bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipidomic and Proteomic Insights from Extracellular Vesicles in Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes
Authors: Okeoma Chioma M. , Naushad Wasifa , Okeoma Bryson C. , Gartner Carlos , Santos-Ortega Yulica , Vary Calvin , Carregari Victor Corasolla , Larsen Martin R. , Noghero Alessio , Grassi-Oliveira Rodrigo , Walss-Bass Consuelo
Published: August 2024

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to glial activation and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD. In particular, our study investigated neuroinflammatory signatures in SUD by isolating EVs from the dorsolateral prefrontal cortex (dlPFC) Brodmann’s area 9 (BA9) in postmortem subjects. We isolated BA9-derived EVs from postmortem brain tissues of eight individuals (controls: n=4, SUD: n=4). The EVs were analyzed for physical properties (concentration, size, zeta potential, morphology) and subjected to integrative multi-omics analysis to profile the lipidomic and proteomic characteristics. We assessed the interactions and bioactivity of EVs by evaluating their uptake by glial cells. We further assessed the effects of EVs on complement mRNA expression in glial cells as well as their effects on microglial migration. No significant differences in EV concentration, size, zeta potential, or surface markers were observed between SUD and control groups. However, lipidomic analysis revealed significant enrichment of glycerophosphoinositol bisphosphate (PIP2) in SUD EVs. Proteomic analysis indicates downregulation of SERPINB12, ACYP2, CAMK1D, DSC1, and FLNB, and upregulation of C4A, C3, and ALB in SUD EVs. Gene ontology and protein-protein interactome analyses highlight functions such as cell motility, focal adhesion, and acute phase response signaling that is associated with the identified proteins. Both control and SUD EVs increased C3 and C4 mRNA expression in microglia, but only SUD EVs upregulated these genes in astrocytes. SUD EVs also significantly enhanced microglial migration in a wound healing assay.This study successfully isolated EVs from postmortem brains and used a multi-omics approach to identify EV-associated lipids and proteins in SUD. Elevated C3 and C4 in SUD EVs and the distinct effects of EVs on glial cells suggest a crucial role in acute phase response signaling and neuroinflammation.
Overcoming toxicity: why boom-and-bust cycles are good for non-antagonistic microbes
Authors: Wang MingYi , Vladimirsky Alexander , Giometto Andrea
Published: August 2024

Antagonistic interactions are critical determinants of microbial community stability and composition, offering host benefits such as pathogen protection and providing avenues for antimicrobial control. While the ability to eliminate competitors confers an advantage to antagonistic microbes, it often incurs a fitness cost. Consequently, many microbes only produce toxins or engage in antagonistic behavior in response to specific cues like quorum sensing molecules or environmental stress. In laboratory settings, antagonistic microbes typically dominate over sensitive ones, raising the question of why both antagonistic and non-antagonistic microbes are found in natural environments and host microbiomes. Here, using both theoretical models and experiments with killer strains ofSaccharomyces cerevisiae, we show that boom-and-bust dynamics caused by temporal environmental fluctuations can favor non-antagonistic microbes that do not incur the growth rate cost of toxin production. Additionally, using control theory, we derive bounds on the competitive performance and identify optimal regulatory toxin-production strategies in various boom- and-bust environments where population dilutions occur either deterministically or stochastically over time. Our findings offer a new perspective on how both antagonistic and non-antagonistic microbes can thrive under varying environmental conditions.
The double-edged effect of environmental fluctuations on evolutionary rescue
Authors: Shibasaki Shota , Yamamichi Masato
Published: August 2024

Recent studies revealed that contemporary evolution can be rapid enough to prevent population extinction in deteriorating environments through “evolutionary rescue”. Researchers have investigated how evolutionary rescue is affected by various factors such as initial population sizes, the amount of genetic variation, and the speed of environmental changes, but few studies focused on environmental fluctuations. As the ongoing global changes are influencing the mean and variance of many environmental variables, it is crucial to explore how environmental fluctuations affect evolutionary rescue for understanding eco-evolutionary dynamics in the wild. Here we show that increasing the amplitude of environmental fluctuations around long-term deteriorating trends has negative and positive effects on evolutionary rescue by analyzing a mathematical model and conducting laboratory experiments on the green algaChlorella vulgarisunder increasing salinity. Increasing the amplitude of environmental fluctuations produces an episode of a huge environmental change, thereby increasing the adaptation lag between the optimal trait value and the population trait mean, which eventually causes population extinction in model simulations. On the other hand, large environmental fluctuations can increase trait variance within a population, potentially promoting adaptive evolution. Indeed, we observed that algal strains that experienced large environmental fluctuations could grow in a harsh environment whereas strains that experienced smaller or no environmental fluctuations could not. These results suggest that we will be able to promote or prohibit evolutionary rescue in nature by carefully considering the double-edged effect of environmental fluctuations on evolutionary rescue.
Non-destructive DNA extraction from specimens and environmental samples using DESS preservation solution for DNA barcoding
Authors: Ogiso-Tanaka Eri , Ito Minako Abe , Shimada Daisuke
Published: August 2024

DESS is a widely used storage solution for the preservation of DNA from biological tissue samples. DESS comprises 20% dimethyl sulfoxide, 250 mM ethylenediaminetetraacetic acid, and saturated sodium chloride, and its efficacy has been confirmed in various taxa and tissues. DESS enables the stable, long-term preservation of both sample morphology and DNA. However, to access the DNA, excising a portion of the sample was necessary. Although DNA is a valuable source of information for species identification, DNA extraction can result in the loss of an entire sample or segment, especially in small-sized organisms, thereby compromising specimen value. Therefore, establishing non-destructive DNA extraction techniques is imperative. Thus, this paper presents a protocol for conducting non-destructive DNA extraction and DNA barcoding using a portion of the DESS supernatant obtained from a nematode specimen. This method was successfully employed for DNA barcoding of nematodes that were stored in DESS at room temperature (-10∼35°C) for ten years. Moreover, the method can be potentially applied in the preservation and non-destructive extraction of DNA from specimens of various species. Following sample collection, a bulk environmental sample from sediment and seagrass is immediately immersed in DESS in the field. Subsequently, DNA is extracted from the supernatant solution, allowing non-destructive DNA barcoding. Overall, this paper presents comprehensive protocols for DNA extraction from DESS supernatants and demonstrates their practical application using meiofauna (small animals) and diatoms as examples.
Pyruvate kinase allostery resist hyperglycemia, obesity and inflammation by inducing TCA vortex and glucose U turn
Authors: Zhang Xuan , Jiang Xudong , Wu Xiaobin , Yang Youhao , Wang Jintian , Zheng Junfeng , Zhou Miao , Chen Qian
Published: August 2024

ATP is the final product of glycolysis and the TCA cycle. However, the counter-regulation of glycosis and TCA by ATP is poorly understood. Here we show that ATP analog celastrol (CLT) binds to the ATP binding pocket on pyruvate kinase PKM (PKM) while inducing allosteric regulation of PKM. Quantum calculation predicts hydrogen bond formation between CLT and asparagine. Liquid chromatography-mass spectrometry further identifies PKM as CLT’s target. The inhibition of PKM is stronger and longer for CLT while weak and short for ATP. Notably, CLT-PKM interaction perfectly underlies the hypoglycemic effects by forming glucose carbon flux U turn before PKM. Besides, the PKM allostery induces a tricarboxylic acid (TCA) vortex which could promote amino acid and lipid degradation as the energy compensation, leading to a significant weight loss. Additionally, CLT exerts efficient antioxidant effects by altering the glucose flux to strengthen the pentose phosphate pathway. Consequently, the CLT-PKM interaction vividly reproduces the ATP-PKM interaction named “ATP resistance” in the diabetes pathogenesis.
Comparative genomic analysis of a Colombian strain ofLeptospira santarosaiserogroup Autumnalis serovar Alice and inference of its virulence factors
Authors: Villarreal-Julio Rafael Guillermo , Ordoñez Brayan , Yepes-Blandón Jonny Andrés
Published: August 2024

Introduction

The study aimed to characterize the genome of a Colombian strain ofLeptospira santarosaito infer bacterial virulence factors.

Materials and methods

Under the approach of a quantitative research, an isolate of Colombian origin ofL. santarosaiwas sequenced using new generation 454 GS FLX Titanium sequencers. Subsequently, bioinformatics programs were used for the physical description of the genome (number of genes, size), open reading frame prediction, prediction of proteins and their orthologs in other pathogenic species, of intermediate pathogenicity and non-pathogenic, cellular localization of proteins.

Results

The assembly of the spirochete genome was achievedLeptospira santarosaiserogroup Autumnalis serovar Aliceand the description of the genetic, structural and functional characteristics of its genes. It is concluded that the core- genome of the isolate is composed of 1747 proteins, which are common to allL. santarosaistrains available in GenBank. It was determined that it has a total of 4,138 proteins, 141 of which are unique to its genome. The possible role of the virulence factors found in the Colombian isolate was identified and described.

Conclusions

The study contributes to the understanding of the pathophysiological mechanisms induced byLeptospira.
Genetic predisposition towards multicellularity in Chlamydomonas reinhardtii
Authors: Chen I-Chen Kimberly , Khatri Shania , Herron Matthew D. , Rosenzweig Frank
Published: August 2024

The evolution from unicellular to multicellular organisms facilitates further phenotypic innovations, notably cellular differentiation. Multiple research groups have shown that in the laboratory simple, obligate multicellularity can evolve from a unicellular ancestor under appropriate selection. However, little is known about the extent to which deterministic factors like ancestral genotype and environmental context influence the likelihood of this evolutionary transition. To test whether certain genotypes are predisposed to evolve multicellularity in different environments, we carried out a set of 24 evolution experiments each founded by a population consisting of 10 different strains of the unicellular green alga Chlamydomonas reinhardtii, all in equal proportions. Twelve of the initially identical replicate populations were subjected to predation by the protist Parmecium tetraurelia while the other 12 were subjected to settling selection by slow centrifugation. Population subsamples were transferred to fresh media on a weekly basis for a total of 40 transfers (~600 generations). Heritable multicellular structures arose in four of 12 predation-selected populations (6 multicellular isolates in total), but never in the settling selection populations. By comparing whole genome sequences of the founder and evolved strains, we discovered that every multicellular isolate arose from one of two founders. Cell cluster size varied not only among evolved strains derived from different ancestors but among strains derived from the same ancestor. These findings show that both deterministic and stochastic factors influence whether initially unicellular populations can evolve simple multicellular structures.
AllerTrans: A Deep Learning Method for Predicting the Allergenicity of Protein Sequences
Authors: Sarlakifar Faezeh , Malek Hamed , Allahyari Fard Najaf , Khotanlou Zahra
Published: August 2024

Recognizing the potential allergenicity of proteins is essential for ensuring their safety. Allergens are a major concern in determining protein safety, especially with the increasing use of recombinant proteins in new medical products. These proteins need careful allergenicity assessment to guarantee their safety. However, traditional laboratory testing for allergenicity is expensive and time-consuming. To address this challenge, bioinformatics offers efficient and cost-effective alternatives for predicting protein allergenicity. In this study, we developed an enhanced deep-learning model to predict the potential allergenicity of proteins based on their primary structure represented as protein sequences. In simple terms, this model classifies proteins into allergenic or non-allergenic classes. Our approach utilizes two protein language models to extract distinct feature vectors for each sequence, which are then input into a deep neural network model for classification. Each feature vector represents a specific aspect of the protein sequence, and combining them enhances the outcomes. Finally, we effectively combined the predictions of our top-performing models using ensemble modeling techniques. This could balance the model’s sensitivity and specificity and improve the outcome. Our proposed model demonstrates admissible improvement compared to existing models, achieving a sensitivity of 97.91%, specificity of 97.69%, accuracy of 97.80%, and an impressive area under the ROC curve of 99% using the standard five-fold cross-validation.
A systematic review of etiopathogenesis and treatment modalities for Moyamoya disease
Authors: Chilukuri Ganesh , Viswanathan Amba , Job Amy , Joshi Vivek
Published: August 2024

Introduction

Moyamoya disease (MMD) is a rare and chronic cerebrovascular disease characterized by progressive stenosis or occlusion of the blood vessels within the terminal intracranial aspect of the internal carotid artery and the circle of Willis, leading to the compensatory development of a fragile collateral vessel network at the base of the brain. These vascular features are responsible for the recurrent ischemic and/or hemorrhagic strokes seen in affected patients. Numerous studies have attempted to clarify the clinical features of Moyamoya, including its etiopathology and interventions. In recent years, the development of neuroimaging and surgical techniques has enhanced the understanding of MMD in patients. The purpose of this review is to discuss the hypothesized etiopathogenesis, clinical manifestations, and the current possible treatment options available for Moyamoya disease.

Methods

The PRISMA protocol was utilized to perform an extensive literature search on Google Scholar, Scopus, Web of Science, and PubMed for articles about etiopathogenesis and clinical presentation of Moyamoya disease and the treatment protocols followed in different parts of the world. A comprehensive analysis was also conducted for original articles to better understand the possible clinical presentation and diagnostic criteria used.

Results

Based on the literature review, the RNF213 mutation, mitochondrial dysfunction, and misregulation of growth factors in endothelial cells are the most acceptable etiopathogenesis of MMD via their involvement in neurovascular inflammation.

Conclusion

The diagnostic test of choice is magnetic resonance angiography while direct & indirect revascularization surgeries are both effective and established treatments for managing symptoms of Moyamoya disease.
Modular Cell Line for Scalable and Rapid In Vitro Evaluation of Chimeric Antigen Receptors
Authors: Dubovik Simon , Dormeshkin Dmitri , Migas Alexandr
Published: August 2024

The development of novel Chimeric Antigen Receptor T-cell (CAR-T-cell) products relies on continuousin vitrotesting of new antigen/antibody pairs, as well as modification of CAR composition itself. Since any Tumor-Associated Antigens (TAA) have been chosen and proven to be specific, and before the firstin vivostudies these CAR compositions have to be extensively validatedin vitro. Conventionalin vitrotests rely on TAA expressing immortalized cell lines or immortalized cell lines derivatives engineered to stably express antigen of interest, making this type of model not fully scalable when it comes to multiple TAA/antibody pairs. Therefore, there is a need for a representative, scalable model for preclinical assessment. Here, we introduce a novel model cell line approach that can be easily adapted for different experiments by anchoring ALFA-tagged proteins on the cell surface using an anti-ALFA-tag membrane single-domain antibody. This modular multi-component system has the potential to reduce novel CARin vitroevaluation procedures from months to weeks.
Discovering nuclear localization signal universe through a novel deep learning model with interpretable attention units
Authors: Li Yi-Fan , Pan Xiaoyong , Shen Hong-Bin
Published: August 2024

Nuclear localization signals (NLSs) are essential peptide fragments within proteins that play a decisive role in guiding proteins into the cell nucleus. Determining the existence and precise locations of NLSs experimentally is time-consuming and complicated, resulting in a scarcity of experimentally validated NLS fragments. Consequently, annotated NLS datasets are relatively limited, presenting challenges for data-driven approaches. In this study, we propose an innovative interpretable approach, NLSExplorer, which leverages large-scale protein language models to capture crucial biological information with a novel attention-based deep network for NLS identification. By enhancing the knowledge retrieved from protein language models with a novel attention to key area module, NLSExplorer achieves superior predictive performance compared to existing methods on two NLS benchmark datasets. Additionally, NLSExplorer is able to detect various kinds of segments highly correlated with nuclear transport, such as nuclear export signals. We employ NLSExplorer to investigate potential NLSs and other domains that are important for nuclear transport in nucleus-localized proteins in the Swiss-Prot database. Furthermore, the comprehensive pattern analysis for all these segments uncovers a potential NLS space and internal relationship of important nuclear transport segments for 416 species. This study not only introduces a powerful tool for predicting and exploring NLS space, but also offers a versatile network that is powerful for detecting characteristic domains and motifs of NLSs.
Dynamic roles of ILC3 in endometrial repair and regeneration
Authors: Cuff Antonia O. , Woon Ee Von , Bainton Thomas , Browne Brendan , Kirkwood Phoebe M. , Collins Frances , Gibson Douglas A. , Saunders Philippa T.K. , Horne Andrew W. , Johnson Mark R. , MacIntyre David A. , Male Victoria
Published: August 2024

Innate lymphoid cells (ILC) are prominent in the human uterine mucosa and play physiological roles in pregnancy. ILC3 are the second-most common ILC subset in the uterine mucosa, but their role remains unclear. Here we define two subsets of lineage-negative CD56+ CD117+ CRTH2-uterine ILC3, distinguished by their expression of CD127. The CD127-subset is most numerous and active during menstruation and immediately after parturition, suggesting a role in repair of the uterine mucosa (called endometrium outside of pregnancy); the CD127+ subset is most numerous and active immediately after menstruation, as the endometrium regenerates. In healthy endometrium, ILC3 are spatially associated with glandular epithelial and endothelial cells, which both express receptors for the ILC3-derived cytokines, IL-22 and IL-8. In the eutopic endometrium of people with endometriosis, ILC3 are located further from glandular epithelial and endothelial cells suggesting that these cells may be less exposed to ILC3 products, potentially with negative consequences for endometrial regeneration. Our findings highlight the dynamic nature of ILC3 in the uterine mucosa and suggest their primary role is in repair and regeneration. An improved understanding of uterine ILC3 will inform future research on endometrial health and disease.
The eduWOSM: a benchtop advanced microscope for education and research
Authors: Carter N.J. , Martin D.S. , Molloy J.E. , Cross R.A.
Published: August 2024

To improve access to advanced optical microscopy in educational and resource-limited settings we have developed the eduWOSM (educationalWarwickOpenSourceMicroscope), an open hardware platform for transmitted-light and epifluorescence imaging in up to 4 colours, including single molecule imaging. EduWOSMs are robust, bright, compact, portable and ultra-stable. They are controlled entirely by open source hardware and software, with an option for remote control from a webpage. Here we describe the core eduWOSM technology and benchmark its performance using 3 example projects, single fluorophore tracking of tubulin heterodimers within gliding microtubules, 4D (deconvolution) imaging/tracking of chromosome motions in dividing human cells, and automated single particle tracking in vitro and in live cells with classification into subdiffusive, diffusive and superdiffusive motion.
Human genetic ancestry,Mycobacterium tuberculosisdiversity and tuberculosis disease severity in Dar es Salaam, Tanzania
Authors: Zwyer Michaela , Xu Zhi Ming , Ross Amanda , Hella Jerry , Sasamalo Mohamed , Rotival Maxime , Hiza Hellen , Rutaihwa Liliana K. , Borrell Sonia , Reither Klaus , Fellay Jacques , Portevin Damien , Quintana-Murci Lluis , Gagneux Sebastien , Brites Daniela
Published: August 2024

Infectious diseases have affected humanity for millennia and are among the strongest selective forces. Tuberculosis (TB) is an ancient disease, caused by the human-adapted members of theMycobacterium tuberculosiscomplex (MTBC). The outcome of TB infection and disease is highly variable, and co-evolution between human populations and their MTBC strains may account for some of this variability. Particular human genetic ancestries have been associated with higher susceptibility to TB, but socio-demographic aspects of the disease can confound such associations. Here, we studied 1,000 TB patients from Dar es Salaam, Tanzania, together with their respective MTBC isolates, by combining human and bacterial genomics with clinical data. We found that the genetic background of the TB patient population was strongly influenced by the Bantu migrations from West Africa, which is in contrast to the corresponding MTBC genotypes that were mainly introduced from outside Africa. These findings suggest a recent evolutionary history of co-existence between the human and MTBC populations in Dar es Salaam. We detected no evidence of an effect of human genetic ancestry, or MTBC phylogenetic diversity alone, nor their interaction, on TB disease severity. Treatment-seeking, social and environmental factors are likely to be the main determinants of disease severity at the point of care in this patient population.

Author Summary

Tuberculosis (TB) is an ancient infectious disease that continues to challenge global health efforts. Here, we explored the interplay between human and bacterial genetics on TB in Dar es Salaam, Tanzania. We found that neither the genetic ancestry of the patient, nor the bacterial genotype alone, nor their interaction, influenced the severity of TB. Our finding indicate that in this patient population, social and environmental factors may be the main determinants of TB disease severity.
Impacts of Cell Ranger versions on Chromium gene expression data
Authors: Abugessaisa Imad , Hasegawa Akira , Walker Scott , Katayama Shintaro , Kere Juha , Kasukawa Takeya
Published: August 2024

In droplet-based single cell gene expression data, cell barcode processing by Cell Ranger (CR) is a standard pipeline. But no systematic evaluation of the impact of CR version on single cell gene expression data has been conducted. To comprehensively evaluate the impact of CR version, we considered six molecular quality criteria, quantified gene expression, and performed downstream analysis for 12 single-cell datasets. Each dataset was processed by 15 versions of CR. We demonstrated that different versions of CR yield different numbers of cell barcodes with significant variation in detected UMIs, features, molecular qualities and average gene expression of protein-coding and lncRNA for the same dataset. Our analysis finds distinction between two diverse categories of cell barcodes: common barcodes unmasked by all versions of CR, and specific barcodes only unmasked/masked by some versions. Surprisingly, we observed variation in molecular read-out between common cell barcodes when called by different versions of CR. The specific barcodes yield skewed gene body coverage and form distinct clusters. The choice of CR version affects scores for quality, average gene expression, clustering results, and top cluster marker genes of the dataset.
In vivoantibody labeling route and fluorophore dictate labeling efficiency, sensitivity, and longevity
Authors: Hagan Natalie B. , Inaku Charles , Kunder Nikesh , White Tayleur , Iraguha Thierry , Meyer Anna , Pauken Kristen E. , Schenkel Jason M.
Published: August 2024

Leukocytes migrate through the blood and extravasate into organs to surveil the host for infection or cancer. Recently, we demonstrated that intravenous (IV) anti-CD45.2 antibody labeling allowed for precise tracking of leukocyte migration. However, the narrow labeling window can make this approach challenging for tracking rare migration events. Here, we show that altering antibody administration route and fluorophore can significantly extend the antibody active labeling time. We found that while both IV and intraperitoneal (IP) anti-CD45.2 antibody labeled circulating leukocytes after injection, they had different kinetic properties that impacted labeling time and intensity. Quantification of circulating antibody revealed that while unbound IV anti-CD45.2 antibody rapidly decreased, unbound IP anti-CD45.2 antibody increased over one hour. Usingin vitroandin vivoserial dilution assays, we found that Alexa Fluor 647 (AF647) and Brilliant Blue 700 (BB700) dyes had the greatest labeling sensitivity compared to other fluorophores. However, IP antibody injection with anti-CD45.2 BB700, but not AF647, resulted in continuous blood leukocyte labeling for over 6 hours. Finally, we leveraged IP anti-CD45.2 BB700 antibody to track slower migrating leukocytes into tumors. We found that IP anti-CD45.2 antibody injection allowed for the identification of ∼seven times as many tumor-specific CD8+T cells that had recently migrated from blood into tumors. Our results demonstrate how different injection routes and fluorophores affect anti-CD45.2 antibody leukocyte labeling and highlight the utility of this approach for defining leukocyte migration in the context of homeostasis and cancer.
Local photo-crosslinking of native tissue matrix regulates cell function
Authors: Ahmed Donia W. , Tan Matthew L. , Gabbard Jackson , Liu Yuchen , Hu Michael M. , Stevens Miriam , Midekssa Firaol S. , Han Lin , Zemans Rachel L. , Baker Brendon M. , Loebel Claudia
Published: August 2024

Within most tissues, the extracellular microenvironment provides mechanical cues that guide cell fate and function. Changes in the extracellular matrix such as aberrant deposition, densification and increased crosslinking are hallmarks of late-stage fibrotic diseases that often lead to organ dysfunction. Biomaterials have been widely used to mimic the mechanical properties of the fibrotic matrix and study cell function. However, the initiation of fibrosis has largely been overlooked, due to the challenges in recapitulating early fibrotic lesions within the native extracellular microenvironment. Using visible light mediated photochemistry, we induced local crosslinking and stiffening of extracellular matrix proteins withinex vivomurine and human tissue. Inex vivolung tissue of epithelial cell lineage-traced mice, local matrix crosslinking mimicked early fibrotic lesions that increased alveolar epithelial cell spreading, differentiation and extracellular matrix remodeling. However, inhibition of cytoskeletal tension or integrin engagement reduced epithelial cell spreading and differentiation, resulting in alveolar epithelial cell dedifferentiation and reduced extracellular matrix deposition. Our findings emphasize the role of local extracellular matrix crosslinking and remodeling in early-stage tissue fibrosis and have implications forex vivodisease modeling and applications to other tissues.
Description of the structural and functional genomic composition ofL. santarosaiserovar Alice
Authors: Villarreal-Julio Rafael Guillermo , Montes Valeria Isabel Manjarrez , Perez Brayan Estiven Ordoñez , Yepes-Blandón Jonny Andrés
Published: August 2024

In Colombia, pathogenic knowledge of endemicLeptospiraspecies is limited.Leptospirasantarosai serogroup Autumnalis serovar Alice Strain JET was isolated from a patient from Urabá Antioquia, so it is necessary to know more about its genomic components and pathogenomics. A comparative analysis of the bacterial genome was carried out by computational biology. Complete information for analysis was obtained fromhttps://www.ncbi.nlm.nih.gov/fromwhere the complete genome sequences of 67 species of the genusLeptospiraspp were accessed. The genome of the Colombian strain consists of a major chromosome (chromosome I) and the minor chromosome (chromosome II), which add up to a total of 4.13 Mb. The chromosomes have a G+C percentage of 41.6% three genes for ribosomal RNA distributed 1 for the 23s subunit, 1 for the 16s subunit and 1 for the 5s subunit, 6 for other types of RNA and 37 transfer RNA genes. Two chromosomal pseudomolecules were inferred for the Colombian strain, assigning proteins 3,796 and 318 to chromosomes I and II respectively. Genomic identity analysis resulted in a nucleotide identity of 92.95% and a high degree of synteny between chromosomes. 53 and 68 exclusive proteins were identified for serovar Shermani and the Colombian strain respectively. Of the 68 proteins, most are hypothetical, however, nine transposases, two integrases and one membrane protein were identified. The Colombian strain shares orthologous proteins with members of the different subgroups of species that range between 3,286-2,600 with pathogenic species, 2,416-2,296 intermediate species and 1,972-1,864 saprophytic species and 40.98% of the proteins present in the genome of The Colombian strain has a high percentage of identity with the proteins of the main pathogenic speciesL. interrogans(80-100% similarity), which demonstrates a strong genetic relationship between the Colombian strain and the pathogenic subgroup. For the Colombian strain, it was found to contain CRISPR/Cas repeats and 9 families of class 1, type I and subtype IA and IE were located where each of these subtypes contained 8 cas genes; In addition, 25 proteins were found involved in the de novo biosynthesis of vitamin B12. In the Colombian strain, three species of different phage structures were found that could facilitate infection and subsequent colonization in the host. Therefore, the objective is to describe the structural and functional genomic composition ofL. santarosaiserovar Alice. The genomic characteristics evidenced are basic in the knowledge of the bacterial mechanisms, the evolutionary, phylogenetic and pathogenic analysis ofLeptospiraspp that affects the population of Colombian endemic areas.
Correlation and Matching Representations of Binocular Disparity across the Human Visual Cortex
Authors: Wundari Bayu Gautama , Fujita Ichiro , Ban Hiroshi
Published: August 2024

Seeing three-dimensional objects requires multiple stages of representational transformation, beginning in the primary visual cortex (V1). Here, neurons compute binocular disparity from the left and right retinal inputs through a mechanism similar to local cross-correlation. However, correlation-based representation is ambiguous because it is sensitive to disparities in both similar and dissimilar features between the eyes. Along the visual pathways, the representation transforms to a cross-matching basis, eliminating responses to falsely matched disparities. We investigated this transformation across the human visual areas using functional magnetic resonance imaging (fMRI) and computational modeling. By fitting a linear weighted sum of cross-correlation and cross-matching model representations to the brain’s representational structure of disparity, we found that areas V1-V3 exhibited stronger cross-correlation components, V3A/B, V7, and hV4 were slightly inclined towards cross-matching, and hMT+ was strongly engaged in cross-matching. To explore the underlying mechanism, we identified a deep neural network optimized for estimating disparity in natural scenes that matched human depth judgment in the random-dot stereograms used in the fMRI experiments. Despite not being constrained to match fMRI data, the network units’ responses progressed from cross-correlation to cross-matching across layers. Activation maximization analysis on the network suggests that the transformation incorporates three phases, each emphasizing different aspects of binocular similarity and dissimilarity for depth extraction. Our findings suggest a systematic distribution of both components throughout the visual cortex, with cross-matching playing a greater role in areas anterior to V3, and that the transformation exploits responses to false matches rather than discarding them.

Significant Statement

Humans perceive the visual world in 3D by exploiting binocular disparity. To achieve this, the brain transforms neural representation from the cross-correlation of signals from both eyes into a cross-matching representation, filtering out responses to disparities from falsely matched features. The location and mechanism of this transformation in the human brain are unclear. Using fMRI, we demonstrated that both representations were systematically distributed across the visual cortex, with cross-matching exerting a stronger effect in cortical areas anterior to V3. A neural network optimized for disparity estimation in natural scenes replicated human depth judgment in various stereograms and exhibited a similar transformation. The transformation from correlation to matching representation may be driven by performance optimization for depth extraction in natural environments.
YAP charge patterning mediates signal integration through transcriptional co-condensates
Authors: Meyer Kirstin , Yserentant Klaus , Cheloor-Kovilakam Rasmi , Ruff Kiersten M. , Chung Chan-I , Shu Xiaokun , Huang Bo , Weiner Orion D.
Published: August 2024

Transcription factor dynamics are used to selectively engage gene regulatory programs. Biomolecular condensates have emerged as an attractive signaling substrate in this process, but the underlying mechanisms are not well-understood. Here, we probed the molecular basis of YAP signal integration through transcriptional condensates. Leveraging light-sheet single-molecule imaging and synthetic condensates, we demonstrate charge-mediated co-condensation of the transcriptional regulators YAP and Mediator into transcriptionally active condensates in stem cells. IDR sequence analysis and YAP protein engineering demonstrate that instead of the net charge, YAP signaling specificity is established through its negative charge patterning that interacts with Mediator’s positive charge blocks. The mutual enhancement of YAP/Mediator co-condensation is counteracted by negative feedback from transcription, driving an adaptive transcriptional response that is well-suited for decoding dynamic inputs. Our work reveals a molecular framework for YAP condensate formation and sheds new light on the function of YAP condensates for emergent gene regulatory behavior.
Systemic identification of functionally conserved lncRNA metabolic regulators in human and mouse livers
Authors: Jiang Chengfei , Li Zhe , Li Ping , Ma Yonghe , Seok Sunmi , Podguski Stephanie K. , Moturi Shria , Yoneda Nao , Kawai Kenji , Uehara Shotaro , Ohnishi Yasuyuki , Suemizu Hiroshi , Zhang Jinwei , Cao Haiming
Published: August 2024

BACKGROUND & AIMS

Unlike protein-coding genes, the majority of human long non-coding RNAs (lncRNAs) lack conservation based on their sequences, posing a challenge for investigating their role in a pathophysiological context for clinical translation. This study explores the hypothesis that non-conserved lncRNAs in human and mouse livers may share similar metabolic functions, giving rise to functionally conserved lncRNA metabolic regulators (fcLMRs).

METHODS

We developed a sequence-independent strategy to select putative fcLMRs, and performed extensive analysis to determine the functional similarities of putative human and mouse LMR pairs (h/mLMRs).

RESULTS

We found that several pairs of putative fcLMRs share similar functions in regulating gene expression. We further demonstrated that a pair of fcLMRs, h/mLMR1, robustly regulated triglyceride levels by modulating the expression of a similar set of lipogenic genes. Mechanistically, h/mLMR1 binds to PABPC1, a regulator of protein translation, via short motifs on either lncRNA with divergent sequences but similar structures. This interaction inhibits protein translation, activating an amino acid-mTOR-SREBP1 axis to regulate lipogenic gene expression. Intriguingly, PABPC1-binding motifs on each lncRNA fully rescued the functions of their corresponding LMRs in the opposite species. Given the elevated expression of h/mLMR1 in humans and mice with hepatic steatosis, the PABPC1-binding motif on hLMR1 emerges as a potential non-conserved human drug target whose functions can be fully validated in a physiologically relevant setting before clinical studies.

CONCLUSIONS

Our study supports that fcLMRs represent a novel and prevalent biological phenomenon, and deep phenotyping of genetic mLMR mouse models constitutes a powerful approach to understand the pathophysiological role of lncRNAs in the human liver.
Accurate and cost-efficient whole genome sequencing of hepatitis B virus using Nanopore
Authors: Stenbäck Joakim B. , Schmidt Daniel , Noborg Ulrika , Gustafsson Joel , Norberg Peter , Andersson Maria E. , Fu Michael X , Harvala Heli , Ringlander Johan
Published: August 2024

Deep sequencing of the whole hepatitis B virus genome increases the analytical resolution and has the potential to improve molecular epidemiology investigations. The aim of this work was to develop and evaluate the performance of such deep sequencing using the Nanopore technology. The method includes an initial PCR step to generate two overlapping amplicons that cover the whole relaxed circular HBV genome found in circulating viral particles and covalently closed circular DNA in infected hepatocytes, followed by sequencing using the Nanopore rapid barcoding kit that allows parallel analysis of several samples in one reaction. The libraries can be sequenced with the standard Nanopore flow cell on MiniIon or GridIon devices, as well as the Flongle. The performance of the method was evaluated by comparing Nanopore and Sanger sequences or qPCR results from 64 clinical samples. The Nanopore-derived consensus sequences were, on average, 99.9% similar to those from Sanger sequencing and the full HBV genome was determined in samples with HBV DNA levels of approximately 3 log10IU/mL with MagNA pure 96 extraction and < 2 log10IU/mL using a high-volume manual extraction protocol on a subset of samples from patients with very low viral load (1.62-3.74 IU/mL). A perfect agreement with Sanger/qPCR-derived genotype was seen. The cost of sequencing per genome using the Nanopore method is low, ranging 6-37euros. We conclude that whole-genome sequencing of HBV with Nanopore is well suited for genomic characterization, antiviral resistance mutation analysis and genotyping of HBV in a routine laboratory setting.
Deep Learning Driven Cell-Type-Specific Embedding for Inference of Single-Cell Co-expression Networks
Authors: Bai Yuting , Qian Kun , Lin Qiang , Fan Wei , Qin Rui , He Bing , Ding Feng , Liu Wanfei , Cui Peng
Published: August 2024

The inference of gene co-expression module in specific cell types is important for understanding of cell-type-specific biological processes. We have developed DeepCSCN, an unsupervised deep-learning framework, to infer gene co-expression modules from single-cell RNA sequencing (scRNA-seq) data. Utilizing a global-to-local network construction approach, DeepCSCN can infer co-expression at the whole sample level and construct cell-type-specific co-expression networks. Systematic evaluations on eight public scRNA-seq datasets show that DeepCSCN significantly outperforms eight existing methods in co-expression network construction. Furthermore, DeepCSCN effectively identifies cell-type-specific co-expression networks that are more enriched for cell-specific functional pathways compared to current methods. Finally, application of DeepCSCN on public scRNA-seq data revealed 280 cell-specific gene modules across 27 cell types, including epithelial cells, immune cells, and myonuclei, demonstrating its versatility and accuracy in elucidating cell-type-specific gene co-expression regulation. DeepCSCN offers a powerful tool for researchers to dissect the intricate gene co-expression networks within distinct cell types.
Pangenome-spanning epistasis and coselection analysis via de Bruijn graphs
Authors: Kuronen Juri , Horsfield Samuel T. , Pöntinen Anna K. , Mallawaarachchi Sudaraka , Arredondo-Alonso Sergio , Thorpe Harry , Gladstone Rebecca A. , Willems Rob J.L. , Bentley Stephen D. , Croucher Nicholas J. , Pensar Johan , Lees John A. , Tonkin-Hill Gerry , Corander Jukka
Published: August 2024

Studies of bacterial adaptation and evolution are hampered by the difficulty of measuring traits such as virulence, drug resistance, and transmissibility in large populations. In contrast, it is now feasible to obtain high-quality complete assemblies of many bacterial genomes thanks to scalable high-accuracy long-read sequencing technologies. To exploit this opportunity, we introduce a phenotype- and alignment-free method for discovering coselected and epistatically interacting genomic variation from genome assemblies covering both core and accessory parts of genomes. Our approach uses a compact colored de Bruijn graph to approximate the intragenome distances between pairs of loci for a collection of bacterial genomes to account for the impacts of linkage disequilibrium (LD). We demonstrate the versatility of our approach to efficiently identify associations between loci linked with drug resistance and adaptation to the hospital niche in the major human bacterial pathogensStreptococcus pneumoniaeandEnterococcus faecalis.
Toward a flourishing workplace: exploring the impact of digitalization on young construction professionals’ physical–mental well-being
Authors: Batra Sachin , Halder Aritra
Published: August 2024

Purpose

The construction industry has more propensity to negatively affect employees’ physical–mental well-being due to the inherently intense and demanding nature of the work involved. Digitalization can streamline the construction processes, and reduce stress, overtime and overall job-related pressure generated due to the nature of employment, contributing to the well-being of employees. Hence, the authors examined how digitalization, technostress and individual resilience could contribute to construction professionals’ physical–mental well-being using the transaction model of stress, self-determination theory and job-demand resources theory.

Design/methodology/approach

Data were collected from 86 young professionals using a structured survey. The professionals were working in Indian construction organizations where digitalization is implemented extensively. The survey consists of 21 items to measure four latent variables namely digitalization, technostress, physical–mental well-being and individual resilience. The study employs a partial least squares structural equation modeling (PLS-SEM) approach to examine the theoretical model empirically.

Findings

The results revealed that digitalization was positively associated with physical–mental well-being and negatively associated with technostress. Further, individual resilience was a moderating variable in the relationship between digitalization and technostress. Finally, technostress partially mediated the relationship between digitalization and physical–mental well-being.

Originality/value

Digitalization has emerged as a valuable tool to tackle these challenges and improve the overall well-being of construction personnel. In the present study, digitalization is found to augment the physical–mental well-being of young construction professionals. Also, digitalization helps to significantly reduce technostress, thereby improving the physical–mental well-being of young professionals.
Veterans in the workplace: a model of factors affecting veteran transition
Authors: Stone Christopher B. , Neely Andrea R. , Phillips William , Terry Ryan P.
Published: August 2024

Purpose

The aim of this work is to enhance workplace diversity and inclusion by exploring and addressing unique barriers faced by veterans during their transition from military service to civilian occupations.

Design/methodology/approach

Building on existing expatriate theory, we introduce the Veteran Employment Transition (VET) model. Drawing parallels between veterans and expatriates, the model illustrates key antecedents crucial for a successful transitional adjustment.

Findings

The proposed VET model outlines essential factors contributing to successful veteran transitions. These factors include individual factors such as language skills, job and organization factors such as role clarity and nonwork factors.

Research limitations/implications

The VET model establishes a foundation for future research on veteran transition and answers the call for theory development in the field.

Practical implications

The insights derived from the VET model offer practical recommendations for designing interventions and transition support programs tailored to the unique needs of returning veterans.

Originality/value

The contribution of this paper lies in the development of the VET model, offering a novel perspective for understanding and addressing the distinctive challenges faced by returning United States (US) military veterans.