bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defective linear and circular RNAs biogenesis in Huntington’s disease: CAG repeat expansion hijacks neuronal splicing
Authors: Ayyildiz Dilara , Monziani Alan , Tripathi Takshashila , Döring Jessica , Bergonzoni Guendalina , Kerschbamer Emanuela , Di Leva Francesca , Pennati Elia , Donini Luisa , Kovalenko Marina , Zasso Jacopo , Conti Luciano , Wheeler Vanessa C. , Dieterich Christoph , Piazza Silvano , Dassi Erik , Biagioli Marta 
Published: December 2021

ABSTRACTAlternative splicing (AS) appears to be altered in Huntington’s disease (HD), but its significance for early, pre-symptomatic disease stages has not been inspected.Here, taking advantage ofHttCAG knock-in mousein vitroandin vivomodels, we demonstrate a strong correlation betweenHttCAG repeat length and increased aberrant linear AS, specifically affecting neural progenitors and,in vivo,the striatum prior to overt behavioral phenotypes stages. Remarkably, expandedHttCAG repeats reflect on a previously neglected, global impairment of back-splicing, leading to decreased circular RNAs production in neural progenitors.Though the mechanisms of this dysregulation remain uncertain, our study unveils network of transcriptionally altered micro-RNAs and RNA-binding proteins (CELF, hnRNPS, PTBP, SRSF) which, in turn, might influence the AS machinery, primarily in neural cells.We suggest that this unbalanced expression of linear and circular RNAs might result in altered neural fitness, contributing to HD striatal vulnerability.
Along the Bos Taurus genome, uncover candidate Imprinting Control Regions
Authors: Wyss Phillip , Song Carol , Bina Minou 
Published: December 2021

ABSTRACTIn mammals, Imprinting Control Regions (ICRs) regulate a subset of genes in a parent-of-origin-specific manner. In both human and mouse, previous studies identified a set of CpG-rich motifs that occurred as clusters in ICRs and germline Differentially Methylated Regions (gDMRs). These motifs consist of the ZFP57 binding site (ZFBS) overlapping a subset of MLL binding units known as MLL morphemes. Furthermore, by creating plots for displaying the density of these overlaps, it became possible to locate known and candidate ICRs in mouse and human genomic DNA. Since genomic imprinting impacts many developmental and key physiological processes, we performed genome-wide analyses to create plots displaying the density of the CpG-rich motifs (ZFBS-morph overlaps) along Bos Taurus chromosomal DNA. We tailored our datasets so that they could be displayed on the UCSC genome browser (the build bosTau8). On the genome browser, we could view the ZFP57 binding sites, the ZFBS-morph overlaps, and peaks in the density-plots in the context of cattle RefSeq Genes, Non-Cow RefSeq Genes, CpG islands, and Single nucleotide polymorphisms (SNPs). Our datasets revealed the correspondence of peaks in plots to known and deduced ICRs in Bos Taurus genomic DNA. We illustrate that by uploading our datasets onto the UCSC genome browser, we could discover candidate ICRs in cattle DNA. In enlarged views, we could pinpoint the genes in the vicinity of candidate ICRs and thus discover potential imprinted genes.
The Functional Logic of Odor Information Processing in the Drosophila Antennal Lobe
Authors: Lazar Aurel A. , Liu Tingkai , Yeh Chung-Heng 
Published: December 2021

AbstractThe early olfactory system of the fruit fly, while sensing a complex odorant landscape, encodes the odorant object identity (semantic information) and the odorant concentration waveform (syntactic information) into a combinatorial neural code. Single-channel physiology recordings at the output of the Antenna Lobe (AL) exhibit concentration-invariance and contrast-boosting properties, indicating a decoupling of the odorant object identity from the concentration waveform in steady-state while responding strongly to odorant concentration onset and offset in transient states.Through exhaustive computational explorations of the AL circuits, we show that the steady-state and transient response features of the AL are, respectively, due to presynaptic and postsynaptic Local Neurons (LNs). Theoretical analysis reveals that the LN pathways can be modeled as parallel differential Divisive Normalization Processors (DNPs). Differential DNPs robustly extract odorant identity (semantic information) and ON/OFF odorant event-timing (syntactic information), thereby providing for the AL the functional logic of ON-OFF odorant identity recovery.
Structural Evolution of the Ancient Enzyme, Dissimilatory Sulfite Reductase
Authors: Colman Daniel R. , Labesse Gilles , Swapna G.V.T. , Stefanakis Johanna , Montelione Gaetano T. , Boyd Eric S. , Royer Catherine A. 
Published: December 2021

AbstractDissimilatory sulfite reductase is an ancient enzyme that has linked the global sulfur and carbon biogeochemical cycles since at least 3.47 Gya. While much has been learned about the phylogenetic distribution and diversity of DsrAB across environmental gradients, far less is known about the structural changes that occurred to maintain DsrAB function as the enzyme accompanied diversification of sulfate/sulfite reducing organisms (SRO) into new environments. Analyses of available crystal structures of DsrAB from Archaeoglobus fulgidus and Desulfovibrio vulgaris, representing early and late evolving lineages, respectively, show that certain features of DsrAB are structurally conserved, including active siro-heme binding motifs. Whether such structural features are conserved among DsrAB recovered from varied environments, including hot spring environments that host representatives of the earliest evolving SRO lineage (e.g., MV2-Eury), is not known. To begin to overcome these gaps in our understanding of the evolution of DsrAB, structural models from MV2.Eury were generated and evolutionary sequence co-variance analyses were conducted on a curated DsrAB database. Phylogenetically diverse DsrAB harbor many conserved functional residues including those that ligate active siro-heme(s). However, evolutionary co-variance analysis of monomeric DsrAB subunits revealed several False Positive Evolutionary Couplings (FPEC) that correspond to residues that have co-evolved despite being too spatially distant in the monomeric structure to allow for direct contact. One set of FPECs corresponds to residues that form a structural path between the two active siro-heme moieties across the interface between heterodimers, suggesting the potential for allostery or electron transfer within the enzyme complex. Other FPECs correspond to structural loops and gaps that may have been selected to stabilize enzyme function in different environments. These structural bioinformatics results suggest that DsrAB has maintained allosteric communication pathways between subunits as SRO diversified into new environments. The observations outlined here provide a framework for future biochemical and structural analyses of DsrAB to examine potential allosteric control of this enzyme.
Techniques for visualizing fibroblast-vessel interactions in the developing and adult CNS
Authors: Jones Hannah E. , Abrams Kelsey A. , Siegenthaler Julie 
Published: December 2021

AbstractFibroblasts are found associated with blood vessels in various locations across the CNS: in the meninges, the choroid plexus, and in the parenchyma within perivascular spaces. CNS fibroblasts have been characterized using transcriptional profiling and aCol1a1-GFPmouse line used to identify CNS fibroblastsin vivo. However, current methods for visualizing CNS fibroblasts are lacking and, in particular, prevent adequate assessment of fibroblast-vessel interactions. Here, we describe methods for whole mount visualization of meningeal and choroid plexus fibroblasts, and optical tissue clearing methods for visualization of parenchymal vessel-associated fibroblasts. Importantly, these techniques can be combined with immunohistochemistry methods for labeling different cell types in the meninges and blood vasculature as well as EdU-based cell proliferation assays. These methods are ideal for visualization of vessel-fibroblast interactions in these CNS structures and provide significant improvement over traditional sectioning and staining methods. We expect these methods will advance studies of CNS fibroblast development and functions in homeostasis, injury, and disease.
TheMybfamily genes in the rice pathogenMagnaporthe oryzae: Finding and deleting more family members involved in pathogenicity
Authors: Li Ya , Zheng Xiuxia , Pei Mengtian , Chen Mengting , Zhang Shengnan , Liang Chenyu , Gao Luyao , Huang Pin , Olsson Stefan 
Published: December 2021

ABSTRACTProteins with DNA binding Myb domains have been suggested in regulating development and stress responses.Magnaporthe oryzaeis considered the most destructive pathogen of rice. We screened the genome for genes with Myb domains encoding since these can be needed for pathogenesis. We foundMyb1-19. Only MoMyb1 was previously shown to be involved in pathogenesis. We succeeded in deleting 12 of the other 18 genes. MoMyb2 deletion affected mainly growth, while MoMyb13 or MoMyb15 deletions gave additional defects in conidiation and plant infection. However, RT-qPCR showed that none of the 19 Myb genes are negligibly expressed. Instead, they have different expression profiles hours post-infection when infecting rice plants. Considering this, the unchanged infection phenotype for 9 gene deletions surprised us, and we extended the analysis to expression co-regulation of all 19 Myb proteins and found 5 co-regulated groups of predicted Myb-domain proteins. MoMyb13 or MoMyb15 are discussed and motivated as candidates for further, more detailed studies with aims also outside of plant pathology. Referring to what is found in other eukaryotes, we finally discuss possible redundancy or compensatory regulations for many of the other Myb genes hiding or compensating for the effect of many complete deletions.IMPORTANCEMagnaporthe oryzaeis considered the most important rice pathogen limiting rice production. Our study attempts to find all genes encoding a DNA-binding gene family called Myb, and we found 19, many of which have not been studied before. The Myb gene family is suspected to regulate stress responses the pathogen needs to overcome plant defenses. Inhibiting or disturbing these genes, if they are indeed regulatory, can open new ways of controlling the pathogen and learning more about its physiology and ecology.
Chromatin state transition underlies the temporal changes in gene expression during cardiomyocyte maturation
Authors: Lin Chia-Yeh , Chang Yao-Ming , Tseng Hsin-Yi , Shih Yen-Ling , Yeh Hsiao-Hui , Liao You-Rou , Hsu Chia-Ling , Chen Chien-Chang , Yan Yu-Ting , Kao Cheng-Fu 
Published: December 2021

AbstractCongenital heart disease (CHD) is often rooted in gene expression anomalies that occur during heart development. As cells commit to a specific lineage, chromatin dynamics and developmental plasticity generally become more limited. However, it remains unclear how differentiated cardiomyocytes (CMs) undergo morphological and functional adaptations to the postnatal environment during their maturation. In this work, we sought to identify the regulatory mechanisms controlling postnatal cardiac gene networks. A time-series transcriptomic analysis of postnatal hearts revealed an integrated, time-ordered transcriptional network that regulates CM maturation. Remarkably, depletion of histone H2B ubiquitin ligase RNF20 after formation of the four-chamber heart disrupted these highly coordinated gene networks. Its ablation also caused early-onset cardiomyopathy, a phenotype reminiscent of CHD. Furthermore, we found that dynamic RNF20-mediated modulation of chromatin accessibility during CM maturation was necessary for the operative binding of cardiac transcription factors known to drive transcriptional gene networks. Together, our results reveal how epigenetic-mediated chromatin state transitions modulate time-ordered gene expression during CM maturation.
Crystal structure of chloroplast fructose-1,6-bisphosphate aldolase from the green algaChlamydomonas reinhardtii
Authors: Le Moigne Théo , Sarti Edoardo , Nourisson Antonin , Carbone Alessandra , Lemaire Stéphane D. , Henri Julien 
Published: December 2021

AbstractThe Calvin-Benson cycle fixes carbon dioxide into organic triosephosphates through the collective action of eleven conserved enzymes. Regeneration of ribulose-1,5-bisphosphate, the substrate of Rubisco-mediated carboxylation, requires two lyase reactions catalyzed by fructose-1,6-bisphosphate aldolase (FBA). While cytoplasmic FBA has been extensively studied in non-photosynthetic organisms, functional and structural details are limited for chloroplast FBA encoded by oxygenic phototrophs. Here we determined the crystal structure of plastidial FBA from the unicellular green algaChlamydomonas reinhardtii(Cr). We confirm that CrFBA folds as a TIM barrel, describe its catalytic pocket and homo-tetrameric state. Multiple sequence profiling classified the photosynthetic paralogs of FBA in a distinct group from non-photosynthetic paralogs. We mapped the sites of thiol- and phospho-based post-translational modifications known from photosynthetic organisms and predict their effects on enzyme catalysis.
Size-dependent secondary nucleation and amplification of α-synuclein amyloid fibrils
Authors: Sakunthala Arunima , Datta Debalina , Navalkar Ambuja , Gadhe Laxmikant , Kadu Pradeep , Patel Komal , Mehra Surabhi , Kumar Rakesh , Chatterjee Debdeep , Sengupta Kundan , Padinhateeri Ranjith , Maji Samir K. 
Published: December 2021

AbstractThe size of the amyloid seeds is known to modulate their autocatalytic amplification and cellular toxicity. However, the seed size-dependent secondary nucleation mechanism, toxicity, and disease-associated biological processes mediated by α-synuclein (α-Syn) fibrils are largely unknown. Using the cellular model andin vitroreconstitution, we showed that the size of α-Syn fibril seeds not only dictates its cellular internalization and associated cell death; but also the distinct mechanisms of fibril amplification pathways involved in the pathological conformational change of α-Syn. Specifically, small-sized fibril seeds showed elongation possibly through monomer addition at the fibril termini; whereas longer fibrils template the fibril amplification by surface-mediated nucleation as demonstrated by super-resolution microscopy. The distinct mechanism of fibril amplification, and cellular uptake along with toxicity suggest that breakage of fibrils into different sizes of seeds determine the underlying pathological outcome of synucleinopathies.
In vitro cytokine expression analysis by droplet microfluidics
Authors: Wong Ada Hang-Heng , Akincilar Semih Can , Chua Joelle , Chanthira Morgan Dhakshayini d/o K. , Hei Dorcas , Tergaonkar Vinay 
Published: December 2021

AbstractDroplet microfluidics provides a miniaturized platform to conduct biological assays. We previously developed a droplet microfluidic chip assay for screening cancer cells against chemical drugs and chimeric antigen receptor T (CAR-T) cells, respectively. In this study, we investigated chip application on a cytokine expression assay using MCF7 breast cancer reporter cells engineered by fusing green fluorescent protein (GFP) to the C-terminus of endogenous interleukin-6 (IL6) gene. Combined tumor necrosis factor α (TNFα) treatment and serum-free medium starvation stimulated IL6-GFP expression and enhanced GFP fluorescence. Our data showed that on-chip assay recapitulates the cellular response in vitro, although absolute quantification of IL6 induction could not be accomplished. The demonstration of multi-timepoint IL6 expression analysis paves the way for our future study on tumor response to immune attack via cytokine signaling.
Unsigned temporal difference errors in cortical L5 dendrites during learning
Authors: Schoenfeld Gwendolin , Kollmorgen Sepp , Tsai Matthias C. , Lewis Christopher , Han Shuting , Bethge Philipp , Reuss Anna Maria , Aguzzi Adriano , Senn Walter , Mante Valerio , Helmchen Fritjof 
Published: December 2021

SummaryLearning goal-directed behavior requires association of pertinent sensory stimuli with behaviorally relevant outcomes. In the mammalian neocortex, dendrites of pyramidal neurons are suitable association sites1–3but how their activities adapt during learning remains elusive. Here, we track calcium signals in apical dendrites of layer 5 (L5) pyramidal neurons in mouse barrel cortex during texture discrimination learning4. We observe diverse task-related responses, either localized to branches or widespread throughout the apical tuft. However, even in expert mice, the tufts’ capability to discriminate go/no-go stimuli remains poor. Yet, we identify two prevailing response types in dendritic branches: 1) responses to unexpected outcome (reward) in naïve mice that decrease with growing task proficiency, and 2) responses associated with salient sensory stimuli, especially the outcome-predicting texture touch, that strengthen upon learning. We demonstrate that these response types match distinct unsigned components of the temporal difference error5by replicating our results with a reinforcement learning model. Moreover, optogenetic apical inhibition of L5 neurons during the outcome time window prevents naïve animals from learning the task, consistent with the effect of equivalent model perturbation. Our findings suggest that salience signals in L5 apical dendrites facilitate the recruitment of task-relevant neurons via dendritic gain modulation.
Prescriptions For The Control Of A Clonal Invasive Species Using Demographic Models
Authors: Arroyo-Cosultchi Gabriel , Golubov Jordan , Solórzano Jonathan V. , Mandujano Maria C. 
Published: December 2021

AbstractUntil recently, little focus has been given to determine the population dynamics of invasive species and evaluate their genetic variation. Consequently, not much is known of what drives clonal invasive species and their demography. Here we describe the population dynamics of Kalanchoe delagoensis (Crassulaceae), considered invasive to several countries. We quantified the demography of a population in central Mexico using integral projection models (IPM) in a population that reproduced asexually exclusively through plantlets. The effect of clonal recruitment on λ was evaluated by changing plantlet survival and simulating management scenarios that used previous data of watering and seven experimental herbicide treatments. The finite rate of population increase indicated that this Kalanchoe delagoensis population is growing (above one) with significant potential increases that correlated with water availability. The IPM showed that plantlet survival and recruitment were the most critical steps in the cycle for the population and simulations of different management scenarios showed that reducing plantlet survival significantly decreased λ only in two out of the seven herbicides used.
Class I DISARM provides anti-phage and anti-conjugation activity by unmethylated DNA recognition
Authors: Aparicio-Maldonado Cristian , Ofir Gal , Salini Andrea , Sorek Rotem , Nobrega Franklin L. , Brouns Stan J.J. 
Published: December 2021

ABSTRACTBacteriophages impose a strong evolutionary pressure on microbes for the development of mechanisms of survival. Multiple new mechanisms of innate defense have been described recently, with the molecular mechanism of most of them remaining uncharacterized. Here, we show that a Class 1 DISARM (defense island system associated with restriction-modification) system from Serratia sp. provides broad protection from double-stranded DNA phages, and drives a population of single-stranded phages to extinction. We identify that protection is not abolished by deletion of individual DISARM genes and that the absence of methylase genes drmMI and drmMII does not result in autoimmunity. In addition to antiphage activity we also observe that DISARM limits conjugation, and this activity is linked to the number of methylase cognate sites in the plasmid. Overall, we show that Class 1 DISARM provides robust anti-phage and anti-plasmid protection mediated primarily by drmA and drmB, which provide resistance to invading nucleic acids using a mechanism enhanced by the recognition of unmethylated cognate sites of the two methylases drmMI and drmMII.
Directed inter-domain motions enable the IsdH Staphylococcus aureus receptor to rapidly extract heme from human hemoglobin
Authors: Clayton Joseph , Ellis-Guardiola Kat , Mahoney Brendan , Soule Jess , Clubb Robert T. , Wereszczynski Jeff 
Published: December 2021

ABSTRACTPathogenic Staphylococcus aureus actively acquires iron from human hemoglobin (Hb) using the IsdH surface receptor. Heme extraction is mediated by a tridomain unit within the receptor that contains its second (N2) and third (N3) NEAT domains joined by a helical linker domain. Extraction occurs within a dynamic complex, in which receptors engage each globin chain; the N2 domain tightly binds to Hb, while substantial inter-domain motions within the receptor enable its N3 domain to transiently distort the globin’s heme pocket. Using molecular simulations, Markov modeling, and quantitative measurements of heme transfer kinetics, we show that directed inter-domain motions within the receptor play a critical role in the extraction process. The directionality of N3 domain motion and the rate of heme extraction is controlled by amino acids within a short, flexible inter-domain tether that connects the N2 and linker domains. In the wild-type receptor directed motions originating from the tether enable the N3 domain to populate configurations capable of distorting Hb’s pocket, whereas mutant receptors containing altered tethers are less able to adopt these conformers and capture heme slowly via indirect processes in which Hb first releases heme into the solvent. Thus, our results show inter-domain motions within the IsdH receptor play a critical role in its ability to extract heme from Hb and highlight the importance of directed motions by the short, unstructured, amino acid sequence connecting the domains in controlling the directionality and magnitude of these functionally important motions.