bluuebunny/crossref_metadata_2025_split huggingface dataset:
PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates
Authors: Xu Yun-Fei , Chen Xu , Yang Zhao , Xiao Peng , Liu Chun-Hua , Li Kang-Shuai , Yang Xiao-Zhen , Wang Yi-Jing , Zhu Zhong-Liang , Xu Zhi-Gang , Zhang Sheng , Wang Chuan , Song You-Chen , Zhao Wei-Dong , Wang Chang-He , Ji Zhi-Liang , Zhang Zhong-Yin , Cui Min , Sun Jin-Peng , Yu Xiao 
Published: October 2019

ABSTRACTTyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrated that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses revealed key residues that the interactions between govern the PTP-MEG2 and NSF-pY83 site, specify PTP-MEG2 substrate selectivity and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface revealed that PTP-MEG2 controls the fusion pore opening through non-NSF dependent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we discovered that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY125 and MUNC18-1-pY145 site. Further structural and biochemical analysis confirmed the interaction of PTP-MEG2 with MUNC18-1-pY145 or DYNAMIN2-pY125 through a distinct structural basis compared with that of the NSF-pY83 site. Our studies extended mechanistic insights in complex exocytosis processes.HIGHLIGHTSPTP-MEG2 regulates multiple steps of exocytosis.A crystal structure of the PTP-MEG2/phosphor-NSF-pY83 segment was obtained.Functional delineation of the PTP-MEG2/NSF interface led to the discovery of new PTP-MEG2 substrates.PTP-MEG2 regulates fusion pore opening and extension through the DYNAMIN2-pY125 site and MUNC18-1 pY145 site.The distinct structural basis of the recognition of substrates by PTP-MEG2 allows selective inhibitor design.
Roles of adenine methylation and genetic mutations in adaptation to different temperatures in Serratia marcescens
Authors: Bruneaux Matthieu , Kronholm Ilkka , Ashrafi Roghaieh , Ketola Tarmo 
Published: October 2019

AbstractEpigenetic modifications can contribute to adaptation, but the relative contributions of genetic and epigenetic variation are unknown. Previous studies on the role of epigenetic changes in adaptation in eukaryotes have nearly exclusively focused on cytosine methylation (m5C), while prokaryotes exhibit a richer system of methyltransferases targetting adenines (m6A) or cytosines (m4C, m5C). DNA methylation in prokaryotes has many roles, but its potential role in adaptation still needs further investigation. We collected phenotypic, genetic, and epigenetic data using single molecule real-time sequencing of clones of the bacterium Serratia marcescens that had undergone experimental evolution in contrasting temperatures to investigate the relationship between environment and genetic, epigenetic, and phenotypic changes. This data provided a detailed description of the methylation landscape of S. marcescens and allowed us to examine the potential contributions of genetic and epigenetic changes to phenotypic adaptation. The genomic distribution of GATC motifs, which are the main target for m6A methylation, and of partially methylated epiloci pointed to a link between m6A methylation and regulation of gene expression in S. marcescens. Evolved strains, while genetically homogeneous, exhibited many polymorphic m6A epiloci. There was no strong support for a genetic control of methylation changes in our experiment, and no clear evidence of parallel environmentally-induced or environmentally-selected methylation changes at specific epiloci was found. Both some genetic and epigenetic variants were associated with some phenotypic traits. Overall, our results suggest that both genetic and adenine methylation changes have potential to contribute to phenotypic adaptation in S. marcescens, but that any environmentally-induced epigenetic change occurring in our experiment would probably have been quite labile.
Optimizing the Accuracy of Cortical Volumetric Analysis in Traumatic Brain Injury
Authors: Diamond Bram R. , Mac Donald Christine L. , Snider Samuel B. , Fischl Bruce , Dams-O’Connor Kristen , Edlow Brian L. 
Published: October 2019

AbstractCortical volumetric analysis is widely used to study the anatomic basis of neurological deficits in patients with traumatic brain injury (TBI). However, patients with TBI-related lesions are often excluded from analysis, because cortical lesions may compromise the accuracy of reconstructed surfaces upon which volumetric measurements are based. Here, we propose a novel FreeSurfer-based lesion correction method and illustrate its impact on cortical volume measures in patients with chronic moderate-to-severe TBI. We performed MRI in 87 patients at mean+/−SD 10.9+/−9.1 years post-injury using a T1-weighted multi-echo MPRAGE sequence at 1 mm resolution. Following surface reconstruction, we parcellated the cerebral cortex into seven functional networks using FreeSurfer’s standard pipeline. Next, we manually labeled vertices on the cortical surface where lesions caused inaccuracies and removed them from network-based cortical volumetric measures. After performing this lesion correction procedure, we measured the surface area of lesion overlap with each network and the percent volume of each network affected by lesions. We identified 120 lesions that caused inaccuracies in the cortical surface in 46 patients. In these 46 patients, the most commonly lesioned networks were the limbic and default mode networks (95.7% each), followed by the executive control (78.3%), and salience (71.7%) networks. The limbic network had the largest average surface area of lesion overlap (4.4+/−3.7%) and the largest percent volume affected by lesions (12.7+/−9.7%). The lesion correction method has the potential to improve the accuracy of cortical volumetric measurements and permit inclusion of patients with lesioned brains in quantitative analyses, providing new opportunities to elucidate network-based mechanisms of neurological deficits in patients with TBI.
Quantitative Measurements of Enlarged Perivascular Spaces in the Brain are Associated with Retinal Microvascular Parameters in Older Community-Dwelling Subjects
Authors: Ballerini Lucia , McGrory Sarah , Valdés Hernández Maria del C. , Lovreglio Ruggiero , Pellegrini Enrico , MacGillivray Tom , Maniega Susana Muñoz , Henderson Ross , Taylor Adele , Bastin Mark E. , Doubal Fergus , Trucco Emanuele , Deary Ian J. , Wardlaw Joanna 
Published: October 2019

ABSTRACTBackgroundPerivascular Spaces (PVS) become increasingly visible with advancing age on brain MRI, yet their relationship to morphological changes in the underlying microvessels remains poorly understood. Retinal and cerebral microvessels share morphological and physiological properties. We compared computationally-derived PVS morphologies with retinal vessel morphologies in older people.MethodsWe analysed data from community-dwelling individuals who underwent multimodal brain MRI and retinal fundus camera imaging at mean age 72.55 years (SD=0.71). We assessed centrum semiovale PVS computationally to determine PVS total volume and count, and mean per-subject individual PVS length, width and size. We analysed retinal images using the VAMPIRE software suite, obtaining the Central Retinal Artery and Vein Equivalents (CRVE and CRAE), Arteriole-to-Venule ratio (AVR), and fractal dimension (FD) of both eyes. We investigated associations using general linear models, adjusted for age, gender, and major vascular risk factors.ResultsIn 381 subjects with all measures, increasing total PVS volume and count were associated with decreased CRAE in the left eye (volume β=-0.170, count β=-0.184, p<0.001). No associations of PVS with CRVE were found. The PVS total volume, individual width and size increased with decreasing FD of the arterioles (a) and venules (v) of the left eye (total volume: FDa β=-0.137, FDv β=-0.139, p<0.01; width: FDa β=-0.144, FDv β=-0.158, p<0.01; size: FDa β=-0.157, FDv β=-0.162, p<0.01).ConclusionsIncrease in PVS number and size visible on MRI reflect arteriolar narrowing and lower retinal arteriole and venule branching complexity, both markers of impaired microvascular health. Computationally-derived PVS metrics may be an early indicator of failing vascular health and should be tested in longitudinal studies.
Association of Model Neurotransmitters with Lipid Bilayer Membranes
Authors: Josey B. , Heinrich F. , Silin V. , Lösche M. 
Published: October 2019

AbstractAimed to reproduce the results of electrophysiological studies of synaptic signal transduction, conventional models of neurotransmission are based on the specific binding of neurotransmitters to ligand-gated receptor ion channels. However, the complex kinetic behavior observed in synaptic transmission cannot be reproduced in a standard kinetic model without the ad hoc postulation of additional conformational channel states. On the other hand, if one invokes unspecific neuro-transmitter adsorption to the bilayer—a process not considered in the established models—the electrophysiological data can be rationalized with only the standard set of three conformational receptor states that also depend on this indirect coupling of neurotransmitters via their membrane interaction. Experimental verification has been difficult because binding affinities of neuro-transmitters to the lipid bilayer are low. We quantify this interaction with surface plasmon resonance to measure equilibrium dissociation constants in neurotransmitter membrane association. Neutron reflectometry on artificial membranes reveals the structural aspects of neurotransmitters association with zwitterionic and anionic bilayers. We establish that serotonin interacts non-specifically with the membrane at physiologically relevant concentrations whilst GABA (γ-aminobutyric acid) does not. Surface plasmon resonance shows that serotonin adsorbs with millimolar affinity and neutron reflectometry shows that it penetrates the membrane deeply whereas GABA is excluded from the bilayer.SignificanceReceptor ion channels in the postsynaptic membrane and their neurotransmitter agonists enable fast communication between neuronal cells. Electrophysiology studies reveal surprisingly complex kinetics that apparently require a variety of protein conformational states for their quantitative interpretation, but an alternate hypothesis invoking neurotransmitter membrane association reduces the complexity of the underlying reaction schemes significantly. While their affinity may be low, and is hard to quantify experimentally, neurotransmitter membrane association can be relevant because of their large temporary concentration in the synaptic cleft. With thermodynamic and structural measurements we quantify membrane-bound states of serotonin, establishing this neurotransmitter as membrane-affine, whereas the affinity of the more hydrophilic GABA is too low to register in our sensitivity-optimized measurement techniques.
Long-read bitter gourd (Momordica charantia) genome and the genomic architecture of domestication
Authors: Matsumura Hideo , Hsiao Min-Chien , Toyoda Atsushi , Taniai Naoki , Tarora Kazuhiko , Urasaki Naoya , Anand Shashi S. , Dhillon Narinder P. S. , Schafleitner Roland , Lee Cheng-Ruei 
Published: October 2019

AbstractBitter gourd (Momordica charantia) is a vegetable and medicinal plant of the family Cucurbitaceae. Here we report a chromosome-level assembly, with highest contig N50 (close to 10 Mb) and proportion of sequences placed on chromosomes (96%) in Cucurbitaceae. Population resequencing revealed the divergence between wild and cultivars at about 6000 years ago. Different cultivar groups have distinct allelic compositions in loci associated with domestication traits, suggesting phenotypic changes were achieved by allele frequency shifts in independent loci. Noticeably, one candidate locus for fruit size locates within a region missing from a recent Illumina-based assembly. Despite breeding efforts to increase female flower proportion, the gynoecy locus exhibits high variation within and low differentiation between wild and cultivar groups, likely because artificial directional selection could not overwhelm natural balancing selection. Our study provides resources to further investigate the genetic architecture of bitter gourd as well highlights the importance of a well-assembled genome.
Actomyosin, vimentin and LINC complex pull on osteosarcoma nuclei to deform on micropillar topography
Authors: Wakhloo Nayana Tusamda , Anders Sebastian , Badique Florent , Eichhorn Melanie , Brigaud Isabelle , Petithory Tatiana , Vassaux Maxime , Milan Jean-Louis , Freund Jean-Noël , Rühe Jürgen , Davidson Patricia M. , Pieuchot Laurent , Anselme Karine 
Published: October 2019

ABSTRACTCell deformation occurs in many critical biological processes, including cell extravasation during immune response and cancer metastasis. These cells deform the nucleus, its largest and stiffest organelle, while passing through narrow constrictions in vivo and the underlying mechanisms still remain elusive. It is unclear which biochemical actors are responsible and whether the nucleus is pushed or pulled (or both) during deformation. Herein we use an easily-tunable poly-L-lactic acid micropillar topography, mimicking in vivo constrictions to determine the mechanisms responsible for nucleus deformation. Using biochemical tools, we determine that actomyosin contractility, vimentin and nucleo-cytoskeletal connections play essential roles in nuclear deformation, but not A-type lamins. We chemically tune the adhesiveness of the micropillars to show that pulling forces are predominantly responsible for the deformation of the nucleus. We confirm these results using an in silico cell model and propose a comprehensive mechanism for cellular and nuclear deformation during confinement. These results indicate that microstructured biomaterials are extremely versatile tools to understand how forces are exerted in biological systems and can be useful to dissect and mimic complex in vivo behaviour.
Quantifying glioblastoma drug response dynamics incorporating resistance and blood brain barrier penetrance from experimental data
Authors: Massey Susan Christine , Urcuyo Javier C. , Marin Bianca Maria , Sarkaria Jann N. , Swanson Kristin R. 
Published: October 2019

AbstractMany drugs investigated for the treatment of glioblastoma (GBM) have had poor clinical outcomes, as their efficacy is dependent on adequate delivery to sensitive tumor cell populations, which is limited by the blood-brain barrier (BBB). Further complicating evaluation of therapeutic efficacy, tumors can become resistant to anti-cancer drugs, and it can be difficult to gauge the extent to which BBB limitations and resistance each contribute to a drug’s failure. To address this question, we developed a minimal mathematical model to characterize these elements of overall drug response, informed by time-series bioluminescence imaging data from a treated patient-derived xenograft (PDX) experimental model. By fitting this mathematical model to a preliminary dataset in a series of nonlinear regression steps, we estimated parameter values for individual PDX subjects that correspond to the dynamics seen in experimental data. Using these estimates, we performed a parameter sensitivity analysis using Latin hypercube sampling and partial rank correlation coefficients. Results from this analysis combined with simulation results suggest that BBB permeability may play a slightly larger role in therapeutic efficacy than drug resistance. Our model and fitting technique to estimate parameters from data may be a useful tool in aiding further exploration of these challenges in future studies of drug efficacy with larger datasets.
Shared neural resources of rhythm and syntax: An ALE Meta-Analysis
Authors: Heard Matthew , Lee Yune S. 
Published: October 2019

AbstractA growing body of evidence has highlighted behavioral connections between musical rhythm and linguistic syntax, suggesting that these may be mediated by common neural resources. Here, we performed a quantitative meta-analysis of neuroimaging studies using activation likelihood estimate (ALE) to localize the shared neural structures engaged in a representative set of musical rhythm (rhythm, beat, and meter) and linguistic syntax (merge movement, and reanalysis). Rhythm engaged a bilateral sensorimotor network throughout the brain consisting of the inferior frontal gyri, supplementary motor area, superior temporal gyri/temporoparietal junction, insula, the intraparietal lobule, and putamen. By contrast, syntax mostly recruited the left sensorimotor network including the inferior frontal gyrus, posterior superior temporal gyrus, premotor cortex, and supplementary motor area. Intersections between rhythm and syntax maps yielded overlapping regions in the left inferior frontal gyrus, left supplementary motor area, and bilateral insula—neural substrates involved in temporal hierarchy processing and predictive coding. Together, this is the first neuroimaging meta-analysis providing detailed anatomical overlap of sensorimotor regions recruited for musical rhythm and linguistic syntax.
TGF-β signaling is critical for maintenance of the tendon cell fate
Authors: Tan Guak-Kim , Pryce Brian A. , Stabio Anna , Brigande John V. , Wang ChaoJie , Xia Zheng , Tufa Sara F. , Keene Douglas R. , Schweitzer Ronen 
Published: October 2019

AbstractStudies of cell fate focus on specification, but little is known about maintenance of the differentiated state. We find that TGFβ signaling plays an essential role in maintenance of the tendon cell fate. To examine the role TGFβ signaling in tenocytes TGFβ type II receptor was targeted in the Scleraxis cell lineage. Tendon development was not disrupted in mutant embryos, but shortly after birth tenocytes lost differentiation markers and reverted to a more stem/progenitor state. Targeting of Tgfbr2 using other Cre drivers did not cause tenocyte dedifferentiation suggesting a critical significance for the spatio-temporal activity of ScxCre. Viral reintroduction of Tgfbr2 to mutants was sufficient to prevent and even rescue mutant tenocytes suggesting a continuous and cell-autonomous role for TGFβ signaling in cell fate maintenance. These results uncover the critical importance of molecular pathways that maintain the differentiated cell fate and a key role for TGFβ signaling in these processes.
STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation
Authors: Kim Jong Wook , Berrios Christian , Kim Miju , Schade Amy E. , Adelmant Guillaume , Yeerna Huwate , Damato Emily , Iniguez Amanda Balboni , Swanson Selene K. , Florens Laurence , Washburn Michael P. , Stegmaier Kim , Gray Nathaniel S. , Tamayo Pablo , Gjoerup Ole , Marto Jarrod A. , DeCaprio James A. , Hahn William C. 
Published: October 2019

AbstractAlterations involving serine-threonine phosphatase PP2A subunits occur in a range of human cancers and partial loss of PP2A function contributes to cell transformation. Displacement of regulatory B subunits by the SV40 Small T antigen (ST) or mutation/deletion of PP2A subunits alters the abundance and types of PP2A complexes in cells, leading to transformation. Here we show that ST not only displaces common PP2A B subunits but also promotes A-C subunit interactions with alternative B subunits (B’’’, striatins) that are components of the Striatin-interacting phosphatase and kinase (STRIPAK) complex. We found that STRN4, a member of STRIPAK, is associated with ST and is required for ST-PP2A-induced cell transformation. ST recruitment of STRIPAK facilitates PP2A-mediated dephosphorylation of MAP4K4 and induces cell transformation through the activation of the Hippo pathway effector YAP1. These observations identify an unanticipated role of MAP4K4 in transformation and show that the STRIPAK complex regulates PP2A specificity and activity.
Emotion regulation and intervention in adults with autism spectrum disorder: a synthesis of the literature
Authors: Lim Jan Mei 
Published: October 2019

Purpose
Emotion regulation is an ongoing multiprocess phenomenon and is a challenging developmental task to acquire in individuals with autism spectrum disorder (ASD) who have different neurobiological profiles and emotion regulation problems. The purpose of this paper is to review recent literature to understand the neurobiological and psychological perspective of emotion regulation in ASD, while converging themes of psychosocial interventions and existing best practices on emotion regulation within this heterogeneous population are reviewed and discussed in consideration of intellectual disability (ID).

Design/methodology/approach
Review of recent literature and common empirically supported interventions addressing emotional regulation implemented in individuals with and without ASD, and with and without ID were included in the electronic database search through PubMed, EBSChost, Science Direct, Wiley Online Library, GALE and SAGE. Search terms used included autism, ID, cognitive control, executive function, sensory processing/intervention, emotion regulation, cognitive behavior therapy, mindfulness, social stories, positive behavior support and behavior therapy.

Findings
Neural systems governing emotion regulation can be divided into “top-down” and “bottom-up” processing. Prefrontal cortex, cognitive and attentional control are critical for effective emotion regulation. Individuals with ASD, and with ID show impairments in these areas have problems with emotion regulation. Targeted psychosocial intervention need to consider bottom-up and top-down processes of emotion regulation, and that standardized interventions require adaptations.

Originality/value
There are limited studies looking into understanding the neurobiological and psychological perspective of emotion regulation in ASD and linking them to interventions. This review highlights psychosocial interventions that are important for further research, investigation and development as treatment in this population is limited.
Improved DEA for motor’s model identification
Authors: Shi Jingzhuo , Huang Wenwen 
Published: October 2019

Purpose
The purpose of this paper is to propose an improved differential evolution algorithm (DEA) suitable for motor’s model identification.

Design/methodology/approach
The mutation operation of the standard DEA is improved, and the adaptive coefficient is designed to adjust the optimization process.

Findings
The application of motor model identification shows that the proposed improved DEA is more robust, with higher modeling accuracy and efficiency, and is more suitable for motor identification modeling applications. Compared with the ultrasonic motor model established by using particle swarm algorithm, the model established in this paper has higher precision.

Originality/value
This paper explores an improved DEA suitable for motor identification modeling. The algorithm can not only obtain the optimal solution but also effectively reduce the iterative generations and time required in the process of optimization identification.