bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Expression Analysis of Glioma Neural Stem Cells Shows Disturbed Amino Acids Metabolism and Axonal Growth Cone Dynamics in Glioblastoma Multiforme
Authors: Vaja Rutvi 
Published: September 2021

AbstractGlioblastoma multiforme(GBM) is a group of fatal and aggressive tumors of the central nervous system. Despite advancements in the treatment of GBM, patients diagnosed with these tumors typically have a poor prognosis and poor quality of life as the disease develops. The single-cell RNA high-throughput sequencing processed data for Glioma cancer stem cells were taken from GEO and analyzed to find out the underlying expression differences at the gene level between glioma neural stem cells(GSCs) and Normal neural stem cells(NSCs). In the current study, we have performed an RNA-sequencing analysis between GSCs and NSCs to better understand the origin of GBM. We have performed bioinformatics analysis on the transcriptional profile of 134 samples which consisted of 75 GSCs and 59 NSCs obtained from the NCBI bio project(PRJNA546254). First, an exploratory analysis was performed which showed significant variation patterns between GSCs and NSCs. Subsequently, Deseq2 differential gene expression analysis identified 1436 differentially expressed genes between GSCs and NSCs[(padj. value <0.05, log2 fold change (>=+/-1.5)]. This study reveals genes like MAOA, MAOB, GATM, GLDC, AMT, and SHMT1 as the key features contributing to the disturbed processes of Glycine, threonine, and serine amino acid metabolism, axonal cone growth curve, and cell migration in Glioma. Conclusively, our study also depicts gene expression changes in amyloid beta-binding protein in between GSCs and NSCs which plays an important role in tumor microenvironment formation. Besides, the results presented here reveal new insight into the progression of GBM and the identification of novel genes involved in gliomagenesis.
Expert-integrated automated machine learning uncovers hemodynamic predictors in spinal cord injury
Authors: Chou Austin , Torres-Espin Abel , Kyritsis Nikos , Huie J. Russell , Khatry Sarah , Funk Jeremy , Hay Jennifer , Lofgreen Andrew , Shah Rajiv , McCann Chandler , Pascual Lisa U , Amorim Edilberto , Weinstein Philip R , Manley Geoffrey T , Dhall Sanjay S , Pan Jonathan Z , Bresnahan Jacqueline C , Beattie Michael S , Whetstone William D , Ferguson Adam R ,   the TRACK-SCI Investigators
Published: September 2021

AbstractAutomated machine learning (AutoML) is positioned to democratize artificial intelligence (AI) by reducing the amount of human input and ML expertise needed to create prediction models. However, successful translation of ML in biomedicine requires moving beyond optimizing only for prediction accuracy and towards discovering reproducible clinical and biological inferences. Here, we present a model-agnostic framework to reinforce AutoML using strategies and tools of explainable and reproducible AI, including novel metrics for performance precision and feature instability. The framework enables clinicians to interpret AutoML-generated models for clinical and biological verifiability and consequently integrate domain expertise during model development. We applied the framework towards spinal cord injury prognostication and identified a detrimental relationship between intraoperative hypertension and patient outcome. Furthermore, our analysis captured evolving clinical practices such as faster time-to-surgery and blood pressure management that affected clinical model validation. Altogether, we illustrate how augmenting AutoML for inferential reproducibility empowers biomedical discovery and builds trust in AI processes towards effective clinical integration.
Plant-based biosensors for detecting CRISPR-mediated genome engineering
Authors: Yuan Guoliang , Hassan Md. Mahmudul , Yao Tao , Lu Haiwei , Vergara Michael Melesse , Labbé Jesse L. , Muchero Wellington , Pan Changtian , Chen Jin-Gui , Tuskan Gerald A. , Qi Yiping , Abraham Paul E. , Yang Xiaohan 
Published: September 2021

AbstractCRISPR/Cas has recently emerged as the most reliable system for genome engineering in various species. However, concerns about risks associated with CRISPR/Cas9 technology are increasing on potential unintended DNA changes that might accidentally arise from CRISPR gene editing. Developing a system that can detect and report the presence of active CRIPSR/Cas tools in biological systems is therefore very necessary. Here, we developed the real-time detection systems that can spontaneously indicate CRISPR-Cas tools for genome editing and gene regulation including CRISPR/Cas9 nuclease, base editing, prime editing and CRISPRa in plants. Using the fluorescence-based molecular biosensors, we demonstrated that the activities of CRISPR/Cas9 nuclease, base editing, prime editing and CRIPSRa can be effectively detected in transient expression via protoplast transformation and leaf infiltration (in Arabidopsis, poplar, and tobacco) and stable transformation in Arabidopsis.
A serotonergic axon-cilium synapse drives nuclear signaling to maintain chromatin accessibility
Authors: Sheu Shu-Hsien , Upadhyayula Srigokul , Dupuy Vincent , Pang Song , Lemire Andrew L. , Walpita Deepika , Pasolli H. Amalia , Deng Fei , Wan Jinxia , Wang Lihua , Houser Justin , Sanchez-Martinez Silvia , Brauchi Sebastian E. , Banala Sambashiva , Freeman Melanie , Xu C. Shan , Kirchhausen Tom , Hess Harald F. , Lavis Luke , Li Yu-Long , Chaumont-Dubel Séverine , Clapham David E. 
Published: September 2021

SummaryChemical synapses between axons and dendrites mediate much of the brain’s intercellular communication. Here we describe a new kind of synapse – the axo-ciliary synapse - between axons and primary cilia. By employing enhanced focused ion beam – scanning electron microscopy on samples with optimally preserved ultrastructure, we discovered synapses between the serotonergic axons arising from the brainstem, and the primary cilia of hippocampal CA1 pyramidal neurons. Functionally, these cilia are enriched in a ciliary-restricted serotonin receptor, 5-hydroxytryptamine receptor 6 (HTR6), whose mutation is associated with learning and memory defects. Using a newly developed cilia-targeted serotonin sensor, we show that optogenetic stimulation of serotonergic axons results in serotonin release onto cilia. Ciliary HTR6 stimulation activates a non-canonical Gαq/11-RhoA pathway. Ablation of this pathway results in nuclear actin and chromatin accessibility changes in CA1 pyramidal neurons. Axo-ciliary synapses serve as a distinct mechanism for neuromodulators to program neuron transcription through privileged access to the nuclear compartment.
The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium
Authors: Niedziółka SM , Datta S , Uśpieński T , Baran B , Skarżyńska W , Humke EW , Rohatgi R , Niewiadomski P 
Published: September 2021

AbstractThe efficient transport of proteins into the primary cilium is a crucial step for many signaling pathways. Dysfunction of this process can lead to the disruption of signaling cascades or cilium assembly, resulting in developmental disorders and cancer. Previous studies on the protein delivery to the cilium were mostly focused on the membrane-embedded receptors. In contrast, how soluble proteins are delivered into the cilium is poorly understood. In our work, we identify the exocyst complex as a key player in the ciliary trafficking of soluble Gli transcription factors. In line with the known function of the exocyst in intracellular vesicle transport, we demonstrate that soluble proteins, including Gli2/3 and Lkb1, can use the endosome recycling machinery for their delivery to the primary cilium. Finally, we identify GTPases: Rab14, Rab18, Rab23, and Arf4 that are involved in vesicle-mediated Gli protein ciliary trafficking. Our data pave the way for a better understanding of ciliary transport and uncover novel transport mechanisms inside the cell.
Towards optimization of oscillatory stimulation during sleep
Authors: Ladenbauer Julia , Khakimova Liliia , Malinowski Robert , Obst Daniela , Tönnies Eric , Antonenko Daria , Obermayer Klaus , Hanna Jeff , Flöel Agnes 
Published: September 2021

AbstractBackgroundOscillatory rhythms during sleep such as slow oscillations (SO) and spindles, and most importantly their coupling, are thought to underlie processes of memory consolidation. External slow oscillatory transcranial direct current stimulation (so-tDCS) with a frequency of 0.75 Hz has been shown to improve this coupling and memory consolidation, however, effects varied quite markedly between individuals, studies, and species. Here, we aimed to determine how precisely the frequency of stimulation has to match the naturally occurring SO frequency in individuals to optimally improve SO-spindle coupling. Moreover, we systematically tested stimulation durations necessary to induce changes.MethodsWe addressed these questions by comparing so-tDCS with individualized frequency to standardized frequency of 0.75 Hz in a within-subject design with 28 older participants during napping while systematically varying stimulation train durations between 30 s, 2 min, and 5 min.ResultsStimulation trains as short as 30 s were sufficient to modulate the coupling between SOs and spindle activity. Contrary to our expectations, so-tDCS with standardized frequency indicated stronger aftereffects with regard to SO-spindle coupling compared to individualized frequency. Angle and variance of spindle maxima occurrence during the SO cycle were similarly modulated.ConclusionIn sum, short stimulation trains were sufficient to induce significant changes in sleep physiology allowing for more trains of stimulation, which provides methodological advantages and possibly even larger behavioral effects in future studies. With regard to individualized stimulation frequency, further options of optimization need to be investigated, such as closed-loop stimulation to calibrate stimulation frequency to the SO frequency at time of stimulation onset.Significance statementApplication of slow oscillatory transcranial direct current stimulation during sleep has been shown to enhance specific memory-relevant sleep parameters and memory performance after sleep, albeit with a high degree of variability. Here, we systematically explored two major stimulation parameters possibly accounting for this variability in humans: frequency and duration of stimulation. We found, contrary to our expectations, standardized frequency stimulation with 0.75 Hz being superior to individualized frequency stimulation in enhancing specific sleep parameters. Moreover short stimulation trains of 30 seconds were as effective as 5 min in modulating aftereffects. These are encouraging findings, implying methodological advantages as larger quantity of aftereffects data can be obtained within the same time window, which may also lead to enhanced behavioral stimulation effects.
HIV-1 hijacks the cell extracellular matrix to spread collectively and efficiently between T lymphocytes
Authors: Inizan C. , Caillet M. , Desrames A. , David A. , Bomme P. , Mallet A. , Bourdic K. , Lambotte O. , Boufassa F. , Mesel-Lemoine M. , Tangy F. , Pancino G. , Mouquet H. , Lagache T. , Dufour A. , Olivo-Marin J.- C. , Rey F.A. , Saez-Cirion A. , Thoulouze M.-I. 
Published: September 2021

ABSTRACTCollective transmissionviastructures containing several virions has recently emerged as a highly efficient mode of viral spread. Here, we demonstrate that HIV-1 spreads between T lymphocytes in the form of viral particles colonies that are concentrated and sheltered in an extracellular matrix (ECM) lattice enabling their collective transmission upon cell contacts. Intrinsically, ECM-clustered viruses infect T lymphocytes more efficiently than individual viral particles. They preserve HIV-1 transmission from antiretroviral treatment (ArT) and potent broadly neutralizing antibodies. We also show that collagen induced by HIV-1 infection controls the clustering of virions and their collective spread, thereby enhancing infectivity. CD4+ T cells from HIV-1-infected patients produce and transmit ECM-virus clusters, supporting that they could be involvedin vivo. This study provides new insights into modes of HIV-1 transmission and identifies a novel fundamental role for collagen in this process. HIV-1 spreadviaECM-virus clusters may have important implications for viral dissemination and persistence, including during therapy.
Quantitative phosphoproteomics reveals regulatory state dependent efficacy of chemical Cdk1 inhibition and distinct Cdk5 complexes as novel Wee1 substrates
Authors: Grassetti Andrew V. , Hards Rufus , Gerber Scott A. 
Published: September 2021

AbstractWee1 kinase plays a central role in the eukaryotic cell cycle via its well-known negative regulation of Cdk1 activity at the G2/M transition, preventing progression into mitosis until DNA replication and/or DNA damage repair is complete. Recent genetic evidence in yeast, flies and human cells have suggested additional functions of Wee1 in mitosis and during mitotic exit, respectively. To discover new candidate substrates of Wee1 kinase, we used SILAC-based phosphoproteomics and selective chemical inhibition to quantitatively compare phosphorylation site abundances in the presence and absence of Wee1 activity. Unexpectedly, we uncovered a role for the Wee1-dependent phosphorylation of Cdk1-cyclin B at tyrosine 15 (Y15) in facilitating chemical inhibition of Cdk1-cyclin B by the inhibitor RO3306. Thermal shift stability assays demonstrated greater binding affinity of RO3306 for Y15-phosphorylated Cdk1-cyclin B versus unphosphorylated complex, providing an additional molecular basis for the observed Wee1 inhibitor-based toxicity in human cells. In addition, our experiments identified Cdk5-CABLES and Cdk5-cyclin B as novel substrates of Wee1 during chemically induced exit from mitosis. Collectively, these experiments facilitate a greater understanding of the Wee1-Cdk1 signaling axis and uncover new candidate substrates for Wee1.
The Clock:cycle complex is a major transcriptional regulator ofDrosophilaphotoreceptors that protects the eye from retinal degeneration and oxidative stress
Authors: Jauregui-Lozano Juan , Hall Hana , Stanhope Sarah C. , Bakhle Kimaya , Marlin Makayla M. , Weake Vikki M. 
Published: September 2021

AbstractThe aging eye experiences physiological changes that include decreased visual function and increased risk of retinal degeneration. Although there are transcriptomic signatures in the aging retina that correlate with these physiological changes, the gene regulatory mechanisms that contribute to cellular homeostasis during aging remain to be determined. Here, we integrated ATAC-seq and RNA-seq data to identify 61 transcription factors that showed differential activity in agingDrosophilaphotoreceptors. These 61 age-regulated transcription factors include two circadian regulators, Clock and cycle, that showed sustained increases in activity during aging. When we disrupted Clock activity in adult photoreceptors, we observed changes in expression of 15 – 20% of genes including key components of the phototransduction machinery and many eye-specific transcription factors. Using ATAC-seq, we showed that loss of Clock activity leads to changes in activity of 31 transcription factors and causes a progressive decrease in global levels of chromatin accessibility in photoreceptors. Supporting a key role for Clock-dependent transcription in the eye, disruption of Clock activity in photoreceptors also induced light-dependent retinal degeneration and increased oxidative stress, independent of light exposure. Together, our data suggests that the circadian regulators Clock and cycle act as neuroprotective factors in the aging eye by directing gene regulatory networks that maintain expression of the phototransduction machinery and counteract oxidative stress.
An Attempt to Develop an Aptamer Lateral-Flow Assay (ALFA) for Easy, Rapid, and Sensitive Detection of Lethal Mushroom Toxin α-amanitin
Authors: Chen Qingchuan , Fan Chen , Huang Haozhe , Xu Binglin , Zong Yeqing 
Published: September 2021

AbstractAmatoxins contribute to the majority of mushroom poisoning, most prominently, α-amanitin. Since mushroom is a common foodstuff worldwide, an easy, rapid, sensitive test for α-amanitin is needed. Several detection methods for α-amanitin have been developed, including HPLC, LC-MS, and ELISA, and LFIA. Aptamers have several advantages compared to antibodies: easy development via SELEX, longer shelf life, and higher temperature- and pH-tolerance. Aptamer Lateral Flow Assay (ALFA) is a similar technology compared to LFIA but incorporates aptamers as target-recognizing agents. This study attempted to develop an ALFA test strip for α-amanitin using a previously-developed aptamer, however failure of generating a colorimetric readout at the test line is persisted throughout all experiments, even though the concept is fully-proved and the control line functions normally. The failure is attributed to the small size of the molecule, leading to immobilization difficulties on the nitrocellulose membrane to form the test line, and the hindering of effective “surround” mechanism of aptamer-target binding (instead of “adhere”, when the target molecule is large, e.g. a protein). It is concluded that ALFAs for small-molecules whose aptamer-target interaction has not yet been studied and modelled in detail remains a challenge, despite ALFAs’ large potential.
Reconstructing Sample-Specific Networks using LIONESS
Authors: Kuijjer Marieke L. , Glass Kimberly 
Published: September 2021

AbstractWe recently developed LIONESS, a method to estimate sample-specific networks based on the output of an aggregate network reconstruction approach. In this manuscript, we describe how to apply LIONESS to different network reconstruction algorithms and data types. We highlight how decisions related to data preprocessing may affect the output networks, discuss expected outcomes, and give examples of how to analyze and compare single sample networks.
Ecological stochasticity and phage induction diversify bacterioplankton communities at the microscale
Authors: Szabo Rachel E. , Pontrelli Sammy , Grilli Jacopo , Schwartzman Julia A. , Pollak Shaul , Sauer Uwe , Cordero Otto X. 
Published: September 2021

AbstractIn many natural environments, microorganisms self-assemble around heterogeneously distributed resource patches. The growth and collapse of populations on resource patches can unfold within spatial ranges of a few hundred micrometers or less, making such microscale ecosystems hotspots of biological interactions and nutrient fluxes. Despite the potential importance of patch-level dynamics for the large-scale evolution and function of microbial communities, we have not yet been able to delineate the ecological processes that control natural populations at the microscale. Here, we addressed this challenge in the context of microbially-mediated degradation of particulate organic matter by characterizing the natural marine communities that assembled on over one thousand individual microscale chitin particles. Through shotgun metagenomics, we found significant variation in microscale community composition despite the similarity in initial species pools across replicates. Strikingly, a subset of particles was highly populated by rare chitin-degrading strains; we hypothesized that their conditional success reflected the impact of stochastic colonization and growth on community assembly. In contrast to the conserved functional structures that emerge in ecosystems at larger scales, this taxonomic variability translated to a wide range of predicted chitinolytic abilities and growth returns at the level of individual particles. We found that predation by temperate bacteriophages, especially of degrader strains, was a significant contributor to the variability in the bacterial compositions and yields observed across communities. Our study suggests that initial stochasticity in assembly states at the microscale, amplified through biotic interactions, may have significant consequences for the diversity and functionality of microbial communities at larger scales.Significance StatementThe biogeochemical consequences of the degradation of particulate organic matter by microorganisms represent the cumulative effect of microbial activity on individual microscale resource patches. The ecological processes controlling community dynamics in these highly localized microenvironments remain poorly understood. Here, we find that complex marine communities growing on microscale resource particles diverge both taxonomically and functionally despite assembling under identical abiotic conditions from a common species pool. We show that this variability stems from bacteriophage predation and history-dependent factors in community assembly, which create stochastic dynamics that are spatially structured at the microscale. This microscale stochasticity may have significant consequences for the coexistence, evolution, and function of diverse bacterial and viral populations in the global ocean.
Modeling tissue-specific breakpoint proximity of structural variations from 2,382 whole-genomes to identify cancer drivers
Authors: Martinez-Fundichely Alexander , Dixon Austin , Khurana Ekta 
Published: September 2021

AbstractStructural variations (SVs) in cancer cells often impact large genomic regions with functional consequences. However, little is known about the genomic features related to the breakpoint distribution of SVs in different cancers, a prerequisite to distinguish loci under positive selection from those with neutral evolution. We developed a method that uses a generalized additive model to investigate the breakpoint proximity curves from 2,382 whole-genomes of 32 cancer types. We find that a multivariate model, which includes linear and nonlinear partial contributions of various tissue-specific features and their interaction terms, can explain up to 57% of the observed deviance of breakpoint proximity. In particular, three-dimensional genomic features such as topologically associating domains (TADs), TAD-boundaries and their interaction with other features show significant contributions. The model is validated by identification of known cancer genes and revealed putative drivers in novel cancers that have previous evidence of therapeutic relevance in other cancers.
Horn trophy seized in illegal wildlife trade assigned to swamp buffalo using a combined morphometric and DNA based approach in wildlife forensics in India
Authors: Vipin  , Sharma Vinita , Sharma Chandra Prakash , Goyal Surendra Prakash , Gupta Sandeep Kumar 
Published: September 2021

AbstractThe illegal wildlife trade has threatened the existence of many extant wild animal species throughout the world. While dealing with the illegal wildlife trade of horns, we face problems of not having a proper protocol and lack of reference database to assign the species for proper implementation of wildlife laws. In one such condition, a horn trophy suspected to be of a wild buffalo was seized by authorities and sent to us for species identification. We used a combined approach of morphological and DNA analysis to ascertain the seized horn’s species. The two measurements, circumference at the base (CAB) and length on the front curve (LOFC) were measured for the seized and other horns of different bovid species, showing morphological resemblance with the seized horn. The 3-D scatter plot, generated by the values of CAB, LOFC and CAB/ LOFC, differentiated the different bovid species into distinct clusters and placed the seized horn in the proximity of domestic buffaloes. The Bayesian evolutionary analysis of the partial D-loop gene (521bp) placed the seized horn in a clade with swamp buffaloes. Since swamp buffaloes are domestic buffaloes, both these approaches concluded the same results. Hence, the current protocol developed may also be used to differentiate among wild buffalo, domestic buffalo, Cattle, Wild yak, Gaur and Takin using a combined approach of morphometric and DNA-based analysis, which may be used to deal with illegal wildlife trade of different bovid species at the world level.