bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative proteomics and network biology approach to identify potential urine based biomarkers for tuberculosis
Authors: Subramaniam Sangeetha , Varshney Ankur , Singla Rupak , Behera Digamber , Nanda Ranjan Kumar 
Published: May 2023

SummaryUrine based biomarker discovery employing proteomics platform has been successfully attempted for multiple diseases. Urine is an excellent source of biomarker discovery but its potential is not fully tapped in tuberculosis (TB) diagnostics. In the present study, proteomic profiling of urine samples from thirty five subjects (Mean age=41 years (15-76), M/F=28/7) belonging to active TB, latent TB, lung cancer, chronic obstructive pulmonary disorders (COPD) and healthy subjects were carried out employing a robust multiplex technique. We identified 131 proteins out of which 16 molecules showed at least two-fold change in TB. The study identified a signature of three putative markers, leucine-rich alpha-2-glycoprotein (up-regulated), roundabout homolog 4 and isoform 2 of prostatic acid phosphatase (down-regulated) that could differentiate active TB from other pulmonary diseases. Besides, we investigated whether a network based approach can be efficiently used to expand dynamic coverage, gain a comprehensive view of underlying perturbed functions during the infection and to discover potential biomarkers. While comparing the functionally associated sub-networks of active TB with healthy urine proteome, we identified 54 proteins from the discriminative TB sub-network, some of which are known to be involved in the infection process. Few examples in this study like serpin peptidase inhibitor and catenin that has not been identified in the experiment but detected in the difference network demonstrate that proteomic profiling when integrated with network biology method could be a holistic approach to expand the dynamic range and identify potential candidate biomarkers and also provide a broad overview of perturbed functions during the infection.
Systematic Review of Monogenic Diabetes Prognostics
Authors: Naylor Rochelle N. , Amouyal Chloé , Philipson Louis H. , Vatier Camille , Dickens Laura T. ,   ADA/EASD PMDI, Greeley Siri Atma W 
Published: May 2023

AbstractBackgroundIndividuals with monogenic diabetes are at risk for diabetes-related complications; however, overall prognosis and whether prognosis is similar to other diabetes forms is poorly understood.AimTo assess diabetes-related microvascular and macrovascular complications in the common forms of monogenic diabetes.MethodsSystematic review with data sources from Pubmed, Medline and Embase was performed to assess diabetes-related complications in KCNJ11-neonatal diabetes, ABBC8-neontal diabetes, HNF1A-diabetes, HNF4-diabetes and GCK-related hyperglycemia.ResultsData was extracted from 67 studies. Most studies had moderate to high risk of bias. In neonatal diabetes, 16 of 20 studies reported at least one microvascular complication, with complications occurring as early as the second decade of life. Macrovascular complications were reported in only 1 individual who was 40 years old at the time of study. Diabetes complications were frequent in HNF1A-diabetes and HNF4A-diabetes, but did show a temporal trend of improved prognosis (e.g., 47% versus 13.6% retinopathy) and better prognosis compared to type 1 diabetes. Death due to cardiovascular disease was higher in HNF1A-diabetes compared to unaffected relatives (66% versus 43%). GCK-related hyperglycemia showed overall low rates of complications.ConclusionWhile KCNJ11-neonatal diabetes, ABBC8-neontal diabetes, HNF1A-diabetes and HNF4-diabetes are clearly at risk for diabetes-related complications, microvascular complications were infrequently reported before the third decade of life. GCK-related hyperglycemia showed a low prevalence of complications with rates not significantly different from control groups except for mild retinopathy. Future prospective studies to determine age at onset of complications and the impact of precision therapy are warranted to best guide surveillance practices for each subtype.
The Protective Effect of Virus Capsids on RNA and DNA Virus Genomes in Wastewater
Authors: Harrison Katherine R. , Snead Delaney , Kilts Anna , Ammerman Michelle L. , Wigginton Krista R. 
Published: May 2023

ABSTRACTVirus concentrations measured in municipal wastewater help inform both the water treatment necessary to protect human health and wastewater-based epidemiology. Wastewater measurements are typically PCR-based, and interpreting gene copy concentrations requires an understanding of the form and stability of the nucleic acids. Here, we study the persistence of model virus genomes in wastewater, the protective effects provided by the virus capsids, and the relative decay rates of genome and infectious viruses. In benchtop batch experiments at 25 °C, extraviral (+)ssRNA and dsDNA amplicons degraded by 90% within 15-19 minutes and 1.6-1.9 hours, respectively. When encapsidated, the T90for MS2 (+)ssRNA increased by 424× and the T90for T4 dsDNA increased by 52×. The (+)ssRNA decay rates were similar for a range of amplicon sizes. For our model phages MS2 and T4, the nucleic acid signal in untreated wastewater disappeared shortly after the viruses lost infectivity. Combined, these results suggest that most viral genome copies measured in wastewater are part of intact virus particles, that measured concentrations are independent of assay amplicon sizes, and that the virus genome decay rates of naked viruses are similar to inactivation rates. These findings will be valuable for the interpretation of wastewater virus measurements.
Utility of Multimodal Longitudinal Imaging Data for Dynamic Prediction of Cardiovascular and Renal Disease: The CARDIA Study
Authors: Nguyen Hieu , Vasconcellos Henrique D. , Keck Kimberley , Carr John , Launer Lenore J , Guallar Eliseo , Lima João A.C. , Ambale-Venkatesh Bharath 
Published: May 2023

AbstractBackgroundMedical examinations contain repeatedly measured data from multiple visits, including imaging variables collected from different modalities. However, the utility of such data for the prediction of time-to-event is unknown, and only a fraction of the data is typically used for risk prediction. We hypothesized that multimodal longitudinal imaging data could improve dynamic disease prognosis of cardiovascular and renal disease (CVRD).MethodsIn a multi-centered cohort of 5114 CARDIA participants, we included 166 longitudinal imaging variables from five imaging modalities: Echocardiography (Echo), Cardiac and Abdominal Computed Tomography (CT), Dual-Energy X-ray Absorptiometry (DEXA), Brain Magnetic Resonance Imaging (MRI) collected from young adulthood to mid-life over 30 years (1985-2016) to perform dynamic survival analysis of CVRD events using machine learning dynamic survival analysis (Dynamic-DeepHit, LTRCforest, and Extended Cox for Time-varying Covariates). Risk probabilities were continuously updated as new data were collected. Model performance was assessed using integrated AUC and C-index and compared to traditional risk factors.ResultsLongitudinal imaging data, even when being irregularly collected with high missing rates, improved CVRD dynamic prediction (0.03 in integrated AUC, up to 0.05 in C-index compared to traditional risk factors) from young adulthood followed up to midlife. Among imaging variables, Echo and CT variables contributed significantly to improved risk estimation. Echo measured in early adulthood predicted midlife CVRD risks almost as well as Echo measured 10-15 years later (0.01 C-index difference). The most recent CT exam provided the most accurate prediction for short-term risk estimation. Brain MRI markers provided additional information from cardiac Echo and CT variables that led to a slightly improved prediction.ConclusionsLongitudinal multimodal imaging data readily collected from follow-up exams can improve CVRD dynamic prediction. Echocardiography measured early can provide a good long-term risk estimation, while CT/calcium scoring variables carry atherosclerotic signatures that benefit more immediate risk assessment starting in middle-age.
Genetic excision of the regulatory cardiac troponin I extension in high heart rate mammal clades
Authors: Joyce William , He Kai , Zhang Mengdie , Ogunsola Samuel , Wu Xini , Joseph Kelvin T. , Bogomolny David , Yu Wenhua , Springer Mark S. , Xie Jiuyong , Signore Anthony V. , Campbell Kevin L. 
Published: May 2023

AbstractMammalian cardiac troponin I (cTnI) contains a highly conserved N-terminal extension harboring protein kinase A targets (Ser23/24) which are phosphorylated during ß-adrenergic stimulation to increase cardiomyocyte relaxation rate. Here, we show that the Ser23/24encoding exon 3 ofTNNI3was pseudoexonized multiple times in shrews and moles to mimic Ser23/24phosphorylation without adrenergic stimulation, facilitating the evolution of exceptionally high resting heart rates (∼1000 beats min-1). We further reveal alternative exon 3 splicing in distantly related bat families and that both exon 3-and exon 3+cTnI isoforms are incorporated into cardiac myofibrils. Finally, exon 3 of humanTNNI3is shown to exhibit a relatively low splice strength score, offering an evolutionarily informed strategy to excise this exon to improve diastolic function during heart failure.
Listening to tropical forest soils
Authors: Metcalf Oliver , Baccaro Fabricio , Barlow Jos , Berenguer Erika , Bradfer-Lawrence Tom , Rossi Liana Chesini , do Vale Érica Marinho , Lees Alexander 
Published: May 2023

AbstractPAM has proven to be an effective tool for monitoring biotic soundscapes in the marine, terrestrial, and aquatic realms. Recently it has been suggested that it could also be an effective method for monitoring soil fauna, but has so far been used in only four studies in temperate and polar regions. We present the first study of soil soundscapes in tropical forests, using a novel analytical pipeline allowing for the use of in-situ recording of soundscapes with minimal soil disturbance. We found significant differences in soil soundscapes between burnt and unburnt forests and the first indications of a diel cycle in soil soundscapes. These promising results and methodological advances highlight the potential of PAM for large-scale and long-term monitoring of soil biodiversity. We use the results to discuss research priorities, including relating soil biophony to biodiversity, community structure and ecosystem functioning, and the use of appropriate hardware and analytical techniques.
Distinct axo-protective and axo-destructive roles for Schwann cells after injury in a novel compartmentalised mouse myelinating coculture system
Authors: Mutschler Clara , Fazal Shaline V. , Schumacher Nathalie , Loreto Andrea , Coleman Michael P. , Arthur-Farraj Peter 
Published: May 2023

AbstractMyelinating Schwann cell (SC)– dorsal root ganglion (DRG) neuron cocultures have been an important technique over the last four decades in understanding cell-cell signalling and interactions during peripheral nervous system (PNS) myelination, injury, and regeneration. While methods using rat SCs and rat DRG neurons are commonplace, there are no established protocols in the field describing the use of mouse SCs with mouse DRG neurons in dissociated myelinating cocultures. There is a great need for such a protocol as this would allow the use of cells from many different transgenic mouse lines. Here we describe a protocol to coculture dissociated mouse SCs and DRG neurons and induce robust myelination. Use of microfluidic chambers permits fluidic isolation for drug treatments, allows cultures to be axotomised to study injury responses, and cells can readily be transfected with lentiviruses to permit live imaging. We used this model to quantify the rate of degeneration after traumatic axotomy in the presence and absence of myelinating SCs and axon aligned SCs that were not induced to myelinate. We find that SCs, irrespective of myelination status, are axo-protective and delay axon degeneration early on. At later time points after injury, we use live imaging of cocultures to show that once axonal degeneration has commenced SCs break up, ingest, and clear axonal debris.Summary statementA novel compartmentalised dissociated mouse myelinating SC-DRG coculture system reveals distinct axo-protective and axo-destructive phases of Schwann cells on axon integrity after trauma.
AMLdb: A comprehensive multi-omics platform to understand the pathogenesis and discover biomarkers for acute myeloid leukemia
Authors: Kumar Keerthana Vinod , Kumar Ambuj , Kundal Kavita , Sengupta Avik , R Kunjulakshmi , Nishana Mayilaadumveettil , Kumar Rahul 
Published: May 2023

AbstractAcute myeloid leukemia (AML) is one of the leading leukemic malignancies in adults. The heterogeneity of the disease makes the diagnosis and treatment extremely difficult. Despite the significant developments and the rapid advancements in finding new medication targets, the treatment for AML remains a challenge. With the advent of next-generation sequencing (NGS) technologies, exploration at the molecular level for the identification of biomarkers and drug targets has been the main focus for the researchers to come up with novel therapies for better prognosis and survival outcomes of AML patients. However, the massive amounts of data generated from the NGS platforms demands the necessity to create a comprehensive platform on AML to save the time invested in mining literature. To facilitate this, we developed AMLdb, an interactive multi-omics platform that allows users to query, visualize, retrieve and analyze AML-related multi-omics data. It provides a diverse collection of data resourced from various repositories allowing for a more comprehensive analysis. AMLdb contains 86 datasets for gene expression profiles, 15 datasets for methylation profiles, CRISPR-Cas9 knockout screens of 26 AML cell lines, sensitivity of 26 AML cell lines to 288 drugs, mutations in 41 unique genes in 23 AML cell lines and information on 27 experimentally validated biomarkers. The data provided can be used for deriving conclusions on potential targets for therapies, sensitivity of these targets towards the drugs, patient classification, prediction of treatment strategies and outcomes, chances of relapse etc. In this study, we have reported five genes i.e.,CBFB, ENO1, IMPDH2, SEPHS2 and MYH9identified via our analysis using AMLdb as potential targets. Amongst this,CBFB, IMPDH2, SEPHS2 and MYH9have been previously validated as targets by experimental studies which is in par with our results. However,ENO1is a novel target identified using AMLdb which needs further investigation. We anticipates that, AMLdb can be a valuable resource to aid the research community accelerate the development of effective therapies for AML. AMLdb is freely accessible athttps://project.iith.ac.in/cgntlab/amldb/without any restrictions.
Flavodiiron proteins associate pH-dependently with the thylakoid membrane for ferredoxin-1 powered O2photoreduction
Authors: Nikkanen Lauri , Vakal Serhii , Santana-Sánchez Anita , Hubáček Michal , Konert Grzegorz , Wang Yingying , Boehm Marko , Gutekunst Kirstin , Salminen Tiina A. , Allahverdiyeva Yagut 
Published: May 2023

AbstractFlavodiiron proteins (FDPs) catalyse light-dependent reduction of oxygen to water in photosynthetic organisms, creating an electron sink on the acceptor side of Photosystem I that protects the photosynthetic apparatus. However, the identity of the electron donor(s) and the molecular mechanisms regulating FDP activity have remained elusive. To elucidate these issues, we employed spectroscopic and gas flux analysis of photosynthetic electron transport, bimolecular fluorescence complementation assays forin vivoprotein–protein interactions in the model cyanobacteriumSynechocystissp. PCC 6803, as well asin silicosurface charge modelling. We demonstrated that Ferredoxin-1 interacts with Flv1, Flv2, and Flv3, and is the main electron donor to FDP heterooligomers, which are responsible for the photoreduction of oxygen. Moreover, we revealed that association of FDP heterooligomers with thylakoid membranes is promoted by dissipation of the trans-thylakoid proton motive force, providing the firstin vivoevidence of a self-regulatory feedback mechanism allowing dynamic control of FDP activity and maintenance of photosynthetic redox balance in fluctuating environments. Our findings have direct implications for rationally directing electron flux toward desired reactions in biotechnological applications.
HEMU: an integrated Andropogoneae comparative genomics database and analysis platform
Authors: Zhu Yuzhi , Wang Zijie , Zhou Zanchen , Liu Yuting , Shi Junpeng 
Published: May 2023

AbstractThe Andropogoneae tribe encompasses various crops with substantial agronomic value such as maize (Zea mays) and sorghum (Sorghum bicolor). Despite the prevalence in released multi-omics data resources, there is a dearth of comprehensive, tribe-level integration and multi-layer omics dataset platform within the tribe, assisting inter- and intra-species comparative analysis from a multi-omics aspect. Here, we first collected a comprehensive atlas of multi-omics datasets within the tribe, including 75 genomes from 20 unique species, transcriptomes from 4,747 samples comprising more than 50 tissues, epigenome data from 90 ChIP-seq samples and 39 ATAC-seq samples, as well as transposable element (TE) annotation for all the genomes. Then, an integrated database and analysis platform, HEMU (http://shijunpenglab.com/HEMUdb/), was constructed. HEMU comprises six sophisticated toolkits, namely genome analysis toolkit, transcriptome-derived analysis toolkit, gene family analysis toolkit, transposable element (TE) analysis toolkit, epigenome analysis toolkit and miscellaneous analysis toolkit, facilitating convenient inter- and intra-species comparative analysis taking advantage of the multi-omics data. Three case studies substantiated the capability of HEMU in conducting gene-centered analysis, transcriptome derived analysis and gene family analysis from a both multi-omics and comparative perspective. In a nutshell, HEMU lowers the barrier of traditional code-based analysis workflow, providing novel insights into modern genetic breeding in the tribe Andropogoneae.
Incidental learning of predictive temporal context within cortical representations of visual shape
Authors: Kakaei Ehsan , Braun Jochen 
Published: May 2023

AbstractIncidental learning of spatio-temporal regularities and consistencies – also termed ‘statistical learning’ – may be important for discovering the causal principles gov-erning the world. We studied statistical learning of temporal structure at two temporal scales: the presentation of rotating visual objects (3 s) and predictive temporal context (30 s) in a sequence of such objects.Observers viewed fifteen initially unfamiliar synthetic objects recurring many times each, intermixed with other similar objects that appeared only once, while whole-brain BOLD activity was recorded. Analyzing multivariate BOLD activity, we located view-independent responses to synthetic objects throughout the ventral occipitotemporal cortex, revealing a view-invariant representation of object shape.Predictive temporal context modified representations of object shape at early and middle levels of the visual processing hierarchy. Approximately 20% of the sites representing shape also exhibited a significant representation of temporal context. A few higher-level sites represented temporal context, without also representing object shape. Additionally, objects marking transitions between communities were distinctly represented at many sites.We conclude that, at the sensitivity afforded by fMRI, the cortical represen-tations of invariant visual shape and of predictive temporal context are largely coextensive. Our results suggest that incidental learning of causal principles and structures operating at different timescales (“structural learning”) may involve vi-sually responsive areas in the ventral occipitotemporal cortex.
Computational models for state-dependent traveling waves in hippocampal formation
Authors: Wu Yuxuan , Chen Zhe Sage 
Published: May 2023

AbstractHippocampal theta (4-10 Hz) oscillations have been identified as traveling waves in both rodents and humans. In freely foraging rodents, the theta traveling wave is a planar wave propagating from the dorsal to ventral hippocampus along the septotemporal axis. Motivated from experimental findings, we develop a spiking neural network of excitatory and inhibitory neurons to generate state-dependent hippocampal traveling waves to improve current mechanistic understanding of propagating waves. Model simulations demonstrate the necessary conditions for generating wave propagation and characterize the traveling wave properties with respect to model parameters, running speed and brain state of the animal. Networks with long-range inhibitory connections are more suitable than networks with long-range excitatory connections. We further generalize the spiking neural network to model traveling waves in the medial entorhinal cortex (MEC) and predict that traveling theta waves in the hippocampus and entorhinal cortex are in sink.
Extracellular vesicle-mediated Transfer of miR-1 from Primary tumor Repress Distant Metastasis Growth
Authors: Kim Hui-Su , Lee Kang-Hoon , Son Keun Hong , Shin Tae-Jin , Cho Je-Yoel 
Published: May 2023

AbstractMetastases originate from primary tumors that conquer distant organs. Growing evidence suggests that metastases are still under primary tumor dominance, even out of the primary territory. However, the mechanism by which primary tumors prime the fate of metastasis is unclear. Here, we investigated the influence of primary tumor-derived extracellular vesicles (pTDEs) on distant metastasis. Metastatic growth was remarkably suppressed when cells were treated with pTDEsin vitroand intravenously in a spontaneous metastatic mouse model. pTDEs from primary tumors with cancer stem cell (CSC) characteristics inhibit metastatic growth by inducing intracellular ROS/DNA double-stranded damage, thus inhibiting G2/M phase accumulation. We found that miR-1 was the most abundant in pTDEs and showed a stronger inhibitory effect when miR-1 was overloaded in pTDEs. Collectively, we demonstrated that the primary tumor could control distant metastatic cancer via primary tumor-derived EV-miR-1. Additionally, our approach suggests the development of anticancer drugs for metastasis based on pTDE-miR-1.
The Secondary Somatosensory Cortex Gates Mechanical and Thermal Sensitivity
Authors: Taub Daniel G. , Jiang Qiufen , Pietrafesa Francesca , Su Junfeng , Greene Caitlin , Blanchard Michael R. , Jain Aakanksha , El-Rifai Mahmoud , Callen Alexis , Yager Katherine , Chung Clara , He Zhigang , Chen Chinfei , Woolf Clifford J. 
Published: May 2023

AbstractThe cerebral cortex is vital for the perception and processing of sensory stimuli. In the somatosensory axis, information is received by two distinct regions, the primary (S1) and secondary (S2) somatosensory cortices. Top-down circuits stemming from S1 can modulate mechanical and cooling but not heat stimuli such that circuit inhibition causes blunted mechanical and cooling perception. Using optogenetics and chemogenetics, we find that in contrast to S1, an inhibition of S2 output increases mechanical and heat, but not cooling sensitivity. Combining 2-photon anatomical reconstruction with chemogenetic inhibition of specific S2 circuits, we discover that S2 projections to the secondary motor cortex (M2) govern mechanical and thermal sensitivity without affecting motor or cognitive function. This suggests that while S2, like S1, encodes specific sensory information, that S2 operates through quite distinct neural substrates to modulate responsiveness to particular somatosensory stimuli and that somatosensory cortical encoding occurs in a largely parallel fashion.