bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cytoskeletal Vortex Drives Phage Nucleus Rotation During Jumbo Phage Replication in E. coli
Authors: Birkholz Erica A. , Laughlin Thomas G. , Suslov Sergey , Armbruster Emily , Lee Jina , Wittmann Johannes , Corbett Kevin D. , Villa Elizabeth , Pogliano Joe 
Published: October 2021

AbstractVortex-like arrays of cytoskeletal filaments that drive cytoplasmic streaming and nucleus rotation have been identified in eukaryotes, but similar structures have not been described in prokaryotes. The only known example of a rotating intracellular body in prokaryotic cells occurs when nucleus-forming jumbo phages infect Pseudomonas. During infection, a bipolar spindle of PhuZ filaments drives intracellular rotation of the phage nucleus, a key aspect of the replication cycle. Here we show the E. coli jumbo phage Goslar assembles a phage nucleus surrounded by an array of PhuZ filaments resembling a vortex instead of a bipolar spindle. Expression of mutant PhuZ strongly reduces Goslar phage nucleus rotation, demonstrating that the PhuZ cytoskeletal vortex is necessary for rotating the phage nucleus. While vortex-like cytoskeletal arrays are important in eukaryotes, this work identifies the first known example of a coherent assembly of filaments into a vortex-like structure driving intracellular rotation within the prokaryotic cytoplasm.
Individual-based modeling of genome evolution in haplodiploid organisms
Authors: Pracana Rodrigo , Burns Richard , Hammond Robert L. , Haller Benjamin C. , Wurm Yannick 
Published: October 2021

AbstractAnts, bees, wasps, bark beetles, and other species have haploid males and diploid females. Although such haplodiploid species play key ecological roles and are threatened by environmental changes, no general framework exists for simulating their genetic evolution. Here, we use the SLiM simulation environment to build a novel model for individual-based forward simulation of genetic evolution in haplodiploid populations. We compare the fates of adaptive and deleterious mutations and find that selection is more effective in haplodiploid species than in diploid species. Our open-source model will help understand the evolution of sociality and how ecologically important species may adapt to changing environments.
Identification of the Park Grass Experiment soil metaproteome
Authors: Quinn Gerry A. , Abdelhameed Alyaa , Banat Ibrahim M. , Berrar Daniel , Doerr Stefan H. , Dudley Ed , Francis Lewis W. , Gazze Salvatore A. , Hallin Ingrid , Matthews G. Peter , Swain Martin T. , Whalley W. Richard , van Keulen Geertje 
Published: October 2021

AbstractThe Park Grass Experiment, is an international reference soil with an impressive repository of temperate grassland (meta)data, however, it still lacks documentation of its soil metaproteome. The identification of these proteins is crucial to our understanding of soil ecology and their role in major biogeochemical processes. However, protein extraction can be fraught with technical difficulties including co-extraction of humic material and lack of a compatible databases to identify proteins. To address these issues, we used two compatible soil protein extraction techniques on Park Grass soil, one that removed humic material, namely a modified freeze-dry, heat/thaw/phenol/chloroform (HTPC) method and another which co-extracted humic material, namely an established surfactant method. Proteins were identified by matching mass spectra against a tailored Park Grass metagenome database. We identified a broad range of proteins from Park Grass soil, mainly in “protein metabolism”, “membrane transport”, “carbohydrate metabolism”, “respiration” and “ribosome associated” categories, enabling reconstitution of specific processes active in grassland soil. The soil microbiome was dominated by Proteobacteria, Actinobacteria, Acidobacteria and Firmicutes at phyla level and Bradyrhizobium, Rhizobium, Acidobacteria, Streptomyces and Pseudolabrys at genus level. Further functional enrichment analysis enabled us to identify many proteins in regulatory and signalling networks of key biogeochemical cycles such as the nitrogen cycle. The combined extraction methods connected previous Park Grass metadata with the metaproteome, biogeochemistry and soil ecology. This could provide a base on which future targeted studies of important soil processes and their regulation can be built.HighlightsParallel protein extraction methods identified 1266 proteins from Park Grass soilProteome was enriched in ribosomal and respiration proteins for the surfactant extraction method and nitrogen associated proteins for the modified phenol/chloroform methodIdentification of regulatory and signalling proteins in key biogeochemical cyclesLinks metaproteome to microbiome, biogeochemical cycles and Park Grass metadataProvides baseline for future targeted studies
Cancer malignancy is correlated with up-regulation of PCYT2-mediated glycerol phosphate modification of α-dystroglycan
Authors: Umezawa Fumiko , Natsume Makoto , Fukusada Shigeki , Nakajima Kazuki , Yamasaki Fumiya , Kawashima Hiroto , Kuo Chu-Wei , Khoo Kay-Hooi , Shimura Takaya , Yagi Hirokazu , Kato Koichi 
Published: October 2021

AbstractThe dystrophin-glycoprotein complex connects the cytoskeleton with base membrane components such as laminin through unique O-glycans displayed on α-dystroglycan (α-DG). Genetic impairment of elongation of these glycans causes congenital muscular dystrophies. We previously identified that glycerol phosphate (GroP) can cap the core part of the α-DG O-glycans and terminate their further elongation. This study examined the possible roles of the GroP modification in cancer malignancy, focusing on colorectal cancer. We found that the GroP modification critically depends on PCYT2, which serves as CDP-Gro synthase. Furthermore, we identified a significant positive correlation between cancer progression and GroP modification, which also correlated positively with PCYT2 expression. Moreover, we demonstrate that GroP modification promotes the migration of cancer cells. Based on these findings, we propose that the GroP modification by PCYT2 disrupts the glycan-mediated cell adhesion to the extracellular matrix and thereby enhances cancer metastasis. Thus, the present study suggests the possibility of novel approaches for cancer treatment by targeting the PCYT2-mediated GroP modification.
Gut microbiota analyses of Saudi populations for type 2 diabetes-related phenotypes reveals significant association
Authors: Al-Muhanna Fahd A , Dodwell Alexa K. , Al Eleq Abdulmohsen H , Albaker Waleed I , Brooks Andrew W. , Al-Sultan Ali I , Al-Rubaish Abdullah M , Alkharsah Khaled R , Sulaiman Raed M , Al-Quorain Abdulaziz A , Cyrus Cyril , Alali Rudaynah A , Vatte Chittibabu , Robinson Fred L. , Nguyen Carrie , Zhou Xin , Snyder Michael P. , Almuhanna Afnan F , Keating Brendan J , Piening Brian D. , Al-Ali Amein K 
Published: October 2021

AbstractLarge-scale gut microbiome sequencing has revealed key links between microbiome dysfunction and metabolic diseases such as T2D. To date, these efforts have largely focused on Western populations, with few studies assessing T2D microbiota associations in Middle Eastern communities where T2D prevalence is now over 20%. We analyzed the composition of stool 16S rRNA from 461 T2D and 119 non-T2Dparticipants from the Eastern Province of Saudi Arabia. We quantified the abundance of microbial communities to examine any significant differences between subpopulations of samples based on diabetes status and glucose level. We observed overall positive enrichment within diabetics compared to healthy individuals and amongst diabetic participants; those with high glucose levels exhibited slightly more positive enrichment compared to those at lower risk of fasting hyperglycemia. In particular, the genus Firmicutes was upregulated in diabetic participants compared to non-diabetic participants, and T2D was associated with an elevated Firmicutes/Bacteroidetes ratio, consistent with previous findings. Based on diabetes status and glucose levels of Saudi participants, relatively stable differences in stool composition were perceived by differential abundance and alpha diversity measures.Author summaryThe rates of Type 2 diabetes (T2D) in Saudi Arabia have risen dramatically in the last several decades due to socio-economic changes resulting in changes in dietary and sedentary lifestyles. This emergence has grown more rapidly and affects larger proportions of the population with estimates of T2D prevalence impacting 25% of the population. There is a paucity of microbiome data from Middle Eastern populations, and previous studies have been conducted on small sample sizes. Here we report on the first-ever characterization of gut microbiota T2D versus non-T2D and largest microbiome study ever conducted in a Middle Eastern country. The datasets from this study are important to create a regional reference T2D-microbiome catalogue which will propel the understanding of regional gut flora which are associated with T2D development. Based on T2D status and quantified glucose levels of Middle Eastern participants, relatively stable differences in stool composition were observed by differential abundance and alpha diversity measures. Comparing overlapping and varying patterns in gut microbiota with other studies is critical to assessing novel treatment options in light of a rapidly growing T2D health epidemic.
Comprehensive analysis of the circadian nuclear and cytoplasmic transcriptome in mouse liver
Authors: Hurni Clémence , Weger Benjamin , Gobet Cédric , Naef Felix 
Published: October 2021

AbstractIn eukaryotes, RNA is synthesised in the nucleus, spliced, and exported to the cytoplasm where it is translated and finally degraded. Any of these steps could be subject to temporal regulation during the circadian cycle, resulting in daily fluctuations of RNA accumulation and affecting the distribution of transcripts in different subcellular compartments. Our study analysed the nuclear and cytoplasmic, poly(A) and total transcriptomes of mouse livers collected over the course of a day. These data provide a genome-wide temporal inventory of enrichment in subcellular RNA, and revealed specific signatures of splicing, nuclear export and cytoplasmic mRNA stability related to transcript and gene lengths. Combined with a mathematical model describing rhythmic RNA profiles, we could test the rhythmicity of export rates and cytoplasmic degradation rates of approximately 1400 genes. With nuclear export times usually much shorter than cytoplasmic half-lives, we found that nuclear export contributes to the modulation and generation of rhythmic profiles of 10% of the cycling nuclear mRNAs. This study contributes to a better understanding of the dynamic regulation of the transcriptome during the day-night cycle.
MeDUsA: A novel system for automated axon quantification to evaluate neuroaxonal degeneration
Authors: Nitta Yohei , Kawai Hiroki , Osaka Jiro , Hakeda-Suzuki Satoko , Nagai Yoshitaka , Doubková Karolína , Suzuki Takashi , Tavosanis Gaia , Sugie Atsushi 
Published: October 2021

AbstractBackgroundDrosophila is an excellent model organism for studying human neurodegenerative diseases (NDs), and the rough eye phenotype (REP) assay is a convenient experimental system for analysing the toxicity of ectopically expressed human disease genes. However, the association between REP and axonal degeneration, an early sign of ND, remains unclear. To address this question, we developed a method to evaluate axonal degeneration by quantifying the number of retinal R7 axons in Drosophila; however, it requires expertise and is time-consuming. Therefore, there is a need for an easy-to-use software that can automatically quantify the axonal degeneration.ResultWe created MeDUsA (a ‘method for the quantification of degeneration using fly axons’), which is a standalone executable computer program based on Python that combines a pre-trained deep-learning masking tool with an axon terminal counting tool. This software automatically quantifies the number of axons from a confocal z-stack image series. Using this software, we have demonstrated for the first time directly that axons degenerate when the causative factors of NDs (αSyn, Tau, TDP-43, HTT) were expressed in the Drosophila eye. Furthermore, we compared axonal toxicity of the representative causative genes of NDs and their pathological alleles with REP and found no significant correlation between them.ConclusionsMeDUsA rapidly and accurately quantifies axons in Drosophila eye. By simplifying and automating time-consuming manual efforts requiring significant expertise, it enables large-scale, complex research efforts on axonal degeneration, such as screening to identify genes or drugs that mediate axonal toxicity caused by ND disease proteins.
Genomic adaptation of the picoeukaryote Pelagomonas calceolata to iron-poor oceans revealed by a chromosome-scale genome sequence
Authors: Guérin Nina , Ciccarella Marta , Flamant Elisa , Frémont Paul , Mangenot Sophie , Istace Benjamin , Noel Benjamin , Romac Sarah , Bachy Charles , Gachenot Martin , Pelletier Eric , Alberti Adriana , Jaillon Olivier , Cruaud Corinne , Wincker Patrick , Aury Jean-Marc , Carradec Quentin 
Published: October 2021

SummaryThe smallest phytoplankton species are key actors in oceans biogeochemical cycling and their abundance and distribution are affected with global environmental changes. Picoalgae (cells <2µm) of the Pelagophyceae class encompass coastal species causative of harmful algal blooms while others are cosmopolitan and abundant in open ocean ecosystems. Despite the ecological importance of Pelagophytes, only a few genomic references exist limiting our capacity to identify them and study their adaptation mechanisms in a changing environment. Here, we report the complete chromosome-scale assembled genome sequence of Pelagomonas calceolata. We identified unusual large low-GC and gene-rich regions potentially representing centromeres. These particular genomic structures could be explained by the absence of genes from a recombination pathway involving double Holiday Junctions. We identified a large repertoire of genes involved in inorganic nitrogen sensing and uptake and several genes replacing iron-requiring proteins potentially explaining P. calceolata ecological success in oligotrophic waters. Finally, based on this high-quality assembly, we evaluated P. calceolata relative abundance in all oceans using environmental Tara Oceans datasets. Our results suggest that P. calceolata is one of the most abundant eukaryotic species in the oceans with a relative abundance favoured by high temperature and iron-poor conditions. Climate change projections based on its relative abundance suggest an extension of the P. calceolata habitat toward the poles at the end of this century. Collectively, these findings reveal the ecological importance of P. calceolata and lay the foundation for a global scale analysis of the adaptation and acclimation strategies of picoalgae in a changing environment.
Identifying barriers to gene flow and hierarchical conservation units from seascape genomics: a modelling framework applied to a marine predator
Authors: Boussarie Germain , Momigliano Paolo , Robbins William D. , Bonnin Lucas , Cornu Jean-François , Fauvelot Cécile , Kiszka Jeremy J. , Manel Stéphanie , Mouillot David , Vigliola Laurent 
Published: October 2021

ABSTRACTThe ongoing decline of large marine vertebrates must be urgently mitigated, particularly under increasing levels of climate change and other anthropogenic pressures. However, characterizing the connectivity among populations remains one of the greatest challenges for the effective conservation of an increasing number of endangered species. Achieving conservation targets requires an understanding of which seascape features influence dispersal and subsequent genetic structure. This is particularly challenging for adult-disperser species, and when distribution-wide sampling is difficult. Here, we developed a two-step modelling framework to investigate how seascape features drive the genetic connectivity of marine species without larval dispersal, to better guide the design of marine protected area networks and corridors. We applied this framework to the endangered grey reef shark, Carcharhinus amblyrhynchos, a reef-associated shark distributed across the tropical Indo-Pacific. In the first step, we developed a seascape genomic approach based on isolation-by-resistance models involving circuit theory applied to 515 shark samples, genotyped for 4,491 nuclear single-nucleotide polymorphisms, to explore which parameters drive their population genetic differentiation. We show that deep oceanic areas act as strong barriers to dispersal, while proximity to habitat facilitates dispersal. In the second step, we predicted the resulting genetic differentiation across the entire distribution range of the species, providing both local and global-scale conservation units for future management guidance. We found that grey reef shark populations are more fragmented than expected for such a mobile species, raising concerns about the resilience of isolated populations under high anthropogenic pressures. We recommend the use of this framework to identify barriers to gene flow and to help in the delineation of conservation units at different scales, together with its integration across multiple species when considering marine spatial planning.
Muscle systems and motility of early animals highlighted by cnidarians from the basal Cambrian
Authors: Wang Xing , Vannier Jean , Yang Xiaoguang , Leclère Lucas , Ou Qiang , Song Xikun , Komiya Tsuyoshi , Han Jian 
Published: October 2021

AbstractAlthough fossil evidence suggest that various animal groups were able to move actively through their environment in the early stages of their evolution, virtually no direct information is available on the nature of their muscle systems. The origin of jellyfish swimming, for example, is of great concern to biologists. Exceptionally preserved muscles are described here in benthic peridermal olivooid medusozoans from the basal Cambrian of China (Kuanchuanpu Formation, ca. 535 Ma) that have direct equivalent in modern medusozoans. They consist of circular fibers distributed over the bell surface (subumbrella) and most probably have a myoepithelial origin. This is the oldest record of a muscle system in cnidarians and more generally in animals. This basic system was probably co-opted by younger early Cambrian jellyfish to develop capacities for the jet-propelled swimming within the water column. Additional lines of fossil evidence obtained from ecdysozoans (worms and panarthropods) show that the muscle systems of early animals underwent a rapid diversification through the early Cambrian and increased their capacity to colonize a wide range of habitats both within the water column and sediment at a critical time of their evolutionary radiation.
Alternative strategy to induce CRISPR-mediated genetic changes in hematopoietic cells
Authors: González-Romero E , Rosal-Vela A , Liquori A , Martínez-Valiente C , García-García G , Millán JM , Sanz MA , Cervera JV , Vázquez-Manrique RP 
Published: October 2021

ABSTRACTAcute Myeloid Leukaemia is a complex heterogenous disease caused by clonal expansion of undifferentiated myeloid precursors. Recently, several haematological models have been developed with CRISPR/Cas9, using viral vectors, because blood cells are hard to transfect. To avoid virus disadvantages, we have developed a strategy to generate CRISPR constructs, by means of PCR, which any lab equipped with basic technology can implement. These PCR-generated constructs enter easily into hard-to-transfect cells. After testing its functionality by editing MYBL2 gene in HEK293 cells, we successfully introduced the R172 mutation in IDH2 gene in NB4 cells that expresses constitutively the Cas9 nuclease. Comparing our methodology with ribonucleoprotein strategies, we found that mutation introduction efficiency was similar between both methodologies, and no off-target events were detected. Our strategy represents a valid alternative to introduce desired mutations in hard to transfect leukemic cells, avoiding using huge vectors or viral transduction.
A novel single-cell RNA-sequencing platform and its applicability connecting genotype to phenotype in ageing-disease
Authors: Shomroni Orr , Sitte Maren , Schmidt Julia , Parbin Sabnam , Ludewig Fabian , Yigit Gökhan , Zelarayan Laura Cecilia , Streckfuss-Bömeke Katrin , Wollnik Bernd , Salinas Gabriela 
Published: October 2021

AbstractAdvances in single cell multi-omics analysis such as the ability of a genotype to show phenotypic diversity lead to a comprehensive understanding of cellular events in human diseases. The cardinal feature to access this information is the technology used for single-cell isolation, barcoding, and sequencing. While numerous platforms have been reported for single-cell RNA-sequencing, technical enhancements are needed in terms of highly purified single cell selection, cell documentation or limitations in cell sizing and chemistry. In this study, we present a novel high-throughput platform using a full-length RNA-sequencing approach that offers substantial technical improvements of all parameters. We applied this platform to dermal fibroblasts derived from six patients with different segmental progeria syndromes and defined phenotype-associated pathway signatures and variant-associated expression modifiers. These results validate the applicability of our platform to highlight genotype–expression relationships for molecular phenotyping in ageing disorders.
Profiling RT-LAMP tolerance of sequence variation for SARS-CoV-2 RNA detection
Authors: Tamanaha Esta , Zhang Yinhua , Tanner Nathan A. 
Published: October 2021

AbstractThe ongoing SARS-CoV-2 pandemic has necessitated a dramatic increase in our ability to conduct molecular diagnostic tests, as accurate detection of the virus is critical in preventing its spread. However, SARS-CoV-2 variants continue to emerge, with each new variant potentially affecting widely-used nucleic acid amplification diagnostic tests. RT-LAMP has emerged as a quick, inexpensive diagnostic alternative to RT-qPCR, but has not been studied as thoroughly. Here we interrogate the effect of SARS-CoV-2 sequence mutations on RT-LAMP amplification, creating 572 single point mutation “variants” covering every position of the LAMP primers in 3 SARS-CoV-2 assays and analyzing their effects with over 4,500 RT-LAMP reactions. Remarkably, we observed only minimal effects on amplification speed and no effect on detection sensitivity, highlighting RT-LAMP as an extremely robust technique for viral RNA detection. Additionally, we describe the use of molecular beacons to sensitively identify variant RNA sequences. Together these data add to the growing body of knowledge on the utility of RT-LAMP and increase its potential to further our ability to conduct molecular diagnostic tests outside of the traditional clinical laboratory environment.