bluuebunny/crossref_metadata_2025_split huggingface dataset:
EVALUATION OF HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH DIABETES IN DIFFERENT CARE SETTINGS A CROSS SECTIONAL STUDY IN ALAIN, UAE
Authors: Al kaabi Mariam Salem Khamis , Al Kaabi Bushra khamis Obaid , Al Marzooqi Fatima Mohammed Ahmed , Al Murri Shaima Ghazi , Baynouna AlKetbi Latifa Mohammad 
Published: June 2021

AbstractPurposeThis study aims to assess health-related quality of life (HRQOL) in type 2 diabetic patients across four domains—physical, psychological, social, and environmental—and explore the possible determinants of these domains.MethodsUsing a cross-sectional study design, 397 type 2 diabetic patients in Alain city were interviewed using validated questionnaires in three different care settings: primary, secondary and private health care facilities. The WHO Quality of Life instrument, generalized anxiety disorder score, and Patient Health Questionnaire (PHQ9) were employed.ResultsThe participants comprised 270 females (68%) and 127 males (32%), with 68.9% in the 41–65 years age group; 49.6% were married. The most common comorbidities were dyslipidemia (69.3%), hypertension (61%), and osteoarthritis (24.7%). On a scale of 0 to 100, the highest QOL mean score was reported in the social relationship domain (78.3), followed by the environmental (77.7), psychological health (74.2), and physical health (70.7) domains.The risk of depression was a strong determinant of poor physical health. Social factors have great impact on a patient’s health and well-being. We noticed no difference in HRQOL outcome between primary, secondary, and private health care facilities.ConclusionThe social and mental health domains were the most influential in HRQOL among the participants. This finding supports targeting QOL assessments of patients with type 2 diabetes at the regular chronic diseases clinics and in the planning of population health management programs to ensure the best outcomes.Plain English SummaryDiabetes mellitus is considered a major cause of morbidity and mortality worldwide. In our study we are aiming to explore difference in quality of life and quality of care in patients who access different health care facilities, primary health care clinics versus patients following in secondary care center and private center in Alain. By doing so, we will expand the knowledge regarding health related quality of life of people with diabetes in the UAE and opens the door for future international collaborative research in Diabetes.
EEG-Based Focus Estimation Using Neurable’s Enten Headphones and Analytics Platform
Authors: Alcaide Ramses , Agarwal Nishit , Candassamy Jegan , Cavanagh Sarah , Lim Michelle , Meschede-Krasa Benyamin , McIntyre James , Ruiz-Blondet Maria V. , Siebert Brandon , Stanley David , Valeriani Davide , Yousefi Ali 
Published: June 2021

ABSTRACTWe introduce Neurable’s research on focus using our recently developed Enten EEG headphones. First we quantify Enten’s performance on standard EEG protocols, including eyes-closed alpha rhythms, auditory evoked response and the P300 event-related potential paradigm. We show that Enten’s performance is on-par with established industry-standard hardware. We then introduce a series of experimental tasks designed to mimic how focus might be maintained or disrupted in a real-world office setting. We show that (A) these tasks induce behavioral changes that reflect underlying changes in focus levels and (B) our proprietary algorithm detects these changes across a large number of sessions without needing to adjust the model per participant or recording session. Through manipulation of our experimental protocol, we show that our algorithm is not dependent on gross EMG artifacts and it is driven by changes in EEG. Finally, we evaluated the model’s performance on the same subject across several days, and show that performance remained consistent over time. Our model correctly captured 80% ± 4.1% of distractions present in our experiments with statistical significance. This indicates that our model generalizes across subjects, time points, and conditions. Our findings are based on EEG data collected from 132 participants across 337 sessions and 45 different experiments.
Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins
Authors: Emmenegger Marc , Saseendran Kumar Sreedhar , Emmenegger Vishalini , Malinauskas Tomas , Büttner Thomas , Rose Laura , Schierack Peter , Sprinzl Martin F. , Sommer Clemens J. , Lackner Karl J. , Aguzzi Adriano , Roggenbuck Dirk , Frauenknecht Katrin B. M. 
Published: June 2021

AbstractAntiphospholipid antibodies (aPL), assumed to cause antiphospholipid syndrome (APS), are notorious for their heterogeneity and detect phospholipids and phospholipid-binding proteins. The persistent presence of Lupus anticoagulant and/or aPL against cardiolipin and/or β2 glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. aPL production is thought to be triggered by – among other factors – viral infections, though infection-associated aPL have mostly been considered non-pathogenic. Recently, the potential pathogenicity of infection-associated aPL has gained momentum since an increasing number of patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been described with coagulation abnormalities and hyperinflammation, together with the presence of aPL. Here, we present data from a multicentric, mixed-severity study including three cohorts of individuals who contracted SARS-CoV-2 as well as non-infected blood donors. We simultaneously measured 10 different criteria and non-criteria aPL (IgM and IgG) by using a line immunoassay. Further, IgG antibody response against three SARS-CoV-2 proteins was investigated using tripartite automated blood immunoassay technology. Our analyses revealed that selected non-criteria aPL were enriched concomitant to or after an infection with SARS-CoV-2. Linear mixed-effects models suggest an association of aPL to prothrombin (PT) with the strength of the antibody response against SARS-CoV-2 and that it is further influenced by SARS-CoV-2 disease severity and sex of the individuals. In conclusion, our study is the first to report an association between disease severity, anti-SARS-CoV-2 immunoreactivity and aPL against PT in patients with SARS-CoV-2.
A UDP-GlcNAc : βGal β1-6 GlcNAc transferase involved in bloodstream formN-glycan and procyclic form GPI anchor elaboration inTrypanosoma brucei
Authors: Duncan Samuel M. , Nagar Rupa , Damerow Manuela , Yashunsky Dmitry V. , Buzzi Benedetta , Nikolaev Andrei V. , Ferguson Michael A.J. 
Published: June 2021

AbstractTrypanosoma bruceihas large carbohydrate extensions on itsN-linked glycans and glycosylphosphatidylinositol (GPI) anchors in its bloodstream form (BSF) and procyclic form (PCF), respectively. The parasite’s glycoconjugate repertoire suggests at least 38 glycosyltransferase (GT) activities, 16 of which are unknown. Here, we probe the function(s) of a putative β3GT gene,TbGT10. The BSF null mutant is viablein vitroandin vivoand can differentiate into PCF, demonstrating non-essentiality. However, the absence of TbGT10 led to impaired elaboration ofN-glycans and GPI anchor sidechains in BSF and PCF parasites, respectively. Glycosylation defects include reduced BSF glycoprotein binding to ricin and to monoclonal antibodies mAb139 and mAbCB1. The latter bind a carbohydrate epitope of lysosomal glycoprotein p67 that we show here, using synthetic glycans, consists of (−6Galβ1-4GlcNAcβ1-)≥ 4poly-N-acetyllactosamine repeats. Methylation linkage analysis of Pronase glycopeptides isolated from BSF wild-type and TbGT10 null parasites show a reduction in 6-O-substituted- and 3,6-di-O-substituted-Gal residues. Together, these data suggest thatTbGT10encodes a UDP-GlcNAc : βGal β1-6 GlcNAc-transferase active in both BSF and PCF life-cycle stages elaborating complexN-glycans and GPI sidechains, respectively. The β1-6 specificity of this β3GT gene product and its dual roles inN-glycan and GPI glycan elaboration are notable.
Connectome-based model predicts individual psychopathic traits in college students
Authors: Ye Shuer , Zhu Bing , Zhao Lei , Tian Xuehong , Yang Qun , Krueger Frank 
Published: June 2021

AbstractBackgroundPsychopathic traits have been suggested to increase the risk of violations of socio-moral norms. Previous studies revealed that abnormal neural signatures are associated with elevated psychopathic traits; however, whether the intrinsic network architecture can predict psychopathic traits at the individual level remains unclear.MethodsThe present study utilized connectome-based predictive modeling (CPM) to investigate whether whole-brain resting-state functional connectivity (RSFC) can predict psychopathic traits in the general population. RS functional magnetic resonance imaging data were collected from 84 college students with varying psychopathic traits measured by the Levenson Self-Report Psychopathy Scale (LSRP).ResultsWe found that RSFC of the negative networks predicted individual differences in total LSRP and secondary psychopathy scores but not primary psychopathy score. Particularly, nodes with the most connections in the predictive connectome anchored in the prefrontal cortex (e.g., anterior prefrontal cortex and orbitofrontal cortex) and limbic system (e.g., anterior cingulate cortex and insula). In addition, the connections between the occipital network (OCCN) and cingulo-opercular network (CON) served as a significant predictive connectome for total LSRP and secondary psychopathy score.ConclusionCPM constituted by whole-brain RSFC significantly predicted psychopathic traits individually in the general population. The prefrontal cortex and limbic system at the anatomic level and the CON and OCCN at the functional network level plays a special role in the predictive model—reflecting atypical executive control and affective processing for individuals with elevated psychopathic traits. These findings may provide some implications for early detection and potential intervention of psychopathic tendency.
PARP7 mono-ADP-ribosylates the Agonist Conformation of the Androgen Receptor in the Nucleus
Authors: Kamata Teddy , Yang Chun-Song , Paschal Bryce M. 
Published: June 2021

AbstractWe recently described a signal transduction pathway that contributes to AR regulation based on sitespecific ADP-ribosylation by PARP7, a mono-ADP-ribosyltransferase implicated in several human cancers. ADP-ribosylated AR is specifically recognized by PARP9/DTX3L, a heterodimeric complex that contains an ADP-ribose reader (PARP9) and a ubiquitin E3 ligase (DTX3L). Here, we have characterized the cellular and biochemical requirements for AR ADP-ribosylation by PARP7. We found that the reaction requires nuclear localization of PARP7 and an agonist-induced conformation of AR. PARP7 contains a Cys3His1-type zinc finger (ZF), which we found is critical for AR ADP-ribosylation. The Parp7 ZF is required for efficient nuclear localization by the nuclear localization signal (NLS) encoded in PARP7, but rescue experiments indicate the ZF makes a contribution to AR ADP-ribosylation that is transport-independent. ZF structure appears to be dispensable for PARP7 catalytic activity and for PARP7 binding to AR. Androgen induction of theMYBPC1gene is regulated by AR and PARP7, and we determined that the ZF is required for the PARP7 transcriptional effect onMYBPC1.Our data indicate the PARP7 ZF plays an important role in modulating the subcellular localization of PARP7 and its capacity to ADP-ribosylate and promote AR-dependent transcription.
Did you see it? A Python tool for psychophysical assessment of the human blind spot
Authors: Ling Xiao , Silson Edward H. , McIntosh Robert D. 
Published: June 2021

AbstractThe blind spot is a region in the temporal monocular visual field in humans, which corresponds to a physiological scotoma within the nasal hemi-retina. This region has no photoreceptors, so is insensitive to visual stimulation. There is no corresponding perceptual scotoma because the visual stimulation is “filled-in” by the visual system. Investigations of visual perception in and around the blind spot allow us to investigate this filling-in process. However, because the location and size of the blind spot are individually variable, experimenters must first map the blind spot in every observer. We present an open-source tool, which runs in Psychopy software, to estimate the location and size of the blind spot psychophysically. The tool will ideally be used with an Eyelink eye-tracker (SR Research), but it can also run in standalone mode. Here, we explain the rationale for the tool and demonstrate its validity in normally-sighted observers. We develop a detailed map of the blind spot in one observer. Then, in a group of 12 observers, we propose a more efficient, pragmatic method to define a “safe zone” within the blind spot, for which the experimenter can be fully confident that visual stimuli will not be seen. Links are provided to this open-source tool and a manual.
Cytoplasmic tail truncation of SARS-CoV-2 Spike protein enhances titer of pseudotyped vectors but masks the effect of the D614G mutation
Authors: Chen Hsu-Yu , Huang Chun , Tian Lu , Huang Xiaoli , Zhang Chennan , Llewellyn George N. , Rogers Geoffrey L. , Andresen Kevin , O’Gorman Maurice R.G. , Chen Ya-Wen , Cannon Paula M. 
Published: June 2021

ABSTRACTThe high pathogenicity of SARS-CoV-2 requires it to be handled under biosafety level 3 conditions. Consequently, Spike protein pseudotyped vectors are a useful tool to study viral entry and its inhibition, with retroviral, lentiviral (LV) and vesicular stomatitis virus (VSV) vectors the most commonly used systems. Methods to increase the titer of such vectors commonly include concentration by ultracentrifugation and truncation of the Spike protein cytoplasmic tail. However, limited studies have examined whether such a modification also impacts the protein’s function. Here, we optimized concentration methods for SARS-CoV-2 Spike pseudotyped VSV vectors, finding that tangential flow filtration produced vectors with more consistent titers than ultracentrifugation. We also examined the impact of Spike tail truncation on transduction of various cell types and sensitivity to convalescent serum neutralization. We found that tail truncation increased Spike incorporation into both LV and VSV vectors and resulted in enhanced titers, but had no impact on sensitivity to convalescent serum inhibition. In addition, we analyzed the effect of the D614G mutation, which became a dominant SARS-CoV-2 variant early in the pandemic. Our studies revealed that, similar to the tail truncation, D614G independently increases Spike incorporation and vector titers, but that this effect is masked by also including the cytoplasmic tail truncation. Therefore, the use of full-length Spike protein, combined with tangential flow filtration, is recommended as a method to generate high titer pseudotyped vectors that retain native Spike protein functions.IMPORTANCEPseudotyped viral vectors are useful tools to study the properties of viral fusion proteins, especially those from highly pathogenic viruses. The Spike protein of SARS-CoV-2 has been investigated using pseudotyped lentiviral and VSV vector systems, where truncation of its cytoplasmic tail is commonly used to enhance Spike incorporation into vectors and to increase the titers of the resulting vectors. However, our studies have shown that such effects can also mask the phenotype of the D614G mutation in the ectodomain of the protein, which was a dominant variant early in the COVID-19 pandemic. To better ensure the authenticity of Spike protein phenotypes when using pseudotyped vectors, we therefore recommend using full-length Spike proteins, combined with tangential flow filtration methods of concentration, if higher titer vectors are required.
Evidence for a bacterial Lands cycle phospholipase A: Structural and mechanistic insights into membrane phospholipid remodeling
Authors: Bleffert Florian , Granzin Joachim , Caliskan Muttalip , Schott-Verdugo Stephan N. , Siebers Meike , Thiele Björn , Rahme Laurence , Felgner Sebastian , Dörmann Peter , Gohlke Holger , Batra-Safferling Renu , Jaeger Karl-Erich , Kovačić Filip 
Published: June 2021

AbstractCells steadily adapt their membrane glycerophospholipid (GPL) composition to changing environmental and developmental conditions. While the regulation of membrane homeostasis via GPL synthesis in bacteria has been studied in detail, the mechanisms underlying the controlled degradation of endogenous GPLs remain unknown. Thus far, the function of intracellular phospholipases A (PLAs) in GPL remodeling (Lands cycle) in bacteria is not clearly established. Here, we identified the first cytoplasmic membrane-bound phospholipase A1 (PlaF) from Pseudomonas aeruginosa involved in the Lands cycle. PlaF is an important virulence factor, as the P. aeruginosa ΔplaF mutant showed strongly attenuated virulence in Galleria mellonella and macrophages. We present a 2.0-Å-resolution crystal structure of PlaF, the first structure that reveals homodimerization of a single-pass transmembrane (TM) full-length protein. PlaF dimerization, mediated solely through the intermolecular interactions of TM and juxtamembrane regions, inhibits its activity. A dimerization site and the catalytic sites are linked by an intricate ligand-mediated interaction network which likely explains the product (fatty acid) feedback inhibition observed with the purified PlaF protein. We used molecular dynamics simulations and configurational free energy computations to suggest a model of PlaF activation through a coupled monomerization and tilting of the monomer in the membrane, which constrains the active site cavity into contact with the GPL substrates. Thus, these data show the importance of the GPL remodeling pathway for virulence and pave the way for the development of a novel therapeutic class of antibiotics targeting PlaF-mediated membrane GPL remodeling.SynopsisMembrane homeostasis can be regulated by phospholipase-controlled deacylation of endogenous glycerophospholipids (GPLs) followed by reacylation of products, known as the Lands cycle in eukaryotes. Here we show that the human pathogen Pseudomonas aeruginosa uses intracellular phospholipase A1 (PlaF) to modulate membrane GPL composition, which is the first example in bacteria. This newly identified PLA1 indirectly regulates the bacterial virulence properties by hydrolyzing a specific set of membrane GPLs. The crystal structure of full-length PlaF dimers bound to natural ligands, MD simulations, and biochemical approaches provide insights into the molecular mechanism of dimerization-mediated inactivation of this single-pass transmembrane PLA1. Our findings shed light on a mechanism by which bacterial intracellular PLAs might regulate membrane homeostasis what showcases these enzymes as a promising target for a new class of antibiotics.
Linker histone dH1K27 dimethylation marks Drosophila heterochromatin independently of H3K9 methylation
Authors: Bernués Jordi , Izquierdo-Boulstridge Andrea , Reina Oscar , Castejón Lucía , Fernández-Castañer Elena , Leal Núria , Guerrero-Pepinosa Nancy , Bonet-Costa Carles , Vujatovic Olivera , Azorín Fernando 
Published: June 2021

ABSTRACTPost-translational modifications (PTMs) of histones are important epigenetic determinants and specific core histones PTMs correlate with functional chromatin states. However, despite linker histone H1s are heavily post-translationally modified, little is known about the genomic distribution of H1s PTMs and their association with epigenetic chromatin states. Here, we address this question in Drosophila that encodes a single somatic linker histone, dH1. We previously reported that dH1 is dimethylated at K27 (dH1K27me2). Here, we show that dH1K27me2 is a major PTM of Drosophila heterochromatin. At mitosis, dH1K27me2 accumulates at pericentromeric heterochromatin, while, in interphase cells, it is also detected at intercalary heterochromatin. ChIPseq experiments show that dH1K27me2 enriched regions cluster at both the assembled and unassembled heterochromatin regions of all four Drosophila chromosomes. More than 98% of the dH1K27me2 enriched regions map to heterochromatic repetitive DNA elements, including transposable elements, simple DNA repeats and satellite DNAs. We also show that dH1K27me2 is independent of H3K9 methylation, as it is equally detected in flies carrying a H3K9R mutation. Moreover, dH1K27me2 is not affected by depletion of Su(var)3-9, HP1a and Su(var)4-20. Altogether these results suggest that dH1K27me2 is a novel epigenetic mark of Drosophila heterochromatin that acts upstream of the major Su(var)3-9/HP1a pathway of heterochromatin formation.
A binocular synaptic network supports interocular response alignment in visual cortical neurons
Authors: Scholl Benjamin , Tepohl Clara , Ryan Melissa A. , Thomas Connon I. , Kamasawa Naomi , Fitzpatrick David 
Published: June 2021

AbstractIn the visual system, signals from the two eyes are combined to form a coherent representation through the convergence of synaptic input populations onto individual cortical neurons. As individual synapses originate from either monocular (representing one eye) or binocular (representing both eyes) cortical networks, it has been unclear how these inputs are integrated coherently. Here, we imaged dendritic spines on layer 2/3 binocular cells in ferret visual cortex with in vivo two-photon microscopy to examine how monocular and binocular synaptic networks contribute to the interocular alignment of orientation tuning. We found that binocular synapses varied in degree of ‘congruency’, namely response correlation between left and right eye visual stimulation. Binocular congruent inputs were functionally distinct from binocular noncongruent and monocular inputs, exhibiting greater tuning selectivity and connection specificity. Using correlative light and electron microscopy, we found no difference in ultrastructural anatomy and instead, observed strength in numbers using a simple model simulating aggregate synaptic input. This model demonstrated a predominate contribution of binocular congruent inputs in sculpting somatic orientation preference and interocular response alignment. Our study suggests that, in layer 2/3 cortical neurons, a binocular network is responsible for forming a coherent representation in individual neurons through recurrent intracortical interactions.
Dynamic Phosphorylation of RGS Provides Spatial Regulation of MAP Kinase and Promotes Completion of Cytokinesis during the Yeast Pheromone Response
Authors: Simke William C. , Johnson Cory P. , Hart Andrew J. , Mayhue Sari , Craig P. Lucas , Sojka Savannah , Kelley Joshua B. 
Published: June 2021

AbstractYeast use a G-protein coupled receptor (GPCR) signaling pathway to detect mating pheromone, arrest in G1, and direct polarized growth towards the potential mating partner. The primary negative regulator of this pathway is the regulator of G-protein signaling (RGS), Sst2, which induces Gα GTPase activity and subsequent inactivation of all downstream signaling including a MAPK cascade. The MAPK Fus3 phosphorylates the RGS in response to pheromone, but the role of this modification is unknown. We set out to examine the role of RGS phosphorylation during the pheromone response. We found that RGS phosphorylation peaks early in the pheromone response and diminishes RGS localization to the polarity site and focuses MAPK complexes there. At later time points, RGS is predominantly unphosphorylated, which promotes RGS localization to the polar cap and broadens the distribution of MAPK complexes relative to the Cdc42 polarity machinery. Surprisingly, we found that phosphorylation of the RGS is required for the completion of cytokinesis prior to pheromone induced growth. The completion of cytokinesis in the presence of pheromone is promoted by the formin Bnr1 and the kelch-repeat protein, Kel1, both proteins previously found to interact with the RGS.