The OUROBOROS and SAMSARA proteins heterodimerise in a similar manner to TALE HD TF life cycle regulators in the green lineage. These observations demonstrate that TALE-HD-TF-based life cycle regulation systems have an extremely ancient origin, and that these systems have been independently recruited to regulate sporophyte developmental programs in at least two different complex multicellular eukaryotic supergroups, Archaeplastida and Chromalveolata.
Modulation ofrpoSfitness by loss ofcpdAactivity during stationary-phase inEscherichia coli
Authors: Chib Savita , Seshasayee Aswin SaiNarain 
Published: November 2018

AbstractExperimental evolution ofEscherichia coliin one month long stationary-phase in lysogeny broth batch cultures repeatedly selected mutations in the genes for the stationary-phase sigma factor RpoS and the cAMP phosphodiesterase CpdA. The founder strain carried a previously identified allele ofrpoS, referred to asrpoS819,a partially functional variant that confers growth advantage in stationary-phase (GASP). The 46 base duplication at the 3’ end ofrpoS819produces a longer protein present at very low levels compared to wild type RpoS. A newrpoSvariantrpoS92, carrying a re-duplication of the original duplication inrpoS819,arose during the first week of our evolution experiment. InrpoS92, an in-frame stop codon truncated RpoS819 creating a shorter RpoS92 whose levels are restored to that of wild type RpoS. Transcription profiling ofrpoS92indicated a shift in gene-expression to that of wild-typerpoS, reversing some of the expression trends ofrpoS819. Δ3cpdA, carrying an in-frame three base deletion, had arisen late in our evolution experiment. It is a loss of function mutation, which elevates cAMP levels. Using mixed culture competition experiments, we demonstrate thatrpoS92confers GASP, whereas Δ3cpdAconfers relatively modest GASP in comparison to the ancestralrpoS819. Δ3cpdAmediates epistatic repression ofrpoS92GASP. The original survivor carrying both rpoS92 and Δ3cpdAbesides other mutations displays robust GASP, highlighting the role of these additional mutations in reversing the epistatic interaction between Δ3cpdAandrpoS92.In 10- and 20-day old spent media, there is a reduction in the competitive fitness ofrpoS92,which is arrested by Δ3cpdA.Thus the activity of RpoS fluctuates via genetic mutations in deep stationary phase, and additional mutations in CpdA helps modulate the competitive fitness of RpoS variants.
Automagic: Standardized Preprocessing of Big EEG Data
Authors: Pedroni Andreas , Bahreini Amirreza , Langer Nicolas 
Published: November 2018

AbstractElectroencephalography (EEG) recordings have been rarely included in large-scale studies. This is arguably not due to a lack of information that lies in EEG recordings but mainly on account of methodological issues. In many cases, particularly in clinical, pediatric and aging populations, the EEG has a high degree of artifact contamination and the quality of EEG recordings often substantially differs between subjects. Although there exists a variety of standardized preprocessing methods to clean EEG from artifacts, currently there is no method to objectively quantify the quality of preprocessed EEG. This makes the commonly accepted procedure of excluding subjects from analyses due to exceeding contamination of artifacts highly subjective. As a consequence, P-hacking is fostered, the replicability of results is decreased, and it is difficult to pool data from different study sites. In addition, in large-scale studies, data are collected over years or even decades, requiring software that controls and manages the preprocessing of ongoing and dynamically growing studies. To address these challenges, we developed Automagic, an open-source MATLAB toolbox that acts as a wrapper to run currently available preprocessing methods and offers objective standardized quality assessment for growing studies. The software is compatible with the Brain Imaging Data Structure (BIDS) standard and hence facilitates data sharing. In the present paper we outline the functionality of Automagic and examine the effect of applying combinations of methods on a sample of resting EEG data. This examination suggests that applying a pipeline of algorithms to detect artifactual channels in combination with Multiple Artifact Rejection Algorithm (MARA), an independent component analysis (ICA)-based artifact correction method, is sufficient to reduce a large extent of artifacts.
NKX2.1 is critical for melanocortin neuron identity, hypothalamicPomcexpression and body weight
Authors: Orquera Daniela P. , Tavella M. Belén , de Souza Flavio S. J. , Nasif Sofía , Low Malcolm J. , Rubinstein Marcelo 
Published: November 2018

AbstractFood intake is tightly regulated by a group of neurons present in the mediobasal hypothalamus which activate satiety by releasingPomc-encoded melanocortins. Although the relevance of hypothalamic POMC neurons in the regulation of energy balance and body weight is well appreciated, little is known about the transcription factors that establish their cellular fate, terminal differentiation and phenotypic maintenance. Here, we report that the transcription factor Nkx2.1 activates hypothalamicPomcexpression from early development to adulthood by binding to conserved canonical NKX motifs present in the neuronalPomcenhancers nPE1 and nPE2. Transgenic and mutant mouse studies showed that the NKX motifs present in nPE1 and nPE2 are essential for their transcriptional enhancer activity. Early inactivation ofNkx2.1in the ventral hypothalamus prevented the onset ofPomcexpression and selectiveNkx2.1ablation from POMC neurons impairedPomcexpression and increased body weight and adiposity. These results demonstrate that NKX2.1 is critical in the early establishment of arcuate melanocortin neurons and the regulation ofPomcexpression and body weight in adulthood.
Opto-activation of cortical somatostatin interneurons alleviates parkinsonian symptoms
Authors: Vandecasteele Marie , Valverde Sébastien , Piette Charlotte , Gangarossa Giuseppe , Derousseaux Willy , Aristieta Arbelaiz Asier , Touboul Jonathan , Degos Bertrand , Venance Laurent 
Published: November 2018

AbstractDeep brain stimulation of the subthalamic nucleus is a symptomatic treatment of Parkinson’s disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics and modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A mathematical model highlights how the decrease in pyramidal neurons activity can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation.One-sentence SummaryDeep brain stimulation recruits cortical somatostatin interneurons, and their opto-activation is beneficial in Parkinson’s.
Oxytocin and vasotocin receptor variation sheds light into the evolution of human prosociality
Authors: Theofanopoulou Constantina , Andirkó Alejandro , Boeckx Cedric , Jarvis Erich D. 
Published: November 2018

AbstractModern human lifestyle strongly depends on complex social traits like empathy, tolerance and cooperation. These diverse facets of social cognition have been associated with variation in the oxytocin receptor (OTR) and its sister genes, the vasotocin/vasopressin receptors (VTR1A/AVPR1A and AVPR1B/VTR1B). Here, we compared the full genomic sequences of these receptors between modern humans, archaic humans, and 12 non-human primate species, and identified sites that show heterozygous variation in modern humans and archaic humans distinct from variation in other primates, and that have associated literature. We performed variant clustering, pathogenicity prediction, regulation, linkage disequilibrium frequency and selection analyses on data in different modern-human populations. We found five sites with modern human specific variation, where the modern human allele is the major allele in the global population (OTR: rs1042778, rs237885, rs6770632; VTR1A: rs10877969; VTR1B: rs33985287). Among them, the OTR-rs6770632 was predicted to be the most functional. We found two sites where alleles (OTR: rs59190448 and rs237888)1 present only in modern humans and archaic humans are under positive selection in modern humans, with rs237888 predicted to be a highly functional site. We identified three sites of convergent evolution between modern humans and bonobos (OTR: rs2228485 and rs237897; VTR1A: rs1042615), with OTR-rs2228485 ranking very highly in terms of functionality and being under balancing selection in modern humans. Our findings shed light on evolutionary questions of modern human and hominid prosociality, as well as on similarities in the social behavior between modern humans and bonobos.
Neural Sampling Strategies for Visual Stimulus Reconstruction fromTwo-photon Imaging of Mouse Primary Visual Cortex
Authors: Garasto Stef , Nicola Wilten , Bharath Anil A. , Schultz Simon R. 
Published: November 2018

AbstractDeciphering the neural code involves interpreting the responses of sensory neurons from the perspective of a downstream population. Performing such a read-out is an important step towards understanding how the brain processes sensory information and has implications for Brain-Machine Interfaces. While previous work has focused on classification algorithms to identify a stimulus in a predefined set of categories, few studies have approached a full-stimulus reconstruction task, especially from calcium imaging recordings. Here, we attempt a pixel-by-pixel reconstruction of complex natural stimuli from two-photon calcium imaging of mouse primary visual cortex. We decoded the activity of 103 neurons from layer 2/3 using an optimal linear estimator and investigated which factors drive the reconstruction performance at the pixel level. We find the density of receptive fields to be the most influential feature. Finally, we use the receptive field data and simulations from a linear-nonlinear Poisson model to extrapolate decoding accuracy as a function of network size. We find that, on this dataset, reconstruction performance can increase by more than 50%, provided that the receptive fields are sampled more uniformly in the full visual field. These results provide practical experimental guidelines to boost the accuracy of full-stimulus reconstruction.
A new species in theAnopheles gambiaecomplex reveals new evolutionary relationships between vector and non-vector species
Authors: Barron Maite G , Paupy Christophe , Rahola Nil , Akone-Ella Ousman , Ngangue Marc F. , Wilson-Bahun Theodel A. , Pombi Marco , Kengne Pierre , Costantini Carlo , Simard Frédéric , Gonzalez Josefa , Ayala Diego 
Published: November 2018

AbstractComplexes of closely related species provide key insights about the rapid and independent evolution of adaptive traits. Here, we described and studied a presumably new species in theAnopheles gambiaecomplex,Anopheles fontenillei, recently discovered in the forested areas of Gabon, Central Africa. Our analysis placed the new taxon in the phylogenetic tree of theAn. gambiaecomplex, revealing important introgression events with other members of the complex. In particular, we detected recent introgression withAn. gambiaeandAn. coluzziiof genes directly involved in vectorial capacity. Moreover, genome analysis of the new species also allowed us to resolve the evolutionary history of inversion 3La. Overall,Anopheles fontenilleihas implemented our understanding about the relationship of species within thegambiaecomplex and provides insight into the evolution of vectorial capacity traits, relevant for the successful control of malaria in Africa.
Non-invasive ultrasound quantification of Scar Tissue Volume predicts functional changes during tendon healing
Authors: Ackerman Jessica E. , Studentsova Valentina , Loiselle Alayna E. 
Published: November 2018

AbstractTendon injuries are very common and disrupt the transmission of forces from muscle to bone, leading to impaired function and quality of life. Successful restoration of tendon function after injury is a challenging clinical problem due to the pathological, scar-mediated manner in which tendons heal. Currently, there are no standard treatments to modulate scar tissue formation and improve tendon healing. A major limitation to the identification of therapeutic candidates has been the reliance on terminal end-point metrics of healing in pre-clinical studies, which require a large number of animals and result in destruction of the tissue. To address this limitation, we have identified quantification of Scar Tissue Volume (STV) from ultrasound imaging as a longitudinal, non-invasive metric of tendon healing. STV was strongly correlated with established endpoint metrics of gliding function including Gliding Resistance (GR) and Metatarsophalangeal (MTP) Flexion Angle. However, no associations were observed between STV and tensile mechanical properties. To define the sensitivity of STV to identify differences between functionally discrete tendon healing phenotypes, we utilized S100a4 haploinsufficient mice (S100a4GFP/+), which heal with improved gliding function relative to wildtype (WT) littermates. A significant decrease in STV was observed in S100a4GFP/+repairs, relative to WT at day 14. Taken together, these data suggest US quantification of STV as a means to facilitate the rapid screening of biological and pharmacological interventions to improve tendon healing, and identify promising therapeutic targets, in an efficient, cost-effective manner.
Inhibition of retrotransposition improves health and extends lifespan of SIRT6 knockout mice
Authors: Simon Matthew , Meter Michael Van , Ablaeva Julia , Ke Zhonghe , Gonzalez Raul S. , Taguchi Taketo , Cecco Marco De , Leonova Katerina I. , Kogan Valeria , Helfand Stephen L. , Neretti Nicola , Roichman Asael , Cohen Haim Y. , Antoch Marina , Gudkov Andrei , Sedivy John M. , Seluanov Andrei , Gorbunova Vera 
Published: November 2018

SUMMARYMice deficient for SIRT6 exhibit a severely shortened lifespan, growth retardation, and highly elevated LINE1 (L1) activity. Here we report that SIRT6 deficient cells and tissues accumulate abundant cytoplasmic L1 cDNA which triggers massive type I interferon response via activation of cGAS. Remarkably, nucleoside reverse transcriptase inhibitors (NRTIs), which inhibit L1 retrotransposition, significantly improved health and lifespan of SIRT6 knockout mice and completely rescued type I interferon response. In tissue culture, inhibition of L1 with siRNA or NRTIs abrogated type I interferon response, in addition to a significant reduction of DNA damage markers. These results indicate that L1 activation contributes to the pathologies of SIRT6 knockout mice. Similarly, L1 transcription, cytoplasmic cDNA copy number and type I interferons were elevated in the wild type aged mice. As sterile inflammation is a hallmark of aging we propose that modulating L1 activity may be an important strategy for attenuating age-related pathologies.HighlightsSIRT6 KO mice accumulate L1 cDNA triggering type I interferon response via cGAS pathwayWild type aged mice accumulate L1 cDNA and display type I interferon responseReverse transcriptase inhibitors rescue type I interferon response and DNA damageReverse transcriptase inhibitors extend lifespan and improve health of SIRT6 KO mice
The WT1-BASP1 complex is required to maintain the differentiated state of taste receptor cells
Authors: Gao Yankun , Banik Debarghya Dutta , Roberts Stefan G. E. , Medler Kathryn F. 
Published: November 2018

AbstractThe WT1-BASP1 complex is a transcriptional repressor that is involved in cell differentiation; however, the mechanisms underlying its effects are not well-characterized in vivo. In the peripheral taste system which endogenously expresses these proteins, BASP1 co-expression with WT1 begins at the end of development, suggesting a role for the WT1-BASP1 complex in terminal cell differentiation within this system. Using a conditional BASP1 mouse, we demonstrate that BASP1 is critical to maintain the differentiated state of adult cells by inhibiting the activation of WT1-dependent target genes. Our results uncover a central role for the WT1-BASP1 complex in maintaining cell differentiation.
Homologous Recombination as an Evolutionary Force in African Swine Fever Viruses
Authors: Zhu Zhaozhong , Xiao Chao-Ting , Fan Yunshi , Cai Zena , Lu Congyu , Zhang Gaihua , Jiang Taijiao , Tan Yongjun , Peng Yousong 
Published: November 2018

AbstractRecent outbreaks of African swine fever virus (ASFV) in China severely influenced the swine industry of the country. Currently, there is no effective vaccine or drugs against ASFVs. How to effectively control the virus is challenging. In this study, we have analyzed all the publicly available ASFV genomes and demonstrated that there was a large genetic diversity of ASFV genomes. Interestingly, the genetic diversity was mainly caused by extensive genomic insertions and/or deletions (indels) instead of the point mutations. The genomic diversity of the virus resulted in proteome diversity. Over 250 types of proteins were inferred from the ASFV genomes, among which only 144 were observed in all analyzed viruses. Further analyses showed that the homologous recombination may contribute much to the indels, as supported by significant associations between the occurrence of extensive recombination events and the indels in the ASFV genomes. Repeated elements of dozens of nucleotides in length were observed to widely distribute and cluster in the adjacent positions of ASFV genomes, which may facilitate the occurrence of homologous recombination. Moreover, two enzymes, which were possibly related to the homologous recombination, i.e., a Lambda-like exonuclease with a YqaJ-like viral recombinase domain, and a DNA topoisomerase II, were found to be conservative in all the analyzed ASFVs. This work highlighted the importance of the homologous recombination in the evolution of the ASFVs, and helped with the strategy development of the prevention and control of the virus.
Pluripotent Stem Cell-derived Cerebral Organoids Reveal Human Oligodendrogenesis with Dorsal and Ventral Origins
Authors: Kim Hyosung , Xu Ranjie , Ragunathan Padmashri , Dunaevsky Anna , Liu Ying , Dreyfus Cheryl F. , Jiang Peng 
Published: November 2018

SUMMARYThe process of oligodendrogenesis has been relatively well delineated in the rodent brain. However, it remains unknown whether analogous developmental processes are manifested in the human brain. Here, we report oligodendrogenesis in forebrain organoids, generated by using OLIG2-GFP knockin human pluripotent stem cell (hPSC) reporter lines. OLIG2/GFP exhibits distinct temporal expression patterns in ventral forebrain organoids (VFOs) vs. dorsal forebrain organoids (DFOs). Interestingly, oligodendrogenesis can be induced in both VFOs and DFOs after neuronal maturation. Assembling VFOs and DFOs to generate fused forebrain organoids (FFOs) promotes oligodendroglia maturation. Furthermore, dorsally-derived oligodendroglial cells outcompete ventrally-derived oligodendroglia and become dominant in FFOs after long-term culture. Thus, our organoid models reveal human oligodendrogenesis with ventral and dorsal origins. These models will serve to study the phenotypic and functional differences between human ventrally- and dorsally-derived oligodendroglia and to reveal mechanisms of diseases associated with cortical myelin defects.