bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways
Authors: Ye Lihua , Bae Munhyung , Cassilly Chelsi D. , Jabba Sairam V. , Thorpe Daniel W. , Martin Alyce M , Lu Hsiu-Yi , Wang Jinhu , Thompson John D. , Lickwar Colin R. , Poss Kenneth D. , Keating Damien J. , Jordt Sven-Eric , Clardy Jon , Liddle Rodger A. , Rawls John F. 
Published: June 2020

SUMMARYThe intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EECs). EECs can communicate nutritional information to the nervous system, but similar mechanisms for microbial information are unknown. Usingin vivoreal-time measurements of EEC and nervous system activity in zebrafish, we discovered that the bacteriaEdwardsiella tardaspecifically activates EECs through the receptor transient receptor potential ankyrin A1 (Trpa1) and increases intestinal motility in an EEC-dependent manner. Microbial, pharmacological, or optogenetic activation of Trpa1+EECs directly stimulates vagal sensory ganglia and activates cholinergic enteric neurons through 5-HT. We identified a subset of indole derivatives of tryptophan catabolism produced byE. tardaand other gut microbes that potently activates zebrafish EEC Trpa1 signaling and also directly stimulates human and mouse Trpa1 and intestinal 5-HT secretion. These results establish a molecular pathway by which EECs regulate enteric and vagal neuronal pathways in response to specific microbial signals.
Towards a better understanding of the low recall of insertion variants with short-read based variant callers
Authors: Delage Wesley , Thevenon Julien , Lemaitre Claire 
Published: June 2020

AbstractSince 2009, numerous tools have been developed to detect structural variants (SVs) using short read technologies. Insertions >50 bp are one of the hardest type to discover and are drastically underrepresented in gold standard variant callsets. The advent of long read technologies has completely changed the situation. In 2019, two independent cross technologies studies have published the most complete variant callsets with sequence resolved insertions in human individuals. Among the reported insertions, only 17 to 37% could be discovered with short-read based tools. In this work, we performed an in-depth analysis of these unprecedented insertion callsets in order to investigate the causes of such failures. We have first established a precise classification of insertion variants according to four layers of characterization: the nature and size of the inserted sequence, the genomic context of the insertion site and the breakpoint junction complexity. Because these levels are intertwined, we then used simulations to characterize the impact of each complexity factor on the recall of several SV callers. Simulations showed that the most impacting factor was the insertion type rather than the genomic context, with various difficulties being handled differently among the tested SV callers, and they highlighted the lack of sequence resolution for most insertion calls. Our results explain the low recall by pointing out several difficulty factors among the observed insertion features and provide avenues for improving SV caller algorithms and their combinations.Contactwesley.delage@irisa.fr
DYNC1LI2 regulates localization of the chaperone-mediated autophagy-receptor LAMP2A and improves cellular homeostasis in cystinosis
Authors: Rahman Farhana , Johnson Jennifer L. , Zhang Jinzhong , He Jing , Cherqui Stephanie , Catz Sergio D. 
Published: June 2020

SUMMARYThe dynein motor protein complex is required for retrograde transport but the functions of the intermediate-light chains that form the cargo-binding complex are not elucidated and the importance of individual subunits in the maintenance of cellular homeostasis is unknown. Here, using mRNA arrays and protein analysis, we show that the dynein subunit, intermediate chain 2 (DYNC1LI2) is downregulated in cystinosis, a lysosomal storage disorder caused by genetic defects in the lysosomal cystine transporter, cystinosin. Reconstitution of the expression of DYNC1LI2 inCtns-/-cells re-established endolysosomal dynamics. Defective vesicular trafficking in cystinotic cells was rescued by DYNC1LI2 expression which correlated with decreased endoplasmic reticulum stress manifested as decreased expression levels of the chaperone Grp78. Mitochondrial fragmentation in cystinotic fibroblasts was also rescued by DYNC1LI2. Survival of cystinotic cells to oxidative stress insult was increased by DYNC1LI2 reconstitution but not by its paralog DYNC1LI1, which also failed to decrease ER stress levels and mitochondrial fragmentation. Restoring DYNC1LI2 expression rescued the localization of the chaperone-mediated autophagy receptor, LAMP2A, and restored cellular homeostasis of cystinotic proximal tubule cells, the primary cell type affected in cystinosis. DYNC1LI2 failed to rescue phenotypes in cystinotic cells when LAMP2A was downregulated or when co-expressed with dominant negative (DN) RAB7 or DN-RAB11, which impair LAMP2A trafficking. DYNC1LI2 emerges as a new target to repair underlying trafficking and CMA defects in cystinosis, a mechanism that is not restored by currently used lysosomal depletion therapies.
The Potential ofCapsicum annumExtracts to PreventLactococcosisin Tilapia
Authors: Ndashe Kunda , Ngh’ake Stellah , Pola Emelda , Sakala Emmanuel Masautso , Kabwali Emmanuel , Moonga Ladslav , Kefi Alexander Shula , Hang’ombe Bernard Mudenda 
Published: June 2020

AbstractThe capsaicin was extracted in-house from locally purchased chili pepper (Capsicum annum) using the conventional solvent extraction method. Varying concentrations of capsaicin were mixed with Lactococcus garvieae each and inoculated on Mueller Hinton agar to determine the minimum bactericidal concentration. Four groups of 100 fish each were injected with either 1) Capsaicin, 2) bacteria and capsaicin, 3) bacteria and 4) normal saline (negative control). The fish were observed for 7 days post treatment and experiment was repeated three times. Protection against infection was measured by the lack of clinical disease and survivability of the fish during period of experimentation. The minimum bactericidal concentration of capsaicin on growth ofLactococcus garvieaewas 0.1967mg/ml. Significantly, more fish in the bacteria and capsaicin group survived (p<0.0001) compared to those injected with bacteria only. The findings suggest that chili pepper extract can preventLactococcus garvieaeinfection in tilapia.
Towards robust and replicable sex differences in the intrinsic brain function of autism
Authors: Floris Dorothea L. , Filho José O. A. , Lai Meng-Chuan , Giavasis Steve , Oldehinkel Marianne , Mennes Maarten , Charman Tony , Tillmann Julian , Dumas Guillaume , Ecker Christine , Dell’Acqua Flavio , Banaschewski Tobias , Moessnang Carolin , Baron-Cohen Simon , Durston Sarah , Loth Eva , Murphy Declan G. M. , Buitelaar Jan K. , Beckmann Christian F. , Milham Michael P. , Di Martino Adriana 
Published: June 2020

AbstractBackgroundMarked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data.MethodsWe addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level P < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research (GENDAAR).ResultsDiscovery analyses in ABIDE revealed significant main effects across the intrinsic functional connectivity (iFC) of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples – EU-AIMS LEAP.LimitationsGiven the lack ofa prioriharmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability.ConclusionsAtypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies.
Arhopalus rusticus(Coleoptera: Cerambycidae): a new vector for pine wood nematode,Bursaphelenchus xylophilus(Nematoda: Aphelenchoididae)
Authors: Wang Yang , Mao Yunfei , Chen Fengmao , Wang Lichao , song Juan , Zhou Lifeng 
Published: June 2020

AbstractIn the study on the transmission of pine wood nematodes byArhopalus rusticus, we research the ability and characteristics ofArhopalus rusticusto transmit pine wood nematodes. A total of 288Arhopalus rusticus(female 142, male 146) were collected and 20 (female 8, male 12) of them were able to carry pine wood nematodes. Results shown that 12 beetles can transmit pine wood nematodes.Arhopalus rusticusdoes not eat the pine bark, but eat the pine needles. Pine wood nematodes are transmitted through the feeding bite mark on the pine needles. In addition experiments further confirmed that pine wood nematodes could transmit through pine needles.
Environmental and genetic contributions to imperfectwMel-likeWolbachiatransmission and frequency variation
Authors: Hague Michael T.J. , Mavengere Heidi , Matute Daniel R. , Cooper Brandon S. 
Published: June 2020

ABSTRACTMaternally transmittedWolbachiabacteria infect about half of all insect species. They usually show imperfect maternal transmission and often produce cytoplasmic incompatibility (CI). Irrespective of CI,Wolbachiafrequencies tend to increase when rare only if they benefit host fitness. SeveralWolbachia, includingwMel that infectsDrosophila melanogastercause weak or no CI and persist at intermediate frequencies. On the island of São Tomé off West Africa, the frequencies ofwMel-likeWolbachiainfectingD. yakuba(wYak) andD. santomea(wSan) fluctuate, and the contributions of imperfect maternal transmission, fitness effects, and CI to these fluctuations are unknown. We demonstrate spatial variation inwYak frequency and transmission on São Tomé. Concurrent field estimates of imperfect maternal transmission do not predict spatial variation inwYak frequencies, which are highest at high altitudes where maternal transmission is the most imperfect. Genomic and genetic analyses provide little support forD. yakubaeffects onwYak transmission. Instead, rearing at cool temperatures reduceswYak titer and increases imperfect transmission to levels observed on São Tomé. Using mathematical models ofWolbachiafrequency dynamics and equilibria, we infer temporally variable imperfect transmission or spatially variable effects on host fitness and reproduction are required to explainwYak frequencies. In contrast, spatially stablewSan frequencies are plausibly explained by imperfect transmission, modest fitness effects, and weak CI. Our results provide insight into causes ofwMel-like frequency variation in divergent hosts. Understanding this variation is crucial to explainWolbachiaspread and to improvewMel biocontrol of human disease in transinfected mosquito systems.
The Distal Polybasic Cleavage Sites of SARS-CoV-2 Spike Protein Enhance Spike Protein-ACE2 Binding
Authors: Qiao Baofu , de la Cruz Monica Olvera 
Published: June 2020

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a crucial role in binding the human cell receptor ACE2 that is required for viral entry. Many studies have been conducted to target the structures of RBD-ACE2 binding and to design RBD-targeting vaccines and drugs. Nevertheless, mutations distal from the SARS-CoV-2 RBD also impact its transmissibility and antibody can target non-RBD regions, suggesting the incomplete role of the RBD region in the spike protein-ACE2 binding. Here, in order to elucidate distant binding mechanisms, we analyze complexes of ACE2 with the wild type spike protein and with key mutants via large-scale all-atom explicit solvent molecular dynamics simulations. We find that though distributed approximately 10 nm away from the RBD, the SARS-CoV-2 polybasic cleavage sites enhance, via electrostatic interactions and hydration, the RBD-ACE2 binding affinity. A negatively charged tetrapeptide (GluGluLeuGlu) is then designed to neutralize the positively charged arginine on the polybasic cleavage sites. We find that the tetrapeptide GluGluLeuGlu binds to one of the three polybasic cleavage sites of the SARS-CoV-2 spike protein lessening by 34% the RBD-ACE2 binding strength. This significant binding energy reduction demonstrates the feasibility to neutralize RBD-ACE2 binding by targeting this specific polybasic cleavage site. Our work enhances understanding of the binding mechanism of SARS-CoV-2 to ACE2, which may aid the design of therapeutics for COVID-19 infection.Abstract FigureTOC:The SARS-CoV-2 spike protein-ACE2 complex showing the polybasic cleavage sites
Combinatorial phosphorylation modulates the structure and function of the G protein gamma subunit in yeast
Authors: Toosi Zahra Nassiri , Su Xinya , Choudhury Shilpa , Li Wei , Pang Yui Tik , Gumbart James C. , Torres Matthew P. 
Published: June 2020

AbstractProtein intrinsically disordered regions (IDRs) are often targets of combinatorial post-translational modifications (PTMs) that serve to regulate protein structure and/or function. Emerging evidence suggests that the N-terminal tails of G protein γ subunits – essential components of heterotrimeric G protein complexes – are intrinsically disordered, highly phosphorylated governors of G protein signaling. Here, we demonstrate that the yeast Gγ Ste18 undergoes combinatorial, multi-site phosphorylation within its N-terminal IDR. Phosphorylation at S7 is responsive to GPCR activation and osmotic stress while phosphorylation at S3 is responsive to glucose stress and is a quantitative indicator of intracellular pH. Each site is phosphorylated by a distinct set of kinases and both are also interactive, such that phosphomimicry at one site affects phosphorylation on the other. Lastly, we show that phosphorylation produces subtle yet clear changes in IDR structure and that different combinations of phosphorylation modulate the activation rate and amplitude of the scaffolded MAPK Fus3. These data place Gγ subunits among the growing list of intrinsically disordered proteins that exploit combinatorial post-translational modification to govern signaling pathway output.
‘Phase Zero’ clinical study platform combining broadband Vis/near-infrared spectroscopy and electrophysiology to study human brain organoid models of neurodevelopmental disorders
Authors: Dutta Anirban , Karanth Sneha Sudhakar , Bhattacharya Mahasweta , Liput Michal , Augustyniak Justyna , Cheung Mancheung , Stachowiak Ewa K. , Stachowiak Michal K. 
Published: June 2020

AbstractHomeostatic control of neuronal excitability by modulation of synaptic inhibition (I) and excitation (E) of the principal neurons is important during brain maturation. The fundamental features of in-utero brain developmental, including local synaptic E-I ratio and bioenergetics, can be modeled by cerebral organoids (CO) that have exhibited highly regular nested oscillatory network events. Therefore, we evaluated a ‘Phase Zero’ clinical study platform combining broadband Vis/near-infrared(NIR) spectroscopy and electrophysiology to study E-I ratio based on the spectral exponent of local field potentials and bioenergetics based on the activity of mitochondrial Cytochrome-C Oxidase (CCO). We found a significant effect of the age of the healthy controls iPSC CO from 23 days to 3 months on the CCO activity (χ2(2,N=10)=20,p=4.5400e-05), and spectral exponent between 30–50Hz (χ2(2,N=16)=13.88,p=0.001). Also, a significant effect of drugs, choline (CHO), idebenone (IDB), R-alpha-lipoic acid plus acetyl-L-carnitine (LCLA), was found on the CCO activity (χ2(3,N=10)=25.44,p = 1.2492e-05), spectral exponent between 1–20Hz (χ2(3,N=16)=43.5,p=1.9273e-09) and 30–50Hz (χ2(3,N=16)=23.47, p=3.2148e-05) in 34 days old CO from schizophrenia (SCZ) patients iPSC. We present a multidimensional approach combining electrophysiology and Vis-NIR spectroscopy to complement traditional drug design approaches that can advance the system towards a normative parameter space.
Super-resolution segmentation network for reconstruction of packed neurites
Authors: Hang Zhou , Tingwei Quan , Qing Huang , Tian Liu , Tingting Cao , Shaoqun Zeng 
Published: June 2020

AbstractNeuron reconstruction can provide the quantitative data required for measuring the neuronal morphology and is crucial in the field of brain research. However, the difficulty in reconstructing packed neuritis, wherein massive labor is required for accurate reconstruction in most cases, has not been resolved. In this work, we provide a fundamental pathway for solving this challenge by proposing the use of the super-resolution segmentation network (SRSNet) that builds the mapping of the neurites in the original neuronal images and their segmentation in a higher-resolution space. SRSNet focuses on enlarging the distances between the boundaries of the packed neurites producing the high-resolution segmentation images. Thus, in the construction of the training datasets, only the traced skeletons of neurites are required, which vastly increase the usability of SRSNet. From the results of the experiments conducted in this work, it has been observed that SRSNet achieves accurate reconstruction of packed neurites where the other state-of-the-art methods fail.
Cholinergic upregulation by optogenetic stimulation of nucleus basalis after photothrombotic stroke in forelimb somatosensory cortex improves endpoint and motor but not sensory control of skilled reaching in mice
Authors: Agha Behroo Mirza , Akbary Roya , Ghasroddashti Arashk , Nazari-Ahangarkolaee Mojtaba , Whishaw Ian Q. , Mohajerani Majid H. 
Published: June 2020

AbstractA network of cholinergic neurons in the basal forebrain innerve the forebrain and are proposed to contribute to a variety of functions including attention, and cortical plasticity. This study examined the contribution of the nucleus basalis cholinergic projection to the sensorimotor cortex on recovery on a skilled reach-to-eat task following photothrombotic stroke in the forelimb region of the somatosensory cortex. Mice were trained to perform a single-pellet skilled reaching task and their pre and poststroke performance, from Day 4 to Day 28 poststroke, was assessed frame-by-frame by video analysis with end point, movement and sensorimotor integration measures. Somatosensory forelimb lesions produced impairments in endpoint and movement component measures of reaching and increased the incidence of fictive eating, a sensory impairment in mistaking a missed reach for a successful reach. Upregulated acetylcholine (ACh) release, as measured by local field potential recording, elicited via optogenetic stimulation of the nucleus basalis improved recovery of reaching and improved movement scores but did not affect a sensorimotor integration impairment poststroke. The results show that the mouse cortical forelimb somatosensory region contributes to forelimb motor behavior and suggest that ACh upregulation could serve as an adjunct to behavioral therapy for the acute treatment of stroke.
Proximity Labeling-assisted Identification of Endogenous Kinase Substrates
Authors: Niinae Tomoya , Imami Koshi , Sugiyama Naoyuki , Ishihama Yasushi 
Published: June 2020

AbstractMass spectrometry-based phosphoproteomics can identify more than 10,000 phosphorylated sites in a single experiment. But, despite the fact that enormous phosphosite information has been accumulated in public repositories, protein kinase-substrate relationships remain largely unknown. Here, we describe a method to identify endogenous substrates of kinases by means of proximity labeling. We used a proximity-dependent biotin identification approach, called BioID, in combination with kinase-perturbed phosphoproteomics profiling and phosphorylation sequence motifs derived fromin vitrokinase assay to find molecules that interact with a target kinase, that show altered phosphorylation in response to kinase perturbation, and that are directly phosphorylated by the kinasein vitro; i.e., endogenous kinase substrates. Application of this methodology to casein kinase 2 (CK2) and protein kinase A (PKA) identified 33 and 52 putative substrates, respectively. We also show that known cancer-associated missense mutations near phosphosites of substrates affect phosphorylation by CK2 or PKA, and thus might alter downstream signaling in cancer cells bearing these mutations.This study extends our knowledge of kinase-substrate networks by proposing a new large-scale approach to identify endogenous substrates of kinases.
Changes in Solo and Partnered Sexual Behaviors during the COVID-19 Pandemic: Findings from a U.S. Probability Survey
Authors: Hensel Devon J. , Rosenberg Molly , Luetke Maya , Fu Tsung-chieh , Herbenick Debby 
Published: June 2020

AbstractBackgroundResearch demonstrates that pandemics adversely impact sexual and reproductive health (SRH), but few have examined their impact on people’s participation in sex. We examined self-reported changes in solo and sexual behaviors in U.S. adults during early stages of the public health response to COVID-19.MethodsWe conducted an online, nationally representative, cross-sectional survey of U.S. adults (N=1010; aged 18-94 years; 62% response rate) from April 10-20, 2020. We used weighted multinomial logistic regression to examine past month self-reported changes (decreased, stable or increased) in ten solo and partnered sexual behaviors. Predictor variables included: having children at home, past month depressive symptoms, (ACHA 3-item scale), past month loneliness (UCLA 3-Item Loneliness scale), COVID-19 protection behaviors (adapted 12-item scale), perceived COVID-19 consequences (adapted 10-item scale) and COVID-19 knowledge (adapted 10-item scale).ResultsNearly half of all adults reported some kind of change – most commonly, a decrease – in their sexual behavior in the past month. Having elementary aged children at home, past month depressive symptoms and loneliness and enacting more COVID-19 protective behaviors were associated with both reduced partnered bonding behaviors, such as hugging, cuddling, holding hands and kissing, as well as reduced partnered sexual behaviors, such as oral sex, partnered genital touching and vaginal sex. Greater COVID-19 risk perception and greater COVID-19 knowledge were associated with mixed effects in behavior outcomes.ConclusionsOur data illustrate the very personal ways in which different pandemic-associated factors may create or inhibit opportunities for solo and partnered sex. The centrality of sexuality to health and well-being – even during pandemics – means that a critical piece of public health prevention and management responses should is ensuring that services and resource that support positive sexual decision making remain open and available.