Postmortem evaluation of the striatum in an NTCELL trial participant five years after transplantation.

In 2017 a novel growth factor administration therapy (termed NTCELL®) was trialled for safety and efficacy for Parkinson's disease treatment. NTCELL® administration is the transplantation of encapsulated porcine choroid plexus cells into the putamen. A clinical study demonstrated safety but failed to meet its primary clinical end-point.

Potent broadly neutralizing antibodies mediate efficient antibody-dependent phagocytosis of HIV-infected cells.

Antibody-dependent cellular phagocytosis (ADCP) has been implicated in protection against HIV-1. However, methods for measuring ADCP currently rely on the phagocytosis of gp120- or gp41-coated beads that do not reflect physiologically relevant conformations of the viral envelope glycoprotein or the size of a virus-infected cell. We therefore developed a novel approach for measuring ADCP of HIV-infected cells expressing natural conformations of Env.

The landscape of Medicare policies for gender-affirming surgeries in Canada: an environmental scan.

Background: Many studies have described barriers to gender-affirming surgery (GAS) in Canada; however, few have explored why these barriers persist. To address this knowledge gap, we sought to describe documents related to public health insurance (Medicare) for GAS to identify the types of procedures covered, variations in coverage across provinces and territories, and changes in policy over time.

Methods: We conducted a descriptive cross-sectional study using an environmental scan approach.

Kelvin-Helmholtz-induced mixing in multi-fluid partially ionized plasmas.

Turbulence is a fundamental process that drives mixing and energy redistribution across a wide range of astrophysical systems. For warm ([Formula: see text]) plasma, the material is partially ionized, consisting of both ionized and neutral species. The interactions between ionized and neutral species are thought to play a key role in heating (or cooling) of partially ionized plasmas.

Potent antibody-dependent cellular cytotoxicity of a V2-specific antibody is not sufficient for protection of macaques against SIV challenge.

Fc-mediated antibody effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can contribute to the containment HIV-1 replication but whether such activities are sufficient for protection is unclear. We previously identified an antibody to the variable 2 (V2) apex of the HIV-1 Env trimer (PGT145) that potently directs the lysis of SIV-infected cells by NK cells but poorly neutralizes SIV infectivity. To determine if ADCC is sufficient for protection, separate groups of six rhesus macaques were treated with PGT145 or a control antibody (DEN3) by intravenous infusion followed five days later by intrarectal challenge with SIVmac239.

Methionine Restriction Impairs Degradation of a Protein that Aberrantly Engages the Endoplasmic Reticulum Translocon.

Proteins that persistently engage endoplasmic reticulum (ER) translocons are degraded by multiple translocon quality control (TQC) mechanisms. In , the model translocon-associated protein -Sec62 is subject to ER-associated degradation (ERAD) by the Hrd1 ubiquitin ligase and, to a lesser extent, proteolysis mediated by the Ste24 protease. In a recent screen, we identified nine methionine-biosynthetic genes as candidate TQC regulators.

Tumor-specific cholinergic CD4 T lymphocytes guide immunosurveillance of hepatocellular carcinoma.

Cholinergic nerves are involved in tumor progression and dissemination. In contrast to other visceral tissues, cholinergic innervation in the hepatic parenchyma is poorly detected. It remains unclear whether there is any form of cholinergic regulation of liver cancer.

Reduction in pollution load to an urban estuary using a sustainable drainage system treatment train.

Rapid urbanisation and industrialisation have placed increased pressure on the ecosystem health of urban estuaries. Sustainable drainage systems (SuDS) are globally accepted practices for managing the water quality of stormwater and effluent discharged into urban systems. The Swartkops Estuary in South Africa is a heavily urbanized estuary that has a long history of pollution, specifically trace metal contamination, originating from industrial sources and urban wastewater.

A Prospective Study of Key Correlates for Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2.

Background: Randomized controlled trials evaluated monoclonal antibodies for the treatment (Study 2067) and prevention (Study 2069) of coronavirus disease 2019 (COVID-19). Household contacts of the infected index case in Study 2067 were enrolled in Study 2069 and prospectively followed; these cohorts provided a unique opportunity to evaluate correlates of transmission, specifically viral load.

Methods: This post hoc analysis was designed to identify and evaluate correlates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, adjusting for potential confounding factors related to source SARS-CoV-2 viral load and risk of SARS-CoV-2 acquisition in this population.

Stratification of stakeholders for participation in the governance of coastal social-ecological systems.

Knowledge co-production has become part of an evolution of participatory and transdisciplinary research approaches that are increasingly important for achieving sustainability. To effectively involve the most appropriate stakeholders there is a need for engagement and increasing prominence of stakeholders in environmental management and governance processes. The paper aims at developing and testing a methodology for stratifying stakeholders by (i) classifying organisations involved in coastal and ocean governance by their agency, and (ii) grouping them into organisational archetypes for representation and selection in research processes.

End effects in low aspect ratio Taylor-Couette flow.

Taylor-Couette flow with a low aspect ratio cylinder suffers from end effects due to the finite-span of the gap between the cylinder sides and the secondary flow in the region below the inner cylinder. We experimentally explore these end effects by varying the cylinder aspect ratio between 6.67 and 40 for a range of wall gap widths and bottom gap heights.

Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS) in which Th17 cells have a crucial but unclear function. Here we show that choline acetyltransferase (ChAT), which synthesizes acetylcholine (ACh), is a critical driver of pathogenicity in EAE. Mice with ChAT-deficient Th17 cells resist disease progression and show reduced brain-infiltrating immune cells.

The transcription factor IRF2 drives interferon-mediated CD8 T cell exhaustion to restrict anti-tumor immunity.

Type I and II interferons (IFNs) stimulate pro-inflammatory programs that are critical for immune activation, but also induce immune-suppressive feedback circuits that impede control of cancer growth. Here, we sought to determine how these opposing programs are differentially induced. We demonstrated that the transcription factor interferon regulatory factor 2 (IRF2) was expressed by many immune cells in the tumor in response to sustained IFN signaling.

Peptidylarginine deiminase enzymes and citrullinated proteins in female reproductive physiology and associated diseases†.

Citrullination, the post-translational modification of arginine residues, is catalyzed by the four catalytically active peptidylarginine deiminase (PAD or PADI) isozymes and alters charge to affect target protein structure and function. PADs were initially characterized in rodent uteri and, since then, have been described in other female tissues including ovaries, breast, and the lactotrope and gonadotrope cells of the anterior pituitary gland. In these tissues and cells, estrogen robustly stimulates PAD expression resulting in changes in levels over the course of the female reproductive cycle.

Substitutions in Nef That Uncouple Tetherin and SERINC5 Antagonism Impair Simian Immunodeficiency Virus Replication in Primary Rhesus Macaque Lymphocytes.

Most simian immunodeficiency viruses (SIVs) use Nef to counteract restriction by the tetherin proteins of their nonhuman primate hosts. In addition to counteracting tetherin, SIV Nef has a number of other functions, including the downmodulation of CD3, CD4, and major histocompatibility complex class I (MHC I) molecules from the surface of SIV-infected cells and the enhancement of viral infectivity by preventing the incorporation of SERINC5 into virions. Although these activities require different surfaces of Nef, they can be difficult to separate because of their dependence on similar interactions with AP-1 or AP-2 for clathrin-mediated endocytosis.

Unmasking governance failures: The impact of COVID-19 on small-scale fishing communities in South Africa.

The COVID-19 pandemic has highlighted the pre-existing vulnerability of the small-scale fisheries sector in South Africa and exposed the structural inequalities and ongoing injustices facing this sector. The failures within the fisheries governance and management system linked to the slow pace of implementing the Small-scale Fisheries Policy of 2012, have further exacerbated their vulnerability. This paper explores the immediate impacts of the COVID-19 pandemic on the small-scale fisheries sector and exposes how governance failures within the fisheries sector have increased their vulnerability.

Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs.

Primary tumor-derived factors (TDFs) act upon normal cells to generate a pre-metastatic niche, which promotes colonization of target organs by disseminated malignant cells. Here we report that TDFs-induced activation of the p38α kinase in lung fibroblasts plays a critical role in the formation of a pre-metastatic niche in the lungs and subsequent pulmonary metastases. Activation of p38α led to inactivation of type I interferon signaling and stimulation of expression of fibroblast activation protein (FAP).

The PTEN and ATM axis controls the G1/S cell cycle checkpoint and tumorigenesis in HER2-positive breast cancer.

The tumor suppressor PTEN is disrupted in a large proportion of cancers, including in HER2-positive breast cancer, where its loss is associated with resistance to therapy. Upon genotoxic stress, ataxia telangiectasia mutated (ATM) is activated and phosphorylates PTEN on residue 398. To elucidate the physiological role of this molecular event, we generated and analyzed knock-in mice expressing a mutant form of PTEN that cannot be phosphorylated by ATM (PTEN-398A).

Progesterone stimulates histone citrullination to increase IGFBP1 expression in uterine cells.

Peptidylarginine deiminases (PAD) enzymes were initially characterized in uteri, but since then little research has examined their function in this tissue. PADs post-translationally convert arginine residues in target proteins to citrulline and are highly expressed in ovine caruncle epithelia and ovine uterine luminal epithelial (OLE)-derived cell line. Progesterone (P4) not only maintains the uterine epithelia but also regulates the expression of endometrial genes that code for proteins that comprise the histotroph and are critical during early pregnancy.

Two-dimensional flow and linear stability properties of smectic A liquid crystals.

We examine some leading-order flow and stability properties of smectic A (SmA) liquid crystals (LCs) in two spatial dimensions by analysing a fully nonlinear continuum theory of these materials. We derive a system of equations for the dynamic variables describing the flow velocity and orientation of the material under suitable assumptions upon these quantities. This system can provide insight into the leading-order behaviour under quite general circumstances, and we provide an example of utilising this system to determine the flow induced by a constant pressure gradient applied normally to the smectic layers.

Concerted roles of PTEN and ATM in controlling hematopoietic stem cell fitness and dormancy.

In order to sustain proficient life-long hematopoiesis, hematopoietic stem cells (HSCs) must possess robust mechanisms to preserve their quiescence and genome integrity. DNA-damaging stress can perturb HSC homeostasis by affecting their survival, self-renewal, and differentiation. Ablation of the kinase ataxia telangiectasia mutated (ATM), a master regulator of the DNA damage response, impairs HSC fitness.

Analysis of Stakeholder Engagement in the Public Comments of ICER Draft Evidence Reports.

Background: Health technology assessment is becoming increasingly important to healthcare payers' decision-making. The Institute for Clinical and Economic Review (ICER) is the most established US-based research group performing value assessments. ICER provides opportunities for stakeholder engagement, including a window of opportunity for public comments on the draft evidence report.