bluuebunny/crossref_metadata_2025_split huggingface dataset:
ILnc: Prioritizing Long Non-coding RNAs for Pan-cancer Analysis of Immune Cell Infiltration
Authors: Li Xinhui , Yang Changbo , Bai Jing , Xie Yunjin , Xu Mengjia , Liu Hui , Shao Tingting , Xu Juan , Li Xia 
Published: March 2022

AbstractThe distribution and extent of immune cell infiltration into solid tumors play pivotal roles in cancer immunology and therapy. Here we introduced an immune long non-coding RNA (lncRNA) signature-based method (ILnc), for estimating the abundance of 14 immune cell types from lncRNA transcriptome data. Performance evaluation through pure immune cell data shows that our lncRNA signature sets can be more accurate than protein-coding gene signatures. We found that lncRNA signatures are significantly enriched to immune functions and pathways, such as immune response and T cell activation. In addition, the expression of these lncRNAs is significantly correlated with expression of marker genes in corresponding immune cells. Application of ILnc in 33 cancer types provides a global view of immune infiltration across cancers and we found that the abundance of most immune cells is significantly associated with patient clinical signatures. Finally, we identified six immune subtypes spanning cancer tissue types which were characterized by differences in immune cell infiltration, homologous recombination deficiency (HRD), expression of immune checkpoint genes, and prognosis. Altogether, these results demonstrate that ILnc is a powerful and exhibits broad utility for cancer researchers to estimate tumor immune infiltration, which will be a valuable tool for precise classification and clinical prediction.
Age- and sex-dependent effects of DNA glycosylase Neil3 on amyloid pathology, adult neurogenesis, and memory in a mouse model of Alzheimer’s disease
Authors: Egiazarian Milena A. , Strømstad Silje , Sakshaug Teri , Nunez-Nescolarde Ana B. , Bethge Nicole , Bjørås Magnar , Scheffler Katja 
Published: March 2022

ABSTRACTOxidative stress generating DNA damage has been shown to be a key characteristic in Alzheimer’s disease (AD). However, how it affects the pathogenesis of AD is not yet fully understood. Neil3 is a DNA glycosylase initiating repair of oxidative DNA base lesions and with a distinct expression pattern in proliferating cells. In brain, its function has been linked to hippocampal-dependent memory and to induction of neurogenesis after stroke and in prion disease. Here, we generated a novel AD mouse model deficient for Neil3 to study the impact of impaired oxidative base lesion repair on the pathogenesis of AD. Our results demonstrate an age-dependent decrease in amyloid-β (Aβ) plaque deposition in female Neil3-deficient AD mice, whereas no significant difference was observed in male mice. Furthermore, male but not female Neil3-deficient AD mice show reduced neural stem cell proliferation in the adult hippocampus and impaired working memory compared to controls. These effects seem to be independent of DNA repair as both sexes show increased level of oxidative base lesions in the hippocampus upon loss of Neil3. Thus, our findings suggest an age- and sex-dependent role of Neil3 in the progression of AD by altering cerebral Aβ accumulation and promoting adult hippocampal neurogenesis to maintain cognitive function.
Reference genome choice and filtering thresholds jointly influence phylogenomic analyses
Authors: Rick Jessica A. , Brock Chad D. , Lewanski Alexander L. , Golcher-Benavides Jimena , Wagner Catherine E. 
Published: March 2022

AbstractMolecular phylogenies are a cornerstone of modern comparative biology and are commonly employed to investigate a range of biological phenomena, such as diversification rates, patterns in trait evolution, biogeography, and community assembly. Recent work has demonstrated that significant biases may be introduced into downstream phylogenetic analyses from processing genomic data; however, it remains unclear whether there are interactions among bioinformatic parameters or biases introduced through the choice of reference genome for sequence alignment and variant-calling. We address these knowledge gaps by employing a combination of simulated and empirical data sets to investigate to what extent the choice of reference genome in upstream bioinformatic processing of genomic data influences phylogenetic inference, as well as the way that reference genome choice interacts with bioinformatic filtering choices and phylogenetic inference method. We demonstrate that more stringent minor allele filters bias inferred trees away from the true species tree topology, and that these biased trees tend to be more imbalanced and have a higher center of gravity than the true trees. We find greatest topological accuracy when filtering sites for minor allele count>3–4 in our 51-taxa data sets, while tree center of gravity was closest to the true value when filtering for sites with minor allele count>1–2. In contrast, filtering for missing data increased accuracy in the inferred topologies; however, this effect was small in comparison to the effect of minor allele filters and may be undesirable due to a subsequent mutation spectrum distortion. The bias introduced by these filters differs based on the reference genome used in short read alignment, providing further support that choosing a reference genome for alignment is an important bioinformatic decision with implications for downstream analyses. These results demonstrate that attributes of the study system and dataset (and their interaction) add important nuance for how best to assemble and filter short read genomic data for phylogenetic inference.
STracking: a free and open-source python library for particle tracking and analysis
Authors: Prigent Sylvain , Valades-Cruz Cesar Augusto , Leconte Ludovic , Salamero Jean , Kervrann Charles 
Published: March 2022

AbstractSummaryAnalysis of intra and extra cellular dynamic like vesicles transport involves particle tracking algorithms. Designing a particle tracking pipeline is a routine but tedious task. Therefore, particle dynamics analysis is often performed by combining several pieces of software (filtering, detection, tracking…) requiring a lot of manual operations, and therefore leading to poorly reproducible results. A good synergy between particle detector with a tracker is of paramount importance. In addition, a user-friendly interface to control the quality of estimated trajectories is necessary. To address these issues, we developed STracking a python library that allows to combine algorithms into standardized particle tracking pipelines.Availability and ImplementationSTracking is available as a python library using “pip install” and the source code is publicly available on GitHub (https://github.com/sylvainprigent/stracking). A graphical interface is available using two napari plugins: napari-stracking and napari-tracks-reader. These napari plugins can be installed via the napari plugins menu or using “pip install”. The napari plugin source codes are available on GitHub (https://github.com/sylvainprigent/napari-tracks-reader, https://github.com/sylvainprigent/napari-stracking).Contactsylvain.prigent@inria.fr, cesar-augusto.valades-cruz@curie.fr
A distinct subset of oligodendrocyte lineage cells interact with the developing dorsal root entry during its genesis
Authors: Green Lauren A. , Gallant Robert , Brandt Jacob P. , Nichols Evan L. , Smith Cody J. 
Published: March 2022

ABSTRACTOligodendrocytes are the myelinating cell of the CNS and are critical for the functionality of the nervous system. In the packed CNS, we know distinct profiles of oligodendrocytes are present. Here, we used intravital imaging in zebrafish to identify a distinct oligodendrocyte lineage cell (OLC) that resides on the dorsal root ganglia sensory neurons in the spinal cord. Our profiling of OLC cellular dynamics revealed a distinct cell cluster that interacts with peripheral sensory neurons at the dorsal root entry zone (DREZ). With pharmacological, physical and genetic manipulations, we show that the entry of dorsal root ganglia pioneer axons across the DREZ is important to produce sensory located oligodendrocyte lineage cells. These oligodendrocyte lineage cells on peripherally derived sensory neurons display distinct processes that are stable and do not express mbp. Upon their removal, sensory behavior related to the DRG neurons is abolished. Together, these data support the hypothesis that peripheral neurons at the DREZ can also impact oligodendrocyte development.
CATHe: Detection of remote homologues for CATH superfamilies using embeddings from protein language models
Authors: Nallapareddy Vamsi , Bordin Nicola , Sillitoe Ian , Heinzinger Michael , Littmann Maria , Waman Vaishali , Sen Neeladri , Rost Burkhard , Orengo Christine 
Published: March 2022

1.AbstractCATH is a protein domain classification resource that combines an automated workflow of structure and sequence comparison alongside expert manual curation to construct a hierarchical classification of evolutionary and structural relationships. The aim of this study was to develop algorithms for detecting remote homologues that might be missed by state-of-the-art HMM-based approaches. The proposed algorithm for this task (CATHe) combines a neural network with sequence representations obtained from protein language models. The employed dataset consisted of remote homologues that had less than 20% sequence identity. The CATHe models trained on 1773 largest, and 50 largest CATH superfamilies had an accuracy of 85.6+−0.4, and 98.15+−0.30 respectively. To examine whether CATHe was able to detect more remote homologues than HMM-based approaches, we employed a dataset consisting of protein regions that had annotations in Pfam, but not in CATH. For this experiment, we used highly reliable CATHe predictions (expected error rate <0.5%), which provided CATH annotations for 4.62 million Pfam domains. For a subset of these domains from homo sapiens, we structurally validated 90.86% of the predictions by comparing their corresponding AlphaFold structures with experimental structures from the CATHe predicted superfamilies.
Quantitative Analysis of Transcriptome Dynamics Provides Novel Insights into Developmental State Transitions
Authors: Johnson Kristin , Freedman Simon , Braun Rosemary , LaBonne Carole 
Published: March 2022

AbstractDuring embryogenesis, the developmental potential of initially pluripotent cells becomes progressively restricted as they transit to lineage restricted states. The pluripotent cells of Xenopus blastula-stage embryos are an ideal system in which to study cell state transitions during developmental decision-making, as gene expression dynamics can be followed at high temporal resolution. Here we use transcriptomics to interrogate the process by which pluripotent cells transit to four different lineage-restricted states: neural progenitors, epidermis, endoderm and ventral mesoderm, providing quantitative insights into the dynamics of Waddington’s landscape. Our findings shed light on why the neural progenitor state is the default lineage state for pluripotent cells, and uncover novel components of lineage-specific gene regulation. These data reveal an unexpected overlap in the transcriptional responses to BMP4/7 and activin signaling, and provide mechanistic insight into how the timing of signaling inputs such as BMP are temporally controlled to ensure correct lineage decisions. Together these analyses provide quantitative insights into the logic and dynamics of developmental decision making in early embryos.
Continuing decline of the eastern quoll in Tasmania
Authors: Cunningham Calum X , Aandahl Zach , Jones Menna E , Hamer Rowena , Johnson Christopher N 
Published: March 2022

AbstractLike many other Australian mammals, the eastern quoll (Dasyurus viverrinus)was widespread on the Australian mainland but went extinct there during the 20th century. The species remained abundant in Tasmania until a rapid decline occurred from 2001 to 2003, coinciding with a period of unsuitable weather. We provide an updated analysis of eastern quoll population trends in Tasmania by analysing a Tasmania-wide time series of annual spotlight counts (1985-2019). Eastern quolls were widespread and abundant in Tasmania until the early 2000s. A distinct change occurred in the early 2000s in the east and northeast, which led to severe population reductions. However, we present new evidence of an earlier decline in the north (mid-1990s) and a more recent decline around 2009 in the south. Range-wide declines have continued unabated during the last decade, resulting in a ∼67% decline (since the late 1990s) in the area with high quoll abundance. Although the timing of the major decline in the early 2000s coincided with unfavourable weather, the continuing decline and more recent change points suggest other causes are also involved. We can no longer assume that the existence of eastern quolls in Tasmania ensures the species’ long-term survival, highlighting the urgent need to increase efforts to conserve the remaining populations in Tasmania.
Influenza A Virus Exacerbates Group A Streptococcus Infection and Thwarts Anti-bacterial Inflammatory Responses in Murine Macrophages
Authors: Aleith Johann , Brendel Maria , Weipert Erik , Müller Michael , Schultz Daniel ,   Ko-Infekt Study Group, Müller-Hilke Brigitte 
Published: March 2022

AbstractSeasonal influenza epidemics pose a considerable hazard for global health. In the past decades, accumulating evidence revealed that influenza A virus (IAV) renders the host vulnerable to bacterial superinfections which in turn are a major cause for morbidity and mortality. However, whether the impact of influenza on anti-bacterial innate immunity is restricted to the vicinity of the lung or systemically extends to remote sites is underexplored. We therefore sought to investigate intranasal infection of adult C57BL/6J mice with IAV H1N1 in combination with bacteremia elicited by intravenous application of Group A Streptococcus (GAS). Co-infectionin vivowas supplementedin vitroby challenging murine bone marrow derived macrophages and exploring gene expression and cytokine secretion. Our results show that viral infection of mice caused mild disease and induced the depletion of CCL2 in the periphery. Influenza preceding GAS infection promoted the occurrence of paw edemas and was accompanied by exacerbated disease scores.In vitroco-infection of macrophages led to significantly elevated expression of TLR2 and CD80 compared to bacterial mono-infection, whereas CD163 and CD206 were downregulated. The GAS-inducible upregulation of inflammatory genes, such asNos2, as well as the secretion of TNFα and IL-1β were notably reduced or even abrogated following co-infection. Our results indicate that IAV primes an innate immune layout that is inadequately equipped for bacterial clearance.
Repetitive Transcranial Magnetic Stimulation for Tobacco Treatment in Cancer Patients: A Preliminary Report of a One-Week Treatment
Authors: Li Xingbao , Toll Benjamin A. , Carpenter Matthew J. , Nietert Paul J , Dancy Morgan , George Mark S. 
Published: March 2022

AbstractBackgroundSmoking cessation represents a significant opportunity to improve cancer survival rates, reduce the risk of cancer treatment complications, and improve quality of life. However, about half of cancer patients who smoke continue to smoke despite the availability of several treatments. Previous studies demonstrate that repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) decreases cue craving, reduces cigarette consumption, and increases the quit rate in tobacco use disorder. We investigated whether 5 sessions of rTMS can be safely and efficaciously used for smoking cessation in cancer patients.MethodsWe enrolled 11 treatment-seeking smokers with cancer (> 5 cigarettes per day) in a randomized, double-blind, sham-controlled proof-of-concept study. Participants received 5 daily sessions of active 10Hz rTMS of the left DLPFC (3000 pulses per session) or sham rTMS, and were followed up for 1 month via phone assessments. Main outcomes included reductions in the number of smoked-cigarettes per day (primary) and craving (secondary). Adverse effects were reported daily by participants.ResultsSeven of 11 participants completed 5 sessions of rTMS over one week. Compared to sham treatment (n = 4), the active rTMS (n = 3) exhibited modest effects overtime on smoking (Cohen’s f2 effect size of 0.16) and large effects on cue craving (Cohen’s f2 = 0.40). No serious side effects related to rTMS were reported in the treatment.ConclusionsFive sessions of daily rTMS over the left DLPFC might benefit cancer patients who smoke cigarettes. However, further evidence is needed to determine with more certainty its therapeutic effect and adverse effects for cancer patients who smoke cigarettes.
PTPRG activates m6A methyltransferase VIRMA to block mitochondrial autophagy mediated neuronal death in Alzheimer’s disease
Authors: Luo Jiefeng , Huang Xiaohua , Li Rongjie , Xie Jieqiong , Chen Liechun , Zou Chun , Pei Zifei , Mao Yingwei , Zou Donghua 
Published: March 2022

AbstractIn Alzheimer’s disease (AD), neuronal death is one of the key pathology. However, the initiation of neuronal death in AD is far from clear, and new targets are urgently needed to develop effective therapeutic methods. This study analyzed sequencing data from single-cell RNAseq and spatialomics, and revealed the impact of global single-cell mapping and cell spatial distribution relationships in early stage of AD. We found that microglia subpopulation Mic_PTPRG can anchor neurons based on ligand-receptor interaction pairs and cause ectopic expression of PTPRG in neurons during AD progression. PTPRG in neurons can bind and upregulate VIRMA expression, which in turn increases the level of m6A methylation, enhances PRKN transcript degradation and represses translation. Repressed PRKN expression blocks the clearance of damaged mitochondria in neurons, which in turn reprograms neuronal energy and nutrient metabolic pathways and leads to neuronal death during AD progression. This study elucidates novel mechanisms, by which the PTPRG-dependent microglia-synaptic modification may play a role in AD, providing a new scientific basis for potential therapeutic targets for AD.
SEROLOGICAL TESTING OF BLOOD DONORS TO CHARACTERISE THE IMPACT OF COVID-19 IN MELBOURNE, AUSTRALIA, 2020
Authors: Machalek Dorothy A , Vette Kaitlyn M , Downes Marnie , Carlin John B , Nicholson Suellen , Hirani Rena , Irving David O , Gosbell Iain B , Gidding Heather F , Shilling Hannah , Aung Eithandee , Macartney Kristine , Kaldor John M 
Published: March 2022

AbstractRapidly identifying and isolating people with acute SARS-CoV-2 infection has been a core strategy to contain COVID-19 in Australia, but a proportion of infections go undetected. We estimated SARS-CoV-2 specific antibody prevalence (seroprevalence) among blood donors in metropolitan Melbourne following a COVID-19 outbreak in the city between June and September 2020. The aim was to determine the extent of infection spread and whether seroprevalence varied demographically in proportion to reported cases of infection. The design involved stratified sampling of residual specimens from blood donors (aged 20–69 years) in three postcode groups defined by low (<3 cases/1,000 population), medium (3-7 cases/1,000 population) and high (>7 cases/1,000 population) COVID-19 incidence based on case notification data. All specimens were tested using the Wantai SARS-CoV-2 total antibody assay. Seroprevalence was estimated with adjustment for test sensitivity and specificity for the Melbourne metropolitan blood donor and residential populations, using multilevel regression and poststratification. Overall, 4,799 specimens were collected between 23 November and 17 December 2020. Seroprevalence for blood donors was 0.87% (90% credible interval: 0.25–1.49%). The highest estimates, of 1.13% (0.25–2.15%) and 1.11% (0.28–1.95%), respectively, were observed among donors living in the lowest socioeconomic areas (Quintiles 1 and 2) and lowest at 0.69% (0.14–1.39%) among donors living in the highest socioeconomic areas (Quintile 5). When extrapolated to the Melbourne residential population, overall seroprevalence was 0.90% (0.26–1.51%), with estimates by demography groups similar to those for the blood donors. The results suggest a lack of extensive community transmission and good COVID-19 case ascertainment based on routine testing during Victoria’s second epidemic wave. Residual blood donor samples provide a practical epidemiological tool for estimating seroprevalence and information on population patterns of infection, against which the effectiveness of ongoing responses to the pandemic can be assessed.
Multi-omics comparison of malignant and normal uveal melanocytes reveals novel molecular features of uveal melanoma
Authors: Gentien David , Saberi-Ansari Elnaz , Servant Nicolas , Jolly Ariane , de la Grange Pierre , Némati Fariba , Liot Géraldine , Saule Simon , Teissandier Aurélie , Bourchis Deborah , Girard Elodie , Wong Jennifer , Planchon Julien Masliah , Rodrigues Manuel , Gaudé Laure Villoing , Reyes Cécile , Bazire Matéo , Chenegros Thomas , Bohec Mylene , Baulande Sylvain , M’kacher Radhia , Jeandidier Eric , Nicolas André , Decaudin Didier , Cassoux Nathalie , Piperno-Neumann Sophie , Stern Marc-Henri , Gibcus Johan Harmen , Dekker Job , Heard Edith , Roman-Roman Sergio , Waterfall Joshua J. 
Published: March 2022

AbstractUveal Melanoma (UM) is a rare cancer resulting from transformation of melanocytes residing in the uveal tract. Integrative analysis has identified four molecular and clinical subsets in UM. To improve our molecular understanding of UM we performed extensive multi-omics characterization comparing two aggressive UM patient-derived xenograft models with normal choroidal melanocytes, including DNA optical mapping, specific histone modifications, and DNA topology analysis by Hi-C. Our gene expression and cytogenetic analyses suggest that genomic instability is a hallmark of UM. We also identified a recurrent deletion in the BAP1 promoter resulting in loss of expression and associated with high risk of metastases in UM patients. Hi-C revealed chromatin topology changes associated with up-regulation of PRAME, an independent prognostic biomarker in UM and potential therapeutic target. Our findings illustrate how multi-omics approaches can improve the understanding of tumorigenesis and reveals two novel mechanisms of gene expression dysregulation in UM.
Accelerating PERx Reaction Enables Covalent Nanobodies for Potent Neutralization of SARS-Cov-2 and Variants
Authors: Yu Bingchen , Li Shanshan , Tabata Takako , Wang Nanxi , Kumar G. Renuka , Liu Jun , Ott Melanie M. , Wang Lei 
Published: March 2022

ABSTRACTThe long-lasting COVID-19 pandemic and increasing SARS-CoV-2 variants demand effective drugs for prophylactics and treatment. Protein-based biologics offer high specificity yet their noncovalent interactions often lead to drug dissociation and incomplete inhibition. Here we developed covalent nanobodies capable of binding with SARS-CoV-2 spike protein irreversibly via proximity-enabled reactive therapeutic (PERx) mechanism. A novel latent bioreactive amino acid FFY was designed and genetically encoded into nanobodies to accelerate PERx reaction rate. After covalent engineering, nanobodies binding with the Spike in the down state, but not in the up state, were discovered to possess striking enhancement in inhibiting viral infection. In comparison with the noncovalent wildtype nanobody, the FFY-incorporated covalent nanobody neutralized both authentic SARS-CoV-2 and its Alpha and Delta variants with potency drastically increased over tens of folds. This PERx-enabled covalent nanobody strategy and uncovered insights on potency increase can be valuable to developing effective therapeutics for various viral infections.