Polimorfizmy genu receptora witaminy D (TaqI oraz ApaI) oraz cyrkulacja osteokalcyny u pacjentów chorujących na cukrzycę typu 2 i osób zdrowych

  Introduction: Vitamin D receptor (VDR) is encoded by the VDR gene. Several studies have supported that this gene is associated with diabetes. Heterodimer VDR/RXR functions as an enhancer of the BGLAP gene and increases the basal transcription rate of osteocalcin (OC) during osteoblast differentiation. OC is a regulator of glucose metabolism in mice. Moreover, OC level is decreased in patients with type 2 diabetes (T2D). Although inversely correlated with serum glucose insulin and glycated haemoglobin, it is unclear whether OC reduction is caused by diabetes or plays a role in the pathogenesis and/or progression of the disease. In this study we analysed the association between TaqI and ApaI VDR gene polymorphisms and OC serum concentration in T2D subjects. Material and methods: Patients underwent clinical and nutritional assessment. Genomic DNA was extracted from leucocytes using a standard salting-out procedure. The polymorphisms were genotyped by PCR-RFLP method. ELISA was used to measure OC and insulin concentrations. Results: Association between TT genotype of TaqI polymorphism and low levels of OC was observed only in the population with overweight and obesity. No association between TaqI and ApaI polymorphisms and T2D was observed (p > 0.05). Furthermore, in T2D subjects, no correlation between ApaI and TaqI genotypes and age, sex, Body Mass Index (BMI), glucose, or OC was observed. Conclusions: The TT genotype of TaqI VDR gene polymorphism was correlated with low levels of OC in overweight and obese subjects. However, TaqI and ApaI VDR gene polymorphisms were not associated with T2D. (Endokrynol Pol 2015; 66 (4): 329–333)    Wstęp: Receptor witaminy D (VDR) kodowany jest przez gen VDR. Kilka badań potwierdziło, że gen ten jest związany z cukrzycą. Heterodimer VDR/RXR funkcjonuje jako stymulator genu BGLAP i zwiększa podstawowy wskaźnik transkrypcji osteokalcyny (OC) podczas różnicowania osteoblastów. Osteokalcyna jest regulatorem metabolizmu glukozy u myszy. Ponadto, stężenie OC jest obniżone u pacjentów z cukrzycą typu 2 (T2D). Pomimo odwrotnej korelacji między stężeniem OC a stężeniem glukozy i insuliny w surowicy, a także hemoglobiną glikowaną, nie jest wiadome czy obniżenie stężenia OC jest wywołane przez cukrzycę lub odgrywa rolę w patogenezie i/lub progresji choroby. W niniejszym badaniu autorzy przeanalizowali związek pomiędzy polimorfizmami genów VDR TaqI oraz ApaI, a także stężenie OC w surowicy u pacjentów z T2D. Materiał i metody: Pacjentów poddano ocenie klinicznej i żywieniowej. Genomowe DNA pobrano z leukocytów dzięki standardowej procedurze wysalania. Polimorfizmy genotypowano metodą PCR-RFLP. Testem ELISA zmierzono stężenia OC oraz insuliny. Wyniki: Związek pomiędzy genotypem TT polimorfizmu TaqI a niskim stężeniem OC zaobserwowano jedynie u populacji z nadwagą i otyłością. Nie wykazano związku pomiędzy polimorfizmami TaqI i ApaI oraz T2D (p > 0,05). Co więcej, u pacjentów z T2D nie wykazano korelacji pomiędzy genotypami ApaI i TaqI oraz wiekiem, płcią, wskaźnikiem masy ciała (BMI), glukozą lub OC. Wnioski: Genotyp TT polimorfizmu genu VDR TaqI jest skorelowany z niskim stężeniem OC u pacjentów z nadwagą i otyłością. Jednakże, polimorfizmy genu VDR TaqI i ApaI nie są związane z T2D. (Endokrynol Pol 2015; 66 (4): 329–333)

Electrical response in poled (Bi0.5Na0.5)0.935Ba0.065TiO3 ceramics

A ferroelectric material (Bi0.5Na0.5)0.935Ba0.065TiO3 (BNBT) with a perovskite structure was poled and characterized by electrical impedance spectroscopy as a function of temperature, X-ray diffraction, and Rietveld refinement. The ac conductivity showed a low-frequency dispersion, supporting the idea of heterogeneous potential wells favored by Bi3þ, Naþ, and Ba2þ on the A site of the perovskite type of structure. The activation energies for ac conduction depended on the studied frequency. The permittivity and electrical modulus showed a distribution of the relaxation time associated with the delay in the orientation of the dipoles and an important contribution to the short-range conductivity

Development and performance evaluation of moisture range system for green coffee grains

The system presented estimates moisture in green coffee during drying process using two methods, which were capacitive sensors and mechanical load detection, to estimate it. Results show it is possible to determine coffee grains moisture from 40 to 10% humidity range, either by dielectric measurements, with a developed sensor, or dryer mechanical load, making it possible to get better storage conditions for coffee beans

Sugar Concentration Measurement System Using Radiofrequency Sensor

A sugar solution measurement system was developed based on the dielectric properties of the sucrose molecule. An ac conductivity and tan δ study as a function of the frequency was performed to find the suitable frequency range for the measuring system. The results indicate that it is possible to obtain a better response of the sensor using the frequencies as the maxima peak in tan δ appears. Developed setup for sucrose solution was appropriate to measure in a 0.15 to 1 g/mL range with an experimental error of about 3%. The proposed system improves the measurement time over some other methods

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old