bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of astrocyte-driven pseudolineages reveals clinical stratification and therapeutic targets in Glioblastoma
Authors: Foerster Leo Carl , Kaya Oguzhan , Wüst Valentin , Bekavac Milica , Ziegler Kevin Chris , Akcay Vuslat , Stinchcombe Nina , Gesteira Perez Noelia , Ma Xiujian , Sadik Ahmed , Le Phuong Uyen , Petrecca Kevin , Opitz Christiane , Liu Haikun , Wirtz Christian Rainer , Anders Simon , Goncalves Angela , Martin-Villalba Ana 
Published: September 2023

SummaryCancer research has predominantly targeted genetic mutations, while only recently has attention shifted to understanding tumor cell-stages. However, the key organizational principles guiding tumor dynamics towards sustainable growth remained unexplored. By analyzing tumor cell ensembles from individuals with glioblastoma through the lens of the healthy adult stem cell lineage, we identified astrocytes as central to glioblastoma progression. We found dormant tumor cells resembling astrocytes progressing to active and differentiated stages, building tumor pseudolineages that ultimately influence patient survival. These tumor stages align with specific methylomes, offering potential for patient classification. Our study identifies the Wnt antagonist SFRP1 as a missing factor in glioblastoma that plays a crucial role in the transition from quiescence to activation in the healthy lineage. Excitingly, re-introduction of SFRP1 in glioblastoma halts tumor dynamics, enhancing survival in a PDX model. This fresh view on glioblastomas underscores the importance of understanding tumor dynamics and unveils novel therapeutic avenues.
HLAfreq: Download and combine HLA allele frequency data
Authors: Wells David A. , McAuley Michael 
Published: September 2023

AbstractThe Allele Frequency Net Database contains publicly available data on human immune gene frequencies for different populations from a variety of sources. We introduce a python packageHLAfreqto download, combine, and analyse this data. In particular,HLAfreqcan combine multiple datasets and/or prior knowledge to improve allele frequency estimates and produce credible intervals. We demonstrate these features using real world data to visualise allele frequencies and compare populations.HLAfreqis hosted atwww.github.com/Vaccitech/HLAfreq/with documentation and detailed examples.
Bayesian model discovery for reverse-engineering biochemical networks from data
Authors: Jørgensen Andreas Christ Sølvsten , Sturrock Marc , Ghosh Atiyo , Shahrezaei Vahid 
Published: September 2023

AbstractThe reverse engineering of gene regulatory networks based on gene expression data is a challenging inference task. A related problem in computational systems biology lies in identifying signalling networks that perform particular functions, such as adaptation. Indeed, for many research questions, there is an ongoing search for efficient inference algorithms that can identify the simplest model among a larger set of related models. To this end, in this paper, we introduce SLInG, a Bayesian sparse likelihood-free inference method using Gibbs sampling. We demonstrate that SLInG can reverse engineer stochastic gene regulatory networks from single-cell data with high accuracy, outperforming state-of-the-art correlation-based methods. Furthermore, we show that SLInG can successfully identify signalling networks that execute adaptation. Sparse hierarchical Bayesian inference thus provides a versatile tool for model discovery in systems biology and beyond.
The Pex6 N1 domain is required for Pex15 binding and proper assembly with Pex1
Authors: Ali Bashir A. , Judy Ryan M. , Chowdhury Saikat , Jacobsen Nicole K. , Castanzo Dominic T. , Carr Kaili L. , Richardson Chris D. , Lander Gabriel C. , Martin Andreas , Gardner Brooke M. 
Published: September 2023

AbstractThe heterohexameric AAA-ATPase Pex1/Pex6 is essential for the formation and maintenance of peroxisomes. Pex1/Pex6, similar to other AAA-ATPases, uses the energy from ATP hydrolysis to mechanically thread substrate proteins through its central pore, thereby unfolding them. In related AAA-ATPase motors, substrates are recruited through binding to the motor’s N-terminal domains or N-terminally bound co-factors. Here we use structural and biochemical techniques to characterize the function of the N1 domain in Pex6 from budding yeast,S. cerevisiae. We found that although Pex1/ΛN1-Pex6 is an active ATPasein vitro, it does not support Pex1/Pex6 function at the peroxisomein vivo. An X-ray crystal structure of the isolated Pex6 N1 domain shows that the Pex6 N1 domain shares the same fold as the N terminal domains of PEX1, CDC48, or NSF, despite poor sequence conservation. Integrating this structure with a cryo-EM reconstruction of Pex1/Pex6, AlphaFold2 predictions, and biochemical assays shows that Pex6 N1 mediates binding to both the peroxisomal membrane tether Pex15 and an extended loop from the D2 ATPase domain of Pex1 that influences Pex1/Pex6 heterohexamer stability. Given the direct interactions with both Pex15 and the D2 ATPase domains, the Pex6 N1 domain is poised to coordinate binding of co-factors and substrates with Pex1/Pex6 ATPase activity.
The Interplay Between Sketching and Graph Generation Algorithms in Identifying Biologically Cohesive Cell-Populations in Single-Cell Data
Authors: Crawford Emma , Plotkin Alec , Ranek Jolene , Stanley Natalie 
Published: September 2023

AbstractHigh-throughput single-cell immune profiling technologies, such as mass cytometry (CyTOF) and single-cell RNA sequencing measure the expression of multiple proteins or genes across many individual cells within a profiled sample. As it is often of interest to identify particularclustersor cell-populations driving clinical phenotypes or experimental outcomes, there is a critical need to develop automated bioinformatics approaches that can handle a large number of profiled cells. For analyzing multi-sample single-cell datasets at scale, the datasets are usually encoded as a graph, where nodes represent cells and edges imply significant between-cell similarity. As multi-sample single-cell experiments can readily result in millions of profiled cells, the construction and analysis of a graph becomes computationally prohibitive and often requires reducing the dataset size through downsampling as a pre-processing step. Here, we explore the interplay between sketching, or downsampling approaches, and the way in which the graph is constructed on the sketched data for ultimately identifying biologically-meaningful cell-populations. Our results suggest that combining a principled sketching approach with a simplek-nearest neighbor graph representation of the data can identify meaningful subsets of cells as robustly as, and sometimes better than, more sophisticated graph generation approaches. This reveals that the practical concern of downsampling or sketching a limited number of cells is a more critical pre-processing step than how the graph representation is constructed.
Differentiation and migration of hematopoietic stem and progenitor cells cross multiple tissues
Authors: Yu Shiya , Li Hui , Wang Xuefei , Chen Guanming , Huang Hongwen , Hong Ni , Song You-Qiang , Zhang Xuegong , Jin Wenfei 
Published: September 2023

AbstractHematopoiesis requires the coordinated differentiation of hematopoietic stem cells and progenitor cells (HSPCs) in multiple tissues. Although differentiation of HSPCs in bone marrow (BM) has been well-studied, our knowledge about the migration and differentiation of HSPCs cross tissues is limited. Here, we collected and integrated single-cell RNA-seq data of human CD34+ cells, which represent HSPCs, from BM, peripheral blood (PB), thymus and mobilized PB (mPB), to investigate the hematopoiesis cross tissues. We constructed a cell atlas of HSPCs cross tissues and found most HSPC subsets in BM had counterparts in PB, indicating migration of HSPCs from BM to PB has a much broad spectrum. We found B progenitors highly expressedCXCR4for anchoring in BM, while cells with low expression ofCXCR4facilitate their migration out of BM. Among the HSPC subsets from thymus, we only found the counterparts of the earliest thymic progenitors (ETPs) in BM and PB, potentially indicating that ETPs were the subsets that migrated from BM to PB and thymus. We found interaction signaling includingCD99-CD99,CXCL12-CXCR4andCCL19-CCR7played important roles in ETP homing to thymus. Briefly, these data provided a single unified developmental spectrum of hematopoiesis cross different tissues, connected by cell migration.
Assessing the environmental impacts of conventional and organic scenarios of rainbow trout farming in France
Authors: Pouil Simon , Besson Mathieu , Phocas Florence , Aubin Joël 
Published: September 2023

AbstractIn France, rainbow trout (Oncorhynchus mykiss) farming traditionally used flow-through systems, which raised concerns about environmental impacts, including limited freshwater availability, and the use of ingredients from intensive agriculture and fishing. To address the growing demand for sustainable food products, there is an increasing interest in organic aquaculture. In this study, we employed an attributional life cycle assessment (LCA) to analyse the environmental impacts of rainbow trout production. We simulated conventional and organic production practices in a hypothetical fish farm to evaluate the differences in environmental impacts at the farm level. The potential impacts were calculated using a product-based functional unit (one tonne of trout) under the two production scenarios and were also expressed using a surface-based functional unit (m2y). Our life cycle impact assessment revealed that organic farming significantly reduced environmental impacts per tonne of trout in seven out of the nine selected impact categories. Notably, freshwater ecotoxicity exhibited the greatest difference, with organic systems showing a 55% decrease. The only exceptions were freshwater eutrophication and water dependence, where organic production led to higher impacts per tonne of trout. In conventional farming, emissions amounted to 14 kg of P eq./tonne, whereas in organic farming, the emissions were slightly higher (15 kg of P eq./tonne). For water dependence, one tonne of trout production in the conventional system mobilized 128 103m3vs. 185 103m3in the organic system. The environmental benefits of organic production were even more marked when using a surface-based functional unit (m2y). We demonstrated the benefits of organic trout production from an environmental perspective. However, our findings highlight the caution needed when interpreting LCA comparisons of such production systems that can be highly influenced by methodological choices such as the functional unit used.
Rendering protein mutation movies with MutAmore
Authors: Weissenow Konstantin , Rost Burkhard 
Published: September 2023

AbstractThe success ofAlphaFold2in reliable protein three-dimensional (3D) structure prediction, assists the move of structural biology toward studies of protein dynamics and mutational impact on structure and function. This transition needs tools that qualitatively assess alternative 3D conformations. We introduceMutAmore, a bioinformatics tool that renders individual images of protein 3D structures for, e.g., sequence mutations into a visually intuitive movie format.MutAmorestreamlines a pipeline casting single amino-acid variations (SAVs) into a dynamic 3D mutation movie providing a qualitative perspective on the mutational landscape of a protein. By default, the tool first generates all possible variants of the sequence reachable through SAVs (L*19 for proteins with L residues). Next, it predicts the structural conformation for all L*19 variants using state-of-the-art models. Finally, it visualizes the mutation matrix and produces a color-coded 3D animation. Alternatively, users can input other types of variants, e.g., from experimental structures.MutAmoresamples alternative protein configurations to study the dynamical space accessible from SAVs in the post-AlphaFold2 era of structural biology. As the field shifts towards the exploration of alternative conformations of proteins,MutAmoreaids in the understanding of the structural impact of mutations by providing a flexible pipeline for the generation of protein mutation movies using current and future structure prediction models.
Widespread position-dependent transcriptional regulatory sequences in plants
Authors: Voichek Yoav , Hristova Gabriela , Mollá-Morales Almudena , Weigel Detlef , Nordborg Magnus 
Published: September 2023

AbstractMuch of what we know about eukaryotic transcription stems from animals and yeast, however, plants have evolved separately for 1.6 billion years, leaving ample time for divergence in transcriptional regulation. Here, we set out to elucidate fundamental properties of cis-regulatory sequences in plants. Using massively parallel reporter assays across four plant species, we demonstrate the central role of sequences downstream of the transcription start site (TSS) in transcriptional regulation. Unlike animal enhancers that are position-independent, plant regulatory elements depend on their position, as altering their location relative to the TSS significantly affects transcription. We highlight the importance of the region downstream of the TSS in regulating transcription by identifying a DNA motif that is conserved across vascular plants and is sufficient to enhance gene expression in a dose-dependent manner. The identification of a large number of position-dependent enhancers points to fundamental differences in gene regulation between plants and animals.
The evolution of transposable elements inBrachypodium distachyonis governed by purifying selection, while neutral and adaptive processes play a minor role
Authors: Horvath Robert , Minadakis Nikolaos , Bourgeois Yann , Roulin Anne C. 
Published: September 2023

AbstractUnderstanding how plants adapt to changing environments and the potential contribution of transposable elements (TEs) to this process is a key question in evolutionary genomics. While TEs have recently been put forward as active players in the context of adaptation, few studies have thoroughly investigated their precise role in plant evolution. Here we used the wild Mediterranean grassBrachypodium distachyonas a model species to identify and quantify the forces acting on TEs during the adaptation of this species to various conditions, across its entire geographic range. Using sequencing data from more than 320 naturalB. distachyonaccessions and a suite of population genomics approaches, we reveal that putatively adaptive TE polymorphisms are rare in wildB. distachyonpopulations. After accounting for changes in past TE activity, we show that only a small proportion of TE polymorphisms evolved neutrally (< 10%), while the vast majority of them are under moderate purifying selection regardless of their distance to genes. TE polymorphisms should not be ignored when conducting evolutionary studies, as they can be linked to adaptation. However, our study clearly shows that while they have a large potential to cause phenotypic variation inB. distachyon, they are not favored during evolution and adaptation over other types of mutations (such as point mutations) in this species.
Ultrastructural localization of calcium homeostasis modulator 1 in the taste buds of mouse circumvallate papillae
Authors: Ikuta Rio , Kakinohana Yuu , Hamada Shun 
Published: September 2023

AbstractTaste receptor cells are morphologically classified as types II and III. These two types of cells transduce different taste modalities and form morphologically distinct synapses with afferent nerve fibers. Type III cells form conventional chemical synapses, whereas type II cells form a unique type of synapses referred to as channel synapses, which release adenosine triphosphate (ATP) as a neurotransmitter through voltage-gated channels comprising calcium homeostasis modulator (CALHM) 1 and CALHM3. Further, channel synapses are associated with large mitochondria with tubular cristae known as atypical mitochondria, which are believed to produce ATP for neurotransmission. Herein, we aimed to generate a monoclonal antibody against CALHM1 and examine its localization in taste buds using immunoelectron microscopy. CALHM1 was detected along the plasma membrane apposed to atypical mitochondria, indicating that CALHM1 is localized at the presynaptic membrane of channel synapses. Additionally, CALHM1 was detected along the plasma membrane lined by subsurface cisternae at sites apposed to afferent nerve fibers.
Autoturbo-DNA: Turbo-Autoencoders for the DNA data storage channel
Authors: Welzel Marius , Dreßler Hagen , Heider Dominik 
Published: September 2023

AbstractDNA, with its high storage density and long-term stability, is a potential candidate for a next-generation storage device. The DNA data storage channel, comprised of synthesis, amplification, storage, and sequencing, exhibits error probabilities and error profiles specific to the components of the channel. Here, we present Autoturbo-DNA, a PyTorch framework for training error-correcting, overcomplete autoencoders specifically tailored for the DNA data storage channel. It allows training different architecture combinations and using a wide variety of channel component models for noise generation during training. It further supports training the encoder to generate DNA sequences that adhere to user-defined constraints.
Multifunctional evolution of palm squirrel coat colour and pattern
Authors: Nivetha M , D’Souza Senan , Shijisha AC , Ligon Russell A. , Nandini R 
Published: September 2023

AbstractComplex colour pattern traits often evolve in response to multiple selective pressures, emphasizing the need for their investigation in an integrative framework. We use museum specimens (n=718) to study the evolution of coat colouration in three palm squirrel species (Funambulusspp.) in the Indian subcontinent, with climate, vegetation, and predators as the potential selective forces. Our results indicate a strong geographical trend in coat colour distribution within and across species, with darker individuals in the southern and lighter individuals in the northern regions. We find significant darkening of coat colouration in more humid, densely vegetated regions with dark soils. Fine-scale intra-specific analyses suggest that species respond differently to multiple abiotic selective pressures. Investigation of stripe pattern elements suggests that the colour-based elements are more visible to raptors, while luminance-based elements are more visible to ferrets. We also find that squirrel species are darker in areas with denser and taller canopies, with low-contrast stripes specific to each predator’s vision. Overall, squirrel coat colouration evolves in response to multiple abiotic factors, including climate and habitat, and specific stripe elements provide particular visual effects on predators depending on the habitat.
Forsythoside A blocks the infection of Avian Infectious Bronchitis Virus through binding S1 subunit
Authors: Shen Ruiting , Liu Xuewei , Yin Peng , Li Xu , Chu Jun , Yao Hua , Hou Xiaolin 
Published: September 2023

AbstractAvian infectious bronchitis (IB) is an acute highly contagious respiratory infectious disease caused by avian infectious bronchitis virus (IBV), causing serious economic losses to poultry industry. Forsythiaside A (FTA) is a phenylethanol glycoside compound in the fruit ofForsythia suspensa, which is widely used for inflammatory respiratory tract disease, including viral infected inflammation. In this study, the mechanism of FTA against IBV was researched. To determine the inhibitory effect of FTA on IBV infection and the interaction between FTA and IBV particles, immunofluorescence assay, plaque assay, RT-qPCR and enzyme-linked immunosorbent assay (ELISA) were performed and it was discovered that FTA inhibited IBV infection and viral attachment to host receptor under non-cytotoxic concentrations, and FTA may bind to virus particles. Then ELISA and isothermal titration calorimetry (ITC) were employed to further study the interaction between FTA and S protein. The results indicated that FTA bound to S1 subunit rather S2 subunit. Besides, the molecular docking showed that FTA form hydrogen bonds with eight amino acids in the S1 subunit. When these amino acids were mutated. the affinity disappeared between the S1 mutant and FTA. In conclusion, FTA prevents IBV infection by blocking viral attachment and contacts with the S1, but not the S2 subunit of IBV. At last, the bind sites were identified by comparing the affinity of wild S1 and mutant S1.
Accurate Bayesian inference of sex chromosome karyotypes and sex-linked scaffolds from low-depth sequencing data
Authors: Caduff Madleina , Eckel Raphael , Leuenberger Christoph , Wegmann Daniel 
Published: September 2023

1AbstractThe identification of sex-linked scaffolds and the genetic sex of individuals, i.e. their sex karyotype, is a fundamental step in population genomic studies. If sex-linked scaffolds are known, single individuals may be sexed based on read counts of next-generation sequencing data. If both sex-linked scaffolds as well as sex karyotypes are unknown, as is often the case for non-model organisms, they have to be jointly inferred. For both cases, current methods rely on arbitrary thresholds, which limits their power for low-depth data. In addition, most current methods are limited to euploid sex karyotypes (XX and XY). Here we developBeXY, a fully Bayesian method to jointly infer the posterior probabilities for each scaffold to be autosomal, X-or Y-linked and for each individual to be any of the sex karyotypes XX, XY, X0, XXX, XXY, XYY and XXYY. If the sex-linked scaffolds are known, it also identifies autosomal trisomies and estimates the sex karyotype posterior probabilities for single individuals. As we show with downsampling experiments,BeXYhas higher power than all existing methods. It accurately infers the sex karyotype of ancient human samples with as few as 20,000 reads and accurately infers sex-linked scaffolds from data sets of just a handful of samples or with highly imbalanced sex ratios, also in the case of low-quality reference assemblies. We illustrate the power ofBeXYby applying it to both whole-genome shotgun and target enrichment sequencing data of ancient and modern humans, as well as several non-model organisms.