bluuebunny/crossref_metadata_2025_split huggingface dataset:
First evidence of a causal link between genetic variation and thermal adaptation in a schistosome host snail
Authors: Maes Tim , Verheyen Julie , Senghor Bruno , Mudavanhu Aspire , Schols Ruben , Hellemans Bart , Geslain Enora , Volckaert Filip A.M. , Gante Hugo F. , Huyse Tine 
Published: January 2024

AbstractFreshwater snails are pivotal in transmitting schistosomiasis, a tropical parasitic disease affecting over 150 million people. The adaptive potential of these snails is a critical factor in determining how climate change and other environmental factors influence disease transmission dynamics, yet it has remained unexplored.Bulinus truncatusis the schistosome intermediate host snail with the widest geographic distribution and therefore plays a pivotal role in determining the maximum range of urogenital schistosomiasis. In this study, we assessed the local adaptation capacity ofB. truncatusto temperature through an integrative approach encompassing phenotypic, ecophysiological, and genomic data. Ten snail populations from diverse thermal environments were collected in three countries, with eight populations reared in a common garden. The F2 generation (total N= 2592) was exposed to eight chronic temperature treatments and various life-history traits were recorded for over 14 weeks. Subsequently, ecophysiological analyses were conducted on the ten last surviving snails per population. Genotyping the parental generation collected in the field using a genotyping-by-sequencing (GBS) approach, revealed 12,875 single nucleotide polymorphisms (SNPs), of which 4.91 % were potentially under selection. We observed a significant association between these outlier SNPs, temperature, and precipitation. Thermal adaptations in life-history traits were evident, with lower survival rates at high temperatures of warm- origin snails compensated for by higher reproduction rates. Cold-origin snails, on the other hand, exhibited higher growth rates adapted to a shorter growing season. Ecophysiological adaptations included elevated sugar and haemoglobin contents in cold-adapted snails. In contrast, warm-adapted snails displayed increased protein levels but also more oxidative damage. Furthermore, heightened phenoloxidase levels indicated a more robust immune response in snails from parasite-rich regions. The substantial local adaptation capacity ofB. truncatusholds profound implications for its response to climate change, future schistosomiasis risk, and the effectiveness of schistosomiasis control measures.HighlightsLocal adaptation influences species’ responses to climate changeThe snailBulinus truncatusshowed a high thermal local adaptation (LA) potentialLA is apparent through variations in life history and ecophysiological traitsWe identified a significant genetic basis underlying this LALA of the hosts could sustain schistosomiasis transmission under global warming
Metabolic heterogeneity of colorectal cancer as a prognostic factor: insights gained from fluorescence lifetime imaging
Authors: Komarova Anastasia D , Sinyushkina Snezhana D , Shchechkin Ilia D , Druzhkova Irina N , Smirnova Sofia A , Terekhov Vitaliy M , Mozherov Artem M , Ignatova Nadezhda I , Nikonova Elena E , Shirshin Evgeny A , Shimolina Liubov E , Gamayunov Sergey V , Shcheslavskiy Vladislav I , Shirmanova Marina V 
Published: January 2024

AbstractHeterogeneity of tumor metabolism is an important, but still poorly understood aspect of tumor biology. Present work is focused on the visualization and quantification of cellular metabolic heterogeneity of colorectal cancer using fluorescence lifetime imaging (FLIM) of redox cofactor NAD(P)H. FLIM-microscopy of NAD(P)H was performed in vitro in four cancer cell lines, in vivo in the four types of tumors in mice and ex vivo in patients’ tumor samples. The dispersion and bimodality of the decay parameters were evaluated to quantify the intercellular metabolic heterogeneity. Our results demonstrate that patients’ tumors have significantly higher heterogeneity of energy metabolism compared with cultured cells and tumor xenografts, which was displayed as a wider and frequently bimodal distribution of a contribution of a free (glycolytic) fraction of NAD(P)H within a sample. Among patients’ tumors, the dispersion was larger in the high-grade and early stage ones, without, however, any association with bimodality. These results indicate that cell-level metabolic heterogeneity assessed from NAD(P)H FLIM has a potential to become a clinical prognostic factor.
Generative whole-brain dynamics models from healthy subjects predict functional alterations in stroke at the level of individual patients
Authors: Idesis Sebastian , Allegra Michele , Vohryzek Jakub , Yonatan Sanz Perl , Metcalf Nicholas V. , Griffis Joseph C. , Corbetta Maurizio , Shulman Gordon L. , Deco Gustavo 
Published: January 2024

AbstractComputational whole-brain models describe the resting activity of each brain region based on a local model, inter-regional functional interactions, and a structural connectome that specifies the strength of inter-regional connections. Strokes damage the healthy structural connectome that forms the backbone of these models and produce large alterations in inter-regional functional interactions. These interactions are typically measured by correlating the timeseries of activity between two brain regions, so-called resting functional connectivity. We show that adding information about the structural disconnections produced by a patient’s lesion to a whole-brain model previously trained on structural and functional data from a large cohort of healthy subjects predicts the resting functional connectivity of the patient about as well as fitting the model directly to the patient’s data. Furthermore, the model dynamics reproduce functional connectivity-based measures that are typically abnormal in stroke patients as well as measures that specifically isolate these abnormalities. Therefore, although whole-brain models typically involve a large number of free parameters, the results show that even after fixing those parameters, the model reproduces results from a population very different than the population on which the model was trained. In addition to validating the model, these results show that the model mechanistically captures relationships between the anatomical structure and functional activity of the human brain.
Rare genetic variation in Fibronectin 1 (FN1) protects againstAPOEe4in Alzheimer’s disease
Authors: Bhattarai Prabesh , Gunasekaran Tamil Iniyan , Reyes-Dumeyer Dolly , Jülich Dörthe , Tayran Hüseyin , Yilmaz Elanur , Flaherty Delaney , Lantigua Rafael , Medrano Martin , Rivera Diones , Recio Patricia , Ertekin-Taner Nilüfer , Teich Andrew F , Dickson Dennis W , Holley Scott , Mayeux Richard , Kizil Caghan , Vardarajan Badri N 
Published: January 2024

AbstractThe risk of developing Alzheimer’s disease (AD) significantly increases in individuals carrying theAPOEε4allele. Elderly cognitively healthy individuals withAPOEε4also exist, suggesting the presence of cellular mechanisms that counteract the pathological effects ofAPOEε4; however, these mechanisms are unknown. We hypothesized thatAPOEε4carriers without dementia might carry genetic variations that could protect them from developingAPOEε4-mediated AD pathology. To test this, we leveraged whole genome sequencing (WGS) data in National Institute on Aging Alzheimer’s Disease Family Based Study (NIA-AD FBS), Washington Heights/Inwood Columbia Aging Project (WHICAP), and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) cohorts and identified potentially protective variants segregating exclusively among unaffectedAPOEε4carriers. In homozygous unaffected carriers above 70 years old, we identified 510 rare coding variants. Pathway analysis of the genes harboring these variants showed significant enrichment in extracellular matrix (ECM)-related processes, suggesting protective effects of functional modifications in ECM proteins. We prioritized two genes that were highly represented in the ECM-related gene ontology terms,(FN1)and collagen type VI alpha 2 chain (COL6A2) and are known to be expressed at the blood-brain barrier (BBB), for postmortem validation andin vivofunctional studies. The FN1 and COL6A2 protein levels were increased at the BBB inAPOEε4carriers with AD. Brain expression of cognitively unaffected homozygousAPOEε4carriers had significantly lower FN1 deposition and less reactive gliosis compared to homozygousAPOEε4carriers with AD, suggesting that FN1 might be a downstream driver ofAPOEε4-mediated AD-related pathology and cognitive decline. To validate our findings, we used zebrafish models with loss-of-function (LOF) mutations infn1b– the ortholog for humanFN1. We found that fibronectin LOF reduced gliosis, enhanced gliovascular remodeling and potentiated the microglial response, suggesting that pathological accumulation of FN1 could impair toxic protein clearance, which is ameliorated withFN1LOF. Our study suggests vascular deposition of FN1 is related to the pathogenicity ofAPOEε4, LOF variants in FN1 may reduceAPOEε4-related AD risk, providing novel clues to potential therapeutic interventions targeting the ECM to mitigate AD risk.
Effects of the overall paradigm context on intensity deviant responses in healthy subjects
Authors: Yukhnovich Ekaterina A , Alter Kai , Sedley William 
Published: January 2024

AbstractThree experiments have been carried out to explore Mismatch Negativity responses to intensity deviants in a roving intensity deviant paradigm in control and tinnitus groups. The first experiment used interspersed blocks of two tinnitus-like frequencies set by each participant with tinnitus, which were usually around 1/3 of an octave apart. On the other hand, two later studies used interspersed blocks tones at tinnitus-like frequencies and at 1 kHz. This was the only difference in the paradigms used, however, there were differences in the patterns displayed by the control group in the first study compared to the other two. Three groups of healthy controls were recruited to measure responses to intensity deviants when different frequencies were used for the alternating blocks. For one group, the whole experiment was set at a single frequency; for the next, blocks were played at 6 kHz and at a frequency 1/3 octave below 6 kHz (small difference); the last group was presented with blocks that had tones at 6 kHz and 1 kHz frequencies (large difference). Overall, the Mismatch Negativity responses in the small difference group were opposite to the large difference and the single frequency group. It would be useful to see whether these results generalise to other experiment designs such as attended and ignored stimulus conditions, different stimulus durations, non-isochronous, or paradigms with frequency deviants.
Genomics 2 Proteins portal: A resource and discovery tool for linking genetic screening outputs to protein sequences and structures
Authors: Kwon Seulki , Safer Jordan , Nguyen Duyen T. , Hoksza David , May Patrick , Arbesfeld Jeremy A. , Rubin Alan F. , Campbell Arthur J , Burgin Alex , Iqbal Sumaiya 
Published: January 2024

AbstractRecent advances in AI-based methods have revolutionized the field of structural biology. Concomitantly, high-throughput sequencing and functional genomics technologies have enabled the detection and generation of variants at an unprecedented scale. However, efficient tools and resources are needed to link these two disparate data types – to “map” variants onto protein structures, to better understand how the variation causes disease and thereby design therapeutics. Here we present the Genomics 2 Proteins Portal (G2P; g2p.broadinstitute.org/): a human proteome-wide resource that maps 19,996,443 genetic variants onto 42,413 protein sequences and 77,923 structures, with a comprehensive set of structural and functional features. Additionally, the G2P portal generalizes the capability of linking genomics to proteins beyond databases by allowing users to interactively upload protein residue-wise annotations (variants, scores, etc.) as well as the protein structure to establish the connection. The portal serves as an easy-to-use discovery tool for researchers and scientists to hypothesize the structure-function relationship between natural or synthetic variations and their molecular phenotype.
Tracing India’s Canine Heritage through SNP-Based Haplotype Identification
Authors: Singh Dapinder , Mahajan Shashi Kant , Kashyap Neeraj , Mukhopadhyay Chandra Sekhar 
Published: January 2024

AbstractDog breeds/germplasm in India is mostly unexplored and the population structure of owned dogs has not been studied at all. The current study was designed to determine the haplotypes and explore the population structure among divergent breeds of dogs using genome-wide distributed SNPs, followed by validation of selected haplotypes through PCR-sequencing. The research employed custom ddRAD-GBS sequencing carried out using Illumina 150bp paired-end sequencing of 50 dog samples generated 2,18,433 high-quality SNPs meeting the screening criteria. The data was further analyzed for population structure assessment and haplotype identification using bash, and R-environment. Subsequently, three haplotypes (on AFAP1, CELSR1, and GBGT1 genes) were selected (based on SNP density and haplotype length) for validation via PCR followed by paired-end Sanger sequencing in seven different dog breeds (n=21). The results revealed notable connections between dog breeds from Punjab and Haryana, while the affiliation with Karnataka was found to be less pronounced. The sequencing results indicated that CELSR1 and GBGT1 genes contained SNPs, with the AFAP1 gene lacking SNPs. The results also provided insights into the molecular-level population structure, SNPs, and haplotypes of diverse dog breeds reared in India. This SNP variation could be used for molecular characterization of indigenous dogs.
Novel metagenomics analysis of stony coral tissue loss disease
Authors: Heinz Jakob M. , Lu Jennifer , Huebner Lindsay K. , Salzberg Steven L. , Sommer Markus , Rosales Stephanie M. 
Published: January 2024

AbstractStony coral tissue loss disease (SCTLD) has devastated coral reefs off the coast of Florida and continues to spread throughout the Caribbean. Although a number of bacterial taxa have consistently been associated with SCTLD, no pathogen has been definitively implicated in the etiology of SCTLD. Previous studies have predominantly focused on the prokaryotic community through 16S rRNA sequencing of healthy and affected tissues. Here, we provide a different analytical approach by applying a bioinformatics pipeline to publicly available metagenomic sequencing samples of SCTLD lesions and healthy tissues from four stony coral species. To compensate for the lack of coral reference genomes, we used data from apparently healthy coral samples to approximate a host genome and healthy microbiome reference. These reads were then used as a reference to which we matched and removed reads from diseased lesion tissue samples, and the remaining reads associated only with disease lesions were taxonomically classified at the DNA and protein levels. For DNA classifications, we used a pathogen identification protocol originally designed to identify pathogens in human tissue samples, and for protein classifications, we used a fast protein sequence aligner. To assess the utility of our pipeline, a species-level analysis of a candidate genus,Vibrio, was used to demonstrate the pipeline’s effectiveness. Our approach revealed both complementary and unique coral microbiome members compared to a prior metagenome analysis of the same dataset.Article SummaryStudies of stony coral tissue loss disease (SCTLD), a devastating coral disease, have primarily used 16S rRNA sequencing approaches to identify putative pathogens. In contrast, this study applied human tissue pathogen identification protocols to SCTLD metagenomic DNA samples. Diseased samples were filtered of host sequences using a k-mer based method since host genomes were unavailable. DNA and protein-level classifications from this novel approach revealed both complementary and unique microbiome members compared to a prior metagenome analysis of the same dataset.
Cardiac Localized Polycystin-2 plays a Functional Role in Natriuretic Peptide Production and its Absence Contributes to Hypertension
Authors: Elliott Brandon , Márquez-Nogueras Karla M. , Thuo Paula , DiNello Elisabeth , Knutila Ryne M. , Fritzmann Geena E. , Willis Monte , Chapman Arlene B. , Cao Quan , Barefield David Y. , Kuo Ivana Y. 
Published: January 2024

ABSTRACTCardiovascular complications are the most common cause of mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Hypertension is seen in 70% of patients by the age of 30 prior to decline in kidney function. The natriuretic peptides (NPs), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are released by cardiomyocytes in response to membrane stretch, increasing urinary excretion of sodium and water. Mice heterozygous forPkd2have attenuated NP responses and we hypothesized that cardiomyocyte-localized polycystin proteins contribute to production of NPs. Cardiomyocyte-specific knock-out models of polycystin-2 (PC2), one of the causative genes of ADPKD, demonstrate diurnal hypertension. These mice have decreased ANP and BNP expression in the left ventricle. Analysis of the pathways involved in production, maturation, and activity of NPs identified decreased transcription of CgB, PCSK6, and NFAT genes in cPC2-KOs. Engineered heart tissue with human iPSCs driven into cardiomyocytes with CRISPR/Cas9 KO ofPKD2failed to produce ANP. These results suggest that PC2 in cardiomyocytes are involved in NP production and lack of cardiac PC2 predisposes to a hypertensive volume expanded phenotype, which may contribute to the development of hypertension in ADPKD.
Biofilm formation and maize root-colonization of seed-endophytic Bacilli isolated from native maize landraces
Authors: Gastélum Gabriela , Ángeles Alejandra , Arellano-Wattenbarger Guillermo , Coronado Yaxk’in , Guevara Eduardo , Rocha Jorge 
Published: January 2024

AbstractAgricultural microbiology seeks to replace the use of agrochemicals with microbe-based products. Plant growth-promoting bacteria (PGPB) are often selected based on their functionsin vitro, and then, their effect on plant development is tested. However, this approach neglects the study of their survival in soil, root-colonization, and the monitoring of beneficial functions in the rhizosphere. This could explain the recurrent lack of success in the transition from lab tests to field applications of natural isolates from novel habitats. In our recent studies, we found that native maize seeds from traditional agroecosystems carry endophytic bacterial communities that are dominated by members of the class Bacilli. As an approach to grasp their PGP potential, we developed protocols to test maize root-colonization of these natural isolates in 1) a short-term hydroponics assayin vitroand 2) a long-term assay in non-sterile soil pots. Our results show thatin vitrobiofilm formation was only partially associated to short-term colonizationin vitro; furthermore, long-term root-colonization in soil pots was not correlated to thein vitroassays. This work highlights the necessity to incorporate root-colonization assays as part of the research strategies in the search for PGPB natural isolates from unexplored habitats, towards the generation of inoculants with increased success in the field.
Non-genetic adaptation by collective migration
Authors: Vo Lam , Avgidis Fotios , Mattingly Henry H. , Edmonds Karah , Burger Isabel , Balasubramanian Ravi , Shimizu Thomas S. , Kazmierczak Barbara I. , Emonet Thierry 
Published: January 2024

AbstractCell populations must adjust their phenotypic composition to adapt to changing environments. One adaptation strategy is to maintain distinct phenotypic subsets within the population and to modulate their relative abundances via gene regulation. Another strategy involves genetic mutations, which can be augmented by stress-response pathways. Here, we studied how a migrating bacterial population regulates its phenotypic distribution to traverse diverse environments. We generated isogenicEscherichia colipopulations with varying distributions of swimming behaviors and observed their phenotype distributions during migration in liquid and porous environments. We found that the migrating populations became enriched with high-performing swimming phenotypes in each environment, allowing the populations to adapt without requiring mutations or gene regulation. This adaptation is dynamic and rapid, reversing in a few doubling times when migration ceases. By measuring the chemoreceptor abundance distributions during migration towards different attractants, we demonstrated that adaptation acts on multiple chemotaxis-related traits simultaneously. These measurements are consistent with a general mechanism in which adaptation results from a balance between cell growth generating diversity and collective migration eliminating under-performing phenotypes. Thus, collective migration enables cell populations with continuous, multi-dimensional phenotypes to flexibly and rapidly adapt their phenotypic composition to diverse environmental conditions.Significance statementConventional cell adaptation mechanisms, like gene regulation and stochastic phenotypic switching, act swiftly but are limited to a few traits, while mutation-driven adaptations unfold slowly. By quantifying phenotypic diversity during bacterial collective migration, we discovered an adaptation mechanism that rapidly and reversibly adjusts multiple traits simultaneously. By balancing the generation of diversity through growth with the loss of phenotypes unable to keep up, this process tunes the phenotypic composition of migrating populations to the environments they traverse, without gene regulation or mutations. Given the prevalence of collective migration in microbes, cancers, and embryonic development, non-genetic adaptation through collective migration may be a universal mechanism for populations to navigate diverse environments, offering insights into broader applications across various fields.