Glyoxylase-1 combats dicarbonyl stress and right ventricular dysfunction in rodent pulmonary arterial hypertension.

Background: Heightened glycolytic flux is associated with right ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH). Methylglyoxal, a glycolysis byproduct, is a highly reactive dicarbonyl that has toxic effects non-enzymatic post-translational modifications (protein glycation). Methylglyoxal is degraded by the glyoxylase system, which includes the rate-limiting enzyme glyoxylase-1 (GLO1), to combat dicarbonyl stress.

Shifting gears: the search for group 3 pulmonary hypertension treatment.

Purpose Of Review: Treatment options for Group 3 pulmonary hypertension, characterized as secondary to chronic hypoxia or lung disease, remain an elusive holy grail for physicians and patients alike. Despite increasing identification and investigation into this pulmonary vasculopathy group with the second-highest frequency and highest mortality, there are no therapeutic interventions that offer the significant improvements in morbidity and mortality comparable to those benefiting other pulmonary hypertension groups including pulmonary arterial hypertension. This review examines the data on available and emerging Group 3 pulmonary hypertension treatments.

Sex Differences in Right Ventricular Dysfunction: Insights From the Bench to Bedside.

There are inherent distinctions in right ventricular (RV) performance based on sex as females have better RV function than males. These differences are magnified and have very important prognostic implications in two RV-centric diseases, pulmonary hypertension (PH), and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). In both PH and ARVC/D, RV dysfunction results in poor patient outcomes.

"Building strength in coming together": A mixed methods study using the arts to explore smoking with staff working in Indigenous tobacco control.

Issue Addressed: Tobacco is a major risk factor contributing to Indigenous health disparities. Art may be a powerful and transformative tool to enable health providers to develop targeted messages for tobacco control.

Methods: Indigenous and non-Indigenous staff, working in Indigenous tobacco control, attended a 2-hour workshop, and were led through a process to create individual artworks.

Engineering the expression of an anti-interleukin-13 antibody through rational design and mutagenesis.

High levels of protein expression are key to the successful development and manufacture of a therapeutic antibody. Here, we describe two related antibodies, Ab001 and Ab008, where Ab001 shows a markedly lower level of expression relative to Ab008 when stably expressed in Chinese hamster ovary cells. We use single-gene expression vectors and structural analysis to show that the reduced titer is associated with the VL CDR2 of Ab001.

Dietary, lifestyle and clinicopathological factors associated with APC mutations and promoter methylation in colorectal cancers from the EPIC-Norfolk study.

The tumour suppressor APC is the most commonly altered gene in colorectal cancer (CRC). Genetic and epigenetic alterations of APC may therefore be associated with dietary and lifestyle risk factors for CRC. Analysis of APC mutations in the extended mutation cluster region (codons 1276-1556) and APC promoter 1A methylation was performed on 185 archival CRC samples collected from participants of the European Prospective Investigation into Cancer (EPIC)-Norfolk study, with the aim of relating these to high-quality seven-day dietary and lifestyle data collected prospectively.

Lifestyle factors and p53 mutation patterns in colorectal cancer patients in the EPIC-Norfolk study.

The tumour suppressor p53 is one of the most commonly altered genes in colorectal cancer (CRC) development. Genetic alterations in p53 may therefore be associated with postulated lifestyle risk factors for CRC, such as red meat consumption. In the European Prospective Investigation into Cancer and Nutrition-Norfolk study, we examined whether detailed estimates of dietary and lifestyle factors measured at baseline related to later development of p53 mutations in CRCs.

Candidate tumor suppressor LUCA-15/RBM5/H37 modulates expression of apoptosis and cell cycle genes.

RBM5 (RNA-binding motif protein 5/LUCA-15/H37) is encoded at the lung cancer tumor suppressor locus 3p21.3 and itself has several important characteristics of a tumor suppressor, including both potentiation of apoptosis and inhibition of the cell cycle. Here, we report the effects of both upregulation and downregulation of LUCA-15/RBM5 on gene expression monitored using cDNA microarrays.

The relationship between measures of executive function, motor performance and externalising behaviour in 5- and 6-year-old children.

In his cognitive-energetic model of information processing Sergeant [Sergeant, J. (2000). The cognitive-energetic model: An empirical approach to ADHD.