Polymorphisms of killer immunoglobulin-like receptors (KIRs) and HLA ligands in northeastern Thais

Killer cell immunoglobulin-like receptors (KIRs) are cell surface receptors on natural killer (NK) cells and subsets of T cells. The functions of NK cells are partly regulated by interactions between KIRs and HLA ligands on target cells. In this study, the presence or absence of 17 KIR genes and their known HLA ligands have been investigated in 235 unrelated individuals living in northeastern Thailand (NET). Subtypes of KIR2DS4 including full length (KIR2DS4F) and deleted forms (KIR2DS4D) have also been determined. Framework genes (KIR2DL4, 3DL2, 3DL3, and 3DP1) were found in all individuals and KIR genes belonging to the A haplotype (KIR2DL1, 2DL3, 3DL1, and 2DS4) were present in more than 90 % of NET. KIR2DS4D (61.7 %) was more common than KIR2DS4F (52.8 %). A total of 33 different KIR genotypes were observed. Of these, three new genotypes were identified. The most common genotype (AA) was observed in 35.7 % of NET, and HLA-C alleles bearing the C1 epitope (HLA-C1) had the highest frequency (97 %). All individuals had at least one inhibitory KIR and its corresponding HLA ligand; 40.9 % of NET had three pairs of receptor–ligand combinations, and 18.3 % had all three receptor–ligand combinations of KIR2DL3+C1, 3DL1+Bw4, and 3DL2+A11. Surprisingly, the patterns of KIR gene frequencies in NET are more similar to those of Caucasians than Japanese, Korean, and Chinese. This is the first report on complete analysis of KIR and known HLA ligands in Thais. These data provide basic knowledge on KIR for further studies on disease associations and transplantation in northeastern Thais.     

Foot insensitivity is associated with renal function decline in patients with type 2 diabetes: a cohort study

Background

Identifying patients with diabetes at increased risk of chronic kidney disease (CKD) is essential to prevent/slow the progression to end-stage renal disease (ESRD). CKD and diabetic peripheral neuropathy (DPN) share common mechanisms. Hence, we aimed to examine the relationship between foot insensitivity and CKD in patients with Type 2 diabetes.

Methods

A prospective observational cohort study in adults with Type 2 diabetes. Patients with ESRD were excluded. Foot insensitivity was assessed using the 10-g monofilament test. Renal function was assessed using estimated glomerular filtration rate (eGFR) based on the MDRD equation. Albuminuria was defined as the presence of urinary albumin/creatinine ratio (ACR) >3.4 mg/mmol.

Results

Two hundred and twenty eight patients were recruited and followed-up for 2.5 years. One hundred and ninety patients (83.4%) had eGFR?≥?60 ml/min/1.73 m². Seventy six (33.3%) patients had foot insensitivity (i.e. abnormal monofilament test). Patients with foot insensitivity had lower eGFR and higher prevalence of albuminuria compared to patients with normal monofilament test. After adjustment for age, gender, ethnicity, diabetes duration, HbA1c, body mass index, insulin treatment, number of anti-hypertensives, history of peripheral vascular disease, and baseline eGFR (R² 0.87), baseline foot insensitivity was associated with study-end eGFR (B?=??3.551, p?=?0.036).

Conclusions

Patients with Type 2 diabetes and foot insensitivity are at increased risk of eGFR decline. Identifying these patients offers an opportunity to intensify metabolic and blood pressure control to prevent/retard the development of CKD. Future studies of larger sample size and longer follow up from multiple centres are needed to assess the diagnostic performance of our findings in predicting CKD development, and to compare the performance of the monofilament test with albuminuria.

     

Cholesterol sensing by CD81 is important for hepatitis C virus entry

CD81 plays a central role in a variety of physiological and pathological processes. Recent structural analysis of CD81 indicates that it contains an intramembrane cholesterol-binding pocket and that interaction with cholesterol may regulate a conformational switch in the large extracellular domain of CD81. Therefore, CD81 possesses a potential cholesterol-sensing mechanism; however, its relevance for protein function is thus far unknown. In this study we investigate CD81 cholesterol sensing in the context of its activity as a receptor for hepatitis C virus (HCV). Structure-led mutagenesis of the cholesterol-binding pocket reduced CD81–cholesterol association but had disparate effects on HCV entry, both reducing and enhancing CD81 receptor activity. We reasoned that this could be explained by alterations in the consequences of cholesterol binding. To investigate this further we performed molecular dynamic simulations of CD81 with and without cholesterol; this identified a potential allosteric mechanism by which cholesterol binding regulates the conformation of CD81. To test this, we designed further mutations to force CD81 into either the open (cholesterol-unbound) or closed (cholesterol-bound) conformation. The open mutant of CD81 exhibited reduced HCV receptor activity, whereas the closed mutant enhanced activity. These data are consistent with cholesterol sensing switching CD81 between a receptor active and inactive state. CD81 interactome analysis also suggests that conformational switching may modulate the assembly of CD81–partner protein networks. This work furthers our understanding of the molecular mechanism of CD81 cholesterol sensing, how this relates to HCV entry, and CD81''s function as a molecular scaffold; these insights are relevant to CD81''s varied roles in both health and disease.     

Prevalence and Factors Associated with High Levels of Aluminum,Arsenic, Cadmium,Lead, and Mercury in Hair Samples of Well-Nourished Thai Children in Bangkok and Perimeters

Biological Trace Element Research - Toxic element exposure increases risk of neurodevelopmental disorders. However, hair element profiles of well-nourished urban resident children were largely...     

Biogenic synthesis of gold nanoparticle using fractioned cellular components from eukaryotic algae and cyanobacteria

In the present investigation fractioned cellular components like intact pigment bearing thylakoids/chloroplasts, carotenoids, protein, polysaccharides were extracted from the cyanobacterium Anabaena sphaerica and green alga Chlorococcum infusionum. Each of these extracts was used separately in search for efficient reducing agents during gold nanoparticle (GNP) production in pro‐ and eukaryotic algal cell systems. The whole biomass and extracted compounds or cellular structures were exposed in 25 mg L^?1 aqueous hydrogen tetrachloroaurate solutions separately at room temperature. Isolated viable chloroplasts from C. infusionum and thylakoids from A. sphaerica were found to be able to reduce gold ions. The protein extracts of both strains were also able to synthesize GNP at 4°C. Extracted polysaccharides of the two strains responded differently. Polysaccharides from A. sphaerica showed positive response in GNP synthesis, whereas no change was observed for C. infusionum. The carotenoids extracts from both strains acted like an efficient reducing agent. Initially the reducing efficiency of these extracted components was confirmed by the appearance of purple color in biomass or in experimental media. The GNPs, synthesized within the biomass were extracted by sonication with sodium citrate. The UV–vis spectroscopy of extracted purple colored suspensions and media showed the absorption bands at approximately 530–540 nm indicating a strong positive signal of GNP synthesis. Transmission electro n microscopy determined the size and shapes of the particles. The X‐ray diffraction study of the synthesized GNP revealed that the 2θ values appeared at 38.2°, 44.5°, 64.8° and 77.8°. Amongst all, isolated thylakoids and chloroplast showed only spherical GNP production with variable size range at pH 4. Monodisperse GNPs were also synthesized by isolated thylakoids and chloroplast at pH 9. A detailed morphological change of gold treated biomass was revealed employing scanning electron microscopy. The fluorescent property of gold loaded cells was studied by fluorescence microscopy.     

Extraction of defatted rice bran by subcritical water treatment

Defatted rice bran was treated with subcritical water in the temperature range of 180–280 °C for 5 min using 117 mL and 9 mL vessels to produce the extracts. The total sugar and protein contents and radical scavenging activity of the extracts were then estimated for both vessels. The total sugar concentration of ca. 0.3 g/L-extract was the highest for the extracts at 200 °C, and it significantly decreased at the higher temperatures. The protein concentration and radical scavenging activity were higher at the higher temperatures. Extraction was also done at 200 °C and 260 °C for various times using the small vessel. The total sugar concentration decreased with the increasing extraction time, while the protein concentration and radical scavenging activity only slightly depended on the extraction time. The extracts at 200 °C or lower temperatures using the large vessel possessed the emulsifying and emulsion-stabilizing activities. The HPLC analysis of the extract at 260 °C for 5 min using the small vessel indicated that it contained both hydrophilic and hydrophobic substances. The hydrophilic fraction of the extract mainly contained low-molecular-mass substances.