bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACME: an Affinity-based Cas9 Mediated Enrichment method for targeted nanopore sequencing
Authors: Iyer Shruti V , Kramer Melissa , Goodwin Sara , McCombie W. Richard 
Published: February 2022

AbstractTargeted sequencing significantly improves accuracy and coverage and aids in providing the depth necessary to detect rare alleles in a heterogenous population of cells. Until the introduction of nanopore Cas9 Targeted-Sequencing (nCATS), a lack of efficient long-read compatible targeting techniques made it difficult to study specific regions of interest on long-read platforms. Existing nCATS-based strategies are currently limited by the per molecule target lengths capturable (<30kb), requiring several Cas9 guides to tile across larger regions of interest, ultimately reducing the number of targets that can be surveyed per reaction. Also, longer read lengths help reduce mapping errors, making it more likely that complex structural rearrangements can be resolved. Absence of a background reduction step in nCATS also increases the competition between non-target and target fragments in the sequencing pool for pore occupancy, decreasing the overall percentage of on-target reads. To address this, we introduce ACME - an Affinity-based Cas9-Mediated Enrichment method - that helps reduce background reads, increasing on-target coverage and size of target regions that can be spanned with single reads to 100kb.ACME uses a HisTag-based isolation and pulldown of Cas-9 bound non-target reads, reducing the background noise in sequencing. We designed a panel of guide RNAs targeting 10 genes to enrich for specific regions of the cancer genome and tested them in two breast cell lines – MCF 10A and SK-BR-3. These gene targets spanned different size ranges (10kb to 150kb) allowing us to identify the largest target sizes that could be optimally captured by single molecules spanning the entire region. When compared with using just nCATS, the ACME method for background reduction increased the overall coverage across the entire length of all targets by 2-fold to 25-fold. By using ACME to eliminate smaller competing non-targets from the sequencing library, we saw a 3- to 7-fold increase in the number of reads spanning 100% of the gene targets when compared to nCATS. For one of our larger targets, BRCA2, we observed >60-fold target enrichment, close to 70x coverage, and 3-20 reads spanning the entire 95kb target. We observed an increase in enrichment, depth, and number of whole gene spanning reads for other genes on the panel as well across both cell lines, with enrichment as high as 4000-fold for some genes. Furthermore, ACME identified all SVs previously called within our targets by ONT and PacBio whole genome sequencing and performed on par with these platforms for SNP detection when compared with Illumina short-read whole genome sequencing.
Interference of Neuronal TrkB Signaling by the Cannabis-Derived Flavonoids Cannflavins A and B
Authors: Holborn Jennifer , Walczyk-Mooradally Alicyia , Perrin Colby , Alural Begüm , Aitchison Cara , Borenstein Adina , Khokar Jibran Y. , Akhtar Tariq A. , Lalonde Jasmin 
Published: February 2022

ABSTRACTCannflavins A and B are flavonoids that accumulate in the Cannabis sativa plant. These specialized metabolites are uniquely prenylated and highly lipophilic, which, a priori, may permit their interaction with membrane-bound enzymes and receptors. Although previous studies found that cannflavins can produce anti-inflammatory responses by inhibiting the biosynthesis of pro- inflammatory mediators, the full extent of their cellular influence remains to be understood. Here, we studied these flavonoids in relation to the Tropomyosin receptor kinase B (TrkB), a receptor tyrosine kinase that is activated by the growth factor brain-derived neurotrophic factor (BDNF). Using mouse primary cortical neurons, we first collected evidence that cannflavins prevent the accumulation of Activity-regulated cytoskeleton-associated (Arc, also known as Arg3.1) protein upon TrkB stimulation by exogenous BDNF in these cells. Consistent with this effect, we also observed a reduced activation of TrkB and downstream signaling effectors that mediate Arc mRNA transcription when BDNF was co-applied with the cannflavins. Of note, we also performed a high-throughput screen that demonstrated a lack of agonist action of cannflavins towards 320 different G protein-coupled receptors, a result that specifically limit the possibility of a TrkB transinactivation scenario via G protein signaling to explain our results with dissociated neurons. Finally, we used Neuro2a cells overexpressing TrkB to show that cannflavins can block the growth of neurites and increased survival rate produced by the higher abundance of the receptor in this model. Taken together, our study offers a new path to understand the reported effects of cannflavins and other closely related compounds in different cellular contexts.
Systematic lncRNA mapping to genome-wide co-essential pathways uncovers cancer dependency on uncharacterized lncRNAs
Authors: Mitra Ramkrishna , Adams Clare M. , Eischen Christine M. 
Published: February 2022

ABSTRACTQuantification of gene dependency across hundreds of cell lines using genome-scale CRISPR screens have revealed co-essential pathways/modules and critical functions of uncharacterized genes. In contrast to protein-coding genes, robust CRISPR-based loss-of-function screens are lacking for long non-coding RNAs (lncRNAs), which are key regulators of many cellular process, leaving many essential lncRNAs unidentified and uninvestigated. Integrating copy- number, epigenetic, and transcriptomic data of >800 cancer cell lines with CRISPR-derived co-essential pathways, our method recapitulates known essential lncRNAs and predicts proliferation/growth dependency of 289 poorly characterized lncRNAs. Analyzing lncRNA dependencies across ten cancer types and their expression alteration by diverse growth- inhibitors across cell types, we prioritize 30 high-confidence pan-cancer proliferation/growth- regulating lncRNAs. Further evaluating two previously uncharacterized top proliferation-suppressive lncRNAs (PSLR-1, PSLR-2) showed they are transcriptionally regulated by p53, induced by multiple cancer treatments, and significantly correlate to increased cancer patient survival. These lncRNAs modulate G2 cell cycle-regulating genes within the FOXM1 transcriptional network, inducing a G2 arrest and inhibiting proliferation and colony formation. Collectively, our results serve as a powerful resource for exploring lncRNA-mediated regulation of cellular fitness in cancer, circumventing current limitations in lncRNA research.
Hindbrain catecholaminergic inputs to the paraventricular thalamus scale feeding and metabolic efficiency in stress-related contexts
Authors: Dumont Clarisse , Li Guangping , Castel Julien , Luquet Serge , Gangarossa Giuseppe 
Published: February 2022

AbstractThe regulation of food intake and energy balance relies on the dynamic integration of exteroceptive and interoceptive signals monitoring nutritional, metabolic, cognitive and emotional states. The paraventricular thalamus (PVT) is a central hub that, by integrating sensory, metabolic and emotional states, may contribute to the regulation of feeding and homeostatic/allostatic processes. However, the underlying PVT circuits remain still elusive. Here, we aimed at unraveling the role of catecholaminergic (CA) inputs to the PVT in scaling feeding and metabolic efficiency. First, using region-specific retrograde disruption of CA projections, we show that PVT CA inputs mainly arise from the hindbrain, notably the locus coeruleus (LC) and the nucleus tractus solitarius (NTS). Second, taking advantage of integrative calorimetric measurements of metabolic efficiency, we reveal that CA inputs to the PVT scale adaptive feeding and metabolic responses in environmental, behavioral, physiological and metabolic stress-like contexts. Third, we show that hindbrainTH→PVT inputs contribute in modulating the activity of PVT as well as lateral (LH) and dorsomedial (DMH) hypothalamic neurons.In conclusion, this study, by assessing the key role of CA inputs to the PVT in scaling homeostatic/allostatic regulations of feeding patterns, reveals the integrative and converging hindbrainTH→PVT paths that contribute to whole-body metabolic adaptations in stress-like contexts.Key pointsThe paraventricular thalamus (PVT) is known to receive projections from the hindbrain. Here, we confirm and further extend current knowledge on the existence of hindbrainTH→PVT catecholaminergic (CA) inputs, notably from the locus coeruleus (LC) and the nucleus tractus solitarius (NTS), with the NTS representing the main source.Disruption of hindbrainTH→PVT inputs contribute to the modulation of PVT-neurons activity.HindbrainTH→PVT inputs scale feeding strategies in environmental, behavioral, physiological and metabolic stress-like contexts.HindbrainTH→PVT inputs participate in regulating metabolic efficiency and nutrient partitioning in stress-like contexts.HindbrainTH→PVT, directly and/or indirectly, contribute in modulating the downstream activity of lateral (LH) and dorsomedial (DMH) hypothalamic neurons.
Lung epithelial cell-derived C3 protects against pneumonia-induced lung injury
Authors: Ozantürk Ayşe N. , Sahu Sanjaya K. , Kulkarni Devesha H. , Ma Lina , Barve Ruteja A , McPhatter Ja’Nia , Garnica Lorena , Dannull Linus , Kunen Jeremy , Wu Xiaobo , Brody Steven L. , Atkinson John P. , Kulkarni Hrishikesh S. 
Published: February 2022

AbstractThe complement component C3 is a fundamental plasma protein for host defense. However, recent work has demonstrated the critical importance of local C3 expression in cell survival. Here we analyzed the effects of local versus peripheral sources of C3 expression in a model of bacterial pneumonia. While mice with global C3 deficiency had severe pneumonia-induced lung injury, those deficient in liver-deficient C3 remain protected, comparable to wildtype mice.Human lung transcriptome analysis showed secretory epithelial cells are a major source of C3. Mice with a C3 gene ablation from lung epithelial cells had worse pulmonary injury compared to wild type, despite maintaining normal circulating C3 levels. Finally, in human cellular and mouse pneumonia models, we show that C3 reduces epithelial cell death mediated through the alternative pathway component Factor B. Thus, our findings suggest that a locally-derived C3-Factor B pathway protects the lung mucosal barrier.One Sentence SummaryLung-derived C3 mitigates severe bacterial pneumonia suggesting a novel cytoprotective role at mucosal barrier surfaces independent of circulating C3.
Interdisciplinary analyses of Bronze Age communities from Western Hungary reveal complex population histories
Authors: Gerber Dániel , Szeifert Bea , Székely Orsolya , Egyed Balázs , Gyuris Balázs , Giblin Julia I. , Horváth Anikó , Köhler Kitti , Kulcsár Gabriella , Kustár Ágnes , Major István , Molnár Mihály , Palcsu László , Szeverényi Vajk , Fábián Szilvia , Mende Balázs Gusztáv , Bondár Mária , Ari Eszter , Kiss Viktória , Szécsényi-Nagy Anna 
Published: February 2022

AbstractIn this study we report 21 ancient shotgun genomes from present-day Western Hungary, from previously understudied Late Copper Age Baden, and Bronze Age Somogyvár-Vinkovci, Kisapostag, and Encrusted Pottery archaeological cultures (3530 – 1620 cal BCE). Our results indicate the presence of high steppe ancestry in the Somogyvár-Vinkovci culture. They were then replaced by the Kisapostag group, who exhibit an outstandingly high (up to ∼47%) Mesolithic hunter-gatherer ancestry, despite this component being thought to be highly diluted by the time of the Early Bronze Age. The Kisapostag population contributed the genetic basis for the succeeding community of the Encrusted pottery culture. We also found an elevated hunter-gatherer component in a local Baden culture associated individual, but no connections were proven to the Bronze Age individuals. The hunter-gatherer ancestry in Kisapostag is likely derived from two main sources, one from a Funnelbeaker or Globular Amphora culture related population and one from a previously unrecognised source in Eastern Europe. We show that this ancestry not only appeared in various groups in Bronze Age Central Europe, but also made contributions to Baltic populations. The social structure of Kisapostag and Encrusted pottery cultures is patrilocal, similarly to most contemporaneous groups. Furthermore, we developed new methods and method standards for computational analyses of ancient DNA, implemented to our newly developed and freely available bioinformatic package. By analysing clinical traits, we found carriers of aneuploidy and inheritable genetic diseases. Finally, based on genetic and anthropological data, we present here the first female facial reconstruction from the Bronze Age Carpathian Basin.
Musical expertise shapes visual-melodic memory integration
Authors: Hoffmann Martina , Schmidt Alexander , Ploner Christoph J. 
Published: February 2022

AbstractMusic can act as a powerful mnemonic device that can elicit vivid episodic memories. However, how musical information is integrated with non-musical information is largely unknown. Here, we investigated whether and how musical expertise modulates binding of melodies and visual information into integrated memory representations. We reasoned that the significant mnemonic demands of musicianship might alter the underlying integration process and reveal mechanisms by which music promotes retrieval of non-musical memories. Professional musicians and musical laypersons learned overlapping pairs of everyday objects and melodies (AB- and BC-pairs, object-melody and melody-object pairs). Participants were then tested for memory of studied pairs (direct trials) and for inferential AC-decisions (indirect trials). Although musicians showed a higher overall performance than non-musicians, both groups performed well above chance level in both trial types. Non-musicians reacted faster in indirect compared to direct trials, whereas the reverse pattern was found in musicians. Differential correlations of trial type performance between groups further suggested that non-musicians efficiently formed integrated ABC-triplets already during the encoding phase of the task, while musicians separately memorized AB- and BC-pairs and recombined them at retrieval for AC-decisions. Our results suggest that integrative encoding is a default mechanism for integration of musical and non-musical stimuli that works with great efficacy even in musically untrained subjects and may contribute to the everyday experience of music-evoked episodic memories. By contrast, recombination at retrieval seems to be an advanced strategy for memory integration that critically depends on an expert ability to maintain and discriminate musical stimuli across extended memory delays.
Testing the Efficacy of Transungual Drug Delivery System (Nail Lacquer) Containing Terbinafine AgainstAspergillus brasiliensisfor the Topical Treatment of Onychomycosis
Authors: Rao Shivani. H. , Bhalekar Mangesh. R. , Kelkar Samruddhi. H. , Godbole Shivani. S. , Kharche Riddhesh. A. 
Published: February 2022

AbstractAccording to a survey of 42 epidemiological studies, the cases of Non-dermatophyte mould onychomycosis (NDMO) caused by Aspergillus species have been found to increase. The number ranges from <1 to 35% of all cases of onychomycosis in the general population and the number is higher in the diabetic population. Around7.7-100% of cases of NDMO are caused by Aspergillus species. Hence the attempt of investigation to test the efficacy of the drug by transungual drug permeation has been made. The antifungal agent ‘Terbinafine’ was incorporated in a topical dosage form (Nail lacquer). The formulation is optimized by a drug design matrix of 23type using Design-Expert®software, version 11 (DX11). The antifungal assay was performed using the Kirby Bauer disk diffusion method and other evaluation parameters like Drying time, Viscosity are evaluated. Optimized formulation with the highest desirability was selected out of all the possible formulations which showed the best results with good physicochemical properties and antifungal activity. Thus, it can be concluded that medicated nail lacquers containing Terbinafine can be used as a successful method to treat non-dermatophyte mould onychomycosis (NDMO) caused by Aspergillus species.
An approachable, flexible, and practical machine learning workshop for biologists
Authors: Magnano Chris S , Mu Fangzhou , Russ Rosemary S , Cvetkovic Milica , Treu Debora , Gitter Anthony 
Published: February 2022

ABSTRACTThe increasing prevalence and importance of machine learning in biological research has created a need for machine learning training resources tailored towards biological researchers. However, existing resources are often inaccessible, infeasible, or inappropriate for biologists because they require significant computational and mathematical knowledge, demand an unrealistic time-investment, or teach skills primarily for computational researchers. We created the Machine Learning for Biologists (ML4Bio) workshop, a short, intensive workshop that empowers biological researchers to comprehend machine learning applications and pursue machine learning collaborations in their own research. The ML4Bio workshop focuses on classification and was designed around 3 principles: (a) focusing on preparedness over fluency or expertise, (b) necessitating minimal coding and mathematical background, and (c) requiring low time investment. It incorporates active learning methods and custom open source software that allows participants to explore machine learning workflows. After multiple sessions to improve workshop design, we performed a study on 3 workshop sessions. Despite some confusion around identifying subtle methodological flaws in machine learning workflows, participants generally reported that the workshop met their goals, provided them with valuable skills and knowledge, and greatly increased their beliefs that they could engage in research that uses machine learning. ML4Bio is an educational tool for biological researchers, and its creation and evaluation provides valuable insight into tailoring educational resources for active researchers in different domains. The workshop materials are available from https://carpentries-incubator.github.io/ml4bio-workshop/ and the ml4bio software is available from https://github.com/gitter-lab/ml4bio.
Mast Cell Derived Histamine Negatively Regulates Hematopoiesis
Authors: Klein Bailey R. , Smith Julianne N.P. , Katabathula Ramachandra , Chaudhary Rahul , Gao Zhenxiang , Cordova Brittany A. , Petroze Frederick , Tiwari Riya , Gerson Stanton L. , Xu Rong , Markowitz Sanford D. , Desai Amar B. 
Published: February 2022

ABSTRACTHematopoietic stem cells (HSCs) are essential for generating all blood cell types and maintaining immune function and oxygen transport. This requires tight regulation of self-renewal, differentiation, and quiescence, driven by intrinsic and extrinsic signals. While the influence of many HSC progeny on HSC decisions are recognized, the role of mast cells (MCs) remain understudied. MCs are known for their immunomodulatory functions through the secretion of factors such as histamine and could offer new insights into HSC regulation. In this study, we describe a novel role for MC-derived histamine in modulating HSC behavior. We observed that genetically MC-deficient “SASH” mice exhibit increased hematopoietic output and bone marrow (BM) HSCs, characterized by an enhanced quiescent signature that increases resistance to myeloablative chemotherapy. The SASH microenvironment also contained increased frequencies of HSC-supportive cell types and expression of genes conducive to HSC maintenance, which together accelerated HSC engraftment when wild-type BM was transplanted into SASH recipients. Moreover, we found lower serum histamine levels in SASH mice, and that the enhanced hematopoietic phenotype observed in these mice could be reversed by administering exogenous histamine. Subsequent experiments with FDA-approved antihistamines in wild-type mice revealed that cetirizine, an H1R inverse agonist, notably increased HSC frequency in the BM. Overall, our findings implicate MCs are negative regulators of HSC function. This lays the groundwork for future studies to elucidate the underlying mechanisms and explore the therapeutic potential of modulating histamine signaling to promote hematopoiesis.
Science in motion: A qualitative analysis of journalists’ use and perception of preprints
Authors: Fleerackers Alice , Moorhead Laura , Maggio Lauren A. , Fagan Kaylee , Alperin Juan Pablo 
Published: February 2022

AbstractThis qualitative study explores how and why journalists use preprints — unreviewed research papers — in their reporting. Through thematic analysis of interviews conducted with 19 health and science journalists in the second year of the COVID-19 pandemic, it applies a theoretical framework that conceptualizes COVID-19 preprint research as a form ofpost-normal science, characterized by high scientific uncertainty and societal relevance, urgent need for political decision-making, and value-related policy considerations. Findings suggest that journalists approach the decision to cover preprints as a careful calculation, in which the potential public benefits and the ease of access preprints provided were weighed against risks of spreading misinformation. Journalists described viewing unreviewed studies with extra skepticism and relied on diverse strategies to find, vet, and report on them. Some of these strategies represent standard science journalism, while others, such as labeling unreviewed studies as preprints, mark a departure from the norm. However, journalists also reported barriers to covering preprints, as many felt they lacked the expertise or the time required to fully understand or vet the research. The findings suggest that coverage of preprints is likely to continue post-pandemic, with important implications for scientists, journalists, and the publics who read their work.