bluuebunny/crossref_metadata_2025_split huggingface dataset:
A scalable, data analytics workflow for image-based morphological profiles
Authors: Forsgren Edvin , Cloarec Olivier , Jonsson Pär , Trygg Johan 
Published: July 2023

AbstractCell Painting is an established community-based, microscopy-assay platform that provides high-throughput, high-content data for biological readouts. In November 2022, the JUMP-Cell Painting Consortium released the largest annotated, publicly available dataset, comprising more than 2 billion cell images. This dataset is designed for predicting the activity and toxicity of 100k drug compounds, with the aim to make cell images as computable as genomes and transcriptomes.In this paper, we have developed a data analytics workflow that is both scalable and computationally efficient, while providing significant, biologically relevant insights for biologists estimating and comparing the effects of different drug treatments.The two main objectives proposed include: 1) a simple, yet sophisticated, scalable data analytics metric that utilizes negative controls for comparing morphological cell profiles. We call this metric the equivalence score (Eq. score). 2) A workflow to identify and amplify subtle morphological image profile changes caused by drug treatments, compared to the negative controls. In summary, we provide a data analytics workflow to assist biologists in interpreting high-dimensional image features, not necessarily limited to morphological ones. This enhances the efficiency of drug candidate screening, thereby streamlining the drug development process. By increasing our understanding of using complex image-based data, we can decrease the cost and time to develop new, life-saving treatments.Author summaryMicroscopy-assays are often used to study cell responses to treatments in the search for new drugs. In this paper, we present a method that simplifies the understanding of the data generated from such assays. The data in this study consists of 750 morphological features, which describe the traits and characteristics of the cells, extracted from the images. By using untreated cells as a biological baseline, we’re able to detect subtle changes that occur in the treated cells. These changes are then transformed into an equivalence score (Eq. score), a metric that lets us compare the similarities among different treatments relative to our baseline of untreated cells. Our Eq. score approach transforms complex, high-dimensional data about cell morphology into something more interpretable and understandable. It reduces the “noise” in the features and highlights important changes, the “signal”. Our method can be integrated into existing workflows, aiding researchers in understanding and interpreting complex morphological data derived from cell images more easily. Understanding cell morphology is crucial to deepening our knowledge of biological systems. Ultimately, this could contribute to the faster and more cost-effective development of new, life-saving treatments.
Cryptic mitochondrial ageing coincides with mid-late life and is pathophysiologically informative in single cells across tissues and species
Authors: Green Alistair P. , Klimm Florian , Marshall Aidan S. , Leetmaa Rein , Aryaman Juvid , Gómez-Durán Aurora , Chinnery Patrick F. , Jones Nick S. 
Published: July 2023

AbstractAgeing is associated with a range of chronic diseases and has diverse hallmarks. Mitochondrial dysfunction is implicated in ageing, and mouse-models with artificially enhanced mitochondrial DNA (mtDNA) mutation rates show accelerated ageing. A scarcely studied aspect of ageing, because it is invisible in aggregate analyses, is the accumulation of somatic mtDNA mutations which are unique to single cells (cryptic mutations). We find evidence of cryptic mtDNA mutations from diverse single-cell datasets, from three species, and discover: cryptic mutations constitute the vast majority of mtDNA mutations in aged post-mitotic tissues, that they can avoid selection, that their accumulation is consonant with theory, hits high levels coinciding with species specific mid-late life, and that their presence covaries with a majority of the hallmarks of ageing including protein misfolding and ER stress. We identify mechanistic links to ER stress experimentally and further give evidence that aged brain cells with high levels of cryptic mutations show markers of neurodegeneration and that calorie restriction slows the accumulation of cryptic mutations.
Genotypic and Phenotypic Diversity ofKluyveromyces marxianusIsolates Obtained from the Elaboration Process of Two Traditional Mexican Alcoholic Beverages Derived from Agave: Pulque and Henequen (Agave fourcroydes) Mezcal
Authors: Lappe-Oliveras Patricia , Avitia Morena , Sánchez-Robledo Sara Darinka , Castillo-Plata Ana Karina , Pedraza Lorena , Baquerizo Guillermo , Borgne Sylvie Le 
Published: July 2023

AbstractSevenKluyveromyces marxianusisolates from the elaboration process of pulque and henequen mezcal were characterized. The isolates were identified based on the sequences of the D1/D2 domain of the 26S rRNA gene and the internal transcribed spacer (ITS-5.8S) region. Genetic differences were found between pulque and henequen mezcal isolates and within henequen mezcal isolates, as shown by different branching patterns in the ITS-5.8S phylogenetic tree and (GTG)5 microsatellite profiles, suggesting that sub-strate and process selective conditions may originate differentK. marxianuspopulations. All the isolates fermented and assimilated inulin and lactose and some henequen isolates could also assimilate xylose and cellobiose. Henequen isolates were more thermotolerant than pulque isolates which in contrast presented more tolerance to the cell wall-disturbing agent calcofluor white (CFW) suggesting that they had a different cell wall structure. Additionally, depending on their origin, the isolates presented different maximum specific growth rates (µmax) patterns at different temperatures. Concerning tolerance to stress factors relevant for lignocellulosic hydrolysates fermentation, tolerance limits were lower at 42 than 30°C except for glucose and furfural. Pulque isolates were less tolerant to ethanol, NaCl, and Cd. Finally, all the isolates could produce ethanol by simultaneous saccharification and fermentation (SSF) of a corncob hydrolysate under laboratory conditions at 42°C.
Structure of a membrane-bound menaquinol:organohalide oxidoreductase
Authors: Cimmino Lorenzo , Duarte Américo G. , Ni Dongchun , Ekundayo Babatunde E. , Pereira Inês A.C. , Stahlberg Henning , Holliger Christof , Maillard Julien 
Published: July 2023

AbstractOrganohalide-respiring bacteria are key organisms for the bioremediation of soils and aquifers contaminated with halogenated organic compounds. The major players in this process are respiratory reductive dehalogenases, corrinoid enzymes that use organohalides as substrates and contribute to energy conservation. Here, we present the first structure of a functional menaquinol:organohalide oxidoreductase (MOOR) obtained by cryo-EM. The membrane-bound protein was isolated fromDesulfitobacterium hafniensestrain TCE1 as a PceA2B2complex catalysing the dechlorination of tetrachloroethene (PCE). Two catalytic PceA subunits are anchored to the membrane by two small integral membrane PceB subunits. The structure reveals two menaquinone molecules bound at the interface of the two different subunits, which are the starting point of a chain of redox cofactors for electron transfer to the active site. This structure elucidates how energy is conserved during organohalide respiration in menaquinone-dependent organohalide-respiring bacteria.
Single-cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma
Authors: Sage Sophie E. , Leeb Tosso , Jagannathan Vidhya , Gerber Vinzenz 
Published: July 2023

AbstractSevere equine asthma (SEA) shares clinical and pathological features with human neutrophilic asthma, serving as a rare natural model for this condition. To uncover the elusive immune mechanisms driving SEA, we performed single-cell mRNA sequencing (scRNA-seq) on cryopreserved bronchoalveolar cells from 11 Warmblood horses, five controls and six with SEA. We identified six major cell types, showing significant heterogeneity and novel subtypes. Notably, we observed monocyte-lymphocyte complexes and detected a robust Th17 signature in SEA, withCXCL13upregulation in intermediate monocytes. Asthmatic horses exhibited expansion of the B cell population, Th17 polarization of the T cell populations, and dysregulation of genes associated with T cell function. Neutrophils demonstrated enhanced migratory capacity and heightened aptitude for neutrophil extracellular trap formation. These findings provide compelling evidence for a predominant Th17 immune response in neutrophilic SEA, driven by dysregulation of monocyte and T cell genes. The dysregulated genes identified through scRNA-seq have potential as biomarkers and therapeutic targets for SEA and provide insights into human neutrophilic asthma.One Sentence SummarySingle-cell mRNA sequencing identifies a predominant Th17-mediated immune response in severe equine asthma
The longer the better: longer acrosomes contain more proteins involved in sperm-egg interactions
Authors: Otčenášková Tereza , Stopková Romana , Stopka Pavel 
Published: July 2023

AbstractSpeciation and sperm competition have been shown to be the major driving forces for sperm morphology variation, swimming velocity and metabolism. We used light microscopy to measure sperm traits and nLC-MS/MS to detect proteomic variation in three species of rodents – promiscuousApodemus flavicollis,less promiscuousMicrotus arvalis,and the least promiscuousMus musculus musculus. We show that the length of sperm apical hook containing the acrosome is the most variable trait and that this variation is reflected by proteomes on interspecific and intraspecific levels. Thus, we provide potential markers of selection such as Ldhc (in Mus and Apodemus) for long acrosomes which is a gene coding L-lactate dehydrogenase that is involved in sperm motility and Spaca1, which is important in sperm-oocyte fusion), and e.g. Mup17 for short acrosomes – a gene coding a Major urinary protein that likely chelates lipophilic compounds after spermiogenesis. In short, longer acrosomes are characteristic of proteins involved in fertilisation and gluconeogenesis, while shorter acrosomes contain more cytoskeletal proteins important for spermiogenesis. For the first time, we demonstrate that there is an innate and evolvable variability in sperm morphology and corresponding proteomes within species that can be driven by sperm competition to species-specific reproductive optima.Summary statementWe show that interspecific and intraspecific variation in sperm morphology traits are detectable on proteomic level thus providing markers of selection due to sperm competition.
A matrisome atlas of germ cell development
Authors: Amran Aqilah , Pigatto Lara , Farley Johanna , Godini Rasoul , Pocock Roger , Gopal Sandeep 
Published: July 2023

AbstractThe extracellular matrix (matrisome) provides chemical and mechanical cues to control the structure and function of cells and tissues. Yet, comprehensive understanding of how matrisome factors individually and collectively control cell and tissue behaviorin vivois lacking. Here, we systematically investigate the function of 443 conserved matrisome-coding genes in controlling germ cell behavior within a complex tissue - theCaenorhabditis elegansgermline. Using high-content imaging, 3D reconstruction and cell behavior analysis of >3500 germlines and >7 million germ cells, we identify specific matrisome factors that regulate germline structure, protein distribution, germ cell cycle and fate, apoptosis, and oocyte health. These findings reveal matrisome networks acting autonomously and non-autonomously to coordinate germ cell behavior, providing new avenues to study and manipulate cell fates.
Highly regenerative species-specific genes improve age-associated features in the adultDrosophilamidgut
Authors: Nagai Hiroki , Adachi Yuya , Nakasugi Tenki , Takigawa Ema , Ui Junichiro , Makino Takashi , Miura Masayuki , Nakajima Yu-ichiro 
Published: July 2023

AbstractBackgroundThe remarkable regenerative abilities observed in planarians and cnidarians are closely linked to the active proliferation of adult stem cells and the precise differentiation of their progeny, both of which typically deteriorate during aging in low regenerative animals. While regeneration-specific genes conserved in highly regenerative organisms may confer regenerative abilities and long-term maintenance of tissue homeostasis, it remains unclear whether introducing these regenerative genes into low regenerative animals can improve their regeneration and aging processes.ResultsHere we ectopically express high regenerative species-specific JmjC domain-encoding genes (HRJDs) inDrosophila, a widely used low regenerative model organism. Surprisingly, HRJD expression impedes tissue regeneration in the developing wing disc but extends organismal lifespan when expressed in the intestinal stem cell lineages of the adult midgut under non-regenerative conditions. Notably, HRJDs enhance the proliferative activity of intestinal stem cells while maintaining their differentiation fidelity, ameliorating age-related decline in gut barrier functions.ConclusionsThese findings together suggest that the introduction of highly regenerative species-specific genes can improve stem cell functions and promote a healthy lifespan when expressed in aging animals.
Single-cell landscape reveals NAMPT mediated macrophage polarization that regulate smooth muscle cell phenotypic switch in pulmonary arterial hypertension
Authors: Wen Zuoshi , Jiang Liujun , Yu Fangcong , Xu Xiaodong , Chen Mengjia , Xue Jianing , Zhu Pengwei , Ying Zhangquan , Li Zhoubin , Chen Ting 
Published: July 2023

AbstractRationalePulmonary arterial hypertension (PAH) is a progressive and lethal disease that leads to elevated pulmonary vascular resistance and right ventricular failure. The phenotypic switching of pulmonary arterial smooth muscle cells (SMCs) plays a crucial role in the pathological progression of PAH. However, the underlying mechanism of SMC phenotypic modulation remains unclear.ObjectivesWe aim to provide a comprehensive understanding of SMC phenotypes and regulatory networks by analyzing hypertensive and non-diseased pulmonary arteries.MethodsWe performed single-cell RNA sequencing (scRNA-seq) on pulmonary arteries obtained from patients with PAH and healthy donors. This was followed by bioinformatics analyses, mouse models, and in vitro studies to construct a normal pulmonary artery atlas, characterize SMC phenotypes, investigate intercellular communication, and explore the molecular mechanisms underlying SMC phenotypic switching.Measurements and Main ResultsOur scRNA-seq analysis identified specific activation of vascular cells, including myofibrocytes, macrophage M2 polarization, endothelial-mesenchymal transition, and chondroid-like SMCs in healthy pulmonary arteries. In PAH pathology, there was an enhanced phenotypic switch of SMCs from contractile to fibroblast-like. Intercellular communication revealed increased M1 macrophage-SMC crosstalk in PAH, which was facilitated by NAMPT. Using a cellular co-culture system, we found that NAMPT-mediated M1 macrophage polarization induced fibroblast-like phenotypic switching in SMCs via the CCR2/CCR5 axis.ConclusionsOur findings provide a comprehensive cell atlas of healthy human pulmonary arteries and demonstrate that NAMPT-driven M1 macrophage polarization plays a critical role in the fibroblast-like phenotypic switching of SMCs through CCR2/CCR5 cellular crosstalk in PAH.
Co-cultivation ofSaccharomyces cerevisiaestrains combines advantages of different metabolic engineering strategies for improved ethanol yield
Authors: van Aalst Aafke C.A. , van der Meulen Igor S. , Jansen Mickel L.A. , Mans Robert , Pronk Jack T. 
Published: July 2023

AbstractGlycerol is the major organic byproduct of industrial ethanol production with the yeastSaccharomyces cerevisiae. Improved ethanol yields have been achieved with engineeredS. cerevisiaestrains in which heterologous pathways replace glycerol formation as the predominant mechanism for anaerobic re-oxidation of surplus NADH generated in biosynthetic reactions. Functional expression of heterologous phosphoribulokinase (PRK) and ribulose-1,5-bisphosphate carboxylase (RuBisCO) genes enables yeast cells to couple a net oxidation of NADH to the conversion of glucose to ethanol. In another strategy, NADH-dependent reduction of exogenous acetate to ethanol is enabled by introduction of a heterologous acetylating acetaldehyde dehydrogenase (A-ALD). This study explores potential advantages of co-cultivating engineered PRK-RuBisCO-based and A-ALD-based strains in anaerobic bioreactor batch cultures. Co-cultivation of these strains, which in monocultures showed reduced glycerol yields and improved ethanol yields, strongly reduced the formation of acetaldehyde and acetate, two byproducts that were formed in anaerobic monocultures of a PRK-RuBisCO-based strain. In addition, co-cultures on medium with low acetate-to-glucose ratios that mimicked those in industrial feedstocks completely removed acetate from the medium. Kinetics of co-cultivation processes and glycerol production could be optimized by tuning the relative inoculum sizes of the two strains. Co-cultivation of a PRK-RuBisCO strain with aΔgpd1 Δgpd2A-ALD strain, which was unable to grow in the absence of acetate and evolved for faster anaerobic growth in acetate-supplemented batch cultures, further reduced glycerol formation but led to extended fermentation times. These results demonstrate the potential of using defined consortia of engineeredS. cerevisiaestrains for high-yield, minimal-waste ethanol production.
A Critical Study in Stereopsis and Listing’s Law
Authors: Turski Jacek 
Published: July 2023

ABSTRACTThe brain uses slightly different 2D retinal images to enhance our vision with stereopsis: spatial depth and 3D shape. Stereopsis is organized by pairs of corresponding retinal elements of zero disparity: a small retinal area in one eye and the corresponding unique area in the other share one subjective visual direction. This organization results in retinal disparity’s spatial coordinates. The study presented here extends the 2D setting of the author’s geometric modeling of the disparity’s spatial coordination in the binocular system with the asymmetric eye (AE) to the 3D framework. The AE models the healthy human eye’s asymmetry of optical components. InGeoGebra’sdynamic geometry simulations, the 3D spatial coordinates of retinal disparity integrated with the eyes’ posture are visualized, and longitudinal and vertical disparities of distal visual stimuli are computed, contributing to stereopsis and visual space geometry study. Further, the torsional disparity is computed in the framework of Euler’s rotation theorem. It can assess the geometric and neural or ocular motor plant constraints to Listing’s law. Finally, epipolar geometry in the binocular system with AEs is discussed. Although this study enhances the geometric description of stereopsis and oculomotor control of eyes 3D orientations, it also simplifies their analyses.
Flow cytometric isolation of drug-like conformational antibodies specific for amyloid fibrils
Authors: Desai Alec A. , Zupancic Jennifer M. , Trzeciakiewicz Hanna , Gerson Julia E. , DuBois Kelly N. , Skinner Mary E. , Sharkey Lisa M. , McArthur Nikki , Ferris Sean P. , Bhatt Nemil N. , Makowski Emily K. , Smith Matthew D. , Chen Hongwei , Huang Jie , Jerez Cynthia , Kane Ravi S. , Kanaan Nicholas M. , Paulson Henry L. , Tessier Peter M. 
Published: July 2023

ABSTRACTAntibodies that recognize specific protein conformational states are broadly important for research, diagnostic and therapeutic applications, yet they are difficult to generate in a predictable and systematic manner using either immunization orin vitroantibody display methods. This problem is particularly severe for conformational antibodies that recognize insoluble antigens such as amyloid fibrils associated with many neurodegenerative disorders. Here we report a quantitative fluorescence-activated cell sorting (FACS) method for directly selecting high-quality conformational antibodies against different types of insoluble (amyloid fibril) antigens using a single, off-the-shelf human library. Our approach uses quantum dots functionalized with antibodies to capture insoluble antigens, and the resulting quantum dot conjugates are used in a similar manner as conventional soluble antigens for multi-parameter FACS selections. Notably, we find that this approach is robust for isolating high-quality conformational antibodies against tau and α-synuclein fibrils from the same human library with combinations of high affinity, high conformational specificity and, in some cases, low off-target binding that rival or exceed those of clinical-stage antibodies specific for tau (zagotenemab) and α-synuclein (cinpanemab). This approach is expected to enable conformational antibody selection and engineering against diverse types of protein aggregates and other insoluble antigens (e.g., membrane proteins) that are compatible with presentation on the surface of antibody-functionalized quantum dots.
Can rural e-commerce narrow the urban–rural income gap? Evidence from coverage of Taobao villages in China
Authors: Liu Yang , Zhou Mi 
Published: July 2023

PurposeThe digital economy is expected to revive the countryside and reduce the current level of urban–rural inequality. Nevertheless, whether rural e-commerce can narrow the urban–rural income gap still requires further analysis. The purpose of this paper is to clarify whether this goal is, in fact, being achieved.Design/methodology/approachTaobao villages have become the epitome of rural e-commerce development in China. Therefore, this paper matches the data of Taobao villages and the data of prefecture-level cities from 2014 to 2019, and employs a two-way fixed effect model, nonlinear model, instrumental variable model and interactive fixed effects model to explore the impact of rural e-commerce on the urban–rural income gap.FindingsFirstly, the ability of urban residents to share rural e-commerce development is higher than that of rural residents, which actually widens the urban–rural income gap. Secondly, the migration to cities of rural families that have profited from e-commerce, and the return of working-class people to the countryside, are two factors that are contributing to the widening of the urban–rural income gap. Thirdly, the farther the distance from the urban area and the higher the spatial agglomeration of the rural e-commerce cluster is, the weaker the impact on widening the urban–rural income gap will be. Finally, while industrial-led rural e-commerce is responsible for widening the urban–rural income gap, agricultural-led rural e-commerce has no significant impact on the urban–rural income gap.Originality/valueTo the best of the authors' knowledge, this paper is the first to analyze the impact of rural e-commerce on the urban–rural income gap from the perspective of the coverage of Taobao villages. This empirical study will enrich existing theoretical perspectives on urban–rural integration under the backdrop of the digital economy.