bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal Imaging Investigation of Rich Club Alterations in Alzheimer’s Disease and Mild Cognitive Impairment: Amyloid Deposition, Structural Atrophy, and Functional Activation Differences
Authors: Markett Sebastian , Boeken Ole J. , Wudarczyk Olga A. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2023

0AbstractAlzheimer’s disease (AD) is characterized by significant cerebral dysfunction, including increased amyloid deposition, gray matter atrophy, and changes in brain function. The involvement of highly connected network hubs, known as the “rich club,” in the pathology of the disease remains inconclusive despite previous research efforts. In this study, we aimed to systematically assess the link between the rich club and AD using a multimodal neuroimaging approach.We employed network analyses of diffusion MRI, longitudinal assessments of gray matter atrophy, amyloid deposition measurements using PET imaging, and meta-analytic data on functional activation differences. Our study focused on evaluating the role of both the core and extended rich club regions in individuals with Mild Cognitive Impairment (MCI) and those diagnosed with Alzheimer’s Disease.Our findings revealed that rich club regions exhibited accelerated gray matter atrophy and increased amyloid deposition in both MCI and Alzheimer’s Disease. Importantly, these regions remained unaffected by altered functional activation patterns observed outside the core rich club regions. These results shed light on the connection between two major AD biomarkers and the rich club, providing valuable insights into AD as a potential disconnection syndrome.
Flexiplex: A versatile demultiplexer and search tool for omics data
Authors: Cheng Oliver , Ling Min Hao , Wang Changqing , Wu Shuyi , Ritchie Matthew E. , Göke Jonathan , Amin Noorul , Davidson Nadia M. 
Published: August 2023

AbstractThe process of analyzing high throughput sequencing data often requires the identification and extraction of specific target sequences. This could include tasks such as identifying cellular barcodes and UMIs in single cell data, and specific genetic variants for genotyping. However, existing tools which perform these functions are often task-specific, such as only demultiplexing barcodes for a dedicated type of experiment, or are not tolerant to noise in the sequencing data. To overcome these limitations, we developed Flexiplex, a versatile and fast sequence searching and demultiplexing tool for omics data, which is based on the Levenshtein distance and thus allows imperfect matches. We demonstrate Flexiplex’s application on three use cases, identifying cell line specific sequences in Illumina short-read single cell data, and discovering and demultiplexing cellular barcodes from noisy long-read single cell RNA-seq data. We show that Flexiplex achieves an excellent balance of accuracy and computational efficiency compared to leading task-specific tools. Flexiplex is available athttps://davidsongroup.github.io/flexiplex/.
Space and epigenetic inheritance determine inter-individual differences in siderophore gene expression in bacterial colonies
Authors: Mridha Subham , Wechsler Tobias , Kümmerli Rolf 
Published: August 2023

AbstractHeterogeneity in gene expression among cells in clonal groups is common in bacteria. Albeit ubiquitous, it often remains unclear what the sources of variation are and whether variation has functional significance. Here, we tracked the expression of genes involved in the synthesis of iron-chelating siderophores (pyoverdine and pyochelin) in individual cells of the bacteriumPseudomonas aeruginosaduring colony growth on surfaces using time-lapse fluorescence microscopy, to explore potential sources and functions of cellular heterogeneity. Regarding sources, we found that the physical position of cells within the colony and epigenetic gene expression inheritance from mother to daughter cells significantly contributed to cellular heterogeneity. In contrast, cell pole age and cellular lifespan had no effect. Regarding functions, our results indicate that cells optimize their siderophore investment strategies (pyoverdine vs. pyochelin) along a gradient from the centre to the edge of the colony. Moreover, we found evidence that cell lineages with above-average siderophore investment increase the fitness of cell lineages with below-average investment through cooperative sharing of secreted siderophores. Altogether, our study highlights that single-cell experiments combined with automated image and cell-tracking analyses can identify sources of heterogeneity and yield adaptive explanations for gene expression variation among clonal bacterial cells.
Mother-Infant Gut Viruses and their Bacterial Hosts: Transmission Patterns and Dynamics during Pregnancy and Early Life
Authors: Garmaeva Sanzhima , Sinha Trishla , Gulyaeva Anastasia , Kuzub Nataliia , Spreckels Johanne E , Andreu-Sánchez Sergio , Gacesa Ranko , Vila Arnau Vich , Brushett Siobhan , Kruk Marloes ,   Lifelines NEXT cohort study, Dekens Jackie , Sikkema Jan , Kuipers Folkert , Shkoporov Andrey , Hill Colin , Scherjon Sicco , Wijmenga Cisca , Fu Jingyuan , Kurilshikov Alexander , Zhernakova Alexandra 
Published: August 2023

AbstractEarly development of the gut ecosystem is crucial for lifelong health. While infant gut bacterial communities have been studied extensively, the infant gut virome remains under-explored. We longitudinally assessed the composition of gut viruses and their bacterial hosts in 322 total metagenomes and 205 metaviromes from 30 mothers during and after pregnancy and from their 32 infants during their first year of life. While the maternal gut virome composition remained stable during late pregnancy and after birth, the infant gut virome was dynamic in the first year of life and contained a higher abundance of active temperate phages compared to the maternal gut viromes. The infant gut virome composition was also influenced by infant feeding mode and place of delivery. Lastly, we provide evidence of viral-bacterial strains co-transmission from mothers to infants, demonstrating that infants acquire some of their virome from their mother’s gut.Highlights-Longitudinal characterisation of the gut microbiome and virome in 30 mothers during pregnancy, at birth and 3 months after birth and in 32 infants from birth across the first year of life.-The maternal gut bacteriome changes from the first to the second trimester and then remains stable through birth and the first 3 months after birth.-The maternal gut virome remains stable during late pregnancy, birth and the first 3 months after birth.-The infant gut virome is highly dynamic during the first year of life and is shaped by infant feeding mode and place of delivery.-The infant gut harbours more temperate bacteriophages than the maternal gut, but their relative abundance decreases with increasing infant age.-Gut viral strains and their bacterial host strains are co-transmitted from mothers to their infants.-Gut viral strains are transferred from mother to infant around birth directly or via transfer of their bacterial hosts followed by the induction of prophages.
Scanning sample-specific miRNA regulation from bulk and single-cell RNA-sequencing data
Authors: Zhang Junpeng , Liu Lin , Wei Xuemei , Zhao Chunwen , Luo Yanbi , Li Jiuyong , Le Thuc Duy 
Published: August 2023

AbstractRNA-sequencing technology provides an effective tool for understanding miRNA regulation in complex human diseases, including cancers. A large number of computational methods have been developed to make use of bulk and single-cell RNA-sequencing data to identify miRNA regulations at the resolution of multiple samples (i.e. group of cells or tissues). However, due to the heterogeneity of individual samples, there is a strong need to infer miRNA regulation specific to individual samples to uncover miRNA regulation at single-sample resolution level. Here, we develop a framework, Scan, for scanningsample-specific miRNA regulation. Since a single network inference method or strategy cannot perform well for all types of new data, Scan incorporates 27 network inference methods and two strategies to infer tissue-specific or cell-specific miRNA regulation from bulk or single-cell RNA-sequencing data. Results on bulk and single-cell RNA-sequencing data demonstrate the effectiveness of Scan in inferring sample-specific miRNA regulation. Moreover, we have found that incorporating priori information of miRNA targets can improve the accuracy of miRNA target prediction. In addition, Scan can contribute to the clustering cells/tissues and construction of cell/tissue correlation networks. Finally, the comparison results have shown that the performance of network inference methods is likely to be data-specific, and selecting optimal network inference methods is required for more accurate prediction of miRNA targets. We have made Scan freely available to the public to help infer sample-specific miRNA regulation for new data, benchmark new network inference methods and deepen the understanding of miRNA regulation at the resolution of individual samples.
On the comparison between pre- and post-surgery nasal anatomies via computational fluid dynamics
Authors: Segalerba Eric , Dini Ciacci Gabriele , Quadrio Maurizio , Pralits Jan O. 
Published: August 2023

AbstractNasal breathing difficulties (NBD) are widespread and difficult to diagnose; the failure rate of their surgical corrections is high. Computational Fluid Dynamics (CFD) enables diagnosis of NBD and surgery planning, by comparing a pre-operative (pre-op) situation with the outcome of virtual surgery (post-op). An equivalent comparison is involved when considering distinct anatomies in the search for the functionally normal nose. Currently, this comparison is carried out in more than one way, under the implicit assumption that results are unchanged, which reflects our limited understanding of the driver of the respiratory function. The study describes how to set up a meaningful comparison. A pre-op anatomy, derived via segmentation from a CT scan, is compared with a post-op anatomy obtained via virtual surgery. State-of-the-art numerical simulations for a steady inspiration carry out the comparison under three types of global constraints, derived from the field of turbulent flow control: a constant pressure drop (CPG) between external ambient and throat, a constant flow rate (CFR) through the airways and a constant power input (CPI) from the lungs can be enforced. A significant difference in the quantities of interest is observed depending on the type of comparison. Global quantities (flow rate, pressure drop, nasal resistance) as well as local ones are affected. The type of flow forcing affects the outcome of the comparison between pre-op and post-op anatomies. Among the three available options, we argue that CPG is the least adequate. Arguments favouring either CFR or CPI are presented.
Genomic analysis of fruit size and shape traits in apple: unveiling candidate genes through GWAS analysis
Authors: Dujak Christian , Aranzana Maria José 
Published: August 2023

ABSTRACTGenomic tools facilitate the efficient selection of improved genetic materials with within a breeding program. In this work, we focused on two apple fruit quality traits: shape and size. We utilized data from 11 fruit morphology parameters gathered across three years of harvest from 355 genotypes of the Apple REFPOP collection, which serves as a representative sample of the genetic variability present in European cultivated apples. The data was then employed for genome-wide association analysis (GWAS) using the FarmCPU and the BLINK models. The analysis identified 59 SNPs associated with fruit size and shape traits (35 with FarmCPU and 45 with BLINK) responsible for 71 QTNs. These QTNs were distributed across all chromosomes except for chromosome10 and 15. Thirty-four QTNs, identified by 27 SNPs, were related for size traits and thirty-seven QTNs, identified by 26 SNPs, were related to shape attributes. The definition of the haploblocks containing the most relevant SNPs served to propose candidate genes, among them the genes of the ovate family protein MdOFP17 and MdOFP4 which were in a 9.7kb haploblock on chromosome 11. RNA-seq data revealed low or null expression of these genes in the oblong cultivar ‘Skovfoged” and higher expression in the flat ‘Grand’mere’. In conclusion, this comprehensive GWAS analysis of the Apple REFPOP collection has revealed promising genetic markers and candidate genes associated with apple fruit shape and size attributes, providing valuable insights that could enhance the efficiency of future breeding programs.
Mechanics of biomimetic free-standing lipid membranes: Insights on lipid chemistry and bilayer elasticity
Authors: Griffo Alessandra , Sparn Carola , Lolicato Fabio , Nolle Friederike , Khangholi Navid , Seemann Ralf , Fleury Jean-Baptiste , Brinkmann Martin , Nickel Walter , Hähl Hendrik 
Published: August 2023

AbstractThe creation of free-standing lipid membranes has been so far of remarkable interest to investigate processes occurring in the cell membrane since its unsupported part enables studies in which it is important to maintain cell-like physicochemical properties of the lipid bilayer, that nonetheless depend on its molecular composition. In this study, we prepare pore-spanning membranes that mimic the composition of plasma membranes and perform force spectroscopy indentation measurements to unravel mechanistic insights depending on lipid composition. We show that this approach is highly effective for studying the mechanical properties of such membranes. Furthermore, we identify a direct influence of cholesterol and sphingomyelin on the elasticity of the bilayer and adhesion between the two leaflets. Eventually, we explore the possibilities of imaging in the unsupported membrane regions. For this purpose, we investigate the adsorption and movement of a peripheral protein, the fibroblast growth factor 2, on the complex membrane.
Epigenetic mediated functional reprogramming of immune cells leads to HBsAg seroconversion in Hepatitis B Virus Reactivation patients
Authors: Sevak Jayesh Kumar , Islam Mojahidul , Verma Gayantika , Saxena Anoushka , Preedia Babu E , Parveen Shahana , Jindal Ankur , Sharma Manoj Kumar , Ramakrishna Gayatri , Sarin Shiv Kumar , Trehanpati Nirupama 
Published: August 2023

AbstractBackgroundHepatitis B virus (HBV) modulates epigenetic landscape by epigenetic regulators. HBsAg seroconversion is possible with immune activation, therefore we aimed to investigate epigenetic modulation in HBV reactivation (rHBV) for viral clearance and seroconversion.MethodsSixteen retrospectively collected rHBV patients [Seroconverters (SC, n=7, HBsAg loss and anti-HBs>10 IU/ml), non- seroconverters (NSC, n=9)], chronic hepatitis B treatment naïve (nCHBV, n=7) patients and healthy controls (HC, n=7) were included in this study. Genome methylation, gene expression, plasma-cytokines, and immune cell profiling was analysed by Reduced Representation Bisulfite Sequencing (RRBS), QRT-PCR, multiplex-cytokine-bead array and flow-cytometry.ResultsrHBV patients having high HBV DNA and ALT showed epigenetic remodellers; KDM2B, NCOR2 and GATA6, immune and metabolic genes; TGF-β, IL-6, IRF8, RPTOR, HK3 significantly (p<0.05) hypomethylated at specific CpG islands compared to nCHBV. TOX was hypomethylated in nCHBV suggesting immune-exhaustion. At-baseline, seroconverters showed hypomethylation of KDM2B, COX19, IRF8, TLR5 and hypermethylation of LAG3 compared to non-seroconverters. Further, in seroconverters at week-24, IL17RA, IFN-γ, TGF-β, and STAT5B (p<0.05) were additionally hypomethylated at specific CpG islands suggesting immune activation. Cytokine-bead analysis revealed increased IL-6 (p=0.009) and decreased LAG3 plasma levels (p=0.01) also imply on significantly differentiated HBV specific CD8, Tfh and Th1/17 cells in seroconverters at baseline and week-24. However, both nCHBV and non-seroconverters had consistent hypomethylation of LAG3 and TOX, which leads to immune exhaustion.ConclusionIn rHBV, seroconversion is driven by position specific CpG islands methylation in epigenetic remodellers, immune and metabolic genes. Immune metabolic reprograming is reflected by Th1/17 differentiation, extensive interleukin production for HBsAg seroconversion.Graphical AbstractLay summaryEpigenetic landscape in nCHBV depicts exhaustion and immune dysfunction. Out of many hypermethylated CpG islands of nCHBV, few become hypomethylated in rHBV and drives immune and metabolic reprogramming. This study provides insights into the cellular and molecular basis of epigenomic programs that regulate the differentiation and activation of immune cells leading to viral clearance and seroconversion. Targeting epigenetic mechanism could be promising strategy for the treatment of nCHBV and non-seroconverters.
Ubiquitin-driven protein condensation initiates clathrin-mediated endocytosis
Authors: Yuan Feng , Gollapudi Sadhana , Day Kasey J. , Ashby Grant , Sangani Arjun , Malady Brandon T. , Wang Liping , Lafer Eileen M. , Huibregtse Jon M. , Stachowiak Jeanne C. 
Published: August 2023

AbstractClathrin-mediated endocytosis is an essential cellular pathway that enables signaling and recycling of transmembrane proteins and lipids. During endocytosis, dozens of cytosolic proteins come together at the plasma membrane, assembling into a highly interconnected network that drives endocytic vesicle biogenesis. Recently, multiple groups have reported that early endocytic proteins form flexible condensates, which provide a platform for efficient assembly of endocytic vesicles. Given the importance of this network in the dynamics of endocytosis, how might cells regulate its stability? Many receptors and endocytic proteins are ubiquitylated, while early endocytic proteins such as Eps15 contain ubiquitin-interacting motifs. Therefore, we examined the influence of ubiquitin on the stability of the early endocytic protein network. In vitro, we found that recruitment of small amounts of polyubiquitin dramatically increased the stability of Eps15 condensates, suggesting that ubiquitylation could nucleate endocytic assemblies. In live cell imaging experiments, a version of Eps15 that lacked the ubiquitin-interacting motif failed to rescue defects in endocytic initiation created by Eps15 knockout. Furthermore, fusion of Eps15 to a deubiquitylase enzyme destabilized nascent endocytic sites within minutes. In both in vitro and live cell settings, dynamic exchange of Eps15 proteins, a hallmark of liquid-like systems, was modulated by Eps15-Ub interactions. These results collectively suggest that ubiquitylation drives assembly of the flexible protein network responsible for catalyzing endocytic events. More broadly, this work illustrates a biophysical mechanism by which ubiquitylated transmembrane proteins at the plasma membrane could regulate the efficiency of endocytic recycling.Significance StatementThe assembly of proteins into dynamic, liquid-like condensates is an emerging principle of cellular organization. During clathrin-mediated endocytosis, a liquid-like protein network catalyzes vesicle assembly. How do cells regulate these assemblies? Here we show that ubiquitin and endocytic proteins form a dynamic, mutually-reinforcing protein network in vitro and in live cells. To probe the impact of ubiquitylation on the dynamics of endocytosis, we engineered opto-genetic control over recruitment of proteins to nascent endocytic sites. While recruitment of wildtype proteins promoted endocytosis, recruitment of deubiquitylases, enzymes capable of removing ubiquitin, resulted in disassembly of endocytic sites within minutes. These results illustrate that ubiquitylation can regulate the fate of endocytic structures, elucidating a functional connection between protein condensates, endocytosis, and ubiquitin signaling.
Multi-omics Analysis of Aging Liver Reveals Changes in Endoplasmic Stress and Degradation Pathways in Female Nonhuman Primates
Authors: Puppala Sobha , Chan Jeannie , Zimmerman Kip D. , Hamid Zeeshan , Ampong Isaac , Huber Hillary F. , Li Ge , Jadhav Avinash Y. L. , Li Cun , Nathanielsz Peter W. , Olivier Michael , Cox Laura A. 
Published: August 2023

AbstractThe liver is critical for functions that support metabolism, immunity, digestion, detoxification, and vitamin storage. Aging is associated with severity and poor prognosis of various liver diseases such as nonalcoholic fatty liver disease (NAFLD). Previous studies have used multi-omic approaches to study liver diseases or to examine the effects of aging on the liver. However, to date, no studies have used an integrated omics approach to investigate aging-associated molecular changes in the livers of healthy female nonhuman primates. The goal of this study was to identify molecular changes associated with healthy aging in the livers of female baboons (Papiosp., n=35) by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. To integrate omics data, we performed unbiased weighted gene co-expression network analysis (WGCNA), and the results revealed 3 modules containing 3,149 genes and 33 proteins were positively correlated with age, and 2 modules containing 37 genes and 216 proteins were negatively correlated with age. Pathway enrichment analysis showed that unfolded protein response (UPR) and endoplasmic reticulum (ER) stress were positively associated with age, whereas xenobiotic metabolism and melatonin and serotonin degradation pathways were negatively associated with age. The findings of our study suggest that UPR and a reduction in reactive oxygen species generated from serotonin degradation could protect the liver from oxidative stress during the aging process in healthy female baboons.
Spatiotemporally distinct responses to mechanical forces shape the developing seed ofArabidopsis
Authors: Bauer Amélie , Bied Camille , Delattre Adrien , Ingram Gwyneth , Golz John F. , Landrein Benoit 
Published: August 2023

AbstractOrgan morphogenesis depends on mechanical interactions between cells and tissues. These interactions generate forces that can be sensed by cells and affect key cellular processes. However, how mechanical forces contribute, together with biochemical signals, to the shaping of complex organs is still unclear. We address this question using the seed ofArabidopsis asa model system. We show that seeds first experience a phase of high anisotropic growth that is dependent on the response of cortical microtubule (CMT) to forces, which guide cellulose deposition according to shape-driven stresses in the outermost layer of the seed coat. However, at later stages of development, we show that seed growth is isotropic and depend on the properties of an inner layer of the seed coat that stiffens its walls in response to tension but has isotropic material properties. Finally, we show that the transition from anisotropic to isotropic growth is due to dampening of CMT responses to shape-driven stresses. Altogether, our work support that spatiotemporally distinct mechanical responses control the shape of developing seeds inArabidopsis.