Quinlanwebb0319

Emerging evidence suggests that exposures in prepuberty, particularly in fathers-to-be, may impact the phenotype of future offspring. Analyses of the RHINESSA cohort find that offspring of father's exposed to tobacco smoking or overweight that started in prepuberty demonstrate poorer respiratory health in terms of more asthma and lower lung function. A role of prepuberty onset smoking for offspring fat mass is suggested in the RHINESSA and ALSPAC cohorts, and historic studies suggest that ancestral nutrition during prepuberty plays a role for grand-offspring's health and morbidity. Support for causal relationships between ancestral exposures and (grand-)offspring's health in humans has been enhanced by advancements in statistical analyses that optimize the gain while accounting for the many complexities and deficiencies in human multigeneration data. The biological mechanisms underlying such observations have been explored in experimental models. A role of sperm small RNA in the transmission of paternal exposures to offspring phenotypes has been established, and chemical exposures and overweight have been shown to influence epigenetic programming in germ cells. For example, exposure of adolescent male mice to smoking led to differences in offspring weight and alterations in small RNAs in the spermatozoa of the exposed fathers. It is plausible that male prepuberty may be a time window of particular susceptibility, given the extensive epigenetic reprogramming taking place in the spermatocyte precursors at this age. In conclusion, epidemiological studies in humans, mechanistic research, and biological plausibility, all support the notion that exposures in the prepuberty of males may influence the phenotype of future offspring.Understanding the neural underpinnings of major depressive disorder (MDD) and its treatment could improve treatment outcomes. So far, findings are variable and large sample replications scarce. We aimed to replicate and extend altered functional connectivity associated with MDD and pharmacotherapy outcomes in a large, multisite sample. Resting-state fMRI data were collected from 129 patients and 99 controls through the Canadian Biomarker Integration Network in Depression. Symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). Connectivity was measured as correlations between four seeds (anterior and posterior cingulate cortex, insula and dorsolateral prefrontal cortex) and all other brain voxels. Partial least squares was used to compare connectivity prior to treatment between patients and controls, and between patients reaching remission (MADRS ≤ 10) early (within 8 weeks), late (within 16 weeks), or not at all. We replicated previous findings of altered connectivity in patients. In addition, baseline connectivity of the anterior/posterior cingulate and insula seeds differentiated patients with different treatment outcomes. The stability of these differences was established in the largest single-site subsample. Our replication and extension of altered connectivity highlighted previously reported and new differences between patients and controls, and revealed features that might predict remission prior to pharmacotherapy. Trial registration ClinicalTrials.gov NCT01655706.The vagina is the site of copulation and serves as the birth canal. It also provides protection against external pathogens. In mice, due to the absence of cervical glands, the vaginal epithelium is the main producer of vaginal mucus. The development and differentiation of vaginal epithelium-constituting cells and the molecular characteristics of vaginal mucus have not been thoroughly examined. Here, we characterized vaginal mucous cell development and the expression of mucus-related factors in pregnant mice. The vaginal mucous epithelium layer thickened and became multilayered after day 12 of pregnancy and secreted increasing amounts of mucus until early postpartum. Using histochemistry and transmission electron microscopy, we found supra-basal mucous cells as probable candidates for precursor cells. In vaginal mucous cells, the expression of TFF1, a stabilizer of mucus, was high, and some members of mucins and antimicrobial peptides (MUC5B and DEFB1) were expressed in a stage-dependent manner. In summary, this study presents the partial characterization of vaginal epithelial mucous cell lineage and expression of genes encoding several peptide substances that may affect vaginal tissue homeostasis and mucosal immunity during pregnancy and parturition.

Septic cardiomyopathy (SCM) increases mortality by 70-90% and results in mechanical dysfunction of cells.

Here, we created a lipopolysaccharide (LPS) -induced in-vitro sepsis model with mouse embryonic stem cell-derived cardiomyocytes (mESC-CM) using the CellDrum technology which simultaneously measures mechanical compliance and beat frequency of mESCs. Visualization of reactive oxygen species (ROS), actin stress fibers, and mRNA quantification of endothelial protein C receptor (EPCR) and protease-activated receptor 1 (PAR1) before/after LPS incubation were used for method validation. Since activated protein C (APC) has cardioprotective effects, samples were treated with human recombinant APC (rhAPC) with/-out LPS pre-damage to demonstrate the application in therapeutic studies.

12-hours LPS-treatment (5 μg/ml) increased ROS and decreased actin stress fiber density and significantly downregulated EPCR and PAR1 compared to control samples (0.26, 0.39-fold respectively). rhAPC application (5 μg/ml, 12-hours) decreased ROS and recovered actin density, EPCR, and PAR1 levels were significantly upregulated compared to LPS pre-damaged samples (4.79, 3.49-fold respectively). The beat frequencies were significantly decreased after 6- (86%) and 12-hours (73%) of LPS application. Mechanical compliance of monolayers significantly increased in a time-dependent manner, up to 8-times upon 12-hour LPS incubation compared to controls. rhAPC incubation increased the beat frequency by 127% (6h-LPS) and 123% (12h-LPS) and decreased mechanical compliance by 68% (12h-LPS) compared to LPS pre-damaged samples.

LPS induced contraction dysfunction and the reversal effects of rhAPC were successfully assessed by the mechanical properties of mESC-CMs. The CellDrum technology proved a decent tool to simulate sepsis in-vitro.

LPS induced contraction dysfunction and the reversal effects of rhAPC were successfully assessed by the mechanical properties of mESC-CMs. The CellDrum technology proved a decent tool to simulate sepsis in-vitro.

Type 1 diabetes (T1DM) is a chronic autoimmune disease characterized by T-cell-mediated destruction of insulin-producing beta cells. Evidence shows that patients with T1DM and mice used in specific diabetic models both exhibit changes in their intestinal microbiota and dysregulated microbiota contributes to the pathogenesis of T1DM. Islet transplantation (Tx) is poised to play an important role in the treatment of T1DM. However, whether treatment of T1DM with islet Tx can rescue dysregulated microbiota remains unclear.

In this study, we induced diabetic C57BL/6 mice with streptozotocin. Then treatment with either insulin administration, or homogenic or allogenic islet Tx was performed to the diabetic mice. Total DNA was isolated from fecal pellets and high-throughput 16S rRNA sequencing was used to investigate intestinal microbiota composition.

The overall microbial diversity was comparable between control (nonstreptozotocin treated) and diabetic mice. Our results showed the ratio of the Bacteroidetes Firmicutes between nondiabetic and diabetic mice was significant different. Treatment with islet Tx or insulin partially corrects the dysregulated bacterial composition. At the genus level, Bacteroides, Odoribacter, and Alistipes were associated with the progression and treatment efficacy of the disease, which may be used as a biomarker to predict curative effect of treatment for patients with T1DM.

Collectively, our results indicate that diabetic mice show changed microbiota composition and that treatment with insulin and islet Tx can partially correct the dysregulated microbiota.

Collectively, our results indicate that diabetic mice show changed microbiota composition and that treatment with insulin and islet Tx can partially correct the dysregulated microbiota.Although the utilization of donation after circulatory death donors (DCDs) for liver transplantation (LT) has increased steadily, much controversy remains, and no common acceptance criteria exist with regard to donor and recipient risk factors and prediction models. A consensus conference was organized by International Liver Transplantation Society on January 31, 2020, in Venice, Italy, to review the current clinical practice worldwide regarding DCD-LT and to develop internationally accepted guidelines. The format of the conference was based on the grade system. International experts in this field were allocated to 6 working groups and prepared evidence-based recommendations to answer-specific questions considering the currently available literature. Working group members and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and recommendations provided by working group 2, covering the entire spectrum of donor and recipient risk factors and prediction models in DCD-LT.Fabricating sulfur host for the cathode with strong confinement effect and high dispersion of sulfur is vitally important to the development of high-performance lithium sulfur batteries. Benefiting from their unique and tunable structure, good conductivity and chemical inertness, hollow porous carbon materials has been considered as a promising candidate. Herein, precisely designed waxberry-like hierarchical hollow carbon spheres (h-CNS) have been synthesized as the sulfur micro-containers for lithium sulfur batteries. The prepared h-CNS/S electrode shows a good rate capability of 1311 mAh g-1at 0.1 C and 962 mAh g-1at 1 C. In addition, the h-CNS/S electrode also shows satisfactory long cycle performance with 622 mAh g-1at 0.5 C and 400 mAh g-1at 4 C over 600 cycles. The desirable performance can be attributed to the wedge-shape micro-containers which improve the high dispersion of sulfur inside the channels and inhibit the loss of intermediate polysulfide. Moreover, the unique structure can also enhance the transfer of both lithium ions and electrons which benefits to the rate capability of the lithium sulfur batteries.Herein, a novel conductive poly(N-phenylglycine) (PNPG) polymer was successfully prepared by in situ electrochemical polymerization method (+0.75 V vs. Ag/AgCl) for 10 min, supported on flexible stainless-steel plate coated with a thin Au film (Au/SS), to serve as binder-free pseudocapacitive PNPG/Au/SS electrodes for energy storage devices. Compared to the electrode without Au coating, PNPG/Au/SS electrode exhibited better electrochemical performance with larger specific capacitance (495 F g-1 at a current density of 2 A g-1), higher rate performance and lower resistance, which are good indications to act as a positive electrode for asymmetric supercapacitor devices. Combined with activated carbon (AC) as a negative electrode, a asymmetric supercapacitor device was constructed and assessed. It displayed a specific capacitance of 38 F g-1 at a current density of 0.5 A g-1 and an energy density of 5.3 Wh kg-1 at a power density of 250 W kg-1. PDGFR inhibitor Experimentally, two asymmetric supercapacitor devices were connected in series to power a home-made windmill continuously for 8 s, revealing the high potential of this novel conductive polymer materials for energy storage application.