Reduced vacuolar ATPase protects mice from Friend virus infection - an unintended but instructive effect in Hif-2afl mice.

During acute viral infections, innate immune cells invade inflamed tissues and face hypoxic areas. Hypoxia-inducible factors (HIFs) adapt cellular responses towards these conditions. We wanted to investigate the effects of a loss of HIF-2α in macrophages during acute Friend murine leukemia retrovirus (FV) infection in C57BL/6 mice using a Cre/loxP system.

The hypoxia-regulated ectonucleotidase CD73 is a host determinant of HIV latency.

Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for human immunodeficiency virus (HIV) infection. Here, we implement a systems approach to discover molecular signatures of HIV latently infected CD4 T cells, identifying the immunosuppressive, adenosine-producing ectonucleotidase CD73 as a key surface marker of latent cells. Hypoxic conditioning, reflecting the lymphoid tissue microenvironment, increases the frequency of CD73 CD4 T cells and promotes HIV latency.

Endogenous myoglobin expression in mouse models of mammary carcinoma reduces hypoxia and metastasis in PyMT mice.

Myoglobin (MB) is expressed in different cancer types and may act as a tumor suppressor in breast cancer. The mechanisms by which basal MB expression level impacts murine mammary tumorigenesis are unclear. We investigated how MB expression in breast cancer influences proliferation, metastasis, tumor hypoxia, and chemotherapy treatment in vivo.

The transcriptional and regulatory identity of erythropoietin producing cells.

Erythropoietin (Epo) is the master regulator of erythropoiesis and oxygen homeostasis. Despite its physiological importance, the molecular and genomic contexts of the cells responsible for renal Epo production remain unclear, limiting more-effective therapies for anemia. Here, we performed single-cell RNA and transposase-accessible chromatin (ATAC) sequencing of an Epo reporter mouse to molecularly identify Epo-producing cells under hypoxic conditions.

Knockout of Factor-Inhibiting HIF () in Colon Epithelium Attenuates Chronic Colitis but Does Not Reduce Colorectal Cancer in Mice.

Inflammatory bowel disease such as chronic colitis promotes colorectal cancer, which is a common cause of cancer mortality worldwide. Hypoxia is a characteristic of inflammation as well as of solid tumors and enforces a gene expression response controlled by hypoxia-inducible factors (HIFs). Once established, solid tumors are immunosuppressive to escape their abatement through immune cells.

Oxygen Sensing in Innate Immune Cells: How Inflammation Broadens Classical Hypoxia-Inducible Factor Regulation in Myeloid Cells.

Oxygen deprivation (hypoxia) is a common feature at sites of inflammation. Immune cells and all other cells present at the inflamed site have to adapt to these conditions. They do so by stabilization and activation of hypoxia-inducible factor subunit α (HIF-1α and HIF-2α, respectively), enabling constant generation of adenosine triphosphate (ATP) under these austere conditions by the induction of, for example, glycolytic pathways.

Glucocorticoids coordinate macrophage metabolism through the regulation of the tricarboxylic acid cycle.

Objectives: Glucocorticoids (GCs) are one of the most widely prescribed anti-inflammatory drugs. By acting through their cognate receptor, the glucocorticoid receptor (GR), GCs downregulate the expression of pro-inflammatory genes and upregulate the expression of anti-inflammatory genes. Metabolic pathways have recently been identified as key parts of both the inflammatory activation and anti-inflammatory polarization of macrophages, immune cells responsible for acute inflammation and tissue repair.

The Importance of Hypoxia-Inducible Factors (HIF-1 and HIF-2) for the Pathophysiology of Inflammatory Bowel Disease.

(1) Background: Hypoxia is a common feature of inflammation when hypoxia inducible factors (HIFs) adapt cells to conditions of low oxygen tension and inflammation. We studied the role of HIF-1 and HIF-2 in cells of the myeloid lineage in a mouse model of acute colitis. (2) Methods: Mice with and without a conditional knockout for either or or and in cells of the myeloid lineage were treated with 2.

Prolyl hydroxylase domain 2 reduction enhances skeletal muscle tissue regeneration after soft tissue trauma in mice.

The transcription factor Hypoxia-inducible factor 1 (HIF-1) plays a pivotal role in tissue regeneration. HIF-1 is negatively controlled by O2-dependent prolyl hydroxylases with a predominant role of prolyl hydroxylase 2 isoform (Phd2). Transgenic mice, hypomorphic for this isoform, accumulate more HIF-1 under normoxic conditions.

Effect of HIV infection and antiretroviral therapy on immune cellular functions.

During chronic HIV infection, immune cells become increasingly dysfunctional and exhausted. Little is known about how immune functions are restored after initiation of antiretroviral therapy (ART). In this study, we assessed cellular and metabolic activity and evaluated the effect of individual antiretrovirals on cellular subsets ex vivo in ART-treated and treatment-naive chronically HIV-infected individuals.

Knockdown of myeloid cell hypoxia-inducible factor-1α ameliorates the acute pathology in DSS-induced colitis.

Inflammation and hypoxia are hallmarks of inflammatory bowel disease. Low oxygen levels activate hypoxia-inducible factors as central transcriptional regulators of cellular responses to hypoxia, particularly in myeloid cells where hypoxia-inducible factors control immune cell function and survival. Still, the role of myeloid hypoxia-inducible factor-1 during inflammatory bowel disease remains poorly defined.

Dendritic Cells under Hypoxia: How Oxygen Shortage Affects the Linkage between Innate and Adaptive Immunity.

Dendritic cells (DCs) are considered as one of the main regulators of immune responses. They collect antigens, process them, and present typical antigenic structures to lymphocytes, thereby inducing an adaptive immune response. All these processes take place under conditions of oxygen shortage (hypoxia) which is often not considered in experimental settings.

Hypoxia-inducible factor 1 in dendritic cells is crucial for the activation of protective regulatory T cells in murine colitis.

Dendritic cells (DCs) serve as a bridge between innate and adaptive immunity and help to maintain intestinal homeostasis. Inflammatory bowel disease (IBD) is associated with dysregulation of the mucosal immune response. The concomitant hypoxic inflammation in IBD will activate the transcription factor hypoxia-inducible factor-1 (HIF-1) to also drive gene expression in DCs.

Hypoxia-inducible factor and target gene expression are decreased in patients with sepsis: prospective observational clinical and cellular studies.

Background: Hypoxia-inducible factor-1 (HIF-1) is a molecular key player in response to hypoxemic/inflammatory conditions prevailing in sepsis. In a prospective observational study, we tested the hypotheses that sepsis affects HIF-1α messenger ribonucleic acid (mRNA) expression (primary hypothesis) and also (secondary hypotheses) the expression of the HIF-1α target genes adrenomedullin and β2-integrins. Furthermore, we tested that lipopolysaccharide administration increases HIF-1α mRNA and protein in naive and endotoxin-tolerant monocytes.

Psychometric properties of the Quick Inventory of Depressive Symptomatology (QIDS-SR) in UK primary care.

It is widely believed that severity of depressive disorder should guide treatment selection and many guidelines emphasise this factor. The Quick Inventory of Depressive Symptomatology (QID-SR16) is a self-complete measure of depression severity which includes all DSM-IV criterion symptoms for major depressive disorder. The object of this study was to assess the psychometric properties of the QIDS-SR16 in a primary care sample.

Role of hypoxia inducible factor-1α for interferon synthesis in mouse dendritic cells.

Dendritic cells (DCs) are an important link between innate and adaptive immunity. DCs get activated in inflamed tissues where oxygen tension is usually low, which requires the transcription factor hypoxia inducible factor (HIF)-1 for cellular adaptation. To investigate whether the HIF-1 transcriptional complex plays a pivotal role in the function of DCs, we compared the effects of exogenous inflammatory stimuli and hypoxia on HIF-1α in bone marrow-derived DCs from wild type and myeloid-specific HIF-1α knock-out mice.

The NFKB1 promoter polymorphism (-94ins/delATTG) alters nuclear translocation of NF-κB1 in monocytes after lipopolysaccharide stimulation and is associated with increased mortality in sepsis.

Background: Because the nuclear factor-κB (NF-κB) coupled pathway is believed to amplify inflammation prevailing in sepsis, the authors tested the hypotheses that the insertion-deletion polymorphism (-94ins/delATTG) (1) alters nuclear translocation of nuclear factor-κB and activator protein-1 (NF-κB1) in monocytes after lipopolysaccharide stimulation; (2) affects lipopolysaccharide-induced NF-κB1 messenger RNA expression, tumor necrosis factor α concentrations, and tissue factor activity; and (3) may be associated with increased 30-day mortality in patients with sepsis.

Methods: Nuclear translocation of NF-κB1 in monocytes after lipopolysaccharide stimulation from healthy blood donors was performed with immunofluorescence staining (n = 5 each). Lipopolysaccharide-induced NF-κB1 messenger RNA expression was measured with real-time polymerase chain reaction (PCR; n = 60), tumor necrosis factor α concentrations with a multiplexing system kit (n = 60), and tissue factor activity with thromboelastometry (n = 105).

Effects of constraint-induced movement therapy on gait, balance, and functional locomotor mobility.

Purpose: This study reports the secondary effects of a constraint-induced movement therapy (CIMT) protocol on spatial temporal parameters of gait, balance, and functional locomotor mobility in children with cerebral palsy.

Methods: Sixteen children (4-12 years old) participated in a 3-week CIMT program. Participants were tested on the first and last day of the CIMT program using the Standardized Walking Obstacle Course (SWOC), the Pediatric Balance Scale (PBS) and the GAITRite Gold system (CIR Systems, Inc, Havertown, Pennsylvania).

Measuring depression severity in general practice: discriminatory performance of the PHQ-9, HADS-D, and BDI-II.

Background: The UK Quality and Outcomes Framework (QOF) rewards practices for measuring symptom severity in patients with depression, but the endorsed scales have not been comprehensively validated for this purpose.

Aim: To assess the discriminatory performance of the QOF depression severity measures.

Design And Setting: Psychometric assessment in nine Scottish general practices.

Acute hypoxia induces HIF-independent monocyte adhesion to endothelial cells through increased intercellular adhesion molecule-1 expression: the role of hypoxic inhibition of prolyl hydroxylase activity for the induction of NF-kappa B.

Myeloid cells recruited to sites of bacterial inflammation are exposed to low oxygen tension, hypoxia, and high concentrations of inflammatory cytokines that significantly affect myeloid cell function. Therefore, we analyzed the direct consequences of acute and severe hypoxia on monocytic adhesion to the endothelium in coculture experiments. Marked upregulation of monocytic ICAM-1, but no other monocytic adhesion molecule, was responsible for an approximately 50-fold increase in adhesion of the monocytic cells THP-1 to human and rat endothelial cells.

Hypoxia-inducible factor (HIF) 1alpha accumulation and HIF target gene expression are impaired after induction of endotoxin tolerance.

The oxygen-sensitive transcription factor hypoxia-inducible factor 1 (HIF-1) is known as the key regulator of hypoxia-induced gene expression. In addition to hypoxia, endotoxins such as bacterial LPS as well as proinflammatory cytokines have been shown to induce HIF-1, suggesting an integrative role for HIF-1 in conditions of hypoxia and inflammation. Cells can become tolerant to endotoxins by repetitive exposure to LPS.

A comparison of two radiographic assessment protocols for patients with periodontal disease.

Objective: Radiographic assessment of patients with generalised severe periodontitis may be undertaken with a panoramic view and supplementary periapicals. The purpose of this study was to estimate the effective radiation dose from this form of radiographic assessment, and to compare it with an estimate of the dose from a series of periapicals of all the affected teeth.

Design: Cross-sectional observational study.

The detection of blood on dental surgery surfaces and equipment following dental hygiene treatment.

The Kastle-Meyer technique, a forensic test for blood, has been employed to assess the frequency and potential routes of contamination by blood between patients, staff and equipment during routine dental hygiene treatment. Fifty treatment sessions were studied and units were cleaned between patients according to the current hospital protocol. The surfaces most frequently contaminated after treatment were the 3-in-1 syringe buttons (40%), protective bibs (22%), tap handles (20%), light handles (18%) and operating cart handles (16%).