bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global surveillance of novel SARS-CoV-2 variants
Authors: Patel Selina , Cumming Fergus , Mayers Carl , Charlett André , Riley Steven 
Published: April 2023

AbstractEarlier global detection of novel SARS-CoV-2 variants gives governments more time to respond. However, few countries can implement timely national surveillance resulting in gaps in monitoring. The UK implemented large-scale community and hospital surveillance, but experience suggests it may be faster to detect new variants through testing UK arrivals for surveillance. We developed simulations of the emergence and importation of novel variants with a range of infection hospitalisation rates (IHR) to the UK. We compared time taken to detect the variant though testing arrivals at UK borders, hospital admissions, and the general community. We found that sampling 10-50% of arrivals at UK borders could confer a speed advantage of 3.5-6 weeks over existing community surveillance, and 1.5–5 weeks (depending on IHR) over hospital testing. We conclude that directing limited global capacity for surveillance to highly connected ports could speed up global detection of novel SARS-CoV-2 variants.
ReCom: A semi-supervised approach to ultra-tolerant database search for improved identification of modified peptides
Authors: Laguillo-Gómez Andrea , Calvo Enrique , Martín-Cófreces Noa , Lozano-Prieto Marta , Sánchez-Madrid Francisco , Vázquez Jesús 
Published: April 2023

AbstractOpen-search methods allow unbiased, high-throughput identification of post-translational modifications in proteins at an unprecedented scale. The performance of current open-search algorithms is diminished by experimental errors in the determination of the precursor peptide mass. In this work we propose a semi-supervised open search approach, called ReCom, that minimizes this effect by taking advantage of a priori known information from a reference database, such as Unimod or a database provided by the user. We present a proof-of-concept study using Comet-ReCom, an improved version of Comet-PTM. Comet-ReCom increased identification performance of Comet-PTM by 68%. This increased performance of Comet-ReCom to score the MS/MS spectrum comes in parallel with a significantly better assignation of the monoisotopic peak of the precursor peptide in the MS spectrum, even in cases of peptide coelution. Our data demonstrate that open searches using ultra-tolerant mass windows can benefit from using a semi-supervised approach that takes advantage from previous knowledge on the nature of protein modifications.For Table of Contents Only
Chimera alert! The threat of chimeric sequences causing inaccurate taxonomic classification of phytoplasma strains
Authors: Tiwarekar Bhavesh , Kirdat Kiran , Sathe Shivaji , Foissac Xavier , Yadav Amit 
Published: April 2023

AbstractThe 16S rRNA gene is a primary marker used to study bacterial taxonomy, particularly for bacteria with ‘Candidatus’ status, where it serves as a primary reference sequence for identification. Despite its usefulness, ensuring the authenticity of publicly available sequences has always posed a challenge. To address this issue, multiple tools and databases with curated collections of reference 16S rRNA gene sequences were established. However, even with these efforts, many sequence chimeras still exist. These chimeric gene sequences are formed by the fusion of sequence parts from multiple organisms and can arise from errors during PCR amplification or sequencing. The objective of this study was to identify chimeric sequences from a dataset of over 4500 phytoplasma 16S rRNA gene sequences using multiple tools. The tools ChimeraSlayer and UCHIME identified 12 and 11 chimeric sequences, respectively. Notably, these sequences included the reference 16S rRNA gene sequence of ‘Ca. Phytoplasma wodyetiae’ strain Bangi-2 (KC844879) and ‘Ca. Phytoplasma allocasuarinae’ (AY135523). The study’s outcomes indicated the existence of chimeric 16S rRNA gene sequences, emphasizing the threat posed by such sequences in correctly assigning taxonomic status to phytoplasma strains. These findings underscore the importance of rigorously verifying the authenticity of 16S rRNA gene sequences to ensure their accuracy in identifying and classifying bacterial species.
Effect of temperature on mosquito olfaction
Authors: Lahondère Chloé , Vinauger Clément , Liaw Jessica E. , Tobin Kennedy K.S. , Joiner Jillian M. , Riffell Jeffrey A. 
Published: April 2023

ABSTRACTMosquitoes use a wide range of cues to find a host to feed on, eventually leading to the transmission of pathogens. Among them, olfactory cues (e.g., host emitted odors, including CO2, and skin volatiles) play a central role in mediating host seeking behaviors. While mosquito olfaction can be impacted by many factors, such as the physiological state of the insect (e.g., age, reproductive state), the impact of environmental temperature on the olfactory system remains unknown. In this study, we quantified the behavioral responses ofAedes aegyptimosquitoes, vectors of dengue, yellow fever and Zika viruses, to host and plant related odors under different environmental temperatures.
A late Neanderthal reveals genetic isolation in their populations before extinction
Authors: Slimak Ludovic , Vimala Tharsika , Seguin-Orlando Andaine , Metz Laure , Zanolli Clément , Joannes-Boyau Renaud , Frouin Marine , Arnold Lee J. , Demuro Martina , Devièse Thibaut , Comeskey Daniel , Buckley Michael , Camus Hubert , Muth Xavier , Lewis Jason E. , Bocherens Hervé , Yvorra Pascale , Tenailleau Christophe , Duployer Benjamin , Coqueugniot Hélène , Dutour Olivier , Higham Thomas , Sikora Martin 
Published: April 2023

SummaryNeanderthal genomes have been recovered from sites across Eurasia, painting an increasingly complex picture of their populations’ structure, mostly indicating that late European Neanderthals belonged to a single metapopulation with no significant evidence of deep population structure. Here we report the discovery of a late Neanderthal individual, nicknamed “Thorin”, from Grotte Mandrin in Mediterranean France, and his genome. These dentognathic fossils, including a rare example of distomolars, are associated with a rich archeological record of their final technological traditions in this region ∼50-42 thousand years ago. Thorin’s genome reveals a deep divergence with other late Neanderthals. Thorin belonged to a population with small group size that showed no genetic introgression with other known late European Neanderthals, revealing genetic isolation of his lineage despite them living in neighboring regions. These results have important implications for resolving competing hypotheses about causes of the Neanderthals’ disappearance.One Sentence SummaryA new French Neanderthal fossil and its genome reveal complex population dynamics during the past 100,000 years.
Time-resolved single-cell and spatial gene regulatory atlas of plants under pathogen attack
Authors: Nobori Tatsuya , Monell Alexander , Lee Travis A. , Zhou Jingtian , Nery Joseph , Ecker Joseph R. 
Published: April 2023

AbstractPlant leaf intercellular space provides a nutrient-rich and heterogeneous niche for microbes that critically impacts plant health. However, how individual plant cells respond to heterogeneous microbial colonization remains largely elusive. Here, by time-resolved simultaneous single-cell transcriptome and epigenome profiling of plants (Arabidopsis thaliana) infected by virulent and avirulent bacterial pathogens (Pseudomonas syringae), we present cell atlases with gene regulatory logic involving transcription factors, putativecis-regulatory elements, and target genes associated with disease and immunity. We also identify previously uncharacterized cell populations with distinct immune gene expression within major developmental cell types. Furthermore, we employ time-resolved spatial transcriptomics to reveal spatial heterogeneity of plant immune responses linked to pathogen distribution. Integrating our single-cell multiomics and spatial omics data enables spatiotemporal mapping of defense gene regulatory logic with pathogen cells. Our study provides a molecularly-defined spatiotemporal map of plant-microbe interaction at the single-cell resolution.
High methane flux in a tropical peatland post-fire is linked to homogenous selection of diverse methanogenic archaea
Authors: Bandla Aditya , Akhtar Hasan , Lupascu Massimo , Sukri Rahayu Sukmaria , Swarup Sanjay 
Published: April 2023

AbstractTropical peatlands in South-East Asia are some of the most carbon dense ecosystems in the world. Recurrent wildfires in repurposed peatlands release massive amounts of carbon and other greenhouse gases, strongly alter peat geochemistry and physicochemical conditions. However, little is known about the impact of fire on peat microbiome composition, microbial guilds contributing to greenhouse gas emissions, and their predictability based on environmental conditions. Here, we address this gap by studying peat microbiomes from fire-affected and intact areas of a tropical peatland in Brunei using high-throughput sequencing and ecological process modelling at the community and clade levels. We show that fire disrupts depth-stratification of peat microbiomes with the strongest effects observed at 1m below the surface. The enrichment of specific taxa and methanogenic archaea at such depths suggests an adaptation to low-energy conditions post-fire. Finally, fire shifts archaeal community composition and clades containing abundant methanogens in a homogeneous manner that can be predicted from environmental conditions and functional traits. Together, our findings provide a biological basis for earlier work which reported elevated methane flux 2-3 years post-fire and show that such changes follow predictable trajectories with important implications for post-fire microbiome forecasting and ecosystem recovery efforts.
Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression
Authors: Huang Kie Kyon , Ma Haoran , Uchihara Tomoyuki , Sheng Taotao , Chong Roxanne Hui Heng , Zhu Feng , Srivastava Supriya , Tay Su Ting , Sundar Raghav , Tan Angie Lay Keng , Ong Xuewen , Lee Minghui , Ho Shamaine Wei Ting , Lesluyes Tom , Van Loo Peter , Chua Joy Shijia , Ramnarayanan Kalpana , Ang Tiing Leong , Khor Christopher , Lee Jonathan Wei Jie , Tsao Stephen Kin Kwok , Teh Ming , Chung Hyunsoo , So Jimmy Bok Yan , Yeoh Khay Guan , Tan Patrick , Cancer Consortium Singapore Gastric 
Published: April 2023

AbstractIntestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We analyzed 1256 gastric samples (1152 IMs) from 692 subjects through a prospective 10-year study. We identified 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9), largely occurring as small clonal events. Analysis of clonal dynamics between and within subjects, and also longitudinally across time, revealed that IM clones are likely transient but increase in size upon progression to dysplasia, with eventual transmission of somatic events to paired GCs. Single-cell and spatial profiling highlighted changes in tissue ecology and lineage heterogeneity in IM, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling revealed expression-based molecular subtypes of IM, including a body-resident “pseudoantralized” subtype associated with incomplete histology, antral/intestinal cell types,ARID1Amutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical- genomic models outperform clinical-only models in predicting IMs likely to progress. Our results raise opportunities for GC precision prevention and interception by highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression.
Comprehensive insight into the alterations in the gut microbiome and the intestinal barrier as a consequence of iron deficiency anaemia
Authors: Soriano-Lerma Ana , García-Burgos María , Barton Wiley , Muñoz-Alférez María José , Crespo-Pérez Jorge Valentín , Soriano Miguel , López-Aliaga Inmaculada , Cotter Paul D. , García-Salcedo José Antonio 
Published: April 2023

AbstractBackgroundIron is an essential micronutrient for all living organisms, and as such, iron deficiency is the top leading cause of anaemia. Iron supplements have been shown to be detrimental to the gut microbiome and the intestinal epithelium, triggering dysbiosis and an impaired gut barrier. However, a comprehensive analysis of these two aspects have not been performed during IDA. This study aims to delve further into the analysis of the gut microbiome in an animal model of IDA and to relate microbial changes to the biological processes occurring in the colonic epithelium, with a special focus on the gut barrier. This in-depth analysis might mean a step forward minimising the negative impact of iron supplements on intestinal health during IDA.MethodsIDA was experimentally induced in an animal model through the use of an iron deficient diet. Shotgun sequencing was used to gain insight into alterations of the gut microbiome in the most affected intestinal region during IDA, the colon. Histological analyses, mRNA sequencing (RNA-Seq), qPCR and immunofluorescence were used to study transcriptionally deregulated processes in the colonic epithelium. Determinations of lipopolysaccharide and bacteria-specific immunoglobulins were performed to assess microbial translocation.ResultsMicrobial metabolism in the colon shifted towards an increased production of certain amino acids, short chain fatty acids and nucleotides, withClostridiumspecies being enriched during IDA. Structural alterations of the colonic epithelium were shown by histological analysis. RNA-Seq revealed a downregulation of extracellular matrix-associated genes and proteins and an overall underdeveloped epithelium. Increased levels of serum LPS in the anaemic animals and an increased immune response against IDA dysbiotic bacteria support an impairment in the integrity of the gut barrier.ConclusionsIDA negatively impacts the gut microbiome and the intestinal barrier, triggering an increased microbial translocation. This study emphasizes the deterioration of gut health during IDA and the fact that it should be addressed when treating the disease.
Universal method for generating knockout mice in multiple genetic backgrounds using zygote electroporation
Authors: Tamari Tomohiro , Ikeda Yoshihisa , Morimoto Kento , Kobayashi Keiko , Mizuno-Iijima Saori , Ayabe Shinya , Kuno Akihiro , Mizuno Seiya , Yoshiki Atsushi 
Published: April 2023

AbstractGenetically engineered mouse models are essential tools for understanding mammalian gene functions and disease pathogenesis. Genome editing allows for the generation of these models in multiple inbred strains of mice without backcrossing. Zygote electroporation dramatically removed the barrier for introducing the CRISPR-Cas9 complex in terms of cost and labour. However, the editing conditions and protocols to produce knockout lines have been optimised for a limited number of strains or stocks. Here, we demonstrate a novel and universal approach for generating knockout mice in multiple inbred strains. By combining in vitro fertilisation and electroporation, we obtained founders for knockout alleles in 8 common inbred strains. Long-read sequencing analysis detected not only intended mutant alleles but also differences in read frequency of intended and unintended alleles among strains. Successful germline transmission of knockout alleles demonstrated that our novel approach can establish mutant mice targeting the same locus in multiple inbred strains for phenotyping analysis, contributing to reverse genetics and human disease research.Summary statementUniversal method for zygote genome editing in multiple inbred mouse strains allows for generation of novel mutant mice for understanding mammalian gene function and human disease pathogenesis.
The exosome degrades chromatin-associated RNAs genome-wide and maintains chromatin homeostasis
Authors: Planells Jordi , Jordán-Pla Antonio , Jain Shruti , Guadalupe Juan José , Proux-Wera Estelle , Euler Anne von , Pelechano Vicent , Visa Neus 
Published: April 2023

ABSTRACTChromatin-associated RNAs (caRNAs) modulate chromatin organization and function. The RNA exosome degrades different types of nuclear transcripts, but its role in chromatin has not been addressed. Here we have usedDrosophila melanogasterS2 cells as a model system to identify the repertoire of caRNAs and establish the role of the exosome in their regulation. We have analyzed both unique and repetitive sequences, and combining RNA-seq and ATAC-seq we show that the simultaneous depletion of the exosome catalytic subunits RRP6 and DIS3 not only affects caRNA levels but also changes the local chromatin accessibility at specific loci. We have identified a group of exosome-sensitive genes that are involved in developmental regulation and are characterized by a balanced chromatin state in which Polycomb and Trithorax factors coexist. Our results reveal that RNA degradation by the exosome is an important mechanism for the homeostasis of such balanced chromatin states. Given that eukaryotic genomes are repetitive to a large extent, we have also analyzed repetitive caRNAs (rep-caRNAs) and we show that the exosome is needed to control repcaRNA levels and to maintain the degree of chromatin packaging in repetitive genomic regions. This role is particularly relevant in the pericentromeric regions where the exosome is required to silence LTR elements and maintain centromere organization.
Clostridium butyricumandClostridium tyrobutyricum: angle or devil for Necrotizing enterocolitis?
Authors: Tao Ruizhi , Zong Gangfan , Pan Yehua , Li Hongxing , Cheng Peng , Deng Rui , Chen Wenxing , Wang Aiyun , Xia Shishan , Tang Weibing , Lu Yin , Wei Zhonghong 
Published: April 2023

AbstractBackgroundNecrotizing enterocolitis (NEC), high incidence and case-fatality rate among premature neonates, is a frustrating gastrointestinal disease which hard to eradicate currently for its unclear pathogenesis and mechanisms. What has been conformed is that the gut microbes dysbiosis happens before the occurrence of NEC, providing robust evidence for the usage of probiotic therapy. Hence, we mainly concentrated on two probiotics: Clostridium butyricum and Clostridium tyrobutyricum especially after the breakthrough in discovering that several clostridia species have associations with NEC.ResultTo verify whether these two clostridia are pathogenic or probiotic, we compared the phenotypic traits of NEC mice treated with two clostridia. Our results proof that treatment with C. tyrobutyricum recovers the intestinal barrier integrity and alleviates inflammatory immune response of NEC, while treatment with C. butyricum aggrevates the intestinal barrier damage and promotes immune disorder including the number of macrophages, monocytes and neutrophils in Intestinal lamina propria. Further analysis of gut micrbiome implies that the positive effect of C. tyrobutyricum treatment is in association with the increase of Akkermansia muciniphila. Meanwhile, C. butyricum treatment decreases the level of A. muciniphila, which accounts for the negative effect to NEC.ConclusionThis study sheds light on that treatment with C. tyrobutyricum but not C. butyricum is entitled to protect against NEC development potentially. The mechanisms behind the opposite effect on NEC may result in different modulation on the level of A. muciniphila, which is deeply associated with intestinal homoeostasis. Briefly, through improving the abundance of A. muciniphila to alleviate intestinal inflammation and enhance intestinal barrier integrity, C. tyrobutyricum supplement may become a promising therapy for NEC.
Deep Learning and Transfer Learning for Brain Tumor Detection and Classification
Authors: Rustom Faris , Parva Pedram , Ogmen Haluk , Yazdanbakhsh Arash 
Published: April 2023

AbstractConvolutional neural networks (CNNs) are powerful tools that can be trained on image classification tasks and share many structural and functional similarities with biological visual systems and mechanisms of learning. In addition to serving as a model of biological systems, CNNs possess the convenient feature of transfer learning where a network trained on one task may be repurposed for training on another, potentially unrelated, task. In this retrospective study of public domain MRI data, we investigate the ability of neural network models to be trained on brain cancer imaging data while introducing a unique camouflage animal detection transfer learning step as a means of enhancing the network’s tumor detection ability. Training on glioma and normal brain MRI data, post-contrast T1-weighted and T2-weighted, we demonstrate the potential success of this training strategy for improving neural network classification accuracy. Qualitative metrics such as feature space and DeepDreamImage analysis of the internal states of trained models were also employed, which show improved generalization ability by the models following camouflage animal transfer learning. Image sensitivity functions further this investigation by allowing us to visualize the most salient image regions from a network’s perspective while learning. Such methods demonstrate that the networks not only ‘look’ at the tumor itself when deciding, but also at the impact on the surrounding tissue in terms of compressions and midline shifts. These results suggest an approach to brain tumor MRIs that is comparatively similar to that of trained radiologists while also exhibiting a high sensitivity to subtle structural changes resulting from the presence of a tumor. These findings present an opportunity for further research and potential use in a clinical setting.