bluuebunny/crossref_metadata_2025_split huggingface dataset:
A one-year hospital-based prospective COVID-19 open-cohort in the Eastern Mediterranean region: The Khorshid COVID Cohort (KCC) study
Authors: Sami Ramin , Soltaninejad Forogh , Amra Babak , Naderi Zohreh , Javanmard Shaghayegh Haghjooy , Iraj Bijan , Ahmadi Somayeh Haji , Shayganfar Azin , Dehghan Mehrnegar , Khademi Nilufar , Hosseini Nastaran Sadat , Mortazavi Mojgan , Mansourian Marjan , Mañanas Miquel Angel , Marateb Hamid Reza , Adibi Peyman 
Published: May 2020

AbstractThe COVID-19 is rapidly scattering worldwide, and the number of cases in the Eastern Mediterranean Region is rising. Thus, there is a need for immediate targeted actions. We designed a longitudinal study in a hot outbreak zone to analyze the serial findings between infected patients for detecting temporal changes from February 2020. In a hospital-based open-cohort study, patients are followed from admission until one year from their discharge (the 1st, 4th, 12th weeks, and the first year). The patient recruitment phase finished at the end of August 2020, and the follow-up continues by the end of August 2021. The measurements included demographic, socio-economics, symptoms, health service diagnosis and treatment, contact history, and psychological variables. The signs improvement, death, length of stay in hospital were considered primary, and impaired pulmonary function and psychotic disorders were considered main secondary outcomes. Moreover, clinical symptoms and respiratory functions are being determined in such follow-ups. Among the first 600 COVID-19 cases, 490 patients with complete information (39% female; the average age of 57±15 years) were analyzed. Seven percent of these patients died. The three main leading causes of admission were: fever (77%), dry cough (73%), and fatigue (69%). The most prevalent comorbidities between COVID-19 patients were hypertension (35%), diabetes (28%), and ischemic heart disease (14%). The percentage of primary composite endpoints (PCEP), defined as death, the use of mechanical ventilation, or admission to an intensive care unit was 18%. The Cox proportional-hazards model for PCEP indicated the following significant risk factors: Oxygen saturation < 80% (HR= 6.3; [CI 95%: 2.5,15.5]), lymphopenia (HR= 3.5; [CI 95%: 2.2,5.5]), Oxygen saturation 80%-90% (HR= 2.5; [CI 95%: 1.1,5.8]), and thrombocytopenia (HR= 1.6; [CI 95%: 1.1,2.5]). This long-term prospective Cohort may support healthcare professionals in the management of resources following this pandemic.
Annexin-A1 tripeptide attenuates surgery-induced neuroinflammation and memory deficits through regulation of the NLRP3 inflammasome
Authors: Zhang Zhiquan , Ma Qing , Velagapudi Ravikanth , Barclay William E. , Rodriguiz Ramona M. , Wetsel William C. , Shinohara Mari L. , Terrando Niccolò 
Published: May 2020

AbstractNeuroinflammation is a growing hallmark of perioperative neurocognitive disorders (PNDs), including delirium and longer-lasting cognitive deficits. We have developed a clinically-relevant orthopedic mouse model to study the impact of a common surgical procedure on the vulnerable brain. The mechanism underlying PNDs remain unknown. Here we evaluated the impact of surgical trauma on the NLRP3 inflammasome signaling, including the expression of apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and IL-1β in the hippocampus of C57BL6/J male mice, adult (3-months) and aged (>18-months). Surgery triggered ASC specks formation in CA1 hippocampal microglia, but without inducing significant morphological changes in NLRP3 and ASC knockout mice. Since no therapies are currently available to treat PNDs, we assessed the neuroprotective effects of a biomimetic peptide derived from the endogenous inflammation-ending molecule, Annexin-A1 (ANXA1). We tested the hypothesis that this peptide (ANXA1sp) inhibits NLRP3 inflammasome activation, thus preventing microglial activation and hippocampal-dependent memory deficits. Together these results uncover a previously underrecognized role of the NLRP3 inflammasome in triggering postoperative neuroinflammation and offer a new target for advancing treatment of PNDs through resolution of inflammation.
Phosphoproteomics identifies microglial Siglec-F inflammatory response during neurodegeneration
Authors: Morshed Nader , Ralvenius William T. , Nott Alexi , Watson L. Ashley , Rodriguez Felicia H. , Akay Leyla A. , Joughin Brian A. , Pao Ping-Chieh , Penney Jay , LaRocque Lauren , Mastroeni Diego , Tsai Li-Huei , White Forest M. 
Published: May 2020

SummaryAlzheimer’s disease (AD) is characterized by the appearance of amyloid-β plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK-p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec-F which was upregulated on a subset of reactive microglia. The human paralog Siglec-8 was also upregulated on microglia in AD. Siglec-F and Siglec-8 were upregulated following microglial activation with interferon gamma (IFNγ) in BV-2 cell line and human stem-cell derived microglia models. Siglec-F overexpression activates an endocytic and pyroptotic inflammatory response in BV-2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine-based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV-2 cells. Collectively, our results point to an important role for mouse Siglec-F and human Siglec-8 in regulating microglial activation during neurodegeneration.HighlightsPhosphoproteomics analysis of CK-p25, 5XFAD, and Tau P301S mouse models finds dysregulated signaling networks associated with Alzheimer’s disease pathologies.A phosphorylation site on Siglec-F is found to be upregulated across all three models of disease.Expression of Siglec-F and its human paralog Siglec-8 is increased in reactive microglia.Overexpression of Siglec-F and Siglec-8in vitrodrives an endocytic and pyroptotic inflammatory response.In BriefPhosphoproteome signaling changes associated with Alzheimer’s disease (AD) are poorly characterized. Here, Morshed et al. apply phosphoproteomics to mouse models of AD to uncover a novel microglial receptor, Siglec-F, that is upregulated on a subset of inflammatory microglia across models of neurodegeneration. The human paralog, Siglec-8 is also found to be upregulated in late-onset AD microglia. Overexpression of Siglec-F and related human Siglecs activates pro-inflammatory signaling responses in BV-2 cells.
The longer the better? General skill but not probabilistic learning improves with the duration of short rest periods
Authors: Fanuel Lison , Plèche Claire , Vékony Teodóra , Quentin Romain , Janacsek Karolina , Nemeth Dezso 
Published: May 2020

AbstractMemory consolidation has mainly been investigated for extended periods, from hours to days. Recent studies suggest that memory consolidation can also occur within shorter periods, from minutes to seconds. Our study aimed at determining (1) whether short rest periods lead to improvements in implicit probabilistic sequence learning and (2) whether length of rest duration influences such offline improvements. Participants performed an implicit probabilistic sequence learning task throughout 45 blocks. Between blocks, participants were allowed to rest and then to continue the task in their pace. The overall reaction times (general skill learning) shortened from pre- to post-rest periods, and this improvement was increased for longer rest durations. However, probabilistic sequences knowledge decreased in these periods, and this decrement was not related to the length of rest duration. These results suggest that (1) general skill learning but not probabilistic sequence knowledge benefits from short rest periods and, possibly, from memory consolidation, (2) ultra-fast offline improvements in general skills, but not forgetting in probabilistic sequence knowledge, are time-dependent. Overall, our findings highlight that ultra-fast consolidation differently affects distinct cognitive processes.
Disrupted object-scene semantics boost scene recall but diminish object recall in drawings from memory
Authors: Bainbridge Wilma A. , Kwok Wan Y. , Baker Chris I. 
Published: May 2020

AbstractHumans are highly sensitive to the statistical relationships between features and objects within visual scenes. Inconsistent objects within scenes (e.g., a mailbox in a bedroom) instantly jump out to us, and are known to capture our attention. However, it is debated whether such semantic inconsistencies result in boosted memory for the scene, impaired memory, or have no influence on memory. Here, we examined the relationship of scene-object consistencies on memory representations measured through drawings made during recall. Participants (N=30) were eye-tracked while studying 12 real-world scene images with an added object that was either semantically consistent or inconsistent. After a 6-minute distractor task, they drew the scenes from memory while pen movements were tracked electronically. Online scorers (N=1,725) rated each drawing for diagnosticity, object detail, spatial detail, and memory errors. Inconsistent scenes were recalled more frequently, but contained less object detail. Further, inconsistent objects elicited more errors reflecting looser memory binding (e.g., migration across images). These results point to a dual effect in memory of boosted global (scene) but diminished local (object) information. Finally, we replicated prior effects showing that inconsistent objects captured eye fixations, but found that fixations during study were not correlated with recall performance, time, or drawing order. In sum, these results show a nuanced effect of scene inconsistencies on memory detail during recall.
Social hierarchy is established and maintained with distinct acts of aggression in maleDrosophila
Authors: Simon Jasper C. , Heberlein Ulrike 
Published: May 2020

ABSTRACTSocial interactions pivot on an animal’s experiences, internal states, and feedback from others. This complexity drives the need for precise descriptions of behavior to dissect the fine detail of its genetic and neural circuit bases. In laboratory assays, maleDrosophila melanogasterreliably exhibit aggression, and its extent is generally measured by scoring lunges, a feature of aggression in which one male quickly thrusts onto his opponent. Here, we introduce an explicit approach to identify both the onset and reversals in hierarchical status among opponents and observe that distinct aggressive acts reproducibly precede, concur, or follow the establishment of dominance. We find that lunges are insufficient for establishing dominance. Rather, lunges appear to reflect the dominant state of a male and help in maintaining his social status. Lastly, we characterize the recurring and escalating structure of aggression that emerges through subsequent reversals in dominance. Collectively, this work provides a framework for studying the complexity of agonistic interactions in male flies enabling its neurogenetic basis to be understood with precision.
Preferred conformations in the disordered region of human CPEB3, a functional amyloid linked to memory consolidation
Authors: de Mingo D. Ramírez , Pantoja-Uceda D. , Hervás R. , Carrión-Vázquez M. , Laurents D. V. 
Published: May 2020

AbstractWhile implicated in neurodegenerative diseases, amyloids are also essential to some physiological processes, including memory consolidation by neuronal-specific isoforms of the Cytoplasmic Polyadenylation Element Binding (CPEB) protein family. CPEB mediates memory persistence by the formation of self-sustaining amyloid assemblies through its intrinsically disordered region (IDR). Here, we characterize the atomic level conformation and ps-ns dynamics of the 426-residue IDR of human CPEB3 (hCPEB3), which has been associated with episodic memory in humans, by NMR spectroscopy. We found that the first 29 residues: M1QDDLLMDKSKTQPQPQQQQRQQQQPQP29, adopt a helical+disordered motif. Residues 86-93: P83QQPPPP93, and 166-175: P166PPPAPAPQP175form polyproline II (PPII) helices. While the (VG)5repeat motif is completely disordered, residues 200-250 adopt three partially populated α-helices. Residues 345–355, which comprise the nuclear localization signal (NLS), form a modestly populated α-helix and border a phosphoTyr which may mediate STAT5B binding. These findings allow us to suggest a model for nascent hCPEB3 structural transitions at single residue resolution, advancing that amyloid breaker residues, like proline, are a key difference between functional versus pathological amyloids. Besides revealing some aspects of the molecular basis of memory, these findings could aid the future development of treatments for post-traumatic stress disorder.Areas:Biophysics, Structural Biology, Biochemistry & Neurosciences.
Working groups, gender and publication impact of Canada’s ecology and evolution faculty
Authors: Wei Qian , Lachapelle Francois , Fuller Sylvia , Corrigall-Brown Catherine , Srivastava Diane S. 
Published: May 2020

ABSTRACTA critical part of science is the extraction of general principles by synthesizing results from many different studies or disciplines. In the fields of ecology and evolution, a popular method to conduct synthesis science is in working groups – that is, research collaborations based around intensive week-long meetings. We present in this report an analysis of the impact of working group participation and gender on the publication impact of ecology and evolution faculty at Canadian universities who were research active over the last three decades (N=1408). Women are underrepresented in this research population relative to the general population, and even the Canadian faculty population. Participation in working groups not only benefits science, but also benefits the researchers involved by accelerating the temporal increase in their H-index. However, this benefit is particularly driven by senior male researchers. The effect is weaker for female researchers and even negative for researchers within 4 years of their PhD. However, gender does not affect current participation rates in working groups, nor reported indirect benefits – such as future collaborations, funding and data resources. The results of this study suggest that working groups can act as career catalysts for researchers, but that – as in many areas of science – there are challenging issues of equity that require action. Because the H-index is a cumulative measure, gender inequities from before the turn of the millenium may still be distorting the perceived publication impact of today’s research-active faculty.
The immunosuppression of macrophages underlies the cardioprotective effects of catestatin (CST)
Authors: Ying Wei , Tang Kechun , Avolio Ennio , Schilling Jan M. , Pasqua Teresa , Liu Matthew A. , Cheng Hongqiang , Gao Hong , Zhang Jing , Mahata Sumana , Ko Myung S. , Bandyopadhyay Gautam , Das Soumita , Roth David M. , Sahoo Debashis , Webster Nicholas J.G. , Sheikh Farah , Ghosh Gourisankar , Patel Hemal H. , Ghosh Pradipta , van den Bogaart Geert , Mahata Sushil K. 
Published: May 2020

ABSTRACTHypertension (HTN) is associated with inflammation and excessive production of catecholamines. Hypertensive patients have reduced plasma levels of Catestatin (CST), a bioactive cleavage product of the prohormone Chromogranin A (CgA). In mouse models, HTN symptoms can be reduced by administration of CST, but the role of CST in the regulation of cardiovascular function is unknown. In this study, we generated mice with knockout (KO) of the region of the CgA gene coding for CST (CST-KO) and found that CST-KO mice are not only hypertensive as predicted, but also display left ventricular hypertrophy, have marked macrophage infiltration of the heart and adrenal gland, and have elevated levels of pro-inflammatory cytokines and catecholamines. Intraperitoneal injection with CST reversed these phenotypes, and ischemic pre-conditioning-induced cardioprotection was also abolished in CST-KO mice. Experiments with chlodronate depletion of macrophages and bone-marrow transfer showed that macrophages produce CST and that the anti-hypertensive effects of CST are mediated in part via CST’s immunosuppression of macrophages as a form of feedback inhibition. The data thus implicate CST as a key autocrine attenuator of the cardiac inflammation in HTN by reducing macrophage inflammation.
Uncovering the locus coeruleus: comparison of localization methods for functional analysis
Authors: Mäki-Marttunen Verónica , Espeseth Thomas 
Published: May 2020

AbstractFunctional neuroimaging of small brainstem structures in humans is gaining increasing interest due to their potential importance in aging and many clinical conditions. Researchers have used different methods to measure activity in the locus coeruleus (LC), the main noradrenergic nucleus in the brain. However, the reliability of the different methods for identifying this small structure is unclear. In the present article, we compared four different approaches to estimate localization of the LC in a large sample (N = 98): 1) a probabilistic map from a previous study, 2) masks segmented from neuromelanin-sensitive scans, 3) components from a masked-independent components analysis of the functional data, and 4) a mask from pupil regression of the functional data. The four methods have been used in the community and find some support as reliable ways of assessing the localization of LCin vivoin humans by using functional imaging. We report several measures of similarity between the LC masks obtained from the different methods. In addition, we compare the similarity between functional connectivity maps obtained from the different masks. We conclude that sample-specific masks appear more suitable than masks from a different sample, that masks based on structural versus functional methods may capture different portions of LC, and that, at the group level, the creation of a “consensus” mask using more than one approach may give a better estimate of LC localization.
A Novel Method of Immunomodulation of Endothelial cells Using Streptococcus Pyogenes and its Lysate
Authors: Arokiaraj Mark Christopher , Wilson Jarad 
Published: May 2020

AbstractBackgroundCoronary artery diseases and autoimmune disorders are common in clinical practice. In this study, a novel method of immune-modulation to modify the endothelial function was studied to modulate the features of the endothelial cells, and thereby to reduce coronary artery disease and other disorders modulated by endothelium.MethodsHUVEC cells were seeded in the cell culture, and streptococcus pyogenes were added to the cell culture, and the supernatant was studied for the secreted proteins. In the second phase, the bacterial lysate was synthesized, and the lysate was added to cell culture; and the proteins in the supernatant were studied at various time intervals.ResultsWhen streptococcus pyogenes alone was added to culture, E Cadherin, Angiostatin, EpCAM and PDGF-AB were some of the biomarkers elevated significantly. HCC1, IGFBP2 and TIMP were some of the biomarkers which showed a reduction. When the lysate was added, the cell-culture was maintained for a longer time, and it showed the synthesis of immune regulatory cytokines. Heatmap analysis showed a significant number of proteins/cytokines concerning the immune/pathways, and toll-like receptors superfamily were modified. BLC, IL 17, BMP 7, PARC, Contactin2, IL 10 Rb, NAP 2 (CXCL 7), Eotaxin 2 were maximally increased. By principal component analysis, the results observed were significant.ConclusionThere is potential for a novel method of immunomodulation of the endothelial cells, which have pleiotropic functions, using streptococcus pyogenes and its lysates.
GEM: Scalable and flexible gene-environment interaction analysis in millions of samples
Authors: Westerman Kenneth E. , Pham Duy T. , Hong Liang , Chen Ye , Sevilla-González Magdalena , Sung Yun Ju , Sun Yan V. , Morrison Alanna C. , Chen Han , Manning Alisa K. 
Published: May 2020

ABSTRACTMotivationGene-environment interaction (GEI) studies are a general framework that can be used to identify genetic variants that modify the effects of environmental, physiological, lifestyle, or treatment effects on complex traits. Moreover, accounting for GEIs can enhance our understanding of the genetic architecture of complex diseases. However, commonly-used statistical software programs for GEI studies are either not applicable to testing certain types of GEI hypotheses or have not been optimized for use in large samples.ResultsHere, we develop a new software program, GEM (Gene-Environment interaction analysis in Millions of samples), which supports the inclusion of multiple GEI terms, adjustment for GEI covariates, and robust inference, while allowing multi-threading to reduce computation time. GEM can conduct GEI tests as well as joint tests of genetic effects for both continuous and binary phenotypes. Through simulations, we demonstrate that GEM scales to millions of samples while addressing limitations of existing software programs. We additionally conduct a gene-sex interaction analysis on waist-hip ratio in 352,768 unrelated individuals from the UK Biobank, identifying 39 novel loci in the joint test that have not previously been reported in combined or sex-specific analyses. Our results demonstrate that GEM can facilitate the next generation of large-scale GEI studies and help advance our understanding of genomic contributions to complex traits.AvailabilityGEM is freely available as an open source project athttps://github.com/large-scale-gxe-methods/GEM.Contactakmanning@mgh.harvard.edu,Han.Chen.2@uth.tmc.eduSupplementary informationSupplementary data are available atBioinformaticsonline.
Invariant chain with an AP3 interacting sorting signal is sorted to late endosomal compartments and may improve MHC class I loading and presentation
Authors: Kucera Ana , Mensali Nadia , Pati Niladri Busan , Inderberg Else Marit , Myhre Marit Renée , Gregers Tone Fredsvik , Wälchli Sébastien , Bakke Oddmund 
Published: May 2020

ABSTRACTInvariant chain (Ii) is traditionally known as the dedicated MHCII chaperone. Recent reports have broadened our understanding about various tasks that Ii plays including its physiological role in MHCI cross-presentation. Ii bound MHCI via the MHCII scaffolding CLIP peptide may facilitate MHCI trafficking to the endosomal pathway. The sorting function of Ii depends on two leucine-based sorting signals present in the cytoplasmic tail that acts as binding sites for the adaptor proteins AP-1/AP-2. Here we increased the Ii cross-presentation potency by replacing these with an AP3 motif resulting an efficient transport of Ii from TGN to late endosomes. We also replaced the CLIP region of li with a therapeutically relevant peptide, MART-1. We found the Ii AP3mutant-MART1 construct was capable of loading MHCI and stimulate specific T-cell response more efficiently than the wild type counterpart. The results show that Ii with an AP3 binding sorting motif carrying peptide epitope(s) can promote efficient antigen presentation to cytotoxic T cells (CTLs) independent of the ER located classical MHCI peptide loading machinery.