bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription-factor centric genome mining strategy for discovery of diverse unprecedented RiPP gene clusters
Authors: Zhu Shaozhou , Zheng Guojun 
Published: November 2018

ABSTRACTRibosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly emerging group of natural products with diverse biological activity. Most of their biosynthetic mechanisms are well studied and the “genome mining” strategy based on homology has led to the unearthing of many new ribosomal natural products, including lantipeptides, lasso peptides, cyanobactins. These precursor-centric or biosynthetic protein-centric genome mining strategies have encouraged the discovery of RiPPs natural products. However, a limitation of these strategies is that the newly identified natural products are similar to the known products and novel families of RiPP pathways were overlooked by these strategies. In this work, we applied a transcription-factor centric genome mining strategy and diverse unique crosslinked RiPP gene clusters were predicted in several sequenced microorganisms. Our research could significantly expand the category of biosynthetic pathways of RiPP natural products and predict new resources for novel RiPPs.
Boundary effects of expectation in human pain perception
Authors: Hird E.J. , Charalambous C. , El-Deredy W. , Jones A.K. , Talmi D. 
Published: November 2018

AbstractPerception of sensory stimulation is influenced by numerous psychological variables. One example is placebo analgesia, where expecting low pain causes a painful stimulus to feel less painful. Yet, because pain evolved to signal threats to survival, it should be maladaptive for highly-erroneous expectations to yield unrealistic pain experiences. Therefore, we hypothesised that a cue followed by a highly discrepant stimulus intensity, which generates a large prediction error, will have a weaker influence on the perception of that stimulus. To test this hypothesis we collected two independent pain-cueing datasets. The second dataset and the analysis plan were preregistered (osf.io/5r6z7). Regression modelling revealed that reported pain intensities were best explained by a quartic polynomial model of the prediction error. The results indicated that the influence of cues on perceived pain decreased when stimulus intensity was very different from expectations, suggesting that prediction error size has an immediate functional role in pain perception.
Phylogenomics, biogeography, and evolution in the American palm genusBrahea
Authors: Barrett Craig F. , Sinn Brandon T. , King Loren T. , Medina Jesus C. , Bacon Christine D. , Lahmeyer Sean C. , Hodel Donald R. 
Published: November 2018

AbstractBackground and AimsSlow rates of molecular evolution at low taxonomic levels hamper studies of relationships among species, and subsequent biogeographic and evolutionary analyses. An example is the genusBrahea, which is among the most poorly understood lineages of American palms and is characterized by a wide variety of growth forms and intermediate morphological features.MethodsWe generated approximately 400 kb of genome-scale data from all three genomes for the 11 currently described species ofBraheato infer phylogenetic relationships, reconstruct ancestral growth form, estimate ancestral geographic ranges, and test for niche equivalency among closely related species with geographic overlap.Key ResultsRelationships receive strong support, and conform to previous subgeneric assignments, except for placement of the dwarf speciesB. mooreiwithin subgenusErythea.Our robust phylogenetic hypothesis reveals trends in growth form including an overall increase in height in theB. armataclade, and independent evolution of dwarf forms from taller ancestors in theB. pimoandB. dulcisclades. Ancestral range estimation reveals roles of dispersal (e.g.B. edulison Guadalupe Island) and sympatric speciation in some cases (e.g. in theB. armataclade), but is equivocal in others (e.g. in theB. pimo clade). We find evidence of niche non-equivalency among species within theB. armataclade in northwestern Mexico, and some evidence of niche non-equivalency betweenB. berlandieriandB. dulcis, the former of which is synonymized underB. dulcis.ConclusionsOur findings have implications for the complex biogeographic history in Central America and Mexico, suggesting that sympatric speciation and dispersal are the predominant processes of species diversification. Future studies should include population-level sampling across the genus, along with morphological and ecological information, to assess distinctness among species and, particularly, levels of gene flow, in an integrative fashion.
Core components of endosomal mRNA transport are evolutionarily conserved in fungi
Authors: Müller Jessica , Pohlmann Thomas , Feldbrügge Michael 
Published: November 2018

AbstractActive movement of mRNAs by sophisticated transport machineries determines precise spatiotemporal expression of encoded proteins. A prominent example discovered in fungi is microtubule-dependent transport via endosomes. This mode of transport was thought to be only operational in the basidiomycete Ustilago maydis. Here, we report that distinct core components are evolutionarily conserved in fungal species of distantly related phyla like Mucoromycota. Interestingly, orthologues of the key RNA-binding protein Rrm4 from the higher basidiomycete Coprinopsis cinerea and the mucoromycete Rhizophagus irregularis shuttle on endosomes in hyphae of U. maydis. Thus, endosomal mRNA transport appears to be more wide-spread than initially anticipated.Highlights‐Core transport components Upa1 and Rrm4 are conserved in different fungal phyla‐Components of the Rrm4 machinery were most likely secondarily lost in ascomycetes‐Upa1 from Microbotryum lychnidis-dioicae is functional in U. maydis‐Rrm4 orthologues from Basidio- and Mucoromycota shuttle in hyphae of U. maydis
Towards feedback control of the cell-cycle across a population of yeast cells
Authors: Perrino Giansimone , Fiore Davide , Napolitano Sara , di Bernardo Mario , di Bernardo Diego 
Published: November 2018

AbstractCells are defined by their unique ability to selfreplicate through cell division. This periodic process is known as the cell-cycle and it happens with a defined period in each cell. The budding yeast divides asymmetrically with a mother cell generating multiple daughter cells. Within the cell population each cell divides with the same period but asynchronously. Here, we investigate the problem of synchronising the cell-cycle across a population of yeast cells through a microfluidics-based feedback control platform. We propose a theoretical and experimental approach for cell-cycle control by considering a yeast strain that can be forced to start the cell-cycle by changing growth medium. The duration of the cell-cycle is strictly linked to the cell volume growth, hence a hard constraint in the controller design is to prevent excessive volume growth. We experimentally characterised the yeast strain and derived a simplified phase-oscillator model of the cell-cycle. We then designed and implemented three impulsive control strategies to achieve maximal synchronisation across the population and assessed their control performance by numerical simulations. The first two controllers are based on event-triggered strategies, while the third uses a model predictive control (MPC) algorithm to select the sequence of control impulses while satisfying built-in constraints on volume growth. We compared the three strategies by computing two cost functions: one quantifying the level of synchronisation across the cell population and the other volume growth during the process. We demonstrated that the proposed control approaches can effectively achieve an acceptable trade-off between two conflicting control objectives: (i) obtaining maximal synchronisation of the cell cycle across the population while (ii) minimizing volume growth. The results can be used to implement effective strategies to unfold the biological mechanisms controlling cell cycle and volume growth in yeast cells.
Inter-generational Consequences for Growing C.elegans in Liquid
Authors: Lev Itamar , Bril Roberta , Liu Yunan , Ceré Lucila Inés , Rechavi Oded 
Published: November 2018

AbstractIn recent years, studies in Caenorhabditis elegans nematodes have shown that different stresses can generate multigenerational changes. Here we show that worms that grow in liquid media, and also their plate-grown progeny, are different from worms whose ancestors were grown on plates. It has been suggested that C.elegans might encounter liquid environments in nature, although actual observations in the wild are few and far between. In contrast, in the lab, growing worms in liquid is commonplace, and often used as an alternative to growing worms on agar plates, to control the composition of the worms’ diet, to starve (and synchronize) worms, or to grow large populations for biochemical assays. We found that plate-grown descendants of M9 liquid media-grown worms were longer than control worms, and the heritable effects were apparent already very early in development. We tested for the involvement of different known epigenetic inheritance mechanisms, but could not find a single mutant in which these intergenerational effects are canceled. While we found that growing in liquid always leads to inter-generational changes in the worms’ size, trans-generational effects were found to be variable, and in some cases the effects were gone after 1 -2 generations. These results demonstrate that standard cultivation conditions in early life can dramatically change the worms’ physiology in adulthood, and can also affect the next generations.
FishResp: R Package and GUI Application for Analysis of Aquatic Respirometry Data
Authors: Morozov Sergey , McCairns R. J. Scott , Merilä Juha 
Published: November 2018

AbstractIntermittent-flow respirometry is widely used to measure oxygen uptake rates and subsequently estimate aerobic metabolic rates of aquatic animals. However, the lack of a standard quality-control software to detect technical problems represents a potential impediment to comparisons across studies. Here, we introduce ‘FishResp’, a versatile R package and its graphical implementation for quality-control and filtering of raw respirometry data. Our goal is to provide a straightforward, cross-platform and free software to help improve the quality and comparability of metabolic rate estimates for reducing methodological fragmentation in the field of aquatic respirometry. FishResp accepts data from various respirometry systems, allows users to detect potential mechanical problems which can occur during oxygen uptake measurements (e.g. chamber leaking, poor water circulation), and offers six options to correct raw data for microbial oxygen consumption. The software performs filtering of raw data based on user criteria, and produces accurate and unbiased estimates of absolute and mass-specific metabolic rates. Using data from three-spined sticklebacks (Gasterosteus aculeatus) and Trinidadian guppies (Poecilia reticulata), we demonstrate the virtues of FishResp, highlighting the importance of detecting mechanical problems and correcting measurements for background respiration.Lay summaryFishResp is a user-friendly tool for calculating oxygen uptake of aquatic organisms. The aim of the software is to improve the quality of metabolic rate estimates based on a straightforward pipeline: background respiration correction, detection of mechanical problems, conduction of QC tests, and filtration based on user-defined criteria.
Predicting trait regulators by identifying co-localization of DNA binding and GWAS variants in regulatory regions
Authors: Quon Gerald , Feizi Soheil , Marbach Daniel , Claussnitzer Melina , Kellis Manolis 
Published: November 2018

AbstractGenomic regions associated with complex traits and diseases are primarily located in non-coding regions of the genome and have unknown mechanism of action. A critical step to understanding the genetics of complex traits is to fine-map each associated locus; that is, to find the causal variant(s) that underlie genetic associations with a trait. Fine-mapping approaches are currently focused on identifying genomic annotations, such as transcription factor binding sites, which are enriched in direct overlap with candidate causal variants. We introduce CONVERGE, the first computational tool to search for co-localization of GWAS causal variants with transcription factor binding sites in the same regulatory regions, without requiring direct overlap. As a proof of principle, we demonstrate that CONVERGE is able to identify five novel regulators of type 2 diabetes which subsequently validated in knockdown experiments in pancreatic beta cells, while existing fine-mapping methods were unable to find any statistically significant regulators. CONVERGE also recovers more established regulators for total cholesterol compared to other fine-mapping methods. CONVERGE is therefore unique and complementary to existing fine-mapping methods and is useful for exploring the regulatory architecture of complex traits.
Gradients of connectivity distance in the cerebral cortex of the macaque monkey
Authors: Oligschläger Sabine , Xu Ting , Baczkowski Blazej M. , Falkiewicz Marcel , Falchier Arnaud , Linn Gary , Margulies Daniel S. 
Published: November 2018

AbstractCortical connectivity conforms to a series of organizing principles that are common across species. Spatial proximity, similar cortical type, and similar connectional profile all constitute factors for determining the connectivity between cortical regions. We previously demonstrated another principle of connectivity that is closely related to the spatial layout of the cerebral cortex. Using functional connectivity from resting-state fMRI in the human cortex, we found that the further a region is located from primary cortex, the more distant are its functional connections with other areas of the cortex. However, it remains unknown whether this relationship between cortical layout and connectivity extends to other primate species. Here, we investigated this relationship using both resting-state functional connectivity as well as gold-standard tract-tracing connectivity in the macaque monkey cortex. For both measures of connectivity, we found a gradient of connectivity distance extending between primary and frontoparietal regions. As in the human cortex, the further a region is located from primary areas, the stronger its connections to distant portions of the cortex, with connectivity distance highest in frontal and parietal regions. The similarity between the human and macaque findings provide evidence for a phylogenetically conserved relationship between the spatial layout of cortical areas and connectivity.
Lineage tracing on transcriptional landscapes links state to fate during differentiation
Authors: Weinreb Caleb , Rodriguez-Fraticelli Alejo , Camargo Fernando , Klein Allon M 
Published: November 2018

AbstractA challenge in stem cell biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Though the development of single cell assays allows for the capture of progenitor cell states in great detail, these assays cannot definitively link cell states to their long-term fate. Here, we use expressed DNA barcodes to clonally trace single cell transcriptomes dynamically during differentiation and apply this approach to the study of hematopoiesis. Our analysis identifies functional boundaries of cell potential early in the hematopoietic hierarchy and locates them on a continuous transcriptional landscape. We reconstruct a developmental hierarchy showing separate ontogenies for granulocytic subtypes and two routes to monocyte differentiation that leave a persistent imprint on mature cells. Finally, we use our approach to benchmark methods of dynamic inference from single-cell snapshots, and provide evidence of strong early fate biases dependent on cellular properties hidden from single-cell RNA sequencing.
An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome
Authors: Richardson Tom G. , Harrison Sean , Hemani Gibran , Smith George Davey 
Published: November 2018

AbstractThe age of large-scale genome-wide association studies (GWAS) has provided us with an unprecedented opportunity to evaluate the genetic liability of complex disease using polygenic risk scores (PRS). In this study, we have analysed 162 PRS (P<5×l005) derived from GWAS and 551 heritable traits from the UK Biobank study (N=334,398). Findings can be investigated using a web application (http://mrcieu.mrsoftware.org/PRS_atlas/), which we envisage will help uncover both known and novel mechanisms which contribute towards disease susceptibility.To demonstrate this, we have investigated the results from a phenome-wide evaluation of schizophrenia genetic liability. Amongst findings were inverse associations with measures of cognitive function which extensive follow-up analyses using Mendelian randomization (MR) provided evidence of a causal relationship. We have also investigated the effect of multiple risk factors on disease using mediation and multivariable MR frameworks. Our atlas provides a resource for future endeavours seeking to unravel the causal determinants of complex disease.
A simple method to co-purify genomic DNA, RNA, and proteins for functional studies
Authors: Jiang Jian , Ma Junfei , Liu Bin , Wang Ying 
Published: November 2018

AbstractUnderstanding the regulation of gene expression, from the epigenetic modifications on genomes to posttranscriptional and translational controls, are critical for elucidating molecular mechanisms underlying distinct phenotypes in biology. With the rapid development of Multi-Omics analyses, it is desirable to minimize sample variations by using DNA, RNA, and proteins co-purified from the same samples. Currently, most of the co-purification protocols rely on Tri Reagent (Trizol as a common representative) and require protein precipitation and dissolving steps, which render difficulties in experimental handling and high-throughput analyses. Here, we established a simple and robust method to minimize the precipitation steps and yield ready-to-use RNA and protein in solutions. This method can be applied to samples in small quantity, such as protoplasts. We demonstrated that the protoplast system equipped with this method may facilitate studies on viroid biogenesis. Given the ease and the robustness of this new method, it will have broad applications for plant research and other disciplines in molecular biology.
Discover Stable Expression Hot Spot in Genome of Chinese Hamster Ovary Cells Using Lentivirus based Random Integration Method
Authors: Zhou Songtao , Ding Xuefeng , Yang Lei , Chen Yun , Gong Xiaohai , Jin Jian , Li Huazhong 
Published: November 2018

AbstractTraditional construction method for stable expression cell line was mainly achieved by using random integration method. However, target gene might be integrated into heterochromatin region or unstable region of chromatin by using this method, and thus required multiple rounds of selection to obtain desirable expression cell lines with stable expression level of target proteins. Rational cell line construction method can overcome this shortcoming by integrating transgenes into stable hot spot within genome specifically. Thus, to discover novel effective hot spot would be critical for this new cell line construction method. Here we reported one practical method to discover new stable hot spot by using lentivirus infection and random integration. One such hot spot located at NW_006880285.1 was thoroughly investigated in this article. The expression stability of this hot spot was verified by detecting Zsgreen1 reporter gene expression for over 50 passages. When cells were adapted to suspension culture, they successfully kept expressing Zsgreen1 reporter gene. In addition, this suspension cell line could keep expressing reporter gene stably for another 50 passages. In summary, this research offered an easy new method for researchers to identify their own stable hot spots within CHO genome, and would contribute to the development of site-specific integration study in the future.
Cryo-EM structure of the receptor-activated TRPC5 ion channel at 2.9 angstrom resolution
Authors: Duan Jingjing , Li Jian , Chen Gui-Lan , Zeng Bo , Xie Kechen , Peng Xiaogang , Zhou Wei , Zhong Jianing , Zhang Yixing , Xu Jie , Xue Changhu , Zhu Lan , Liu Wei , Tian Xiao-Li , Wang Jianbin , Clapham David E. , Li Zongli , Zhang Jin 
Published: November 2018

AbstractThe transient receptor potential canonical subfamily member 5 (TRPC5) is a non-selective calcium-permeant cation channel. As a depolarizing channel, its function is studied in the central nervous system and kidney. TRPC5 forms heteromultimers with TRPC1, but also forms homomultimers. It can be activated by reducing agents through reduction of the extracellular disulfide bond. Here we present the 2.9 Å resolution electron cryo-microscopy (cryo-EM) structure of TRPC5. The structure of TRPC5 in its apo state is partially open, which may be related to the weak activation of TRPC5 in response to extracellular pH. We also report the conserved negatively charged residues of the cation binding site located in the hydrophilic pocket between S2 and S3. Comparison of the TRPC5 structure to previously determined structures of other TRPC and TRP channels reveals differences in the extracellular pore domain and in the length of the S3 helix. Together, these results shed light on the structural features that contribute to the specific activation mechanism of the receptor-activated TRPC5.
ImmuneRegulation: A web-based tool for identifying human immune regulatory elements
Authors: Kalayci Selim , Selvan Myvizhi Esai , Ramos Irene , Cotsapas Chris , Montgomery Ruth R. , Poland Gregory , Pulendran Bali , Tsang John , Klein Robert J. , Gümüş Zeynep H. 
Published: November 2018

ABSTRACTHumans can vary considerably in their healthy immune phenotypes and in their immune responses to various stimuli. We have developed an interactive web-based tool, ImmuneRegulation, to enable discovery of human regulatory elements that drive some of the phenotypic differences observed in gene expression profiles. ImmuneRegulation currently provides the largest centrally integrated resource available in the literature on transcriptome regulation in whole blood and blood cell types, including genotype data from 23,040 individuals, with associated gene expression data from 30,562 experiments, that provide genetic variant-gene expression associations on ∼200 million eQTLs. In addition, it includes 14 million transcription factor (TF) binding region hits extracted from 1945 TF ChIP-seq peaks and the latest GWAS catalog of 67,230 published SNP-trait associations. Users can interactively explore ImmuneRegulation to visualize and discover associations between their gene(s) of interest and their regulators (genetic variants or transcription factors) across multiple cohorts and studies. These regulators can explain cohort or cell type dependent gene expression variations and may be critical in selecting the ideal cohorts or cell types for follow-up studies. Overall, ImmuneRegulation aims to contribute to our understanding of the effects of eQTLs and TFs on heterogeneous transcriptional responses reported in studies on the blood; in the development of molecular signatures of immune response; and facilitate their future application in patient management. ImmuneRegulation is freely available at http://icahn.mssm.edu/immuneregulation.