These were tested for their ability to produce monoterpenes and sesquiterpenes by in vivo production of sesquiterpenes in E. coli, and by in vitro enzyme assays. This analysis pinpointed three residues in the sequence which could mediate the change in product specificity from a monoterpene synthase to a sesquiterpene synthase. Another set of three residues defined the sesquiterpene product profile, including the ratios between sesquiterpene products.Saccharides have bioprotective properties, with a high capacity to preserve biological proteins and membranes during sperm cryopreservation. The aim of this study was to evaluate how replacing the lactose of cryopreservation media by sucrose (SUC) or trehalose (TRE) at concentrations of 0.2 M (SUC-1 and TRE-1) and 0.25 M (SUC-2 and TRE-2) affects frozen/thawed pig spermatozoa. The media used were composed of medium A (saccharide/egg yolk) and B (saccharide/egg yolk/glycerol), their osmolality being determined prior to freezing. Cell viability, membrane lipid disorder, acrosome integrity, mitochondrial membrane potential (MMP), lipid peroxidation, thiol group oxidation, total reactive oxygen species (ROS), peroxynitrite and superoxide anion (O2●-) were determined through flow cytometry; total motility (TM), progressive motility (PM) and kinetic parameters motility were determined immediately after thawing (T0) and again 30 (T30) and 60 (T60) minutes later. The SUC-2 and TRE-2 groups maintained viability significantly and presented fewer lipid membrane disorders, respectively, both with a significant increase in MMP. The production of O2●- and peroxynitrite was lower in the TRE-2 groups compared to the control (P less then 0.05). Total motility at T0 was greater in the TRE-2 group (P less then 0.05). Sperm kinetics was not affected by the treatment. The use of saccharides SUC and TRE at a concentration of 0.25 M improves sperm quality, so that both non-penetrating cryoprotectants can be utilized in pig sperm freezing media.Adipogenesis is a finely orchestrated program involving a transcriptional cascade coordinated by CEBP and PPAR family members and by hormonally induced signaling pathways. Alterations in any of these factors result into impaired formation of fully differentiated adipocytes. Tm7sf2 gene encodes for a Δ(14)-sterol reductase primarily involved in cholesterol biosynthesis. Furthermore, TM7SF2 modulates the expression of the master gene of adipogenesis PPARγ, suggesting a role in the regulation of adipose tissue homeostasis. We investigated the differentiation of Tm7sf2-/- MEFs into adipocytes, compared to Tm7sf2+/+ MEFs. Tm7sf2 expression was increased at late stage of differentiation in wild type cells, while Tm7sf2-/- MEFs exhibited a reduced capacity to differentiate into mature adipocytes. Indeed, Tm7sf2-/- MEFs had lower neutral lipid accumulation and reduced expression of adipogenic regulators. At early stage, the reduction in C/EBPβ expression impaired mitotic clonal expansion, which is needed by preadipocytes for adipogenesis induction.  https://www.selleckchem.com/products/BIBF1120.html  At late stage, the expression and activity of C/EBPα and PPARγ were inhibited in Tm7sf2-/- cells, leading to the reduced expression of adipocyte genes like Srebp-1c, Fasn, Scd-1, Adipoq, Fabp4, and Glut4. Loss of the acquisition of adipocyte phenotype was accompanied by a reduction in the levels of Irs1, and phosphorylated Akt and ERK1/2, indicating a blunted insulin signaling in differentiating Tm7sf2-/- cells. Moreover, throughout the differentiation process, increased expression of the antiadipogenic Mmp3 was observed in MEFs lacking Tm7sf2. These findings indicate Tm7sf2 as a novel factor influencing adipocyte differentiation that could be relevant to adipose tissue development and maintenance of metabolic health.
  To investigate the efficacy of biosimilar infliximab compared to that of the originator infliximab for the treatment of chronic non-infectious uveitis.
 
  Before-and-after study.
 
  All patients in the Central Norway Health Region between 2007 and 2018 were included. They were switched from originator to biosimilar infliximab therapy from 2014 to 2017. The primary outcome was quiescence of uveitis before and after the switch. All patients were seen every 1-3months. Visits were binned into 3-month long periods for each patient takingboth medications. Poisson regression analysis was used to estimate the incidence rate ratio (IRR) of quiescence between the 2 treatments.
 
  Twenty-nine patients were treated with infliximab. Twenty-three of those patients were switched from originator to biosimilar infliximab. The majority were white (87%), female (92%), and had chronic anterior uveitis (65%). For patients taking the originator and biosimilar drugs, the median treatment duration was38months (range 8-131months) and 15months (range 5-55months), respectively. Concomitant immunosuppressive medications and topical and oral steroids were used similarly during treatment with both originator and biosimilar infliximab. The IRR for quiescence was 0.91 (95% confidence intervals [CI] 0.7-1.1; P= 0.38), which indicated no statistically significant differences in achieving quiescence after the switch. Also, there were no differences in the incidence rate of flare events with the switch (IRR 1.04; 95% CI 0.36-2.98; P= 0.95). IRR adjusted for intraocular surgery was 0.90 (95% CI 0.7-1.1; P= 0.37).
 
  No evidence of differences in effectiveness were found in comparing biosimilar to originator infliximab in patients with chronic non-infectious uveitis.
 No evidence of differences in effectiveness were found in comparing biosimilar to originator infliximab in patients with chronic non-infectious uveitis.
  To rescue medical genetics concepts that are necessary to understand the advances in the genetic-molecular characterization of primary immunodeficiencies, to help in the understanding and adequate interpretation of their results.
 
  Non-systematic literature review, searching for articles since 2000 on PubMed using the terms "genetic evaluation" OR "whole exome sequence" or "whole genome sequence" OR "next generation sequence" AND "immunologic deficiency syndromes" OR "Immune deficiency disease" OR "immune deficiency" NOT HIV.
 
  Knowledge of medical genetics is essential for the understanding of the principles of heredity and disease inheritance patterns, types of genetic variants, types of genetic sequencing and interpretation of their results. The clinical and immunophenotypic evaluation of each patient is essential for the correlation with the genetic variants observed in the genetic study of patients with primary immunodeficiencies. The discussion of the benefits and limitations of genetic tests should always guide the performance of genetic tests.