bluuebunny/crossref_metadata_2025_split huggingface dataset:
Northeast India: Genetic Inconsistency across Ethnicity and Geography
Authors: Bankura Biswabandhu , Basak Bishnupriya , Singh Prajjval Pratap , Vanlalruata Albert , Chatterjee Arindam , Ghosh Sudakshina , Tamang Rakesh , Hazarika Manjil , Chaubey Gyaneshwer , Das Madhusudan 
Published: January 2024

AbstractThe genetic landscape of South Asia is intriguing. In a vast geographical region like India, mostly genes follow geography, whereas in a smaller geographical region e.g., Nepal, the genetic landscape is more akin to languages. Moreover, in neighboring regions like East and Southeast Asia, language is the major denominator of the genes. However, these are not just the two alternatives, in many geographical pockets, ethnicity plays a stronger role than either of these. Being a crossroads of South and Southeast Asia, the Himalayan region is mostly populated by people speaking the Trans-Himalayan language. Archaeological and anthropological studies suggest migration and cultural diffusion in this region with the Tibetan plateau in the North. To understand this complex pattern, we have performed a fine-grained genetic analysis of the major Mizo population and its various clans living in the Himalayan geography. We have investigated 110 individuals belonging to seven different clans of Mizo people for a hundred thousand autosomal markers. We have used various statistical methods and tested the role of ethnicity and geography in shaping the genetic landscape of the Himalayan region. In contrast to the East and Southeast Asian genetic landscape, our results suggested that the fine-scaled genetic structure of Northeast India is much more complex and a mixture of interplay between languages, ethnicity, and geography. Allelic frequency-based analyses indicated that a novel Trans-Himalayan ancestry unite all the populations of this region.
Tcf12 controls dynamic calvarial bone growth and motor learning in mice
Authors: Yamada Takahiko , Anderson-Ramirez Jesse , Gao Lu , Chen Peng , Zhang Mingyi , Guo Tingwei , Feng Jifan , Ho Thach-Vu , Vorobyova Ivetta , Santa Maria Naomi , Jacobs Russell , Chen Jian-Fu , Chai Yang 
Published: January 2024

AbstractHeterozygous loss-of-function mutations ofTCF12andTWIST1can each cause craniosynostosis and neurodevelopmental delay in humans. Twist1-Tcf12 interaction plays an important role in regulating suture development. Although the molecular and cellular mechanisms underlying craniosynostosis and neurocognitive dysfunctions inTwist1+/-mice have been studied, less information on the role ofTcf12in these defects is available. To investigate the functional mechanism of Tcf12 in regulating skull and brain development, we analyzed the skull shape ofWnt1-Cre;Mesp1-Cre;Tcf12fl/flmice and found that, despite mild coronal synostosis, their skull shape appears to be similar to that of controls. We also found evidence of impaired motor learning ability inTcf12mutant mice. Furthermore, loss of Tcf12 in neural crest lineage leads to upregulatedRunx2expression in the calvarial mesenchyme and posterior expansion of the frontal bone inWnt1-Cre;Tcf12fl/flmice. Mechanistically, we show thatLmx1bis a direct downstream target of Tcf12 for the regulation of osteogenic differentiation in the calvarial mesenchyme during embryonic development. Importantly, overexpression ofLmx1binhibits osteogenic differentiation in the calvarial mesenchyme ofWnt1-Cre;Tcf12fl/flmice, indicating Tcf12’s regulation ofLmx1bexpression is crucial for controlling osteogenesis during calvarial bone development. Our study suggests that Tcf12 expression in the brain is crucial for motor learning. Moreover, this study establishes a new molecular mechanism underlying regulation of calvarial bone formation.Author SummaryCraniosynostosis is characterized by premature fusion of cranial sutures and associated with abnormal skull growth, delayed brain development, and often impaired brain functions. Loss-of-function mutation ofTCF12can cause coronal synostosis and neurodevelopmental delay in humans. In developing mouse sutures,Tcf12is essential for maintaining the boundary between sutural and osteogenic cells. However, roles ofTcf12in skull formation and brain development have not been fully investigated. In this study, we show that loss ofTcf12leads to brain abnormalities even in the absence of coronal synostosis and that frontal bone expansion results from upregulated osteogenic differentiation in the calvarial mesenchyme in mice. Furthermore, we identifyLmx1bas a downstream target of Tcf12 for the regulation of osteogenic differentiation in the calvarial mesenchyme during frontal bone development. Our findings highlight the role of Tcf12 in the development of calvarial bones and provide new insight into molecular mechanisms for regulation of calvarial bone formation.
Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma
Authors: Ang Daniel A. , Carter Jean-Michel , Deka Kamalakshi , Tan Joel H.L. , Zhou Jianbiao , Chen Qingfeng , Chng Wee Joo , Harmston Nathan , Li Yinghui 
Published: January 2024

AbstractIn multiple myeloma, abnormal plasma cells establish oncogenic niches within the bone marrow by engaging the NF-κB pathway to nurture their survival while they accumulate pro- proliferative mutations. Under these conditions, many cases eventually develop genetic abnormalities endowing them with constitutive NF-κB activation. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire. Furthermore, through targeted disruption of p52, we characterise how such enhancers are complicit in the formation of super-enhancers and the establishment ofcis-regulatory interactions with myeloma dependencies during constitutive activation of p52. Finally, we functionally validate the pathological impact of thesecis- regulatory modules on cell and tumour phenotypes usingin vitroandin vivomodels, confirmingRGS1as a novel p52-dependent myeloma driver. We conclude that the divergent epigenomic reprogramming enforced by aberrant non-canonical NF-κB signalling potentiates transcriptional programs beneficial for multiple myeloma progression.
shRNAI: a deep neural network for the design of highly potent shRNAs
Authors: Park Seokju , Park Sung-Ho , Oh Jin-Seon , Noh Yung-Kyun , Hur Junho K , Nam Jin-Wu 
Published: January 2024

AbstractmiRNA-mimicking short hairpin RNA (shRNAmir), which depends on whole miRNA biogenesis, has been used to elucidate the function of target genes and to develop therapeutic approaches due to its stable, robust downregulation. Despite efforts to design potent shRNAmir guide RNAs (gRNAs), biological features other than the sequence have not been fully considered. Here, we developed shRNAI, a convolutional neural network model for the prediction of highly potent shRNAmir gRNAs. The shRNAI model trained with gRNA sequences alone predicted more potent shRNAmir gRNAs than the existing algorithms. The shRNAI+ model, trained with the additional features of shRNAmir processibility and target site context, was further improved on both public and our experimental test datasets. Although the shRNAI models were trained on datasets generated with the CNNC motif-free shRNAmir backbone, they also exhibited better performance for the CNNC motif. Our study provides not only a rational framework for designing shRNAmir gRNAs for targets but also a means of designing optimal RNA interference drugs necessary for RNA therapeutics.
Menaquinone-specific oxidation byM. tuberculosiscytochromebdis redox regulated by the Q-loop disulfide bond
Authors: van der Velden Tijn T. , Waterham Caspar Y. J. , Jeuken Lars J. C. 
Published: January 2024

AbstractCytochromebdfromMycobacterium tuberculosis(Mtbd) is a menaquinol oxidase that has gained considerable interest as an antibiotic target due to its importance in survival under infectious conditions.Mtbdcontains a characteristic disulfide bond that has been hypothesized to confer a redox regulatory role during infection by constraining the movement of the menaquinone-binding Q-loop. Interference of reductants used in the standard activity assay of quinol oxidases has prevented testing of this hypothesis. Here, the role of the disulfide bond and quinone specificity ofMtbdhas been determined by the reconstitution of a minimal respiratory chain consisting of a NADH dehydrogenase andMtbd, both in detergent and native-like lipid environments. Comparison to cytochromebdfromEscherichia coli(Ecbd) confirms thatMtbdis under tight redox regulation and is selective for menaquinol, unable to oxidize either ubiquinol or demethylmenaquinol. Reduction of theMtbddisulfide bond resulted in a decrease in oxidase activity up to 90%, depending on menaquinol concentrations. In addition, the catalytic rates ofEcbdandMtbdare over 10 times lower with the natural lipophilic quinones in comparison to their often-used hydrophilic analogs. Additionally, unlikeEcbd, the activity ofMtbdis substrate inhibited at physiologically relevant menaquinol concentrations. We signifyMtbdas the first redox sensory terminal oxidase and propose that this enablesMtbdto adapt its activity in defence against reactive oxygen species encountered during infection byM. tuberculosis.
JNK1 And Downstream Signalling Hubs Regulate Anxiety-Like Behaviours In A Zebrafish Larvae Phenotypic Screen
Authors: Hong Ye , Sourander Christel , Hackl Benjamin , Patton Jedidiah S. , John Jismi , Paatero Ilkka , Coffey Eleanor 
Published: January 2024

ABSTRACTCurrent treatments for anxiety and depression show limited efficacy in many patients indicating that research into new underlying mechanisms is needed. Inhibition of JNK1 has been shown to evoke an anxiolytic-and antidepressant-like phenotype in mice however the downstream effectors that elicit these behavioural effects are unknown. Here we employ a zebrafish (D. Rerio) larvae behavioural assay to identify an antidepressant-/anxiolytic-like phenotype based on 2759 measured stereotypic responses to clinically proven antidepressant and anxiolytic (AA) drugs. Employing machine learning, we classify an AA phenotype from behavioural features measured during and after a startle battery in fish exposed to AA drugs (fluoxetine, imipramine, diazepam, lithium chloride, ketamine). We demonstrate that structurally independent JNK inhibitors replicate the AA classification with high accuracy, consistent with findings in mice. We go on to identify signalling hubs downstream from JNK1 by comparing phosphoproteome data from wildtype andJnk1-/-mouse brains, and test these hubs as possible mediators of the AA phenotype in zebrafish larvae. Among these, we find that AKT, GSK-3, 14-3-3ζ/ε and PKCε, when pharmacologically targeted, phenocopy clinically proven AA drugs. This assay shows promise as an early phase screening for compounds with anti-stress-axis/anxiolytic-like properties, and for mode of action analysis.
Diagnostic of head blight and leaf blotch diseases of wheat in Sweden using a mycobiome isolation approach
Authors: Kaur Harleen , Vilvert Elisa , Corrales Gutiérrez Miguel Ángel , Zhan Jiasui , Douchkov Dimitar , Desiderio Francesca , Vélëz Heriberto , Bourras Salim 
Published: January 2024

AbstractIncreasing the durability of crop resistance to plant pathogens has become a major concern in plant pathology. There are 32 diseases of agronomical importance in wheat, which makes disease management in this crop of worldwide importance extremely challenging. Two important groups of wheat pathogens driving the consumption of chemical fungicides in Sweden and worldwide are those causing head blight diseases and leaf blotch diseases. Swedish fields are regularly infested with head blight diseases typically driven by a complex ofFusariumand non-fusarium taxa includingF. graminearum,F. culmorum, while leaf blotches are typically caused byZymoseptoria tritici,Pyrenophora tritici-repentis, andParastagonospora nodorum. In this work, we present a survey of the larger diversity of taxa associated with head blight and leaf blotch diseases in Sweden, with the primary aim to assess the usefulness of such an approach to develop new understanding and tools for disease diagnostics and managementsensu lato. Here, we analyze nearly a thousand isolates collected from wheat fields across eight counties in Sweden and report the identification of pathogenic and non-pathogenic taxa as well as candidate biological control agents associated with head blight and leaf blotch diseases. We argue that such surveys represent an important tool for improving disease diagnostics, disease forecasting, and integrated management in wheat.
Feedback control of the heat shock response by spatiotemporal regulation of Hsp70
Authors: Garde Rania , Dea Annisa , Herwig Madeline F. , Pincus David 
Published: January 2024

ABSTRACTCells maintain homeostasis via dynamic regulation of stress response pathways. Stress pathways transiently induce response regulons via negative feedback loops, but the extent to which individual genes provide feedback has not been comprehensively measured for any pathway. Here, we disrupted induction of each gene in theSaccharomyces cerevisiaeheat shock response (HSR) and quantified cell growth and HSR dynamics following heat shock. The screen revealed a core feedback loop governing expression of the chaperone Hsp70 reinforced by an auxiliary feedback loop controlling Hsp70 subcellular localization. Mathematical modeling and live imaging demonstrated that multiple HSR targets converge to promote Hsp70 nuclear localization via its release from cytosolic condensates. Following ethanol stress, a distinct set of factors similarly converged on Hsp70, suggesting that nonredundant subsets of the HSR regulon confer feedback under different conditions. Flexible spatiotemporal feedback loops may broadly organize stress response regulons and expand their adaptive capacity.
Comparative analysis of the plasma metabolome of migrating passerines during stopover: Novel insights into flight metabolism
Authors: Domer By Adi , Jasinska Weronika , Rosental Leah , Shochat Eyal , Alseekh Saleh , Fernie Alisdair R. , Brotman Yariv , Ovadia Ofer 
Published: January 2024

AbstractDuring long distance migration, many birds may experience periods of either prolonged fasting, during endurance flights, or extensive feeding during stopovers. It was previously shown that habitat selection during stopover can largely affect the migration outcome of an individual. Despite decades of research of the avian metabolism during stopover and migration, many questions have remained unanswered, as such research mainly focused on targeted metabolites and fat metabolism. Here, we examined the plasma-metabolome of migrating passerines prior to their crossing the Sahara Desert. Birds were sampled at two sites populated by Pistacia trees, bearing fat-rich fruits, and at an additional site dominated by blooming Eucalyptus trees. The blood samples were analyzed using both GC-MS and LC-MS, using an untargeted approach. We found that birds from one of the sites had a distinguish metabolic profile, suggesting recent landing. Examination of metabolic pathways activated during stopovers indicated a crucial role for cycling glucose through the Cori and Cahill cycles in resting and recovery processes. This novel perspective, conducted on free-ranging birds, suggests the evolution of avian insulin resistance due to factors such as endurance exercise, fasting, and a preference for fatty acid oxidation during migration, akin to cell trauma recovery. Additionally, we investigated inter-site variations in birds’ metabolic profiles. Significant variations were observed in both polar and lipophilic metabolites among the sites. Differences in polar metabolites were primarily attributed to variations in the physiological state of the birds between sites, while distinctions in the lipophilic profiles of rested birds were linked to variations in their primary food sources. This study underscores the challenge of interpreting commonly used indicators for assessing migrating birds’ physiological states and site quality, which are predominantly derived from lipid metabolism, in complex ecological systems.
Experimental variables that impact outcomes inCaenorhabditis elegansaging stress response
Authors: Hull Bradford , Irby Isabella M. , Miller Kayla M. , Anderson Ally , Gardea Emily A. , Sutphin George L. 
Published: January 2024

AbstractCellular stress is a fundamental component of age-associated disease. Cells encounter various forms of stress – oxidative stress, protein misfolding, DNA damage, etc. – and respond by activating specific, well-defined stress response pathways. As we age, the burden of stress and resulting damage increases while our cells’ ability to deal with the consequences becomes diminished due to dysregulation of cellular stress response pathways. Many interventions that extend lifespan activate one or more stress response pathways or allow cells to maintain normal stress response later in life. The nematodeCaenorhabditis elegansis a commonly used model for both aging and stress response research. As such, stress response experiments are regularly conducted as part of studies focused on mechanisms of aging inC. elegans. However, experimental design across experiments in the field are highly variable, including stressor dose, age at exposure, culture type (liquid vs. solid), bacterial strain used as a food source, and environmental temperature. These differences can result in different experimental outcomes, making comparison of results between studies challenging. Here we evaluate several experimental variables that are variable in the published literature and find that each can meaningfully alter experimental outcomes for multiple stressors. Our goal is to raise awareness of the issue of experimental variability within the field and suggest a standardized experimental design to serve as a set of guidelines for future experiments. By adopting these guidelines as a starting point, and explicitly noting differences in specific experiments, we aim to promote rigor and reproducibility, ultimately fostering more interpretable and translatable outcomes in geroscience research.
ASY3 has dosage-dependent diverse effects on meiotic crossover formation
Authors: Chu Lei , Zhuang Jixin , Geng Miaowei , Zhang Yashi , Zhang Chunyu , Schnittger Arp , Yi Bin , Yang Chao 
Published: January 2024

AbstractCrossovers create genetic diversity and are required for equal chromosome segregation during meiosis. Their number and distribution are highly regulated by different, yet not fully understood mechanisms including crossover interference. Crucial for crossover formation is the chromosome axis. Here, we explore the function of the axis protein ASY3. To this end, we use the allotetraploid speciesBrassica napusand due to its polyploid nature, this system allows a fine-grained dissection of the dosage of meiotic regulators. The simultaneous mutation of all fourASY3alleles results in defective synapsis and drastic reduction of crossovers, which is largely rescued by the presence of only one functionalASY3allele. Crucially, while the number of class I crossovers in mutants with two functionalASY3alleles is comparable to that in wildtype, this number is significantly increased in mutants with only one functionalASY3allele, indicating that reducing the dosage of ASY3 increases crossover formation. Moreover, the class I crossovers on each bivalent in mutants with one functionalASY3allele follow a random distribution, indicating compromised crossover interference. These results reveal the dosage-dependent distinct effects of ASY3 on crossover formation, and provide insights into the role of chromosome axis in patterning recombination.
How do German and French expatriates develop social networks?
Authors: Walther Matthias , Mayrhofer Ulrike , Dominguez Noémie 
Published: January 2024

PurposeThis exploratory research aims to identify the types of social networks established by German and French expatriates.Design/methodology/approachThe authors use the concepts of social capital and social networks, as well as the societal and cultural approaches, to investigate the way expatriates develop their social networks. The authors' empirical study is based on 40 semi-structured interviews conducted with German and French expatriates.FindingsThe authors' findings show that German expatriates mainly establish professional networks, whereas their French counterparts also focus on personal networks. They further indicate that managing social capital lies within the individual responsibility of German expatriates, whereas it is part of higher education institutions in France.Originality/valueThe authors highlight the way German and French expatriates manage their social networks and provide novel insights into the role played by higher education systems and the cultural characteristics of their home country context.
On the differences between CNNs and vision transformers for COVID-19 diagnosis using CT and chest x-ray mono- and multimodality
Authors: El-Ateif Sara , Idri Ali , Fernández-Alemán José Luis 
Published: January 2024

PurposeCOVID-19 continues to spread, and cause increasing deaths. Physicians diagnose COVID-19 using not only real-time polymerase chain reaction but also the computed tomography (CT) and chest x-ray (CXR) modalities, depending on the stage of infection. However, with so many patients and so few doctors, it has become difficult to keep abreast of the disease. Deep learning models have been developed in order to assist in this respect, and vision transformers are currently state-of-the-art methods, but most techniques currently focus only on one modality (CXR).Design/methodology/approachThis work aims to leverage the benefits of both CT and CXR to improve COVID-19 diagnosis. This paper studies the differences between using convolutional MobileNetV2, ViT DeiT and Swin Transformer models when training from scratch and pretraining on the MedNIST medical dataset rather than the ImageNet dataset of natural images. The comparison is made by reporting six performance metrics, the Scott–Knott Effect Size Difference, Wilcoxon statistical test and the Borda Count method. We also use the Grad-CAM algorithm to study the model's interpretability. Finally, the model's robustness is tested by evaluating it on Gaussian noised images.FindingsAlthough pretrained MobileNetV2 was the best model in terms of performance, the best model in terms of performance, interpretability, and robustness to noise is the trained from scratch Swin Transformer using the CXR (accuracy = 93.21 per cent) and CT (accuracy = 94.14 per cent) modalities.Originality/valueModels compared are pretrained on MedNIST and leverage both the CT and CXR modalities.