Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates

In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological conditions associated with mitochondrial deficiency. With the goal to decipher the role of the ATPase inhibitory factor 1 (IF1) in brain development, we employed the zebrafish as elected model reporting that the Atpif1a−/− zebrafish mutant, pinotage (pnttq209), which lacks one of the two IF1 paralogous, exhibits visual impairment alongside increased apoptotic bodies and neuroinflammation in both brain and retina. This associates with increased processing of the dynamin-like GTPase optic atrophy 1 (OPA1), whose ablation is a direct cause of inherited optic atrophy. Defects in vision associated with the processing of OPA1 are specular in Atpif1−/− mice thus confirming a regulatory axis, which interlinks IF1 and OPA1 in the definition of mitochondrial fitness and specialised brain functions. This study unveils a functional relay between IF1 and OPA1 in central nervous system besides representing an example of how the zebrafish model could be harnessed to infer the activity of mitochondrial proteins during development

Lipoprotein (a), C-reactive protein and some metabolic cardiovascular risk factors in type 2 DM

<p>Abstract</p> <p>Background</p> <p>Lipoprotein (a) (LP (a) is an independent cardiovascular risk factor that is not widely studied in people of sub-Saharan African origin. The aim of this report is to determine the frequency of occurrence of elevated Lp (a) and possible relationship with total cholesterol (TCHOL), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), C reactive protein (CRP) and serum uric acid (SUA).</p> <p>Methods</p> <p>This is a cross sectional study carried out in 200 Nigerian patients with type 2 DM and 100 sex and age matched healthy Controls aged between 32-86 years. We determined the frequency of occurrence of elevated Lp (a) levels in the study subjects and compared clinical and biochemical variables between type 2 diabetic patients and non-diabetic patients. Clinical and biochemical parameters were also compared between subjects with type 2 DM who had elevated LP (a) and normal LP (a) levels. Long term glycaemic control using glycosylated haemoglobin was determined and compared in the study subjects. Test statistics used include chi square, correlation coefficient analysis and Student's t test.</p> <p>Results</p> <p>The mean Lp(a) concentration differed significantly between type 2 diabetic patients and the Control subjects (18.7 (5.8) mg/dl vs 23 (6.8) mg/dl, 0.00001). Similarly, the prevalence of high LP (a) levels in type 2 DM patients was significantly higher than that of the Control subjects (12.5% vs 4%, p-0.019). The mean levels of the lipid profile parameters (TCHOL, LDL-C, TG, LDL/HDL) and CRP were significantly higher in DM patients than in the Control subjects. The mean LP (a) levels were comparable in both sexes and in DM subjects with and without hypertension. TG was the only parameter that differed significantly between subjects with elevated Lp (a) levels and those with normal Lp (a) levels. There was a significant positive correlation (r) between Lp(a) levels and TG, LDL-C. TCHOL, LDL/HDL and uric acid. No association was found between Lp(a) and clinical parameters such as age and anthropometric indices.</p> <p>Conclusion</p> <p>We have showed that Lp (a), CRP and other CVS risk factors cluster more in patients with DM than non DM patients. Serum Lp (a) levels are not associated with anthropometric and glycaemic indices.</p

Collaborative denoising autoencoder for high glycated haemoglobin prediction.

A pioneering study is presented demonstrating that the presence of high glycated haemoglobin (HbA1c) levels in a patient’s blood can be reliably predicted from routinely collected clinical data. This paves the way for performing early detection of Type-2 Diabetes Mellitus (T2DM). This will save healthcare providers a major cost associated with the administration and assessment of clinical tests for HbA1c. A novel collaborative denoising autoencoder framework is used to address this challenge. The framework builds an independent denoising autoencoder model for the high and low HbA1c level, which extracts feature representations in the latent space. A baseline model using just three features: patient age together with triglycerides and glucose level achieves 76% F1-score with an SVM classifier. The collaborative denoising autoencoder uses 78 features and can predict HbA1c level with 81% F1-score

Correspondence between the international diabetes federation criteria for metabolic syndrome and insulin resistance in a cohort of Italian nondiabetic caucasians: The GISIR database [4]

[No abstract available

Hyperuricaemia and the metabolic syndrome in type 2 DM

<p>Abstract</p> <p>Background</p> <p>Elevated serum uric acid levels (SUA) have been associated with an increased risk of cardiovascular diseases and the metabolic syndrome (MetS) and are often reported to be higher in females than in males. The aim of this report is to determine the prevalence and clinical correlates of hyperuricaemia and also to evaluate associations with the MetS in people with type 2 diabetes mellitus (DM).</p> <p>Methods</p> <p>This was a cross-sectional study conducted in people with type 2 DM in Lagos, Nigeria. Hyperuricaemia was defined by cut-off values of > 7 mg/dl for men and > 6 mg/dl for women. The diagnosis of MetS was made using the new definition by the American Heart Association and other related bodies. Clinical and biochemical parameters were compared between subjects with hyperuricaemia and normouricaemia. Statistical analysis included usage of Student's t test, Pearson correlation coefficients, multivariate regression analysis and chi square.</p> <p>Results</p> <p>601 patients with type 2 DM aged between 34-91 years were recruited for the study. The prevalence rates of hyperuricaemia and the MetS were 25% and 60% respectively. The frequency of occurrence of hyperuricaemia was comparable in both genders (59% vs 41%, p = 0.3). Although, the prevalence of the MetS in subjects with hyperuricaemia and normouricaemia was comparable (61 vs 56%, p = 0.1), a higher proportion of hyperuricaemic subjects had 3 or more components of the Mets compared with normouricaemic subjects. Possible predictors of hyperuricaemia include central obesity, smoking and elevated serum triglycerides (TG). SUA levels were found to be positively and significantly associated with serum TG (r = 0.2, p = 0.0001) and total cholesterol (r = 13, p = 0.001).</p> <p>Conclusion</p> <p>The prevalence of hyperuricaemia in subjects with type 2 DM is comparable in both genders and possible predictors of hyperuricaemia are potentially modifiable. SUA is positively and significantly associated with serum TG and total cholesterol.</p

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death