bluuebunny/crossref_metadata_2025_split huggingface dataset:
Namco: A microbiome explorer
Authors: Dietrich Alexander , Matchado Monica Steffi , Zwiebel Maximilian , Ölke Benjamin , Lauber Michael , Lagkouvardos Ilias , Baumbach Jan , Haller Dirk , Brandl Beate , Skurk Thomas , Hauner Hans , Reitmeier Sandra , List Markus 
Published: December 2021

Abstract16S rRNA gene profiling is currently the most widely used technique in microbiome research and allows for studying microbial diversity, taxonomic profiling, phylogenetics, functional and network analysis. While a plethora of tools have been developed for the analysis of 16S rRNA gene data, only a few platforms offer a user-friendly interface and none comprehensively covers the whole analysis pipeline from raw data processing down to complex analysis. We introduce Namco, an R shiny application that offers a streamlined interface and serves as a one-stop solution for microbiome analysis. We demonstrate Namco’s capabilities by studying the association between a rich fibre diet and the gut microbiota composition. Namco helped to prove the hypothesis that butyrate-producing bacteria are prompted by fibre-enriched intervention. Namco provides a broad range of features from raw data processing and basic statistics down to machine learning and network analysis, thus covering complex data analysis tasks that are not comprehensively covered elsewhere. Namco is freely available athttps://exbio.wzw.tum.de/Namco/.Impact statementAmplicon sequencing is a key technology of microbiome research and has yielded many insights into the complexity and diversity of microbiota. To fully leverage these data, a wide range of tools have been developed for raw data processing, normalization, statistical analysis and visualization. These tools are mostly available as R packages but cannot be easily linked in an automated pipeline due to the heterogeneous characteristics of microbiome data. Instead, user-friendly tools for explorative analysis are needed to give biomedical researchers without experience in scripting languages the possibility to fully exploit their data. Several tools for microbiome data analysis have been proposed in recent years which cover a broad range of functionality but few offer a user-friendly and beginner-friendly interface while covering the entire value whole value chain from raw data processing down to complex analysis. With Namco(https://exbio.wzw.tum.de/namco/), we present a beginner-friendly one-stop solution for microbiome analysis that covers upstream analyses like raw data processing, taxonomic binning and downstream analyses like basic statistics, machine learning and network analysis, among other features.
Dynamic interplay between structural variations and 3D chromosome organization in pancreatic cancer
Authors: Du Yongxing , Gu Zongting , Li Zongze , Yuan Zan , Zhao Yue , Zheng Xiaohao , Bo Xiaochen , Chen Hebing , Wang Chengfeng 
Published: December 2021

SummaryStructural variations (SVs) are the greatest source of variation in the genome and can lead to oncogenesis. However, the identification and interpretation of SVs in human pancreatic cancer remain largely undefined due to technological limitations. Here, we investigate the spectrum of SVs and three-dimensional (3D) chromatin architecture in human pancreatic ductal epithelial cell carcinogenesis by using state-of-the-art long- read single-molecule real-time (SMRT) and high-throughput chromosome conformation capture (Hi-C) sequencing techniques. We find that the 3D genome organization is remodeled and correlated with gene expressional change. The bulk remodeling effect of cross-boundary SVs in the 3D genome partly depends on intercellular genomic heterogeneity. Meanwhile, contact domains tend to minimize these disrupting effects of SVs within local adjacent genomic regions to maintain overall stability of 3D genome organization. Moreover, our data also demonstrates complex genomic rearrangements involving two key driver genes CDKN2A and SMAD4, and elucidates their influence on cancer-related gene expression from both linear view and 3D perspective. Overall, this study provides a valuable resource and highlights the impact, complexity and dynamicity of the interplay between SVs and 3D genome organization, which further expands our understanding of pathogenesis of SVs in human pancreatic cancer.
Intact rDNA arrays of Potentilla-origin detected in Erythronium nucleus suggest recent eudicot-to-monocot horizontal transfer
Authors: Bartha László , Mandáková Terezie , Kovařík Aleš , Bulzu Paul-Adrian , Rodde Nathalie , Mahelka Václav , Lysak Martin A. , Fustier Margaux-Alison , Šafář Jan , Cápal Petr , Keresztes Lujza , Banciu Horia L. 
Published: December 2021

AbstractThe occurrence of horizontal gene transfer (HGT) in Eukarya is increasingly gaining recognition. Nuclear-to-nuclear jump of DNA between plant species at high phylogenetic distance and devoid of intimate association (e.g., parasitism) is still scarcely reported. Within eukaryotes, components of ribosomal DNA (rDNA) multigene family have been found to be horizontally transferred in protists, fungi and grasses. However, in neither case HGT occurred between phylogenetic families, nor the transferred rDNA remained tandemly arrayed and transcriptionally active in the recipient organism. This study aimed to characterize an alien eudicot-type of 45S nuclear rDNA, assumingly transferred horizontally to the genome of monocot European Erythronium (Liliaceae). Genome skimming coupled by PacBio HiFi sequencing of a BAC clone were applied to determine DNA sequence of the alien rDNA. A clear phylogenetic signal traced the origin of the alien rDNA of Erythronium back to the Argentea clade of Potentilla (Rosaceae) and deemed the transfer to have occurred in the common ancestor of E. dens-canis and E. caucasicum. Though being discontinuous, transferred rDNA preserved its general tandemly arrayed feature in the host organism. Southern blotting, molecular cytogenetics, and sequencing of a BAC clone derived from flow-sorted nuclei indicated integration of the alien rDNA into the recipient’s nuclear genome. Unprecedently, dicot-type alien rDNA was found to be transcribed in the monocot Erythronium albeit much less efficiently than the native counterpart. This study adds a new example to the growing list of naturally transgenic plants while holding the scientific community continually in suspense about the mode of DNA transfer.Significance StatementRibosomal DNA is an essential component of all cellular genomes. In plants, accidental movement of rDNA via horizontal gene transfer has only been reported in sexually incompatible grasses (monocots) where it involved non-functional rDNA units. In this study, we propose that evolutionary trajectories of eudicots and monocots were bypassed by the jump of rDNA from a Potentilla species (Rosaceae) to a common ancestor of Erythronium dens-canis and E. caucasicum (Liliaceae). The alien eudicot-type rDNA appeared relatively well conserved in the examined host Erythronium genome, being able to be expressed while preserving its general tandemly repeated feature, evidences that have no match in earlier literature.
A mixture of innate cryoprotectants is key for freeze tolerance and cryopreservation of a drosophilid fly larva
Authors: Kučera Lukáš , Moos Martin , Štětina Tomáš , Korbelová Jaroslava , Vodrážka Petr , Marteaux Lauren Des , Grgac Robert , Hůla Petr , Rozsypal Jan , Faltus Miloš , Šimek Petr , Sedlacek Radislav , Koštál Vladimír 
Published: December 2021

AbstractInsects that naturally tolerate internal freezing produce complex mixtures of multiple cryoprotectants (CPs). Better knowledge on composition of these mixtures, and on mechanisms of how the individual CPs interact, could inspire development of laboratory CP formulations optimized for cryopreservation of cells and other biological material. Here we identify and quantify (using high resolution mass spectrometry) a range of putative CPs in larval tissues of a subarctic fly,Chymomyza costatathat survives long-term cryopreservation in liquid nitrogen. The CPs (proline, trehalose, glutamine, asparagine, glycine betaine, glycerophosphoethanolamine, glycerophosphocholine, and sarcosine) accumulate in hemolymph in a ratio of 313:108:55:26:6:4:3:0.5 mmol.L-1. Using calorimetry, we show that the artificial mixtures, mimicking the concentrations of major CPs’ in hemolymph of freeze-tolerant larvae, suppress the melting point of water and significantly reduce the ice fraction. We demonstrate in a bioassay that mixtures of CPs administered through the diet act synergistically rather than additively to enable cryopreservation of otherwise freeze-sensitive larvae. Using MALDI-MSI, we show that during slow extracellular freezing trehalose becomes concentrated in partially dehydrated hemolymph where it stimulates transition to the amorphous glass phase. In contrast, proline moves to the boundary between extracellular ice and dehydrated hemolymph and tissues where it likely forms a layer of dense viscoelastic liquid. We propose that amorphous glass and viscoelastic liquids may protect macromolecules and cells from thermomechanical shocks associated with freezing and transfer into and out of liquid nitrogen.Summary statementThe composition of natural cryoprotectant mixture of the extremely freeze-tolerant insect is revealed. Components of the mixture work in synergy and behave differently during organismal freezing and cryopreservation.
Chromosome-scale haplotype-phased genome assemblies of the male and female lines of wild asparagus (Asparagus kiusianus), a dioecious plant species
Authors: Shirasawa Kenta , Ueta Saki , Murakami Kyoko , Abdelrahman Mostafa , Kanno Akira , Isobe Sachiko 
Published: December 2021

AbstractAsparagus kiusianus is a disease-resistant dioecious plant species and a wild relative of garden asparagus (A. officinalis). To enhance A. kiusianus genomic resources, advance plant science, and facilitate asparagus breeding, we determined the genome sequences of the male and female lines of A. kiusianus. Genome sequence reads obtained with a linked-read technology were assembled into four haplotype-phased contig sequences (~1.6 Gb each) for the male and female lines. The contig sequences were aligned onto the chromosome sequences of garden asparagus to construct pseudomolecule sequences. Approximately 55,000 potential protein-encoding genes were predicted in each genome assembly, and ~70% of the genome sequence was annotated as repetitive. Comparative analysis of the genomes of the two species revealed structural and sequence variants between the two species as well as between the male and female lines of each species. Genes with high sequence similarity with the male-specific sex determinant gene in A. officinalis, MSE1/AoMYB35/AspTDF1, were presented in the genomes of the male line but absent from the female genome assemblies. Overall, the genome sequence assemblies, gene sequences, and structural and sequence variants determined in this study will reveal the genetic mechanisms underlying sexual differentiation in plants, and will accelerate disease-resistance breeding in garden asparagus.
The African Swine Fever Isolate ASFV-Kenya-1033-IX is highly virulent and stable after growth in the wild boar cell line WSL
Authors: Hemmink Johanneke D. , Abkallo Hussein M. , Henson Sonal P. , Khazalwa Emmanuel M. , Oduor Bernard , Lacasta Anna , Okoth Edward , Fuchs Walter , Bishop Richard P. , Steinaa Lucilla 
Published: December 2021

AbstractIn this study, we describe an African swine fever genotype IX virus (ASFV-Kenya-1033-IX), which was isolated from a domestic pig in Western Kenya during a reported outbreak, including efficiency of virus replication, in vivo virulence, and genome stability in pulmonary alveolar macrophages (PAM) and in a wild boar cell line (WSL). The ASFV-Kenya-1033-IX stock, which underwent multiple passages in WSL (more than 20), retained its ability to replicate in primary macrophages and it also retained the virulence in vivo. At the genomic level, only a few single nucleotide differences were observed between the macrophage and WSL-grown virus. Thus, we propose that the WSL cell line is suitable to produce live attenuated ASFV vaccine candidates based on this isolate and probably of similar viruses. The genome sequences for ASFV-Kenya-1033-IX grown in macrophages and in WSL cells was submitted to GenBank and a challenge model based on this isolate was set up, which will aid the development of vaccines against genotype IX ASFV circulating in Eastern and Central Africa.
DNMT3A knockouts in human iPSCs prevent de novo DNA methylation and reveal growth advantage during hematopoietic differentiation
Authors: Cypris Olivia , Franzen Julia , Frobel Joana , Glück Philipp , Kuo Chao-Chung , Schmitz Stephani , Nüchtern Selina , Zenke Martin , Wagner Wolfgang 
Published: December 2021

SummaryDNA methyltransferase 3A (DNMT3A) is a frequently mutated gene in many hematological malignancies, indicating that it may be essential for hematopoietic differentiation. Here, we addressed the functional relevance of DNMT3A for differentiation of human induced pluripotent stem cells (iPSCs) by knocking out exon 2, 19, or 23. Exon 19-/- and 23-/- lines revealed absence of almost the entire de novo DNA methylation during mesenchymal and hematopoietic differentiation. Yet, differentiation was only slightly reduced in exon 19-/- and increased in exon 23-/- lines, whereas there was no significant impact on gene expression in hematopoietic progenitors (iHPCs). Notably, DNMT3A-/- iHPCs recapitulate some DNA methylation differences of acute myeloid leukemia with DNMT3A mutations. Furthermore, multicolor genetic barcoding revealed competitive growth advantage of exon 23-/- iHPCs. Our results demonstrate that de novo DNA methylation during hematopoietic differentiation of iPSCs is almost entirely dependent on DNMT3A and exon 23-/- iHPCs even gained growth advantage.
Exceptions to the rule: Why does resistance evolution not undermine antibiotic therapy in all bacterial infections?
Authors: Bhattacharya Amrita , Aluquin Anton , Kennedy David A 
Published: December 2021

AbstractAntibiotic resistance poses one of the greatest public health challenges of the 21st century. Yet not all pathogens are equally affected by resistance evolution. Why? Here we examine what underlies variation in antibiotic resistance across human bacterial pathogens and the drugs used to treat them. We document the observed prevalence of antibiotic resistance for ‘pathogen x drug’ combinations across 57 different human bacterial pathogens and 53 antibiotics from 15 drug classes used to treat them. Using AIC-based model selection we analyze 14 different traits of bacteria and antibiotics that are believed to be important in resistance evolution. Using these data, we identify the traits that best explain observed variation in resistance evolution. Our results show that nosocomial pathogens and indirectly transmitted pathogens are significantly associated with increased prevalence of resistance whereas zoonotic pathogens, specifically those with wild animal reservoirs, are associated with reduced prevalence of resistance. We found partial support for associations between drug resistance and gram classification, human microbiome reservoirs, horizontal gene transfer, and documented human-to human transfer. Global drug use, time since drug discovery, mechanism of drug action, and environmental reservoirs did not emerge as statistically robust predictors of drug resistance in our analyses. To the best of our knowledge this work is the first systematic analysis of resistance across such a wide range of human bacterial pathogens, encompassing the vast majority of common bacterial pathogens. Insights from our study may help guide public health policies and future studies on resistance control.
A Precision Medicine Approach to Metabolic Therapy for Breast Cancer in Mice
Authors: Akingbesote Ngozi D. , Norman Aaron , Zhu Wanling , Halberstam Alexandra A. , Zhang Xinyi , Foldi Julia R. , Lustberg Maryam B. , Perry Rachel J. 
Published: December 2021

AbstractIncreasing evidence highlights the possibility for approaches targeting metabolism as potential adjuvants to cancer therapy. Sodium-glucose transport protein 2 (SGLT2) inhibitors are the newest class of antihyperglycemic therapies, and have recently been highlighted as a novel therapeutic approach to breast cancer. To our knowledge, however, SGLT2 inhibitors have not been applied in the neoadjuvant setting as a precision medicine approach to combining metabolic therapy with standard of care therapy for this devastating disease. In this study we combine the SGLT2 inhibitor dapagliflozin with paclitaxel chemotherapy in both lean and obese mice. We show that dapagliflozin enhances the efficacy of paclitaxel, reducing tumor glucose uptake and prolonging survival in an insulin-dependent manner in some but not all breast tumors. Our data find a genetic signature for breast tumors most likely to respond to dapagliflozin in combination with paclitaxel. Tumors driven by mutations upstream of canonical insulin signaling pathways are likely to respond to such treatment, whereas tumors driven by mutations downstream of canonical insulin signaling are not. These data demonstrate that dapagliflozin enhances the response to chemotherapy in mice with breast cancer and suggest that breast cancer patients with driver mutations upstream of canonical insulin signaling may be most likely to benefit from this neoadjuvant approach. A clinical trial is currently in preparation, with an application recently submitted for Yale Human Investigations Committee approval, to test this hypothesis in breast cancer patients.One Sentence SummaryWe identify a driver mutation signature by which glucose-wasting metabolic therapy (dapagliflozin) enhances the efficacy of chemotherapy in mice with breast cancer.
Interferon-□ Exposure of Human iPSC-derived Neurons Alters Major Histocompatibility Complex I and Synapsin I Protein Expression
Authors: Pavlinek Adam , Matulevicute Rugile , Sichlinger Laura , Polit Lucia Dutan , Armeniakos Nikolaos , Vernon Anthony C. , Srivastava Deepak P. 
Published: December 2021

AbstractHuman epidemiological data links maternal immune activation during gestation with increased risk for neurodevelopmental disorders including schizophrenia. Animal models of maternal immune activation (MIA) provide causal evidence for this association and strongly suggest that inflammatory cytokines act is a critical link between maternal infection and aberrant offspring brain and behavior development. This includes evidence for reduced synapse formation, consistent with post-mortem and in vivo evidence of reduced synaptic density in schizophrenia. However, to what extent specific cytokines are necessary and sufficient for these effects remains unclear. Using a human cellular model, we recently demonstrated that acute exposure to interferon-□ (IFN□) recapitulates molecular and cellular phenotypes associated with neurodevelopmental disorders. Here, we extend this work to test whether IFN□ affects synapse formation in an induced neuron model that generates forebrain glutamatergic neurons. Using immunocytochemistry and quantitative PCR, we demonstrate that acute IFN□ exposure results in significantly increased MHCI expression at the mRNA and protein level. Furthermore, acute IFN□ exposure decreases synapsin I protein in neurons but does not affect synaptic gene mRNA levels. Interestingly, complement component 4A (C4A) mRNA is also significantly increased following acute IFN□ exposure. This study builds on our previous work by showing that IFN□-mediated disruption of relevant synaptic proteins can occur at early stages of synapse formation, potentially contributing to neurodevelopmental disorder phenotypes such as schizophrenia.
Social evolution of shared biofilm matrix components
Authors: Tai Jung-Shen B. , Mukherjee Saikat , Nero Thomas , Olson Rich , Tithof Jeffrey , Nadell Carey D. , Yan Jing 
Published: December 2021

AbstractBiofilm formation is an important and ubiquitous mode of growth among bacteria. Central to the evolutionary advantage of biofilm formation is cell-cell and cell-surface adhesion achieved by a variety of factors, some of which are diffusible compounds that may operate as classical public goods – factors that are costly to produce but may benefit other cells. An outstanding question is how diffusible matrix production, in general, can be stable over evolutionary timescales. In this work, using Vibrio cholerae as a model, we show that shared diffusible biofilm matrix proteins are indeed susceptible to cheater exploitation, and that the evolutionary stability of producing these matrix components fundamentally depends on biofilm spatial structure, intrinsic sharing mechanisms of these components, and flow conditions in the environment. We further show that exploitation of diffusible adhesion proteins is localized within a well-defined spatial range around cell clusters that produce them. Based on this exploitation range and the spatial distribution of cell clusters, we construct a model of costly diffusible matrix production and relate these length scales to the relatedness coefficient in social evolution theory. Our results show that production of diffusible biofilm matrix components is evolutionarily stable under conditions consistent with natural biofilm habitats and host environments. We expect the mechanisms revealed in this study to be relevant to other secreted factors that operate as cooperative public goods in bacterial communities, and the concept of exploitation range and the associated analysis tools to be generally applicable.
Fatty acid profile and lipid indices of the porker meat supplemented with pro-health herbal probiotics, ascorbic acid and allicin
Authors: Goluch Zuzanna Sabina , Rybarczyk Artur , Drozd Arleta , Drozd Radosław 
Published: December 2021

PurposeThe objective of this study is to assess whether pro-health herbal probiotics, ascorbic acid and allicin added to the finishing diets of hybrid pig influenced the intramuscular fat (IMF) content inlongissimus lumborum(LL) muscle, the fatty acid profile and lipid quality indices, as it has an impact on human health.Design/methodology/approachAfter 80 days of equal fattening, the pigs were divided into the control group (CT,n = 30 received commercially allowed and applicable antibiotics) and the experimental group (EX,n = 30), which until 95 days of rearing were supplied with fermented herbs extract (FHE Multikraft® Austria) with probioticsSaccharomyces cerevisiae,Lactobacillus casei,Lactobacillusplantarum, L-ascorbic acid and extract of garlic (10% allicin). After slaughter, crude fat content and fatty acid profile were determined in LL muscle samples, and on that basis lipid indices were calculated.FindingsSupplementation with FHE, probiotics, L-ascorbic acid and allicin has significantly impacted the crude fat content in the meat and the percentage of fatty acids content: tricosanoic (C23:0), heptadecanoid (C17:1n-7), eicosanic (C22:1 11cisn-9) and eicosatrienoic (C20:3 11cisn-3), in comparison to CT group. Amongst lipid quality indices, IMF in LL of pigs from EX group, the C18:2n-6/C18:3n-3 ratio is characterised by a significantly higher value and thus is more beneficial to the health of the consumer.Originality/valueThe authors have indicated that using FHE, probiotic supplements with ascorbic acid and allicin in commercial fattening of pigs, as an alternative for antibiotic growth promoters (AGP), improves the fatty acid profile of the meat.