bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo NMDA receptor function in people with NMDA receptor antibody encephalitis
Authors: Galovic Marian , Al-Diwani Adam , Vivekananda Umesh , Torrealdea Francisco , Erlandsson Kjell , Fryer Tim D , Hong Young T , Thomas Benjamin A , McGinnity Colm J , Edmond Evan , Sander Kerstin , Årstad Erik , Jelcic Ilijas , Aigbirhio Franklin I , Groves Ashley M , Thielemans Kris , Hutton Brian , Hammers Alexander , Duncan John S , Coles Jonathan P , Barnes Anna , Stagg Charlotte J , Walker Matthew C , Irani Sarosh R , Koepp Matthias J ,   for the NEST investigators
Published: December 2021

AbstractIn N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis, NMDAR-autoantibodies are hypothesised to cause prominent neuropsychiatric symptoms by internalizing NMDARs. However, supporting evidence comes chiefly from in vitro and rodent data with scant direct evidence from affected humans. Here, we used in vivo positron emission tomography (PET) with [18F]GE-179 to show a mean 30% reduction of the density of open, activated NMDARs in grey matter of persistently NMDAR-autoantibody seropositive patients following NMDAR-antibody encephalitis compared to healthy controls. The reduction was most prominent in the anterior temporal and superior parietal cortices. These patients had normal structural MRIs and mild residual symptoms. In contrast, one symptom-free patient who recovered from NMDAR-antibody encephalitis and was not NMDAR-autoantibody seropositive had normal density of active NMDARs. These findings reveal a functional deficit of open, activated NMDARs in humans with NMDAR-autoantibodies. Moreover, we observed a functional NMDAR deficit for up to 8 months following the disease peak, despite only mild residual symptoms, highlighting the considerable compensatory capacity of the human brain.One Sentence SummaryReductions of activated NMDA receptors detected in vivo in female patients following NMDA-receptor-antibody encephalitis.
A mixed-methods study of risk factors and experiences of healthcare workers tested for the novel coronavirus in Canada
Authors: Okpani Arnold Ikedichi , Barker Stephen , Lockhart Karen , Grant Jennifer , Delgado-Ron Jorge Andrés , Zungu Muzimkhulu , Naicker Nisha , Ehrlich Rodney , Yassi Annalee 
Published: December 2021

ObjectivesWe aimed to investigate the contribution of occupational and non-work-related factors to the risk of novel coronavirus (SARS-CoV-2) infection among healthcare workers (HCWs) in Vancouver Coastal Health, British Columbia, Canada. We also aimed to examine how HCWs described their experiences.MethodsWe conducted a matched case-control study using data from online and phone questionnaires with optional open-ended questions completed by HCWs who sought SARS-CoV-2 testing between March 2020 and March 2021. Conditional logistic regression and thematic analysis were utilized.ResultsData from 1340 HCWs were included. Free-text responses were provided by 257 respondents. Adjusting for age, gender, race, occupation, and number of weeks since pandemic was declared, community exposure to a known COVID-19 case (adjusted odds ratio -aOR: 2.45; 95% CI 1.67-3.59), and difficulty accessing personal protective equipment -PPE- (aOR: 1.84; 95% CI 1.07-3.17) were associated with higher infection odds. Care-aides/licensed practical nurses had substantially higher risk (aOR: 2.92; 95% CI 1.49-5.70) than medical staff who had the lowest risk. Direct COVID-19 patient care was not associated with elevated risk. HCWs’ experiences reflected the phase of the pandemic when they were tested. Suboptimal communication, mental stress, and situations perceived as unsafe were common sources of dissatisfaction.ConclusionsCommunity exposures and occupation were important determinants of infection among HCWs in our study. The availability of PPE and clear communication enhanced a sense of safety. Varying levels of risk between occupational groups call for wider targeting of infection prevention measures. Strategies for mitigating community exposure and supporting HCW resilience are required.
S glycoprotein diversity of the Omicron variant
Authors: Sarkar Rakesh , Lo Mahadeb , Saha Ritubrita , Dutta Shanta , Chawla-Sarkar Mamta 
Published: December 2021

AbstractOn the backdrop of ongoing Delta variant infection and vaccine-induced immunity, the emergence of the new Variant of Concern, the Omicron, has again fuelled the fears of COVID-19 around the world. Currently, very little information is available about the S glycoprotein mutations, transmissibility, severity, and immune evasion behaviour of the Omicron variant. In the present study, we have performed a comprehensive analysis of the S glycoprotein mutations of 309 strains of the Omicron variant and also discussed the probable effects of observed mutations on several aspects of virus biology based on known available knowledge of mutational effects on S glycoprotein structure, function, and immune evasion characteristics.
Estimating area-level variation in SARS-CoV-2 infection fatality ratios
Authors: Ladau Joshua , Kuo Chaincy , Brodie Eoin L. , Falco Nicola , Bansal Ishan , Hoffman Elijah B. , Joachimiak Marcin P. , Mora Ana M. , Walker Angelica M. , Wainwright Haruko M. , Wu Yulun , Jacobson Daniel , Hess Matthias , Brown James B. , Abuabara Katrina 
Published: December 2021

AbstractBackgroundDuring a pandemic, estimates of geographic variability in disease burden are important but limited by the availability and quality of data.MethodsWe propose a framework for estimating geographic variability in testing effort, total number of infections, and infection fatality ratio (IFR). Because symptomatic people are more likely to seek testing, we use a noncentral hypergeometric model that accounts for differential probability of positive tests. We apply this framework to the United States (U.S.) COVID-19 pandemic to estimate county-level SARS-CoV-2 IFRs from March 1, 2020 to October 31, 2020. Using data on population size, number of observed cases, number of reported deaths in each U.S. county and state, and number of tests in each U.S. state, we develop a series of estimators to identify the number of SARS-CoV-2 infections and IFRs at the county level. We then perform a simulation and compare the estimated values to simulated values to demonstrate the validity of our approach.FindingsApplying the county-level estimators to the real, unsimulated COVID-19 data spanning March 1, 2020 to October 31, 2020 from across the U.S., we found that IFRs varied from 0 to 0.0273, with an interquartile range of 0.0022 and a median of 0.0018. The estimators for IFRs, number of infections, and number of tests showed high accuracy and precision; for instance, when applied to simulated validation data sets, across counties, Pearson correlation coefficients between estimator means and true values were 0.88, 0.95, and 0.74, respectively.InterpretationWe propose an estimation framework that can be used to identify area-level variation in IFRs and performs well to estimate county-level IFRs in the U.S. COVID-19 pandemic.
Serum uric acid and total bilirubin as putative biomarkers of resistance in Prodromal Parkinson’s disease: Longitudinal data from the PPMI study
Authors: Koros Christos , Simitsi Athina-Maria , Bougea Anastasia , Papagiannakis Nikolaos , Prentakis Andreas , Papadimitriou Dimitra , Pachi Ioanna , Angelopoulou Efthalia , Beratis Ion , Efthymiopoulou Efthymia , Lourentzos Konstantinos , Bozi Maria , Papageorgiou Sokratis G. , Trapali Xenia Geronicola , Bonakis Anastasios , Stamelou Maria , Stefanis Leonidas 
Published: December 2021

AbstractBackgroundThe role of blood uric acid and more recently bilirubin as biomarkers in symptomatic motor PD has been increasingly established in the literature.ObjectiveOur present study assessed the role of serum uric acid and total bilirubin as putative biomarkers in a prodromal PD cohort followed longitudinally.MethodsLongitudinal 5-year serum uric acid and total bilirubin measurement data of 65 Prodromal PD patients (including REM Sleep Behavior disorder (RBD), N=39 and Hyposmia, N=26) with an abnormal DATSCAN imaging were downloaded from the Parkinson’s Progression Markers Initiative (PPMI) database. This cohort was compared with 423 de novo sporadic PD patients and 196 healthy controls enrolled in the same study.ResultsAfter adjusting for age, sex and Body Mass Index (BMI), baseline and 5-year longitudinal serum uric acid levels were higher in the Prodromal cohort and RBD subgroup as compared to the motor PD cohort. This was also true for longitudinal measurements in the Hyposmic subgroup. In contrast, baseline and longitudinal serum total bilirubin did not differ between each prodromal group and the PD cohort.ConclusionsOur results are indicative of a role of serum uric acid (but probably not of total bilirubin) as a marker of neuroprotection, in a certain subgroup of premotor patients exhibiting exclusively non motor features (hyposmia or RBD). It is possible that an inherent antioxidant resistance of a subset of RBD or hyposmia patients with high serum uric acid level delayed or precluded the emergence of a motor PD phenotype as opposed to the PD cohort.
Characteristics of Patients Referred to a Cardiovascular Disease Clinic for Post-Acute Sequelae of SARS-CoV-2 Infection
Authors: Wang Stephen Y. , Adejumo Philip , See Claudia , Onuma Oyere K. , Miller Edward J. , Spatz Erica S. 
Published: December 2021

ABSTRACTThere is limited literature on the cardiovascular manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC). We aimed to describe the characteristics, diagnostic evaluations, and cardiac diagnoses in patients referred to a cardiovascular disease clinic designed for patients with PASC from May 2020 to September 2021. Of 126 patients, average age was 46 years (range 19-81 years), 43 (34%) were male. Patients presented on average five months after COVID-19 diagnosis. 30 (24%) patients were hospitalized for acute COVID-19. Severity of acute COVID-19 was mild in 37%, moderate in 41%, severe in 11%, and critical in 9%. Patients were also followed for PASC by pulmonology (53%), neurology (33%), otolaryngology (11%), and rheumatology (7%). Forty-three patients (34%) did not have significant comorbidities. The most common symptoms were dyspnea (52%), chest pain/pressure (48%), palpitations (44%), and fatigue (42%), commonly associated with exertion or exercise intolerance. The following cardiovascular diagnoses were identified: nonischemic cardiomyopathy (5%); new ischemia (3%); coronary vasospasm (2%); new atrial fibrillation (2%), new supraventricular tachycardia (2%); myocardial involvement (15%) by cardiac MRI, characterized by late gadolinium enhancement (LGE; 60%) or inflammation (48%). The remaining 97 patients (77%) exhibited common symptoms of fatigue, dyspnea on exertion, tachycardia, or chest pain, which we termed “cardiovascular PASC syndrome.” Three of these people met criteria for postural orthostatic tachycardia syndrome. Lower severity of acute COVID-19 was a significant predictor of cardiovascular PASC syndrome. In this cohort of patients referred to cardiology for PASC, 23% had a new diagnosis, but most displayed a pattern of symptoms associated with exercise intolerance.
Increasing trends in mental health problems among Chinese young adolescents: results from repeated cross-sectional data in Changsha 2016-2020
Authors: Wu Zhipeng , Wang Biao , Zou Zhulin , Liu Zhening , Chen Xudong , Long Yicheng 
Published: December 2021

AbstractThis study performed a repeated cross-sectional analysis to explore possible trends in mental health problems among Chinese adolescents during 2016 to 2020. A total of 2837 seventh-grade students from Changsha city were surveyed in three waves in 2016, 2019 and 2020. The results showed that obsessive-compulsive tendencies, interpersonal sensitivity, depression, anxiety, academic stress and emotional disturbance problems were significantly increased in surveyed adolescents during 2016 to 2020. Moreover, positive rates of most of these problems were higher in females than males, and were significantly increased in only females. These results highlight the importance of focusing on mental health among Chinese adolescents, especially girls.
Duplication of NRAMP3 gene in poplars generated two homologous transporters with distinct functions
Authors: Pottier Mathieu , Le Thi Van Anh , Primard-Brisset Catherine , Marion Jessica , Bianchi Michele , Victor Cindy , Déjardin Annabelle , Pilate Gilles , Thomine Sébastien 
Published: December 2021

ABSTRACTTransition metals are essential for a wealth of metabolic reactions, but their concentrations need to be tightly controlled across cells and cell compartments, as metal excess or imbalance has deleterious effects. Metal homeostasis is achieved by a combination of metal transport across membranes and metal binding to a variety of molecules. Gene duplication is a key process in evolution, as emergence of advantageous mutations on one of the copies can confer a new function. Here, we report that the poplar genome contains two paralogues encoding NRAMP3 metal transporters localized in tandem. All Populus species analyzed had two copies of NRAMP3, whereas only one could be identified in Salix species indicating that duplication occurred when the two genera separated. Both copies are under purifying selection and encode functional transporters, as shown by expression in the yeast heterologous expression system. However, genetic complementation revealed that only one of the paralogues has retained the original function in release of metals stored in the vacuole previously characterized in A. thaliana. Confocal imaging showed that the other copy has acquired a distinct localization to the Trans Golgi Network (TGN). Expression in poplar suggested that the copy of NRAMP3 localized on the TGN has a novel function in the control of cell-to-cell transport of manganese. This work provides a clear case of neo-functionalization through change in the subcellular localization of a metal transporter as well as evidence for the involvement of the secretory pathway in cell-to-cell transport of manganese.
Dynamic interplay between RPL3- and RPL3L-containing ribosomes modulates mitochondrial activity in the mammalian heart
Authors: Milenkovic Ivan , Santos Vieira Helaine Graziele , Lucas Morghan C , Ruiz-Orera Jorge , Patone Giannino , Kesteven Scott , Wu Jianxin , Feneley Michael , Espadas Guadalupe , Sabidó Eduard , Hubner Norbert , van Heesch Sebastiaan , Voelkers Mirko , Novoa Eva Maria 
Published: December 2021

ABSTRACTThe existence of naturally occurring ribosome heterogeneity is now a well-acknowledged phenomenon. However, whether this heterogeneity leads to functionally diverse ‘specialized ribosomes’ is still a controversial topic. Here, we explore the biological function of RPL3L (uL3L), a ribosomal protein (RP) paralog of RPL3 (uL3) that is exclusively expressed in muscle and heart tissues, by generating a viable homozygousRpl3lknockout mouse strain. We identify a rescue mechanism in which, upon RPL3L depletion, RPL3 becomes upregulated, yielding RPL3-containing ribosomes instead of RPL3L-containing ribosomes that are typically found in cardiomyocytes. Using both ribosome profiling (Ribo-Seq) and a novel orthogonal approach consisting of ribosome pulldown coupled to nanopore sequencing (Nano-TRAP), we find that RPL3L neither modulates translational efficiency nor ribosome affinity towards a specific subset of transcripts. By contrast, we show that depletion of RPL3L leads to increased ribosome-mitochondria interactions in cardiomyocytes, which is accompanied by a significant increase in ATP levels, potentially as a result of mitochondrial activity fine-tuning. Our results demonstrate that the existence of tissue-specific RP paralogs does not necessarily lead to enhanced translation of specific transcripts or modulation of translational output. Instead, we reveal a complex cellular scenario in which RPL3L modulates the expression of RPL3, which in turn affects ribosomal subcellular localization and, ultimately, mitochondrial activity.
Long-term labeling and imaging of synaptically-connected neuronal networksin vivousing double-deletion-mutant rabies viruses
Authors: Jin Lei , Sullivan Heather A. , Zhu Mulangma , Lavin Thomas K. , Matsuyama Makoto , Fu Xin , Lea Nicholas E. , Xu Ran , Hou YuanYuan , Rutigliani Luca , Pruner Maxwell , Babcock Kelsey R. , Ip Jacque Pak Kan , Hu Ming , Daigle Tanya L. , Zeng Hongkui , Sur Mriganka , Feng Guoping , Wickersham Ian R. 
Published: December 2021

AbstractMonosynaptic tracing is a widely-used technique for mapping neural circuitry, but its cytotoxicity has confined it primarily to anatomical applications. Here we present a second-generation system for labeling direct inputs to targeted neuronal populations with minimal toxicity, using double-deletion-mutant rabies viruses. Spread of the viruses requires expression of both deleted viral genesin transin postsynaptic source cells; suppressing this expression with doxycycline following an initial period of viral replication reduces toxicity to postsynaptic cells. Longitudinal two-photon imagingin vivoindicated that over 90% of both presynaptic and source cells survived for the full twelve-week course of imaging.Ex vivowhole-cell recordings at 5 weeks postinfection showed that the second-generation system perturbs input and source cells much less than does the first-generation system. Finally, two-photon calcium imaging of labeled networks of visual cortex neurons showed that their visual response properties appeared normal for 10 weeks, the longest we followed them.
Population genetics reveals divergent lineages and ongoing hybridization in a declining migratory fish species complex
Authors: Rougemont Quentin , Perrier Charles , Besnard Anne-Laure , Lebel Isabelle , Abdallah Yann , Feunteun Eric , Réveillac Elodie , Lasne Emilien , Acou Anthony , Nachón David José , Cobo Fernando , Evanno Guillaume , Baglinière Jean-Luc , Launey Sophie 
Published: December 2021

AbstractDeciphering the effects of historical and recent demographic processes responsible for the spatial patterns of genetic diversity and structure is a key objective in evolutionary and conservation biology. Using population genetic analyses, we investigated the demographic history, the contemporary genetic diversity and structure, and the occurrence of hybridization and introgression of two species of anadromous fish with contrasting life history strategies and which have undergone recent demographic declines, the allis shad (Alosa alosa) and the twaite shad (Alosa fallax). We genotyped 706 individuals from 20 rivers and 5 sites at sea in Southern Europe at thirteen microsatellite markers. Genetic structure between populations was lower for the nearly semelparous species A. alosa, which disperses greater distances compared to the iteroparous species, A. fallax. Individuals caught at sea were assigned at the river level for A. fallax and at the region level for A. alosa. Using an approximate Bayesian computation framework, we inferred that the most likely long term historical divergence scenario between both species and lineages involved historical separation followed by secondary contact accompanied by strong population size decline. Accordingly, we found evidence for contemporary hybridization and bidirectional introgression due to gene flow between both species and lineages. Moreover, our results support the existence of at least one distinct species in the Mediterrannean sea: A. agone in Golfe du Lion area, and another divergent lineage in Corsica. Overall, our results shed light on the interplay between historical and recent demographic processes and life history strategies in shaping population genetic diversity and structure of closely related species. The recent demographic decline of these species’ populations and their hybridization should be carefully considered while implementing conservation programs.
PncA from bacteria improves diet-induced NAFLD by enabling the transition from NAM to NA in mice
Authors: Feng Shengyu , Guo Liuling , Liu Hailiang 
Published: December 2021

AbstractNicotinamide adenine dinucleotide (NAD+) is crucial for energy metabolism, oxidative stress, DNA damage repair, longevity regulation, and several signaling processes. To date, three NAD+ synthesis pathways have been found in microbiota and hosts, but the potential relationship between gut microbiota and their hosts in regulating NAD+ homeostasis remains unknown. Here, we show that an analog of the first-line tuberculosis drug pyrazinamide (a bacterial NAD+ synthesis inhibitor) affected NAD+ levels in the intestines and liver of mice and disrupted the intestinal microecological balance. Furthermore, using microbiota expressing the pyrazinamidase/nicotinamidase (PncA) gene, which is a target of pyrazinamide, hepatic NAD+ levels were greatly increased and significantly increased compared with other NAD+ precursors, and diet-induced non-alcoholic fatty liver disease (NAFLD) in mice was improved. Overall, the PncA gene in microbiota plays an important role in regulating NAD+ synthesis in the host, thereby providing a potential target for modulating the host’s NAD+ level.HighlightsPncA inhibitors disrupt gut microbiome homeostasis and reduce host NAD+ levels but do not affect NAD+ levels in cultured cellsPncA gene in microbiota affects host liver NAD metabolismPncA affects lipid metabolism-related genes and metabolites in mice with NAFLDDiet-induced NAFLD is improved by PncA overexpression in the liver of miceGraphical abstract
Spatially Resolved Phosphoproteomics Reveals Fibroblast Growth Factor Receptor Recycling-driven Regulation of Autophagy and Survival
Authors: Watson Joanne , Ferguson Harriet R. , Brady Rosie M. , Ferguson Jennifer , Fullwood Paul , Mo Hanyi , Bexley Katherine H. , Knight David , Schwartz Jean-Marc , Smith Michael P. , Francavilla Chiara 
Published: December 2021

SummaryReceptor Tyrosine Kinase (RTK) endocytosis-dependent signalling drives cell proliferation and motility during development and adult homeostasis, but is dysregulated in diseases, including cancer. The recruitment of RTK signalling partners during endocytosis, specifically during recycling to the plasma membrane, is still unknown. Focusing on Fibroblast Growth Factor Receptor 2b (FGFR2b) recycling, we revealed FGFR signalling partners proximal to recycling endosomes (REs) by developing a Spatially Resolved Phosphoproteomics (SRP) approach based on APEX2-driven biotinylation followed by phosphopeptide enrichment. Combining this with traditional phosphoproteomics, bioinformatics, and targeted assays, we uncovered that FGFR2b stimulated by its recycling ligand FGF10 activates mTOR-dependent signalling and ULK1 at the REs, leading to autophagy suppression and cell survival. This adds to the growing importance of RTK recycling in orchestrating cell fate and suggests a therapeutically targetable vulnerability in ligand-responsive cancer cells. Integrating SRP with other systems biology approaches provides a powerful tool to spatially resolve celllar signalling.