bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Model For Hierarchical Memory Storage in Piriform Cortex
Authors: Kumar Achint 
Published: October 2022

AbstractHow the brain stores and retrieves memories is an important unsolved problem in neuroscience. It is commonly believed that memories are represented in the brain by distinct patterns of neural activity. Attractor dynamics has been proposed as one of the theoretical frameworks for learning and memory in neural networks. However, most of the prior theoretical work typically assumes that the neural network consists of fully-connected, binary neurons and that neuronal representations of memories are uncorrelated. In this paper, we propose a model consisting of continuously varying, rate-based, sparse neural network with a local learning rule which stores correlated patterns organized into multiple uncorrelated classes. We perform analytical calculations to compute maximum storage capacity and basin of attraction. It is found that increasing pattern correlation decreases storage capacity, and increasing the memory load decreases basin of attraction. We also study rate-based and spiking based neural network with separate excitatory and inhibitory populations and tight EI balance. Recent experimental work indicates that piriform cortex exhibits attractor dynamics and possibly stores hierarchically correlated patterns. So, we consider this work as a model for olfactory memory storage.
ISG15 is required for the dissemination ofVaccinia virusextracellular virions
Authors: Bécares Martina , Albert Manuel , Tarrega Celine , Coloma Rocío , Falqui Michela , Luhmann Emma K. , Radoshevich Lilliana , Guerra Susana 
Published: October 2022

AbstractViruses have developed many different strategies to counteract immune responses, andVaccinia virus(VACV) is one of a kind in this aspect. To ensure an efficient infection, VACV undergoes a complex morphogenetic process resulting in the production of two types of infective virions: intracellular mature virus (MV) and extracellular enveloped virus (EV), whose spread depends on different dissemination mechanisms. MVs disseminate after cell lysis, whereas EVs are released or propelled in actin tails from living cells. Here we show that ISG15 participates in the control of VACV dissemination. Infection ofIsg15-/-mouse embryonic fibroblasts with VACV International Health Department-J (IHD-J) strain resulted in decreased EV production, concomitant with reduced induction of actin tails and the abolition of comet-shaped plaque formation, comparing withIsg15+/+cells. Transmission electron microscopy revealed accumulation of intracellular and a decrease in extracellular virus particles in the absence of Interferon Stimulated Gene 15 (ISG15), consistent with altered virus egress. Immunoblot and quantitative proteomic analysis of sucrose gradient-purified virions from both genotypes reported differences in protein levels and composition of viral proteins present on virions, suggesting an ISG15-mediated control of viral proteome. Last, the generation of a recombinant IHD-J expressing V5-tagged ISG15 (IHD-J-ISG15) allowed us to identify several viral proteins as potential ISG15 targets, highlighting the proteins A34 and A36, essential for EV formation. Altogether, our results indicate that ISG15 is an important host factor in the regulation of VACV dissemination.Author SummaryViral infections are a constant battle between the virus and the host. While the host’s only goal is victory, the main purpose of the virus is to spread and conquer new territories at the expense of the host’s resources. Along millions of years of incessant encounters, Poxviruses have developed a unique strategy consisting in the production two specialized “troops”: intracellular mature virions (MVs) and extracellular virions (EVs). MVs mediate transmission between hosts, and EVs ensure advance on the battlefield mediating the long-range dissemination.The mechanism by which the virus ‘decides’ to shed from the primary site of infection and its significant impact in viral transmission is not yet fully established. Here, we demonstrate that this process is finely regulated by ISG15/ISGylation, an interferon-induced ubiquitin-like protein with broad antiviral activity. Studying the mechanism that viruses use during infection could result in new ways of understanding our perpetual war against disease and how we might win the next great battle.
Evidence for an one-step mechanism of endosymbiont-induced thelytoky in the parasitoid wasp,Muscidifurax uniraptor
Authors: Wang Yidong , Verhulst Eveline C. 
Published: October 2022

AbstractWolbachiamanipulates host reproduction in various haplodiploid insect species, in which fertilized eggs normally develop into diploid females while unfertilized eggs develop into haploid males. Females infected with a thelytoky-inducingWolbachiaproduce diploid daughters from unfertilized eggs (thelytoky), but in some infected species diploid males spontaneously occur in low numbers. This suggests that diploidization and feminization are induced separately. In theWolbachia-infected thelytokous parasitoid wasp,Muscidifurax uniraptor, occasional males have been found but with unknown ploidy. Therefore, we studied the mechanism ofWolbachia-induced thelytoky inM. uniraptorin the context of sex determination. We started by feeding different concentrations of tetracycline (antibiotic) toM. uniraptorfemales to gradually reduce theWolbachiatitre. We found that a decreasedWolbachiatitre leads to an increased proportion of haploid male offspring, but we found no diploid males. Next, we studied the effect ofWolbachiainfection on the expression and splicing of the sex determination genestransformer(Mutra) andtransformer-2(Mutra2) in female ovaries and conclude thatWolbachiadoes neither affect the expression nor the splicing ofMutraandMutra2. We then measuredMutraandMutra2expression levels in developing zygotes at different time points and found a two-foldMutraexpression increase inWol+ compared toWol-. Finally, we used the sexually reproducing sister species,Muscidifurax raptorellusand artificially created triploid females to determine whether diploidization is sufficient for feminization. These triploid females, when virgin, produced haploid sons and diploid daughters, showing that inMuscidifuraxfeminization solely depends on ploidy level. This strongly suggests thatWolbachiaonly needs to induce diploidization and that bi-allelicMutraexpression is sufficient for female development.
Membrane curvature-generating proteins crucial for autophagosome formation
Authors: Wang Ning , Shibata Yoko , Paulo Joao A. , Gygi Steven P. , Rapoport Tom A. 
Published: October 2022

AbstractAutophagy is essential for cellular homeostasis and begins with the formation of a phagophore, a cup-like membrane sheet consisting of two closely apposed lipid bilayers connected by a highly curved rim. How the membrane sheet forms, bends, and eventually generates an autophagosome that enwraps cargo remains enigmatic. Specifically, it is unclear how the high membrane curvature of the phagophore rim, an energetically unfavorable state, is stabilized. Here, we demonstrate that phagophore formation requires the conserved, membrane curvature-generating REEP1 proteins. The REEP1 family proteins (REEP1-4 in vertebrates) differ from the related endoplasmic reticulum-shaping REEPs in abundance and membrane topology. In fission yeast, the single REEP1 ortholog is involved in both bulk and selective autophagy. It is recruited at early stages of phagophore formation and required for their maturation into autophagosomes. The function of REEP1 relies on its ability to generate high membrane curvature and its localization to the phagophore rim. Mammalian REEP1 proteins also associate with phagophores upon induction of autophagy and colocalize with early autophagic markers. We propose that REEP1 proteins stabilize the phagophore’s highly curved rim so that the two membrane sheets are kept in close proximity to form the autophagosome. Defective autophagy may underlie the effect of curvature-compromising mutations in human REEP1 proteins linked to neurological disease.
Representational similarity learning reveals a graded multidimensional semantic space in the human anterior temporal cortex
Authors: Cox Christopher R. , Rogers Timothy T. , Shimotake Akihiro , Kikuchi Takayuki , Kunieda Takeharu , Miyamoto Susumu , Takahashi Ryosuke , Matsumoto Riki , Ikeda Akio , Ralph Matthew A. Lambon 
Published: October 2022

AbstractNeurocognitive models of semantic memory have proposed that the ventral anterior temporal lobes (vATLs) encode a graded and multidimensional semantic space—yet neuroimaging studies seeking brain regions that encode semantic structure rarely identify these areas. In simulations we show that this discrepancy may arise from a crucial mismatch between theory and analysis approach. Utilizing an analysis recently formulated to investigate graded multidimensional representations,representational similarity learning(RSL), we decoded semantic structure from ECoG data collected from the vATL cortical surface while participants named line drawings of common items. The results reveal a graded, multidimensional semantic space encoded in neural activity across the vATL, which evolves over time and simultaneously expresses both broad and finer-grained semantic structure amongst animate and inanimate concepts. The work resolves the apparent discrepancy within the semantic cognition literature and, more importantly, suggests a new approach to discovering representational structure in neural data more generally.Conflict of interestThe Department of Epilepsy, Movement Disorders, and Physiology, Kyoto University Graduate School of Medicine conducts Industry-Academia Collaboration Courses, supported by Eisai Co., Ltd, Nihon Kohden Corporation, Otsuka Pharmaceutical Co., and UCB Japan Co., Ltd.
Transcriptomic Profiling of Plasma Extracellular Vesicles Enables Reliable Annotation of the Cancer-specific Transcriptome and Molecular Subtype
Authors: Bahrambeigi Vahid , Lee Jaewon J. , Branchi Vittorio , Rajapakshe Kimal I. , Xu Zhichao , Henry Jason T. , Kun Wang , Stephens Bret M. , Dhebat Sarah , Hurd Mark W. , Sun Ryan , Yang Peng , Ruppin Eytan , Wang Wenyi , Kopetz Scott , Maitra Anirban , Guerrero Paola A. 
Published: October 2022

AbstractLongitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predict consensus molecular subtypes in metastatic colorectal cancer patients. We further demonstrate the ability to monitor changes in transcriptomic subtype under treatment selection pressure and identify molecular pathways in evRNA associated with recurrence. Our approach also identified expressed gene fusions and neoepitopes from evRNA. These results demonstrate the feasibility of transcriptomic-based liquid biopsy platforms for precision oncology approaches, spanning from the longitudinal monitoring of tumor subtype changes to identification of expressed fusions and neoantigens as cancer-specific therapeutic targets,sansthe need for tissue-based sampling.Statement of significanceWe have developed an approach to interrogate changes in cancer molecular subtypes and differentially expressed genes, through the analysis and deconvolution of RNA sequencing of plasma EVs. Serial analyses of tumor-encoded transcriptomes in liquid biopsies can enable facile cancer detection and monitor for recurrences and therapy-induced tumor evolution.
Effect of age and sex on gene expression-based radiation biodosimetry using mouse peripheral blood
Authors: Broustas Constantinos G. , Shuryak Igor , Duval Axel J. , Amundson Sally A. 
Published: October 2022

AbstractBlood-based gene expression profiles that can reconstruct radiation exposure are being developed as a practical approach to radiation biodosimetry. However, age and sex could potentially limit the accuracy of the approach. In this study, we determined the impact of age on the peripheral blood cell gene expression profile of female mice exposed to radiation and identified differences and similarities with a previously obtained transcriptomic signature of male mice. Young (2 months) and old (24 months) female mice were irradiated with 4 Gy X-rays, total RNA was isolated from blood 24hr later and subjected to whole genome microarray analysis. Dose reconstruction analyses using a gene signature trained on gene expression data from irradiated young male mice showed accurate reconstruction of 0 or 4 Gy doses with root mean square error of ± 0.75 Gy (R^2 = 0.90) in young female mice. Although dose reconstruction for irradiated old female mice was less accurate than young female mice, the deviation from the actual radiation dose was not statistically significant. Pathway analysis of differentially expressed genes revealed that after irradiation, apoptosis-related functions were overrepresented, whereas functions related to quantities of various immune cell subtypes were underrepresented, among differentially expressed genes from young female mice, but not older animals. Furthermore, young mice significantly upregulated genes involved in phagocytosis, a process that eliminates apoptotic cells and preserves tissue homeostasis. Both functions were also overrepresented in young, but not old, male mice following 4 Gy X-irradiation. Lastly, functions associated with neutrophil activation that is essential for killing invading pathogens and regulating the inflammatory response were predicted to be uniquely enriched in young but not old female mice. This work supports the concept that peripheral blood gene expression profiles can be identified in mice that accurately predict physical radiation dose exposure irrespective of age and sex. However, inclusion of age and sex as biological factors is essential for effectively predicting radiation injury and for developing radiation medical countermeasures.
A subpopulation of peripheral sensory neurons expressing the Mas-related G Protein-Coupled Receptor d (Mrgprd) generates pain hypersensitivity in painful diabetic neuropathy
Authors: George Dale S , Jayaraj Nirupa D , Ren Dongjun , Miller Rachel E. , Malfait Anne-Marie , Miller Richard J , Menichella Daniela M 
Published: October 2022

ABSTRACTPainful diabetic neuropathy (PDN) is one of the most common and intractable complications of diabetes. PDN is characterized by neuropathic pain accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability, axonal degeneration, and loss of cutaneous innervation. However, the complete molecular profile underlying the hyper-excitable cellular phenotype of DRG nociceptors in PDN has not been elucidated. This gap in our knowledge is a critical barrier to developing effective, mechanism-based, and disease-modifying therapeutic approaches which are urgently needed to relieve the symptoms of PDN. Using single-cell RNA sequencing we demonstrated an increased expression of the Mas-related G Protein-Coupled Receptor d (Mrgprd) in a subpopulation of DRG neurons in the well-established High-Fat Diet (HFD) mouse model of PDN.In vivocalcium imaging allowed us to demonstrate that activation of Mrgprd receptors expressed by cutaneous afferents produced DRG neuron hyper-excitability and oscillatory calcium waves. Furthermore, Mrgprd-positive cutaneous afferents persist in diabetic mice skin. Importantly, limiting Mrgprd signaling or Mrgprd-positive DRG neuron excitability, reversed mechanical allodynia in the HFD mouse model of PDN. Taken together, our data highlights a key role of Mrgprd-mediated DRG neuron excitability in the generation and maintenance of neuropathic pain in a mouse model of PDN. Hence, we propose Mrgprd as a promising accessible target for developing effective therapeutics currently unavailable for treating neuropathic pain in PDN. Furthermore, understanding which DRG neurons cell type is mediating mechanical allodynia in PDN is of fundamental importance to our basic understanding of somatosensation and may provide an important way forward for identifying cell-type-specific therapeutics to optimize neuropathic pain treatment and nerve regeneration in PDN.
Characterisation of organised smooth endoplasmic reticulum suggests a route towards synthetic compartmentalisation
Authors: Sandor Andras , Samalova Marketa , Brandizzi Federica , Kriechbaumer Verena , Moore Ian , Fricker Mark D , Sweetlove Lee J 
Published: October 2022

AbstractEngineering of subcellular compartmentalisation is one of synthetic biology’s key challenges. Among different approaches,de novoconstruction of a synthetic compartment is the most coveted but also most difficult option. Restructuring the endoplasmic reticulum (ER), via the introduction of recombinant oligomerising ER-membrane resident proteins, is an alternative starting point for building a new compartment. The presence of such proteins leads to a massive expansion of the ER and the formation of organised smooth endoplasmic reticulum (OSER), a large membranous compartment. However, OSER is poorly characterised and our understanding of its effect on the underlying biology of the plant is limited. Here we characterise a range of OSER compartments and show how the structure of the inducing polyprotein constructs affect the final compartment morphology, with the cytosolic-facing antiparallel oligomerisation domain demonstrated to be an essential component to trigger OSER formation. We show that while OSER retains a connection to the ER, a diffusional barrier exists to both the ER and the cytosol. Using high-resolution quantitative image analysis, we also show that the presence of this large compartment does not disrupt the rest of the ER network. Moreover, transgenicArabidopsisconstitutively expressing the compartment-forming polyproteins grew and developed normally. These properties collectively suggest that OSER could be developed as a plant synthetic biology tool for compartmentalisation, combining the benefits of several existing strategies. Only a single protein construct is necessary to induce its formation, and the compartment retains a delimiting membrane and a diffusional barrier to the rest of the cell.
Disentangling contact and ensemble epistasis in a riboswitch
Authors: Wonderlick Daria R. , Widom Julia R. , Harms Michael J. 
Published: October 2022

AbstractMutations introduced into macromolecules often exhibit epistasis, where the effect of one mutation alters the effect of another. Knowledge of the mechanisms that lead to epistasis is important for understanding how macromolecules work and evolve, as well as for effective macromolecular engineering. Here we investigate the interplay between “contact epistasis” (epistasis arising from physical interactions between mutated residues) and “ensemble epistasis” (epistasis that occurs when a mutation redistributes the conformational ensemble of a macromolecule, thus changing the effect of the second mutation). We argue that the two mechanisms can be distinguished in allosteric macromolecules by measuring epistasis at differing allosteric effector concentrations. Contacts give rise to epistasis in the microscopic equilibrium constants describing the conformational ensemble. Ensemble epistasis manifests in thermodynamic observables, such as the energy of ligand binding or enzyme activation, that depend on the concentration of allosteric effector. Using this framework, we experimentally investigated the origins of epistasis in three mutant cycles introduced into the adenine riboswitch aptamer domain. We found evidence for both contact and ensemble epistasis in all cycles. Further, we found that the two mechanisms of epistasis can interact with each other. For example, in one mutant cycle we observe contact epistasis of 6 kcal/mol attenuated by the ensemble to only 1.5 kcal/mol in the final thermodynamic observable. Finally, our work yields simple heuristics for identifying contact and ensemble epistasis using limited experimental measurements.Statement of significanceMutations to protein or RNA molecules often have different effects when introduced individually versus together. To understand and engineer biological macromolecules, we must identify the mechanistic origins of this phenomenon. Here, we measured the interplay between direct, physical interactions between mutations (“contact epistasis”) and indirect interactions mediated by conformational ensembles (“ensemble epistasis”). We introduced pairs of mutations into an RNA molecule that transitions between several different conformations. We found epistasis arising from both contacts and the ensemble, and that the two mechanisms could synergize with one another. Our work reveals that one must consider the effects of mutations on multiple conformations to understand epistasis and suggests a few rules-of-thumb for disentangling contact and ensemble epistasis in other macromolecules.
Mobile self-efficacy as predictor of mobile-based personal digital archiving practices: a study of Pakistani undergraduates
Authors: Ali Irfan , Warraich Nosheen Fatima 
Published: October 2022

PurposeThe purpose of this study is to investigate the impact of mobile self-efficacy on personal digital archiving (PDA) practices of undergraduate students.Design/methodology/approachThis study used a quantitative research design for achieving the objectives. The population consisted of undergraduate students from public sector universities (the top five) of Punjab, Pakistan, listed in the Higher Education Commission recognized general universities. The data were analysed by using SmartPLS, mobile self-efficacy was the independent variable that consisted of two constructs (basic mobile phone operations and using the internet and emails). PDA practices was the dependent variable (information backup, clearing and deleting).FindingsThe analysis consisted of two major parts: first the assessment of measurement model and second the structural equation modelling analysis. A significant impact of mobile self-efficacy (basic mobile phone operations, using internet and email) was found on all the sub-constructs (information backup, information clearing and information deleting) of PDA practices. However, using internet and email has no significant impact on the information clearing practices of undergraduate students of Pakistani universities.Originality/valueThis study is a valuable addition to the extant literature because no comprehensive research has been carried out on the impact of mobile self-efficacy and PDA through mobile phones. It also contributes theoretically in the form of the development of a validated instrument on mobile-based PDA. Additionally, it possesses practical value for information literacy instruction programs.