bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 Omicron BA.1 variant infection of human colon epithelial cells
Authors: Antia Avan , Alvarado David M. , Zeng Qiru , Davis Deanna L. , Ciorba Matthew A. , Ding Siyuan 
Published: April 2022

AbstractOmicron B.1.1.529 became the predominant SARS-CoV-2 variant in early 2022, causing a new wave of public anxiety. Compared to the ancestral strain, Omicron has 50 mutations, with over 30 mutations in the spike protein. These differences likely underlie the changes in Omicron biology noted in other studies, including an attenuation in the lung parenchyma, compared to the ancestral SARS-CoV-2 strain and other variants, as well as a preference for endosomal entry, in place of the TMPRSS2-mediated membrane fusion pathway. This raises questions on Omicron tropism and infectivity in various target organ systems, including the gastrointestinal (GI) tract. Up to 70% of COVID-19 patients report GI symptoms, including nausea, vomiting, and diarrhea. Here, we show that in the context of donor intrinsic genetic heterogeneity, the SARS-CoV-2 Omicron variant infects human colonoids similarly, if not less effectively, than the ancestral WT (WA1) strain or the Delta variant. Additionally, we note a higher ratio of viral RNA to infectious virus titer, which may suggest that Omicron is potentially less infectious in the intestine. This study lays the foundation for further work defining mechanisms mediating intestinal infection and pathogenesis by Omicron.
CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer
Authors: Tsujino Takuya , Takai Tomoaki , Hinohara Kunihiko , Gui Fu , Tsutsumi Takeshi , Bai Xiao , Miao Chenkui , Feng Chao , Gui Bin , Sztupinszki Zsofia , Simoneau Antoine , Xie Ning , Fazli Ladan , Dong Xuesen , Azuma Haruhito , Choudhury Atish D. , Mouw Kent W. , Szallasi Zoltan , Zou Lee , Kibel Adam S. , Jia Li 
Published: April 2022

ABSTRACTProstate cancer (PCa) harboring BRCA1/2 mutations is often exquisitely sensitive to PARP inhibition. However, genomic alterations in other DNA damage response genes have not been consistently predictive of clinical response to PARP inhibitors (PARPis). Here, we perform genome-wide CRISPR-Cas9 knockout screens in BRCA1/2-proficient PCa cell lines and identify novel genes whose loss has a profound impact on PARPi sensitivity and resistance. Specifically, MMS22L deletion, frequently observed (up to 14%) in PCa, renders cells hypersensitive to PARPis by disrupting RAD51 loading required for homologous recombination repair, although this response is TP53-dependent. Unexpectedly, loss of CHEK2 confers resistance rather than sensitivity to PARPis in PCa cells through increased expression of BRCA2, a target of CHEK2-TP53-E2F7-mediated transcriptional repression. Combined PARP and ATR inhibition overcomes PARPi resistance caused by CHEK2 loss. Our findings may inform the use of PARPis beyond BRCA1/2-deficient tumors and support reevaluation of currently used biomarkers for PARPi treatment in PCa.
Evaluation of Long-Short Term Memory Networks for M/EEG Source Imaging with Simulated and Real EEG Data
Authors: Hecker Lukas , Maschke Moritz , Rupprecht Rebekka , Tebartz van Elst Ludger , Kornmeier Jürgen 
Published: April 2022

1AbstractMagneto- and electroencephalography (M/EEG) are widespread techniques to measure neural activityin-vivoat a high temporal resolution but relatively low spatial resolution. Locating the sources underlying the M/EEG poses an inverse problem, which is itself ill-posed. In recent years, a new class of source imaging methods was developed based on artificial neural networks. We present a long-short term memory (LSTM) network to solve the M/EEG inverse problem. It integrates low computational cost, exploitation of both the coarse spatial but also the excellent temporal information from the EEG, input flexibility and robustness to noise. We compared the LSTM network with classical inverse solutions using both simulation data and real EEG data, recorded in epileptic patients during intracranial stimulation. The LSTM network shows higher accuracy on multiple metrics and for varying numbers of neural sources, compared to classical inverse solutions but also compared to our alternative architecture without integration of temporal information. The performance of the LSTM network regarding its robustness to noise and low localization errors renders it a promising inverse solution to be considered in future source localization studies and for clinical applications.
Moss functional traits are important drivers for moss and underlying soil bacterial communities: evidence from a chronosequence in an Icelandic glacier forefield
Authors: Klarenberg Ingeborg J. , Keuschnig Christoph , Salazar Alejandro , Benning Liane G. , Vilhelmsson Oddur 
Published: April 2022

AbstractMosses are among the first colonizing organisms after glacier retreat and can develop into thick moss mats during later successional stages. They are key players in N2fixation through their microbiome, which is an important process for nutrient build-up during primary succession. How these moss-microbe interactions develop during succession is not well-studied and is relevant in the light of climate change and increased glacier retreat.We examined how the bacterial communities associated with two moss species of the genusRacomitriumand the underlying substrate, as well as moss traits and nitrogen fixation, develop along a successional gradient in the glacier forefield of Fláajökull in southeast Iceland. In addition, tested whether moss functional traits, such as total carbon (TC) and nitrogen contents (TN) are drivers of moss and underlying soil bacterial communities.Although time since deglaciation did not affect TN and moisture content, TC and shoot length increased with time since deglaciation. Moss and underlying soil bacterial communities were distinct. While the soil bacterial community structure was driven by the time since deglaciation and moss C/N ratios, the moss bacterial community structure was linked to time since deglaciation and moss moisture content. Moss N2-fixation rates were linked to bacterial community composition andnifHgene abundance rather than moss TN or time since deglaciation. This was accompanied by a shift from autotrophic to heterotrophic diazotrophs.Overall, our results suggest that there is little lateral transfer between moss and soil bacterial communities and that moss traits and time since deglaciation affect moss and soil bacterial community structure. In addition, moss N2-fixation rates are determined by bacterial community structure, rather than moss traits or time since deglaciation.
Tree diversity effects on productivity depend on mycorrhizae and life strategies in a temperate forest experiment
Authors: Dietrich Peter , Ferlian Olga , Huang Yuanyuan , Luo Shan , Quosh Julius , Eisenhauer Nico 
Published: April 2022

AbstractTree species are known to predominantly interact either with arbuscular mycorrhizal (AM) or ectomycorrhizal (EM) fungi. However, there is a knowledge gap whether these mycorrhizae differently influence biodiversity-ecosystem functioning (BEF) relationships and whether a combination of both can increase community productivity. In 2015, we established a tree-diversity experiment by growing tree communities with varying species-richness levels (1, 2, or 4 species), and either with AM or EM tree species, or a combination of both. We investigated basal area and annual basal area increment from 2015 to 2020 as proxy for community productivity. We found significant positive relationships between tree species richness and community productivity, which strengthened over time. Further, AM and EM tree species differently influenced productivity; however, there was no overyielding when AM and EM trees grew together. EM tree communities were characterized by low productivity in the beginning, but an increase of increment over time, and showed overall strong biodiversity effects. For AM tree communities the opposite was true. While young trees did not benefit from the presence of the other mycorrhizal type, dissimilar mechanisms underlying BEF relationships in AM and EM trees indicate that maximizing tree and mycorrhizal diversity may increase ecosystem functioning in the long run.
Spatiotemporal proximity labeling tools to track GlcNAc sugar-modified functional protein hubs during cellular signaling
Authors: Liu Yimin , Nelson Zachary M. , Reda Ali , Fehl Charlie 
Published: April 2022

AbstractA fundamental mechanism that all eukaryotic cells use to adapt to their environment is dynamic protein modification with monosaccharide sugars. In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. The objective of this study was to create intracellular proximity labeling tools to identify functional changes in O-GlcNAc patterns with spatiotemporal control. We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation that we directed to O-GlcNAc protein modifications inside cells, a set of tools we called “GlycoID.” Localized variants to the nucleus and cytosol, nuc-GlycoID and cyt-GlycoID, labeled O-GlcNAc proteins and their interactomes in subcellular space. Labeling during insulin as well as serum stimulation revealed functional changes in O-GlcNAc proteins as soon as 30 minutes of signaling. We demonstrated using proteomic analysis that the GlycoID strategy captured O-GlcNAcylated “activity hubs” consisting of O-GlcNAc proteins and their associated protein-protein interactions. The ability to follow changes in O-GlcNAc hubs during physiological events like insulin stimulation poises these tools to be used for determining mechanisms of glycobiological cell regulation. Our functional O-GlcNAc datasets in human cells will be a useful resource for O-GlcNAc-driven mechanisms.Abstract Figure
Automated detection of sow posture changes with millimeter-wave radars and deep learning
Authors: Dore Alexandre , Lihoreau Mathieu , Bailly Jean , Billon Yvon , Bompa Jean-François , Ricard Edmond , Henry Dominique , Canario Laurianne , Aubert Hervé 
Published: April 2022

AbstractAutomated behavioural monitoring is increasingly required for animal welfare and precision agriculture. In pig farming, detailed analyses of sow activity are essential to identify and reduce the risks of piglets being crushed during postural changes of their mothers. Here we introduce a new, non-invasive, fast and accurate method for monitoring sow behaviour based on millimeter-wave radars and deep learning analysis. We used our method to predict postural changes in crated sows and distinguish the dangerous one that lie down abruptly from those that lie down carefully using transient postures. Two radars were placed on a metal backing above the head and the upper part of the back of each of ten sows to monitor their activity during 5 hours. We analysed the radar data with a convolutional neural network and identified five postures. The average sensitivity was 96.9% for standing, 90.8% for lying, 91.4% for nursing, 87.6% for sitting, but only 11.9% for kneeling. However, the average specificity and accuracy were greater than 92% for the five postures. Interestingly, two of the ten sows occasionally moved directly from standing to lying, without using the transient postures sitting and kneeling, thereby displaying risky behaviours for their piglets. Our radar-based classifier is more accurate, faster and require less memory than current computer vision approaches. Using more sows will improve the algorithm performance and facilitate future applications for large scale deployment in animal farming.HighlightsAutomated behavioural analysis is a major challenge for precision farming.We developed automated detection of lactating sow postures with radars and deep learning.We identified five postures, including transitions risky for the piglets.Our method is accurate, fast and requires less memory than computer vision.Radars thus hold considerable promises for high through-put recording of livestock activity.
Do orexin/hypocretin neurons track sensory, cognitive, or motor information?
Authors: Bracey Eva , Aravind Aditi , Grujic Nikola , Peleg-Raibstein Daria , Burdakov Denis 
Published: April 2022

ABSTRACTActivation of hypothalamic hypocretin/orexin neurons (HONs) is a neural substrate of arousal. HONs activate during sensory stimuli, and are thus thought to regulate arousal according to sensory input. Here, we measured body movements occurring during sound cues or associated reward outcomes, and used an encoding model to ask whether HONs indeed specialize in tracking certain features, or multiplex diverse types of features. Although some single HONs multiplexed feature combinations, during the cue period the overall HON signal primarily tracked body movements. This persisted across cues signaling different reward probabilities, and substantially diverged from reward-probability tracking in concurrently-recorded VTA dopamine neurons. In contrast, during reward outcome, HONs predominantly signaled the presence or absence of reward, and not body movements, nor surprise or reward prediction error. These results describe an unexpectedly specialized and flexible logic of HON activation, suggesting a role for HONs in tracking actions and subsequent reinforcements.
Human blood plasma proteins modeling and binding affinities with Δ9-tetrahydrocannabinol active metabolites: In silico approach
Authors: Rathod Shravan B. , Soni Jinal C. , Verma Priyanshu , Rawat Yogita , Periwal Neha , Arora Pooja , Sood Vikas , Mansuri Mohmedyasin F. 
Published: April 2022

AbstractTetrahydrocannabinol (THC) is a key psychotropic constituent of cannabis sativa. It is also known as Δ9-tetrahydrocannabinol (Δ9-THC). Previous study suggested that owing to its high lipophilicity, it piles up in adipose tissue and it is disseminated into blood stream for prolonged time. Research suggests that numerous diseases such as multiple sclerosis, neurodegenerative disorders, epilepsy, schizophrenia, osteoporosis, cancer, glaucoma and cardiovascular disorders can be treated using this substance. However, apart from having therapeutic potential, many studies have reported detrimental outcomes along with addiction of Δ9-THC for short-term and long-term consumption. Thus, in this study, we determined the binding affinities of Δ9-THC and its two active metabolites, 11-Hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC) and 8beta,11-dihydroxy-Δ9-tetrahydrocannabinol (8β,11-diOH-Δ9-THC) with 401 human blood plasma proteins using molecular docking analysis. Results show that Δ9-THC has greater binding potential with plasma proteins as compared to other two metabolites. Overall, ADGRE5, ALB, APOA5, APOD, CP, PON1 and PON3 proteins showed the highest binding affinities with three cannabis metabolites.
In-cell penetration selection—mass spectrometry produces noncanonical peptides for antisense delivery
Authors: Schissel Carly K. , Farquhar Charlotte E. , Loas Andrei , Malmberg Annika B. , Pentelute Bradley L. 
Published: April 2022

AbstractPeptide-mediated delivery of macromolecules in cells has significant potential therapeutic benefits, but no therapy employing cell-penetrating peptides (CPPs) has reached the market after 30 years of investigation due to challenges in the discovery of new, more efficient sequences. We developed a method for in-cell penetration selection-mass spectrometry (in-cell PS-MS) to discover peptides from a synthetic library capable of delivering macromolecule cargo to the cytosol. This method was inspired by recent in vivo selection approaches for cell-surface screening, with an added spatial dimension resulting from subcellular fractionation. A representative peptide discovered in the cytosolic extract, Pep1a, is nearly 100-fold more active toward antisense phosphorodiamidate morpholino oligomer (PMO) delivery compared to a sequence identified from a whole cell extract, which includes endosomes. Pep1a is composed of D-amino acids and two non-α-amino acids. Pulse-chase and microscopy experiments revealed that while the PMO-Pep1a conjugate is likely taken up by endosomes, it can escape to localize to the nucleus. In-cell PS-MS introduces a means to empirically discover unnatural synthetic peptides for subcellular delivery of therapeutically relevant cargo.
Understanding community level influences on the prevalence of SARS-CoV-2 infection in England
Authors: Joshi Chaitanya , Ali Arif , ÓConnor Thomas , Chen Li , Jahanshahi Kaveh 
Published: April 2022

ABSTRACTUnderstanding and monitoring the major influences on SARS-CoV-2 prevalence is essential to inform policy making and devise appropriate packages of non-pharmaceutical interventions (NPIs). Through evaluating community level influences on the prevalence of SARS-CoV-2 infection and their spatiotemporal variations in England, this study aims to provide some insights into the most important risk parameters. We used spatial clusters developed in Jahanshahi and Jin, 2021 as geographical areas with distinct land use and travel patterns. We also segmented our data by time periods to control for changes in policies or development of the disease over the course of the pandemic. We then used multivariate linear regression to identify influences driving infections within the clusters and to compare the variations of those between the clusters. Our findings demonstrate the key roles that workplace and commuting modes have had on some of the sections of the working population after accounting for several interrelated influences including mobility and vaccination. We found communities of workers in care homes and warehouses and to a lesser extent textile and ready meal industries and those who rely more on public transport for commuting tend to carry a higher risk of infection across all residential area types and time periods.
Overexpressing eukaryotic elongation factor 1 alpha (eEF1A) proteins to promote corticospinal axon repair after injury
Authors: Romaus-Sanjurjo Daniel , Saikia Junmi M. , Kim Hugo J. , Tsai Kristen M. , Le Geneva Q. , Zheng Binhai 
Published: April 2022

AbstractAlthough protein synthesis is hypothesized to have a pivotal role in axonal repair after central nervous system (CNS) injury, the role of core components of the protein synthesis machinery has not been examined. Notably, some elongation factors possess non-canonical functions that may further impact axonal repair. Here, we examined whether overexpressing eukaryotic elongation factor 1 alpha (eEF1A) proteins enhances the collateral sprouting of corticospinal tract (CST) neurons after unilateral pyramidotomy, along with the underlying molecular mechanisms. Compared with axonal regeneration from injured neurons, axonal sprouting from uninjured neurons occurs spontaneously after injury and may represent a more accessible form of axonal repair for clinical translation. We found that overexpressing eEF1A1, eEF1A2 or both proteins in CST neurons increased the levels of pS6, an indicator for mTOR activity, in neuronal somas. In contrast, the levels of pSTAT3 and pAKT were not increased. Strikingly, overexpressing eEF1A2 alone, but neither eEF1A1 alone nor both factors simultaneously, increased protein synthesis and actin rearrangement in CST neurons. While eEF1A1 overexpression only slightly enhanced CST sprouting across the midline into the denervated side in the cervical spinal after pyramidotomy, eEF1A2 overexpression substantially enhanced this sprouting. Surprisingly, co-overexpression of both eEF1A1 and eEF1A2 led to a sprouting phenotype similar to wild-type controls, suggesting an antagonistic effect of overexpressing both proteins. These data provide the first evidence that overexpressing a core component of the translation machinery, eEF1A2, enhances CST sprouting, likely by a combination of increased protein synthesis, mTOR signaling and actin cytoskeleton rearrangement.
Critical race theory, counter-accounting, and the emancipatory potential of counter-stories
Authors: Twyford Erin Jade , Tanima Farzana Aman , George Sendirella 
Published: April 2022

PurposeIn this paper, the authors explore racialisation through human-centric counter-accounts (counter-stories) to bring together critical race theory (CRT) and counter-accounting.Design/methodology/approachThe authors utilise CRT to demonstrate the emancipatory role of counter-stories in (re)telling racialized narratives, specifically the narrative of asylum seekers who arrive by sea and are subjected to the inhumane and oppressive nature of the Australian government's policy of offshore immigration detention.FindingsCounter-stories, as tools of accountability, can make visible oppressive forces and the hidden practices of racialized social practices and norms.Research limitations/implicationsThis paper emphasises that we are not in a post-racial world, and racialisation remains a fundamental challenge. We must continue to refute race as an ontological truth and strive to provide a platform for counter-stories that can spark or drive social change. This requires allies, including academics, to give that platform, support their plight, and offer avenues for change.Originality/valueThe authors introduce CRT as a theoretical tool for examining racialisation, opening space for a more critical confluence of accounting and race with potentially wide-reaching implications for our discipline. The paper also contributes to the limited accounting literature concerning asylum seekers, particularly in the use of counter-stories that offer a way of refuting, or challenging, the majoritarian/dominant narratives around asylum-seeking.