bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular dynamics simulations illuminate the role of sequence context in the ELF3-PrD-based temperature sensing mechanism in plants
Authors: Lindsay Richard J. , Viegas Rafael Giordano , Leite Vitor B. P. , Wigge Philip A. , Hanson Sonya M. 
Published: August 2024

AbstractThe evening complex (EC) is a tripartite DNA repressor and a core component of the circadian clock that provides a mechanism for temperature-responsive growth and development of many plants. ELF3, a component of the EC, is a disordered scaffolding protein that blocks transcription of growth genes at low temperature. At increased temperature EC DNA binding is disrupted and ELF3 is sequestered in a reversible nuclear condensate, allowing transcription and growth to proceed. The condensation is driven by a low complexity prion-like domain (PrD), and the sensitivity of the temperature response is modulated by the length of a variable polyQ tract, with a longer polyQ tract corresponding to enhanced condensate formation and hypocotyl growth at increased temperature. Here, a series of computational studies provides evidence that polyQ tracts promote formation of temperature-sensitive helices in flanking residues with potential impacts for EC stability under increasing temperature. REST2 simulations uncover a heat-induced population of condensation-prone conformations that results from the exposure of ‘sticky’ aromatic residues by temperature-responsive breaking of long-range contacts. Coarse-grained Martini simulations reveal both polyQ tract length and sequence context modulate the temperature dependence of cluster formation. Understanding the molecular mechanism underlying the ELF3-PrD temperature response in plants has implications for technologies including modular temperature-response elements for heat-responsive protein design and agricultural advances to enable optimization of crop yields and allow plants to thrive in increasingly inhospitable environments.
Overcoming toxicity: why boom-and-bust cycles are good for non-antagonistic microbes
Authors: Wang MingYi , Vladimirsky Alexander , Giometto Andrea 
Published: August 2024

AbstractAntagonistic 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

AbstractRecent 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

AbstractDESS 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

SummaryATP 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

IntroductionThe study aimed to characterize the genome of a Colombian strain ofLeptospira santarosaito infer bacterial virulence factors.Materials and methodsUnder 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.ResultsThe 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.ConclusionsThe study contributes to the understanding of the pathophysiological mechanisms induced byLeptospira.
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

AbstractRecognizing 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

AbstractIntroductionMoyamoya 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.MethodsThe 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.ResultsBased 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.ConclusionThe 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

AbstractThe 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

AbstractNuclear 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.
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

AbstractTo 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

AbstractInfectious 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 SummaryTuberculosis (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.
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

ABSTRACTLeukocytes 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

AbstractWithin 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.