bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol, Opioid, and Combined Alcohol and Opioid Use Disorders Affect Shared and Unique Pathways: A Proteomic Analysis of Postmortem Brains
Authors: Leung Edison , Stertz Laura , Teixeira Antonio L. , Meyer Thomas D. , Selvaraj Sudhakar , Walss-Bass Consuelo 
Published: May 2022

AbstractSubstance misuse is a major burden for not only patients but the healthcare system. Understanding how substance misuse alters a patient’s genome, proteome, and neurocircuitry is an important step toward identifying targets for treatments. In this exploratory study, we performed a proteomic analysis of postmortem brain from individuals with substance misuse disorder (n=29), including alcohol (n=11) and opioid misuse disorder (n=12), or comorbidity with both disorders (n=6), compared to controls (n=12). The results demonstrate that these substances affect both common and different biological pathways compared to controls. Alcohol misuse affects primarily protein translation, rRNA processing, and energy metabolism pathways, while opioid influences G-protein signaling, protein translation, rRNA processing, energy metabolism, and angiogenesis pathways. Alcohol and opioid misuse combined appears to have a synergistic effect on protein expression of the TCA cycle, respiratory transport, mitochondrial function, LGI-ADAM interactions, interleukin signaling, neuronal system changes, and actin polymerization. These findings offer new insights into how substance misuse leads to protein alterations and how combined substance misuse leads to different protein changes compared to single substance misuse.
PAM binding ensures orientational integration during Cas4-Cas1-Cas2 mediated CRISPR adaptation
Authors: Dhingra Yukti , Suresh Shravanti K. , Juneja Puneet , Sashital Dipali G. 
Published: May 2022

AbstractAdaptation in CRISPR-Cas systems immunizes bacteria and archaea against mobile genetic elements. In many DNA-targeting systems, the Cas4-Cas1-Cas2 complex is required for selection and processing of DNA segments containing PAM sequences, prior to integration of these “prespacer” substrates as spacers in the CRISPR array. We determined cryo-EM structures of the Cas4-Cas1-Cas2 adaptation complex from the type I-C system that encodes standalone Cas1 and Cas4 proteins. The structures reveal how Cas4 specifically reads out bases within the PAM sequence and how interactions with both Cas1 and Cas2 activate Cas4 endonuclease activity. The Cas4-PAM interaction ensures tight binding between the adaptation complex and the prespacer, significantly enhancing integration of the non-PAM end into the CRISPR array and ensuring correct spacer orientation. Corroborated with our biochemical results, Cas4-Cas1-Cas2 structures with substrates representing various stages of CRISPR adaptation reveal a temporally resolved mechanism for maturation and integration of functional spacers into the CRISPR array.
Decoding imagined speech reveals speech planning and production mechanisms
Authors: Orpella Joan , Mantegna Francesco , Assaneo M. Florencia , Poeppel David 
Published: May 2022

AbstractSpeech imagery (the ability to generate internally quasi-perceptual experiences of speech) is a fundamental ability linked to cognitive functions such as inner speech, phonological working memory, and predictive processing. Speech imagery is also considered an ideal tool to test theories of overt speech. The study of speech imagery is challenging, primarily because of the absence of overt behavioral output as well as the difficulty in temporally aligning imagery events across trials and individuals. We used magnetoencephalography (MEG) paired with temporal-generalization-based neural decoding and a simple behavioral protocol to determine the processing stages underlying speech imagery. We monitored participants’ lip and jaw micromovements during mental imagery of syllable production using electromyography. Decoding participants’ imagined syllables revealed a sequence of task-elicited representations. Importantly, participants’ micromovements did not discriminate between syllables. The decoded sequence of neuronal patterns maps well onto the predictions of current computational models of overt speech motor control and provides evidence for hypothesized internal and external feedback loops for speech planning and production, respectively. Additionally, the results expose the compressed nature of representations during planning which contrasts with the natural rate at which internal productions unfold. We conjecture that the same sequence underlies the motor-based generation of sensory predictions that modulate speech perception as well as the hypothesized articulatory loop of phonological working memory. The results underscore the potential of speech imagery, based on new experimental approaches and analytical methods, and further pave the way for successful non-invasive brain-computer interfaces.
Elicitors of plant defense induce the accumulation of amino acids that suppress both bacterial virulence and growth
Authors: Zhang Xiaomu , Tubergen Phil , Agorsor Israel , Khadka Pramod , Tempe Connor , Collakova Eva , Pilot Guillaume , Danna Cristian H. 
Published: May 2022

AbstractPlant immunity relies on the perception of Microbe-Associate Molecular Patterns (MAMPs) from invading microbes to induce defense responses that suppress attempted infections. It has been proposed that MAMP-triggered immunity (MTI) suppresses bacterial infections by suppressing the onset of bacterial virulence. However, the mechanisms by which plants exert this action are poorly understood. Here we uncover that MAMP-perception in Arabidopsis induces the accumulation of free amino acids (AA) in a salicylic acid (SA) dependent manner. When co-infiltrated with Glutamine and Serine, two of the MAMP-induced highly accumulating amino acids, Pseudomonas syringae pv. tomato DC3000 expressed low levels of virulence genes and failed to produce robust infections in otherwise susceptible plants. When applied exogenously, Glutamine and Serine suppressed bacterial virulence and bacterial growth directly without the need for MAMP-perception and SA-signaling, bypassing MAMP-elicited defense. In addition, an increased level of endogenous Glutamine in the leaf apoplast of a gain-of-function mutant of Glutamine Dumper-1 rescued the partially compromised bacterial virulence and growth suppressing phenotype of the SA-induced deficient-2 (sid2) mutant. Our data suggest that MTI suppresses bacterial infections by the direct suppressing effect of accumulating amino acids on the onset of bacterial virulence.
NeuroCI: Continuous Integration of Neuroimaging Results Across Software Pipelines and Datasets
Authors: Sanz-Robinson Jacob , Jahanpour Arman , Phillips Natalie , Glatard Tristan , Poline Jean-Baptiste 
Published: May 2022

Abstract—Neuroimaging study results can vary significantly depending on the datasets and processing pipelines utilized by researchers to run their analyses, contributing to reproducibility issues. These issues are compounded by the fact that there are a large variety of seemingly equivalent tools and methodologies available to researchers for processing neuroimaging data. Here we present NeuroCI, a novel software framework that allows users to evaluate the variability of their results across multiple pipelines and datasets. NeuroCI makes use of Continuous Integration (CI), a software engineering technique, to facilitate the reproducibility of computational experiments by launching a series of automated tests when code or data is added to a repository. However, unlike regular CI services, our CI-based framework uses distributed computation and storage to meet the large memory and storage requirements of neuroimaging pipelines and datasets. Moreover, the framework’s modular design enables it to continuously ingest pipelines and datasets provided by the user, and to compute and visualize results across the multiple different pipelines and datasets. This allows researchers and practitioners to quantify the variability and reliability of results in their domain across a large range of computational methods.
Facultative winter accession ofCamelina sativa(L. Crantz) with early maturity contributes to understanding of the role ofFLOWERING LOCUS Cin camelina flowering
Authors: Ott Matthew A. , Chopra Ratan , Frels Katherine , Brusa Anthony , Gjesvold Eva Serena , Marks M. David , Anderson James A. 
Published: May 2022

AbstractCamelina is being developed as a winter oilseed cover crop. Early flowering and maturity are desired traits in camelina to allow for relay planting or seeding of a summer annual following camelina harvest. Here we report that while all winter biotype accessions of camelina have a functional allele ofFLOWERING LOCUS C (FLC)on chromosome 20, there are also at least 20 previously characterized spring biotype accessions that have a functionalFLCallele at this locus. We observed this by analyzing 75 accessions (67 spring type, one facultative, and seven winter type) that were resequenced by Li et al., (2020) as well as 21 additional accessions for this analysis. This discovery will inform marker assisted selection efforts that are underway to increase genetic variation in the genetically narrow base of winter camelina germplasm. Furthermore, we optimized a KASP genotyping approach that effectively differentiates the presence of either the functional or subfunctionalFLCallele on chromosome 20. These analyses identified a facultative winter biotype accession of camelina (PI650163-1, winter hardy with subfunctional chromosome 20FLCallele) that has demonstrated two years of winter-hardiness and has flowered at least a week earlier than the common winter accession, ‘Joelle’. A bioinformatics approach to cytotype analysis in camelina also provided more precise categorizing of camelina accessions in the USDA-NPGS germplasm into 2n=38 and 2n=40 cytotypes. Early maturing winter-hardy camelina will reduce stress on a subsequent soybean crop and improve total cropping system yields when camelina and soybean are grown sequentially in the same season on the same land.
MEBOCOST: Metabolite-mediated Cell Communication Modeling by Single Cell Transcriptome
Authors: Zheng Rongbin , Zhang Yang , Tsuji Tadataka , Gao Xinlei , Wagner Allon , Yosef Nir , Chen Hong , Zhang Lili , Tseng Yu-Hua , Chen Kaifu 
Published: May 2022

AbstractWe developed MEBOCOST, a computational algorithm for quantitatively inferring metabolite-mediated intercellular communications using single cell RNA-seq data. The algorithm identifies cell-cell communications in which metabolites, such as lipids, are secreted by sender cells and traveled to interact with sensor proteins of receiver cells. The sensor proteins on receiver cell might be cell surface receptors, transporters across the cell membrane, or nuclear receptors. MEBOCOST relies on a comprehensive database of metabolite-sensor partners, which we manually curated from the literatures and other public sources. MEBOCOST defines sender and receiver cells for an extracellular metabolite based on the expression levels of the enzymes and sensors, respectively, thus identifies metabolite-sensor communications between the cells. Applying MEBOCOST to mouse brown adipose tissue (BAT) successfully recaptured known metabolite-mediated cell communications and further identified new communications. Additionally, MEBOCOST identified a set of BAT intercellular metabolite-sensor communications that was regulated by cold exposure of the mice. MEBOCOST will be useful to numerous researchers to investigate metabolite-mediated cell-cell communications in many biological and disease models. The MEBOCOST software is freely available athttps://github.com/zhengrongbin/MEBOCOST.
Computational multiphase characterization of perfusion trends inside biomimetic reduced-order dense tumors
Authors: Akash Mohammad Mehedi Hasan , Chakraborty Nilotpal , Mohammad Jiyan , Reindl Katie , Basu Saikat 
Published: May 2022

AbstractDense fibrous extracellular constitution of solid tumors exerts high resistance to diffusive transport into it; additionally, the scarcity of blood and lymphatic flows hinders convection. The complexity of fluidic transport mechanisms in such tumor environments still presents open questions with translational end goals. For example, clinical diagnosis and targeted drug delivery platforms for such dense tumors can ideally benefit from a quantitative framework on plasma uptake into the tumor. In this study, we present a computational model for physical parameters that may influence blood percolation and penetration into a simple biomimetic solid tumor geometry. The model implements 3-phase viscous laminar transient simulation to mimic the transport physics inside a tumor-adhering blood vessel and measures the constituent volume fractions of the three considered phases, viz. plasma, RBCs (Red Blood Cells, also known as “erythrocytes”), and WBCs (White Blood Cells, also known as “leukocytes”) at three different flow times, while simultaneously recording the plasma pressure and velocity at the entry point to the tumor’s extracellular space. Subsequently, to quantify plasma perfusion within the tumor zone, we have proposed a reduced-order 2D transport model for the tumor entry zone and its extracellular space for three different fenestra diameters: 0.1, 0.3, and 0.5 μm; the simulations were 2-phase viscous laminar transient. The findings support the hypothesis that plasma percolation into the tumor is proportional to the leakiness modulated by the fenestra openings, quantifiable through the opening sizes.
Genetic evidence for parthenogenesis in small carpenter bee, Ceratina dallatoreana in its native distribution area
Authors: Mikát Michael , Straka Jakub 
Published: May 2022

AbstractArrhenotoky is typical mode of reproduction for Hymenoptera – females originate from fertilized eggs, males from unfertilized eggs. However, some lineages of Hymenoptera have switched to thelytoky, where diploid females originate instead from unfertilized diploid eggs. In the contras with some other hymenopteran lineages, thelytoky is generally very rare in bees.Here, we examined reproduction in the small carpenter bee Ceratina dallatoreana, which is assumed to be thelytokous. We compared genotype of microsatellite loci between mothers and their offspring. Offspring were genetically identical with mother in all cases. We did not detect any male offspring. Therefore, we conclude that parthenogeny is the prevailing, and perhaps obligate, mode of reproduction in C. dallatoreana. Offspring were clones of their mother with no observed decrease of heterozygosity. Thus the cytological mode of parthenogenesis is apomixis, or automimic with central fusion and extremely reduced or non-existing recombination.Ceratina bees are originally facultatively eusocial, therefore thelytoky may influence social evolution by causing extremely high within-colony relatedness. However, to date no multifemale nests have been recorded in C. dallatoreana.
Aridity modulates biogeographic distribution and community assembly of cyanobacterial morphotypes in drylands
Authors: Guo Xiaoyu , Li Hua , Huo Da , Li Renhui , Zhang Silong , Hu Chunxiang , Yu Gongliang , Song Lirong 
Published: May 2022

AbstractThe patterns of biogeographical distribution and assembly processes of microbiota are of vital importance for understanding ecological adaptation and functioning maintenance that microorganisms provide. Although the assembly of microbial communities was increasingly inspected, the role of their morphological characteristics is still poorly ascertained. Here, by integrating high-throughput sequencing and traditional trait-based classification, we investigated taxonomic and phylogenetic turnovers of different morphotypes of terrestrial cyanobacteria in biocrusts, as a model system, to evaluate the contributions of deterministic and stochastic processes across a large scale in drylands. The results showed that the bundle-forming category dominated in arid ecosystems with high tolerance against environmental fluctuations. Despite strong distance-decay relationships ofβ-diversity in all categories, both spatial composition and phylogenetic turnover rates of bundle-forming cyanobacteria were significantly lower than unicellular/colonial, heterocystous, and other non-heterocyst filamentous cyanobacteria. Null model analysis of phylogenetic signals and abundance-based neutral model found that stochastic processes prevailed in the assembly, while aridity mediated the balance between determinism and stochasticity and prompted a shifting threshold among morphotypes. Our findings provide a unique perspective to understand the role of microbial morphology, highlighting the differentiation of biogeographic distribution, environmental response, and species preference between morphotypes with consideration of potential functional consequences, and therefore facilitated the prediction of biodiversity loss under climate change.
Genetic structure and differentiation of the endemic Bolle’s Laurel Pigeon (Columba bollii) in the Canary Islands
Authors: Marrero Patricia , Fregel Rosa , Richardson David S. 
Published: May 2022

ABSTRACTIsland archipelagos are global biodiversity hotspots since they often foster high concentrations of diverse lineages and endemic species. Here, we examine the population genetics of the endemic Bolle’s Laurel PigeonColumba bollii, a frugivorous bird inhabiting subtropical laurel forests. We genotyped ten microsatellite loci using DNA obtained from moulted tail feathers collected at eight sampling sites on the four western islands of the Canarian archipelago. Analyses including F-statistics, Bayesian clustering approaches, isolation by distance tests and population graph topologies, were used to infer the genetic diversity and the population differentiation within and among insular populations. Additionally, we evaluated the effect of null alleles on data analysis. Low genetic diversity was found in all populations of Bolle’s Laurel Pigeon, with no significant differences in diversity among them. However, significant genetic differentiation was detected among all populations, with pigeons from La Palma and El Hierro exhibiting the closest affinity. Bayesian clustering supported population separation between islands, and also detected fine-scale structure within the Tenerife and La Gomera populations. Present-day pigeon movements appear to occur between islands, however, this has not been sufficient to remove the signature of genetic divergence among the populations of Bolle’s Laurel Pigeon, which was moderately linked to geographical distance. According to metapopulation structure, this study suggests that the evolutionary history ofC. bolliiis closely related to the geological past of these oceanic islands and the distribution range of its habitat, the laurel forest. Finally, conservation implications for the species are discussed.
Semantic Surprise Predicts the N400 Brain Potential
Authors: Lindborg Alma , Musiolek Lea , Ostwald Dirk , Rabovsky Milena 
Published: May 2022

AbstractLanguage is central to human life; however, how our brains derive meaning from language is still not well understood. A commonly studied electrophysiological measure of on-line meaning related processing is the N400 component, the computational basis of which is still actively debated. Here, we test one of the recently proposed, computationally explicit hypotheses on the N400 – namely, that it reflects surprise with respect to a probabilistic representation of the semantic features of the current stimulus in a given context. We devise a Bayesian sequential learner model to derive trial-by-trial semantic surprise in a semantic oddball like roving paradigm experiment, where single nouns from different semantic categories are presented in sequences. Using experimental data from 40 subjects, we show that model-derived semantic surprise significantly predicts the N400 amplitude, substantially outperforming a non-probabilistic baseline model. Investigating the temporal signature of the effect, we find that the effect of semantic surprise on the EEG is restricted to the time window of the N400. Moreover, comparing the topography of the semantic surprise effect to a conventional ERP analysis of predicted vs. unpredicted words, we find that the semantic surprise closely replicates the N400 topography. Our results make a strong case for the role of probabilistic semantic representations in eliciting the N400, and in language comprehension in general.Significance StatementWhen we read or listen to a sentence, our brain continuously analyses its meaning and updates its understanding of it. The N400 brain potential, measured with electrophysiology, is modulated by on-line, meaning related processing. However, its computational underpinnings are still under debate. Inspired by studies of mismatch potentials in perception, here we test the hypothesis that the N400 indexes the surprise of a Bayesian observer of semantic features. We show that semantic surprise predicts the N400 amplitude to single nouns in an oddball like roving paradigm with nouns from different semantic categories. Moreover, the semantic surprise predicts the N400 to a much larger extent than a non-probabilistic baseline model. Our results thus yield further support to the Bayesian brain hypothesis.
Shallow nanopore RNA sequencing enables transcriptome profiling for precision cancer medicine
Authors: Mock Andreas , Braun Melissa , Scholl Claudia , Fröhling Stefan , Erkut Cihan 
Published: May 2022

ABSTRACTTranscriptome profiling is a mainstay of translational cancer research and is increasingly finding its way into precision oncology. While bulk RNA sequencing (RNA-seq) is widely available, high costs and long data return time are limiting factors for clinical applications. We investigated a portable nanopore long-read sequencing device (MinION, Oxford Nanopore Technologies) for transcriptome profiling of tumors. In particular, we investigated the impact of lower coverage than that of larger sequencing devices by comparing shallow nanopore RNA-seq data with short-read RNA-seq data generated using reversible dye terminator technology (Illumina) for ten samples representing four cancer types. Coupled with ShaNTi (Shallow Nanopore Sequencing for Transcriptomics), a newly developed data processing pipeline, a turnaround time of five days was achieved. The correlation of normalized gene-level counts between nanopore and Illumina RNA-seq was high for MinION but not for very low-throughput Flongle flow cells (r = 0.89 and r = 0.24, respectively). A cost-saving approach based on multiplexing of four samples per MinION flow cell maintained a high correlation with Illumina data (r = 0.56 – 0.86). In addition, we compared the utility of nanopore and Illumina RNA-seq data for analysis tools commonly applied in translational oncology: (i) Shallow nanopore and Illumina RNA-seq were equally useful for inferring signaling pathway activities with PROGENy. (ii) Highly expressed genes encoding kinases targeted by clinically approved small-molecule inhibitors were reliably identified by shallow nanopore RNA-seq. (iii) In tumor microenvironment composition analysis, quanTIseq performed better than CIBERSORT, likely due to higher average expression of the gene set used for deconvolution. (iv) Shallow nanopore RNA-seq was successfully applied to validate known gene fusions by breakpoint analysis. These findings suggest that shallow nanopore RNA-seq enables rapid, cost-effective, and biologically meaningful transcriptome profiling of tumors and warrants further exploration in precision cancer medicine studies.