Deletion of Dysregulates ERK and STAT3 Activity in Mouse Embryonic Stem Cells, Enhancing Their Naive-Like Self-Renewal in the Presence of Leukemia Inhibitory Factor.

The ShcA adapter protein is necessary for early embryonic development. The role of ShcA in development is primarily attributed to its 52 and 46 kDa isoforms that transduce receptor tyrosine kinase signaling through the extracellular signal regulated kinase (ERK). During embryogenesis, ERK acts as the primary signaling effector, driving fate acquisition and germ layer specification.

Selecting Normalizers for MicroRNA RT-qPCR Expression Analysis in Murine Preimplantation Embryos and the Associated Conditioned Culture Media.

Normalizing RT-qPCR miRNA datasets that encompass numerous preimplantation embryo stages requires the identification of miRNAs that may be used as stable reference genes. A need has also arisen for the normalization of the accompanying conditioned culture media as extracellular miRNAs may serve as biomarkers of embryo developmental competence. Here, we evaluate the stability of six commonly used miRNA normalization candidates, as well as small nuclear U6, using five different means of evaluation (BestKeeper, NormFinder, geNorm, the comparative Delta Ct method and RefFinder comprehensive analysis) to assess their stability throughout murine preimplantation embryo development from the oocyte to the late blastocyst stages, both in whole embryos and the associated conditioned culture media.

Increased fire activity under high atmospheric oxygen concentrations is compatible with the presence of forests.

Throughout Earth's history, the abundance of oxygen in our atmosphere has varied, but by how much remains debated. Previously, an upper limit for atmospheric oxygen has been bounded by assumptions made regarding the fire window: atmospheric oxygen concentrations higher than 30-40% would threaten the regeneration of forests in the present world. Here we have tested these assumptions by adapting a Dynamic Global Vegetation Model to run over high atmospheric oxygen concentrations.

Expression and localization of NRF2/Keap1 signalling pathway genes in mouse preimplantation embryos exposed to free fatty acids.

Obese women experience greater incidence of infertility, with reproductive tracts exposing preimplantation embryos to elevated free fatty acids (FFA) such as palmitic acid (PA) and oleic acid (OA). PA treatment impairs mouse preimplantation development in vitro, while OA co-treatment rescues blastocyst development of PA treated embryos. In the present study, we investigated the effects of PA and OA treatment on NRF2/Keap1 localization, and relative antioxidant enzyme (Glutathione peroxidase; Gpx1, Catalase; Cat, Superoxide dismutase; Sod1 and γ-Glutamylcysteine ligase catalytic unit; Gclc) mRNA levels, during in vitro mouse preimplantation embryo development.

Cognitive trajectories following onset of psychosis: a meta-analysis.

Background: Cognitive impairment is a core feature of schizophrenia, associated with poor functional outcomes. The course of cognitive function in the years following illness onset has remained a subject of debate, with a previous analysis finding no worsening, providing support for the neurodevelopmental model of schizophrenia. Since then, many more studies have reported on longitudinal cognitive performance in early psychosis, with some indicating deterioration, which does not align with this view.

Flow Cytometric Characterization of Pluripotent Cell Protein Markers in Naïve, Formative, and Primed Pluripotent Stem Cells.

Here we describe methodologies to characterize, delineate, and quantify pluripotent cells between naïve, formative, and primed pluripotent state mouse embryonic stem cell (mESCs) populations using flow cytometric analysis. This methodology can validate pluripotent states, sort individual cells of interest, and determine the efficiency of transitioning naïve mESCs to a primed-like state as mouse epiblast-like cells (mEpiLCs) and onto fully primed mouse epiblast stem cells (mEpiSCs). Quantification of the cell surface markers; SSEA1(CD15) and CD24 introduces an effective method of distinguishing individual cells from a population by their respective positioning in the pluripotent spectrum.

3D Immunofluorescent Image Colocalization Quantification in Mouse Epiblast Stem Cells.

This chapter details 3D morphological topography of colony architecture optimization and nuclear protein localization by co-immunofluorescent confocal microscopy analysis. Colocalization assessment of nuclear and cytoplasmic cell regions is detailed to demonstrate nuclear and cytoplasmic localization in mEpiSCs by confocal microscopy and orthogonal colocalization assessment. Protein colocalization within mESCs, mEpiLCs, and mEpiSCs can be efficiently completed using these optimized protocols.

Modulation of PKM1/2 Levels by Steric Blocking Morpholinos Alters the Metabolic and Pluripotent State of Murine Pluripotent Stem Cells.

Cellular metabolism plays both an active and passive role in embryonic development, pluripotency, and cell-fate decisions. However, little is known regarding the role of metabolism in regulating the recently described "formative" pluripotent state. The pluripotent developmental continuum features a metabolic switch from a bivalent metabolism (both glycolysis and oxidative phosphorylation) in naive cells, to predominantly glycolysis in primed cells.

Free fatty acid treatment of mouse preimplantation embryos demonstrates contrasting effects of palmitic acid and oleic acid on autophagy.

Treatment of mouse preimplantation embryos with elevated palmitic acid (PA) reduces blastocyst development, whereas cotreatment with PA and oleic acid (OA) together rescues blastocyst development to control frequencies. To understand the mechanistic effects of PA and OA treatment on early mouse embryos, we investigated the effects of PA and OA, alone and in combination, on autophagy during preimplantation development in vitro. We hypothesized that PA would alter autophagic processes and that OA cotreatment would restore control levels of autophagy.

Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers.

Background: Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation.

Method: 161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited.

Effects of palmitic acid on localization of embryo cell fate and blastocyst formation gene products.

As obese and overweight patients commonly display hyperlipidemia and are increasingly accessing fertility clinics for their conception needs, our studies are directed at understanding the effects of hyperlipidemia on early pregnancy. We have focused on investigating palmitic acid (PA) and oleic acid (OA) treatment alone and in combination from the mouse two-cell stage embryos as a model for understanding their effects on the mammalian preimplantation embryo. We recently reported that PA exerts a negative effect on mouse two-cell progression to the blastocyst stage, whereas OA co-treatment reverses that negative effect.

A systematic review of the effects of psychiatric medications on social cognition.

Introduction: Social cognition is an important area of mental functioning relevant to psychiatric disorders and social functioning, that may be affected by psychiatric drug treatments. The aim of this review was to investigate the effects of medications with sedative properties, on social cognition.

Method: This systematic review included experimental and neuroimaging studies investigating drug effects on social cognition.

In vitro fertilization cycles stimulated with follitropin delta result in similar embryo development and quality when compared with cycles stimulated with follitropin alfa or follitropin beta.

Objective: To study the impact of follitropin delta for ovarian stimulation on embryo development and quality compared with that of follitropin alfa or beta in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.

Design: Retrospective cohort study.

Setting: University-affiliated, hospital-based fertility clinic.

Differential localization patterns of pyruvate kinase isoforms in murine naïve, formative, and primed pluripotent states.

Mouse embryonic stem cells (mESCs) and mouse epiblast stem cells (mEpiSCs) represent opposite ends of the pluripotency continuum, referred to as naïve and primed pluripotent states, respectively. These divergent pluripotent states differ in several ways, including growth factor requirements, transcription factor expression, DNA methylation patterns, and metabolic profiles. Naïve cells employ both glycolysis and oxidative phosphorylation (OXPHOS), whereas primed cells preferentially utilize aerobic glycolysis, a trait shared with cancer cells referred to as the Warburg Effect.

Murine Blastocysts Release Mature MicroRNAs Into Culture Media That Reflect Developmental Status.

Extracellular microRNA (miRNA) sequences derived from the pre-implantation embryo have attracted interest for their possible contributions to the ongoing embryonic-uterine milieu, as well as their potential for use as accessible biomarkers indicative of embryonic health. Spent culture media microdroplets used to culture late-stage E4.0 murine blastocysts were screened for 641 mature miRNA sequences using a reverse transcription-quantitative polymerase chain reaction-based array.

Analysis of TERT Isoforms across TCGA, GTEx and CCLE Datasets.

Reactivation of the multi-subunit ribonucleoprotein telomerase is the primary telomere maintenance mechanism in cancer, but it is rate-limited by the enzymatic component, telomerase reverse transcriptase (TERT). While regulatory in nature, TERT alternative splice variant/isoform regulation and functions are not fully elucidated and are further complicated by their highly diverse expression and nature. Our primary objective was to characterize TERT isoform expression across 7887 neoplastic and 2099 normal tissue samples using The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Project (GTEx), respectively.

The rise of angiosperms strengthened fire feedbacks and improved the regulation of atmospheric oxygen.

The source of oxygen to Earth's atmosphere is organic carbon burial, whilst the main sink is oxidative weathering of fossil carbon. However, this sink is to insensitive to counteract oxygen rising above its current level of about 21%. Biogeochemical models suggest that wildfires provide an additional regulatory feedback mechanism.

Extracellular vesicles, microRNA and the preimplantation embryo: non-invasive clues of embryo well-being.

Elective single embryo transfer is rapidly becoming the standard of care in assisted reproductive technology for patients under the age of 35 years with a good prognosis. Clinical pregnancy rates have become increasingly dependent on the selection of a single viable embryo for transfer, and diagnostic techniques facilitating this selection continue to develop. Current progress in elucidating the extracellular vesicle and microRNA components of the embryonic secretome is reviewed, and the potential for these findings to improve clinical embryo selection discussed.

Revised estimates of ocean-atmosphere CO flux are consistent with ocean carbon inventory.

The ocean is a sink for ~25% of the atmospheric CO emitted by human activities, an amount in excess of 2 petagrams of carbon per year (PgC yr). Time-resolved estimates of global ocean-atmosphere CO flux provide an important constraint on the global carbon budget. However, previous estimates of this flux, derived from surface ocean CO concentrations, have not corrected the data for temperature gradients between the surface and sampling at a few meters depth, or for the effect of the cool ocean surface skin.

Oleic Acid Counters Impaired Blastocyst Development Induced by Palmitic Acid During Mouse Preimplantation Development: Understanding Obesity-Related Declines in Fertility.

Obesity is associated with altered fatty acid profiles, reduced fertility, and assisted reproductive technology (ART) success. The effects of palmitic acid (PA), oleic acid (OA), and their combination on mouse preimplantation development, endoplasmic reticulum (ER) stress pathway gene expression, lipid droplet formation, and mitochondrial reactive oxygen species (ROS) were characterized. Two-cell stage mouse embryos collected from superovulated and mated CD1 females were placed into culture with KSOMaa medium, or PA alone or in combination with OA for 46 h.

Knockdown of p66Shc Alters Lineage-Associated Transcription Factor Expression in Mouse Blastocysts.

The p66Shc adaptor protein regulates apoptosis and senescence during early mammalian development. However, p66Shc expression during mouse preimplantation development is upregulated at the blastocyst stage. Our objective was to determine the biological function of p66Shc during mouse blastocyst development.

Long-Term Planetary Habitability and the Carbonate-Silicate Cycle.

The potential habitability of an exoplanet is traditionally assessed by determining whether its orbit falls within the circumstellar "habitable zone" of its star, defined as the distance at which water could be liquid on the surface of a planet (Kopparapu et al., 2013 ). Traditionally, these limits are determined by radiative-convective climate models, which are used to predict surface temperatures at user-specified levels of greenhouse gases.

CD-1 mouse fertility rapidly declines and is accompanied with early pregnancy loss under conventional housing conditions.

CD-1 mice are commonly employed as a research model for defining mechanisms controlling early mammalian development and for understanding environmental impacts on mammalian fertility. CD-1 female mice were kept four to eight months under conventional animal care housing, and were fed ad libitum with normal laboratory mouse chow. Female weight, mating success, oocyte morphology, blastocyst development in vivo and in vitro, and RT-qPCR analysis of trophectoderm cell markers (Cdx2, Slc2a1, and Atp1a1 transcript abundance, and CDX2 localization) were assessed and contrasted with outcomes from four-week-old control CD-1 mice.

Treatment with AICAR inhibits blastocyst development, trophectoderm differentiation and tight junction formation and function in mice.

Study Question: What is the impact of adenosine monophosphate-activated protein kinase (AMPK) activation on blastocyst formation, gene expression, and tight junction formation and function?

Summary Answer: AMPK activity must be tightly controlled for normal preimplantation development and blastocyst formation to occur.

What Is Known Already: AMPK isoforms are detectable in oocytes, cumulus cells and preimplantation embryos. Cultured embryos are subject to many stresses that can activate AMPK.