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  • Beier posted an update 10 months, 3 weeks ago

    We studied the effect of an amyloidogenic intrinsically disordered protein, α-synuclein, which is associated with Parkinson’s disease (PD), on the conformational dynamics of a DNA hairpin (DNA-HP) employing the single-molecule Förster resonance energy transfer method. The open-to-closed conforma-tional equilibrium of the DNA-HP is drastically affected by binding of monomeric α-synuclein to the loop region of the DNA-HP. Formation of a protein-bound intermediate conformation is fostered in the presence of an aqueous two-phase system mimicking intracellular liquid-liquid phase separation. Using pressure modulation, additional mechanistic informa-tion of the binding complex could be retrieved. Hence, in addition to toxic amyloid formation, α-synuclein may alter expression profiles of disease-modifying genes in PD. Further, these findings might also have significant bearings on the understanding of the physiology of organisms thriving at high pressures in the deep sea.A simple, quick, selective, sensitive, and effective field-friendly method capable of being used by nonexperts has been developed for detecting mitragynine in Mitragyna speciosa (kratom) using surface-enhanced Raman spectroscopy (SERS). Over 100 samples and blanks (known to be either positive or negative for the presence of mitragynine) were examined in duplicate using five identical handheld Raman spectrometers, which provided a data set of over 1,000 examinations. Based on the results of these analyses, the method yielded a true-positive rate of 99.3%, a true-negative rate of 97.9%, a false-positive rate of 2.1%, and a false-negative rate of 0.7%. The average minimum detectable concentration (Cm ) of mitragynine that reproducibly yielded a match for one of the library spectra on all five instruments was determined to be 342 ng/mL (ppb). This Cm value is a conservative estimate considering that the extraction process was not fully optimized by this study, which was not necessary since the Cm value achieved was well below typical mitragynine concentrations in kratom (1.3-2.3%). The method is ideal (i) for prioritizing samples for additional testing using other more time-consuming laboratory-based techniques needed to detect and quantify mitragynine and (ii) for field use at international mail facility (IMF) satellite laboratories to help interdict kratom and prevent this dangerous product from reaching the U.S. supply chain.Human-induced habitat conversion and degradation, along with accelerating climatic change, have resulted in considerable global biodiversity loss. Nevertheless, how local ecological assemblages respond to the interplay between climate and land-use change remains poorly understood. Here, we examined the effects of climate and land-use interactions on butterfly diversity in different ecosystems of southwestern China. Specifically, we investigated variation in the alpha and beta diversities of butterflies in different landscapes along human-modified and climate gradients. 2,4-Thiazolidinedione PPAR agonist We found that increasing land-use intensity not only caused a dramatic decrease in butterfly alpha diversity but also significantly simplified butterfly species composition in tropical rainforest and savanna ecosystems. These findings suggest that habitat modification by agricultural activities increases the importance of deterministic processes and leads to biotic homogenization. The land-use intensity model best explained species richness variation in the tropical rainforest, whereas the climate and land-use intensity interaction model best explained species richness variation in the savanna. These results indicate that climate modulates the effects of land-use intensity on butterfly alpha diversity in the savanna ecosystem. We also found that the response of species composition to climate varied between sites specifically, species composition was strongly correlated with climatic distance in the tropical rainforest but not in the savanna. Taken together, our long-term butterfly monitoring data reveal that interactions between human-modified habitat change and climate change have shaped butterfly diversity in tropical rainforest and savanna. These findings also have important implications for biodiversity conservation under the current era of rapid human-induced habitat loss and climate change. This article is protected by copyright. All rights reserved.Background and aim 11β-Hydroxysteroid dehydrogenase 1 has been implicated in insulin resistance (IR) in the setting of metabolic disorders, and single nucleotide polymorphisms (SNPs) in its encoding gene (HSD11B1) have been associated with type 2 diabetes and metabolic syndrome. In type 1 diabetes (T1D), IR has been related to the development of chronic complications. We investigated the association of HSD11B1 SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals. Materials and methods Five SNPs were genotyped in 466 T1D individuals (57% women; median of 37 years old, diabetes duration of 25 years and HbA1c of 8.4%). Results The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR = 0.52; confidence interval [CI] 95% = 0.28-0.96; P = .036). The minor allele C of rs17389016 was nominally associated with overt diabetic kidney disease (DKD) (OR = 1.90; CI 95% = 1.07-3.37; P = .028). A follow-up study revealed that 29% of the individuals lost ≥5 mL min-1 × 1.73 m2 per year of the estimated glomerular filtration rate (eGFR). In these individuals (eGFR decliners), C allele of rs17389016 was more frequent than in non-decliners (OR = 2.10; CI 95% = 1.14-3.89; P = .018). Finally, minor allele T of rs846906 associated with higher prevalence of arterial hypertension, higher body mass index and waist circumference, thus conferring risk to a lower estimated glucose disposal rate, a surrogate marker of insulin sensitivity (OR = 1.23; CI 95% = 1.06-1.42; P = .004). Conclusion SNPs in the HSD11B1 gene may confer susceptibility to DKD and to IR in T1D individuals.Subvalvular aortic stenosis (SAS) can be either a fixed stenosis resulting from subaortic anatomical obstacle or a dynamic stenosis because of hypertrophic cardiomyopathy. Here, we report a patient with a rare subaortic circumferential fibromuscular tunnel who became unusually symptomatic in her sixth decade of life. Transthoracic and mostly transesophageal echocardiography with 3D application is the preferred diagnostic modality. Indications for surgery include symptoms and LVOT gradient of 50 mm Hg. Our purpose is an image focus on this infrequent case.

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