Cutting Edge: ATP13A2 Is an Endolysosomal Regulator of TLR9/7 Activation in Human Plasmacytoid Dendritic Cells.

ATPase cation transporting 13A2 (ATP13A2) is an endolysosomal P-type ATPase known to be a polyamine transporter, explored mostly in neurons. As endolysosomal functions are also crucial in innate immune cells, we aimed to explore the potential role of ATP13A2 in the human immunocellular compartment. We found that human plasmacytoid dendritic cells (pDCs), the professional type I IFN-producing immune cells, especially have a prominent enrichment of ATP13A2 expression in endolysosomal compartments.

Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells.

T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, plays a very critical role. T cell extravasation in inflamed tissues depends on chemotactic cues and interaction between endothelial adhesion molecules and cellular integrins. A migrating T cell is expected to sense diverse external and membrane-intrinsic mechano-physical cues, but molecular mechanisms of such mechanosensing in cell migration are not established.

Suppressed transcript diversity and immune response in COVID-19 ICU patients: a longitudinal study.

Understanding the dynamic changes in gene expression during Acute Respiratory Distress Syndrome (ARDS) progression in post-acute infection patients is crucial for unraveling the underlying mechanisms. Study investigates the longitudinal changes in gene/transcript expression patterns in hospital-admitted severe COVID-19 patients with ARDS post-acute SARS-CoV-2 infection. Blood samples were collected at three time points and patients were stratified into severe and mild ARDS, based on their oxygenation saturation (SpO/FiO) kinetics over 7 d.

Energetic Electron Precipitation Driven by Electromagnetic Ion Cyclotron Waves from ELFIN's Low Altitude Perspective.

We review comprehensive observations of electromagnetic ion cyclotron (EMIC) wave-driven energetic electron precipitation using data collected by the energetic electron detector on the Electron Losses and Fields InvestigatioN (ELFIN) mission, two polar-orbiting low-altitude spinning CubeSats, measuring 50-5000 keV electrons with good pitch-angle and energy resolution. EMIC wave-driven precipitation exhibits a distinct signature in energy-spectrograms of the precipitating-to-trapped flux ratio: peaks at >0.5 MeV which are abrupt (bursty) (lasting ∼17 s, or ) with significant substructure (occasionally down to sub-second timescale).

Association of gut microbial dysbiosis with disease severity, response to therapy and disease outcomes in Indian patients with COVID-19.

Background: Severe coronavirus disease 2019 (COVID-19) is associated with systemic hyper-inflammation. An adaptive interaction between gut microbiota and host immune systems is important for intestinal homeostasis and systemic immune regulation. The association of gut microbial composition and functions with COVID-19 disease severity is sparse, especially in India.

Circulating Interleukin-8 Dynamics Parallels Disease Course and Is Linked to Clinical Outcomes in Severe COVID-19.

Severe COVID-19 frequently features a systemic deluge of cytokines. Circulating cytokines that can stratify risks are useful for more effective triage and management. Here, we ran a machine-learning algorithm on a dataset of 36 plasma cytokines in a cohort of severe COVID-19 to identify cytokine/s useful for describing the dynamic clinical state in multiple regression analysis.

Clinical Trial Subgroup Analyses to Investigate Clinical and Immunological Outcomes of Convalescent Plasma Therapy in Severe COVID-19.

Objective: To assess the clinical and immunological benefits of passive immunization using convalescent plasma therapy (CPT).

Materials And Methods: A series of subclass analyses were performed on the previously published outcome data and accompanying clinical metadata from a completed randomized controlled trial (RCT) (Clinical Trial Registry of India, number CTRI/2020/05/025209). The subclass analyses were performed on the outcome data and accompanying clinical metadata from a completed RCT (patient recruitment between May 15, 2020 and October 31, 2020).

Plasma Gradient of Soluble Urokinase-Type Plasminogen Activator Receptor Is Linked to Pathogenic Plasma Proteome and Immune Transcriptome and Stratifies Outcomes in Severe COVID-19.

Disease caused by SARS-CoV-2 coronavirus (COVID-19) led to significant morbidity and mortality worldwide. A systemic hyper-inflammation characterizes severe COVID-19 disease, often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients.

Nature and Dimensions of Systemic Hyperinflammation and its Attenuation by Convalescent Plasma in Severe COVID-19.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has led to significant morbidity and mortality. While most suffer from mild symptoms, some patients progress to severe disease with acute respiratory distress syndrome (ARDS) and associated systemic hyperinflammation.

Methods: First, to characterize key cytokines and their dynamics in this hyperinflammatory condition, we assessed abundance and correlative expression of a panel of 48 cytokines in patients progressing to ARDS as compared to patients with mild disease.

The ELFIN Mission.

The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93 inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime.

Lactate Induces Pro-tumor Reprogramming in Intratumoral Plasmacytoid Dendritic Cells.

Plasmacytoid dendritic cells are the most efficient producers of type I interferons, viz. IFNα, in the body and thus have the ability to influence anti-tumor immune responses. But repression of effective intra-tumoral pDC activation is a key immuno-evasion strategy exhibited in tumors-tumor-recruited pDCs are rendered "tolerogenic," characterized by deficiency in IFNα induction and ability to expand regulatory T cells .

Computer-aided diagnosis system for characterizing ISUP grade≥2 prostate cancers at multiparametric MRI: A cross-vendor evaluation.

Purpose: To assess the performance of a computer-aided diagnosis (CADx) system trained at characterizing International Society of Urological Pathology (ISUP) grade≥2 peripheral zone (PZ) prostate cancers on multiparametric magnetic resonance imaging (mpMRI) examinations from a different institution and acquired on different scanners than those used for the training database.

Patients And Methods: Preoperative mpMRIs of 74 men (median age, 65.7 years) treated by prostatectomy between 2014 and 2017 were retrospectively selected.

Effect of peripheral cryoneurotomy and nerve transection on the trigeminal ganglion in rats.

In this experimental study, we did peripheral neurectomyand peripheral cryoneurotomy of the mental nerve in rats and histologically assessed their effects on the trigeminal ganglion at timed intervals for six months. There were marked irreversible changes in the neurectomy group whereas the cryoneurotomy group made a full recovery. These results help to explain the differing effects of these procedures on trigeminal neuralgia.

Cross cultural translation, adaptation and reliability of the Malay version of the Canadian Acute Respiratory Illness and Flu Scale (CARIFS).

Background: The Canadian Acute Respiratory Illness and Flu Scale (CARIFS) is a parent-proxy questionnaire that assesses severity of acute respiratory infections in children. The aim was to (a) perform a cross-cultural adaptation and (b) prove that the Malay CARIFS is a reliable tool.

Findings: The CARIFS underwent forward and backward translations as recommended by international guidelines.

Prevalence of stress among medical students: a comparative study between public and private medical schools in Bangladesh.

Background: Throughout the world all health professionals face stress because of time-pressures, workload, multiple roles and emotional issues. Stress does not only exist among the health professionals but also in medical students. Bangladesh has currently 77 medical colleges 54 of which are private.

A phase I clinical trial of CD1c (BDCA-1)+ dendritic cells pulsed with HLA-A*0201 peptides for immunotherapy of metastatic hormone refractory prostate cancer.

Preclinical studies have suggested that purified populations of CD1c (BDCA-1) blood-derived dendritic cells (BDC) loaded with tumor-specific peptides may be a feasible option for prostate cancer immunotherapy. We performed an open-label dose-finding Phase I study to evaluate the safe use of CD1c BDC in patients with advanced metastatic hormone refractory prostate cancer. HLA-A*0201-positive patients with advanced metastatic prostate cancer were recruited and consented.

Physical training induced resting bradycardia and its association with cardiac autonomic nervous activities.

Regular physical exercise causes resting bradycardia. This exercise-induced resting bradycardia may be associated with exercise-induced changes in Cardiac autonomic nervous activities (CANA). Power Spectral Analysis (PSA) of Heart rate variability (HRV) is one of the most promising new techniques to quantify CANA.

Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients.

Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the lack of suitable target antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested.

Antioxidant effect of valsartan in experimental model of myocardial infarction.

This study was done to investigate the antioxidant effect of valsartan, an AT1 receptor blocker, when administered in experimental model of myocardial infarction (MI). MI was induced in rats by administration of adrenaline at a dose of 2 mg/kg body weight subcutaneously two injections 24 hrs apart and was assessed by significant elevation of marker enzymes (CK-MB and AST). Valsartan (30 mg/kg body weight) was administered through intragastric tube daily for 2 weeks in both pre- and post- MI groups.

A multiscale simulation study of carbon nanotube interactions with designed amphiphilic peptide helices.

The dispersion and manipulation of carbon nanotubes (CNTs) are of great importance if we are to utilise the unique properties of CNTs in a range of biological, electrical and mechanical applications. Recently, a designed amphiphilic peptide helix termed nano-1 has been shown to solubilise CNTs in aqueous solution. Furthermore, the peptide is capable of assembling these coated tubes into fibres.

The interaction of C60 and its derivatives with a lipid bilayer via molecular dynamics simulations.

Coarse-grained molecular dynamics simulations have been used to explore the interactions of C(60) and its derivatives with lipid bilayers. Pristine C(60) partitions into the bilayer core, whilst C(60)(OH)(20) experiences a central energetic barrier to permeation across the bilayer. For intermediate levels of derivatization, e.

Helix dynamics in a membrane transport protein: comparative simulations of the glycerol-3-phosphate transporter and its constituent helices.

The glycerol-3-phosphate transporter (GlpT) is a member of the major facilitator superfamily (MFS). GlpT is an organic phosphate/inorganic phosphate antiporter. It shares a similar fold with other MFS transporters (e.

Asymmetric stability among the transmembrane helices of lactose permease.

Combining structure determinations from nuclear magnetic resonance (NMR) data and molecular dynamics simulations (MD) under the same environmental conditions revealed a startling asymmetry in the intrinsic conformational stability of secondary structure in the transmembrane domain of lactose permease (LacY). Eleven fragments, corresponding to transmembrane segments (TMs) of LacY, were synthesized, and their secondary structure in solution was determined by NMR. Eight of the TMs contained significant regions of helical structure.

Laryngeal rhinosporidiosis: report of a rare case.

Extranasal manifestations of rhinosporidiosis are relatively uncommon. Laryngeal involvement is extremely rare, as only 3 cases have been previously reported. We describe a new case, which occurred in a patient with coexisting nasal rhinosporidiosis who presented with inspiratory stridor.