Safety, tolerability and toxicokinetics of the novel mitochondrial drug SUL-138 administered orally to rat and minipig.

Noncommunicable Chronic Diseases (NCD) are a socioeconomic burden and considered one of the major health challenges for coming decades. Mitochondrial dysfunction has been implicated mechanistically in their pathophysiology. Therefore, targeting mitochondria holds great promise to improve clinical outcomes in NCDs.

Widespread Pesticide Distribution in the European Atmosphere Questions their Degradability in Air.

Risk assessment of pesticide impacts on remote ecosystems makes use of model-estimated degradation in air. Recent studies suggest these degradation rates to be overestimated, questioning current pesticide regulation. Here, we investigated the concentrations of 76 pesticides in Europe at 29 rural, coastal, mountain, and polar sites during the agricultural application season.

Towards prevention of ischemia-reperfusion kidney injury: Pre-clinical evaluation of 6-chromanol derivatives and the lead compound SUL-138.

Acute kidney injury (AKI) is a global healthcare burden attributable to high mortality and staggering costs of dialysis. The underlying causes of AKI include hypothermia and rewarming (H/R), ischemia/reperfusion (I/R), mitochondrial dysfunction and reactive oxygen species production. Inspired by the mechanisms conferring organ protection in hibernating hamster, 6-chromanol derived compounds were developed to address the need of effective prevention and treatment of AKI.

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure.

Chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) is featured by oxidative stress and chronic inflammation. Due to the poor efficacy of standard glucocorticoid therapy, new treatments are required. Here, we investigated whether the novel compound SUL-151 with mitoprotective properties can be used as a prophylactic and therapeutic treatment in a murine CS-induced inflammation model.

Electric vehicle sound stimuli data and enhancements.

Data for six electric vehicle WOT interior sound measurements and eight enhanced sound signatures are presented. The measurement of electric vehicle interior sound signature data and the enhancement of these stimuli are documented in this data article. The procedures and equipment that were used to record the data, as well as the transposition, harmony and order addition, frequency filtering and modulation enhancement techniques that were applied to these stimuli are explained in detail.

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet-transplantation enhances immediate post-transplant islet graft function but not long-term normoglycemia.

The liver as transplantation site for pancreatic islets is associated with significant loss of islets, which can be prevented by grafting in a prevascularized, subcutaneous scaffold. Supporting vascularization of a scaffold to limit the period of ischemia is challenging and was developed here by applying liposomes for controlled release of angiogenic factors. The angiogenic capacity of platelet-derived growth factor, vascular endothelial growth factor, acidic fibroblast growth factor (aFGF), and basic FGF were compared in a tube formation assay.

Ground-based assessment of the bias and long-term stability of fourteen limb and occultation ozone profile data records.

The ozone profile records of a large number of limb and occultation satellite instruments are widely used to address several key questions in ozone research. Further progress in some domains depends on a more detailed understanding of these data sets, especially of their long-term stability and their mutual consistency. To this end, we made a systematic assessment of fourteen limb and occultation sounders that, together, provide more than three decades of global ozone profile measurements.

A study of energy-related injuries from hospital admissions among children and adults in South Africa.

Introduction: Burn and ingestion injuries are common in developing countries because of poor access to safe energy sources, crowded living conditions, and insufficient knowledge of potential risks. The purpose of this study is to understand the scope of burn and ingestion injuries due to various energy source usages in South Africa.

Methods: Patients at 16 regional hospitals throughout South Africa presenting with an energy-related injury between 2006 and 2012 were interviewed to obtain demographics and injury characteristics.

Deletion of the ST2 proximal promoter disrupts fibroblast-specific expression but does not reduce the amount of soluble ST2 in circulation.

IL-33 signals through ST2, which is expressed either as a full-length signaling receptor or a truncated soluble receptor that can suppress IL-33 activity. Previous data suggest that soluble ST2 mRNA in fibroblasts is coupled to a serum-inducible proximal promoter, while full-length ST2 expression in immune cells is directed from a distal promoter. In order to better understand the function of the alternative promoters and how they ultimately affect the regulation of IL-33, we generated a mouse in which the ST2 proximal promoter is deleted.

Effect of ammonium-iron-hexa-cyanoferrate and of the covariates age, gender, weight, season and calendar time on radiocaesium contamination of wild boars living in the wild in Bavaria.

Feed with Ammonium-iron-hexa-cyanoferrate (AFCF; 1250 mg AFCF/kg) was fed between March 2009 and March 2011 to wild boars in a territory of 4.5 km(2) (experimental group, EXP). One hundred and forty similar territories in the same county (500 km(2) , spruce forest, agriculture) served as control (CON).

Paraffin-related injury in low-income South African communities: knowledge, practice and perceived risk.

Objective: To explore what individuals at risk of injury from using paraffin (also known as kerosene) know about paraffin safety, what they do to protect themselves and their families from paraffin-related injury, and how they perceive their risk for such injury. Also, to explore interrelations between these factors and age, sex, education and income.

Methods: A sample of 238 individuals was randomly recruited from low-income housing districts near Cape Town, South Africa in 2007.

An intervention to reduce kerosene-related burns and poisonings in low-income South African communities.

Objective: Unintentional injury rates in low- and middle-income countries are up to 50 times higher than high-income nations. In South Africa, kerosene (paraffin) is a leading cause of poisoning and burns, particularly in low-income communities where it serves as a primary fuel for light, cooking, and heating. This study tested a community-based intervention to reduce kerosene-related injury risk.

Preventing paraffin-related injury.

Paraffin (called kerosene in North America and other parts of the world) is the most commonly used fuel in ‎non-electrified dwellings worldwide. It is especially popular in Africa and South Asia. Although paraffin ‎offers many advantages-especially its comparatively low cost to produce-it poses two major risks of ‎injury.

Development of ultratrace laser spectrometry techniques for measurements of arsenic.

Several techniques based on laser induced fluorescence (LIF) spectrometry and laser enhanced ionization (LEI) spectrometry have been investigated for ultratrace measurements of arsenic. Studies by our group in this area that have been published previously are reviewed here, and are presented along with the results of recent studies that have not yet been published. The techniques presented include LIF detection in the inductively coupled plasma atomizer, the electrothermal atomizer, the tungsten coil atomizer, the flame atomizer and LEI detection in the flame atomizer, and include approaches that utilize hydride generation or laser ablation sample introduction.

Identification of functional roles for both IL-17RB and IL-17RA in mediating IL-25-induced activities.

IL-25 (IL-17E) is a unique IL-17 family ligand that promotes Th2-skewed inflammatory responses. Intranasal administration of IL-25 into naive mice induces pulmonary inflammation similar to that seen in patients with allergic asthma, including increases in bronchoalveolar lavage fluid eosinophils, bronchoalveolar lavage fluid IL-5 and IL-13 concentrations, goblet cell hyperplasia, and increased airway hyperresponsiveness. IL-25 has been reported to bind and signal through IL-17RB (IL-17BR, IL-17Rh1).

Ozone differential absorption lidar algorithm intercomparison.

An intercomparison of ozone differential absorption lidar algorithms was performed in 1996 within the framework of the Network for the Detection of Stratospheric Changes (NDSC) lidar working group. The objective of this research was mainly to test the differentiating techniques used by the various lidar teams involved in the NDSC for the calculation of the ozone number density from the lidar signals. The exercise consisted of processing synthetic lidar signals computed from simple Rayleigh scattering and three initial ozone profiles.

Burns and injuries from non-electric-appliance fires in low- and middle-income countries Part II. A strategy for intervention using the Haddon Matrix.

A large proportion of burns in developing countries are related to the nature of domestic appliances used for cooking, heating, and lighting. Our overview of the problem elucidated the need for better surveillance with epidemiologic studies, which will more accurately assess the true incidence in vulnerable populations. This paper will create a framework for envisaging new approaches to the problem and begin to evaluate the strengths and weaknesses of proposed interventions.

Cutting edge: identification of a pre-ligand assembly domain (PLAD) and ligand binding site in the IL-17 receptor.

IL-17 is the hallmark cytokine of the newly described "Th17" lymphocyte population. The composition, subunit dynamics, and ligand contacts of the IL-17 receptor are poorly defined. We previously demonstrated that the IL-17RA subunit oligomerizes in the membrane without a ligand.

Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression.

IL-17 is the founding member of a novel family of proinflammatory cytokines that defines a new class of CD4+ effector T cells, termed "Th17." Mounting evidence suggests that IL-17 and Th17 cells cause pathology in autoimmunity, but little is known about mechanisms of IL-17RA signaling. IL-17 through its receptor (IL-17RA) activates genes typical of innate immune cytokines, such as TNFalpha and IL-1beta, despite minimal sequence similarity in their respective receptors.

Interferon-gamma regulates susceptibility to collagen-induced arthritis through suppression of interleukin-17.

Objective: The enhanced expression of experimental arthritis in the absence of interferon-gamma (IFNgamma) suggests that IFNgamma suppresses arthritis. Interleukin-17 (IL-17) is a pivotal T cell cytokine in arthritis, and in vitro studies have indicated that IFNgamma suppresses IL-17 production. We undertook this study to test the hypothesis that resistance to collagen-induced arthritis (CIA) in C57BL/6 (B6) mice is regulated by IFNgamma-mediated suppression of IL-17.

Access point analysis: what do adolescents in South Africa say about tobacco control programmes?

This paper explores adolescent preferences for the setting, timing, delivery format, provider and key elements of tobacco control programmes. The need for programme sensitivity towards urban/rural, gender and ethnic subgroups is also discussed. Schools were purposively selected from the Southern Cape-Karoo Region, South Africa.

Variance components for live weight, body measurements and reproductive traits of pair-mated ostrich females.

Estimates of genetic parameters for reproductive traits, live weight and body measurements were obtained using data from a pair-mated ostrich flock at Oudtshoorn in South Africa. Reproductive traits included total egg and chick production, along with hatchability percentage. Live weight, chest circumference and tail circumferences were recorded at the commencement and cessation of breeding.

No defect in T-cell priming, secondary response, or tolerance induction in response to inhaled antigens in Fms-like tyrosine kinase 3 ligand-deficient mice.

Background: Respiratory tract dendritic cells (DCs) are crucial for the regulation of immune responses to inhaled antigens. However, the precise function of the multiple DC subsets present in the lungs and the lung-draining lymph nodes is unknown. Fms-like tyrosine kinase 3 ligand (FLT3L) is a hematopoietic growth factor that drives the development of multiple subsets of DCs in the lymphoid organs.

Paradoxical role of programmed death-1 ligand 2 in Th2 immune responses in vitro and in a mouse asthma model in vivo.

Programmed death-1 ligand 2 (PD-L2) is a ligand for programmed death-1 (PD-1), a receptor that plays an inhibitory role in T cell activation. Since previous studies have shown up-regulation of PD-L2 expression by Th2 cytokines, and asthma is driven by a Th2 response, we hypothesized that PD-L2 might be involved in regulation of the immune response in this disease. We have found that lungs from asthmatic mice had sustained up-regulation of PD-1 and PD-L2, with PD-L2 primarily on dendritic cells.