bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial intelligence reveals nuclear pore complexity
Authors: Mosalaganti Shyamal , Obarska-Kosinska Agnieszka , Siggel Marc , Turonova Beata , Zimmerli Christian E. , Buczak Katarzyna , Schmidt Florian H. , Margiotta Erica , Mackmull Marie-Therese , Hagen Wim , Hummer Gerhard , Beck Martin , Kosinski Jan 
Published: October 2021

AbstractNuclear pore complexes (NPCs) mediate nucleocytoplasmic transport. Their intricate 120 MDa architecture remains incompletely understood. Here, we report a near-complete structural model of the human NPC scaffold with explicit membrane and in multiple conformational states. We combined AI-based structure prediction with in situ and in cellulo cryo-electron tomography and integrative modeling. We show that linker Nups spatially organize the scaffold within and across subcomplexes to establish the higher-order structure. Microsecond-long molecular dynamics simulations suggest that the scaffold is not required to stabilize the inner and outer nuclear membrane fusion, but rather widens the central pore. Our work exemplifies how AI-based modeling can be integrated with in situ structural biology to understand subcellular architecture across spatial organization levels.One sentence summaryAn AI-based, dynamic model of the human nuclear pore complex reveals how the protein scaffold and the nuclear envelope are coupled inside cells.
Experience-induced remodeling of the hippocampal post-synaptic proteome and phosphoproteome
Authors: Heo Seok , Kang Taewook , Bygrave Alexei M. , Larsen Martin R. , Huganir Richard L. 
Published: October 2021

SummaryThe post synaptic density (PSD) of excitatory synapses contains a highly organized protein network with thousands of proteins and is key node in the regulation of synaptic plasticity. To gain new mechanistic insight into experience-induced changes in the PSD, we examined the global dynamics of the PSD proteome and phosphoproteome in mice following various treatments. Mice were trained using an inhibitory avoidance (IA) task and hippocampal PSD fractions were isolated for quantitative proteomic and phosphoproteomics analysis. We used a sequential enrichment strategy to explore the concurrent events of protein expression and phosphorylation in the hippocampal PSD following IA training (IA) or immediate shock (Shock). We identified more than 6,200 proteins and 3,000 phosphoproteins in the sequential strategy covering a total of 7,429 proteins. On the phosphoproteins we identified a total of 9,589 phosphosites. Strikingly, of the significantly IA-regulated proteins and phosphoproteins, a large fraction of the proteins displayed an overall decrease in phosphorylation level. Bioinformatic analysis of proteins and phosphoproteins that were regulated by IA were annotated for an involvement in regulation of glutamate receptor functionality, calcium signaling, and synaptic plasticity. We also identified synaptic kinases, phosphatases and their respective phosphosites regulated by IA training or immediate shock. Furthermore, we found that AMPA receptor surface expression was regulated by protein phosphatase, Mg2+/Mn2+ dependent 1H (Ppm1h). Together, these results unravel the dynamic remodeling of the PSD upon IA learning or immediate shock and serve as a resource for elucidating the synaptic proteome dynamics induced by experience-dependent plasticity.HighlightsThe proteome and phosphoproteome of mouse hippocampal PSD fractions were examined using quantitative phosphoproteomics and bioinformatics following inhibitory avoidance training or non-associative immediate shock.Approximately 6,200 proteins and 3,000 phosphoproteins were identified and quantified in the hippocampal PSD fractions.IA mediates widespread decreases in the abundance and phosphorylation of proteins in the hippocampal PSD fraction.Kinases, phosphatases and their phosphorylation status were dynamically and significantly regulated by IA and immediate shock.Functional validation shows that the protein phosphatase Ppm1h is linked to the regulation of synaptic plasticity in vitro and in vivo.In BriefQuantitative proteomics and phosphoproteomics combined with subcellular protein fractionation and bioinformatic analysis identifies a highly dynamic regulation of synaptic protein phosphorylation at the postsynaptic density following IA training and immediate shock.
Altered circadian rhythms and sleep in a new Angelman Syndrome mouse model
Authors: Shi Shu-qun , Mahoney Carrie E. , Houdek Pavel , Zhao Wenling , Anderson Matthew P. , Zhuo Xinming , Beaudet Arthur , Sumova Alena , Scammell Thomas E. , Johnson Carl Hirschie 
Published: October 2021

AbstractNormal neurodevelopment requires precise expression of the key ubiquitin ligase gene Ube3a. Comparing newly generated mouse models for Ube3a down-regulation (models of Angelman syndrome) vs. Ube3a up-regulation (models for autism), we find reciprocal effects of Ube3a gene dosage on phenotypes associated with circadian rhythmicity, including the amount of locomotor activity. In contrast to previous reports, we find that Ube3a is imprinted in neurons of the suprachiasmatic nuclei, the pacemaking circadian brain locus. In addition, Ube3a-deficient mice lack the typical drop in wake late in the dark period and have blunted responses to sleep deprivation. Suppression of physical activity by light in Ube3a-deficient mice is not due to anxiety as measured by behavioral tests and stress hormones; quantification of stress hormones may serve as an easily measurable biomarker for evaluating potential therapeutic treatments for Angelman syndrome. We conclude that reduced Ube3a gene dosage affects not only neurodevelopment but also sleep patterns and circadian rhythms.
CaPti1/CaERF4 module positively regulates pepper resistance to bacterial wilt disease through coupling enhanced immunity and dehydration tolerance
Authors: Shi Lanping , Li Xia , Weng Yahong , Cai Hanyang , Liu Kaisheng , Xie Baixue , Ansar Hussain , Guan Deyi , He Shuilin , Liu Zhiqin 
Published: October 2021

AbstractBacterial wilt, a severe disease that affects over 250 plant species, is caused byRalstonia solanacearumthrough vascular system blockade. Although both plant immunity and dehydration tolerance might contribute to disease resistance, whether and how they are related are still unclear. Herein, we provide evidence that immunity againstR. solanacearumand dehydration tolerance are coupled and regulated byCaPti1-CaERF4 module. By expression profiling, virus-induced gene silencing in pepper and overexpression inNicotiana benthamiana, bothCaPti1andCaERF4were upregulated byR. solanacearuminoculation, dehydration stress and exogenously applied ABA. They in turn phenocopied with each other in promoting pepper resistance to bacterial wilt not only by activating HR cell death and SA-dependentCaPR1, but also by activating dehydration tolerance relatedCaOSM1andCaOSR1, and stomata closure to reduce water loss in ABA signaling dependent manner. Yeast-two hybrid assay showed thatCaERF4 interacts withCaPti1, which was confirmed by co-immunoprecipitation and pull-down assays. Chromatin immunoprecipitation and electrophoretic mobility shift assay showed that, uponR. solanacearuminoculation,CaPR1, CaOSM1andCaOSR1were directly targeted and positively regulated byCaERF4 via binding GCC-box or DRE-box, which was potentiated byCaPti1. In addition, our data indicate thatCaPti1-CaERF4 complex might act downstream ABA signaling, since the exogenously applied ABA did not alter stomata aperture regulated byCaPti1-CaERF4 module. Importantly,CaPti1-CaERF4 module was found also acts positively in pepper growth and response to dehydration stress. Collectively, the results suggest that immunity and dehydration tolerance are coupled and positively regulated byCaPti1-CaERF4 in pepper plants to enhance resistance againstR. solanacearum.SummaryPepper immunity and dehydration tolerance are coupled and regulated by theCaPti1-CaERF4 module partially in a way related to ABA signaling and stomata closure.
A cautionary tale on proper use of branch-site models to detect convergent positive selection
Authors: Kowalczyk Amanda , Chikina Maria , Clark Nathan L 
Published: October 2021

AbstractComparative genomics has become a powerful tool to elucidate genotype-phenotype relationships, particularly through the study of convergently acquired phenotypes. By identifying genes under positive selection specifically on branches with the convergent phenotype we can potentially link genes to that phenotype. Such gene scans are often done using branch-site codon models. However, we have observed a recent troubling trend of misinterpretation of branch-site models in which phylogeny-wide positive selection is not distinguished from positive selection specific to convergent branches. Here, we use simulations and real data to demonstrate how failing to discern between these two cases leads to false inferences of positive selection associated with a convergent trait. We then present a “ drop-out” test solution to distinguish the two cases and thereby truly capture positive selection events associated with convergent phenotypes, thus allowing for further insights into both genetic and phenotypic evolution.
Aging decreases the lateralization of gravity-related effort minimization during vertical arm movements
Authors: Poirier Gabriel , Papaxanthis Charalambos , Lebigre Mélanie , Juranville Adrien , Mathieu Robin , Savoye-Laurens Timothée , Manckoundia Patrick , Mourey France , Gaveau Jeremie 
Published: October 2021

AbstractMotor lateralization refers to differences in the neural organization of cerebral hemispheres, resulting in different control specializations between the dominant and the non-dominant motor systems. Multiple studies proposed that the dominant hemisphere is specialized for open-loop optimization-like processes. Recently, comparing arm kinematics between upward and downward movements, we found that the dominant arm outperformed the non-dominant one regarding gravity-related motor optimization in healthy young participants. The literature about aging effects on motor control presents several neurophysiological and behavioral evidences for an age-related reduction of motor lateralization. Here, we compare the lateralization of a well-known gravity-related optimal motor control process between young and older adults. Forty-one healthy young (mean age = 24.3 ± 3 years) and forty-two healthy older adults (mean age = 72.0 ± 6 years) performed single degree-of-freedom vertical arm movements between two targets (upward and downward). Participants alternatively reached with their dominant and non-dominant arms. We recorded arm kinematics and electromyographic activities of the prime movers (Anterior and Posterior Deltoids) and we analyzed parameters thought to represent the hallmark of the gravity-related optimization process (i.e directional asymmetries and negative epochs on the phasic EMG activity). We found strong age x arm interaction effects on all parameters; i.e., relative durations to peak acceleration and peak velocity and the negativity of antigravity muscles’ phasic signals. Although all three parameters showed a lateralization effect where the dominant arm was superior to the non-dominant arm in young adults (as in Poirier et al. 2022), we found no such effect in older adults. With both arms, the results of older adults lied between those of the dominant and non-dominant arm of young adults. These results add to those of recent literature showing that feedforward motor control remains functional in older adults. More, the results obtained with the non-dominant arm may support a previously hypothesized increased reliance on predictive mechanisms in older adults.
The hormone Fibroblast Growth Factor 19 stimulates water intake
Authors: Ursic-Bedoya José , Chavey Carine , Meunier Lucy , Desandré Guillaume , Dupuy Anne-Marie , Reyes Iria Gonzalez-Dopeso , Tordjmann Thierry , Assénat Eric , Hibner Urszula , Gregoire Damien 
Published: October 2021

AbstractFibroblast growth factor 19 (FGF19) is a hormone with pleiotropic metabolic functions, leading to ongoing development of analogues for the treatment of metabolic disorders. On the other hand, FGF19 is overexpressed in a sub-group of hepatocellular carcinoma (HCC) patients and has oncogenic properties. It is therefore crucial to precisely define FGF19 effects, notably chronic exposure to elevated concentrations of the hormone. We used hydrodynamic gene transfer approach to generate a transgenic mouse model with long-term FGF19 hepatic overexpression. Here we describe a novel effect of FGF19, namely stimulation of water intake. This phenotype, lasting at least over a 6-month period, depends on signaling in the central nervous system and is independent of FGF21, although it mimics some of its features. We further show that HCC patients with high levels of circulating FGF19 have a reduced natremia, indicating dispogenic features. The present study provides evidence of a new activity for FGF19, which could be clinically relevant in the context of FGF19 overexpressing cancers and treatment of metabolic disorders by FGF19 analogues.
Diversity analysis of soil microbial population abundance before and after planting JunCao “Oasis No. 1” in saline-alkali soil
Authors: Zhi Qi Xiao , Zhan Xi Lin 
Published: October 2021

AbstractIn order to explore the difference of soil microbial population structure and abundance before and after planting JunCao “Oasis No. 1” in saline-alkali soil, verify the improvement effect of JunCao “Oasis No. 1” on microbial population structure and abundance in saline-alkali soil. Samples were collected from the blank saline area with and without JunCao “Oasis NO.1” and no plant growth on the surface, respectively, as Experimental group soil samples (S.Y.1-S.Y.8) and Blank group soil samples (K.B.1-K.B.8).16sDNA high-throughput sequencing technology was used for sequencing analysis respectively, and the diversity of microbial population abundance between them was compared and analyzed.The results showed that the diversity of microbial population abundance in the experimental group was significantly higher than that in the blank group, and the diversity of microbial population abundance in the experimental group was significantly different from that in the blank group, indicating that the composition of microbial population in the experimental group was significantly different from that in the blank group. In the OTU cluster analysis, the number of OTU clusters in the Experimental group soil samples (S.Y.1-S.Y.8) was significantly higher than that in the Blank group soil samples (K.B.1-K.B.8). In the sample complexity analysis of α-diversity analysis, the richness and diversity of microbial population in soil samples of Experimental group (S.Y.1-S.Y.8) were significantly higher than that in soil samples of Blank group (K.B.1-K.B.8), which was clearly reflected in the Species accumulation boxplot and Graph of species diversity. In the β-diversity analysis, PcoA, PCA and NMDS analysis methods were used to analyze the difference of microbial population diversity between Experimental soil samples (S.Y.1-S.Y.8) and Blank soil samples (K.B.1-K.B.8). The results showed that the diversity of microbial population in Experimental soil sample (S.Y.1-S.Y.8) was significantly different from that in Blank soil sample (K.B.1-K.B.8). In this paper, 16sDNA high-throughput sequencing technology was used to analyze the diversity of microbial population abundance between Blank soil samples and Experimental soil samples, and it was proved that JunCao “Oasis No. 1” had good saline-alkali soil improvement characteristics. It can effectively increase the abundance of microbial population in saline-alkali soil, so as to restore the microbial population ecosystem in saline-alkali soil, which has important application value in soil saline-alkali control.
Characterising severe traumatic brain injury from fresh cerebral biopsy in living patients
Authors: Yip Ping K. , Hasan Shumaila , Uff Christopher E.G. 
Published: October 2021

AbstractTraumatic brain injury (TBI) is one of the most complex disorder in the most complex organ in the body and current classifications of mild, moderate and severe often fail to capture this complexity. Although the mainstay of prognosis involves several clinical classification systems, these systems are confined to macroscopic analysis. Therefore, we aim to use immunohistochemical examination of fresh brain biopsy samples to study the cellular and molecular changes caused by severe TBI.Twenty-five adult patients suffering severe TBI were recruited into the Severe Head Injury Brain Analysis (SHIBA) study. Fresh brain biopsies obtained prior intracranial pressure (ICP) monitor insertion or during craniotomy underwent immunohistochemical analysis using the neuronal marker (NeuN), dendritic marker (MAP2), vascular markers (claudin-5 and vWF), and neuroinflammation markers (Iba1 and P2Y12) to investigate the injury severity at microscopic level.Obtaining brain biopsy from the twenty-five patients in the study did not cause any additional burden to patient’s standard care and there were no adverse effects. The mean (± SD) Glasgow Outcome Scale-Extended (GOS-E) 3-months after injury was 4.0 (± 2.7), consisting of 64% unfavourable outcomes and 36% favourable outcomes. Immunostaining of brain tissue revealed various qualitative changes resulting in neuronal injury, dendritic injury, neurovascular injury, and neuroinflammation, which we classified into 4 subgroups for each injury type using the newly devised Yip, Hasan and Uff (YHU) grading system. Using this grading scale, patients with a total YHU grade of ≥ 11, 100% (n=11) had a GOS-E of ≤ 4, including death (54.5%), vegetative state (18.2%) and severe disability (27.3%) 3-months post injury. In contrast, those with a YHU grade of ≤ 8, 100% (n=8) had a GOS-E of 5 or higher, indicating a favourable outcome. Linear regression showed a significant negative correlation between the GOS-E and neuronal injury (R2 =0.240, p= 0.0129), dendritic injury (R2 =0.430, p= 0.0004), neurovascular injury (R2 =0.538, p<0.0001), and neuroinflammation (R2 =0.361, p= 0.0015).Brain biopsy in severe TBI is a simple and safe procedure. Furthermore, immunofluorescence staining enables classification of this heterogeneous patient population into various categories of injury severity based on the cellular and molecular pathophysiology according to the YHU grading system. This new grading scale should facilitate a more precise diagnosis, similar to what is currently standard in oncology, allowing earlier and more accurate prognosis than current grading systems, thereby adding to the arsenal of resources available to guide clinical decision making in treating patients with severe TBI.
Conscious processing of global and local auditory irregularities causes differentiated heartbeat-evoked responses
Authors: Candia-Rivera Diego , Raimondo Federico , Pérez Pauline , Naccache Lionel , Tallon-Baudry Catherine , Sitt Jacobo D. 
Published: October 2021

AbstractRecent research suggests that brain-heart interactions are associated with perceptual and self-consciousness. In this line, the neural responses to visceral inputs have been hypothesized to play a leading role in shaping our subjective experience. This study aims to investigate whether the contextual processing of auditory irregularities modulates both direct neuronal responses to the auditory stimuli (ERPs) and the neural responses to heartbeats, as measured with heartbeat-evoked responses (HERs). HERs were computed in patients with disorders of consciousness, diagnosed with a minimally conscious state or unresponsive wakefulness syndrome. We tested whether HERs reflect conscious auditory perception, which can potentially provide additional information for the consciousness diagnosis. EEG recordings were taken during the local-global paradigm, which evaluates the capacity of a patient to detect the appearance of auditory irregularities at local (short-term) and global (long-term) levels. The results show that local and global effects produce distinct ERPs and HERs, which can help distinguish between the minimally conscious state and unresponsive wakefulness syndrome patients. Furthermore, we found that ERP and HER responses were not correlated suggesting that independent neuronal mechanisms are behind them. These findings suggest that HER modulations in response to auditory irregularities, especially local irregularities, may be used as a novel neural marker of consciousness and may aid in the bedside diagnosis of disorders of consciousness with a more cost-effective option than neuroimaging methods.
The effects of modifiable maternal pregnancy exposures on offspring molar-incisor hypomineralisation: A negative control study
Authors: Lim Qui-Yi , Taylor Kurt , Dudding Tom 
Published: October 2021

AbstractObjectivesExplore associations between modifiable maternal pregnancy exposures: pre-pregnancy body mass index (BMI), pregnancy smoking and alcohol consumption with offspring molar-incisor hypomineralisation (MIH).Use negative control analyses to explore for the presence of confounding.MethodsUsing prospectively collected data from Avon Longitudinal Study of Parents and Children (ALSPAC), we performed logistic regression to explore confounder adjusted associations between maternal pre-pregnancy BMI and smoking and alcohol consumption during pregnancy with MIH. We compared these with negative control exposure (paternal BMI, smoking and alcohol) and outcome (offspring dental trauma) analyses.Results5,536 mother/offspring pairs were included (297 MIH cases [5.4%]). We found a weak, positive association between maternal mean BMI and offspring MIH (OR per 1□kg/m2 difference in BMI: 1.04, 95%CI: 1.00, 1.08). Results of subsequent analyses suggested this effect was non-linear and being driven by women in the highest BMI quintile (OR for women in the highest BMI quintile versus the lowest: 1.61 95%CI: 1.02, 2.60). Negative control analyses showed no evidence of an association between paternal BMI and offspring MIH (OR: 0.94, 95%CI: 0.89,1.00) and maternal BMI and offspring dental trauma (OR: 0.99, 95%CI: 0.96, 1.02). There was no clear evidence of an association for maternal smoking (OR: 0.76, 95%CI: 0.46,1.22) or alcohol consumption (OR: 0.79, 95%CI: 0.56, 1.21) with offspring MIH with results imprecisely estimated.ConclusionWe found evidence of a possible intrauterine effect for high maternal pre-pregnancy BMI on offspring MIH, but no robust evidence of an intrauterine effect for maternal pregnancy smoking or alcohol consumption. A key limitation includes possible misclassification of MIH. Replication of these results is warranted.