Neuronal autophagy in the control of synapse function.

Neurons are long-lived postmitotic cells that capitalize on autophagy to remove toxic or defective proteins and organelles to maintain neurotransmission and the integrity of their functional proteome. Mutations in autophagy genes cause congenital diseases, sharing prominent brain dysfunctions including epilepsy, intellectual disability, and neurodegeneration. Ablation of core autophagy genes in neurons or glia disrupts normal behavior, leading to motor deficits, memory impairment, altered sociability, and epilepsy, which are associated with defects in synapse maturation, plasticity, and neurotransmitter release.

Intraspecific divergence within mediates the dynamics of freshwater harmful algal blooms under climate warming scenarios.

Intraspecific biodiversity can have ecosystem-level consequences and may affect the accuracy of ecological forecasting. For example, rare genetic variants may have traits that prove beneficial under future environmental conditions. The cyanobacterium responsible for most freshwater harmful algal blooms worldwide, , occurs in at least three types.

Biodiversity within phytoplankton-associated microbiomes regulates host physiology, host community ecology, and nutrient cycling.

Unlabelled: Biological diversity is declining across the tree of life, including among prokaryotes. With the increasing awareness of host-associated microbes as potential regulators of eukaryotic host physiology, behavior, and ecology, it is important to understand the implications of declining diversity within host microbiomes on host fitness, ecology, and ecosystem function. We used phytoplankton and their associated environmental microbiomes as model systems to test the independent and interactive effects of declining microbiome diversity with and without other stressors often caused by human activity-elevated temperature and altered nutrient availability.

[Hirsutism: a common problem; when to consider rare causes?].

Excessive hair growth is a common and distressing complaint in women. It is imperative to differentiate excessive hair growth from hirsutism with possible other signs of virilization. Hirsutism is commonly attributed to polycystic ovary syndrome (PCOS).

Suppressed ORAI1-STIM1-dependent Ca entry by protein kinase C isoforms regulating platelet procoagulant activity.

Agonist-induced rises in cytosolic Ca control most platelet responses in thrombosis and hemostasis. In human platelets, we earlier demonstrated that the ORAI1-STIM1 pathway is a major component of extracellular Ca entry, in particular when induced via the ITAM-linked collagen receptor, glycoprotein VI (GPVI). In the present article, using functionally defective platelets from patients with a loss-of-function mutation in ORAI1 or STIM1, we show that Ca entry induced by the endoplasmic reticulum ATPase inhibitor, thapsigargin, fully relies on this pathway.

Statistical analysis of feature-based molecular networking results from non-targeted metabolomics data.

Feature-based molecular networking (FBMN) is a popular analysis approach for liquid chromatography-tandem mass spectrometry-based non-targeted metabolomics data. While processing liquid chromatography-tandem mass spectrometry data through FBMN is fairly streamlined, downstream data handling and statistical interrogation are often a key bottleneck. Especially users new to statistical analysis struggle to effectively handle and analyze complex data matrices.

Multi-phased Kinetics and Interaction of Protein Kinase Signaling in Glycoprotein VI-Induced Platelet αIIbβ3 Integrin Activation and Degranulation.

Background:  Platelet glycoprotein VI (GPVI) stimulation activates the tyrosine kinases Syk and Btk, and the effector proteins phospholipase Cγ 2 (PLCγ2) and protein kinase C (PKC). Here, the activation sequence, crosstalk, and downstream effects of this Syk-Btk-PKC signalosome in human platelets were analyzed.

Methods And Results:  Using immunoblotting, we quantified 14 regulated phospho-sites in platelets stimulated by convulxin with and without inhibition of Syk, Btk, or PKC.

Design, manufacturing and testing of a green non-isocyanate polyurethane prosthetic heart valve.

The sole effective treatment for most patients with heart valve disease is valve replacement by implantation of mechanical or biological prostheses. However, mechanical valves represent high risk of thromboembolism, and biological prostheses are prone to early degeneration. In this work, we aim to determine the potential of novel environmentally-friendly non-isocyanate polyurethanes (NIPUs) for manufacturing synthetic prosthetic heart valves.

Ultra-high throughput-based screening for the discovery of antiplatelet drugs affecting receptor dependent calcium signaling dynamics.

Distinct platelet activation patterns are elicited by the tyrosine kinase-linked collagen receptor glycoprotein VI (GPVI) and the G-protein coupled protease-activated receptors (PAR1/4) for thrombin. This is reflected in the different platelet Ca responses induced by the GPVI agonist collagen-related peptide (CRP) and the PAR1/4 agonist thrombin. Using a 96 well-plate assay with human Calcium-6-loaded platelets and a panel of 22 pharmacological inhibitors, we assessed the cytosolic Ca signaling domains of these receptors and developed an automated Ca curve algorithm.

Ancient genomes illuminate Eastern Arabian population history and adaptation against malaria.

The harsh climate of Arabia has posed challenges in generating ancient DNA from the region, hindering the direct examination of ancient genomes for understanding the demographic processes that shaped Arabian populations. In this study, we report whole-genome sequence data obtained from four Tylos-period individuals from Bahrain. Their genetic ancestry can be modeled as a mixture of sources from ancient Anatolia, Levant, and Iran/Caucasus, with variation between individuals suggesting population heterogeneity in Bahrain before the onset of Islam.

Endothelium-mediated regulation of platelet activation: Involvement of multiple protein kinases.

The endothelial regulation of platelet activity is incompletely understood. Here we describe novel approaches to find molecular pathways implicated on the platelet-endothelium interaction. Using high-shear whole-blood microfluidics, employing coagulant or non-coagulant conditions at physiological temperature, we observed that the presence of human umbilical vein endothelial cells (HUVEC) strongly suppressed platelet adhesion and activation, via the collagen receptor glycoprotein VI (GPVI) and the PAR receptors for thrombin.

microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data.

microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms' role in ecology and human health.

Restraining of glycoprotein VI- and integrin α2β1-dependent thrombus formation by platelet PECAM1.

The platelet receptors, glycoprotein VI (GPVI) and integrin α2β1 jointly control collagen-dependent thrombus formation via protein tyrosine kinases. It is unresolved to which extent the ITIM (immunoreceptor tyrosine-based inhibitory motif) receptor PECAM1 and its downstream acting protein tyrosine phosphatase PTPN11 interfere in this process. Here, we hypothesized that integrin α2β1 has a co-regulatory role in the PECAM1- and PTPN11-dependent restraint of thrombus formation.

Impact of Unilateral Alveolar Bone Grafting on Nasal Volume and Nasolabial Surface: A 3D Analysis.

Objective: To determine possible effects of unilateral alveolar cleft closure on internal nasal volume and external nasolabial surface.

Design: Retrospective, single-arm, cohort study.

Setting: Institutional, tertiary care.

Protective Effect of Ticagrelor Against Infective Endocarditis Induced by Virulent in Mice.

In addition to its potent antiplatelet activity, ticagrelor possesses antibacterial properties against gram-positive bacteria. We wondered whether the typical clinical dosage of ticagrelor could prevent the development of infective endocarditis caused by highly virulent . Ticagrelor prevented vegetation formation in a mouse model of inflammation-induced endocarditis.

Validation of the Incidence of Reported Periprosthetic Joint Infections in Total Hip and Knee Arthroplasty in the Dutch Arthroplasty Register.

Background: Arthroplasty registers underreport the incidence of periprosthetic joint infections (PJIs). We validated the incidence of reported PJIs in total hip arthroplasties (THAs) and total knee arthroplasties (TKAs) in the Dutch Arthroplasty Register (LROI) using data from the Dutch National Nosocomial Surveillance Network (PREZIES).

Methods: All primary THAs and TKAs from the LROI and all primary THAs and TKAs performed in consenting hospitals from PREZIES between 2012 and 2018 were matched on date of birth, date of surgery, sex, hospital, and type of procedure (THA n = 91,208; TKA n = 80,304).

Prevalence of type II endoleak after elective endovascular aneurysm repair with polytetrafluoroethylene- or polyester-based endografts.

Objective: Type II endoleak is the most frequent complication after endovascular abdominal aneurysm repair. Polytetrafluoroethylene and polyester (PE) are the two most commonly used graft materials in endovascular aneurysm repair (EVAR) devices. Biological properties of the material might influence the appearance and persistence of type II endoleak (T2EL).

A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data.

MicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without knowledge, will vastly enhance the understanding of microorganisms' role in ecology and human health.

Antagonistic Roles of Human Platelet Integrin αIIbβ3 and Chemokines in Regulating Neutrophil Activation and Fate on Arterial Thrombi Under Flow.

Background: Platelets and neutrophils are the first blood cells accumulating at sites of arterial thrombus formation, and both cell types contribute to the pathology of thrombotic events. We aimed to identify key interaction mechanisms between these cells using microfluidic approaches.

Methods: Whole-blood perfusion was performed over a collagen surface at arterial shear rate.

COVID-19 Hospitalization Outcomes Among Patients With Autoimmune Rheumatic Diseases in the United States.

Objectives: To investigate the outcomes of COVID-19-related hospitalizations among patients with autoimmune rheumatic diseases (ARDs) in the United States in 2020. The primary outcome was in-hospital mortality, and secondary outcomes included intubation rate, length of hospital stay (LOS), and total hospital charges (THCs).

Methods: Data for the study were obtained from the National Inpatient Sample database and included patients who were hospitalized with a principal diagnosis of COVID-19.

Role of SHP2 (PTPN11) in glycoprotein VI-dependent thrombus formation: Improved platelet responsiveness by the allosteric drug SHP099 in Noonan syndrome patients.

Introduction: The protein tyrosine phosphatase SHP2 (PTPN11) is a negative regulator of glycoprotein VI (GPVI)-induced platelet signal under certain conditions. Clinical trials with derivatives of the allosteric drug SHP099, inhibiting SHP2, are ongoing as potential therapy for solid cancers. Gain-of-function mutations of the PTPN11 gene are observed in part of the patients with the Noonan syndrome, associated with a mild bleeding disorder.

Tumor-educated platelet blood tests for Non-Small Cell Lung Cancer detection and management.

Liquid biopsy approaches offer a promising technology for early and minimally invasive cancer detection. Tumor-educated platelets (TEPs) have emerged as a promising liquid biopsy biosource for the detection of various cancer types. In this study, we processed and analyzed the TEPs collected from 466 Non-small Cell Lung Carcinoma (NSCLC) patients and 410 asymptomatic individuals (controls) using the previously established thromboSeq protocol.

Continuous IV infusion of anakinra.

A review of the use of continuous IV infusion of anakinra; a description of the protocol for continuous IV infusion of anakinra in the treatment of cytokine storm developed over the past 4 years at a tertiary level academic medical center in the United States. We reviewed published reports of continuous IV infusion of anakinra in cytokine storm and summarize this method of treatment in other diseases. As well, over the past 4 years, continuous IV infusions of anakinra were administered at our tertiary level academic medical center in the United States (Regions Hospital, St.