Comparison of Three Chimeric Zika Vaccine Prototypes Developed on the Genetic Background of the Clinically Proven Live-Attenuated Japanese Encephalitis Vaccine SA-14-2.

Zika virus (ZIKV) is a medically important mosquito-borne orthoflavivirus, but no vaccines are currently available to prevent ZIKV-associated disease. In this study, we compared three recombinant chimeric viruses developed as candidate vaccine prototypes (rJEV/ZIKV, rJEV/ZIKV, and rJEV/ZIKV), in which the two neutralizing antibody-inducing prM and E genes from each of three genetically distinct ZIKV strains were used to replace the corresponding genes of the clinically proven live-attenuated Japanese encephalitis virus vaccine SA-14-2 (rJEV). In WHO-certified Vero cells (a cell line suitable for vaccine production), rJEV/ZIKV exhibited the slowest viral growth, formed the smallest plaques, and displayed a unique protein expression profile with the highest ratio of prM to cleaved M when compared to the other two chimeric viruses, rJEV/ZIKV and rJEV/ZIKV, as well as their vector, rJEV.

Mpox virus (MPXV): comprehensive analysis of pandemic risks, pathophysiology, treatments, and mRNA vaccine development.

Mpox, formerly known as monkeypox, is a zoonotic disease caused by the Mpox virus (MPXV), which has recently attracted global attention due to its potential for widespread outbreaks. Initially identified in 1958, MPXV primarily spreads to humans through contact with infected wild animals, particularly rodents. Historically confined to Africa, the virus has expanded beyond endemic regions, with notable outbreaks in Europe and North America in 2022, especially among men who have sex with men (MSM).

An Epigenetic Locus Associated with Loss of Smell in COVID-19.

Background/aim: Loss of smell, also known as anosmia, is a prevalent and often prolonged symptom following infection with SARS-CoV-2. While many patients regain olfactory function within weeks, a significant portion experience persistent anosmia lasting over a year post-infection. The underlying mechanisms responsible for this sensory deficit remain largely uncharacterized.

Stellate cells are in utero markers of pancreatic disease in cystic fibrosis.

Background: Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion.

The Role of Fenugreek in the Management of Type 2 Diabetes.

The number of people diagnosed with type 2 diabetes is on the increase worldwide. Of growing concern, the prevalence of type 2 diabetes in children and youths is increasing rapidly and mirrors the increasing burden of childhood obesity. There are many risk factors associated with the condition; some are due to lifestyle, but many are beyond our control, such as genetics.

Both enantiomers of β-aminoisobutyric acid BAIBA regulate Fgf23 via MRGPRD receptor by activating distinct signaling pathways in osteocytes.

With exercise, muscle and bone produce factors with beneficial effects on brain, fat, and other organs. Exercise in mice increased fibroblast growth factor 23 (FGF23), urine phosphate, and the muscle metabolite L-β-aminoisobutyric acid (L-BAIBA), suggesting that L-BAIBA may play a role in phosphate metabolism. Here, we show that L-BAIBA increases in serum with exercise and elevates Fgf23 in osteocytes.

Dynamic Single Cell Transcriptomics Defines Kidney FGF23/KL Bioactivity and Novel Segment-Specific Inflammatory Targets.

Unlabelled: FGF23 via its coreceptor αKlotho (KL) provides critical control of phosphate metabolism, which is altered in rare and very common syndromes, however the spatial-temporal mechanisms dictating renal FGF23 functions remain poorly understood. Thus, developing approaches to modify specific FGF23-dictated pathways has proven problematic. Herein, wild type mice were injected with rFGF23 for 1, 4 and 12h and renal FGF23 bioactivity was determined at single cell resolution.

Post-Civil War modernity and the nurse training movement: The "Experiment" of the Boston Training School for Nurses.

Background/purpose: This paper describes the origins of the Boston Training School for Nurses (1873), later named the Massachusetts General Hospital School of Nursing, and the role played by a Boston civic group, the Woman's Education Association, in its founding.

Methods: Social and political forces in the post-Civil War modern era and the challenges the founders encountered in establishing and managing a nursing school are delineated.

Discussion: Themes that highlight the significance of the Boston Training School's creation relative to the nurse training movement in America are identified.

Characterization of neural stem cells derived from human stem cells from the apical papilla undergoing three-dimensional neurosphere induction.

Objectives: The endogenous repairing based on the activation of neural stem cells (NSCs) is impaired by neurodegenerative diseases. The present study aims to characterize human stem cells from the apical papilla (hSCAPs) with features of mesenchymal stem cells (MSCs) and to demonstrate the neuronal differentiation of hSCAPs into NSCs through the formation of three-dimensional (3D) neurospheres, verifying the structural, immunophenotyping, self-renewal, gene expression and neuronal activities of these cells to help further improve NSCs transplantation.

Methodology: The hSCAPs were isolated from healthy impacted human third molar teeth and characterized as MSCs.

Cytokine supplemented maturation medium improved development to term following somatic cell nuclear transfer (SCNT) in cattle.

Context: In vitro maturation is an important process in the production of embryos. It has been shown that three cytokines, fibroblast growth factor 2, leukemia inhibitory factor and insulin-like growth factor 1 (FLI), increased efficiency of in vitro maturation, somatic cell nuclear transfer (SCNT) blastocyst production, and in vivo development of genetically engineered piglets.

Aims: Assess effects of FLI on oocyte maturation, quality of oocytes, and embryo development in bovine in vitro fertilisation (IVF) and SCNT.

Chromatin Reprogramming of In Vitro Fertilized and Somatic Cell Nuclear Transfer Bovine Embryos During Embryonic Genome Activation.

Reprogramming of the gamete into a developmentally competent embryo identity is a fundamental aspect of preimplantation development. One of the most important processes of this reprogramming is the transcriptional awakening during embryonic genome activation (EGA), which robustly occurs in fertilized embryos but is defective in most somatic cell nuclear transfer (SCNT) embryos. However, little is known about the genome-wide underlying chromatin landscape during EGA in SCNT embryos and how it differs from a fertilized embryo.

Transcriptomic analysis of lung development in wildtype and CFTR sheep suggests an early inflammatory signature in the CF distal lung.

The precise molecular events initiating human lung disease are often poorly characterized. Investigating prenatal events that may underlie lung disease in later life is challenging in man, but insights from the well-characterized sheep model of lung development are valuable. Here, we determine the transcriptomic signature of lung development in wild-type sheep (WT) and use a sheep model of cystic fibrosis (CF) to characterize disease associated changes in gene expression through the pseudoglandular, canalicular, saccular, and alveolar stages of lung growth and differentiation.

Single cell cortical bone transcriptomics define novel osteolineage gene sets altered in chronic kidney disease.

Introduction: Due to a lack of spatial-temporal resolution at the single cell level, the etiologies of the bone dysfunction caused by diseases such as normal aging, osteoporosis, and the metabolic bone disease associated with chronic kidney disease (CKD) remain largely unknown.

Methods: To this end, flow cytometry and scRNAseq were performed on long bone cells from Sost-cre/Ai9 mice, and pure osteolineage transcriptomes were identified, including novel osteocyte-specific gene sets.

Results: Clustering analysis isolated osteoblast precursors that expressed , , and , and a mature osteoblast population defined by , , and .

Osteocyte Egln1/Phd2 links oxygen sensing and biomineralization via FGF23.

Osteocytes act within a hypoxic environment to control key steps in bone formation. FGF23, a critical phosphate-regulating hormone, is stimulated by low oxygen/iron in acute and chronic diseases, however the molecular mechanisms directing this process remain unclear. Our goal was to identify the osteocyte factors responsible for FGF23 production driven by changes in oxygen/iron utilization.

Early developmental phenotypes in the cystic fibrosis sheep model.

Highly effective modulator therapies for cystic fibrosis (CF) make it a treatable condition for many people. However, although CF respiratory illness occurs after birth, other organ systems particularly in the digestive tract are damaged before birth. We use an ovine model of CF to investigate the in utero origins of CF disease since the sheep closely mirrors critical aspects of human development.

Regulation of FGF23 production and phosphate metabolism by bone-kidney interactions.

The bone-derived hormone fibroblast growth factor 23 (FGF23) functions in concert with parathyroid hormone (PTH) and the active vitamin D metabolite, 1,25(OH) vitamin D (1,25D), to control phosphate and calcium homeostasis. A rise in circulating levels of phosphate and 1,25D leads to FGF23 production in bone. Circulating FGF23 acts on the kidney by binding to FGF receptors and the co-receptor α-Klotho to promote phosphaturia and reduce circulating 1,25D levels.

Association between iron metabolism and SARS-COV-2 infection, determined by ferritin, hephaestin and hypoxia-induced factor-1 alpha levels in COVID-19 patients.

Background: Due to the growing evidence of the importance of iron status in immune responses, the biomarkers of iron metabolism are of interest in novel Coronavirus Disease 2019 (COVID-19). The present prospective study was carried out to compare iron status indicated by levels of ferritin with the levels of two novel biomarkers related to iron homeostasis, hephaestin and hypoxia-inducible factors-1 (HIF-1α) in the serum of patients with COVID-19 in comparison with a control group.

Methods And Results: Blood samples from 34 COVID-19 patients and from 43 healthy volunteers were collected and the levels of HEPH and HIF-1α were measured by ELISA and compared with levels of serum ferritin.

Gabapentin Disrupts Binding of Perlecan to the αδ Voltage Sensitive Calcium Channel Subunit and Impairs Skeletal Mechanosensation.

Our understanding of how osteocytes, the principal mechanosensors within bone, sense and perceive force remains unclear. Previous work identified "tethering elements" (TEs) spanning the pericellular space of osteocytes and transmitting mechanical information into biochemical signals. While we identified the heparan sulfate proteoglycan perlecan (PLN) as a component of these TEs, PLN must attach to the cell surface to induce biochemical responses.