Non HLA genetic markers association with type-1 diabetes mellitus

The currently available data identified IDDM1 and IDDM2 as 2 susceptibility loci for type 1 diabetes (T1D). The major histocompatibility complex (MHC)/HLA region referred to as IDDM1 contains several 100 genes known to have a great influence on T1D risk. Within IDDM2, a minisatellite variable number of tandem repeats (VNTR) locus in the insulin gene (INS) promoter region is likely to represent the etiologic polymorphism. The aim of the present work was to study the association between genotypes and susceptibility to T1D among Egyptian diabetic children and their family members. Twenty-five nuclear Egyptian families with 27 children having T1D, aged 3–14 years, their nondiabetic 44 sibs, aged 3–15 years and their parents were included in our study. All studied children were subjected to: detailed history and family pedigree. Thorough clinical examination and anthropometric measurements. Laboratory work up of diabetes including random blood sugar (RBS) and HbA1C. Molecular genetics of INS was studied in four steps; nucleic acid purification, amplification, sequencing and haplotyping using flanking single nucleotide  polymorphisms (SNPs) as surrogate markers for minisatellite alleles identification. Analysis of variant repeat distribution among Egyptian families combined with flanking haplotypes revealed that all our diabetic children had class I alleles of INS; 9 had class IC+, 9 had classID+ and 9 had class ID, while all non-diabetic family members had class III alleles of INS. Therefore the three class I alleles were considered to be equally predisposing to T1D, while class III alleles are dominantly protective. There was significant positive correlations between body massindex (BMI) and both HbA1C and AST liver enzyme among diabetic children with class IC+ but not other alleles; indicating that they need close monitoring of their diabetic control and liver functions beside following specific dietary regimens. It can be concluded that all class I alleles (IC+, ID+ and ID) are equally important susceptibility factors for T1D among Egyptian children, while class III alleles (IIIA and IIIB) are dominantlyprotective. It is concluded also that our diabetic children with class IC+ are an especially endangered subgroup of diabetics. Genotyping for INS-VNTR alleles is recommended for diabetic children as an important step of diagnostic and follow up regimens and for their non-diabetic familymembers for family counseling and early identification of potential diabetics. Further studies of INS-VNTR alleles and HLA haplotypes all over Egypt are recommended to define the Egyptian susceptibility loci for T1D and their relations to the clinical and laboratory findings as an importantnational programs

Diffracting addicting binaries: An analysis of personal accounts of alcohol and other drug ‘addiction’

Associated with social and individual harm, loss of control and destructive behaviour, addiction is widely considered to be a major social problem. Most models of addiction, including the influential disease model, rely on the volition/compulsion binary, conceptualising addiction as a disorder of compulsion. In order to interrogate this prevailing view, this article draws on qualitative data from interviews with people who describe themselves as having an alcohol or other drug ‘addiction’, ‘dependence’ or ‘habit’. Applying the concept of ‘diffraction’ elaborated by science studies scholar Karen Barad, we examine the process of ‘addicting’, or the various ways in which addiction is constituted, in accounts of daily life with regular alcohol and other drug use. Our analysis suggests not only that personal accounts of addiction exceed the absolute opposition of volition/compulsion but also that the polarising assumptions of existing addicting discourses produce many of the negative effects typically attributed to the ‘disease of addiction’

Salt Dependence of the Tribological Properties of a Surface-Grafted Weak Polycation in Aqueous Solution

The nanoscopic adhesive and frictional behaviour of end-grafted poly[2-(dimethyl amino)ethyl methacrylate] (PDMAEMA) films (brushes) in contact with gold- or PDMAEMA-coated atomic force microscope tips in potassium halide solutions with different concentrations up to 300 mM is a strong function of salt concentration. The conformation of the polymers in the brush layer is sensitive to salt concentration, which leads to large changes in adhesive forces and the contact mechanics at the tip–sample contact, with swollen brushes (which occur at low salt concentrations) yielding large areas of contact and friction–load plots that fit JKR behaviour, while collapsed brushes (which occur at high salt concentrations) yield sliding dominated by ploughing, with conformations in between fitting DMT mechanics. The relative effect of the different anions follows the Hofmeister series, with I − collapsing the brushes more than Br − and Cl − for the same salt concentration

Booster vaccination with Ad26.COV2.S or an Omicron-adapted vaccine in pre-immune hamsters protects against Omicron BA.2

Since the original outbreak of the SARS-CoV-2 virus, several rapidly spreading SARS-CoV-2 variants of concern (VOC) have emerged. Here, we show that a single dose of Ad26.COV2.S (based on the Wuhan-Hu-1 spike variant) protects against the Gamma and Delta variants in naive hamsters, supporting the observed maintained vaccine efficacy in humans against these VOC. Adapted spike-based booster vaccines targeting Omicron variants have now been authorized in the absence of human efficacy data. We evaluated the immunogenicity and efficacy of Ad26.COV2.S.529 (encoding a stabilized Omicron BA.1 spike) in naive mice and in hamsters with pre-existing immunity to the Wuhan-Hu-1 spike. In naive mice, Ad26.COV2.S.529 elicited higher neutralizing antibody titers against SARS-CoV-2 Omicron BA.1 and BA.2, compared with Ad26.COV2.S. However, neutralizing titers against the SARS-CoV-2 B.1 (D614G) and Delta variants were lower after primary vaccination with Ad26.COV2.S.529 compared with Ad26.COV2.S. In contrast, we found comparable Omicron BA.1 and BA.2 neutralizing titers in hamsters with pre-existing Wuhan-Hu-1 spike immunity after vaccination with Ad26.COV2.S, Ad26.COV2.S.529 or a combination of the two vaccines. Moreover, all three vaccine modalities induced equivalent protection against Omicron BA.2 challenge in these animals. Overall, our data suggest that an Omicron BA.1-based booster in rodents does not improve immunogenicity and efficacy against Omicron BA.2 over an Ad26.COV2.S booster in a setting of pre-existing immunity to SARS-CoV-2

Patterns of peroxidative ethane emission from submerged rice seedlings indicate that damage from reactive oxygen species takes place during submergence and is not necessarily a post-anoxic phenomenon

Contains fulltext : 36303pub.pdf (publisher's version ) (Closed access)Using ethane as a marker for peroxidative damage to membranes by reactive oxygen species (ROS) we examined the injury of rice seedlings during submergence in the dark. It is often expressed that membrane injury from ROS is a post-submergence phenomenon occurring when oxygen is re-introduced after submergence-induced anoxia. We found that ethane production, from rice seedlings submerged for 24-72 h, was stimulated to 4-37 nl gFW(-1), indicating underwater membrane peroxidation. When examined a week later the seedlings were damaged or had died. On de-submergence in air, ethane production rates rose sharply, but fell back to less than 0.1 nl gFW(-1) h(-1) after 2 h. We compared submergence-susceptible and submergence-tolerant cultivars, submergence starting in the morning (more damage) and in the afternoon (less damage) and investigated different submergence durations. The seedlings showed extensive fatality whenever total ethane emission exceeded about 15 nl gFW(-1). Smaller amounts of ethane emission were linked to less extensive injury to leaves. Partial oxygen shortage (O-2 levels < 1%) imposed for 2 h in gas phase mixtures also stimulated ethane production. In contrast, seedlings under anaerobic gas phase conditions produced no ethane until re-aerated: then a small peak was observed followed by a low, steady ethane production. We conclude that damage during submergence is not associated with extensive anoxia. Instead, injury is linked to membrane peroxidation in seedlings that are partially oxygen deficient while submerged. On return to air, further peroxidation is suppressed within about 2 h indicating effective control of ROS production not evident during submergence itself