bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain-inspired replay for continual learning with artificial neural networks
Authors: van de Ven Gido M. , Siegelmann Hava T. , Tolias Andreas S. 
Published: August 2020

AbstractArtificial neural networks suffer from catastrophic forgetting. Unlike humans, when these networks are trained on something new, they rapidly forget what was learned before. In the brain, a mechanism thought to be important for protecting memories is the reactivation of neuronal activity patterns representing those memories. In artificial neural networks, such memory replay can be implemented as ‘generative replay’, which can successfully – and surprisingly efficiently – prevent catastrophic forgetting on toy examples even in a class-incremental learning scenario. However, scaling up generative replay to complicated problems with many tasks or complex inputs is challenging. We propose a new, brain-inspired variant of replay in which internal or hidden representations are replayed that are generated by the network’s own, context-modulated feedback connections. Our method achieves state-of-the-art performance on challenging continual learning benchmarks (e.g., class-incremental learning on CIFAR-100) without storing data, and it provides a novel model for replay in the brain.
Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites
Authors: Bosc Claudie , Broin Nicolas , Fanjul Marjorie , Saland Estelle , Farge Thomas , Courdy Charly , Batut Aurélie , Masoud Rawand , Larrue Clément , Skuli Sarah , Espagnolle Nicolas , Pagès Jean-Christophe , Carrier Alice , Bost Frédéric , Bertrand-Michel Justine , Tamburini Jérôme , Récher Christian , Bertoli Sarah , Mansat-De Mas Véronique , Manenti Stéphane , Sarry Jean-Emmanuel , Joffre Carine 
Published: August 2020

AbstractAutophagy has been associated with oncogenesis with one of its emerging key functions being its contribution to the metabolism of tumors. Therefore, deciphering the mechanisms of how autophagy supports tumor cell metabolism is essential. Here, we demonstrate that the inhibition of autophagy induces an accumulation of lipid droplets (LD) due to a decrease in fatty acid β-oxidation, that leads to a reduction of oxidative phosphorylation (OxPHOS) in acute myeloid leukemia (AML), but not in normal cells. Thus, the autophagic process participates in lipid catabolism that supports OxPHOS in AML cells. Interestingly, the inhibition of OxPHOS leads to LD accumulation with the concomitant inhibition of autophagy. Mechanistically, we show that the disruption of mitochondria–endoplasmic reticulum (ER) contact sites (MERCs) phenocopies OxPHOS inhibition. Altogether, our data establish that mitochondria, through the regulation of MERCs, controls autophagy that, in turn finely tunes lipid degradation to fuel OxPHOS supporting proliferation and growth in leukemia.
Genome-wide specificity of dCpf1 cytidine base editors
Authors: Kim Daesik , Lim Kayeong , Kim Da-eun , Kim Jin-Soo 
Published: August 2020

AbstractCpf1-linked base editors broaden the targeting scope of programmable cytidine deaminases by recognizing thymidine-rich protospacer-adjacent motifs (PAM) without inducing DNA double-strand breaks (DSBs). Here we present an unbiased in vitro method for identifying genome-wide off-target sites of Cpf1 base editors via whole genome sequencing. First, we treat human genomic DNA with dLbCpf1-BE ribonucleoprotein (RNP) complexes, which convert C-to-U at on-target and off-target sites and, then, with a mixture of E. coli uracil DNA glycosylase (UDG) and DNA glycosylase-lyase Endonuclease VIII, which removes uracil and produces single-strand breaks (SSBs) in vitro. Whole-genome sequencing of the resulting digested genome (Digenome-seq) reveals that, on average, dLbCpf1-BE induces 12 SSBs in vitro per crRNA in the human genome. Off-target sites with an editing frequency as low as 0.1% are successfully identified by this modified Digenome-seq method, demonstrating its high sensitivity. dLbCpf1-BEs and LbCpf1 nucleases often recognize different off-target sites, calling for independent analysis of each tool.
Single-trial cross-area neural population dynamics during long-term skill learning
Authors: Veuthey T. L. , Derosier K. , Kondapavulur S. , Ganguly K. 
Published: August 2020

AbstractMammalian cortex has both local and cross-area connections, suggesting vital roles for both local and cross-area neural population dynamics in cortically-dependent tasks, like movement learning. Prior studies of movement learning have focused on how single-area population dynamics change during short-term adaptation. It is unclear how cross-area dynamics contribute to movement learning, particularly long-term learning and skill acquisition. Using simultaneous recordings of rodent motor (M1) and premotor (M2) cortex and computational methods, we show how cross-area activity patterns evolve during reach-to-grasp learning in rats. The emergence of reach-related modulation in cross-area activity correlates with skill acquisition, and single-trial modulation in cross-area activity predicts reaction time and reach duration. Local M2 neural activity precedes local M1 activity, supporting top–down hierarchy between the regions. M2 inactivation preferentially affects cross-area dynamics and behavior, with minimal disruption of local M1 dynamics. Together, these results indicate that cross-area population dynamics are necessary for learned motor skills.
A hidden gene in astroviruses encodes a viroporin
Authors: Lulla Valeria , Firth Andrew E. 
Published: August 2020

AbstractHuman astroviruses are small non-enveloped viruses with positive-sense single-stranded RNA genomes. Astroviruses cause acute gastroenteritis in children worldwide and have been associated with encephalitis and meningitis in immunocompromised individuals. It is still unknown how astrovirus particles exit infected cells following replication. Through comparative genomic analysis and ribosome profiling we here identify and confirm the expression of a conserved alternative-frame ORF, encoding the protein XP. XP-knockout astroviruses are attenuated and pseudo-revert on passaging. Further investigation into the function of XP revealed plasma and trans Golgi network membrane-associated roles in virus assembly and/or release through a viroporin-like activity. XP-knockout replicons have only a minor replication defect, demonstrating the role of XP at late stages of infection. The discovery of XP advances our knowledge of these important human viruses and opens an additional direction of research into their life cycle and pathogenesis.
FGF2 alters macrophage polarization, tumour immunity and growth and can be targeted during radiotherapy
Authors: Im Jae Hong , Buzzelli Jon N. , Jones Keaton , Franchini Fanny , Gordon-Weeks Alex , Markelc Bostjan , Chen Jianzhou , Kim Jin , Cao Yunhong , Muschel Ruth J. 
Published: August 2020

AbstractRegulation of the programming of tumour-associated macrophages (TAMs) controls tumour growth and anti-tumour immunity. We examined the role of FGF2 in that regulation. Tumours in mice genetically deficient in low-molecular weight FGF2 (FGF2LMW) regress dependent on T cells. Yet, TAMS not T cells express FGF receptors. Bone marrow derived-macrophages from Fgf2LMW−/− mice co-injected with cancer cells reduce tumour growth and express more inflammatory cytokines. FGF2 is induced in the tumour microenvironment following fractionated radiation in murine tumours consistent with clinical reports. Combination treatment of in vivo tumours with fractionated radiation and a blocking antibody to FGF2 prolongs tumour growth delay, increases long-term survival and leads to a higher iNOS+/CD206+ TAM ratio compared to irradiation alone. These studies show for the first time that FGF2 affects macrophage programming and is a critical regulator of immunity in the tumour microenvironment.
Identification of modified peptides using localization-aware open search
Authors: Yu Fengchao , Teo Guo Ci , Kong Andy T. , Haynes Sarah E. , Avtonomov Dmitry M. , Geiszler Daniel J. , Nesvizhskii Alexey I. 
Published: August 2020

AbstractIdentification of post-translationally or chemically modified peptides in mass spectrometry-based proteomics experiments is a crucial yet challenging task. We have recently introduced a fragment ion indexing method and the MSFragger search engine to empower an open search strategy for comprehensive analysis of modified peptides. However, this strategy does not consider fragment ions shifted by unknown modifications, preventing modification localization and limiting the sensitivity of the search. Here we present a localization-aware open search method, in which both modification-containing (shifted) and regular fragment ions are indexed and used in scoring. We also implement a fast mass calibration and optimization method, allowing optimization of the mass tolerances and other key search parameters. We demonstrate that MSFragger with mass calibration and localization-aware open search identifies modified peptides with significantly higher sensitivity and accuracy. Comparing MSFragger to other modification-focused tools (pFind3, MetaMorpheus, and TagGraph) shows that MSFragger remains an excellent option for fast, comprehensive, and sensitive searches for modified peptides in shotgun proteomics data.
Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic
Authors: Worby Colin J. , Chang Hsiao-Han 
Published: August 2020

AbstractThe ongoing novel coronavirus disease (COVID-19) pandemic has already infected millions worldwide and, with no vaccine available, interventions to mitigate transmission are urgently needed. While there is broad agreement that travel restrictions and social distancing are beneficial in limiting spread, recommendations around face mask use are inconsistent. Here, we use mathematical modeling to examine the epidemiological impact of face masks, considering resource limitations and a range of supply and demand dynamics. Even with a limited protective effect, face masks can reduce total infections and deaths, and can delay the peak time of the epidemic. However, random distribution of masks is generally suboptimal; prioritized coverage of the elderly improves outcomes, while retaining resources for detected cases provides further mitigation under a range of scenarios. Face mask use, particularly for a pathogen with relatively common asymptomatic carriage, is an effective intervention strategy, while optimized distribution is important when resources are limited.
Dscam1 establishes the columnar units through lineage-dependent repulsion between sister neurons in the fly brain
Authors: Liu Chuyan , Trush Olena , Han Xujun , Wang Miaoxing , Takayama Rie , Yasugi Tetsuo , Hayashi Takashi , Sato Makoto 
Published: August 2020

AbstractThe brain is organized morphologically and functionally into a columnar structure. According to the radial unit hypothesis, neurons from the same lineage form a radial unit that contributes to column formation. However, the molecular mechanisms that link neuronal lineage and column formation remain elusive. Here, we show that neurons from the same lineage project to different columns under control of Down syndrome cell adhesion molecule (Dscam) in the fly brain. Dscam1 is temporally expressed in newly born neuroblasts and is inherited by their daughter neurons. The transient transcription of Dscam1 in neuroblasts enables the expression of the same Dscam1 splice isoform within cells of the same lineage, causing lineage-dependent repulsion. In the absence of Dscam1 function, neurons from the same lineage project to the same column. When the splice diversity of Dscam1 is reduced, column formation is significantly compromised. Thus, Dscam1 controls column formation through lineage-dependent repulsion.
ACDC, a global database of amphibian cytochrome-b sequences using reproducible curation for GenBank records
Authors: van den Burg Matthijs P. , Herrando-Pérez Salvador , Vieites David R. 
Published: August 2020

AbstractGenetic data are a crucial and exponentially growing resource across all biological sciences, yet curated databases are scarce. The widespread occurrence of sequence and (meta)data errors in public repositories calls for comprehensive improvements of curation protocols leading to robust research and downstream analyses. We collated and curated all available GenBank cytochrome-b sequences for amphibians, a benchmark marker in this globally declining vertebrate clade. The Amphibia’s Curated Database of Cytochrome-b (ACDC) consists of 36,514 sequences representing 2,309 species from 398 genera (median = 2 with 50% interquartile ranges of 1–7 species/genus). We updated the taxonomic identity of >4,800 sequences (ca. 13%) and found 2,359 (6%) conflicting sequences with 84% of the errors originating from taxonomic misidentifications. The database (accessible athttps://doi.org/10.6084/m9.figshare.9944759) also includes anRscript to replicate our study for other loci and taxonomic groups. We provide recommendations to improve genetic-data quality in public repositories and flag species for which there is a need for taxonomic refinement in the face of increased rate of amphibian extinctions in the Anthropocene.
Impact of low-intensity pulsed ultrasound on transcription and metabolite compositions in proliferation and functionalization of human adipose-derived mesenchymal stromal cells
Authors: Huang Denggao , Gao Yuanhui , Wang Shunlan , Zhang Wei , Cao Hui , Zheng Linlin , Chen Yang , Zhang Shufang , Chen Jie 
Published: August 2020

AbstractTo investigate the effect of low-intensity pulsed ultrasound (LIPUS) on the proliferation of human adipose-derived mesenchymal stromal cells (hASCs) and uncovered its stimulation mechanism. LIPUS at 30 mW/cm2 was applied for 5 min/day to promote the proliferation of hASCs. Flow cytometry was used to study the cell surface markers, cell cycle, and apoptosis of hASCs. The proliferation of hASCs was detected by cell counting kit-8, cell cycle assay, and RT-PCR. The expression of hASCs cytokines was determined by ELISA. The differences between transcriptional genes and metabolites were analyzed by transcript analysis and metabolomic profiling experiments. The number of cells increased after LIPUS stimulation, but there was no significant difference in cell surface markers. The results of flow cytometry, RT-PCR, and ELISA after LIPUS was administered showed that the G1 and S phases of the cell cycle were prolonged. The expression of cell proliferation related genes (CyclinD1 and c-myc) and the paracrine function related gene (SDF-1α) were up-regulated. The expression of cytokines was increased, while the apoptosis rate was decreased. The results of transcriptome experiments showed that there were significant differences in 27 genes;15 genes were up-regulated, while 12 genes were down-regulated. The results of metabolomics experiments showed significant differences in 30 metabolites; 7 metabolites were up-regulated, and 23 metabolites were down-regulated. LIPUS at 30 mW/cm2 intensity can promote the proliferation of hASCs cells in an undifferentiating state, and the stem-cell property of hASCs was maintained. CyclinD1 gene, c-myc gene, and various genes of transcription and products of metabolism play an essential role in cell proliferation. This study provides an important experimental and theoretical basis for the clinical application of LIPUS in promoting the proliferation of hASCs cells.
Time-dependent branching processes: a model of oscillating neuronal avalanches
Authors: Pausch Johannes , Garcia-Millan Rosalba , Pruessner Gunnar 
Published: August 2020

AbstractRecently, neuronal avalanches have been observed to display oscillations, a phenomenon regarded as the co-existence of a scale-free behaviour (the avalanches close to criticality) and scale-dependent dynamics (the oscillations). Ordinary continuous-time branching processes with constant extinction and branching rates are commonly used as models of neuronal activity, yet they lack any such time-dependence. In the present work, we extend a basic branching process by allowing the extinction rate to oscillate in time as a new model to describe cortical dynamics. By means of a perturbative field theory, we derive relevant observables in closed form. We support our findings by quantitative comparison to numerics and qualitative comparison to available experimental results.
Autophagy is a pro-survival adaptive response to heat shock in bovine cumulus-oocyte complexes
Authors: Latorraca Lais B. , Feitosa Weber B. , Mariano Camila , Moura Marcelo T. , Fontes Patrícia K. , Nogueira Marcelo F. G. , Paula-Lopes Fabíola F. 
Published: August 2020

AbstractAutophagy is a physiological mechanism that can be activated under stress conditions. However, the role of autophagy during oocyte maturation has been poorly investigated. Therefore, this study characterized the role of autophagy on developmental competence and gene expression of bovine oocytes exposed to heat shock (HS). Cumulus-oocyte-complexes (COCs) were matured at Control (38.5 °C) and HS (41 °C) temperatures in the presence of 0 and 10 mM 3-methyladenine (3MA; autophagy inhibitor). Western blotting analysis revealed that HS increased autophagy marker LC3-II/LC3-I ratio in oocytes. However, there was no effect of temperature for oocytes matured with 3MA. On cumulus cells, 3MA reduced LC3-II/LC3-I ratio regardless of temperature. Inhibition of autophagy during IVM of heat-shocked oocytes (3MA-41 °C) reduced cleavage and blastocyst rates compared to standard in vitro matured heat-shocked oocytes (IVM-41 °C). Therefore, the magnitude of HS detrimental effects was greater in the presence of autophagy inhibitor. Oocyte maturation under 3MA-41 °C reduced mRNA abundance for genes related to energy metabolism (MTIF3), heat shock response (HSF1), and oocyte maturation (HAS2 and GREM1). In conclusion, autophagy is a stress response induced on heat shocked oocytes. Inhibition of autophagy modulated key functional processes rendering the oocyte more susceptible to the deleterious effects of heat shock.
Mycoplasma hyopneumoniae J elicits an antioxidant response and decreases the expression of ciliary genes in infected swine epithelial cells
Authors: Mucha Scheila G. , Ferrarini Mariana G. , Moraga Carol , Di Genova Alex , Guyon Laurent , Tardy Florence , Rome Sophie , Sagot Marie-France , Zaha Arnaldo 
Published: August 2020

AbstractMycoplasma hyopneumoniaeis the most costly pathogen for swine production. Although several studies have focused on the host-bacterium association, little is known about the changes in gene expression of swine cells upon infection. To improve our understanding of this interaction, we infected swine epithelial NPTr cells withM. hyopneumoniaestrain J to identify differentially expressed mRNAs and miRNAs. The levels of 1,268 genes and 170 miRNAs were significantly modified post-infection. Up-regulated mRNAs were enriched in genes related to redox homeostasis and antioxidant defense, known to be regulated by the transcription factor NRF2 in related species. Down-regulated mRNAs were enriched in genes associated with cytoskeleton and ciliary functions. Bioinformatic analyses suggested a correlation between changes in miRNA and mRNA levels, since we detected down-regulation of miRNAs predicted to target antioxidant genes and up-regulation of miRNAs targeting ciliary and cytoskeleton genes. Interestingly, most down-regulated miRNAs were detected in exosome-like vesicles suggesting thatM. hyopneumoniaeinfection induced a modification of the composition of NPTr-released vesicles. Taken together, our data indicate thatM. hyopneumoniaeelicits an antioxidant response induced by NRF2 in infected cells. In addition, we propose that ciliostasis caused by this pathogen is partially explained by the down-regulation of ciliary genes.
Comprehensive retinal vascular measurements: a novel association with renal function in type 2 diabetic patients in China
Authors: Xu Xiayu , Sun Fei , Wang Qiong , Zhang Maiye , Ding Wenxiang , Yang Aili , Gao Bin 
Published: August 2020

AbstractTo examine the association between various retinal vascular measurements and microalbuminuria in patients with type 2 diabetes in a northwestern China study. Data from 911 patients with type 2 diabetes were analyzed. Novel retinal vascular measurements from the whole vascular tree were extracted using a validated fully automatic computer program. Retinal vascular measurements were analyzed continuously and categorically for associations with microalbuminuria using multiple logistic regressions, adjusted for related variables. In logistic regression adjusting for multiple variables, microalbuminuria was associated with smaller peripheral arteriolar caliber, larger peripheral venular caliber, larger arteriolar tortuosity, and smaller arteriolar fractal dimension (p = 0.028, p < 0.001, p = 0.038, p = 0.035, respectively). In further categorical analyses, microalbuminuria was related to smaller peripheral arteriolar caliber [T1 vs. T3: odds ratio (OR) 2.029; 95% confidence interval (CI) 1.186–3.473], larger peripheral venular caliber (T1 vs. T3: OR 0.609; 95% CI 0.362–1.024), and smaller arteriolar fractal dimension (T1 vs. T3: OR 1.659; 95% CI 1.028–2.675). Microalbuminuria in type 2 diabetes is associated with both retinal vascular caliber and geometry. These noninvasive vascular measurements serve as potential preclinical markers to identify populations at high risk of early kidney disease in the course of diabetes.
Effect of cereal fermentation and carbohydrase supplementation on growth, nutrient digestibility and intestinal microbiota in liquid-fed grow-finishing pigs
Authors: Torres-Pitarch Alberto , Gardiner Gillian E. , Cormican Paul , Rea Mary , Crispie Fiona , O’Doherty John V. , Cozannet Pierre , Ryan Tomas , Cullen James , Lawlor Peadar G. 
Published: August 2020

AbstractThis study aimed to determine the impact of fermenting the cereal fraction of the diet (Cferm) and enzyme supplementation (ENZ) on the bacterial composition of the feed, nutrient digestibility, pig growth, feed efficiency (FE), intestinal volatile fatty acid (VFA) concentrations and intestinal microbiota composition. A total of 252 grow-finisher pigs (~ 40.4 kg; 7 pigs/pen) were randomly allocated to 4 diets in a 2 × 2 factorial arrangement for 55d. The diets were: (1) fresh liquid feed (Fresh); (2) Cferm liquid feed (Ferm); (3) Fresh + ENZ and (4) Ferm + ENZ. Cferm increased total tract nutrient digestibility, reduced caecal butyrate and propionate concentrations, and increased average daily gain (ADG). ENZ increased ileal and total tract nutrient digestibility, reduced caecal isobutyrate and propionate concentrations, and improved FE. Bacterial taxa positively correlated with pig growth (Lactobacillus kisonensis in the ileum and Roseburia faecis in the caecum) were more abundant in pigs fed ENZ diets, whereas most of the ileal bacterial taxa negatively correlated with growth (Megasphaera, Bifidobacterium and Streptococcus) had lower abundance in pigs fed Cferm diets. In conclusion, Cferm increased ADG and ENZ improved FE, with these improvements possibly mediated by increased nutrient digestibility, and beneficial modulation of the intestinal microbiota.