Altered erythrocyte membrane protein composition mirrors pleiotropic effects of hypertension susceptibility genes and disease pathogenesis

The study was designed to assess the effects of polymorphisms in genes associated with essential hypertension on the variation of erythrocyte membrane proteins (EMPs) in hypertensive patientsyesBelgorod State National Research Universit

A comprehensive contribution of genes for aryl hydrocarbon receptor signaling pathway to hypertension susceptibility

The present study was designed to investigate whether genetic polymorphisms of the aryl hydrocarbon receptor (AHR) signaling pathway are involved in the molecular basis of essential hypertension (EH

The ‘Galilean Style in Science’ and the Inconsistency of Linguistic Theorising

Chomsky’s principle of epistemological tolerance says that in theoretical linguistics contradictions between the data and the hypotheses may be temporarily tolerated in order to protect the explanatory power of the theory. The paper raises the following problem: What kinds of contradictions may be tolerated between the data and the hypotheses in theoretical linguistics? First a model of paraconsistent logic is introduced which differentiates between week and strong contradiction. As a second step, a case study is carried out which exemplifies that the principle of epistemological tolerance may be interpreted as the tolerance of week contradiction. The third step of the argumentation focuses on another case study which exemplifies that the principle of epistemological tolerance must not be interpreted as the tolerance of strong contradiction. The reason for the latter insight is the unreliability and the uncertainty of introspective data. From this finding the author draws the conclusion that it is the integration of different data types that may lead to the improvement of current theoretical linguistics and that the integration of different data types requires a novel methodology which, for the time being, is not available

The ‘Galilean Style in Science’ and the Inconsistency of Linguistic Theorising

Chomsky’s principle of epistemological tolerance says that in theoretical linguistics contradictions between the data and the hypotheses may be temporarily tolerated in order to protect the explanatory power of the theory. The paper raises the following problem: What kinds of contradictions may be tolerated between the data and the hypotheses in theoretical linguistics? First a model of paraconsistent logic is introduced which differentiates between week and strong contradiction. As a second step, a case study is carried out which exemplifies that the principle of epistemological tolerance may be interpreted as the tolerance of week contradiction. The third step of the argumentation focuses on another case study which exemplifies that the principle of epistemological tolerance must not be interpreted as the tolerance of strong contradiction. The reason for the latter insight is the unreliability and the uncertainty of introspective data. From this finding the author draws the conclusion that it is the integration of different data types that may lead to the improvement of current theoretical linguistics and that the integration of different data types requires a novel methodology which, for the time being, is not available

What is the effect of alcohol consumption on the risk of chronic widespread pain? : A Mendelian randomisation study using UK Biobank

This research has been conducted using the UK Biobank resource, application no. 1144, and was funded by the University of Aberdeen. MF is funded by the EU FP7 project PainOmics (contract #602736). The authors have no conflicts of interest to declarePeer reviewedPostprin

Acetylation of C-terminal lysines modulates protein turnover and stability of Connexin-32

Background The gap junction protein, Connexin32 (Cx32), is expressed in various tissues including liver, exocrine pancreas, gastrointestinal epithelium, and the glia of the central and peripheral nervous system. Gap junction-mediated cell-cell communication and channel-independent processes of Cx32 contribute to the regulation of physiological and cellular activities such as glial differentiation, survival, and proliferation; maintenance of the hepatic epithelium; and axonal myelination. Mutations in Cx32 cause X-linked Charcot–Marie–Tooth disease (CMT1X), an inherited peripheral neuropathy. Several CMT1X causing mutations are found in the cytoplasmic domains of Cx32, a region implicated in the regulation of gap junction assembly, turnover and function. Here we investigate the roles of acetylation and ubiquitination in the C-terminus on Cx32 protein function. Cx32 protein turnover, ubiquitination, and response to deacetylase inhibitors were determined for wild-type and C-terminus lysine mutants using transiently transfected Neuro2A (N2a) cells. Results We report here that Cx32 is acetylated in transfected N2a cells and that inhibition of the histone deacetylase, HDAC6, results in an accumulation of Cx32. We identified five lysine acetylation targets in the C-terminus. Mutational analysis demonstrates that these lysines are involved in the regulation of Cx32 ubiquitination and turnover. While these lysines are not required for functional Cx32 mediated cell-cell communication, BrdU incorporation studies demonstrate that their relative acetylation state plays a channel-independent role in Cx32-mediated control of cell proliferation. Conclusion Taken together these results highlight the role of post translational modifications and lysines in the C-terminal tail of Cx32 in the fine-tuning of Cx32 protein stability and channel-independent functions

SERPINE1 mRNA Binding Protein 1 Is Associated with Ischemic Stroke Risk: A Comprehensive Molecular–Genetic and Bioinformatics Analysis of SERBP1 SNPs

The SERBP1 gene is a well-known regulator of SERPINE1 mRNA stability and progesterone signaling. However, the chaperone-like properties of SERBP1 have recently been discovered. The present pilot study investigated whether SERBP1 SNPs are associated with the risk and clinical manifestations of ischemic strok

Genetics of «atopic march» syntropy

The study of the phenomenon of a combination of several diseases at the same time in an individual, actualized in the second half of the 19th century, is being actively analyzed 150 years later using genetic approaches. We present an overview of the results of such studies in relation to allergic diseases, in particular, a special variant, the so-called «atopic march», the sequential development of eczema, allergic rhinitis and asthma («atopic march» syntropy). The data of genetic and epidemiological studies were summarized, the analysis of genome-wide associative studies was carried out, and the role of mutations in the filaggrin gene (FLG) in the development of the «atopic march» syntropy was considered

Inertia based microfluidic capture and characterisation of circulating tumour cells for the diagnosis of lung cancer

Background: Routine clinical application of circulating tumour cells (CTCs) for blood based diagnostics is yet to be established. Despite growing evidence of their clinical utility for diagnosis, prognosis and treatment monitoring, the efficacy of a robust platform and universally accepted diagnostic criteria remain uncertain. We evaluate the diagnostic performance of a microfluidic CTC isolation platform using cytomorphologic criteria in patients undergoing lung cancer surgery. Methods: Blood was processed from 51 patients undergoing surgery for known or suspected lung cancer using the ClearBridge ClearCell FX systemTM (ClearBridge Biomedics, Singapore). Captured cells were stained on slides with haematoxylin and eosin (H&E) and independently assessed by two pathologist teams. Diagnostic performance was evaluated against the pathologists reported diagnosis of cancer from surgically obtained specimens. Results: Cancer was diagnosed in 43.1% and 54.9% of all cases. In early stage primary lung cancer, between the two reporting teams, a positive diagnosis of CTCs was made for 50% and 66.7% of patients. The agreement between the reporting teams was 80.4%, corresponding to a kappa-statistic of 0.61±0.11 (P<0.001), indicating substantial agreement. Sensitivity levels for the two teams were calculated as 59% (95% CI, 41–76%) and 41% (95% CI, 24–59%), with a specificity of 53% for both. Conclusions: The performance of the tested microfluidic antibody independent device to capture CTCs using standard cytomorphological criteria provides the potential of a diagnostic blood test for lung cancer

Association Between Medication-Taking and Refractive Error in a Large General Population-Based Cohort

PURPOSE. Refractive errors, particularly myopia, are common and a leading cause of blind-ness. This study aimed to explore associations between medications and refractive error in an aging adult cohort and to determine whether childhood-onset refractive errors predict future medication use to provide novel insights into disease mechanisms. METHODS. The study compared the spherical equivalent values measured in 102,318 UK Biobank participants taking the 960 most commonly used medications. The strengths of associations were evaluated against the self-reported age of spectacle wear. The causality of refractive error changes was inferred using sensitivity and Mendelian randomization analyses. RESULTS. Anti-glaucoma drugs were associated with 1 to 2 diopters greater myopic refrac-tion, particularly in subjects who started wearing correction in the first two decades of life, potentially due to the association of higher intraocular pressure since early years with both myopia and, later in life, glaucoma. All classes of pain-control medications, including paracetamol, opiates, non-steroidal antiinflammatory drugs, and gabapentinoids, were associated with greater hyperopia (+0.68-1.15 diopters), after correction for deprivation, education, and polypharmacy and sensitivity analyses for common diagnoses. Oral hypoglycemics (metformin, gliburonide) were associated with myopia, as was allopurinol, and participants using bronchodilators (ipratropium and salbutamol) were more hyperopic. CONCLUSIONS. This study finds for the first time, to our knowledge, that medication use is associated with refractive error in adults. The novel finding that analgesics are associated with hyperopic refraction, and the possibility that multisite chronic pain predisposes to hyperopia, deserves further research. Some drugs, such as antihyperglycemic or bronchodilators, may directly alter refractive error. Intraocular pressure appears causative for myopia