bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two neuronal models of TDP-43 proteinopathy display reduced axonal translation, increased oxidative stress, and defective exocytosis
Authors: Pisciottani Alessandra , Croci Laura , Lauria Fabio , Marullo Chiara , Savino Elisa , Ambrosi Alessandro , Podini Paola , Marchioretto Marta , Casoni Filippo , Cremona Ottavio , Taverna Stefano , Quattrini Angelo , Cioni Jean-Michel , Viero Gabriella , Codazzi Franca , Consalez G. Giacomo 
Published: May 2023

ABSTRACTAmyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative disease mostly affecting people around 50-60 years of age. TDP-43, a ubiquitously expressed RNA-binding protein involved in pre-mRNA splicing and controlling mRNA stability and translation, forms neuronal cytoplasmic inclusions in an overwhelming majority of ALS patients, of both sporadic and familial origin, a phenomenon referred to as TDP-43 proteinopathy. These cytoplasmic aggregates disrupt the subcellular transport and localization of mRNA. The axon, like dendrites, is a site of mRNA translation, permitting the local synthesis of selected proteins, both constitutively and in response to stimuli reaching the axon and presynaptic terminal. This is especially relevant in upper and lower motor neurons, whose axon spans long distances, likely accentuating their susceptibility to ALS-related noxae. In this work we have generated and characterized two models of TDP-43 proteinopathy, consisting of virtually pure populations of mouse cortical neurons expressing a human TDP-43 fusion protein, wt or mutant, which accumulates as cytoplasmic aggregates. Neurons expressing human TDP-43 exhibit a global impairment in axonal protein synthesis, an increase in oxidative stress, and defects in presynaptic function and electrical activity. These changes correlate with deregulation in the axonal levels of polysome-engaged mRNAs playing relevant roles in those processes. Our data support the emerging notion that deregulation of mRNA metabolism and of axonal mRNA transport may trigger the dying-back neuropathy that initiates motor neuron degeneration in ALS.
Atypical flagella assembly and haploid genome coiling during male gamete formation inPlasmodium
Authors: Hair Molly , Moreira-Leite Flavia , Ferguson David , Zeeshan Mohammed , Tewari Rita , Vaughan Sue 
Published: May 2023

AbstractPlasmodiumspp. sexual reproduction occurs within theAnophelesmosquito and is essential for gametogenesis and onwards transmission to mammalian hosts. Upon activation, the maleP. bergheigametocyte undergoes three rounds of inter-nuclear mitosis and assembles eight basal bodies and axonemes around the nucleus prior to ex-flagellation, resulting in 8 flagellated male gametes in 12-15 minutes. However there is little understanding of the 3D organisation of this rapid process of male gametogenesis. In this study we used serial block face scanning electron microscopy (SBF-SEM) and cellular electron tomography (ssET) ofP. bergheimicrogametocytes to examine the 3D architecture of key structures during male gamete formation. Our data has revealed an exquisite organisation of axonemes coiling around the nucleus in opposite directions forming a central ‘axoneme band’ in microgametocytes. Furthermore, we discovered that the nucleus of microgametes is tightly coiled around the axoneme in an exquisitely complex structure whose formation starts before microgamete emergence during ex-flagellation. Our discoveries of the detailed 3D organisation of the flagellated microgamete and the haploid genome highlights some of the atypical mechanisms of axoneme assembly and haploid genome organisation during male gamete formation in the malaria parasitePlasmodium spp.
GABA and Glutamate response to social processing; a functional MRS study
Authors: Pasanta Duanghathai , White David J. , He Jason L. , Ford Talitha C. , Puts Nicolaas A. 
Published: May 2023

AbstractSeveral studies have suggested that atypical social processing in multiple psychiatric conditions (e.g., autism) is associated with differences in excitation and inhibition, through changes in the levels of glutamate and GABA levels. While associations between baseline metabolite levels and behaviours can be insightful, assessing the neurometabolic response of GABA and Glutamate during social processing may inform altered neurochemical function in more depth. Thus far, there have been no attempts to determine whether changes in metabolite levels are detectable using functional magnetic resonance spectroscopy (fMRS) during social processing in a control population. We performed MEGA-PRESS edited fMRS to measure the dynamic response of GABA and glutamate in the superior temporal sulcus (STS) and visual cortex (V1) while viewing social stimuli, using a design that allows for analysis in both block and event-related approaches. Sliding window analyses were used to investigate GABA and glutamate dynamics at higher temporal resolution. A small decrease in GABA levels was observed during social stimulus presentation in V1, but no change was observed in STS. Conversely, non-social stimulus elicited changes in both GABA and glutamate levels in both regions. We discuss the feasibility of using fMRS analysis approaches to assess changes in metabolite response during social processing.
mRNA display reveals a class of high-affinity bromodomain-binding motifs that are not found in the human proteome
Authors: Low Jason K K , Patel Karishma , Solomon Paul , Norman Alexander , Pachl Petr , Jones Natasha , Payne Richard J , Passioura Toby , Suga Hiroaki , Walport Louise J , Mackay Joel P 
Published: May 2023

ABSTRACTBromodomains regulate gene expression by recognizing protein motifs containing acetyllysine. Although originally characterized as histone-binding proteins, it has since become clear that these domains interact with other acetylated proteins, perhaps most prominently transcription factors. The likely transient nature and low stoichiometry of such modifications, however, has made it challenging to fully define the interactome of any given bromodomain. To begin to address this knowledge gap in an unbiased manner, we carried out mRNA display screens against a bromodomain – theN-terminal bromodomain of BRD3 – using peptide libraries that contained either one or two acetyllysine residues. We discovered peptides with very strong consensus sequences and with affinities that are significantly higher than typical bromodomain-peptide interactions. X-ray crystal structures also revealed modes of binding that have not been seen with natural ligands. Intriguingly, however, our selected sequences are not found in the human proteome, perhaps suggesting that strong binders to bromodomains might have been selected against.
GbyE: A New Genome Wide Association and Prediction Model based on Genetic by Environmental Interaction
Authors: Liu Xinrui , Wang Mingxiu , Qin Jie , Liu Yaxin , Zhong Jincheng , Wang Jiabo 
Published: May 2023

AbstractNowadays, studies on genetic by environment interactions (G×E) are receiving increasing attention because of its theoretical and practical importance in explaining individual behavioral traits. Use information from different environments to improve the statistical power of genome-wide association and prediction in the hope of obtaining individuals with better breeding value is the most expedient way. However, there are significant challenges when performing genome-wide association studies (GWAS) and genomic selection (GS) using multiple environments or traits, mainly because most diseases and quantitative traits have numerous associated loci with minimal effects. Therefore, this study constructed a new genotype design model program (GbyE) for genome-wide association and prediction using Kronecker product, which can enhance the statistical power of GWAS and GS by utilizing the interaction effects of multiple environments or traits. The data of 282 maize, 354 yaks and 255 peaches were used to evaluate the power of the model at different levels of heritability and genetic correlation. The results show that GbyE can provide higher statistical power for the traditional GWAS and GS models in any heritability and genetic correlation, and can detect more real loci. In addition, GbyE has increased statistical power to three Bayesian models (BRR, BayesA, and BayesCpi). GbyE can make full use of multiple environment or trait informations to increase the statistical power of the model, which can help us understand the G×E and provide a method for predicting association loci for complex traits.
Cbl and Cbl-b Ubiquitin Ligases are Essential for Intestinal Epithelial Stem Cell Maintenance
Authors: Zutshi Neha , Mohapatra Bhopal C. , Mondal Pinaki , An Wei , Goetz Benjamin T. , Wang Shuo , Li Sicong , Storck Matthew D. , Mercer David F. , Black Adrian R. , Thayer Sarah P. , Black Jennifer D. , Lin Chi , Band Vimla , Band Hamid 
Published: May 2023

SUMMARYAmong the signaling pathways that control the stem cell self-renewal and maintenance vs. acquisition of differentiated cell fates, those mediated by receptor tyrosine kinase (RTK) activation are well established as key players. CBL family ubiquitin ligases are negative regulators of RTKs but their physiological roles in regulating stem cell behaviors are unclear. While hematopoieticCbl/Cblbknockout (KO) leads to a myeloproliferative disease due to expansion and reduced quiescence of hematopoietic stem cells, mammary epithelial KO led to stunted mammary gland development due to mammary stem cell depletion. Here, we examined the impact of inducibleCbl/Cblbdouble-KO (iDKO) selectively in the Lgr5-defined intestinal stem cell (ISC) compartment.Cbl/CblbiDKO led to rapid loss of theLgr5HiISC pool with a concomitant transient expansion of theLgr5Lotransit amplifying population. LacZ reporter-based lineage tracing showed increased ISC commitment to differentiation, with propensity towards enterocyte and goblet cell fate at the expense of Paneth cells. Functionally,Cbl/CblbiDKO impaired the recovery from radiation-induced intestinal epithelial injury.In vitro,Cbl/CblbiDKO led to inability to maintain intestinal organoids. Single cell RNAseq analysis of organoids revealed Akt-mTOR pathway hyperactivation in iDKO ISCs and progeny cells, and pharmacological inhibition of the Akt-mTOR axis rescued the organoid maintenance and propagation defects. Our results demonstrate a requirement forCbl/Cblbin the maintenance of ISCs by fine tuning the Akt-mTOR axis to balance stem cell maintenance vs. commitment to differentiation.
Unraveling human, rodent and snakeKolmioviridaereplication to anticipate cross-species transmission
Authors: Khalfi Pierre , Denis Zoé , Merolla Giovanni , Chavey Carine , Ursic-Bedoya José , Soppa Lena , Szirovicza Leonora , Hetzel Udo , Dufourt Jeremy , Leyrat Cedric , Goldmann Nora , Goto Kaku , Verrier Eloi , Baumert Thomas F. , Glebe Dieter , Courgnaud Valérie , Grégoire Damien , Hepojoki Jussi , Majzoub Karim 
Published: May 2023

AbstractThe recent discovery of Hepatitis D (HDV)-likeviruses across a wide range of taxa led to the establishment of theKolmioviridaefamily. Recent studies suggest that kolmiovirids can be satellites of viruses other than Hepatitis B virus (HBV), challenging the strict HBV/HDV-association dogma. Studying whether kolmiovirids are able to replicate in any animal cell they enter is essential to assess their zoonotic potential. Here, we compared replication of three kolmiovirids: HDV, rodent (RDeV) and snake deltavirus (SDeV)in vitroandin vivo. We show that SDeV has the narrowest and RDeV the broadest host cell range. High resolution imaging of infected cells revealed nuclear viral hubs with a peculiar RNA-protein organization. Finally,in vivohydrodynamic delivery of infectious clones showed that both HDV and RDeV, but not SDeV, efficiently replicate in mouse liver, forming massive nuclear viral hubs. Our comparative analysis lays the foundation for the discovery of specific host factors controllingKolmioviridaehost-shifting.
Improving bioplastic production byRhodopseudomonas palustrisTIE-1 using synthetic biology and metabolic engineering
Authors: Ranaivoarisoa Tahina Onina , Bai Wei , Rengasamy Karthikeyan , Steele Hope , Silberman Miriam , Olabode Jennifer , Bose Arpita 
Published: May 2023

AbstractWith the increasing demand for sustainably produced renewable resources, it is important to look towards microorganisms capable of producing bioproducts such as biofuels and bioplastics. Though many systems for bioproduct production are well documented and tested in model organisms, it is essential to look beyond to non-model organisms to expand the field and take advantage of metabolically versatile strains. This investigation centers onRhodopseudomonas palustrisTIE-1, a purple, non-sulfur autotrophic, and anaerobic bacterium capable of producing bioproducts that are comparable to their petroleum-based counterparts. To induce bioplastic overproduction, genes that might have a potential role in the PHB biosynthesis such as the regulator,phaR,andphaZknown for its ability to degrade PHB granules were deleted using markerless deletion. Mutants in pathways that might compete with polyhydroxybutyrate (PHB) production such as glycogen and nitrogen fixation previously created to increasen-butanol production by TIE-1 were also tested. In addition, a phage integration system was developed to insert RuBisCO (RuBisCO form I and II genes) driven by a constitutive promoterPaphIIinto TIE- 1 genome. Our results show that deletion of thephaRgene of the PHB pathway increases PHB productivity when TIE-1 was grown photoheterotrophically with butyrate and ammonium chloride (NH4Cl). Mutants unable to make glycogen or fix dinitrogen gas show an increase in PHB productivity under photoautotrophic growth conditions with hydrogen. In addition, the engineered TIE-1 overexpressing RuBisCO form I and form II produces significantly more polyhydroxybutyrate than the wild type under photoheterotrophy with butyrate and photoautotrophy with hydrogen. Inserting RuBisCO genes into TIE-1 genome is a more effective strategy than deleting competitive pathways to increase PHB production in TIE-1. The phage integration system developed for TIE-1 thus creates numerous opportunities for synthetic biology in TIE-1.
Reorganization of Pancreas Circadian Transcriptome with Aging
Authors: Sharma Deepak , Wessel Caitlin R. , Mahdavinia Mahboobeh , Preuss Fabian , Bishehsari Faraz 
Published: May 2023

SummaryThe evolutionarily conserved circadian system allows organisms to synchronize internal processes with 24-h cycling environmental timing cues, ensuring optimal adaptation. Like other organs, the pancreas function is under circadian control. Recent evidence suggests that aging by itself is associated with altered circadian homeostasis in different tissues which could affect the organ’s resiliency to aging-related pathologies. Pancreas pathologies of either endocrine or exocrine components are age-related. Whether pancreas circadian transcriptome output is affected by age is still unknown. To address this, here we profiled the impact of age on the pancreatic transcriptome over a full circadian cycle and elucidated a circadian transcriptome reorganization of pancreas by aging. Our study highlights gain of rhythms in the extrinsic cellular pathways in the aged pancreas and extends a potential role to fibroblast-associated mechanisms.
Information Geometry of the Retinal Representation Manifold
Authors: Ding Xuehao , Lee Dongsoo , Melander Joshua B. , Sivulka George , Ganguli Surya , Baccus Stephen A. 
Published: May 2023

AbstractThe ability for the brain to discriminate among visual stimuli is constrained by their retinal representations. Previous studies of visual discriminability have been limited to either low-dimensional artificial stimuli or pure theoretical considerations without a realistic encoding model. Here we propose a novel framework for understanding stimulus discriminability achieved by retinal representations of naturalistic stimuli with the method of information geometry. To model the joint probability distribution of neural responses conditioned on the stimulus, we created a stochastic encoding model of a population of salamander retinal ganglion cells based on a three-layer convolutional neural network model. This model not only accurately captured the mean response to natural scenes but also a variety of second-order statistics. With the model and the proposed theory, we computed the Fisher information metric over stimuli to study the most discriminable stimulus directions. We found that the most discriminable stimulus varied substantially across stimuli, allowing an examination of the relationship between the most discriminable stimulus and the current stimulus. By examining responses generated by the most discriminable stimuli we further found that the most discriminative response mode is often aligned with the most stochastic mode. This finding carries the important implication that under natural scenes, retinal noise correlations are information-limiting rather than increasing information transmission as has been previously speculated. We additionally observed that sensitivity saturates less in the population than for single cells and that as a function of firing rate, Fisher information varies less than sensitivity. We conclude that under natural scenes, population coding benefits from complementary coding and helps to equalize the information carried by different firing rates, which may facilitate decoding of the stimulus under principles of information maximization.
Spatial proteomics in neurons at single-protein resolution
Authors: Unterauer Eduard M. , Boushehri Sayedali Shetab , Jevdokimenko Kristina , Masullo Luciano A. , Ganji Mahipal , Sograte-Idrissi Shama , Kowalewski Rafal , Strauss Sebastian , Reinhardt Susanne C.M. , Perovic Ana , Marr Carsten , Opazo Felipe , Fornasiero Eugenio F. , Jungmann Ralf 
Published: May 2023

SUMMARYTo fully understand biological processes and functions, it is necessary to reveal the molecular heterogeneity of cells and even subcellular assemblies by gaining access to the location and interaction of all biomolecules. The study of protein arrangements has seen significant advancements through super-resolution microscopy, but such methods are still far from reaching the multiplexing capacity of spatial proteomics. Here, we introduce Secondary label-based Unlimited Multiplexed DNA-PAINT (SUM-PAINT), a high-throughput imaging method capable of achieving virtually unlimited multiplexing at better than 15 nm spatial resolution. Using SUM-PAINT, we generated the most extensive multiprotein dataset to date at single-protein spatial resolution, comprising up to 30 distinct protein targets in parallel and adapted omics-inspired analysis workflows to explore these feature-rich datasets. Remarkably, by examining the multiplexed protein content of almost 900 individual synapses at single-protein resolution, we revealed the complexity of synaptic heterogeneity, ultimately leading to the discovery of a new synapse type. This work provides not only a feature-rich resource for researchers, but also an integrated data acquisition and analysis workflow for comprehensive spatial proteomics at single-protein resolution, paving the way for ‘Localizomics’.
Predictive and Interpretable: Combining Artificial Neural Networks and Classic Cognitive Models to Understand Human Learning and Decision Making
Authors: Eckstein Maria K. , Summerfield Christopher , Daw Nathaniel D. , Miller Kevin J. 
Published: May 2023

AbstractQuantitative models of behavior are a fundamental tool in cognitive science. Typically, models are hand-crafted to implement specific cognitive mechanisms. Such “classic” models are interpretable by design, but may provide poor fit to experimental data. Artificial neural networks (ANNs), on the contrary, can fit arbitrary datasets at the cost of opaque mechanisms. Here, we adopt a hybrid approach, combining the predictive power of ANNs with the interpretability of classic models. We apply this approach to Reinforcement Learning (RL), beginning with classic RL models and replacing their components one-by-one with ANNs. We find that hybrid models can provide similar fit to fully-general ANNs, while retaining the interpretability of classic cognitive models: They reveal reward-based learning mechanisms in humans that are strikingly similar to classic RL. They also reveal mechanisms not contained in classic models, including separate rewardblind mechanisms, and the specific memory contents relevant to reward-based and reward-blind mechanisms.
Genetic landscape of idiopathic pulmonary fibrosis: A systematic review, meta-analysis and epidemiological evidence of case-control studies
Authors: Singh Pooja , Guin Debleena , Pattnaik Bijay , Kukreti Ritushree 
Published: May 2023

AbstractBackgroundIdiopathic pulmonary fibrosis (IPF) is a fibrotic lung disorder of unknown cause, affecting about three million people worldwide. Being a multifactorial disease, complex genetic and environmental factors contribute to its susceptibility. Therefore, we conducted a two-staged systematic literature search and meta-analyses of published genetic association studies on IPF.MethodsThe first search was performed using PubMed and Web of Science, retrieving a total of 5642 articles, of which 57 publications were eligible for inclusion in the first stage. The Second search was performed using PubMed, Web of Science and Scopus for all genetic variants, identified from the first search, with 2 or more studies. Thus, six variants [rs35705950 (MUC5B), rs2736100 (TERT), rs2609255 (FAM13A), rs2076295 (DSP), rs12610495 (DPP9) and rs1800470 (TGF-β1)] from this search qualified for meta-analyses. Additionally, the epidemiological credibility of these six variants was evaluated using the Venice criteria.ResultsIn this systematic review, 291 polymorphisms were found to be associated with IPF susceptibility. Meta-analyses findings revealed significant (p < 0.05) risk association of rs35705950 [T vs C; OR = 3.85(3.24-4.47)], rs2609255 [G vs T; OR = 1.37(1.27-1.47)], rs2076295 [G vs T; OR = 1.31(1.00-1.63)], rs12610495 [G vs A; OR = 1.29(1.21-1.37)] and rs1800470 [T vs C; OR = 1.08(0.82-1.34)] and protective association of rs2736100 [C vs A; OR = 0.70(0.61-0.79)] with IPF susceptibility. Cumulative epidemiological evidence was graded as strong for rs35705950, moderate for rs2736100, rs2609255 and rs12610495, and weak for rs2076295 and rs1800470.ConclusionsOur findings present the most prominent IPF-associated genetic risk variants involved in alveolar epithelial injuries (MUC5B, TERT, FAM13A, DSP, DPP9) and epithelial-mesenchymal transition (TGF-β1), providing genetic and biological insights into IPF pathogenesis.