bluuebunny/crossref_metadata_2025_split huggingface dataset:
How ancient forest fragmentation and riparian connectivity generate high levels of genetic diversity in a microendemic Malagasy tree
Authors: Salmona Jordi , Dresen Axel , Ranaivoson Anicet E. , Manzi Sophie , Le Pors Barbara , Hong-Wa Cynthia , Razanatsoa Jacqueline , Andriaholinirina Nicole V. , Rasoloharijaona Solofonirina , Vavitsara Marie-Elodie , Besnard Guillaume 
Published: November 2020

AbstractUnderstanding landscape changes is central to predicting evolutionary trajectories and defining conservation practices. While human-driven deforestation is intense throughout Madagascar, exceptions in areas like the Loky-Manambato region (North) raise questions. Such regions also harbor a rich and endemic flora, whose evolutionary origin remains poorly understood. We assessed the genetic diversity of an endangered microendemic Malagasy olive species (Noronhia spinifolia Hong-Wa) to better understand the vegetation dynamic in the Loky-Manambato region and its influence on past evolutionary processes. We characterized 72 individuals sampled across eight forests through nuclear and mitochondrial restriction associated sequencing data (RADseq) and chloroplast microsatellites (cpSSR). Combined population and landscape genetics analyses indicate that N. spinifolia diversity is largely explained by the current forest cover, highlighting a long-standing habitat mosaic in the region. This sustains a major and long-term role of riparian corridors in maintaining connectivity across those antique mosaic-habitats, calling for the study of organismal interactions that promote gene flow.
N-terminal VP1 truncations favorT=1 norovirus-like particles
Authors: Pogan Ronja , Weiss Victor U. , Bond Kevin , Dülfer Jasmin , Krisp Christoph , Lyktey Nicholas , Müller-Guhl Jürgen , Zoratto Samuele , Allmaier Günter , Jarrold Martin F. , Muñoz-Fontela Cesar , Schlüter Hartmut , Uetrecht Charlotte 
Published: November 2020

AbstractNoroviruses cause immense sporadic gastroenteritis outbreaks worldwide. Emerging genotypes, which are divided based on VP1 sequence, further enhance this public threat. Self-assembling properties of the human norovirus major capsid protein VP1 are crucial for using virus-like particles (VLPs) for vaccine development. However, there is no vaccine available yet. Here, VLPs from different variants produced in insect cells are characterized in detail using a set of biophysical and structural tools. We are using native mass spectrometry, gas-phase electrophoretic mobility molecular analysis and proteomics to get clear insights into particle size, structure, composition as well as stability. Generally, noroviruses have been known to form mainlyT=3 particles. Importantly, we identify a major truncation in the capsid proteins as a likely cause for the formation of merelyT=1 particles. For vaccine development, particle production needs to be a reproducible, reliable process. Understanding the underlying processes in capsid size variation will help to produce particles of a defined capsid size presenting antigens consistent with intact virions. Next to vaccine production itself, this would be immensely beneficial for bio-/nano-technological approaches using viral particles as carriers or triggers for immunological reactions.
AKAP79/150 coordinates leptin-induced PKA activation to regulate KATPchannel trafficking in pancreatic β-cells
Authors: Cochrane Veronica A. , Yang Zhongying , Dell’Acqua Mark , Shyng Show-Ling 
Published: November 2020

AbstractThe adipocyte hormone leptin regulates glucose homeostasis both centrally and peripherally. A key peripheral target is the pancreatic β-cell, which secretes insulin upon glucose stimulation. Leptin suppresses glucose-stimulated insulin secretion by promoting trafficking of KATPchannels to the β-cell surface, which increases K+conductance and causes β-cell hyperpolarization. Here we investigate the signaling mechanism underlying leptin-induced KATPchannel translocation with a focus on protein kinase A (PKA). Using FRET-based PKA activity reporters, we show that leptin increases PKA activity at the cell membrane via a signaling pathway involving NMDA receptors, CaMKKβ and AMPK. Genetic knockdown and rescue experiments reveal that leptin activation of PKA requires tethering of PKA to the membrane-targeted PKA-anchoring protein AKAP79/150. Interestingly, disrupting protein phosphatase 2B (PP2B) anchoring to AKAP79/150, known to elevate basal PKA signaling, increases surface KATPchannels. Our findings uncover a novel role of AKAP79/150 in coordinating leptin and PKA signaling to regulate β-cell function.
SpheroidPicker: An Automated 3D cell culture manipulator robot using deep learning
Authors: Grexa Istvan , Diosdi Akos , Kriston Andras , Moshkov Nikita , Harmati Maria , Buzas Krisztina , Pietiainen Vilja , Koos Krisztian , Horvath Peter 
Published: November 2020

AbstractRecent statistics report that more than 3.7 million new cases of cancer occur in Europe yearly, and the disease accounts for approximately 20 % of all deaths. High-throughput screening of cancer cell cultures has dominated the search for novel, effective anticancer therapies in the past decades. Recently, ex vivo 3D cell cultures from the patient’s own cancer cells have gained importance. We recently evaluated the major advancements and needs of the 3D cell cultures screening field, and we concluded that strictly standardized sample preparation is the most desired development. Here we propose an artificial intelligence-guided low-cost 3D cell culture delivery system. It consists of a light microscope, a micromanipulator, a syringe pump, and a controller computer. The system performs morphology-based feature analysis on spheroids and transfers the most appropriate ones between various sample holders. It can select the samples from standard sample holders, including Petri dishes and microwell plates, and then transfer them to a variety of holders up to 384 well plates. The device performs reliable semi- and fully automated spheroid transfer. This results in highly controlled experimental conditions and eliminates non-trivial side effects of sample variability that is a key aspect towards next-generation precision medicine.
Control of stem cell niche and fruit development inArabidopsis thalianabyAGO10/ZWLrequires the bHLH transcription factorINDEHISCENT
Authors: Valluru Manoj , Sorefan Karim 
Published: November 2020

AbstractBackgroundThe shoot apical meristem (SAM) in plants is composed of a small mound of pluripotent stem cells that generate new organs. ARGONAUTE10 (AGO10) is known to be critical for maintenance of the embryonic SAM by regulating the expression ofClass III HOMEODOMAIN-LEUCINE ZIPPER(HD-ZIP III) transcription factors, which then modulate downstream responses to the key phytohormone auxin. However, we do not understand how AGO10 modulates auxin responses after embryogenesis in the mature plant.ResultsHere we show thatAGO10regulates auxin responses in the post-embryonic SAM via the bHLH transcription factorINDEHISCENT(IND). IND directly regulates auxin responses in the SAM regulating the auxin transporter PIN1 via direct transcriptional regulation ofPINOIDkinase. We show that a loss of functionindmutation significantly restoresago10zwl-3mutant SAM and fruit phenotypes.ago10zwl-3mutants overexpressINDand overexpression of IND phenocopies theago10zwl-3SAM phenotypes, and regulates auxin transport and responses in the SAM. AGO10 also regulates post-embryonic development in the fruit via a similar genetic pathway.ConclusionsWe characterise a molecular mechanism that is conserved during post embryonic development linkingAGO10directly to auxin responses.
Prognostic Biomarkers for Predicting Papillary Thyroid Carcinoma Patients at High Risk Using Nine Genes of Apoptotic Pathway
Authors: Arora Chakit , Kaur Dilraj , Raghava G.P.S 
Published: November 2020

AbstractObjectivesAberrant expression of apoptotic genes has been associated with papillary thyroid carcinoma (PTC) in the past, however, their prognostic role and utility as biomarkers remains poorly understood.Materials and methodsIn this study, we analysed 505 PTC patients by employing Cox-PH regression techniques, prognostic index models and machine learning methods to elucidate the relationship between overall survival (OS) of PTC patients and 165 apoptosis related genes.ResultsIt was observed that nine genes (ANXA1, TGFBR3, CLU, PSEN1, TNFRSF12A, GPX4, TIMP3, LEF1, BNIP3L) showed significant association with OS of PTC patients. Five out of nine genes were found to be positively correlated with OS of the patients, while the remaining four genes were negatively correlated. These genes were used for developing risk prediction models. Our voting-based model achieved highest performance (HR=41.59, p=3.36×10−4, C=0.84, logrank-p=3.8×10−8). The performance of voting-based model improved significantly when we used the age of patients with prognostic biomarker genes and achieved HR=57.04 with p=10−4(C=0.88, logrank-p=1.44×10−9). We also developed classification models that can classify high risk patients (survival ≤ 6 years) and low risk patients (survival > 6 years). Our best model achieved AUROC of 0.92. Since these genes can also be used as potential therapeutic targets in PTC, we identified potential drug molecules which could modulate their expression profile.ConclusionThis study briefly revealed the key prognostic biomarker genes in the apoptotic pathway whose altered expression is associated with PTC progression and aggressiveness. In addition to this, risk assessment models proposed here can help in efficient management of PTC patients.
Integration in or Near Oncogenes Plays Only a Minor Role in Determining the in Vivo Distribution of HIV Integration Sites Before or During Suppressive Antiretroviral Therapy
Authors: Coffin John M. , Bale Michael J. , Wells Daria , Guo Shuang , Luke Brian , Zerbato Jennifer M. , Sobolewskii Michele D. , Sia Twan , Shao Wei , Wu Xiaolin , Maldarelli Frank , Kearney Mary F. , Mellors John W. , Hughes Stephen H. 
Published: November 2020

AbstractHIV persists during antiretroviral therapy (ART) as integrated proviruses in cells descended from a small fraction of the CD4+ T cells infected prior to the initiation of ART. To better understand what controls HIV persistence and the distribution of integration sites (IS), we compared about 16,000 and 54,000 IS from individuals pre-ART and on ART, respectively, with approximately 385,000 IS from PBMC infected in vitro. The distribution of IS in vivo is quite similar to the distribution in PBMC, modified by selection against proviruses in expressed genes, by selection for proviruses integrated into one of 6 specific genes, and by clonal expansion. The clones in which a provirus integrated in an oncogene contributed to the survival of the clone comprise only a small fraction of the clones that persist in HIV-infected individuals on ART. Mechanisms that do not involve the provirus, or its location in the host genome, are more important in determining which clones expand and persist.Author SummaryIn HIV-infected individuals, a small fraction of the infected cells persist and divide. This reservoir persists on ART and can rekindle the infection if ART is discontinued. Because the number of possible sites of HIV DNA integration is very large, each infected cell, and all of its descendants, can be identified by the site where the provirus is integrated (IS). To understand the selective forces that determine the fates of infected cells in vivo, we compared the distribution of HIV IS in freshly-infected cells to cells from HIV-infected donors sampled both before and during ART. We found that, as has been previously reported, integration favors highly-expressed genes. However, over time the fraction of cells with proviruses integrated in highly-expressed genes decreases, implying that they grow less well. There are exceptions to this broad negative selection. When a provirus is integrated in a specific region in one of six genes, the proviruses affect the expression of the target gene, promoting growth and/or survival of the cell. Although this effect is striking, it is only a minor component of the forces that promote the growth and survival of the population of infected cells during ART.
Arabidopsis thalianagenes contributing to differences in the outcome of infection with generalist and specialist strains ofTurnip mosaic virusidentified by genome-wide association studies
Authors: Butković Anamarija , González Rubén , Rivarez Mark Paul Selda , Elena Santiago F. 
Published: November 2020

AbstractPathogens can be classified as generalists or specialists depending on their host breadth. While generalists are able to successfully infect a wide variety of host species, the host range of specialists is limited to a few related species. Even though generalists seem to gain an advantage due to their wide host range, they usually pay a cost in terms of fitness within each host species (i.e., the jack-of-all trades, master of none). On the contrary, specialists have high fitness within their own host. A highly relevant yet poorly explored question is whether generalist and specialist viruses differ in the way they interact with their host’s gene expression networks. To identify host genetic factors relevant for the infection of specialist or generalist viruses, we undertook a genome-wide association study (GWAS) approach. Four hundred fifty natural accessions ofArabidopsis thalianawere inoculated with turnip mosaic potyvirus strains that were either generalist (TuMV-G) or specialist (TuMV-S). Several disease-related traits have been associated with different sets of host genes for each TuMV strain. While most of the mapped loci were traitor strain-specific, one shared locus was mapped for both strains, a disease resistance TIR-NBS-LRR class protein. Likewise, only one locus was found involved in more than one of the disease-related traits evaluated, a putative cysteine-rich receptor-like protein kinase 20. To validate these results, the corresponding null mutant plants were inoculated with TuMV-G or -S and the outcome of infection was characterized.Author summaryGeneralist and specialist viruses are commonly found in nature, where they have potential for epidemics, and are classified depending on their host breath. In this study we used a genome-wide association study to characterize differences in the genetic basis of both infection strategies from a host perspective. Our experimental setup consisted of 450 accessions ofA. thalianaand two strains of TuMV. We found differences in the number of associated genes and their functions in disease-related traits. Results were validated by characterization of viral infections in null mutant plants deficient for a set of the identified genes.
Extensive phylogenies of human development reveal variable embryonic patterns
Authors: Coorens Tim H. H. , Moore Luiza , Robinson Philip S. , Sanghvi Rashesh , Christopher Joseph , Hewinson James , Cagan Alex , Oliver Thomas R. W. , Neville Matthew D. C. , Hooks Yvette , Noorani Ayesha , Mitchell Thomas J. , Fitzgerald Rebecca C. , Campbell Peter J. , Martincorena Iñigo , Rahbari Raheleh , Stratton Michael R. 
Published: November 2020

ABSTRACTStarting from the zygote, all cells in the developing and adult human body continuously acquire mutations. A mutation shared between two different cells implies a shared progenitor cell and can thus be used as a naturally occurring marker for lineage tracing. Here, we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissected samples from multiple organs. Early embryonic progenitor cells inferred from the phylogenies often contribute in different proportions to the adult body and the extent of this asymmetry is variable between individuals, with ratios between the first two reconstructed cells ranging from 56:44 to 92:8. Asymmetries also pervade subsequent cell generations and can differ between tissues in the same individual. The phylogenies also resolve the spatial embryonic origins and patterning of tissues, revealing a spatial effect in the development of the human brain. Supplemented by data on eleven men, we timed the split between soma and germline, with the earliest observed segregation occurring at the first cell divisions. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals.
Single-nucleus full-length RNA profiling in plants incorporates isoform information to facilitate cell type identification
Authors: Long Yanping , Liu Zhijian , Jia Jinbu , Mo Weipeng , Fang Liang , Lu Dongdong , Liu Bo , Zhang Hong , Chen Wei , Zhai Jixian 
Published: November 2020

AbstractThe broad application of large-scale single-cell RNA profiling in plants has been restricted by the prerequisite of protoplasting. We recently found that the Arabidopsis nucleus contains abundant polyadenylated mRNAs, many of which are incompletely spliced. To capture the isoform information, we combined 10x Genomics and Nanopore long-read sequencing to develop a protoplasting-free full-length single-nucleus RNA profiling method in plants. Our results demonstrated using Arabidopsis root that nuclear mRNAs faithfully retain cell identity information, and single-molecule full-length RNA sequencing could further improve cell type identification by revealing splicing status and alternative polyadenylation at single-cell level.
A Synergistic Workspace for Human Consciousness Revealed by Integrated Information Decomposition
Authors: Luppi Andrea I. , Mediano Pedro A.M. , Rosas Fernando E. , Allanson Judith , Pickard John D. , Carhart-Harris Robin L. , Williams Guy B. , Craig Michael M , Finoia Paola , Owen Adrian M. , Naci Lorina , Menon David K. , Bor Daniel , Stamatakis Emmanuel A. 
Published: November 2020

AbstractA central goal of neuroscience is to understand how the brain orchestrates information from multiple input streams into a unified conscious experience. Here, we address two fundamental questions: how is the human information-processing architecture functionally organised, and how does its organisation support consciousness? We combine network science and a rigorous information-theoretic notion of synergy to delineate a “synergistic global workspace”, comprising gateway regions that gather synergistic information from specialised modules across the brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the brain’s default mode network, whereas broadcasters coincide with the executive control network. Demonstrating the empirical relevance of our proposed architecture for neural information processing, we show that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to a diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory. Taken together, this work provides a new perspective on the role of prominent resting-state networks within the human information-processing architecture, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information.
Early-life mitochondrial DNA damage results in lifelong deficits in energy production mediated by redox signaling inCaenorhabditis elegans
Authors: Rooney John P. , Hershberger Kathleen A. , Turner Elena A. , Donoghue Lauren J. , Maurer Laura L. , Ryde Ian T. , Kim Jina J , Joglekar Rashmi , Hibshman Jonathan D. , Smith Latasha L. , Bhatt Dhaval P. , Ilkayeva Olga R. , Hirschey Matthew D. , Meyer Joel N. 
Published: November 2020

AbstractThe consequences of damage to the mitochondrial genome (mtDNA) are poorly understood, although mtDNA is more susceptible to damage than nuclear DNA (nucDNA), and many environmental toxicants target the mitochondria. Reports from the toxicological literature suggest that exposure to early-life mitochondrial damage could lead to deleterious consequences later in life (the “Developmental Origins of Health and Disease” paradigm) but reports from other fields often report beneficial (“mitohormetic”) responses to such damage. Here, we test the effects of low (causing no change in lifespan) levels of ultraviolet C (UVC)-induced, irreparable mtDNA damage during early development inCaenorhabditis elegans. This exposure led to life-long reductions in mtDNA copy number and steady-state ATP levels, accompanied by increased oxygen consumption and altered metabolite profiles, suggesting inefficient mitochondrial function. Exposed nematodes were also developmentally delayed, reached smaller adult size, and were rendered more susceptible to subsequent exposure to chemical mitotoxicants. Metabolomic and genetic analysis of key signaling and metabolic pathways supported redox signaling during early development as a mechanism for establishing these persistent alterations. Our results highlight the importance of early-life exposures to environmental pollutants, especially in the context of exposure to chemicals that target mitochondria.
Changes in presynaptic gene expression during homeostatic compensation at a central synapse
Authors: Harrell Evan R. , Pimentel Diogo , Miesenböck Gero 
Published: November 2020

AbstractHomeostatic matching of pre- and postsynaptic function has been observed in many species and neural structures, but whether transcriptional changes contribute to this form of trans-synaptic coordination remains unknown. To identify genes whose expression is altered in presynaptic neurons as a result of perturbing postsynaptic excitability, we applied a transcriptomics-friendly, temperature-inducible Kir2.1-based activity clamp at the first synaptic relay of the Drosophila olfactory system, a central synapse known to exhibit trans-synaptic homeostatic matching. Twelve hours after adult-onset suppression of activity in postsynaptic antennal lobe projection neurons, we detected changes in the expression of many genes in the third antennal segment, which houses the somata of presynaptic olfactory receptor neurons. These changes affected genes with roles in synaptic vesicle release and synaptic remodeling, including several genes implicated in homeostatic plasticity at the neuromuscular junction. At 48 hours and beyond, the transcriptional landscape was tilted toward proteostasis, energy metabolism, and cellular stress defenses, indicating that the system had been pushed to its homeostatic limits. Our data provide insights into the nature of homeostatic compensation at a central synapse and identify many genes engaged in synaptic homeostasis. The presynaptic transcriptional response to genetically targeted postsynaptic perturbations could be exploited for the construction of novel connectivity tracing tools.Significance StatementHomeostatic feedback mechanisms adjust intrinsic and synaptic properties of neurons to keep their average activity levels constant. We show that, at a central synapse in the fruit fly brain, these mechanisms include changes in presynaptic gene expression that are instructed by an abrupt loss of postsynaptic excitability. The trans-synaptically regulated genes have roles in synaptic vesicle release and synapse remodeling; protein synthesis, folding, and degradation; and energy metabolism. Our analysis suggests that similar homeostatic machinery operates at peripheral and central synapses, identifies some of its components, and potentially opens new opportunities for the development of connectivity-based gene expression systems.