Multistability and predominant hybrid phenotypes in a four node mutually repressive network of Th1/Th2/Th17/Treg differentiation.

Elucidating the emergent dynamics of cellular differentiation networks is crucial to understanding cell-fate decisions. Toggle switch - a network of mutually repressive lineage-specific transcription factors A and B - enables two phenotypes from a common progenitor: (high A, low B) and (low A, high B). However, the dynamics of networks enabling differentiation of more than two phenotypes from a progenitor cell has not been well-studied.

Drinking water quality impacts oocyte viability and embryo development.

Normal reproductive function and fertility is considered a "sixth vital sign" because disruptions to this sensitive physiological system can forewarn other health issues, including exposure to environmental toxicants. We found that female mice exhibited profound loss of embryos during pre-implantation and fetal development coincident with a change to the source of their drinking water. When female mice were provided with tap water from the building in which they were housed (Water 2), instead of tap water from a neighboring building which was their previous supply (Water 1), ovulated oocytes were degenerated or had impaired meiotic maturation, and failed to form embryos.

REPRODUCTIVE AGEING: BGP-15 mitigates adverse impacts of aging on sperm quality, fertility, and offspring health in male mice.

In Brief: Aging in men is associated with diminished sperm quality and a higher incidence of altered fetal development and miscarriage in resultant pregnancies. This study in mice identifies a therapeutic compound that, when administered to aged males, improves sperm quality, subsequent embryo development and post-natal offspring health.

Abstract: Aging in men is associated with diminished sperm quality and a higher incidence of altered fetal development and miscarriage in resultant pregnancies.

Quality of life in breast reconstruction: a comparison of lightweight and conventional breast implants.

Background: Due to the declining mortality rates of breast carcinoma and the rising incidence of risk-reducing mastectomies, enhancing the quality of life after breast reconstructions has become an increasingly important goal. The advantages of lightweight breast implants (B-Lite®) may significantly contribute to achieving this objective. This study aims to investigate whether lightweight implants are suitable for patients undergoing breast reconstruction and could improve the quality of life in comparison to conventional implants.

Quantifying robustness of the gap gene network.

Early development of Drosophila melanogaster (fruit fly) facilitated by the gap gene network has been shown to be incredibly robust, and the same patterns emerge even when the process is seriously disrupted. We investigate this robustness using a previously developed computational framework called DSGRN (Dynamic Signatures Generated by Regulatory Networks). Our mathematical innovations include the conceptual extension of this established modeling technique to enable modeling of spatially monotone environmental effects, as well as the development of a collection of graph theoretic robustness scores for network models.

Converting an infant with borderline left heart structures to biventricular circulation after an initial hybrid Norwood approach: a case report.

Background: Hybrid approach in hypoplastic left heart syndrome (HLHS) implies placement of bilateral pulmonary artery bands and ductal stenting. This approach serves as a less invasive surgical-interventional alternative to the Norwood procedure with reported equivalent survival. Potential benefits include deferrable surgical risks and in some borderline left ventricle patients, when combined with a restrictive inter-atrial communication, it offers a chance for biventricular circulation.

Does supplementation of oocytes with additional mtDNA influence developmental outcome?

Introducing extra mitochondrial DNA (mtDNA) into oocytes at fertilization can rescue poor quality oocytes. However, supplementation alters DNA methylation and gene expression profiles of preimplantation embryos. To determine if these alterations impacted offspring, we introduced mtDNA from failed-to-mature sister (autologous) or third party (heterologous) oocytes into mature oocytes and transferred zygotes into surrogates.

The role of mtDNA in oocyte quality and embryo development.

The mitochondrial genome resides in the mitochondria present in nearly all cell types. The porcine (Sus scrofa) mitochondrial genome is circa 16.7 kb in size and exists in the multimeric format in cells.

Female reproductive life span is extended by targeted removal of fibrotic collagen from the mouse ovary.

The female ovary contains a finite number of oocytes, and their release at ovulation becomes sporadic and disordered with aging and with obesity, leading to loss of fertility. Understanding the molecular defects underpinning this pathology is essential as age of childbearing and obesity rates increase globally. We identify that fibrosis within the ovarian stromal compartment is an underlying mechanism responsible for impaired oocyte release, which is initiated by mitochondrial dysfunction leading to diminished bioenergetics, oxidative damage, inflammation, and collagen deposition.

The regulatory role of miR-20a in bovine cumulus cells and its contribution to oocyte maturation.

Dynamic changes in microRNAs in oocyte and cumulus cells before and after maturation may explain the spatiotemporal post-transcriptional gene regulation within bovine follicular cells during the oocyte maturation process. miR-20a has been previously shown to regulate proliferation and differentiation as well as progesterone levels in cultured bovine granulosa cells. In the present study, we aimed to demonstrate the function of miR-20a during the bovine oocyte maturation process.

Characterization of dendritic cells in human and experimental myocarditis.

Aims: Dendritic cells (DCs) are central mediators of adaptive immunity, and there is growing evidence of their role in myocardial inflammatory disease. We hypothesized that plasmacytoid and myeloid DCs are involved in the mechanisms of myocarditis and analysed these two main subtypes in human myocarditis subjects, as well as in a murine model of experimental autoimmune myocarditis (EAM).

Methods And Results: Circulating DCs were analysed by flow cytometry in patients with acute myocarditis, dilated cardiomyopathy, and controls.

The effect of maternal high-fat/high-sugar diet on offspring oocytes and early embryo development.

Observational human data and several lines of animal experimental data indicate that maternal obesity impairs offspring health. Here, we comprehensively tested the model that maternal obesity causes defects in the next three generations of oocytes and embryos. We exposed female F0 mice to a high-fat/high-sugar (HF/HS) diet for 6 weeks before conception until weaning.

Cultural Sensitivity and Global Pharmacy Engagement in the Caribbean: Dominica, Jamaica, Puerto Rico, and St. Kitts.

Sustainable and reciprocal partnerships in pharmacy education and practice exist between schools and colleges of pharmacy in the United States and Caribbean countries and territories. This paper discusses the cultural considerations for such partnerships to flourish. First, general information on Caribbean countries and territories is covered.

Reversal of anticoagulation with four-factor prothrombin complex concentrate without concurrent vitamin K (phytonadione) for urgent surgery in a patient at moderate-to-high risk for thromboembolism.

Successful vitamin K antagonist (eg, warfarin) reversal with 4-factor prothrombin complex concentrate (4F-PCC) without vitamin K (phytonadione) for emergent surgery in a patient at moderate-to-high risk for thromboembolism is reported. This approach may decrease the risk for development of thrombus, as it limits the amount of time the patient's anticoagulation is subtherapeutic. It also may increase the risk of bleeding, so patient selection is essential if this strategy is employed.

MicroRNA 17-92 cluster regulates proliferation and differentiation of bovine granulosa cells by targeting PTEN and BMPR2 genes.

Granulosa cell proliferation and differentiation are key developmental steps involved in the formation of the dominant follicle eligible for ovulation. This process is, in turn, regulated by spatiotemporally emerging molecular events. MicroRNAs (miRNAs) are one of the molecular signatures believed to regulate granulosa cell function by fine-tuning gene expression.

Intravital microscopy - A novel tool in characterizing congestive heart failure in experimental autoimmune myocarditis.

Aims: Experimental autoimmune myocarditis (EAM) is a widely used murine model, in which cellular myocardial infiltration resembles human viral myocarditis. Although myocarditis can be readily assessed on histology, heart failure has not been fully characterized, as there are limitations in available markers and difficulties in hemodynamic measurements, especially on small rodents. We investigated whether intravital microscopy of the microcirculation can be used to characterize heart failure in EAM.

Plantaricin IIA-1A5 from Lactobacillus plantarum IIA-1A5 displays bactericidal activity against Staphylococcus aureus.

Plantaricin IIA-1A5 is a bacteriocin produced by Lactobacillus plantarum IIA-1A5 isolated from Indonesian beef. This research aimed to identify the genes involved in plantaricin IIA-1A5 production and examine its mode of action against Staphylococcus aureus. It has been reported that a bacteriocin structural gene, plnW, is present in genome of L.

Preclinical studies in rats and squirrel monkeys for safety evaluation of the bivalent anti-human T cell immunotoxin, A-dmDT390-bisFv(UCHT1).

The bivalent anti-human T cell immunotoxin A-dmDT390-bisFv(UCHT1) for treatment of patients with T cell malignancies is a single chain fusion protein composed of the catalytic domain and translocation domains of diphtheria toxin fused to two tandem sFv molecules reactive with human CD3 epsilon. This immunotoxin selectively kills CD3 epsilon positive T cells. To determine the maximum tolerated dose (MTD), pharmacokinetics and immunogenicity of A-dmDT390-bisFv(UCHT1), rat and squirrel monkey studies were performed.

Anthrax toxin-induced shock in rats is associated with pulmonary edema and hemorrhage.

Bacillus anthracis infections are frequently associated with severe and often irreversible hypotensive shock despite appropriate antibiotics and aggressive hemodynamic and pulmonary support. Based on the observations that the anthrax secreted proteins-protective antigen (PA), lethal factor (LF), and edema factor (EF) also produce shock and mortality in animal models, we chose to characterize further the clinical chemistries and microscopic pathology of toxin treated rats. Groups of three male Sprague Dawley rats received bolus intravenous infusions of PA/LF, PA/EF, LF, or EF alone and blood samples and tissues were collected and assayed for chemistries and tissue pathology.

Characterization of uncertainty in outdoor sound propagation predictions.

Predictive skill for outdoor sound propagation is assessed using high-resolution atmospheric fields from large-eddy simulations (LES). Propagation calculations through the full LES fields are compared to calculations through subsets of the LES fields that have been processed in typical ways, such as mean vertical profiles and instantaneous vertical profiles synchronized to the sound propagation. It is found that mean sound pressure levels can be predicted with low errors from the mean profiles, except in refractive shadow regions.

[Quantitation of Acinetobacter calcoaceticus in mixed bacterial cultures by an enzyme immunoassay].

An enzyme-linked immunosorbent assay using polyclonal antibodies from rabbits has been developed for quantification of Acinetobacter calcoaceticus. Bacteria were added to the wells of a microtiter plate coated with anti-Acinetobacter immunoglobulin. For detecting bound cells the peroxidase-labelled immunoglobulin fraction was used.