bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex without crossing over in the yeastSaccharomycodes ludwigii
Authors: Papaioannou Ioannis A. , Dutreux Fabien , Peltier France A. , Maekawa Hiromi , Delhomme Nicolas , Bardhan Amit , Friedrich Anne , Schacherer Joseph , Knop Michael 
Published: April 2021

AbstractMeiotic recombination is a ubiquitous function of sexual reproduction throughout eukaryotes. Here we report that recombination is extremely suppressed during meiosis in the yeast speciesSaccharomycodes ludwigii. DNA double-strand break formation, processing and repair are required for normal meiosis but do not lead to crossing over. Although the species has retained an intact meiotic gene repertoire, genetic and population analyses suggest the exceptionally rare occurrence of meiotic crossovers. We propose thatSd. ludwigiihas followed a unique evolutionary trajectory that possibly derives fitness benefits from the combination of frequent fertilization within the meiotic tetrad with the absence of meiotic recombination.
Distorted tonotopy severely degrades neural representations of natural speech in noise following acoustic trauma
Authors: Parida Satyabrata , Heinz Michael G. 
Published: April 2021

SUMMARYListeners with sensorineural hearing loss (SNHL) struggle to understand speech, especially in noise, despite audibility compensation. These real-world suprathreshold deficits are hypothesized to arise from degraded frequency tuning and reduced temporal-coding precision; however, peripheral neurophysiological studies testing these hypotheses have been largely limited to in-quiet artificial vowels. Here, we measured single auditory-nerve-fiber responses to a natural speech sentence in noise from anesthetized chinchillas with normal hearing (NH) or noise-induced hearing loss (NIHL). Our results demonstrate that temporal precision was not degraded, and broader tuning was not the major factor affecting peripheral coding of natural speech in noise. Rather, the loss of cochlear tonotopy, a hallmark of normal hearing, had the most significant effects (both on vowels and consonants). Because distorted tonotopy varies in degree across etiologies (e.g., noise exposure, age), these results have important implications for understanding and treating individual differences in speech perception for people suffering from SNHL.
TAOK2 is an ER-localized Kinase that Catalyzes the Dynamic Tethering of ER to Microtubules
Authors: Nourbakhsh Kimya , Ferreccio Amy A. , Bernard Matthew J. , Yadav Smita 
Published: April 2021

SummaryThe endoplasmic reticulum (ER) depends on extensive association with the microtubule cytoskeleton for its structure, function and mitotic inheritance. The identity of molecular tethers that mediate ER-microtubule coupling, and mechanisms through which dynamic tethering is regulated are poorly understood. Here, we identify, Thousand And One amino acid Kinase 2 (TAOK2) as a pleiotropic protein kinase that mediates tethering of ER to microtubules. We show that TAOK2 is a unique multipass membrane spanning serine/threonine kinase localized in distinct ER domains via four transmembrane and amphipathic helices. Usingin vitroand cellular assays, we find that TAOK2 directly binds microtubules with high affinity. We define the minimal TAOK2 determinants that induce ER-microtubule tethering, and delineate the mechanism for its autoregulation. While ER membrane dynamics are increased in TAOK2 knockout cells, the movement of ER along growing microtubule plus-ends is disrupted. We show that ER-microtubule tethering is tightly regulated by catalytic activity of TAOK2 in both interphase and mitotic cells, perturbation of which leads to profound defects in ER morphology and cell division. Our study identifies TAOK2 as an ER-microtubule tether, and reveals a kinase-regulated mechanism for control of ER dynamics critical for cell growth and division.
EEG Spectral Feature Modulations Associated with Fatigue in Robot-Mediated Upper Limb Gross Motor and Fine Motor Interactions
Authors: Dissanayake Udeshika Chaturangee , Steuber Volker , Amirabdollahian Farshid 
Published: April 2021

AbstractThis paper investigates the EEG spectral feature modulations associated with fatigue induced by robot-mediated upper limb gross motor and fine motor interactions. Twenty healthy participants were randomly assigned to either perform a gross motor interaction with HapticMASTER or a fine motor interaction with SCRIPT passive orthosis for 20 minutes or until volitional fatigue. EEG relative and ratio band power measures were estimated from the data recorded before and after the interactions. Paired-samplest-tests found a significant increase in relative alpha band power on FC3, C3, P3 electrodes, and (θ+α)/βandα/βon C3 electrode following the gross motor interaction. Conversely, relative delta band power on C3 significantly decreased. A significant increase in relative alpha band power on FP1, C3 electrodes and relative theta band power on C4 electrode were found following the fine motor interaction whereas relative delta band power on FP1 electrode significantly decreased. Most participants reported an increase in their physical fatigue level following the gross movements and an increase in their mental fatigue level following the fine movements. Findings affirm that changes to localised brain activity patterns are an indication of fatigue developed from the robot-mediated interactions. It can be concluded that regional differences in the prominent EEG spectral features are most likely due to the differences in the nature of the task (fine/gross motor and distal/proximal upper limb) that may have differently altered an individual’s physical and mental fatigue level. The findings could potentially be utilised to monitor and moderate fatigue during robot-mediated post-stroke therapies.
Optoception: perception of optogenetic brain stimulation
Authors: Luis-Islas Jorge , Luna Monica , Floran Benjamin , Gutierrez Ranier 
Published: April 2021

SummaryHow do animals experience brain manipulations? Optogenetics has allowed us to manipulate selectively and interrogate neural circuits underlying brain function in health and disease. However, it is currently unknown whether mice could perceive arbitrary optogenetic stimulation in addition to their evoked physiological functions. To address this issue, mice were trained to report an optogenetic stimulation as a cue to obtain rewards and avoid punishments. It was found that mice could perceive optogenetic manipulations regardless of the brain area modulated, their rewarding effects, or the stimulation of glutamatergic, GABAergic, and dopaminergic cell types. We named this phenomenon optoception. Using optoception, mice could learn to execute two different sets of instructions based on the laser frequency. Importantly, optoception can occur either activating or silencing a single cell type. Our findings revealed that mice’s brains are capable of “monitoring” their self-activity, albeit indirectly, perhaps via interoception or as a discriminative stimulus, opening a new way to introduce information to the brain and control brain-computer interfaces.
Undersampling and the inference of coevolution in proteins
Authors: Kleeorin Yaakov , Russ William P. , Rivoire Olivier , Ranganathan Rama 
Published: April 2021

AbstractProtein structure, function, and evolution depend on local and collective epistatic interactions between amino acids. A powerful approach to defining these interactions is to construct models of couplings between amino acids that reproduce the empirical statistics (frequencies and correlations) observed in sequences comprising a protein family. The top couplings are then interpreted. Here, we show that as currently implemented, this inference is always biased, a problem that fundamentally arises from the distinct scales at which epistasis occurs in proteins in the context of limited sampling. We show that these issues explain the ability of current approaches to predict tertiary contacts between amino acids and the inability to obviously expose larger networks of functionally-relevant, collectively evolving residues called sectors. This work provides a necessary foundation for more deeply understanding and improving evolution-based models of proteins.
Abundance and Microbial Diversity from Surface to Deep Water Layers Over the Rio Grande Rise, South Atlantic
Authors: Ferreira Juliana Correa Neiva , Bergo Natascha M. , Tura Pedro M. , Chuqui Mateus Gustavo , Brandini Frederico P. , Jovane Luigi , Pellizari Vivian H. 
Published: April 2021

AbstractMarine microbes control the flux of matter and energy essential for life in the oceans. Until now, the distribution and diversity of planktonic microorganisms above Fe-Mn crusts has received relatively little attention. Future mining\dredging of these minerals is predicted to affect microbial diversity and functioning in the deep sea. Here, we studied the ecology of planktonic microbes among pelagic environments of an Fe-Mn deposit region, at Rio Grande Rise, Southwestern Atlantic Ocean. We investigated microbial community composition using high-throughput sequencing of 16S rRNA genes and their abundance estimated by flow cytometry. Our results showed that the majority of picoplanktonic was found in epi- and mesopelagic waters, corresponding to the Tropical Water and South Atlantic Central Water. Bacterial and archaeal groups related to phototrophy, heterotrophy and chemosynthesis, such asSynechococcales, Sar11 (Proteobacteria) and Nitrosopumilales (Thaumarchaeota) were the main representatives of the pelagic microbial community. Additionally, we detected abundant assemblages involved in biodegradation of marine organic matter and iron oxidation at deep waters, i.e.,PseudoalteromonasandAlteromonas. No differences were observed in microbial community alpha diversity. However, we detected differences in community structure between water masses, suggesting that changes in an environmental setting (i.e. nutrient availability or circulation) play a significant role in structuring the pelagic zones, also affecting the meso- and bathypelagic microbiome.HighlightsRio Grande Rise pelagic microbiomePicoplankton carbon biomass partitioning through pelagic zonesUnique SAR11 Clade I oligotype in the shallowest Tropical WaterHigher number of shared oligotypes between deepest water massesNitrogen, carbon and sulfur may be important contributors for the pelagic microbiome
MG53 slows neuromuscular junction loss and prolongs survival in ALS
Authors: Yi Jianxun , Li Ang , Li Xuejun , Park Ki Ho , Zhou Xinyu , Yi Frank , Xiao Yajuan , Yoon Dosuk , Tan Tao , Ostrow Lyle W. , Ma Jianjie , Zhou Jingsong 
Published: April 2021

AbstractRespiratory failure from progressive respiratory muscle weakness is the most common cause of death in amyotrophic lateral sclerosis (ALS). Defects in neuromuscular junctions (NMJs) and progressive NMJ loss occur at early stages, thus stabilizing and preserving NMJs represents a potential therapeutic strategy to slow ALS disease progression. Here we demonstrate that NMJ damage is repaired by MG53, an intrinsic muscle protein involved in plasma membrane repair. Compromised diaphragm muscle membrane repair and NMJ integrity are early pathological findings in ALS. Diaphragm muscles from ALS mouse models show increased susceptibility to injury and intracellular MG53 aggregation, which is also a hallmark of human muscle samples from ALS patients. We show that systemic administration of recombinant human MG53 protein (rhMG53) in ALS mice protects against injury to diaphragm muscle, preserves NMJ integrity, and slows ALS disease progression. As MG53 is present in circulation in rodents and humans under physiological conditions, our findings provide proof-of-concept data supporting MG53 as a potentially safe and effective therapy to mitigate ALS progression.
Fine carbohydrate structure governs the structure and function of human gut microbiota independently of variation in glycosyl residue composition
Authors: Marcia Arianna D. Romero , Yao Tianming , Chen Ming-Hsu , Oles Renee E. , Lindemann Stephen R. 
Published: April 2021

AbstractIncreased dietary fiber consumption has been shown to increase human gut microbial diversity, but the mechanisms driving this effect remain unclear. One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation. However, as naturally derived fibers vary in both sugar composition and linkage structure, it is challenging to separate out the impact of each of these variables. We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition. To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements,in vitrowith fecal inocula from each of three individuals. We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing. We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures. However, specific operational taxonomic units responded similarly in growth responses across individuals’ microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others. Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.ImportancePrevious studies have reported how physical and chemical structures of carbohydrates influence the gut microbiota, however, variability across dietary fibers in monosaccharide composition and linkage structure obscures the relationship between fine polysaccharide linkage structure and microbial fitness. Revealing connections between subtle differences in glucan structure and microbial composition and metabolic responses, this study suggests much greater attention to substrate structure in the design of experiments to test fiber-microbiome responsesin vitroandin vivo. Further, it underscores that, although microbiome responses to distinct fibers are individual and vary among specific glucans, similar carbohydrate structure-microbe relationships occur across individual donor communities. Together, these data may help explain why some individuals may respond (while others do not) to fiber treatments in human feeding trials and support the long-term goal of rational inclusion of specific fibers in dietary patterns to modulate the gut microbiome in support of health.
Torsions-Driven Root Helical Growth, Waving And Skewing InArabidopsis
Authors: Zhou Ke 
Published: April 2021

AbstractHelical growth broadly exists in immobile plants to support their limited movement, andArabidopsisseedling root exhibiting natural left-handedness helical growth is considered as a simplified model for investigating this interesting behavior. Efforts have been made for understanding the mechanism of root helical growth and consequent root waving and skewing on tilted and impenetrable surface, and several models have been established. Here, previous reports are reviewed and a straightforward torsions-driven mechanism has been emphasized, and additional experiments have been performed to fill up the gaps of this theory in our study.This study implies that, torsions originating from handedness of both cortical microtubules and cellulose microfibrils play central role in root handed helical growth. Different from torsions directly provided by handed assembled cortical microtubules, torsions originating from right-handed assembled cellulose microfibrils are relaxed by their cross-linking with pectin within cell wall, but only exhibited when their cross-linking is interrupted due to damaged cell wall integrity. To topologically relax these torsions, supercoils of cortical microtubules and/or cellulose microfibrils exhibiting as oblique alignments are formed in root cells, which alter the orientation of root cell files and generate handed helical roots. Working together with gravitropic response, relaxation of torsions originating from helical roots drives roots to elongate with handedness, which therefore produces waved and skewed roots on tilted and impenetrable surface.
Augmentation of CD47-SIRPα signaling protects cones in genetic models of retinal degeneration
Authors: Wang Sean K. , Xue Yunlu , Cepko Constance L. 
Published: April 2021

ABSTRACTInherited retinal diseases such as retinitis pigmentosa (RP) can be caused by thousands of different mutations, a small number of which have been successfully treated with gene replacement. However, this approach has yet to scale and may be infeasible in many cases, highlighting the need for interventions that could benefit more patients. Here, we found that microglial phagocytosis is upregulated during cone degeneration in RP, suggesting that expression of “don’t eat me” signals such as CD47 might confer protection to cones. To test this, we delivered an adeno-associated viral (AAV) vector expressing CD47 on cones, which promoted cone survival in three mouse models of RP and preserved visual function. Cone rescue with CD47 required signal regulatory protein alpha (SIRPα) but not microglia or thrombospondin-1 (TSP1), suggesting that CD47 interacts with SIRPα on non-microglial cells to alleviate degeneration. These findings establish augmentation of CD47-SIRPα signaling as a potential treatment strategy for RP and possibly other forms of neurodegeneration.
Altered synaptic connectivity and brain function in mice lacking microglial adapter protein Iba1
Authors: Lituma Pablo J. , Woo Evan , O’Hara Bruce F. , Castillo Pablo E. , Sibinga Nicholas E. S. , Nandi Sayan 
Published: April 2021

AbstractGrowing evidence indicates that microglia impact brain function by regulating synaptic pruning and formation, as well as synaptic transmission and plasticity. Iba1 (Ionized Ca+2-binding adapter protein 1), encoded by theAllograft inflammatory factor 1(Aif1) gene, is an actin-interacting protein in microglia. Although Iba1 has long been used as a cellular marker for microglia, its functional role remains unknown. Here, we used global Iba1-deficient (Aif1-/-) mice to characterize microglial activity, synaptic function and behavior. Microglial imaging in acute hippocampal slices and fixed tissues from juvenile mice revealed thatAif1-/-microglia display reductions in ATP-induced motility and ramification, respectively. Biochemical assays further demonstrated thatAif1-/-brain tissues exhibit an altered expression of microglial-enriched proteins associated with synaptic pruning. Consistent with these changes, juvenileAif1-/-mice displayed deficits in excitatory synapse number and synaptic transmission assessed by neuronal labeling and whole-cell patch-clamp recording in acute hippocampal slices. Unexpectedly, microglial synaptic engulfment capacity was diminished in juvenileAif1-/-mice. During early postnatal development when synapse formation is a predominant event in the hippocampus, excitatory synapse number was still reduced inAif1-/-mice. Together these findings support an overall role of Iba1 in excitatory synaptic growth in juvenile mice. Lastly, postnatal synaptic deficits persisted in the adulthood and correlated with significant behavioral changes in adultAif1-/-mice, which exhibited impairments in object recognition memory and social interaction. These results suggest that Iba1 critically contributes to microglial activity underlying essential neuro-glia developmental processes that may deeply influence behavior.SignificanceAbnormal microglia-neuron interaction is increasingly implicated in neurodevelopmental and neuropsychiatric conditions such as autism spectrum disorders and schizophrenia, as well as in neurodegenerative disorders such as Alzheimer’s disease. This study demonstrates that deletion of the microglia-specific protein Iba1, which has long been utilized as a selective microglial marker but whose role has remained unidentified, results in microglial structural and functional impairments that significantly impact synaptic development and behavior. These findings not only highlight the importance of microglia in brain function but may also suggest that modifying microglial function could provide a therapeutic strategy for treatment of neurodevelopmental, neuropsychiatric and neurodegenerative disorders.
MSH2-MSH3 promotes DNA end resection during HR and blocks TMEJ through interaction with SMARCAD1 and EXO1
Authors: Oh Jung-Min , Kang Yujin , Park Jumi , Sung Yubin , Kim Dayoung , Seo Yuri , Lee Eun A , Ra Jae Sun , Amarsanaa Enkhzul , Park Young-Un , Kim Hongtae , Schärer Orlando , Cho Seung Woo , Lee Changwook , Takata Kei-ichi , Lee Ja Yil , Myung Kyungjae 
Published: April 2021

SUMMARYDNA double strand break (DSB) repair by Homologous recombination (HR) is initiated by the end resection, a process during which 3’ ssDNA overhangs are generated by the nucleolytic degradation. The extent of DNA end resection determines the choice of the DSB repair pathway. The role of several proteins including nucleases for end resection has been studied in detail. However, it is still unclear how the initial, nicked DNA generated by MRE11-RAD50-NBS1 is recognized and how subsequent proteins including EXO1 are recruited to DSB sites to facilitate extensive end resection. We found that the MutSβ (MSH2-MSH3) mismatch repair (MMR) complex is recruited to DSB sites by recognizing the initial nicked DNA at DSB sites through the interaction with the chromatin remodeling protein SMARCAD1. MSH2-MSH3 at DSB sites helps to recruit EXO1 for long-range resection and enhances its enzymatic activity. MSH2-MSH3 furthermore inhibits the access of DNA polymerase θ (POLQ), which promotes polymerase theta-mediated end-joining (TMEJ) of DSB. Collectively, our data show a direct role for MSH2-MSH3 in the initial stages of DSB repair by promoting end resection and influencing DSB repair pathway by favoring HR over TMEJ. Our findings extend the importance of MMR in DSB repair beyond established role in rejecting the invasion of sequences not perfectly homologous to template DNA during late-stage HR.
Identification of the three zinc-binding sites on Tau protein
Authors: La Rocca Romain , Tsvetkov Philipp O. , Golovin Andrey V. , Allegro Diane , Barbier Pascale , Malesinski Soazig , Guerlesquin Françoise , Devred François 
Published: April 2021

AbstractTau protein has been extensively studied due to its key roles in microtubular cytoskeleton regulation and in the formation of aggregates found in some neurodegenerative diseases. Recently it has been shown that zinc is able to induce tau aggregation by interacting with several binding sites. However, the precise location of these sites and the molecular mechanism of zinc-induced aggregation remain unknown. Here we used Nuclear Magnetic Resonance (NMR) to identify zinc binding sites on hTau40 isoform. These experiments revealed three distinct zinc binding sites on tau, located in the N-terminal part (H14, H32, H94, and H121), the repeat region (H299, C322, H329 and H330) and the C-terminal part (H362, H374, H388 and H407). Further analysis enabled us to show that the C-terminal and the N-terminal sites are independent of each other. Using molecular simulations, we modeled the structure of each site in a complex with zinc. Given the clinical importance of zinc in tau aggregation, our findings pave the way for designing potential therapies for tauopathies.HighlightsZinc is known to induce tau aggregation in neurodegenerative diseasesZinc binding locations and mechanism are not yet clearUsing NMR we localized 3 zinc binding site on tauBy molecular simulations, we proposed a modeled structure of each siteOur findings pave the way for designing potential therapies for tauopathies