bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust Rhythmogenesis via Spike Timing Dependent Plasticity
Authors: Socolovsky Gabi , Shamir Maoz 
Published: July 2020

Rhythmic activity has been observed in numerous animal species ranging from insects to humans, and in relation to a wide range of cognitive tasks. Various experimental and theoretical studies have investigated rhythmic activity. The theoretical efforts have mainly been focused on the neuronal dynamics, under the assumption that network connectivity satisfies certain fine-tuning conditions required to generate oscillations. However, it remains unclear how this fine tuning is achieved.Here we investigated the hypothesis that spike timing dependent plasticity (STDP) can provide the underlying mechanism for tuning synaptic connectivity to generate rhythmic activity. We addressed this question in a modeling study. We examined STDP dynamics in the framework of a network of excitatory and inhibitory neuronal populations that has been suggested to underlie the generation of oscillations in the gamma range. Mean field Fokker Planck equations for the synaptic weights dynamics are derived in the limit of slow learning. We drew on this approximation to determine which types of STDP rules drive the system to exhibit rhythmic activity, and demonstrate how the parameters that characterize the plasticity rule govern the rhythmic activity. Finally, we propose a novel mechanism that can ensure the robustness of self-developing processes, in general and for rhythmogenesis in particular.
SEPIA - SuscEptibility mapping PIpeline tool for phAse images
Authors: Chan Kwok-Shing , Marques José P. 
Published: July 2020

AbstractQuantitative susceptibility mapping (QSM) is a physics-driven computational technique that has a high sensitivity in quantifying iron deposition based on MRI phase images. Furthermore, it has a unique ability to distinguish paramagnetic and diamagnetic contributions such as haemorrhage and calcification based on image contrast. These properties have contributed to a growing interest to use QSM not only in research but also in clinical applications. However, it is challenging to obtain high quality susceptibility map because of its ill-posed nature, especially for researchers who have less experience with QSM and the optimisation of its pipeline. In this paper, we present an open-source processing pipeline tool called SuscEptibility mapping PIpeline tool for phAse images (SEPIA) dedicated to the post-processing of MRI phase images and QSM. SEPIA connects various QSM toolboxes freely available in the field to offer greater flexibility in QSM processing. It also provides an interactive graphical user interface to construct and execute a QSM processing pipeline, simplifying the workflow in QSM research. The extendable design of SEPIA also allows developers to deploy their methods in the framework, providing a platform for developers and researchers to share and utilise the state-of-the-art methods in QSM.
Multiple-labeled antibodies behave like single emitters in photoswitching buffer
Authors: Helmerich Dominic A. , Beliu Gerti , Sauer Markus 
Published: July 2020

AbstractThe degree of labeling (DOL) of antibodies has so far been optimized for high brightness and specific and efficient binding. The influence of the DOL on the blinking performance of antibodies used indirectstochastic optical reconstruction microscopy (dSTORM) has so far attained limited attention. Here, we investigated the spectroscopic characteristics of IgG antibodies labeled at DOLs of 1.1- 8.3 with Alexa Fluor 647 (Al647) at the ensemble and single-molecule level. Multiple-Al647-labeled antibodies showed weak and strong quenching interactions in aqueous buffer but could all be used fordSTORM imaging with spatial resolutions of ∼ 20 nm independent of the DOL. Photon antibunching experiments in aqueous buffer demonstrate that the emission of multiple-Al647-labeled antibodies switches from classical to non-classical light in photoswitching buffer. We developed a model that explains the observed blinking of multiple-labeled antibodies and can be used advantageously to develop improved fluorescent probes fordSTORM experiments.
Twists and turns of the salicylate catabolism inAspergillus terreus
Authors: Martins Tiago M. , Martins Celso , Pereira Cristina Silva 
Published: July 2020

ABSTRACTIn fungi, salicylate catabolism was believed to proceed only through the catechol branch of the 3-oxoadipate pathway, as showne.g.inAspergillus nidulans. However, the observation of a transient accumulation of gentisate upon cultivation ofAspergillus terreusin salicylate media questions this concept. To address this we have run a comparative analysis of the transcriptome of these two species after growth in salicylate using acetate as a control condition. The results revealed the high complexity of the salicylate metabolism inA. terreuswith the concomitant positive regulation of several pathways for the catabolism of aromatic compounds. This included the unexpected joint action of two pathways: the nicotinate and the 3-hydroxyanthranilate, possibly crucial for the catabolism of aromatics in this fungus. New genes participating in the nicotinate metabolism are here proposed, whereas the 3-hydroxyanthranilate catabolic pathway in fungi is described for the first time. The transcriptome analysis showed also for the two species an intimate relationship between salicylate catabolism and secondary metabolism. This study emphasizes that the central pathways for the catabolism of aromatic hydrocarbons in fungi hold many mysteries yet to be discovered.IMPORTANCEAspergilli are versatile cell factories used in industry for production of organic acids, enzymes and pharmaceutical drugs. To date, organic acids bio-based production relies on food substrates. These processes are currently being challenged to switch to renewable non-food raw materials; a reality that should inspire the use of lignin derived aromatic monomers. In this context, Aspergilli emerge at the forefront of future bio-based approaches due to their industrial relevance and recognized prolific catabolism of aromatic compounds. Notwithstanding considerable advances in the field, there are still important knowledge gaps in the central catabolism of aromatic hydrocarbons in fungi. Here, we disclosed a novel central pathway, defying previous established ideas on the central metabolism of the aromatic amino acid tryptophan in Ascomycota. We also observed that the catabolism of the aromatic salicylate greatly activated the secondary metabolism, furthering the significance of using lignin derived aromatic hydrocarbons as a distinctive biomass source.
Tendon-derived biomimetic surface topographies induce phenotypic maintenance of tenocytesin vitro
Authors: Dede Eren Aysegul , Vasilevich Aliaksei , Eren E. Deniz , Sudarsanam Phanikrishna , Tuvshindorj Urandelger , de Boer Jan , Foolen Jasper 
Published: July 2020

AbstractThe tenocyte niche contains biochemical and biophysical signals that are needed for tendon homeostasis. The tenocyte phenotype is correlated with cell shapein vivoandin vitro, and shape-modifying cues are needed for tenocyte phenotypical maintenance. Indeed, cell shape changes from elongated to spread when cultured on a flat surface, and rat tenocytes lose the expression of phenotypical markers throughout five passages. We hypothesized that tendon gene expression can be preserved by culturing cells in the native tendon shape. To this end, we reproduced the tendon topographical landscape into tissue culture polystyrene, using imprinting technology. We confirmed that the imprints forced the cells into a more elongated shape, which correlated with the level of Scleraxis expression. When we cultured the tenocytes for seven days on flat surfaces and tendon imprints, we observed a decline in tenogenic marker expression on flat but not on imprints. This research demonstrates that native tendon topography is an important factor contributing to the tenocyte phenotype. Tendon imprints therefore provide a powerful platform to explore the effect of instructive cues originating from native tendon topography on guiding cell shape, phenotype and function of tendon-related cells.
Isoprenylcysteine carboxylmethyltransferase-based therapy for Hutchinson–Gilford progeria syndrome
Authors: Marcos-Ramiro Beatriz , Gil-Ordóñez Ana , Marín-Ramos Nagore I. , Ortega-Nogales Francisco J. , Balabasquer Moisés , Gonzalo Pilar , Rolas Loïc , Barkaway Anna , Nourshargh Sussan , Andrés Vicente , Martín-Fontecha Mar , López-Rodríguez María L. , Ortega-Gutiérrez Silvia 
Published: July 2020

ABSTRACTProgerin is a mutant prelamin A variant that causes Hutchinson–Gilford progeria syndrome (HGPS, progeria), a rare genetic disease characterized by premature aging and death in childhood. Although several therapeutic approaches have been explored in experimental models, clinical trials have shown very limited benefits in HGPS patients. Here, we describe the development of UCM-13207, a new potent inhibitor of isoprenylcysteine carboxylmethyltransferase (ICMT) that reduces progerin nuclear accumulation and ameliorates the typical alterations in progeroid human and mouse cells. UCM-13207 also improves phenotypic anomalies and extends lifespan in progerin-expressingLmnaG609G/G609Gmice. These results support the potential use of UCM-13207 as a new treatment for progeria.
The prevalence ofAngiostrongylus cantonensisin rodent hosts in China and several Asian countries: a systematic review and meta-analysis
Authors: Bai Huifang , Cao Yizhen , Chen Yunqiu , Zhang Lingmin , Wu Chunyun , Cheng Mei 
Published: July 2020

AbstractBackgroundAngiostrogylus cantonensis(A.cantonensis) is a zoonotic parasitic nematode, with a worldwide distribution, causing eosinophilic meningitis or meningoencephalitis in humans. Although the biology ofA.cantonensisis relatively well known, little is understood about the transmission level in different zoogeographical regions, especially in Asia. Here, to evaluate the prevalence ofA.cantonensisin rodent hosts in China and several Asian countries, we conducted a systematic review registered with PROSPERO (CRD42020161665).MethodsRecords were selected systematically from 7 databases (Medline via to Pubmed, Web of science, Scopus, Google Scholar, CNKI, Wangfang, CBM). Forest plots and random-effects model were used to display pooled estimates. The Freeman-Tukey double arcsine transformation of R software was used to conduct meta-analysis and statistical significance was set at 0.05.ResultsA total of 67 studies met the inclusion criteria and were included in the systematic review and meta-analysis. The pooled prevalence estimates ofA.cantonensisinfection in rodents was 0.1003 (95%CI: 0.0765, 0.1268). There was significant heterogeneity in reported outcomes (p<0.0001). So we considered that there was no publication bias in the included studies.ConclusionTheA.cantonensisinfection rate among rodent hosts was still high in Asia, particularly in China, especially inRattus norvegicus, and thus comprehensive measures should be taken for rodent hosts control to avoid an angiostrongyliasis outbreak. Due to the wide distribution and movement of rodent hosts, people in all regions of China, even in other Asia area live at risk of an infection. Hence, the development of more reliable diagnostic tests will be key for an effective identification of cases as well as improved patient care. Consequently, further studies are required to updated strategies for controllingA.cantonensisinfection among human population.
Litter expansion alters metabolic homeostasis in a sexually divergent manner
Authors: Kurup Kavitha , Mann Shivani N , Jackson Jordan , Matyi Stephanie , Ranjo-Bishop Michelle , Freeman Willard M. , Stout Michael B , Richardson Arlan , Archana Unnikrishnan 
Published: July 2020

AbstractNutritional manipulations early in life have been shown to influence growth rate and elicit long lasting effects which in turn has been found to impact lifespan. Therefore, we studied the long-term effects of pre-weaning dietary restriction implemented by litter expansion (4, 6, 8, 10, and 12 pups per dam: LS4, LS6, LS8, LS10, LS12) on male and female C57BL/6 mice. After weaning, these mice were fedad libituma commercial lab chow for the 15-month duration of the study. The mice from large litter sizes (LS12) were significantly leaner and had reduced total fat mass compared to the normal size litters (LS 6) starting from weaning through to 15 months of age. Male LS10 & 12 mice showed significant reduction in their fat depot masses at 15 months of age: gonadal, subcutaneous, and brown fat whereas the females did not mimic these findings. At 9 months of age, both male and female LS10 and 12 mice showed improved glucose tolerance; however, only male LS10 and LS12 mice showed improved insulin tolerance starting at 5 months of age. In addition, we found that the male LS8, 10 & 12 mice at 15 months of age showed significantly reduced IGF-1 levels in the serum and various other organs (liver, gastrocnemius and brain cortex). Interestingly, the female LS8, 10, 12 mice showed a different pattern with reduced IGF-1 levels in serum, liver and gastrocnemius but not in the brain cortex. Similarly, the litter expanded mice showed sexual divergence in levels of FGF21 and adiponectin with only the male mice showing increased FGF21 and adiponectin levels at 15 months of age. In summary, our data show that, litter expansion results in long-lasting metabolic changes that are age and sex dependent with the male mice showing an early and robust response compared to female mice.
Impacts of thermal fluctuations on heat tolerance and its metabolomic basis across plant and animal species
Authors: Noer Natasja Krog , Pagter Majken , Bahrndorff Simon , Malmendal Anders , Kristensen Torsten Nygaard 
Published: July 2020

AbstractTemperature varies on a daily and seasonal scale and thermal fluctuations are likely to become even more pronounced under future climate changes. Studies suggest that plastic responses are crucial for species’ ability to cope with thermal stress, but traditionally laboratory studies on ectotherms are performed at constant temperatures and often limited to a few model species and thus not representative for the natural environment. We argue that thermoregulatory behavior and microhabitat shape the response exerted by different organisms to fluctuating temperatures. Thus, a sessile organism incapable of significant behavioral temperature avoidance will be more plastic and exert greater physiological response to thermal fluctuations than mobile organisms that can quickly evade temperature stress. Here we investigate how acclimation to fluctuating (13.2-26.9°C) and constant (20.4°C) temperatures impact heat stress tolerance across a plant (Arabidopsis thaliana) and two animal species (Orchesella cinctaandDrosophila melanogaster) inhabiting widely different thermal microhabitats and selective pasts. Moreover, we investigate the underlying metabolic responses of acclimation using an NMR metabolomics approach. We find increased heat tolerance for all species exposed to fluctuating acclimation temperatures; most pronounced forA. thalianawhich also showed a strong metabolic response to thermal fluctuations. Generally, sugars were more abundant acrossA. thalianaandD. melanogasterwhen exposed to fluctuating compared to constant temperatures, whereas amino acids were less abundant. However, we do not find much evidence for similar metabolomics responses to fluctuating temperature acclimation across species. Differences between the investigated species’ ecology, their distinct selective past and different ability to behaviorally thermoregulate may have shaped their physiological response to thermal fluctuations.
Adults vs. neonates: Differentiation of functional connectivity between the basolateral amygdala and occipitotemporal cortex
Authors: Hansen Heather A. , Li Jin , Saygin Zeynep M. 
Published: July 2020

AbstractThe amygdala, a subcortical structure known for social and emotional processing, consists of multiple subnuclei with unique functions and connectivity patterns. Tracer studies in adult macaques have shown that the basolateral subnuclei differentially connect to parts of visual cortex, with stronger connections to anterior regions and weaker connections to posterior regions; infant macaques show robust connectivity even with posterior visual regions. Do these developmental differences also exist in the human amygdala, and are there specific functional regions that undergo the most pronounced developmental changes in their connections with the amygdala? To address these questions, we explored the functional connectivity (from resting-state fMRI data) of the basolateral amygdala to occipitotemporal cortex in human neonates scanned within one week of life and compared the connectivity patterns to those observed in young adults. Specifically, we calculated amygdala connectivity to anterior-posterior gradients of the anatomically-defined occipitotemporal cortex, and also to putative occipitotemporal functional parcels, including primary and high-level visual and auditory cortices (V1, A1, face, scene, object, body, high-level auditory regions). Results showed a decreasing gradient of functional connectivity to the occipitotemporal cortex in adults – similar to the gradient seen in macaque tracer studies – but no such gradient was observed in neonates. Further, adults had stronger connections to high-level functional regions associated with face, body, and object processing, and weaker connections to primary sensory regions (i.e., A1, V1), whereas neonates showed the same amount of connectivity to primary and high-level sensory regions. Overall, these results show that functional connectivity between the amygdala and occipitotemporal cortex is not yet differentiated in neonates, suggesting a role of maturation and experience in shaping these connections later in life.
SARS-CoV2 genome analysis of Indian isolates and molecular modelling of D614G mutated spike protein with TMPRSS2 depicted its enhanced interaction and virus infectivity
Authors: Raghav Sunil , Ghosh Arup , Turuk Jyotirmayee , Kumar Sugandh , Jha Atimukta , Madhulika Swati , Priyadarshini Manasi , Biswas Viplov K. , Shyamli P. Sushree , Singh Bharati , Singh Neha , Singh Deepika , Datey Ankita , Kiran Avula , Smita Shuchi , Sabat Jyotsnamayee , Bhattacharya Debdutta , Dash Rupesh , Senapati Shantibhushan , Beuria Tushar K. , Swain Rajeeb , Chattopadhyay Soma , Syed Gulam Hussain , Dixit Anshuman , Prasad Punit ,   Odisha COVID-19 study group,   ILS COVID-19 team, Pati Sanghamitra , Parida Ajay 
Published: July 2020

AbstractCOVID-19 that emerged as a global pandemic is caused by SARS-CoV-2 virus. The virus genome analysis during disease spread reveals about its evolution and transmission. We did whole genome sequencing of 225 clinical strains from the state of Odisha in eastern India using ARTIC protocol-based amplicon sequencing. Phylogenetic analysis identified the presence of all five reported clades 19A, 19B, 20A, 20B and 20C in the population. The analyses revealed two major routes for the introduction of the disease in India i.e. Europe and South-east Asia followed by local transmission. Interestingly, 19B clade was found to be much more prevalent in our sequenced genomes (17%) as compared to other genomes reported so far from India. The haplogroup analysis for clades showed evolution of 19A and 19B in parallel whereas the 20B and 20C appeared to evolve from 20A. Majority of the 19A and 19B clades were present in cases that migrated from Gujarat state in India suggesting it to be one of the major initial points of disease transmission in India during month of March and April. We found that with the time 20A and 20B clades evolved drastically that originated from central Europe. At the same time, it has been observed that 20A and 20B clades depicted selection of four common mutations i.e. 241 C>T (5’UTR), P323L in RdRP, F942F in NSP3 and D614G in the spike protein. We found an increase in the concordance of G614 mutation evolution with the viral load in clinical samples as evident from decreased Ct value of spike and Orf1ab gene in qPCR. Molecular modelling and docking analysis identified that D614G mutation enhanced interaction of spike with TMPRSS2 protease, which could impact the shedding of S1 domain and infectivity of the virus in host cells.
Crystal structure of steroid reductase SRD5A reveals conserved steroid reduction mechanism
Authors: Han Yufei , Zhuang Qian , Sun Bo , Lv Wenping , Wang Sheng , Xiao Qingjie , Pang Bin , Zhou Youli , Wang Fuxing , Chi Pengliang , Wang Qisheng , Li Zhen , Zhu Lizhe , Li Fuping , Deng Dong , Chiang Ying-Chih , Li Zhenfei , Ren Ruobing 
Published: July 2020

AbstractSteroid hormones are essential in stress response, immune system regulation, and reproduction in mammals. Steroids with 3-oxo-Δ4structure, such as testosterone, androstenedione and progesterone, could be catalyzed by steroid 5α-reductases (SRD5As) to generate their corresponding 3-oxo-5α steroids, which are essential for multiple physiological and pathological processes. Abnormal activities of SRD5As will lead to benign prostatic hyperplasia, alopecia, prostatic cancer or infertility due to the poor quality of sperms. However, the detailed reduction mechanisms of SRD5As remain elusive. Here we report the crystal structure of PbSRD5A, which shares 60.6% and 51.5% sequence similarities with human SRD5A1 and −2 respectively, fromProteobacteria bacteriumin complex with the cofactor NADPH at 2.0 Å resolution. PbSRD5A exists as a monomer comprised of seven transmembrane segments (TMs). The TM1-4 enclose a hydrophobic cavity for steroids substrates binding, whereas TM5-7 coordinate with cofactor NADPH through extensive hydrogen bonds network. Homology-based structural models of HsSRD5A1 and −2, together with extensive biochemical characterizations, for the first time unveiled the substrate recognition of SRD5As and provide an important framework for further understanding of the mechanism of NADPH mediated steroids 3-oxo-Δ4reduction. Based on these analyses, the design of therapeutic molecules targeting SRD5As with improved specificity and therapeutic efficacy would be possible.One Sentence SummaryStructural and biochemical characterizations decipher the evolutionarily conserved mechanism in steroid 5α-reductases catalyzing NADPH mediated steroids reduction.
Single-cell analysis reveals cellular heterogeneity and molecular determinants of hypothalamic leptin-receptor cells
Authors: Kakava-Georgiadou N. , Severens J.F. , Jørgensen A.M. , Stoltenborg I. , Garner K.M. , Luijendijk M.C.M , Drkelic V. , van Dijk R. , Dickson S.L. , Pers T.H. , Basak O. , Adan R.A.H. 
Published: July 2020

AbstractHypothalamic nuclei which regulate homeostatic functions express leptin receptor (LepR), the primary target of the satiety hormone leptin. Single-cell RNA sequencing (scRNA-seq) has facilitated the discovery of a variety of hypothalamic cell types. However, low abundance of LepR transcripts prevented further characterization of LepR cells. Therefore, we perform scRNA-seq on isolated LepR cells and identify eight neuronal clusters, including three uncharacterized Trh-expressing populations as well as 17 non-neuronal populations including tanycytes, oligodendrocytes and endothelial cells. Food restriction had a major impact on Agrp neurons and changed the expression of obesity-associated genes. Multiple cell clusters were enriched for GWAS signals of obesity. We further explored changes in the gene regulatory landscape of LepR cell types. We thus reveal the molecular signature of distinct populations with diverse neurochemical profiles, which will aid efforts to illuminate the multi-functional nature of leptin’s action in the hypothalamus.