bluuebunny/crossref_metadata_2025_split huggingface dataset:
Observing the self and other in motion modulates the excitability of vestibulocollic reflexes
Authors: Nakul Estelle , Deroualle Diane , Montava Marion , Lavieille Jean-Pierre , Lopez Christophe 
Published: September 2022

AbstractVestibular inputs from the inner ear are at the basis of the vestibulo-spinal and vestibulocollic reflexes involved in balance control. Studies have focused on how attentional load and emotions influence balance, but low-level social cues, such as observing human bodies in motion, have been neglected. Yet, individuals observing another person in a challenging posture or in motion can experience imbalance, indicating that sensorimotor resonance between self and others is involved. The present study examines how the observation of videos depicting human bodies in motion modulates well-established neurophysiological signatures of vestibular information processing. The excitability of vestibulocollic reflexes was assessed by analyzing the waveform of vestibular-evoked myogenic potentials (VEMPs) over the sternocleidomastoid and trapezius muscles of 25 healthy participants (13 females, 12 males). Here we show that observing human bodies undergoing passive whole-body rotations reduced the VEMPs amplitude when compared to observing an object. Importantly, the modulation depended on the person depicted in the video as VEMPs were reduced when observing oneself, compared to someone else being moved. Direction-specific effects and electromyography recordings ruled out non-specific emotional and attentional effects. These results show that the vestibular system is sensitive to observing human bodies in motion, establishing new connections between social neuroscience and vestibular neurophysiology.Significance StatementVestibulocollic reflexes are thought to be consistent and of short latency. Yet, previous results show that observing conspecifics influences balance. We combined approaches from social neuroscience and vestibular electrophysiology to describe how the observation of self and other bodies in motion influences vestibular information processing. The results show that observing human bodies in motion reduces the amplitude of vestibulocollic reflexes involved in the stabilization of the head and balance. These results establish new relations between the sense of balance and social cognition and challenge classical views in vestibular neuroscience.
Metabotropic glutamate group II receptor activation in the dorsal striatum suppresses the motivation for cocaine in rats
Authors: Khoo Shaun Yon-Seng , Samaha Anne-Noël 
Published: September 2022

AbstractAfter a history of intermittent cocaine intake, rats develop patterns of drug use characteristic of addiction. The dorsal striatum is involved in the increased pursuit of cocaine after intermittent drug self-administration experience. Within the dorsal striatum, chronic cocaine use changes metabotropic glutamate type II receptor (mGlu2/3) density and function. We examined the extent to which activity at these receptors mediates responding for cocaine after intermittent cocaine use. In Experiment 1, male Wistar rats (n = 11) self-administered 0.25 mg/kg/infusion cocaine during 10 daily intermittent access (IntA) sessions (5 min ON/25 min OFF, for 5 h/session). We then examined the effects of intra-dorsal striatum infusions of the mGlu2/3 receptor agonist LY379268 (0, 1, and 3 μg/hemisphere) on cocaine self-administration under a progressive ratio schedule of reinforcement. We observed a non-significant tendency for LY379268 to reduce responding for cocaine. In Experiment 2, we used a larger sample of male (n = 11) and female (n = 10) rats. Across 10 IntA sessions, the sexes showed similar levels of cocaine intake. Across the sexes, locomotion significantly increased over sessions, suggesting that rats developed psychomotor sensitization to self-administered cocaine. After 10 IntA sessions, intra-dorsal striatum LY379268 significantly reduced breakpoints achieved for cocaine, active lever presses, and cocaine infusions earned under progressive ratio. LY379268 had no effects on locomotion or inactive lever presses, indicating no motor effects. These results suggest that mGlu2/3 receptor activation in the dorsal striatum suppresses incentive motivation for cocaine, and this holds promise for anti-addiction therapeutics.
Purification and biochemical analysis of native AMPA receptors from three different mammalian species
Authors: Rao Prashant , Gouaux Eric 
Published: September 2022

AbstractThe majority of fast, excitatory synaptic transmission in the central nervous system (CNS) is mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), which are glutamate-activated ion channels integral to synaptic plasticity, motor coordination, learning, and memory. AMPARs are multiprotein assemblies comprised of a tetrameric receptor core that co-assembles with a broad range of peripheral auxiliary proteins which shape subcellular localization and signaling properties of the resulting complexes. Structure determination of AMPARs has traditionally relied on recombinant expression systems; however, these methods are not well suited to elucidate the diverse array of AMPAR assemblies that are differentially expressed in mammalian brains. While recent studies of native receptor complexes have advanced our understanding of endogenous assemblies, receptors thus far have only been isolated from rodent brain tissue. Here, we employed an immunoaffinity purification strategy to isolate native AMPARs from the brains of three different mammals - pigs, sheep, and cows. Compared to rodents; pigs, sheep, and cows are from a unique clade of mammals - ungulates, that share a closer genomic identity with humans. We determined the molecular size, overall yield, and purity of native AMPARs isolated from these three mammals, thereby demonstrating that structural determination and biochemical analysis is possible from a clade of mammals evolutionarily distinct from rodents.
Global genomic analysis reveals the genetic origin and secondary invasion of fall armyworm in the Eastern hemisphere
Authors: Zhang Lei , Li Zaiyuan , Peng Yan , Liang Xinyue , Wilson Kenneth , Chipabika Gilson , Karangwa Patrick , Uzayisenga Bellancile , Mensah Benjamin A. , Kachigamba Donald L. , Xiao Yutao 
Published: September 2022

AbstractThe major plant pest fall armyworm (FAW),Spodoptera frugiperda, is native to the Americas and has colonized African and Asian countries in the Eastern hemisphere since 2016, causing severe damage to multiple agricultural crop species. However, the genetic origin of these invasive populations require more in-depth exploration. We analyzed genetic variation across FAW genomes of 153 newly sequenced individuals from Eastern hemisphere and 127 individuals mostly originating from the Americas. The global genetic structure of FAW shows that the FAW in American has experienced deep differentiation, largely consistent with the Z-chromosomalTpihaplotypes commonly used to differentiate “corn-strain” and “rice-strain” populations. Results indicate that the invasive Eastern hemisphere populations are different from the American ones and have relatively homogeneous population structure, consistent with the common origin and recent spreading from Africa to Asia. Our analyses suggest that north-and central American “corn-strain” FAW are the most likely sources of the invasion into the Eastern hemisphere. Furthermore, evidence based on genomic, transcriptomic and mitochondrial haplotype network analysis suggest that there has been an earlier independent introduction of FAW into Africa that introgressed into the recent invasive population.
On the origin ofR2orientation dependence angle offsets in white matter
Authors: Pang Yuxi 
Published: September 2022

ABSTRACTPurposeto identify the origin of confounding angle offsetε0inR2orientation dependence and to propose a novel framework for better characterizing anisotropicR2in brain white matter (WM).MethodsAnisotropic (ε) rather than principal diffusivity direction (Φ) was theorized along axon fiber, withεdetermined by all eigenvalues and eigenvectors from diffusion tensor. An extra parameterε0was introduced into generalized magic angle effect function to account for any offset inR2orientation dependence derived fromT2-weighted image (b=0). These dependences referenced byεwere compared to those referenced as usual by Φ atb-values of 1000 and 2000 (s/mm2) on both linear and planar tensor image voxels in WM, based on public domain ultrahigh-resolution (760µm3) Connectome DTI datasets of a healthy young adult brain. A Student’s t-test was used to assess the mean differences and the statistical significance was considered atP< 0.05.ResultsFittedε0became zero if referenced byεor nonzero if referenced by Φ, signifying the origin ofε0. Nonzeroε0relied onb-values and tensor shapes so did other model parameters, e.g., the amplitude of anisotropicR2(1/s) significantly increased when using a higherb-value for the linear tensor image voxels, i.e., 3.3±0.1 vs. 1.8±0.1,P< 0.01.ConclusionThe origin ofR2orientation dependence angle offsets has been identified and the combined anisotropic diffusion and transverse relaxation models have fully quantifiedR2orientational anisotropies, thus providing novel insights otherwise unattainable on microstructural alterations in WM.
Antiviral effect of thiazolides relies on mitochondrial mild uncoupling
Authors: Hammad Noureddine , Ransy Céline , Pinson Benoit , Talmasson Jeremy , Bréchot Christian , Bouillaud Frédéric , Rossignol Jean-François 
Published: September 2022

AbstractBackgroundViruses are dependent on cellular energy metabolism for their replication, the drug Nitazoxanide (Alinia) was shown to interfere with both. An effect of Alinia on cellular energy metabolism is the uncoupling of mitochondrial oxidative phosphorylation (OXPHOS). Our hypothesis was that uncoupling grounds the antiviral properties of Alinia.MethodsAlinia or an unrelated uncoupler were applied to a viral releasing cell line to obtain the same increasing levels of uncoupling hence identical interference with OXPHOS.FindingsDecrease in infectious viral particles release reflected the intensity of interference irrespective of the nature of the drug and was significant with modest deviation (≤25%) from normal.InterpretationsA mild interference on cellular energy metabolism impacts significantly on viral replication cycle. This would explain Alinia’s antiviral properties in vitro moreover antiviral action of Alinia is supported by clinical trials.PerspectivesAltogether this indicates that moderate interference with mitochondrial bioenergetics should be considered as a ground for a therapeutic effect. In addition, Alinia would constitute example for a safe therapeutical use of an uncoupler, which deserves consideration for a wider range of applications.
Pan-cancer genomic analysis shows hemizygousPTENloss tumors are associated with immune evasion and poor outcome
Authors: Vidotto T , Melo CM , Lautert-Dutra W , Chaves LP , Reis RB , Squire JA 
Published: September 2022

ABSTRACTIn tumors, somatic mutations of thePTENsuppressor gene are associated with advanced disease, chemotherapy resistance, and poor survival.PTENloss of function may occur by inactivating mutation, by deletion, either affecting one copy (hemizygous loss) leading to reduced gene expression or loss of both copies (homozygous) with expression absent. Various murine models have shown that minor reductions in PTEN protein levels strongly influence tumorigenesis. MostPTENbiomarker assays dichotomize PTEN (i.e. presence vs. absence) ignoring the role of one copy loss. We performed aPTENcopy number analysis of 9,793 TCGA cases from 30 different tumor types. There were 419 (4.28%) homozygous and 2484 (25.37%) hemizygousPTENlosses. Hemizygous deletions led to reduced PTEN gene expression, accompanied by increased levels of instability and aneuploidy across tumor genomes. Outcome analysis of the pan-cancer cohort showed that losing one copy ofPTENreduced survival to comparable levels as complete loss, and was associated with transcriptomic changes controlling immune response and the tumor microenvironment. Immune cell abundances were significantly altered forPTENloss, with changes in head and neck, cervix, stomach, prostate, brain, and colon more evident in hemizygous loss tumors. These data suggest that reduced expression ofPTENin tumors with hemizygous loss leads to tumor progression and influences anticancer immune response pathways.
Computational remodeling of an enzyme conformational landscape for altered substrate selectivity
Authors: St-Jacques Antony D. , Rodriguez Joshua M. , Eason Matthew G. , Foster Scott M. , Khan Safwat T. , Damry Adam M. , Goto Natalie K. , Thompson Michael C. , Chica Roberto A. 
Published: September 2022

AbstractStructural plasticity of enzymes dictates their function. Yet, our ability to rationally remodel enzyme conformational landscapes to tailor catalytic properties remains limited. Here, we report a computational procedure for tuning conformational landscapes that is based on multistate design. Using this method, we redesigned the conformational landscape of a natural aminotransferase to preferentially stabilize a less populated but reactive conformation, and thereby increase catalytic efficiency with a non-native substrate to alter substrate selectivity. Steady-state kinetics of designed variants revealed selectivity switches of up to 1900-fold, and structural analyses by room-temperature X-ray crystallography and multitemperature nuclear magnetic resonance spectroscopy confirmed that conformational equilibria favoured the target conformation. Our computational approach opens the door to the fine-tuning of enzyme conformational landscapes to create designer biocatalysts with tailored functionality.
Influenza virus membrane fusion is promoted by the endosome-resident phospholipid bis(monoacylglycero)phosphate
Authors: Mannsverk Steinar , Villamil Giraldo Ana M. , Kasson Peter M. 
Published: September 2022

AbstractThe phospholipid bis(monoacylglycero)phosphate (BMP) is enriched in late endosomal and endo-lysosomal membranes and is believed to be involved in membrane deformation and generation of intralumenal vesicles within late endosomes. Previous studies have demonstrated that BMP promotes membrane fusion of several enveloped viruses, but a limited effect has been found on influenza virus. Here, we report the use of single-virus fusion assays to dissect BMP’s effect on influenza virus fusion in greater depth. In agreement with prior reports, we found that hemifusion kinetics and efficiency were unaffected by the addition of 10-20 mol % BMP to the target membrane. However, using an assay for fusion pore formation and genome exposure, we found full fusion efficiency to be substantially enhanced by the addition of 10-20 mol % BMP to the target membrane, while the kinetics remained unaffected. By comparing BMP to other negatively charged phospholipids, we found the effect on fusion efficiency mainly attributable to headgroup charge, although we also hypothesize a role for BMP’s unusual chemical structure. Our results suggest that BMP function as a permissive factor for a wider range of viruses than previously reported. We hypothesize that BMP may be a general co-factor for endosomal entry of enveloped viruses.
Antigenic characterisation of human monoclonal antibodies for therapeutic use against H7N9 avian influenza virus
Authors: Chang Pengxiang , Lukosaityte Deimante , Sealy Joshua E. , Rijal Pramila , Sadeyen Jean-Remy , Bhat Sushant , Crossley Sylvia , Daines Rebecca , Huang Kuan-Yin A. , Townsend Alain R. , Iqbal Munir 
Published: September 2022

ABSTRACTSince 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1500 human deaths and millions of poultry culling. Despite large-scale poultry vaccination, H7N9 AIVs continue to circulate among poultry in China and pose a threat to human health. Previously, we isolated and generated four monoclonal antibodies (mAbs) derived from humans naturally infected with H7N9 AIV. Here, we investigated the haemagglutinin (HA) epitopes of H7N9 AIV targeted by these mAbs (L3A-44, K9B-122, L4A-14 and L4B-18) using immune escape studies. Our results revealed four key antigenic epitopes at HA amino acid positions 125, 133, 149, and 217. The mutant H7N9 viruses representing escape mutations containing Alanine to Threonine at residue 125 (A125T), Glycine to Glutamic acid at residue 133 (G133E), Asparagine to Aspartic acid at residue 149 (N149D), or Leucine to Glutamine at residue 217 (L217Q) showed reduced or completely abolished cross-reactivity with the mAbs, as measured by hemagglutination inhibition (HI) assay. We further assessed the potential risk of these mutants to humans should they emerge following mAb treatment by measuring the impact of these HA mutations on virus fitness and evasion of host adaptive immunity. Here we showed that the L4A-14 mAb had broad neutralizing capability, and its escape mutant N149D had reduced viral stability and human receptor binding and could be neutralized by both post-infection and antigen-induced sera. Therefore, L4A-14 mAb could be a therapeutic candidate for H7N9 AIV infection in humans and warrants further investigation for therapeutic application.IMPORTANCEAvian Influenza virus (AIV) H7N9 continues to circulate and evolve in birds, posing a credible threat to humans. Antiviral drugs have been proven useful for the treatment of severe influenza infections in humans, however, concerns have been raised as antiviral resistant mutants have emerged. Monoclonal antibodies (mAbs) have been studied for both prophylactic and therapeutic applications in infectious disease control and have demonstrated great potential. For example, mAb treatment has significantly reduced the risk of people developing severe disease with SARS-COV 2 infection. In addition to the protection efficiency, we should also consider the potential risk of the escape mutants generated by mAb treatment to public health by assessing their viral fitness and potential to compromise host adaptive immunity. Considering these parameters, we assessed four human mAbs derived from humans naturally infected with H7N9 AIV and showed that the mAb L4A-14 displayed potential as a therapeutic candidate.
Dorsolateral Prefrontal Cortex Metabolic Profiles in Autism Spectrum Disorder Correlate Atypically with Nonverbal IQ and Typically with Attention Switching
Authors: Weerasekera Akila , Ion-M□rgineanu Adrian , McGuiggan Nicole M. , Shetty Nandita , Joseph Robert M. , Ghosh Shantanu , Alshikho Mohamad , Herbert Martha R. , Kenet Tal , Ratai Eva-Maria 
Published: September 2022

ABSTRACTBackgroundThe neurometabolic profile of associated with autism spectrum disorder (ASD) has been reported to be abnormal by some studies showing region specific metabolite levels in ASD, while others report no group differences. The neurometabolic profile of the left dorsolateral prefrontal cortex (DLPFC) is of particular interest due to the DLPFC relevance to cognitive and executive function, and to ASD.MethodWe used 1H-MRS to investigate neurometabolic profiles in the DLPFC of ASD and sex/IQ-matched typically developing (TD) children (ages 9-13). We focused on levels of Glutamate and Glutamine (Glx) due to many reported Glx abnormalities ASD, and of Choline (Cho) because of its relationship to intelligence quotient (IQ) and to attentional re-orienting difficulties.ResultsWhile no significant group differences were observed in absolute concentrations, metabolite levels were correlated with the behavioral phenotype of ASD children. In the ASD group but not the TD group, nonverbal IQ (NVIQ) was negatively associated with Cho (r=-0.59, p=0.026) and positively associated with Glx/Cr (r=0.66, p=0.011). Furthermore, attentional-switching scores in the ASD group correlated negatively with Cho (r=-0.69, p=0.009), and positively with Glx/Cr for both the ASD (r=0.73, p=0.004) and TD (r=0.54, p=0.040) groups.ConclusionsCho and Glx/Cr have different neurometabolic roles in modulating NVIQ in ASD compared to TD children, while their role in attentional switching seems preserved in ASD. Elucidating the apparently divergent role of neurometabolites in ASD in the absence of significant group differences in absolute levels is an important step towards understanding and mapping the neural correlates of ASD. These results are also relevant in the context of the significant cognitive function heterogeneity associated with the ASD phenotype, as they suggest possible underlying neural mechanisms that do not overlap which those expected from typical development.
Chaperonin activity of Plasmodium prefoldin complex is essential to guard proteotoxic stress response and presents a new target for drug discovery
Authors: Shoaib Rumaisha , Kumar Vikash , Garg Swati , Saini Monika , Kumari Jyoti , Maurya Preeti , Gupta Aashima , Gupta Nutan , Singh Harshita , Verma Pritee , Jain Ravi , Biswas Shreeja , Behl Ankita , Abid Mohammad , Singh Shailja 
Published: September 2022

SummaryThe intraerythrocytic growth of malaria parasite is challenged by the presence of proteotoxic stress and intrinsically unstructured proteins in the cytoplasm due to formation of toxic heme during haemoglobin digestion. To overcome the unavoidable stress and maintain the cellular protein homeostasis, parasite encodes for a number of chaperones and co-chaperones. Here, we functionally characterize the Plasmodium falciparum prefoldins (PfPFD1-6), a hexameric co-chaperone complex, for their role in protein homeostasis. We demonstrate that PfPFD1-6 localise to cytosol of the parasite and the subunits perform an orchestrated interaction (-PFD3-PFD2-PFD1-PFD5-PFD6-PFD4-) to form an active jelly-fish like complex. Biperiden, an N-propylpiperidine analogue identified by chemotype search from FDA, strongly binds and restricts the formation of prefoldin complex and inhibited its interaction with the substrates, PfMSP-1 and α-tubulin-I. Biperiden treatment potently inhibited the in vitro (IC50: 1μM) and in vivo growth of malaria parasite. Thus, this study provides novel virtues towards understanding the role of PfPFDs in regulating protein homeostasis and opens new avenues for drug discovery against malaria.
Sub-Saharan Africa's rising public debt stock: before another debt relief!
Authors: Olaoye Olumide 
Published: September 2022

PurposeIn light of the recent calls for another round of debt relief for African countries, by African finance ministers and governments, the aim of the study is twofold. First, the study examined the effect of public debt on macroeconomic performance. Two, the study also examined whether previous debt relief has impacted positively on sub-Saharan African economies.Design/methodology/approachThe study adopts the two-step system GMM that accounts for potential endogeneity and feedback effect in dynamic panel models. As robustness, the study performs the two-stage least square (2SLS) estimation method.FindingsThe study reveals that previous debt relief programmes only had a marginal effect on economic growth in the region. The study found that corruption impacts negatively on the effectiveness of debt relief to achieve the desired economic outcomes. The study also found that sub-Saharan African economies seem to have shifted away from traditional concessional sources of financing towards market-based lenders dominated by China.Originality/valueThe study adds to the growing evidence in the public debt literature by looking at the separate impact of domestic and foreign debts on macroeconomic indicators of economic growth, inflation, unemployment and exchange rate. The study also controlled for previous debt relief in light of the call for another round of debt relief.Graphical Abstract