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Lentivirus vector gene expression during ES cell-derived hematopoietic development in vitro

The murine embryonal stem (ES) cell virus (MESV) can express transgenes from the long terminal repeat (LTR) promoter/enhancer in undifferentiated ES cells, but expression is turned off upon differentiation to embryoid bodies (EBs) and hematopoietic cells in vitro. We examined whether a human immunodeficiency virus type 1-based lentivirus vector pseudotyped with the vesicular stomatitis virus G pro

Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application : a prospective, observational study

Background: As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention. Methods: In this prospective, observational study, we did modelling using longitudinal, self-reported data from users of the COVID Symptom Study app in England between March 24,

Housing Temperature-Induced Stress Is Suppressing Murine Graft-versus-Host Disease through β2-Adrenergic Receptor Signaling

Graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic cell transplantation, a potentially curative therapy for hematologic diseases. It has long been thought that murine bone marrow-derived T cells do not mediate severe GVHD because of their quantity and/or phenotype. During the course of experiments testing the impact of housing temperatures on GVHD, we discovered

Granzyme B-mediated damage of CD8+ T cells impairs graft-versus-tumor effect

Allogeneic hematopoietic cell transplantation is an established treatment for hematologic and other malignancies. Donor-derived immune cells can identify and attack host tumor cells, producing a graft-versus-tumor (GVT) effect that is crucial to the treatment. Using multiple tumor models and diverse donor-host combinations, we have studied the role of granzyme B (GzmB) in GVT effect. We first conf

Worldwide comparison of survival from childhood leukaemia for 1995-2009, by subtype, age, and sex (CONCORD-2) : a population-based study of individual data for 89 828 children from 198 registries in 53 countries

BACKGROUND: Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia.METHODS: Cancer registries participating in CONCORD

Bovine alpha 1-microglobulin/bikunin. Isolation and characterization of liver cDNA and urinary alpha 1-microglobulin

cDNA coding for alpha 1-microglobulin, an immunoregulatory plasmaprotein, was isolated from bovine liver. The sequence of a total of 1258 nucleotides revealed an open reading frame of 352 amino acids. This included alpha 1-microglobulin, 182 amino acids, and bikunin, the light chain of the plasmaprotein inter-alpha-inhibitor, 147 amino acids. The two proteins were connected by a basic tetrapeptide

High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families

BACKGROUND: : Inherited mutations in the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene confer susceptibility to cutaneous malignant melanoma. We analyzed families with two or more cases of melanoma for germline mutations in CDKN2A and CDK4 to elucidate the contribution of these gene defects to familial malignant melanoma and to

Cardiovagal Function Measured by the Deep Breathing Test : Relationships With Coronary Atherosclerosis

Background The cardiovagal function can be assessed by quantification of respiratory sinus arrhythmia (RSA) during a deep breathing test. However, population studies of RSA and coronary atherosclerosis are lacking. This population-based study examined the relationship between RSA during deep breathing and coronary atherosclerosis, assessed by coronary artery calcium score (CACS). Methods and Resul

Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection

Background: Helicobacter pylori (H. pylori) uses various strategies that attenuate mucosal immunity to ensure its persistence in the stomach. We recently found evidence that H. pylori might modulate the natural killer group 2, member 2 (NKG2D) system. The NKG2D receptor and its ligands are a major activation system of natural killer and cytotoxic T cells, which are important for mucosal immunity a

Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue

Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across the follicle associated epithelium into the subepithelial dome. The initial response to antigens and how bacteria are handled is incompletely understood. By iterative application of spatial transcriptomics and multiplexed single-cell technologies, we identify that the double negati

High Level of HIV Drug Resistance and Virologic Nonsuppression among Female Sex Workers in Ethiopia : A Nationwide Cross-Sectional Study

Objective:To determine viral load (VL) nonsuppression (VLN) rates, HIV drug resistance (HIVDR) prevalence, and associated factors among female sex workers (FSWs) in Ethiopia.Methods:A cross-sectional biobehavioral survey was conducted among FSWs in 11 cities in Ethiopia in 2014. Whole blood was collected, and HIVDR genotyping was performed. Logistic regression analysis was performed to identify fa

Nasal boost with adjuvanted heat-killed BCG or arabinomannan-protein conjugate improves primary BCG-induced protection in C57BL/6 mice

Today it is generally accepted that the Bacillus Calmette-Guerin (BCG) vaccine protects against childhood tuberculosis (TB) but this immunity wanes with age, resulting in insufficient protection against adult pulmonary TB. Hence, one possible strategy to improve the protective efficacy of the BCG vaccine would be to boost in adulthood. In this study, using the mouse model, we evaluated the ability

Clonal repertoire diversification of a neutralizing cytomegalovirus glycoprotein B-specific antibody results in variants with diverse anti-viral properties.

Cytomegalovirus induces a chronic infection that in normal individuals is controlled by the immune system. In the case of humoral immunity, epitopes, in particular antigenic domain-1, in glycoprotein B have proven to be important for the induction of virus-neutralizing activity. Such antibodies can exert potent virus-neutralizing activity but can also block neutralizing antibodies from binding. Fu

Geographical differences in cancer treatment and survival for patients with oesophageal and gastro-oesophageal junctional cancers

BACKGROUND: Only around one-quarter of patients with cancer of the oesophagus and the gastro-oesophageal junction (GOJ) undergo surgical resection. This population-based study investigated the rates of treatment with curative intent and resection, and their association with survival.METHODS: Patients diagnosed with oesophageal and GOJ cancer between 2006 and 2015 in Sweden were identified from the

Causal Association Between Subtypes of Excessive Daytime Sleepiness and Risk of Cardiovascular Diseases

BACKGROUND: Excessive daytime sleepiness (EDS), experienced in 10% to 20% of the population, has been associated with cardiovascular disease and death. However, the condition is heterogeneous and is prevalent in individuals having short and long sleep duration. We sought to clarify the relationship between sleep duration subtypes of EDS with cardiovascular outcomes, accounting for these subtypes.

Peptidoglycan from Staphylococcus aureus induces tissue factor expression and procoagulant activity in human monocytes.

Staphylococcus aureus is one of the most significant pathogens in human sepsis and endocarditis. S. aureus can initiate blood coagulation, leading to the formation of microthrombi and multiorgan dysfunction in sepsis, whereas in endocarditis the bacterium induces fibrin clots on the inner surface of the heart, so-called endocardial vegetations. In the present study, we show that live and heat-kill

Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia

Anemia because of insufficient production of and/or response to erythropoietin (Epo) is a major complication of chronic kidney disease and cancer. The mechanisms modulating the sensitivity of erythroblasts to Epo remain poorly understood. We show that, when cultured with Epo at suboptimal concentrations, the growth and clonogenic potential of erythroblasts was rescued by transferrin receptor 1 (Tf

Short-term HIV-1 treatment interruption is associated with dysregulated TLR-stimuli responsiveness.

Viremia during human immunodeficiency virus type-1 (HIV-1) infection results in progressive impairment of several components of the immune system. Here a unique model of repeated treatment interruptions (TIs) was used with the aim to reveal the effect of controlled short-term viremia on innate stimuli responsiveness and circulating dendritic cells (DCs). Sequential peripheral blood samples from HI

Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis.

Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-deri

Systematic evaluation of non-animal test methods for skin sensitisation safety assessment.

The need for non-animal data to assess skin sensitisation properties of substances, especially cosmetics ingredients, has spawned the development of many in vitro methods. As it is widely believed that no single method can provide a solution, the Cosmetics Europe Skin Tolerance Task Force has defined a three-phase framework for the development of a non-animal testing strategy for skin sensitisatio