Johannesencramer3262
Methods for the conversion of human induced pluripotent stem cells (hiPSCs) into motor neurons (MNs) have opened to the generation of patient-derived in vitro systems that can be exploited for MN disease modelling. However, the lack of simplified and consistent protocols and the fact that hiPSC-derived MNs are often functionally immature yet limit the opportunity to fully take advantage of this technology, especially in research aimed at revealing the disease phenotypes that are manifested in functionally mature cells. In this study, we present a robust, optimized monolayer procedure to rapidly convert hiPSCs into enriched populations of motor neuron progenitor cells (MNPCs) that can be further amplified to produce a large number of cells to cover many experimental needs. These MNPCs can be efficiently differentiated towards mature MNs exhibiting functional electrical and pharmacological neuronal properties. Finally, we report that MN cultures can be long-term maintained, thus offering the opportunity to study degenerative phenomena associated with pathologies involving MNs and their functional, networked activity. These results indicate that our optimized procedure enables the efficient and robust generation of large quantities of MNPCs and functional MNs, providing a valid tool for MNs disease modelling and for drug discovery applications.Diet is an important factor affecting intestinal microbiota in horses. Fecal microbiota is commonly used as a substitute for studying hindgut microbiota when investigating the relationship between intestinal microbial changes and host health. So far, no study has compared the difference between the fecal microbiota found in horses that are fed pasture grass, silage, and hay. The present study aims to characterize the fecal microbiota in horses that were exclusively on one of the three forage diets, and to analyze the potential impact of these forages, especially silage, on horse intestinal health. There were 36 horses randomly assigned to each of the three groups; each group was fed only one type of forage for 8 weeks. High throughput sequencing was applied to analyze the bacterial taxa in fecal samples collected from the horses at the end of the feeding trial. The Lachnospiraceae family was statistically more abundant in horses fed with hay, while it was the least abundant in horses fed with silage. The Streptococcaceae spp., considered a core microbial component in equine intestinal microbiota, were present in significantly lower quantities in feces from horses that were fed pasture grass as compared to those from horses fed hay or silage. The novel data may help promote the balancing of horse intestinal microbiota and the maintenance of intestinal health in horses.Thin polycrystalline Co2FeGe films with composition close to stoichiometry have been fabricated using magnetron co-sputtering technique. 1,2,3,4,6-O-Pentagalloylglucose Effects of substrate temperature (TS) and post-deposition annealing (Ta) on structure, static and dynamic magnetic properties were systematically studied. It is shown that elevated TS (Ta) promote formation of ordered L21 crystal structure. Variation of TS (Ta) allow modification of magnetic properties in a broad range. Saturation magnetization ~920 emu/cm3 and low magnetization damping parameter α ~ 0.004 were achieved for TS = 573 K. This in combination with soft ferromagnetic properties (coercivity below 6 Oe) makes the films attractive candidates for spin-transfer torque and magnonic devices.
Vitamin D deficiency (VDD) may be considered an independent cardiovascular (CV) risk factor, and it is well known that CV risk is higher in males. Our goal was to investigate the pharmacological reactivity and receptor expression of intramural coronary artery segments of male rats in cases of different vitamin D supply.
Four-week-old male Wistar rats were divided into a control group (
= 11) with optimal vitamin D supply (300 IU/kgbw/day) and a VDD group (
= 11, <0.5 IU/kgbw/day). After 8 weeks of treatment, intramural coronary artery segments were microprepared, their pharmacological reactivity was examined by in vitro microangiometry, and their receptor expression was investigated by immunohistochemistry.
Thromboxane A
(TXA
)-agonist induced reduced vasoconstriction, testosterone (T) and 17-β-estradiol (E2) relaxations were significantly decreased, a significant decrease in thromboxane receptor (TP) expression was shown, and the reduction in estrogen receptor-α (ERα) expression was on the border of significance in the VDD group.
VD-deficient male coronary arteries showed deteriorated pharmacological reactivity to TXA
and sexual steroids (E2, T). Insufficient vasoconstrictor capacity was accompanied by decreased TP receptor expression, and vasodilator impairments were mainly functional. The decrease in vasoconstrictor and vasodilator responses results in narrowed adaptational range of coronaries, causing inadequate coronary perfusion that might contribute to the increased CV risk in VDD.
VD-deficient male coronary arteries showed deteriorated pharmacological reactivity to TXA2 and sexual steroids (E2, T). Insufficient vasoconstrictor capacity was accompanied by decreased TP receptor expression, and vasodilator impairments were mainly functional. The decrease in vasoconstrictor and vasodilator responses results in narrowed adaptational range of coronaries, causing inadequate coronary perfusion that might contribute to the increased CV risk in VDD.BRAF is the most common gene mutated in malignant melanoma, and predominately it is a missense mutation of codon 600 in the kinase domain. This oncogenic BRAF missense mutation results in constitutive activation of the mitogen-activate protein kinase (MAPK) pro-survival pathway. Several BRAF inhibitors (BRAFi) have been developed to specifically inhibit BRAFV600 mutations that improve melanoma survival, but resistance and secondary cancer often occur. Causal mechanisms of BRAFi-induced secondary cancer and resistance have been identified through upregulation of MAPK and alternate pro-survival pathways. In addition, overriding of cellular senescence is observed throughout the progression of disease from benign nevi to malignant melanoma. In this review, we discuss melanoma BRAF mutations, the genetic mechanism of BRAFi resistance, and the evidence supporting the role of senescent cells in melanoma disease progression, drug resistance and secondary cancer. We further highlight the potential benefit of targeting senescent cells with senotherapeutics as adjuvant therapy in combating melanoma.
