bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Variable Clock Underlies Internally Generated Hippocampal Sequences
Authors: Deng Xinyi , Chen Shizhe , Sosa Marielena , Karlsson Mattias P. , Wei Xue-Xin , Frank Loren M. 
Published: April 2020

AbstractHumans have the ability to store and retrieve memories with various degrees of specificity, and recent advances in reinforcement learning have identified benefits to learning when past experience is represented at different levels of temporal abstraction. How this flexibility might be implemented in the brain remains unclear. We analyzed the temporal organization of rat hippocampal population spiking to identify potential substrates for temporally flexible representations. We examined activity both during locomotion and during memory-associated population events known as sharp wave-ripples (SWRs). We found that spiking during SWRs is rhythmically organized with higher event-to-event variability than spiking during locomotion-associated population events. Decoding analyses using clusterless methods further indicate that similar spatial experience can be replayed in multiple SWRs, each time with a different rhythmic structure whose periodicity is sampled from a lognormal distribution. This variability increases with experience despite the decline in SWR rates that occurs as environments become more familiar. We hypothesize that the variability in temporal organization of hippocampal spiking provides a mechanism for storing experiences with various degrees of specificity.
MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes
Authors: Chelakkot Vipin Shankar , Liu Kaiwen , Yoshioka Ema , Saha Shaykat , Xu Danyang , Licursi Maria , Dorward Ann , Hirasawa Kensuke 
Published: April 2020

AbstractThe efficacy of aminolevulinic acid (5-ALA)-based photodynamic diagnosis (5-ALA-PDD) and photodynamic therapy (5-ALA-PDT) is dependent on the 5-ALA-induced cancer-specific accumulation of protoporphyrin IX (PpIX). We previously reported that inhibition of oncogenic Ras/MEK increases PpIX accumulation in cancer cells by reducing PpIX efflux through ATP-binding cassette sub-family B member 1 (ABCB1) as well as PpIX conversion to heme by ferrochelatase (FECH). Here, we sought to identify the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation via ABCB1 and FECH. First, we demonstrated that Ras/MEK activation reduced PpIX accumulation in RasV12-transformed NIH3T3 cells and HRAS transgenic mice. Knockdown of p90 ribosomal S6 kinases (RSK) 2, 3, or 4 increased PpIX accumulation in the RasV12-transformed NIH3T3 cells. Further, treatment with an RSK inhibitor reduced ABCB1 expression and increased PpIX accumulation. Moreover, HIF-1α expression was reduced when the RasV12-transformed NIH3T3 cells were treated with a MEK inhibitor, demonstrating that HIF-1α is a downstream element of MEK. HIF-1α inhibition decreased the activity of FECH and increased PpIX accumulation. Finally, we demonstrated the involvement of RSKs and HIF-1α in the regulation of PpIX accumulation in human cancer cell lines (DLD-1, SNB-75, Hs 578T, and MDA MB 231). These results demonstrate that the RSK-ABCB1 and HIF-1α-FECH axes are the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation.
Establishment of a Human Induced Pluripotent Stem Cell-Derived Neuromuscular Co-Culture Under Optogenetic Control
Authors: Swartz Elliot W. , Shintani Greg , Wan Jijun , Maffei Joseph S. , Wang Sarah H. , Miller Bruce L. , Havton Leif A. , Coppola Giovanni 
Published: April 2020

SummaryThe failure of the neuromuscular junction (NMJ) is a key component of degenerative neuromuscular disease, yet how NMJs degenerate in disease is unclear. Human induced pluripotent stem cells (hiPSCs) offer the ability to model disease via differentiation toward affected cell types, however, the re-creation of anin vitroneuromuscular system has proven challenging. Here we present a scalable, all-hiPSC-derived co-culture system composed of independently derived spinal motor neurons (MNs) and skeletal myotubes (sKM). In a model ofC9orf72-associated disease, co-cultures form functional NMJs that can be manipulated through optical stimulation, eliciting muscle contraction and measurable calcium flux in innervated sKM. Furthermore, co-cultures grown on multi-electrode arrays (MEAs) permit the pharmacological interrogation of neuromuscular physiology. Utilization of this co-culture model as a tunable, patient-derived system may offer significant insights into NMJ formation, maturation, repair, or pathogenic mechanisms that underlie NMJ dysfunction in disease.
Using seedling phenotypic traits to select local seed sources for large-scale restoration: methods and outcomes in a Great Basin case study
Authors: Leger Elizabeth A. , Barga Sarah , Agneray Alison C. , Baughman Owen , Burton Robert , Williams Mark 
Published: April 2020

AbstractEstablishing plants from seed is often a limitation to restoration success in semi-arid systems. For restoration purposes, managers can either use widely-available commercial seeds, which are often sourced from far outside the seeding area, or take extra steps to use locally collected seeds. If local seeds have traits more conducive to seedling establishment in degraded sites, they could increase restoration success. Here, we asked whether wild-collected seeds of two native perennial grasses,Elymus elymoidesandPoa secunda, had more favorable characteristics than commercial sources. Seeds were collected from four populations within the Winnemucca District of the Nevada Bureau of Land Management, which manages lands within the Great Basin, US. Collections were screened for seed and seedling characteristics associated with increased plant performance in invaded Great Basin systems, and we provide a detailed methodology for these measurements. Relative to commercial seeds, wild-collected seeds had more characteristics identified as beneficial for seedling establishment including earlier emergence, higher specific root length, more root tips, and smaller overall size (E. elymoides), and earlier emergence, longer roots, higher root mass ratio, and more root tips (P. secunda). Commercial sources had significantly larger seeds than wild populations, a trait that had mixed effects on performance in previous research, and one that may change as wild collections are increased in agronomic conditions. These results suggest that locally-sourced populations are more likely to perform well in invaded areas, providing support for efforts to collect, screen, and increase local sources of seeds to improve restoration success.Implications for PracticeCollecting and increasing local seeds requires more time and effort than purchasing commercially-available seeds, but if these sources have a greater chance at surviving in restoration sites, this effort is warrantedIn our study, remnant local populations possessed more potentially adaptive traits than commercially-available alternatives, indicating they may be superior sources for the restoration of disturbed sites in their local regionsScreening multiple seed sources for potentially adaptive seed and seedling traits can be a relatively quick and effective way to select the most promising seeds for increase
Predicting Tumor Cell Response to Synergistic Drug Combinations Using a Novel Simplified Deep Learning Model
Authors: Zhang Heming , Feng Jiarui , Zeng Amanda , Payne Philip , Li Fuhai 
Published: April 2020

AbstractDrug combinations targeting multiple targets/pathways are believed to be able to reduce drug resistance. Computational models are essential for novel drug combination discovery. In this study, we proposed a new simplified deep learning model,DeepSignalingSynergy, for drug combination prediction. Compared with existing models that use a large number of chemical-structure and genomics features in densely connected layers, we built the model on a small set of cancer signaling pathways, which can mimic the integration of multi-omics data and drug target/mechanism in a more biological meaningful and explainable manner. The evaluation results of the model using the NCI ALMANAC drug combination screening data indicated the feasibility of drug combination prediction using a small set of signaling pathways. Interestingly, the model analysis suggested the importance of heterogeneity of the 46 signaling pathways, which indicates that some new signaling pathways should be targeted to discover novel synergistic drug combinations.
Interpretable Deep Learning for De Novo Design of Cell-Penetrating Abiotic Polymers
Authors: Schissel Carly K. , Mohapatra Somesh , Wolfe Justin M. , Fadzen Colin M. , Bellovoda Kamela , Wu Chia-Ling , Wood Jenna A. , Malmberg Annika B. , Loas Andrei , Gómez-Bombarelli Rafael , Pentelute Bradley L. 
Published: April 2020

AbstractThere are more amino acid permutations within a 40-residue sequence than atoms on Earth. This vast chemical search space hinders the use of human learning to design functional polymers. Here we couple supervised and unsupervised deep learning with high-throughput experimentation to drive the design of high-activity, novel sequences reaching 10 kDa that deliver antisense oligonucleotides to the nucleus of cells. The models, in which natural and unnatural residues are represented as topological fingerprints, decipher and visualize sequence-activity predictions. The new variants boost antisense activity by 50-fold, are effective in animals, are nontoxic, and can also deliver proteins into the cytosol. Machine learning can discover functional polymers that enhance cellular uptake of biotherapeutics, with significant implications toward developing therapies for currently untreatable diseases.One sentence summaryDeep learning generates de novo large functional abiotic polymers that deliver antisense oligonucleotides to the nucleus.
Large hydrogen isotope fractionations distinguish nitrogenase-derived methane from other sources
Authors: Luxem Katja E. , Leavitt William D. , Zhang Xinning 
Published: April 2020

AbstractNitrogenase is the main source of natural fixed nitrogen for the biosphere. Two forms of this metalloenzyme, the vanadium (V) and iron (Fe)-only nitrogenases, were recently found to reduce small amounts of carbon dioxide into the potent greenhouse gas methane. Here we report carbon and hydrogen stable isotopic compositions and fractionations of methane generated by V- and Fe-only nitrogenases in the metabolically versatile nitrogen fixerRhodopseudomonas palustris. The stable carbon isotope fractionation imparted by both forms of alternative nitrogenase are within the range observed for hydrogenotrophic methanogenesis (13αCO2/CH4= 1.051 ± 0.002 for V-nitrogenase and 1.055 ± 0.001 for Fe-only nitrogenase, mean ± SE). In contrast, the hydrogen isotope fractionations (2αH2O/CH4= 2.071 ± 0.014 for V-nitrogenase and 2.078 ± 0.018 for Fe-only nitrogenase) are the largest of any known biogenic or geogenic pathway. The large2αH2O/CH4shows that the reaction pathway nitrogenases use to form methane strongly discriminates against2H, and that2αH2O/CH4distinguishes nitrogenase-derived methane from all other known biotic and abiotic sources. These findings on nitrogenase-derived methane will help constrain carbon and nitrogen flows in microbial communities and the role of the alternative nitrogenases in global biogeochemical cycles.ImportanceAll forms of life require nitrogen for growth. Many different kinds of microbes living in diverse environments make inert nitrogen gas from the atmosphere bioavailable using a special protein,nitrogenase. Nitrogenase has a wide substrate range, and in addition to producing bioavailable nitrogen, some forms of nitrogenase also produce small amounts of the greenhouse gas methane. This is different from other microbes that produce methane to generate energy. Until now, there was no good way to determine when microbes with nitrogenases are making methane in nature. Here, we developed an isotopic fingerprint that allows scientists to distinguish methane from microbes making it for energy versus those making it as a byproduct of nitrogen acquisition. With this new fingerprint, it will be possible to improve our understanding of the relationship between methane production and nitrogen acquisition in nature.
Functional screening of β-Glucanase Producing Actinomycetes Strains from Western Ghats ecosystems of Kerala, India
Authors: Edison Lekshmi K. , Pradeep N. S. 
Published: April 2020

AbstractScreening of potential soil actinomycetes is static at infant phase because less than one part of soil biodiversity has been explored. An important factor considered before isolating microorganisms with potential application is understanding the biodiversity and environmental features associated with growth. Search of distinctive enzymes from unusual ecological habitats are highly fascinating and have great opportunities that may also pointed the developments in high throughput screening programs. In the present study Western Ghats hot spot regions of Kerala has been explored for the actinomycetes strains with beta glucanase activity. A total of 127 actinomycetes strains were isolated. After qualitative primary screening 106 strains (83%) produced exo-β-1,4-glucanase enzyme and 79 strains (62%) produced endo-β-1,3-glucanase enzyme. The quantitative secondary screening confirmed the strains TBG-MR17 and TBG-AL13 recognised as respective dominant producers of exo-β-1,4-glucanase and endo-β-1,3-glucanase enzymes. The study reveals the richness of the Western Ghats soils with innumerable actinomycetes having potential β-glucanase activities.
Long Noncoding RNA Derived from LncRNA–mRNA Co-expression Networks Modulates the Locust Phase Change
Authors: Li Ting , Chen Bing , Yang Pengcheng , Wang Depin , Du Baozhen , Kang Le 
Published: April 2020

AbstractLong noncoding RNAs (lncRNAs) regulate various biological processes from gene expression to animal behavior. Although protein-coding genes, microRNAs, and neuropeptides play important roles in the regulation of phenotypic plasticity in migratory locust, empirical studies on the function of lncRNAs in the process remain limited. Here, we applied high-throughput RNA-seq to characterize the expression patterns of lncRNAs and mRNAs in the time course of the locust phase change. LncRNAs displayed more rapid response at the early stages of the time-course treatments than mRNA expression. Functional annotations demonstrated that early changed lncRNAs employed different pathways in isolation and crowding processes to cope up with the changes in population density. Finally, two overlapping hub lncRNA loci in the crowding and isolation networks were screened to be functionally verified. Experimental validation indicated that LNC1010057 could act as a potential regulator to modulate the locust phase change. This work offers new insights into the mechanism underlying the locust phase change and expands the scope of lncRNA functions in animal behavior.
Algal growth at environmentally relevant concentrations of suspended solids: implications for microplastic hazard assessment
Authors: Gorokhova Elena , Ek Karin , Reichelt Sophia 
Published: April 2020

AbstractHazard assessment of microplastic is challenging because standard toxicity testing is mostly developed for soluble (at least partially) chemicals. Adverse effects can occur when test organisms are exposed to turbid environments with various particulate matter (PM), both natural, such as sediment, and anthropogenic, such as microplastic. It is, therefore, relevant to compare responses to PM exposure between the microplastic and other suspended solids present at ecologically relevant concentrations; this can be done by using reference materials when assessing hazard potential of microplastics. Here, we evaluated growth inhibition in unicellular algaRaphidocelis subcapitataexposed to different suspended solids (microplastic, kaolin, and cellulose; 10, 100 and 1000 mg/L) during 72 h; algae without added solids were used as a control. In addition, aggregate formation in the exposure systems was analyzed using particle size distribution data. At 10 and 100 mg/L, no adverse growth effects were observed in any treatments; moreover, algal growth was significantly stimulated in kaolin and cellulose treatments compared to the control. However, at 1000 mg/L, all tested materials exerted growth inhibition, with no significant differences among the treatments. The comparison among particle size distributions across the treatments showed that both PM concentration and size of the particle aggregates were significant growth predictors for all materials tested. Therefore, at high concentrations, both natural and anthropogenic materials have similar capacity to cause adverse effects in algal growth inhibition tests, which must be taken into account in hazard assessment of plastic litter.
Gray Matter alterations in MS and CIS: a Coordinate based Meta-analysis and regression
Authors: Singh Sonika , Tench Christopher , Tanasescu Radu , Constantinescu Cris 
Published: April 2020

AbstractThe purpose of this coordinate based meta-analysis (CBMA) was to summarise the available evidence related to regional grey matter (GM) changes in patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS). CBMA is a way to find the consistent results across multiple independent studies that are otherwise not easily comparable due to methodological differences. The coordinate based random effect size (CBRES) meta-analysis method utilizes the reported coordinates (foci of the clusters of GM loss) and Z score standardised by number of subjects, controlling type I error rate by false cluster discovery rate (FCDR). Thirty-four published articles reporting forty-five independent studies using voxel-based morphometry (VBM) for the assessment of GM atrophy between MS or CIS patients and healthy controls were identified from electronic databases. The primary meta-analysis identified clusters of spatially consistent cross-study reporting of GM atrophy; subgroup analyses and meta-regression were also performed. This meta-analysis demonstrates consistent areas of GM loss in MS or CIS, in the form of significant clusters. Some clusters also demonstrate correlation with disease duration.
Studies on trans-sutural distraction osteogenesis-related genes based on transcriptome sequencing
Authors: Wang Baicheng , Xue Hongyu , Tong Haizhou , Zhang Peiyang , Wang Mei , Sun Yidan , Zhao Zhenmin 
Published: April 2020

AbstractTrans-sutural distraction osteogenesis (TSDO) is an important approach to improve mid-face hypoplasia. In recent years, many studies have been carried out on physical mechanisms of TSDO; however, it’s specific cytological and molecular mechanisms are still unclear. In this study, we performed transcriptome sequencing analysis in Sprague Dawley rats at 1 and 2 weeks after suture osteogenesis and compared RNA expression levels between experimental and control groups. At one week, enrichment pathways were mainly up-regulated in muscle- and bone-related pathways. By contrast, pathways of the immune system showed a state of inhibition and down-regulation, especially for B cells; the main immune pathways showed significant down-regulation. However, two weeks later, the experimental group showed positive up-regulation of the pathways related to DNA synthesis and replication, cell cycle, and chromosome replication. At the same time, the immune pathways that were down-regulated in the first week were up-regulated in the second week. In other words, the up-regulated muscle- and bone-related pathways show opposite trends. The expression of bone- and myogenesis-related transcriptome was up-regulated and the immune-related pathways were down-regulated in the experimental group at 1 week. At 2 weeks, the pathways related to bone- and muscle were down-regulated, while those related to cell cycle regulation and DNA replication were up-regulated. These results suggest that musculoskeletal-related molecules may play an important role during suture osteogenesis at 1 week, and immune regulation may be involved in this process; however, at 2 weeks, molecules related to cell proliferation and replication may be a major role.
Transcriptional profiling and single-cell chimerism analysis identifies human tissue resident T cells in the human skin after allogeneic stem cell transplantation
Authors: de Almeida Gustavo P. , Lichtner Peter , Mädler Sophia , Chu Chang-Feng , Zielinski Christina E. 
Published: April 2020

AbstractTissue resident memory T cells (TRM) have recently emerged as crucial cellular players for host defense in a wide variety of tissues and barrier sites. Mouse models revealed that they are maintained long-termin locounlike recirculating effector memory T cells (TEM). Insights into the maintenance and regulatory checkpoints of human tissue resident T cells (TRM) remain scarce, especially due to the obstacles in tracking T cells over time and system-wide in humans. We present a clinical model that allowed us to overcome these limitations. We demonstrate that allogeneic stem cell transplantation resulted in compartmentalization of host T cells in the human skin despite complete donor T cell chimerism in the blood, thus unmasking long-term persistence of tissue resident T cell subsets of host origin within the diverse skin T cell community. Single-cell transcriptional profiling paired with single-cell chimerism analysis provided an in-depth characterization of thesebona fideskin resident T cells. Their phenotype, functions and regulatory checkpoints may serve therapeutic strategies for the treatment of autoimmune diseases and chronic infections, where their specific depletion versus maintenance, respectively, will have to be harnessed pharmaceutically.
Capture-based enrichment ofTheileria parvaDNA enables full genome assembly of first buffalo-derived strain and reveals exceptional intra-specific genetic diversity
Authors: Palmateer Nicholas C , Tretina Kyle , Orvis Joshua , Ifeonu Olukemi O , Crabtree Jonathan , Drabék Elliott , Pelle Roger , Awino Elias , Gotia Hanzel T , Munro James B , Tallon Luke , Morrison W Ivan , Daubenberger Claudia A , Nene Vish , Knowles Donald P , Bishop Richard P , Silva Joana C 
Published: April 2020

AbstractTheileria parvais an economically important, intracellular, tick-transmitted parasite of cattle. A live vaccine against the parasite is effective against challenge from cattle-transmissibleT. parvabut not against genotypes originating from the African Cape buffalo, a major wildlife reservoir, prompting the need to characterize genome-wide variation within and between cattle- and buffalo-associatedT. parvapopulations. Here, we describe a capture-based target enrichment approach that enables, for the first time,de novoassembly of nearly completeT. parvagenomes derived from infected host cell lines. This approach has exceptionally high specificity and sensitivity and is successful for both cattle- and buffalo-derivedT. parvaparasites.De novogenome assemblies generated for cattle genotypes differ from the reference by ∼54K single nucleotide polymorphisms (SNPs) throughout the 8.31 Mb genome, an average of 6.5 SNPs/kb. We report the first buffalo-derivedT. parvagenome, which is larger than the genome from the reference, cattle-derived, Muguga strain. The average non-synonymous nucleotide diversity (πN) per gene, between buffalo-derivedT. parvaand the Muguga strain, was 1.3%. This remarkably high level of genetic divergence is supported by an averageFST, genome-wide, of 0.44, reflecting a degree of genetic differentiation between cattle- and buffalo-derivedT. parvaparasites more commonly seen between, rather than within, species, with clear implications for vaccine development. The DNA capture approach used provides clear advantages over alternativeT. parvaDNA enrichment methods used previously and enables in-depth comparative genomics in this apicomplexan parasite.