bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene-environment interactions in face categorisation: experience with a nanny and oxytocin receptor genotype interact to reduce face categorization reaction times
Authors: Neoh Michelle Jin Yee , Setoh Peipei , Bizzego Andrea , Tandiono Moses , Foo Jia Nee , Esposito Gianluca 
Published: December 2020

AbstractHuman faces are relevant stimuli that capture attention, provide information about group belonging and elicit automatic prepared responses. While early experiences with other race faces plays a critical role in acquiring face expertise, the exact mechanism through which it exerts its influence is still to be elucidated. In particular, the influence of genetic factors and the role of a multi-ethnic context has not been explored. The aim of this study was to investigate how caregiving experiences with nannies and oxytocin receptor gene (OXTR) genotypes interact in regulating other-race categorisation mechanisms in adults. Information about single nucleotide polymorphisms of the OXTR (rs53576) and experiences with own- and other-race nannies was collected from 89 Singaporean adults, who completed a visual categorization task of face stimuli (Chinese or Javanese). Participants were grouped into A/A homozygotes and G-carriers and assigned a score to account for the type of nanny experience. A General Linear Model was used to estimate the effect of nanny experience, genetic group and their interaction on categorization reaction time. A significant main effect of the nanny experience (p<.001) and of the interaction between genetic group and experience (p=.008) was found. Post-hoc analysis revealed a significant negative correlation between nanny experience and reaction time for A/A homozygotes (r=−0.52, p<.001) but no significant correlation for G-carriers. In summary, a significant gene-environment interaction on face categorization was found. This finding appears to represent an indirect pathway through which genes and experiences interact to shape mature social sensitivity in human adults.HighlightsEarly nanny experience interacts with oxytocin receptor genotype in affecting the speed of face categorisation.Individuals with other-race nanny experience show faster categorisation response times. Gene-environment interactions are present in face categorisation.
DOT1L interaction partner AF10 controls patterning of H3K79 methylation and RNA polymerase II to maintain cell identity
Authors: Wille Coral K. , Neumann Edwin N. , Deshpande Aniruddha J. , Sridharan Rupa 
Published: December 2020

ABSTRACTHistone 3 Lysine 79 methylation (H3K79me) is enriched on gene bodies proportional to gene expression levels, and serves as a strong barrier for reprogramming of somatic cells to induced pluripotent stem cells (iPSCs). DOT1L is the sole histone methyltransferase that deposits all three orders - mono, di, and tri methylation – at H3K79. Here we leverage genetic and chemical approaches to parse the specific functions of the higher orders of H3K79me in maintaining cell identity. DOT1L interacts with AF10 (Mllt10) which recognizes unmodified H3K27 and boosts higher order H3K79 methylation. AF10 deletion evicts higher order H3K79me2/3, and reorganizes H3K79me1 to the transcription start site, to facilitate iPSC formation in the absence of steady state transcriptional changes. Instead, AF10 loss redistributes RNA polymerase II to a uniquely pluripotent pattern at highly expressed, rapidly transcribed housekeeping genes. Taken together, we reveal a mechanism for higher order histone methylation located at the gene body in reinforcing cell identity.
Molecular insights into substrate recognition and discrimination by the N-terminal domain of Lon AAA+ protease
Authors: Tzeng Shiou-Ru , Tseng Yin-Chu , Lin Chien-Chu , Hsu Chia-Ying , Huang Shing-Jong , Kuo Yi-Ting , Chang Chung-I 
Published: December 2020

AbstractThe Lon AAA+ proteases (LonA) is a ubiquitous ATP-dependent proteolytic machine, which selectively degrades damaged proteins or native proteins carrying exposed motifs (degrons). Here we characterize the structural basis for substrate recognition and discrimination by the N-terminal domain(NTD) of LonA. The results reveal that the six NTDs are attached to the hexameric LonA chamber by flexible linkers such that the formers tumble independently of the latter. Further spectral analyses show that the NTD selectively interacts with unfolded proteins, protein aggregates, and degron-tagged proteins by two hydrophobic patches of its N-lobe, but not intrinsically disordered substrate, α-casein. Moreover, the NTD selectively binds to protein substrates when they are thermally induced to adopt unfolded conformations. Collectively, our findings demonstrate that NTDs enable LonA to perform protein quality control to selectively degrade proteins in damaged states and suggest that substrate discrimination and selective degradation by LonA are mediated by multiple NTD interactions.Impact StatementThe N-terminal domains enable Lon protease to discriminate and capture selected protein species for degradation by exposed hydrophobic patches and flexible linkages to the hexameric core complex.
Temporal Microbial Community Dynamics within a Unique Acid Saline Lake
Authors: Ghori Noor-ul-Huda , Wise Michael. J. , Whiteley Andrew. S. 
Published: December 2020

AbstractLake Magic is one of the acidic hypersaline lakes (ca. 1 km in diameter) present within the Yilgarn Craton in WA. This unique lake exhibits extremely low pH (<1.6) coupled to very high salinity (32% TDS) with the highest concentration of aluminium (1774 mg/L) and silica (510 mg/L) in the world. Previous studies on Lake Magic diversity has revealed that the lake hosts acidophilic, acidotolerant, halophilic and halotolerant bacterial species. These studies provide indicators of the population residing within the lake. However, they do not emphasize the survival mechanisms adopted by the resident microorganisms and how the diversity of microbial populations residing within the lake changes during the dynamic stages of flooding, evapo-concentration and desiccation. We have studied the bacterial and fungal diversity in Lake Magic via amplicon sequencing and functional analysis through different stages of the lake in a span of one year, in the salt and sediment layer. Our results highlight that the diversity in Lake Magic is strongly driven by the pH and salt concentrations at different stages of the lake. The microbial community becomes more specialised in specific functions during more extreme stages. This also suggests that microbial interactions are involved in stabilising the ecosystem and is responsible for the resistance and resilience of these communities as the interactions of these microbes create a safe haven for other microbes to survive during more extreme stages.
Conformational dynamics of auto-inhibition in the ER calcium sensor STIM1
Authors: van Dorp Stijn , Qiu Ruoyi , Choi Ucheor B. , Wu Minnie M. , Yen Michelle , Kirmiz Michael , Brunger Axel T. , Lewis Richard S. 
Published: December 2020

AbstractThe dimeric ER Ca2+sensor STIM1 controls store-operated Ca2+entry (SOCE) through the regulated binding of its CRAC activation domain (CAD) to Orai channels in the plasma membrane. In resting cells, the STIM1 CC1 domain interacts with CAD to suppress SOCE, but the structural basis of this interaction is unclear. Using single-molecule Förster resonance energy transfer (smFRET) and protein crosslinking approaches, we show that CC1 interacts dynamically with CAD in a domain-swapped configuration with an orientation predicted to sequester its Orai- binding region adjacent to the ER membrane. Following ER Ca2+depletion and release from CAD, cysteine crosslinking indicates that the two CC1 domains become closely paired along their entire length in the active Orai-bound state. These findings provide a structural basis for the dual roles of CC1: sequestering CAD to suppress SOCE in resting cells and propelling it towards the plasma membrane to activate Orai and SOCE after store depletion.
Is mRNA decapping activity of ApaH like phosphatases (ALPH’s) the reason for the loss of cytoplasmic ALPH’s in all eukaryotes but Kinetoplastida?
Authors: Castañeda Londoño Paula Andrea , Banholzer Nicole , Bannermann Bridget , Kramer Susanne 
Published: December 2020

ABSTRACTBackgroundApaH like phosphatases (ALPHs) originate from the bacterial ApaH protein and are present in eukaryotes of all eukaryotic super-groups; still, only two proteins have been functionally characterised. One is ALPH1 from the KinetoplastidTrypanosoma bruceithat we recently found to be the mRNA decapping enzyme of the parasite. mRNA decapping by ALPHs is unprecedented in eukaryotes, which usually use nudix hydrolases, but the bacterial ancestor protein ApaH was recently found to decap non-conventional caps of bacterial mRNAs. These findings prompted us to explore whether mRNA decapping by ALPHs is restricted to Kinetoplastida or more widespread among eukaryotes.ResultsWe screened 824 eukaryotic proteomes with a newly developed Python-based algorithm for the presence of ALPHs and used the data to refine phylogenetic distribution, conserved features, additional domains and predicted intracellular localisation of ALPHs. We found that most eukaryotes have either no ALPH (500/824) or very short ALPHs, consisting almost exclusively of the catalytic domain. These ALPHs had mostly predicted non-cytoplasmic localisations, often supported by the presence of transmembrane helices and signal peptides and in two cases (one in this study) by experimental data. The only exceptions were ALPH1 homologues from Kinetoplastida, that all have unique C-terminal and mostly unique N-terminal extension, and at least theT. bruceienzyme localises to the cytoplasm. Surprisingly, despite of these non-cytoplasmic localisations, ALPHs from all eukaryotic super-groups hadin vitromRNA decapping activity.ConclusionsALPH was present in the last common ancestor of eukaryotes, but most eukaryotes have either lost the enzyme since, or use it exclusively outside the cytoplasm in organelles in a version consisting of the catalytic domain only. While our data provide no evidence for the presence of further mRNA decapping enzymes among eukaryotic ALPHs, the broad substrate range of ALPHs that includes mRNA caps provides an explanation for the selection against the presence of a cytoplasmic ALPH protein as a mean to protect mRNAs from unregulated degradation. Kinetoplastida succeeded to exploit ALPH as their mRNA decapping enzyme, likely using the Kinetoplastida-unique N- and C-terminal extensions for regulation.
Nuclear myocardial perfusion studies do not predict vascular or myocardial architecture in advanced heart failure
Authors: Farris Stephen , Don Creighton , Soine Laurie , Lombardi William , Caldwell James , Stempien-Otero April 
Published: December 2020

AbstractObjectivesTo determine predictors of tissue that would benefit from improved blood flow in subjects with advanced heart disease.BackgroundAdvanced regeneration and percutaneous revascularization strategies including revascularization of chronic total occlusions (CTO) are being used to potentially restore myocardial function in the growing population of patients with advanced heart disease. Predictors of myocardial recovery in this population have not been established.MethodsCardiac tissue was collected from 27 subjects undergoing LVAD or cardiac transplantation who had nuclear perfusion imaging prior to procedure. Histologic analysis for fibrosis, vascular density and inflammation was performed and correlated with nuclear perfusion images from the same areas. In a subset of subjects, correlations of nuclear perfusion with TIMI flow by coronary arteriography was also performed.ResultsAreas of both normal and abnormal epicardial coronary blood flow had a large variation in radiotracer uptake. There were no statistically significant correlations between uptake of radiotracer at rest and degree of cardiac fibrosis, vascular density or inflammation and the matched area of myocardium. Fibrosis varied from 5-50% in areas with severe defects and areas of normal radiotracer uptake. Endothelial density correlated with inflammation in end-stage heart disease.ConclusionsRadiotracer uptake poorly predicted both areas of severe fibrosis that will not benefit from increased blood flow and areas of minimal fibrosis that may recover. Correlation of inflammation and endothelial density support a hypothesis that inflammatory cytokines augment vascularity in myocardium. Novel strategies to improve function in advanced heart disease are in need of better markers of recovery.
Deep Learning to Estimate Cardiac Magnetic Resonance-Derived Left Ventricular Mass
Authors: Khurshid Shaan , Friedman Samuel , Pirruccello James P. , Di Achille Paolo , Diamant Nathaniel , Anderson Christopher D. , Ellinor Patrick T. , Batra Puneet , Ho Jennifer E. , Philippakis Anthony , Lubitz Steven A. 
Published: December 2020

ABSTRACTBackgroundCardiac magnetic resonance (CMR) is the gold standard for left ventricular hypertrophy (LVH) diagnosis. CMR-derived LV mass can be estimated using proprietary algorithms (e.g., inlineVF), but their accuracy and availability may be limited.ObjectiveTo develop an open-source deep learning model to estimate CMR-derived LV mass.MethodsWithin participants of the UK Biobank prospective cohort undergoing CMR, we trained two convolutional neural networks to estimate LV mass. The first (ML4Hreg) performed regression informed by manually labeled LV mass (available in 5,065 individuals), while the second (ML4Hseg) performed LV segmentation informed by inlineVF contours. We compared ML4Hreg, ML4Hseg, and inlineVF against manually labeled LV mass within an independent holdout set using Pearson correlation and mean absolute error (MAE). We assessed associations between CMR-derived LVH and prevalent cardiovascular disease using logistic regression adjusted for age and sex.ResultsWe generated CMR-derived LV mass estimates within 38,574 individuals. Among 891 individuals in the holdout set, ML4Hsegreproduced manually labeled LV mass more accurately (r=0.864, 95% CI 0.847-0.880; MAE 10.41g, 95% CI 9.82-10.99) than ML4Hreg(r=0.843, 95% CI 0.823-0.861; MAE 10.51, 95% CI 9.86-11.15, p=0.01) and inlineVF (r=0.795, 95% CI 0.770-0.818; MAE 14.30, 95% CI 13.46-11.01, p<0.01). LVH defined using ML4Hsegdemonstrated the strongest associations with hypertension (odds ratio 2.76, 95% CI 2.51-3.04), atrial fibrillation (1.75, 95% CI 1.37-2.20), and heart failure (4.53, 95% CI 3.16-6.33).ConclusionsML4Hsegis an open-source deep learning model providing automated quantification of CMR-derived LV mass. Deep learning models characterizing cardiac structure may facilitate broad cardiovascular discovery.
Fronto-limbic neural variability as a transdiagnostic correlate of emotion dysregulation
Authors: Kebets Valeria , Favre Pauline , Houenou Josselin , Polosan Mircea , Aubry Jean-Michel , Van De Ville Dimitri , Piguet Camille 
Published: December 2020

AbstractBackgroundEmotion dysregulation is central to the development and maintenance of psychopathology, and is common across many psychiatric disorders. Neurobiological models of emotion dysregulation involve the fronto-limbic brain network, including in particular the amygdala and prefrontal cortex (PFC). Neural variability has recently been suggested as an index of cognitive flexibility. We hypothesized that within-subject neural variability in the fronto-limbic network would be related to inter-individual variation in emotion dysregulation in the context of low affective control.MethodsIn a multi-site cohort (N= 166, 93 females) of healthy individuals and individuals with emotional dysregulation (attention deficit/hyperactivity disorder (ADHD), bipolar disorder (BD), and borderline personality disorder (BPD)), we applied partial least squares (PLS), a multivariate data-driven technique, to derive latent components yielding maximal covariance between blood-oxygen level-dependent (BOLD) signal variability at rest and emotion dysregulation, as expressed by affective lability, depression and mania scores.ResultsPLS revealed one significant latent component (r= 0.62,p= 0.001), whereby greater emotion dysregulation was associated with increased neural variability in the amygdala, hippocampus, ventromedial, dorsomedial and dorsolateral PFC, insula and motor cortex, and decreased neural variability in occipital regions. This spatial pattern bears a striking resemblance to the fronto-limbic network, which is thought to subserve emotion regulation, and is impaired in individuals with ADHD, BD, and BPD.ConclusionsOur work supports emotion dysregulation as a transdiagnostic dimension with neurobiological underpinnings that transcend diagnostic boundaries, and adds evidence to neural variability being a relevant proxy of neural efficiency.
The effect of remote ischemic preconditioning on postoperative cardiac and inflammatory biomarkers in pancreatic surgery: a randomized controlled trial
Authors: van Zeggeren Laura , Visser Remco A. , Vernooij Lisette M. , Dijkstra Ineke M. , Bosma Madeleen , Molenaar Izaak Q. , van Santvoort Hjalmar C. , Noordzij Peter G. 
Published: December 2020

ABSTRACTBackgroundCardiac and inflammatory biomarkers have been associated with adverse outcome after major abdominal surgery. Remote ischemic preconditioning (RIPC) may protect organs from ischemic insults during and after cardiac surgery, but the effect in major abdominal surgery is largely unknown.ObjectiveTo study the effect of RIPC on cardiac and inflammatory biomarkers in patients undergoing pancreatic resection.MethodsSingle-center, double-blind, randomized controlled trial in ninety patients undergoing elective pancreatic resection between March 2017 and February 2019. Three cycles of upper-limb ischemia and reperfusion (each 5 minutes) were applied before surgery. The primary endpoint was the maximum postoperative high-sensitive cardiac troponin (hs-cTn) T concentration within 48 hours after surgery. Secondary endpoints were postoperative myocardial injury (PMI, defined as a postoperative hs-cTnT ≥14 ng L-1), the maximum concentration of interleukin (IL)-6 within 48 hours after surgery, and postoperative complications within 30-days of surgery.ResultsRIPC did not reduce the maximum hs-cTnT concentration after surgery (12.6 ng L-1 vs 16.6 ng L-1 in the control group (P=0.23), nor did it lessen the incidence of PMI (15 (33.3%) patients in the RIPC group versus 19 (42.2%) controls, P=0.93). The maximum postoperative IL-6 concentration was 239 pg mL-1 [115-360] in the RIPC group, as compared to 317 pg mL-1 [174-909] in the control group (P=0.13). A postoperative complication occurred in 23 (51%) RIPC patients and 24 (53%) controls.ConclusionsRemote ischemic preconditioning did not reduce the maximum postoperative hs-cTnT concentration. Postoperative myocardial injury, IL-6 concentrations and postoperative complications were not statistically different between RIPC patients and controls.Trial RegistrationClinicaltrials.gov identifier NCT03460938FundingFunding for biomarker analysis was provided by Roche Diagnostics. Roche Diagnostics had no role in design and conduct of the study, analysis and interpretation of the data, preparation and approval of the manuscript.Article summaryStrengths and limitations of this studyWell-designed clinical trial in a selected group of high-risk abdominal surgery patients.Serial assessment of high-sensitive cardiac troponin T and interleukin-6 concentrations.Postoperative cardiac biomarker concentrations were relatively low.This trial was not primarily designed to detect differences in IL-6 concentrations and postoperative complications.
Mental health among pregnant women during the pandemic in Sweden– a mixed methods approach using data from the Mom2B mobile application for research
Authors: Fransson Emma , Karalexi Maria , Kimmel Mary , Bränn Emma , Kollia Natasa , van Zoest Vera , Nordling Eira , Papadopoulos Fotios C , Skalkidou Alkistis 
Published: December 2020

AbstractPublic health emergencies such as the coronavirus (SARS-CoV-2) pandemic have significant impact on mental health, and have been shown to impact on already prevalent affective disorders during and after pregnancy. The aim of this study was to utilize modern tools to assess depressive and anxiety symptoms, as well as wellbeing and life changes in pregnant women during the pandemic in Sweden, where no lockdown has been in place.Data from the Mom2B, a national ongoing mobile application-based study of pregnant and newly-delivered women were utilized. Participants (n= 1345) filled out self-report screeners of depression, anxiety and wellbeing. Questions about COVID symptoms and effects on life and health care were added from March 2020. Movement data was collected using the phone’s GPS sensor. Mood scores were compared with throughout the months of 2020 and to the levels of a previous collected material. Highest levels of depression and anxiety were evident in April and October 2020. Symptoms were higher among those feeling socially isolated, but not for those infected or with symptomatic family members. Wellbeing and mobility were strongly positively correlated and were lowest in April. Women reported on cancelled healthcare appointments and worry about their partners being absent from the delivery.The Mom2B application enabled gathering information at a national level in real-time as the pandemic has been evolving. Levels of perinatal affective symptoms and low wellbeing were elevated compared with previous years as well as with months with fewer cases of SARS-Cov-2. Similar applications can help healthcare providers and governmental bodies to in real time monitor high-risk groups during crises, as well as to adjust measures and the support offered.FundingThis project was funded by the Uppsala Region to AS, the Swedish Association of Local Authorities and Regions (SKR) to the department of Obstetrics and Gynecology, Akademiska University Hospital, the Swedish Research Council (Grant number 2020-01965) to AS, as well as the Fredrik and Inger Thuring’s Foundation to EF.
The Influence of Phenotyping Method on Structural Neuroimaging Associations with Depression in UK Biobank
Authors: Harris Mathew A. , Cox Simon R. , de Nooij Laura , Barbu Miruna C. , Adams Mark J. , Shen Xueyi , Deary Ian J. , Lawrie Stephen M. , McIntosh Andrew M. , Whalley Heather C. 
Published: December 2020

AbstractBackgroundDepression is assessed in many different ways, with large population studies often relying on minimal phenotyping approaches. Genetic results suggest that more formal clinical diagnoses and simpler self-report measures of depression show some core similarities, but also important differences. It is not yet clear whether this is also the case for neuroimaging measures.MethodsWe studied 39,300 UK Biobank imaging participants (20,701 female; aged 44.6 to 82.3 years, M = 64.1, SD = 7.5) with structural neuroimaging (T1 and DTI) and depression data. Depression phenotypes included a minmal single-item self-report measure, an intermediate symptom-based measure of ‘probable’ depression, and a more clinically robust measure based on DSM-IV criteria. We tested i) associations between brain structural measures and each depression phenotype, and ii) the effects of depression phenotype on these associations.ResultsSmall depression-brain structure associations (β < 0.1) were significant after FDR correction for many global and regional metrics for all three phenotypes. The most consistent imaging associations across depression phenotypes were for measures of white matter integrity. There were small but significant effects of phenotype definition primarily for cortical thickness, which showed stronger negative associations with Self-reported Depression than the symptom-based measures.ConclusionSimilar to previous genetic studies, we found some consistent associations indicating a core component of depression across phenotypes, and some additional associations that were phenotype-specific. Although these specific results did not relate to depth of phenotyping as expected, effects of phenotype definition are still an important consideration for future depression research.