bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural variation in hippocampal dentations among healthy young adults
Authors: ten Hove Julia , Poppenk Jordan
Published: February 2020

Little is known about hippocampus dentations – or “bumps” on the inferior surface of the hippocampus – and whether they hold functional significance. Empirical work on these features is beginning to emerge, but no study has yet been conducted in which their spatial positions are demarcated, and their putative role in individual differences in memory is based on a single small study. We gathered ultra-high resolution isotropic MTL scans from young-adult sample and performed such measurements. On the long axis, we found smaller and denser dentations moving towards the hippocampus’ posterior extent. Although other reports have distinguished the functional characteristics of anterior and posterior hippocampal dentations, we found hardly any were actually localized in the hippocampal head, with half of participants featuring no anterior dentations at all. We also observed more numerous dentations in the left hemisphere than right, and found this asymmetry tracked right-hand dominance. All dentations lay specifically within in the CA1 subfield, which was thicker at dentations – protruding below standard lower boundary of the hippocampus – as well as larger in participants with more dentations, suggesting dentations reflect CA1 growth rather than mere folding. Finally, we observed an association between dentations and visual source memory, but not recognition memory. The current report is the first to characterize the spatial properties of this intriguing neuroanatomical feature, which requires the direct spatial labeling of dentations. Further to better characterizing this intriguing neuroanatomical feature, we provide some confirmatory evidence for a link to episodic memory, although we found evidence for this link to be less overwhelming than initially reported.
Genome Wide Association Study of Resistance to PstS2 and Warrior Races of Stripe (Yellow) Rust in Bread Wheat Landraces
Authors: Tehseen Muhammad Massub , Tonk Fatma Aykut , Tosun Muzaffer , Amri Ahmed , Sansaloni Carolina P. , Kurtulus Ezgi , Yazbek Mariana , Al-Sham’aa Khaled , Ozseven Izzet , Safdar Luqman Bin , Shehadeh Ali , Nazari Kumarse
Published: February 2020

Stripe rust, caused byPuccinia striiformisWestend. f. sp.triticiis a major threat to wheat production worldwide. The breakdown in resistance of certain major genes and new emerging aggressive races of stripe rusts are causing serious concerns in all main wheat growing areas of the world. To search for new sources of resistance genes and associated QTL for effective utilization in future breeding programs an association mapping panel comprising of 600 bread wheat landraces collected from eight different countries conserved at ICARDA gene bank were evaluated for seedling and adult plant resistance againstPstS2andWarriorraces of stripe rust at the Regional Cereal Rust Research Center (RCRRC), Izmir, Turkey during 2016, 2018 and 2019. A set of 25,169 informative SNP markers covering the whole genome were used to examine the population structure, linkage disequilibrium and marker-trait associations in the association mapping panel. The genome-wide association study (GWAS) was carried out using a Mixed Linear Model (MLM). We identified 47 SNP markers at 19 genomic regions with significant SNP-trait associations for both seedling and adult plant stage resistance, the threshold of significance for all SNP-trait associations was determined by the false discovery rate (q) ≤ 0.05. Three genomic regions (QYr.1D_APR, QYr.3A_seedlingandQYr.7D_seedling) identified in this study are far away from any previously reportedYrgene or QTL hence, tagging novel genomic regions. TheIn-silicoanalysis of the novel QTL regions identified candidate resistance genes encoding proteins putative to plants disease resistance and defense mechanism.
Dynamics of coherent activity between cortical areas defines a two-stage process of selective attention
Authors: Levichkina E. , Kermani M. , Saalmann Y.B. , Vidyasagar T.R.
Published: February 2020

Analysing a visual scene requires the brain to briefly keep in memory potentially relevant parts and then direct attention to their locations for detailed processing. To reveal the neuronal basis of the underlying working memory and top-down attention processes, we trained macaques to match two patterns presented with a delay between them. As the above processes are likely to require communication between brain regions, and the parietal cortex is involved in spatial attention, we simultaneously recorded neuronal activities from the interconnected parietal and middle temporal areas. We found that mnemonic information about the first pattern was retained in coherent oscillating activity between the areas in high-frequency bands, followed by coherent activity in low-frequency bands that mediate top-down attention on the relevant location.

ONE SENTENCE SUMMARY

Gamma coherence allows retaining object features in a saliency map while lower frequency coherence facilitates attention.
SAR1 paralogs differ biochemically in assembly of the COPII coat
Authors: Melville David B. , Studer Sean , Schekman Randy
Published: February 2020

COPII-coated vesicles are the primary mediators of vesicular traffic from the ER to the Golgi apparatus. SAR1 is a small GTPase, which, upon GTP binding, recruits the other COPII proteins to the ER membrane. In mammals, there are two SAR1 paralogs which genetic data suggest may have distinct physiological roles, e.g. in lipoprotein secretion for SAR1B. We identified two clusters of amino acids that have conserved, paralog-specific sequences. One cluster is adjacent to the SAR1 GTP-binding pocket and alters the kinetics of GTP exchange. The other cluster is adjacent to the binding site of COPII components SEC31 and SEC23. We found that the latter cluster confers a SEC23A binding preference to SAR1B over SAR1A. In contrast to SAR1B, SAR1A is prone to oligomerize on a membrane surface. Importantly, in relation to its physiological function, SAR1B, but not SAR1A, can compensate for loss of SAR1B in lipoprotein secretion. The SEC31/SEC23-binding site-adjacent divergent cluster is critical for this function. These data identify the novel paralog-specific function for SAR1B, and provide insights into the mechanisms of large cargo secretion and COPII related diseases.
Vezatin is required for the retrograde axonal transport of endosomes inDrosophilaand zebrafish
Authors: Spinner Michael A. , Pinter Katherine , Drerup Catherine M. , Herman Tory G.
Published: February 2020

Active transport of organelles within axons is critical for neuronal health. Retrograde axonal transport, in particular, relays neurotrophic signals received by axon terminals to the nucleus and circulates new material amongen passantsynapses. The single retrograde motor, cytoplasmic dynein, is linked to diverse cargos by adaptors that promote dynein motility. Here we identify Vezatin as a new, cargo-specific regulator of retrograde axonal transport. Loss-of-function mutations in theDrosophila vezatin-like(vezl) gene prevent signaling endosomes containing activated BMP receptors from initiating transport out of motor neuron terminal boutons.vezlloss also decreases the transport of endosomes and dense core vesicles (DCVs) within axon shafts. While vertebrate Vezatin (Vezt) has not previously been implicated in axonal transport, we show thatveztloss in zebrafish impairs the retrograde movement of late endosomes, causing their accumulation in axon terminals. Our work establishes a new, conserved, cargo-specific role for Vezatin proteins in axonal transport.
Quantifying ecoacoustic activity in the Amazon rainforest through Information Theory quantifiers
Authors: Colonna Juan G. , Carvalho José Reginaldo H. , Rosso Osvaldo A.
Published: February 2020

Automatic monitoring of biodiversity by acoustic sensors has become an indispensable tool to assess environmental stress at an early stage. Due to the difficulty in recognizing the Amazon’s high acoustic diversity and the large amounts of raw audio data recorded by the sensors, the labeling and manual inspection of this data is not feasible.

Therefore, we propose an ecoacoustic index that allows us to quantify the complexity of an audio segment and correlate this measure with the biodiversity of the soundscape. The approach uses unsupervised methods to avoid the problem of labeling each species individually. The proposed index, named the Ecoacoustic Global Complexity Index (EGCI), makes use of Entropy, Divergence and Statistical Complexity. A distinguishing feature of this index is the mapping of each audio segment, including those of varied lenghts, as a single point in a 2D-plane, supporting us in understanding the ecoacoustic dynamics of the rainforest. The main results show a regularity in the ecoacoustic richness of a floodplain, considering different temporal granularities, be it between hours of the day or between consecutive days of the monitoring program. We observed that this regularity does a good job of characterizing the soundscape of the environmental protection area of Mamirauá, in the Amazon, differentiating between species richness and environmental phenomena.
MethPanel: a parallel pipeline and interactive analysis tool for multiplex bisulphite PCR sequencing to assess DNA methylation biomarker panels for disease detection
Authors: Luu Phuc-Loi , Ong Phuc-Thinh , Loc Tran Thai Huu , Lam Dilys , Pidsley Ruth , Stirzaker Clare , Clark Susan J.
Published: February 2020

Background

Multiplex bisulphite PCR sequencing is a convenient and scalable method to comprehensively profile DNA methylation at selected loci. The method is useful for validation of methylation biomarker panels on large clinical cohorts, as it can be applied to DNA isolated from fresh tissue, archival formalin fixed paraffin embedded tissue (FFPET) or circulating cell free DNA in plasma. However, successful clinical implementation of DNA methylation biomarkers for disease detection using multiplex bisulphite PCR sequencing, requires user-friendly sample analysis methods and a diversity of visualisation options, which are not met by current tools.

Results

We have developed a computational pipeline with an interactive graphical interface, calledMethPanel, in order to rapidly analyse multiplex bisulphite PCR sequencing data.MethPanelcomprises a complete analysis workflow from genomic alignment to DNA methylation calling and supports an unlimited number of PCR amplicons and input samples. Moreover,MethPaneloffers important and unique features, such as calculation of a polymorphism score and bisulphite PCR bias correction capabilities.MethPanelis designed so that the methylation data from all samples can be run in parallel on either a personal computer or a high performance computer. The outputs are also automatically forwarded to a shinyApp for convenient display, visualisation and sharing data with collaborators and clinicians. Importantly the data is centralised in one location, which aids storage management.

Availability and Implementation

MethPanelis freely available athttps://github.com/thinhong/MethPanel

Conclusion

MethPanelprovides a novel parallel pipeline and interactive analysis tool for multiplex bisulphite PCR sequencing to assess DNA methylation marker panels for disease detection.
A Software Toolkit for TMS Electric-Field Modeling with Boundary Element Fast Multipole Method: An Efficient MATLAB Implementation
Authors: Makarov Sergey N. , Wartman William A. , Daneshzand Mohammad , Fujimoto Kyoko , Raij Tommi , Nummenmaa Aapo
Published: February 2020

Background

Transcranial magnetic stimulation (TMS) is currently the only non-invasive neurostimulation modality that enables painless and safe supra-threshold stimulation by employing electromagnetic induction to efficiently penetrate the skull. Accurate, fast, and high resolution modeling of the electric fields (E-fields) may significantly improve individualized targeting and dosing of TMS and therefore enhance the efficiency of existing clinical protocols as well as help establish new application domains.

Objective

To present and disseminate our TMS modeling software toolkit, including several new algorithmic developments, and to apply this software to realistic TMS modeling scenarios given a high-resolution model of the human head including cortical geometry and an accurate coil model.

Method

The recently developed charge-based boundary element fast multipole method (BEM-FMM) is employed as an alternative to the 1st order finite element method (FEM) most commonly used today. The BEM-FMM approach provides high accuracy and unconstrained field resolution close to and across cortical interfaces. Here, the previously proposed BEM-FMM algorithm has been improved in several novel ways.

Results and Conclusions

The improvements resulted in a threefold increase in computational speed while maintaining the same solution accuracy. The computational code based on the MATLAB®platform is made available to all interested researchers, along with a coil model repository and examples to create custom coils, head model repository, and supporting documentation. The presented software toolkit may be useful for post-hoc analyses of navigated TMS data using high-resolution subject-specific head models as well as accurate and fast modeling for the purposes of TMS coil/hardware development.
Combinatorial effect of miR-486-5p & miR-22-3p mimics thrombopoietin’s impact on hematopoietic stem & progenitor cells
Authors: Kao Chen-Yuan , Jiang Jinlin , Papoutsakis Eleftherios T.
Published: February 2020

Megakaryocytes shed and release submicron size microparticles (MkMPs), the most abundant microparticle in circulation. We have previously reported that MkMPs target peripheral-blood CD34+hematopoietic stem/progenitor cells (HSPCs) to induce megakaryocytic differentiation and proliferation, and that small RNAs delivered to HSPCs via MkMPs play an important role in the development of this phenotype. Here, using single-molecule real-time (SMRT) RNA sequencing (RNAseq), we identify the top seven most abundant microRNAs (miRs) in MkMPs as potential candidates in mediating the effect of MkMPs on HSPCs. Using miR mimics, we demonstrate that among the seven most abundant miRs, two, miR-486-5p and miR-22-3p, are able to drive the Mk differentiation of HSPCs in the absence of thrombopoietin (TPO). The effect of these two miRs is comparable to the TPO- or MkMP-induced megakaryocytic differentiation of HSPCs, thus suggesting that these two miRs are responsible for this MkMP-induced phenotype. To probe the signaling through which MkMPs might enable this phenotype, we used kinase inhibitors of potential signaling pathways engaged in megakaryocytic differentiation. Our data suggest that MkMP-induced Mk differentiation of HSPCs is enabled through JNK and PI3K/Akt/mTOR signaling. Our data show that MkMPs activate Akt and mTOR phosphorylation. Furthermore, MkMPs downregulate PTEN expression, a direct target of miR-486-5p and a negative regulator of PI3K/Akt signaling, via JNK signaling. Taken together, our data provide a mechanistic understanding of the biological effect of MkMPs in inducing megakaryocytic differentiation of HSPCs, which, as was previously suggested, is a phenotype of potential physiological significance in stress megakaryopoiesis.

Key Points

miR-486-5p and miR-22-3p drive megakaryocytic differentiation in the absence of thrombopoietin.

Megakaryocytic microparticles trigger megakaryocytic differentiation of CD34+cells through JNK and PI3K/Akt/mTOR signaling.

Visual Abstract
Major discrepancy between factual antibiotic resistance and consumption in South of France: analysis of 539,037 bacterial strains
Authors: Diallo Ousmane Oumou , Baron Sophie Alexandra , Dubourg Gregory , Chaudet Hervé , Halfon Philippe , Camiade Sabine , Comte Béatrice , Joubert Stéphanie , François Arnaud , Seyral Philippe , Parisot François , Casalta Jean-Paul , Ruimy Raymond , Maruejouls Christophe , Achiardy Jean-Christophe , Burignat Sophie , Carvajal Joseph , Delaunay Edouard , Meyer Sandra , Levy Pierre-Yves , Roussellier Patricia , Brunet Patrick , Bosi Claude , Stolidi Philippe , Arzouni Jean-Pierre , Gay Gisele , Hance Pierre , Colson Philippe , Raoult Didier , Rolain Jean-Marc
Published: February 2020

Introduction

The burden of antibiotic resistance is currently estimated by mathematical modeling, without real count of resistance to key antibiotics. Here we report the real rate of resistance to key antibiotics in bacteria isolated from humans during a 5 years period in a large area in southeast in France.

Methods

We conducted a retrospective study on antibiotic susceptibility of 539,107 clinical strains isolated from hospital and private laboratories in south of France area from January 2014 to January 2019. The resistance rate to key antibiotics as well as the proportion of bacteria classified as Difficult-to-Treat (DTR) were determined and compared with the Mann-Whitney U test, the χ2 test or the Fisher’s exact test.

Results

Among 539,037 isolates, we did not observe any significant increase or decrease in resistance to key antibiotics for 5 years, (oxacillin resistance inStaphylococcus aureus, carbapenem resistance in enterobacteria andPseudomonas aeruginosaand 3rdgeneration cephalosporin resistance inEscherichia coliandKlebsiella pneumoniae). However, we observed a significant decrease in imipenem resistance forAcinetobacter baumanniifrom 2014 to 2018 (24.19% to 12.27%; p=0.005) and a significant increase of ceftriaxone resistance inKlebsiella pneumoniae(9.9% to 24,03%; p=0.001) andEnterobacter cloacae(24,05% to 42,05%; p=0.004). Of these 539,037 isolates, 1,604 (0.3%) had a DTR phenotype.

Conclusion

Over a 5-year period, we did not observe a burden of AR in our region despite a high rate of antibiotic consumption in our country. These results highlight the need for implementation of real-time AR surveillance systems which use factual data.
Recent ultra-rare inherited mutations identify novel autism candidate risk genes
Authors: Wilfert Amy B , Turner Tychele N , Murali Shwetha C , Hsieh PingHsun , Sulovari Arvis , Wang Tianyun , Coe Bradley P , Guo Hui , Hoekzema Kendra , Bakken Trygve E , Winterkorn Lara H , Evani Uday S , Byrska-Bishop Marta , Earl Rachel K , Bernier Raphael A ,   The SPARK Consortium, Zody Michael C , Eichler Evan E
Published: February 2020

Autism is a highly heritable, complex disorder wherede novomutation (DNM) variation contributes significantly to disease risk. Using whole-genome sequencing data from 3,474 families, we investigate another source of large-effect risk variation, ultra-rare mutations. We report and replicate a transmission disequilibrium of private likely-gene disruptive (LGD) mutations in probands but find that 95% of this burden resides outside of known DNM-enriched genes. This variant class more strongly affects multiplex family probands and supports a multi-hit model for autism. Candidate genes with private LGD variants preferentially transmitted to probands converge on the E3 ubiquitin-protein ligase complex, intracellular transport, and Erb signaling protein networks. We estimate these mutations are ~2.5 generations old and significantly younger than other mutations of similar type and frequency in siblings. Overall, private LGD variants are under strong purifying selection and act on a distinct set of genes not yet associated with autism.

One sentence summary

Ultra-rare autism variants preferentially transmitted to probands are younger and identify distinct gene candidates and functional networks.
The induciblelacoperator-repressor system is functional in zebrafish cells
Authors: Nishizaki Sierra S. , McDonald Torrin L. , Farnum Gregory A. , Holmes Monica J. , Drexel Melissa L. , Switzenberg Jessica A. , Boyle Alan P.
Published: February 2020

Background

Zebrafish are a foundational model organism for studying the spatio-temporal activity of genes and their regulatory sequences. A variety of approaches are currently available for editing genes and modifying gene expression in zebrafish, including RNAi, Cre/lox, and CRISPR-Cas9. However, thelacoperator-repressor system, a component of theE. coli lacoperon which has been adapted for use in many other species and is a valuable, flexible tool for studying the inducible modulation of gene expression, has not previously been tested in zebrafish.

Results

Here we demonstrate that thelacoperator-repressor system robustly decreases expression of firefly luciferase in cultured zebrafish fibroblast cells. Our work establishes thelacoperator-repressor system as a promising tool for the manipulation of gene expression in whole zebrafish.

Conclusions

Our results lay the groundwork for the development oflac-based reporter assays in zebrafish, and adds to the tools available for investigating dynamic gene expression in embryogenesis. We believe that this work will catalyze the development of new reporter assay systems to investigate uncharacterized regulatory elements and their cell-type specific activities.
Parallel mechanisms of visual memory formation across distinct regions of the honey bee brain
Authors: Avalos Arián , Traniello Ian M. , Claudio Eddie Perez , Giray Tugrul
Published: February 2020

Visual learning is vital to the behavioral ecology of the Western honey bee (Apis mellifera). Honey bee workers forage for floral resources, a behavior that requires the learning and long-term memory of visual landmarks, but how these memories are mapped to the brain remains poorly understood. To address this gap in our understanding, we collected bees that successfully learned visual associations in a conditioned aversion paradigm and compared gene expression correlates of memory formation in the mushroom bodies, a higher-order sensory integration center classically thought to contribute to learning, as well as the optic lobes, the primary visual neuropil responsible for sensory transduction of visual information. We quantitated expression ofCREBandCaMKii, two classical genetic markers of learning andfen-1, a gene specifically associated with punishment learning in vertebrates. As expected, we report substantial involvement of the mushroom bodies for all three markers but additionally demonstrate an unexpected involvement of the optic lobes across a similar time course. Our findings imply the molecular involvement of a sensory neuropil during visual associative learning parallel to a higher-order brain region, furthering our understanding of how a tiny brain processes environmental signals.
Shaping Brain Structure: Genetic and Phylogenetic Axes of Macro Scale Organization of Cortical Thickness
Authors: Valk Sofie L. , Xu Ting , Margulies Daniel S. , Masouleh Shahrzad Kahrabian , Paquola Casey , Goulas Alexandros , Kochunov Peter , Smallwood Jonathan , Yeo B.T. Thomas , Bernhardt Boris C. , Eickhoff Simon B.
Published: February 2020

Structural and functional characteristics of the cortex systematically vary along global axes as a function of cytoarchitecture, gene expression, and connectivity. The topology of the cerebral cortex has been proposed to be a prerequisite for the emergence of human cognition and explain both the impact and progression of pathology. However, the neurogenetic origin of these organizational axes in humans remains incompletely understood. To address this gap in the literature our current study assessed macro scale cortical organization through an unsupervised machine learning analysis of cortical thickness covariance patterns and used converging methods to evaluate its genetic basis. In a large-scale sample of twins (n=899) we found structural covariance of thickness to be organized along both an anterior-to-posterior and inferior-to-superior axis. We found that both axes showed a high degree of correspondence in pairs of identical twins, suggesting a strong heritable component in humans. Furthermore, comparing these dimensions in macaques and humans highlighted similar organizational principles in both species demonstrating that these axes of cortical organization are phylogenetically conserved within primate species. Finally, we found that in both humans and macaques the inferior-superior dimension of cortical organization was aligned with the predictions of the dual-origin theory, highlighting the possibility that the macroscale organization of primate brain structure is subject to multiple distinct neurodevelopmental trajectories. Together, our study establishes the genetic basis of natural axes in the cerebral cortex along which structure is organized and so provides important insights into the organization of human cognition that will inform both our understanding of how structure guides function and for the progression of pathology in diseases.
unCOVERApp: an interactive graphical application for clinical assessment of sequence coverage at the base-pair level
Authors: Iovino Emanuela , Seri Marco , Pippucci Tommaso
Published: February 2020

Motivation

Next Generation Sequencing (NGS) is increasingly adopted in the clinical practice largely thanks to concurrent advancements in bioinformatic tools for variant detection and annotation. Despite improvements in available approaches, the need to assess sequencing quality down to the base-pair level still poses challenges for diagnostic accuracy. One of the most popular quality parameters of diagnostic NGS is the percentage of targeted bases characterized by low depth of coverage (DoC). These regions potentially hide a clinically-relevant variant, but no annotation is usually returned for them.

However, visualizing low-DoC data with their potential functional and clinical consequences may be useful to prioritize inspection of specific regions before re-sequencing all coverage gaps or making assertions about completeness of the diagnostic test.

To meet this need we have developed unCOVERApp, an interactive application for graphical inspection and clinical annotation of low-DoC genomic regions containing genes.

Results

unCOVERApp is a suite of graphical and statistical tools to support clinical assessment of low-DoC regions. Its interactive plots allow to display gene sequence coverage down to the base-pair level, and functional and clinical annotations of sites below a user-defined DoC threshold can be downloaded in a user-friendly spreadsheet format. Moreover, unCOVERApp provides a simple statistical framework to evaluate if DoC is sufficient for the detection of somatic variants, where the usual 20x DoC threshold used for germline variants is not adequate. Amaximum credible allele frequencycalculator is also available allowing users to set allele frequency cut-offs based on assumptions about the genetic architecture of the disease instead of applying a general one (e.g. 5%). In conclusion, unCOVERApp is an original tool designed to identify sites of potential clinical interest that may be hidden in diagnostic sequencing data.

Availability

unCOVERApp is a freely available application written in R and developed with Shiny packages and available in GitHub.
Drosophila SWR1 and NuA4 complexes are defined by DOMINO isoforms
Authors: Scacchetti Alessandro , Schauer Tamas , Reim Alexander , Apostolou Zivkos , Sparr Aline Campos , Krause Silke , Heun Patrick , Wierer Michael , Becker Peter B.
Published: February 2020

Histone acetylation and deposition of H2A.Z variant are integral aspects of active transcription. InDrosophila, the single DOMINO chromatin regulator complex is thought to combine both activitiesviaan unknown mechanism. Here we show that alternative isoforms of the DOMINO nucleosome remodeling ATPase, DOM-A and DOM-B, directly specify two distinct multi-subunit complexes. Both complexes are necessary for transcriptional regulation but through different mechanisms. The DOM-B complex incorporates H2A.V (the fly ortholog of H2A.Z) genome-wide in an ATP-dependent manner, like the yeast SWR1 complex. The DOM-A complex, instead, functions as an ATP-independent histone acetyltransferase complex similar to the yeast NuA4, targeting lysine 12 of histone H4. Our work provides an instructive example of how different evolutionary strategies lead to similar functional separation. In yeast and humans, nucleosome remodeling and histone acetyltransferase complexes originate from gene duplication and paralog specification.Drosophilagenerates the same diversity by alternative splicing of a single gene.

Highlights

Isoforms of DOMINO dictate the formation of distinct complexes

DOM-B complex is theDrosophilaSWR1 and incorporates H2A.V genome-wide

DOM-A complex acetylates H4K12 and is theDrosophilaNuA4
Anthropogenic factors influence the occupancy of an invasive carnivore in a suburban preserve system
Authors: Vanek John P. , Rutter Andrew U. , Preuss Timothy S. , Jones Holly P. , Glowacki Gary A.
Published: February 2020

Domestic cats (Felis catus) are one of the world’s most damaging invasive species. Free-ranging cats kill billions of wild animals every year, spread parasites and diseases to both wildlife and humans, and are responsible for the extinction or extirpation of at least 63 species. While the ecology and conservation implications of free-ranging cats have well studied in some locations, relatively little is known about cats inhabiting urban nature preserves in the United States. To address this knowledge gap, we used camera traps to study the occupancy and activity patterns of free-ranging cats in 55 suburban nature preserves in the Chicago, IL metropolitan area. From 2010–2018 (4,440 trap days), we recorded 355 photos of free-ranging cats across 26 preserves (ψnaïve= 0.45) and 41 randomly distributed monitoring points (ψnaïve= 0.18). Cats were detected every year, but rarely at the same point or preserve, and cats were largely crepuscular/diurnal. Using single-season occupancy models and a “stacked” design, we found that cat occupancy increased with building density and detectability was highest near the urban/preserve boundary. Based on our top-ranked model, predicted occupancy within individual preserves ranged from 0.09 to 0.28 (ψmean= 0.11) and was poorly correlated with preserve size or shape. Overall, our results suggest that free-ranging cats are rare within suburban preserves in our study area, and that these cats are most likely owned or heavily subsidized by people (which pose different risks and management challenges than truly feral cats). We discuss the conservation and management implications for urban natural areas.

Highlights

We surveyed for domestic cats across 55 suburban preserves from 2010-2018.

We modeled occupancy and detectability as a function of urban covariates.

Cat occupancy was low overall and best predicted by building density.

The risk to native species is highest near preserve boundaries bordered by built environments.
Measuring aptamer folding energy using a molecular clamp
Authors: Qu Hao , Ma Qihui , Wang Lu , Mao Yu , Eisenstein Michael , Soh Hyongsok Tom , Zheng Lei
Published: February 2020

Folding energy offers a useful metric for characterizing the stability and function of aptamers. However, experimentally measuring the folding energy is challenging and there is currently no general technique to measure this parameter directly. In this work, we present a simple approach for measuring aptamer folding energy. First, the aptamer is stretched under equilibrium conditions with a double-stranded DNA “molecular clamp” that is coupled to the aptamer ends. We then measure the total internal energy of stressed DNA molecules using time-lapse gel electrophoresis and compare the folding and unfolding behavior of molecular clamp-stressed molecules that incorporate either the aptamer or unstructured random single-stranded DNA in order to derive the aptamer folding energy. Using this approach, we measured a folding energy of 10.40 kJ/mol for the HD22 thrombin aptamer, which is consistent with other predictions and estimates. We also analyzed a simple hairpin structure, generating a folding energy result of 9.05 kJ/mol, consistent with the value predicted by computational models (9.24 kJ/mol). We believe our strategy offers an accessible and generalizable approach for obtaining such measurements with virtually any aptamer.
Transcriptomic and Proteomic analysis of clear cell foci (CCF) in the human non-cirrhotic liver identifies several differentially expressed genes and proteins with functions in cancer cell biology and glycogen metabolism
Authors: Metzendorf Christoph , Wineberger Katharina , Rausch Jenny , Cigliano Antonio , Calvisi Diego F. , Peters Kristin , Sun Baodong , Mennerich Daniela , Kietzmann Thomas , Dombrowski Frank , Ribback Silvia
Published: February 2020

Clear cell foci (CCF) of the liver are considered to be pre-neoplastic lesions of hepatocellular adenomas and carcinomas. They are hallmarked by glycogen-overload and activation of AKT/mTOR-signaling.

Here we report the transcriptome and proteome of CCF extracted from human liver biopsies by laser capture microdissection. We mainly found genes and proteins with lower expression in CCF compared to control samples. Of 14 differentially expressed transcripts only 3 were overexpressed and belong to previously uncharacterized long non-coding RNAs. At the protein level, 3 proteins were at least 1.5-fold higher expressed in CCF than in control samples, while 22 proteins were at least 1.5-fold less abundant. Using immunohistochemistry, the reduced expressions of STBD1, USP28, monad/WDR92, CYB5B and HSPE1 were validated in CCF. Knockout ofSTBD1, the gene coding for Starch-binding domain-containing protein 1, in mice did not have an effect on liver glycogen levels. Similiarly,Usp28knockout in mice did not affect glycogen storage in diethylnitrosamine-induced liver carcinoma. Thus, these data indicate that reduced expression of STBD1 or USP28 in CCF is unlikely to explain glycogen overload.

Our study revealed several novel proteins and RNAs that are differentially expressed in CCF and have functions relevant for carcinogenesis or the glycogen metabolism.
Acetylation of isoniazid - a novel mechanism of isoniazid resistance inMycobacterium tuberculosis
Authors: Arun K. B. , Madhavan Aravind , Abraham Billu , Balaji M. , Sivakumar K. C. , Nisha P. , Kumar R. Ajay
Published: February 2020

Isoniazid (INH), one of the first-line drugs used for the treatment of tuberculosis, is a pro-drug which is converted into its active form by the intracellular KatG enzyme ofMycobacterium tuberculosis. The activated drug hinders cell wall biosynthesis by inhibiting InhA protein. INH resistant strains ofM. tuberculosisusually have mutations inkatG,inhA,ahpC,kasA, andndhgenes. However, INH resistant strains which do not have mutations in any of these genes are reported, suggesting that these strains may adopt some other mechanism to become resistant to INH. In the present study we characterized Rv2170, a putative acetyltransferase inM. tuberculosis, to elucidate its role in inactivating isoniazid. The purified recombinant protein was able to catalyze transfer of acetyl group to INH from acetyl CoA. HPLC and LC-MS analyses showed that following acetylation by Rv2170, INH is broken down into isonicotinic acid and acetylhydrazine. Drug susceptibility assay and confocal analysis showed thatM. smegmatis, which is susceptible to INH, is not inhibited by INH acetylated with Rv2170. RecombinantM. smegmatisandM. tuberculosisH37Ra overexpressing Rv2170 were found to be resistant to INH at minimum inhibitory concentrations that inhibited wildtype strains. In addition, intracellularM. tuberculosisH37Ra overexpressing Rv2170 survived better in macrophages when treated with INH. Our results strongly indicate that Rv2170 acetylates INH, and this could be one of the strategies adopted by at least someM. tuberculosisstrains to overcome INH toxicity.
Universality of clonal dynamics poses fundamental limits to identify stem cell self-renewal strategies
Authors: Parigini Cristina , Greulich Philip
Published: February 2020

How adult stem cells maintain self-renewing tissues isin vivocommonly assessed by analysing clonal data from cell lineage tracing assays. To identify strategies of stem cell self-renewal requires that different models of stem cell fate choice predict sufficiently different clonal statistics. Here we show that models of cell fate choice can, in homeostatic tissues, be categorized by exactly two ‘universality classes’, whereby models of the same class predict, under asymptotic conditions, the same clonal statistics. Those classes relate to generalizations of the canonical asymmetric vs. symmetric stem cell self-renewal strategies and are differentiated by a conservation law. This poses both challenges and opportunities to identify stem cell self-renewal strategies: while under asymptotic conditions, self-renewal models of the same universality class cannot be distinguished by clonal data only, models of different classes can be distinguished by simple means.
Autosomal Recessive Alzheimer’s disease (arAD): homozygosity mapping of genomic regions containing arAD loci
Authors: Moreno-Grau Sonia , Fernández Maria Victoria , de Rojas Itziar , Hernández Isabel , Farias Fabiana , Budde John P , Quintela Inés , Madrid Laura , González-Perez Antonio , Montrreal Laura , Garcia-Gonzalez Pablo , Alarcón-Martín Emilio , Alegret Montserrat , Maroñas Olalla , Pineda Juan Antonio , Macías Juan ,   GR@ACE & DEGESCO consortia,   Alzheimer’s Disease Neuroimaging Initiative, Marquié Marta , Valero Sergi , Benaque Alba , Clarimón Jordi , Bullido Maria Jesus , García-Ribas Guillermo , Pástor Pau , Sánchez-Juan Pascual , Álvarez Victoria , Piñol-Ripoll Gerard , García-Alberca Jose María , Royo José Luis , Franco-Macías Emilio , Mir Pablo , Calero Miguel , Medina Miguel , Rábano Alberto , Ávila Jesús , Antúnez Carmen , Real Luis Miguel , Orellana Adelina , Carracedo Ángel , Sáez María Eugenia , Tárraga Lluis , Boada Mercè , Cruchaga Carlos , Ruiz Agustín
Published: February 2020

Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of recent inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD). However, the search for recessive variants has been poorly assessed to date. To investigate homozygosity in AD, we performed a fine-scale ROH analysis including 21,100 individuals from 10 cohorts of European ancestry (11,919 AD cases and 9,181 controls). We detected an increase of homozygosity in AD cases compared to controls [βFROH(CI95%) = 0.051 (0.023 – 0.078); P = 3.25 x 10-4]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 x 10-16). The top associated ROH with AD risk (β (CI95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 x 10-4) was detected upstream theHS3ST1locus (chr4:11,189,482‒11,305,456), previously related to AD. Next, to construct a homozygosity map of AD cases, we selected ROHs shared by inbred AD cases extracted from an outbred population. We used whole-exome sequencing data from 1,449 individuals from the Knight-ADRC-NIA-LOAD (KANL) cohort to identify potential recessive variants in candidate ROHs. We detected a candidate marker, rs117458494, mapped in theSPON1locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability.
Tissue-specific transcriptome profiling of theArabidopsis thalianainflorescence stem reveals local cellular signatures
Authors: Shi Dongbo , Jouannet Virginie , Agustí Javier , Kaul Verena , Levitsky Victor , Sanchez Pablo , Mironova Victoria V , Greb Thomas
Published: February 2020

Genome-wide gene expression maps with a high spatial resolution have substantially accelerated molecular plant science. However, the number of characterized tissues and growth stages is still small because of the limited accessibility of most tissues for protoplast isolation. Here, we provide gene expression profiles of the mature inflorescence stem ofArabidopsis thalianacovering a comprehensive set of distinct tissues. By combining fluorescence-activated nucleus sorting and laser-capture microdissection with next generation RNA sequencing, we characterize transcriptomes of xylem vessels, fibers, the proximal and the distal cambium, phloem, phloem cap, pith, starch sheath, and epidermis cells. Our analyses classify more than 15,000 genes as being differentially expressed among different stem tissues and reveal known and novel tissue-specific cellular signatures. By determining transcription factor binding regions enriched in promoter regions of differentially expressed genes, we furthermore provide candidates for tissue-specific transcriptional regulators. Our datasets predict expression profiles of an exceptional amount of genes and allow generating hypotheses toward the spatial organization of physiological processes. Moreover, we demonstrate that information on gene expression in a broad range of mature plant tissues can be established with high spatial resolution by nuclear mRNA profiling.

One sentence summary

A genome-wide high-resolution gene expression map of the Arabidopsis inflorescence stem is established.
Abundance and Distribution ofHeterelmis cf. glabra(Coleoptera: Elmidae) within Dolan Falls Preserve and the Devils River State Natural Area, Texas, USA
Authors: Diaz Peter H. , Gibson J. Randy , Norris Chad W. , Thompson Carrie L.
Published: February 2020

The Devils River watershed in south-central Texas has baseflows entirely attributable to groundwater primarily sourced from the Edwards-Trinity and Edwards Aquifers. The largest known populations of a species of riffle beetle,Heterelmis cf. glabra, are located in springs associated with the upper Devils River. The focus of this study was to 1) determine site-level abundances ofH. cf. glabrausing open system N-mixture models, 2) test mesohabitat associations of members in the riffle beetle family Elmidae and, 3) measure and examine abiotic and habitat associations for adult and larval beetles within the study area. We sampled 32 spring sources to determine occupancy and abundance of adult and larval riffle beetles (Elmidae) within the study area. Spring sources were mapped and categorized by type (orifice, upwelling, group of springs, or seep). Basic water chemistry and flow rate categorization were also performed at each site. Model results suggest that rainfall, flow and site are important for detection ofH. cf. glabra. Based on our results, regular monitoring of these 32 sites using these methods, is recommended to conduct hypotheses tests on covariates influencing abundance. Such baseline information will be important in measuring impacts to this and other spring-associated species as the habitats of this region are impacted by natural or anthropogenic phenomena.
High throughput screening identifies SOX2 as a Super Pioneer Factor that inhibits DNA methylation maintenance at its binding sites
Authors: Vanzan Ludovica , Soldati Hadrien , Ythier Victor , Anand Santosh , Francis Nicole , Murr Rabih
Published: February 2020

Access of mammalian transcription factors (TFs) to regulatory regions, an essential event for transcription regulation, is hindered by chromatin compaction involving nucleosome wrapping, repressive histone modifications and DNA methylation. Moreover, methylation of TF binding sites (TBSs) affects TF binding affinity to these sites. Remarkably, a special class of TFs called pioneer transcription factors (PFs) can access nucleosomal DNA, leading to nucleosome remodelling and chromatin opening. However, whether PFs can bind to methylated sites and induce DNA demethylation is largely unknown.

Here, we set up a highly parallelized approach to investigate PF ability to bind methylated DNA and induce demethylation. Our results indicate that the interdependence between DNA methylation and TF binding is more complex than previously thought, even within a select group of TFs that have a strong pioneering activity; while most PFs do not induce changes in DNA methylation at their binding sites, we identified PFs that can protect DNA from methylation and PFs that can induce DNA demethylation at methylated binding sites. We called the latter “super pioneer transcription factors” (SPFs), as they are seemingly able to overcome several types of repressive epigenetic marks. Importantly, while most SPFs induce TET-dependent active DNA demethylation, SOX2 binding leads to passive demethylation by inhibition of the maintenance methyltransferase DNMT1 during replication. This important finding suggests a novel mechanism allowing TFs to interfere with the epigenetic memory during DNA replication.
Genomic evidence reveals SPA-regulated developmental and metabolic pathways in dark-grownArabidopsisseedlings
Authors: Pham Vinh Ngoc , Paik Inyup , Hoecker Ute , Huq Enamul
Published: February 2020

Photomorphogenesis is repressed in the dark mainly by an E3 ubiquitin ligase complex comprising CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) and four homologous proteins called SUPPRESSOR OF PHYA-105 (SPA1-SPA4) in Arabidopsis. This complex induces the ubiquitination and subsequent degradation of positively acting transcription factors (e.g., HY5, HFR1, PAP1 and others) in the dark to repress photomorphogenesis. Genomic evidence showed a large number of genes regulated by COP1 in the dark, of which many are direct targets of HY5. However, the genomic basis for the constitute photomorphogenic phenotype ofspaQremains unknown. Here, we show that >7200 genes are differentially expressed in thespaQbackground compared to wild-type in the dark. Comparison of the RNA Sequencing (RNA-Seq) data betweencop1andspaQrevealed a large overlapping set of genes regulated by the COP1-SPA complex. In addition, many of the genes coordinately regulated by the COP1-SPA complex are also regulated by HY5 directly and indirectly. Taken together, our data reveal that SPA proteins repress photomorphogenesis by controlling gene expression in concert with COP1, likely through regulating the abundance of downstream transcription factors in light signaling pathways. Moreover, SPA proteins may function both in a COP1-dependent and –independent manner in regulating many biological processes and developmental pathways in Arabidopsis.

Summary statement

Comparison of transcriptome analyses betweencop1andspaQmutants reveal overlapping pathways regulated by COP1 and SPAs.