bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrogel-coating improves the in-vivo stability of electrochemical aptamer-based biosensors
Authors: Li Shaoguang , Dai Jun , Zhu Man , Arroyo-Currás Netzahualcóyotl , Li Hongxing , Wang Yuanyuan , Wang Quan , Lou Xiaoding , Kippin Tod E. , Wang Shixuan , Plaxco Kevin W. , Li Hui , Xia Fan 
Published: November 2020

AbstractThe ability to track the levels of specific molecules, such as drugs, metabolites, and biomarkers, in the living body, in real time and for long durations would improve our understanding of health and our ability to diagnose, treat and monitor disease. To this end, we are developing electrochemical aptamer-based (E-AB) biosensors, a general platform supporting high-frequency, real-time molecular measurements in the living body. Here we report that the addition of an agarose hydrogel protective layer to E-AB sensors significantly improves their baseline stability when deployed in the complex, highly time-varying environments found in vivo. The improved stability is sufficient that these hydrogel-protected sensors achieved good baseline stability when deployed in situ in the veins, muscles, bladder, or tumors of living rats without the use of the drift correction approaches traditionally required in such placements. Finally, this improved stability is achieved without any significant, associated “costs” in terms of detection limits, response times, or biocompatibility.
Predicting potential impacts of ocean acidification on marine calcifiers from the Southern Ocean
Authors: Figuerola Blanca , Hancock Alyce M. , Bax Narissa , Cummings Vonda , Downey Rachel , Griffiths Huw J. , Smith Jodie , Stark Jonathan S. 
Published: November 2020

AbstractUnderstanding the vulnerability of marine calcifiers to ocean acidification is a critical issue, especially in the Southern Ocean (SO), which is likely to be the one of the first, and most severely affected regions. Since the industrial revolution, ~30% of anthropogenic CO2has been absorbed by the oceans. Seawater pH levels have already decreased by 0.1 and are predicted to decline by ~ 0.3 by the year 2100. This process, known as ocean acidification (OA), is shallowing the saturation horizon, which is the depth below which calcium carbonate (CaCO3) dissolves, likely increasing the vulnerability of many marine calcifiers to dissolution. The negative impact of OA may be seen first in species depositing more soluble CaCO3mineral phases such as aragonite and high-Mg calcite (HMC). These negative effects may become even exacerbated by increasing sea temperatures. Here we combine a review and a quantitative meta-analysis to provide an overview of the current state of knowledge about skeletal mineralogy of major taxonomic groups of SO marine calcifiers and to make predictions about how OA might affect different taxa. We consider their geographic range, skeletal mineralogy, biological traits and potential strategies to overcome OA. The meta-analysis of studies investigating the effects of the OA on a range of biological responses such as shell state, development and growth rate shows response variation depending on mineralogical composition. Species-specific responses due to mineralogical composition suggest taxa with calcitic, aragonitic and HMC skeletons may be more vulnerable to the expected carbonate chemistry alterations, and low magnesium calcite (LMC) species may be mostly resilient. Environmental and biological control on the calcification process and/or Mg content in calcite, biological traits and physiological processes are also expected to influence species specific responses.
HOX13-MEDIATEDDBX2REGULATION IN LIMBS SUGGESTS INTER-TAD SHARING OF ENHANCERS
Authors: Beccari Leonardo , Jaquier Gabriel , Lopez-Delisle Lucille , Rodriguez-Carballo Eddie , Mascrez Bénédicte , Gitto Sandra , Woltering Joost , Duboule Denis 
Published: November 2020

ABSTRACTBackgroundDuring tetrapod limb development, the HOXA13 and HOXD13 transcription factors are critical for the emergence and organization of the autopod, the most distal aspect where digits will develop. Since previous work had suggested that theDbx2gene is a target of these factors, we set up to analyze in detail this potential regulatory interaction.ResultsWe show that HOX13 proteins bind to eutherian-specific sequences at the vicinity of theDbx2locus that have enhancer activity in developing digits. However, the functional inactivation of the DBX2 protein did not elicit any particular phenotype related toHoxgenes inactivation in digits, suggesting either redundant or compensatory mechanisms. We report that the neighboringNell2andAno6genes are also expressed in distal limb buds and are, in part, controlled by the sameDbx2enhancers despite being localized into two different topologically associating domains (TADs) flanking theDbx2locus.ConclusionsWe conclude thatHoxa13andHoxdgenes cooperatively activateDbx2expression in developing digits through binding to eutherian specific regulators elements in theDbx2neighborhood. Furthermore, these enhancers can overcome TAD boundaries in either direction to co-regulate a set of genes located in distinct chromatin domains.Bullet pointsHoxa13andHoxdgenes cooperatively regulateDbx2expression in developing digits via eutherian specific enhancers.Dbx2is expressed in different digit joint precursors but its function there is not essential.Dbx2enhancers also control the expression of theNell2andAno6genes, which are located in different TADs, thus overcoming the boundary effect.Dbx2chromatin architecture and enhancers evolved in the mammalian lineage.Grant Sponsor and NumberSwiss National Research Foundation #310030B_138662.European Research Council grants RegulHox#588029
Threat-induced hippocampal connectivity fingerprints do not generalize to psychosocial stress
Authors: Kühnel Anne , Czisch Michael , Sämann Philipp G. ,   BeCOME study team, Binder Elisabeth B. , Kroemer Nils B. 
Published: November 2020

AbstractStress is an everyday experience and maladaptive responses play a crucial role in the etiology of affective disorders. Despite its ubiquity, the neural underpinnings of subjective stress experiences have not yet been elucidated, particularly at an individual level. In an important advance, Goldfarb et al.1showed recently that subjective stress and arousal levels in response to threatening stimuli were successfully predicted based on changes in hippocampal connectivity during the task using a machine learning approach. Crucially, stress responses were predicted by interpretable hippocampal connectivity networks, shedding new light on the role of the hippocampus in regulating stress reactivity2. However, the authors induced stress by displaying aversive pictures, while stress research often relies on the extensively validated Trier social stress task (TSST)3. The TSST incorporates crucial factors such as unpredictability of success and the social-evaluative threat of the stressor thereby eliciting cortisol responses more robustly compared to threatening images4. Towards generalization, cross validation within a sample as conducted by Goldfarb et al.1or independent replications are important steps, but the generalizability to different stressors allows to draw broader conclusions about the potential use of hippocampal connectivity to predict subjective stress5. Arguably, translating these findings to clinical applications would require a broad generalization of the results or the prediction algorithm to psychosocial stress. Here, we assessed the predictive performance of Goldfarb et al’s1algorithm for subjective stress in an independent sample using an MR adaption of the TSST6,7. In line with Goldfarb et al.1, we observed robust stress-induced changes in hippocampal connectivity. However, the spatial correlation of the changes in connectivity was low indicating little convergence across alleged stress paradigms. Critically, stress-induced changes of hippocampal connectivity were not robustly predictive of subjective stress across a multiverse of analyses based on connectivity changes. Collectively, this indicates that the generalizability of the reported stress connectivity fingerprint to other stressors is limited at best, suggesting that specific tasks might require tailored algorithms to robustly predict stress above chance levels.
Disclosing the actual efficiency of G-quadruplex-DNA–disrupting small molecules
Authors: Mitteaux Jérémie , Lejault Pauline , Pirrotta Marc , Wojciechowski Filip , Joubert Alexandra , Desbois Nicolas , Gros Claude P. , Hudson Robert H. E. , Boulé Jean-Baptiste , Granzhan Anton , Monchaud David 
Published: November 2020

AbstractThe quest for small molecules that avidly bind to G-quadruplex-DNA (G4-DNA, or G4), so called G4-ligands, has invigorated the G4 research field from its very inception. Massive efforts have been invested toi- screen or design G4-ligands,ii- evaluate their G4-interacting propertiesin vitrothrough a series of now widely accepted and routinely implemented assays, andiii- use them as unique chemical biology tools to interrogate cellular networks that might involve G4s. In sharp contrast, only uncoordinated efforts at developing small molecules aimed at destabilizing G4s have been invested to date, even though it is now recognized that such molecular tools would have tremendous application to neurobiology as many genetic and age-related diseases are caused by an over-representation of G4s, itself caused by a deficiency of G4-resolving enzymes, the G4-helicases. Herein, we report on our double effort toi- develop a reliablein vitroassay to identify molecules able to destabilize G4s, the G4-unfold assay, andii- fully characterize the first prototype of G4-disrupting small molecule, a phenylpyrrolcytosine (PhpC)-based G-clamp analog.
Comparative analysis of antibody- and lipid-based multiplexing methods for single-cell RNA-seq
Authors: Mylka Viacheslav , Aerts Jeroen , Matetovici Irina , Poovathingal Suresh , Vandamme Niels , Seurinck Ruth , Hulselmans Gert , Van Den Hoecke Silvie , Wils Hans , Reumers Joke , Van Houdt Jeroen , Aerts Stein , Saeys Yvan 
Published: November 2020

ABSTRACTMultiplexing of samples in single-cell RNA-seq studies allows significant reduction of experimental costs, straightforward identification of doublets, increased cell throughput, and reduction of sample-specific batch effects. Recently published multiplexing techniques using oligo-conjugated antibodies or - lipids allow barcoding sample-specific cells, a process called ‘hashing’. Here, we compare the hashing performance of TotalSeq-A and -C antibodies, custom synthesized lipids and MULTI-seq lipid hashes in four cell lines, both for single-cell RNA-seq and single-nucleus RNA-seq. Hashing efficiency was evaluated using the intrinsic genetic variation of the cell lines. Benchmarking of different hashing strategies and computational pipelines indicates that correct demultiplexing can be achieved with both lipid- and antibody-hashed human cells and nuclei, with MULTISeqDemux as the preferred demultiplexing function and antibody-based hashing as the most efficient protocol on cells. Antibody hashing was further evaluated on clinical samples using PBMCs from healthy and SARS-CoV-2 infected patients, where we demonstrate a more affordable approach for large single-cell sequencing clinical studies, while simultaneously reducing batch effects.
Establishment and characterisation of primary skeletal muscle cell cultures from patients with advanced Chronic Kidney Disease
Authors: Baker Luke A , O’Sullivan Tom F , Robinson Kate A , Redshaw Zoe , Graham-Brown Matthew , Ashford Robert U , Smith Alice C , Philp Andrew , Watson Emma L 
Published: November 2020

AbstractSkeletal muscle wasting and dysfunction is a common characteristic of non-dialysis dependent chronic kidney disease (NDD-CKD). The mechanisms by which this occurs are not clearly understood and one reason for this is a lack of well controlledin-vitromethodologies to simulate NDD-CKD induced muscle wasting for mechanistic investigation at the cellular level. Here we sought to conduct the initial investigations into developing a CKD-induced skeletal muscle model for use as a mechanistic analysis tool as well as a test bed for potential novel therapeutics in this population. Human derived muscle cells (HDMCs) were isolated from n=5 NDD-CKD patients and n=3 matched healthy controls (HC) and taken through proliferation and differentiation phases in cell culture. Upon comparison of the 2 donor types, significantly greater mRNA expression of myogenic markers was noted in the NDD-CKD cultures in comparison to HC cultures, which was carried through to greater mRNA expression of myosin heavy chains (MyHCs) post differentiation. However, this was not carried over to protein expression where Pax7 and MyoD were seen to be expressed to a greater extent in HC cultures. mRNA expression markers of protein degradation were noted to be elevated in NDD-CKD cultures in comparison to HC cultures. In light of our findings, future work should seek to investigate the role of the ‘CKD environment’ as well as mechanisms implicated in transcription regulation to further advance the current model development as well as the mechanistic understanding of skeletal muscle wasting in CKD.
Biomolecular Condensation Drives Leukemia Caused by NUP98-Fusion Proteins
Authors: Terlecki-Zaniewicz Stefan , Eder Thomas , Schmöllerl Johannes , Humer Theresa , Kuchynka Natalie , Parapatics Katja , Heyes Elizabeth , Liberante Fabio G. , Müller André C. , Grebien Florian 
Published: November 2020

AbstractNUP98-fusion proteins cause acute myeloid leukemia via unknown molecular mechanisms. All NUP98-fusion proteins share an intrinsically disordered region (IDR) featuring >35 repeats of Phenylalanine-Glycine (FG) in the NUP98 N-terminus. Conversely, different C-terminal NUP98-fusion partners are often transcriptional and epigenetic regulators. Given these structural features we hypothesized that mechanisms of oncogenic transformation by NUP98-fusion proteins are hard-wired in their protein interactomes. Affinity purification coupled to mass spectrometry of five distinct NUP98-fusion proteins revealed a conserved set of interactors that was highly enriched for proteins involved in biomolecular condensation. We developed biotinylated isoxazole-mediated condensome mass spectrometry (biCon-MS) to show that NUP98-fusion proteins alter the global composition of biomolecular condensates. In addition, an artificial FG-repeat containing fusion protein was able to phenocopy the induction of leukemic gene expression as mediated by NUP98-KDM5A. Thus, we propose that IDR-containing fusion proteins have evolved to uniquely combine biomolecular condensation with gene control to induce cancer.AML, NUP98, fusion protein, AP-MS, LLPS, biCon-MS, condensate
Incidence and Risk Factors of Combined-Antiretroviral Therapy-Induced Hepatotoxicity among HIV Patients at the Bali District Hospital, Cameroon
Authors: Ngah Yayah Emerencia , Cho Frederick Nchang , Etagha Bisong Shauna , Fusi Neh Gladys , Francisca Neba , Ikomey Mondinde George , Ibrahim Njimona 
Published: November 2020

AbstractIntroductionThe incidence of hepatotoxicity is life-threatening and can result to an end-stage liver disease in long-term patients on combined antiretroviral therapy (cART). Our study sought to evaluate the incidence and predictors of cART-induced hepatotoxicity (CIH) among long term users on cART in a rural District hospital.MethodsThis was a hospital-based cross-sectional study in the Bali District Hospital. Spectrophotometric method was use for the quantitative measurement of alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) levels. Patients with elevations of both ALT and AST were considered CIH. The Chi (χ2) square test, ANOVA and Kaplan Meier log-ranked/ survival analyses were used to analyse the data.ResultsOf the 350 participants enrolled [156 (44.6%) males and 194 (55.4%) females], aged 43.87 ± 0.79 years (range 20 – 84 years) included in this analysis, 26 (4.4%) experienced moderate CIH. We observed 57 (16.3%), 62 (17.7%) and 238 (68%) elevated levels ALT + AST, ALT and AST respectively. Two independent predictive factors of CIH were, the male sex and alcoholism during the study period.ConclusionThe prevalence of CIH in HIV-infected patients in Bali was lower than that observed in previous studies. The duration of therapy had no influence on the frequency of CIH. Alcoholism and smoking showed significant differences in the development of CIH.
Apoptotic Cells May Drive Cell Death in Hair Follicles During their Regression Cycle
Authors: Keister Bradley D. , Mesa Kailin R. , Blagoev Krastan B. 
Published: November 2020

AbstractIntravital microscopy in live mice have shown that the elimination of epithelial cells during hair follicle regression involves supra-basal cell differentiation and basal cell apoptosis through synergistic action of TGF-β (transforming growth factor) and mesenchymal-epithelial interactions. In this process the basal epithelial cells are not internally committed to death and the mesenchymal dermal papilla (DP) plays essential role in death induction. Because the DP cells are not necessary for completion of the cycle but only for its initiation it is still an open question what is the mechanism leading to the propagation of apoptosis towards the “immortal” stem cell population. Here, we use a quantitative analysis of the length of hair follicles during their regression cycle. The data is consistent with a propagation mechanism driven by apoptotic cells inducing apoptosis in their neighboring cells. The observation that the apoptosis slows down as the apoptotic front approaches the stem cells at the end of the follicle is consistent with a gradient of a pro-survival signal sent by these stem cells. An experiment that can falsify this mechanism is proposed.
Agricultural production and CO2 emissions causes in the developing and developed countries: New insights from quantile regression and decomposition analysis
Authors: Khan Rabnawaz 
Published: November 2020

AbstractAgriculture is the dominant economic activity of the economies. The developing and developed countries are responsible for the most greenhouse gasses emitted in the developing areas. Are there heterogeneous determinants of environmental degradation and CO2 emitters in developing and developed countries? and estimating the significance of agricultural production, renewable energy consumption, the industrial revolution, and economic growth. In this study, 22 countries’ environmental degradation analyze by two (per-capita and liquid) sources of CO2 emissions and using panel data from 1991 through 2016. This study adopts a panel regression (non-additive effects) and quantile regression techniques to explore the connection between agriculture and economic factors. And the extent of the CO2 emitter gap between developing and developed countries. The outcome of agriculture has a positive and significant influence on CO2 emission from liquid with a 36.75% increase in environmental degradation and a negative impact on CO2 emission in the total emissions by 19.12%. The agriculture-related activities negatively influence the environment, such as deforestation for feed cropping, burning of biomass, and deep soil cropping in the developing countries. Furthermore, the quantiles decomposition procedure in agriculture production is signifying heterogeneity of the determinants of environmental degradation, low and high CO2 emitters.
ARID1A regulates R-loop associated DNA replication stress
Authors: Tsai Shuhe , Chang Emily Yun-chia , Fournier Louis-Alexandre , Wells James P. , Minaker Sean W. , Zhu Yi Dan , Wang Alan Ying-Hsu , Wang Yemin , Huntsman David G. , Stirling Peter C. 
Published: November 2020

ABSTRACTARID1A is lost in up to 7% of all cancers, and this frequency increases in certain cancer types, such as clear cell ovarian carcinoma where ARID1A protein is lost in about 50% of cases. While the impact of ARID1A loss on the function of the BAF chromatin remodeller complexes is likely to drive oncogenic gene expression programs in specific contexts, ARID1A also binds genome stability regulators such as ATR and TOP2. Here we show that ARID1A loss leads to DNA replication stress associated with R-loops and transcription-replication conflicts in human cells. These effects correlate with altered transcription and replication dynamics in ARID1A knockout cells and to reduced TOP2A binding at R-loop sites. Together this work extends mechanisms of replication stress in ARID1A deficient cells with implications for targeting ARID1A deficient cancers.
Selection for Decreased BRCA2 Functional Activity inHomo sapiensAfter Divergence from the Chimpanzee-Human Last Common Ancestor
Authors: Huang Jinlong , Zhong Yi , Makohon-Moore Alvin P. , White Travis , Jasin Maria , Norell Mark A. , Wheeler Ward C. , Iacobuzio-Donahue Christine A. 
Published: November 2020

AbstractHumans have an increased incidence of epithelial neoplasia compared to non-human primates. We performed a comparative analysis of 21 non-human primate genomes and 54 ancient human genomes to identify variations in known cancer genes that may explain this difference. We identified 299 human-specific fixed non-silent single nucleotide polymorphisms. Bioinformatics analyses for functional consequences identified a number of variants predicted to have altered protein function, one of which was located at the most evolutionarily conserved domain of human BRCA2. This variant, in which a polar threonine residue replaces a hydrophobic methionine residue to codon 2662 within the DSS1 binding domain, decreases the interactions of BRCA2 with other proteins, specifically the binding of BRCA2 and RAD51, as well as the repairing ability of cells for DNA double-strand breaks. We conclude that a 20% reduction in BRCA2 DNA repair ability was positively selected for in the course of human evolution.One Sentence SummaryReduction of BRCA2 functional activity has been selected for during human evolution since the chimpanzee-human last common ancestor.
Transmission of SARS-CoV-2 from humans to animals and potential host adaptation
Authors: Tan Cedric C.S. , Lam Su Datt , Richard Damien , Owen Christopher , Berchtold Dorothea , Orengo Christine , Nair Meera Surendran , Kuchipudi Suresh V. , Kapur Vivek , van Dorp Lucy , Balloux François 
Published: November 2020

AbstractSARS-CoV-2, the agent of the COVID-19 pandemic, can infect a wide range of mammals. Since its spread in humans, secondary host jumps of SARS-CoV-2 from humans to a variety of domestic and wild populations of mammals have been documented. The evolution of SARS-CoV-2 in different host species is of fundamental interest while also providing indication of how SARS-CoV-2 may have adapted to human hosts soon after the initial host jump, a time window for which there are no genome sequences available. Moreover, the study of SARS-CoV-2 circulating in animals is critical to assess the risk that the transmission of animal-adapted viral lineages back into humans (i.e., spillback) may pose. Here, we compared the genomic landscapes of SARS-CoV-2 isolated from animal species relative to that in humans, profiling the mutational biases indicative of potentially different selective pressures in animals. We focused on viral genomes collected in infected mink (Neovison vison) and white-tailed deer (Odocoileus virginianus) for which reports of multiple independent spillover events and subsequent animal-to-animal transmission are available. We identified six candidate mutations for animal-specific adaptation in mink (NSP9_G37E, Spike_F486L, Spike_N501T, Spike_Y453F, ORF3a_T229I, ORF3a_L219V), and one in deer (NSP3a_L1035F), though these mutations appear to confer minimal advantage for circulation in humans. Additionally, circulation of SARS-CoV-2 in mink and deer has not caused considerable changes to the evolutionary trajectory of SARS-CoV-2 thus far. Finally, our results suggest that minimal adaptation was required for human-to-animal spillover and subsequent onward transmission in mink and deer, highlighting the ‘generalist’ nature of SARS-CoV-2 as a pathogen of mammalian hosts.