Novel Variants of Angiotensin Converting Enzyme-2 of Shorter Molecular Size to Target the Kidney Renin Angiotensin System.

ACE2 is a monocarboxypeptidase which generates Angiotensin (1-7) from Angiotensin II (1-8). Attempts to target the kidney Renin Angiotensin System using native ACE2 to treat kidney disease are hampered by its large molecular size, 100 kDa, which precludes its glomerular filtration and subsequent tubular uptake. Here, we show that both urine and kidney lysates are capable of digesting native ACE2 into shorter proteins of ~60-75 kDa and then demonstrate that they are enzymatically very active.

A Broad Spectrum Protein Glycosylation System Influences Type II Protein Secretion and Associated Phenotypes in .

Protein secretion plays a crucial role for bacterial pathogens, exemplified by facultative human-pathogen , which secretes various proteinaceous effectors at different stages of its lifecycle. Accordingly, the identification of factors impacting on protein secretion is important to understand the bacterial pathophysiology. PglL, a predicted oligosaccharyltransferase of , has been recently shown to exhibit -glycosylation activity with relaxed glycan specificity in an engineered system.

Effects of cardioselective beta-blockade on plasma catecholamines and performance during different forms of exercise.

Background: Beta-blockers are still frequently used in cardiovascular diseases but may negatively influence the exercise capacity. The aim of the study was to analyze the effect of beta-blockade on physical performance and plasma level of catecholamine during different forms of exercise.

Methods: Ten prehypertensive athletes (age: 25.

Greasing the Wheels of the Cancer Machine: The Role of Lipid Metabolism in Cancer.

Altered lipid metabolism is among the most prominent metabolic alterations in cancer. Enhanced synthesis or uptake of lipids contributes to rapid cancer cell growth and tumor formation. Lipids are a highly complex group of biomolecules that not only constitute the structural basis of biological membranes but also function as signaling molecules and an energy source.

[Current Aspects of Cholesteatoma Surgery - Part 1: Fundamentals and Diagnostics].

Cholesteatoma is a chronic inflammation of the middle ear, which leads to a progressive bony destruction of the petrous bone. Main symptoms are fetid otorrhea, hearing loss and dizziness. Left untreated, cholesteatoma may be fatal due to intracranial complications.

Ang II (Angiotensin II) Conversion to Angiotensin-(1-7) in the Circulation Is POP (Prolyloligopeptidase)-Dependent and ACE2 (Angiotensin-Converting Enzyme 2)-Independent.

The Ang II (Angiotensin II)-Angiotensin-(1-7) axis of the Renin Angiotensin System encompasses 3 enzymes that form Angiotensin-(1-7) [Ang-(1-7)] directly from Ang II: ACE2 (angiotensin-converting enzyme 2), PRCP (prolylcarboxypeptidase), and POP (prolyloligopeptidase). We investigated their relative contribution to Ang-(1-7) formation in vivo and also ex vivo in serum, lungs, and kidneys using models of genetic ablation coupled with pharmacological inhibitors. In wild-type (WT) mice, infusion of Ang II resulted in a rapid increase of plasma Ang-(1-7).

Prediction of Ergogenic Mouthguard Effects in Volleyball: A Pilot Trial.

Dental occlusion may affect static and dynamic balance. The effects of a mouthguard on pinpoint accuracy in volleyball were investigated in 28 players who completed a volleyball specific test. Also, masticatory electromyographic tests were performed.

Prognostic impact of CD34 and SMA in cancer-associated fibroblasts in stage I-III NSCLC.

Background: Epithelial-to-mesenchymal transition (EMT) is a crucial step in lung cancer pathogenesis. Among others, cancer-associated fibroblasts (CAFs) are reported to regulate this process.

Objectives: To investigate the prognostic and clinical impact, we analyzed CD34+ and SMA+ CAFs in non-small cell lung cancer (NSCLC).

Towards improved health service quality in Tanzania: contribution of a supportive supervision approach to increased quality of primary healthcare.

Background: Universal Health Coverage only leads to the desired health outcomes if quality of health services is ensured. In Tanzania, quality has been a major concern for many years, including the problem of ineffective and inadequate routine supportive supervision of healthcare providers by council health management teams. To address this, we developed and assessed an approach to improve quality of primary healthcare through enhanced routine supportive supervision.

Mevalonate Pathway Provides Ubiquinone to Maintain Pyrimidine Synthesis and Survival in p53-Deficient Cancer Cells Exposed to Metabolic Stress.

Oncogene activation and loss of tumor suppressor function changes the metabolic activity of cancer cells to drive unrestricted proliferation. Moreover, cancer cells adapt their metabolism to sustain growth and survival when access to oxygen and nutrients is restricted, such as in poorly vascularized tumor areas. We show here that p53-deficient colon cancer cells exposed to tumor-like metabolic stress in spheroid culture activated the mevalonate pathway to promote the synthesis of ubiquinone.

Blood clot removal by cryoextraction in critically ill patients with pulmonary hemorrhage.

Background: Severe pulmonary hemorrhage is a life-threatening complication in critically ill patients. Due to tracheobronchial obstruction, ventilation is often impaired. Traditionally, rigid bronchoscopy is an option for recanalization.

Lipid Metabolism at the Nexus of Diet and Tumor Microenvironment.

Obesity is a leading contributing factor to cancer development worldwide. Epidemiological evidence suggests that diet affects cancer risk and also substantially alters therapeutic outcome. Therefore, studying the impact of diet in the development and treatment of cancer should be a clinical priority.

A MYC-GCN2-eIF2α negative feedback loop limits protein synthesis to prevent MYC-dependent apoptosis in colorectal cancer.

Tumours depend on altered rates of protein synthesis for growth and survival, which suggests that mechanisms controlling mRNA translation may be exploitable for therapy. Here, we show that loss of APC, which occurs almost universally in colorectal tumours, strongly enhances the dependence on the translation initiation factor eIF2B5. Depletion of eIF2B5 induces an integrated stress response and enhances translation of MYC via an internal ribosomal entry site.

The utility of dried blood spot monitoring of branched-chain amino acids for maple syrup urine disease: A retrospective chart review study.

Background: Branched-chain amino acid (BCAA) concentrations must be tracked and maintained within an optimal range to minimize disease phenotypes in patients with maple syrup urine disease (MSUD). In 2014, the Hospital for Sick Children (SickKids) implemented a dried blood spot (DBS) home monitoring system, allowing patients to track BCAA concentrations without the inconvenience of having to travel to the hospital.

Methods: We conducted a retrospective chart review study (n = 15) to assess the impacts of DBS monitoring implementation on biochemical control.

FSP1 is a glutathione-independent ferroptosis suppressor.

Ferroptosis is an iron-dependent form of necrotic cell death marked by oxidative damage to phospholipids. To date, ferroptosis has been thought to be controlled only by the phospholipid hydroperoxide-reducing enzyme glutathione peroxidase 4 (GPX4) and radical-trapping antioxidants. However, elucidation of the factors that underlie the sensitivity of a given cell type to ferroptosis is crucial to understand the pathophysiological role of ferroptosis and how it may be exploited for the treatment of cancer.

Production of IFNβ by Conventional Dendritic Cells after Stimulation with Viral Compounds and IFNβ-Independent IFNAR1-Signaling Pathways are Associated with Aggravation of Polymicrobial Sepsis.

Viral infections are associated with increased incidence of severe sepsis. Particularly during the early stages, type I interferons (IFNs) are known mediators of detrimental effects. However, the functional role of early interferon β (IFNβ) and its cellular source during sepsis in the context of preexisting viral infections has not been defined.

Insert Stability and In Vivo Testing of MicroRNA-Detargeted Oncolytic Picornaviruses.

Although a variety of oncolytic viruses under clinical investigation have proven to be safe, the overall efficacy of oncolytic viruses as monotherapies has been suboptimal. While responses to combination therapies are much more promising, the development of oncolytic virus monotherapies with enhanced potency is imperative. With this initiative comes the need for improved mechanisms of virus targeting to prevent off-target toxicities.

The MYC Oncogene Cooperates with Sterol-Regulated Element-Binding Protein to Regulate Lipogenesis Essential for Neoplastic Growth.

Lipid metabolism is frequently perturbed in cancers, but the underlying mechanism is unclear. We present comprehensive evidence that oncogene MYC, in collaboration with transcription factor sterol-regulated element-binding protein (SREBP1), regulates lipogenesis to promote tumorigenesis. We used human and mouse tumor-derived cell lines, tumor xenografts, and four conditional transgenic mouse models of MYC-induced tumors to show that MYC regulates lipogenesis genes, enzymes, and metabolites.

General Movements and Outcome in Children with Birthweights ≤ 500 Grams at Age 5 to 6 Years.

Background: The prognosis of long-term outcome in the delicate subgroup of preterm infants born with a birthweight ≤ 500 g is difficult. We wanted to determine whether general movements (GMs) correlate with outcome at 5 to 6 years of age in preterm children with birthweights ≤500 g.

Methods: GMs were assessed up to 20 weeks postterm age in a cohort of infants born consecutively in our unit between 1998 until 2003.

Biocatalytic Degradation Efficiency of Postconsumer Polyethylene Terephthalate Packaging Determined by Their Polymer Microstructures.

Polyethylene terephthalate (PET) is the most important mass-produced thermoplastic polyester used as a packaging material. Recently, thermophilic polyester hydrolases such as TfCut2 from have emerged as promising biocatalysts for an eco-friendly PET recycling process. In this study, postconsumer PET food packaging containers are treated with TfCut2 and show weight losses of more than 50% after 96 h of incubation at 70 °C.

Connecting lysosomes and mitochondria - a novel role for lipid metabolism in cancer cell death.

Background: The understanding of lysosomes has been expanded in recent research way beyond their view as cellular trash can. Lysosomes are pivotal in regulating metabolism, endocytosis and autophagy and are implicated in cancer. Recently it was discovered that the lysosomal V-ATPase, which is known to induce apoptosis, interferes with lipid metabolism in cancer, yet the interplay between these organelles is poorly understood.