Cone photoreceptors are required for color discrimination and high-resolution central vision lost in macular degenerations, cone cone/rod dystrophies. transplantation could represent a therapeutic solution. However, an abundant source of human cones remains difficult to obtain. Work performed model organisms suggests that anterior neural cell fate is induced ‘by default' if BMP, TGFβ Wnt activities blocked, photoreceptor genesis operates through S-cone default pathway. We report here Coco...

Abstract Glioblastoma multiforme (GBM) is an incurable primary brain tumor containing a sub-population of cancer stem cells (CSCs). Polycomb Repressive Complex (PRC) proteins BMI1 and EZH2 are enriched in CSCs, promoting clonogenic growth resistance to genotoxic therapies. We report here that when used at appropriate concentrations, pharmaceutical inhibitors could efficiently prevent GBM colony CSC self-renewal vitro significantly extend lifespan terminally ill tumor-bearing mice. Notably,...

DNA sequences containing consecutive guanines organized in 4-interspaced tandem repeats can form stable single-stranded secondary structures, called G-quadruplexes (G4). Herein, we report that the Polycomb group protein BMI1 is enriched at heterochromatin regions putative G4 sequences, and structures accumulate cells with reduced expression and/or relaxed chromatin, including sporadic Alzheimer's disease (AD) neurons. In AD neurons, preferentially lamina-associated domains, this rescued by...

Bardet-Biedl syndrome (BBS) is a syndromic ciliopathy leading to progressive blindness starting in childhood, but the mechanism of photoreceptor degeneration remains unclear. The basal body primary cilium originates from centrosome's mother centriole, and BBS-related proteins form complex at body. Centrosomes also organize microtubules mitotic spindle. We show here that photoreceptors Bbs10 -/- mouse pups present DNA damage response (DDR) becomes persistent localizes In patient-derived...

Retinal development occurs through the sequential but overlapping generation of six neuronal and one glial cell types. Of these, rod cone photoreceptors represent functional unit light detection phototransduction are frequently affected in retinal degenerative diseases. During mouse development, Polycomb group protein Bmi1 is expressed immature progenitors differentiated neurons, including cones. We show here that required to prevent post-natal degeneration bipolar inactivation Chk2 or p53...

ABSTRACT Retinal degenerative diseases affect millions of people worldwide, and legal blindness is generally associated with the loss cone photoreceptors located in central region retina called macula. Currently, there no treatment to replace Addressing this unmet need, we employed control isogenic hypoimmunogenic induced pluripotent stem cell lines generate spontaneously polarized retinal sheets (RSs). RSs were enriched progenitor precursor cells, which could differentiate into mature S-...

Ciliopathies are heterogeneous genetic diseases affecting primary cilium structure and function. Meckel-Gruber (MKS) Bardet-Biedl (BBS) syndromes severe ciliopathies characterized by skeletal neurodevelopment anomalies, including polydactyly, cognitive impairment, retinal degeneration. We describe the generation molecular characterization of human induced pluripotent stem cell (iPSC)-derived sheets (RSs) from controls, MKS (TMEM67) BBS (BBS10) cases. RSs displayed significant common...

Neovascularization contributes to multiple visual disorders including age-related macular degeneration (AMD) and retinopathy of prematurity. Current therapies for treating ocular angiogenesis are centered on the inhibition vascular endothelial growth factor (VEGF). While clinically effective, some AMD patients refractory or develop resistance anti-VEGF concerns increased risks developing geographic atrophy following long-term treatment have been raised. Identification alternative pathways...

Upon treatment with TSH the intracellular location of 3’, 5’-nucleotide phospho diesterase changes time. Before hormonal histochemical reaction detects enzyme at periphery thyroidocyte. One hour after administration seems concentrated apical part cells. Two hours stain appears scattered throughout cytoplasm. The coincidence possible cyclic AMP sites action is stressed.

<title>Abstract</title> Presenilin 1 (PSEN1) is the most frequently mutated gene in early-onset sporadic and familial Alzheimer’s disease (FAD). The PSEN1 complex displays gamma-secretase activity promotes cleavage of C99-terminal fragment Amyloid Precursor Protein (APP) into Aβ42 peptide. also involved vesicle transport across ER mitochondria so called associated membranes. We generated induced pluripotent stem cells (iPSCs) from 4 controls 5 FAD cases carrying A246E L286V mutations....

ABSTRACT Retinal degenerative diseases affect millions of people worldwide, and legal blindness is generally associated with the loss cone photoreceptors located in retina’s central region called macula. Currently, there no treatment to replace Addressing this unmet need, we employed control isogenic hypoimmunogenic induced pluripotent stem cell (iPSC) lines generate spontaneously polarized retinal sheets (RSs). They presented advantage facile customization large-scale production, exhibiting...

Abstract We studied the phenotype of T‐lymphocytes isolated from 18 patients with head and neck cancer, their capacity to express Ia antigens upon activation by lectin in vitro , function either as responder or stimulator cells autologous mixed lymphocyte reaction, thier cooperate normal adherent suppressor (NASC). The these have several functional defects including an impaired activate allogeneic lymphocytes reactions (MLRs), a lack proliferative MLRs, sensitivity inhibition NASC, mitogens...

Serum aldosterone values were determined in 6 elderly (70-82 years) and adult (31-43 male subjects after the intravenous administration of 10 mg metoclopramide. A significant difference metoclopramide-induced serum rise was found between two groups, it being blunted older (serum peak values: 15.8 +/- 3.6 ng/dl 38.7 4.9 subjects, respectively). The existence an impaired secretion response to dopaminergic blockade is postulated.

The efficacy of oral ibopamine 100 mg three times daily was evaluated in a double-blind, randomized, placebo-controlled study 40 elderly patients including 20 females with mild heart failure (New York Heart Association Class II) over 12-week period. Ibopamine induced statistically significant increase exercise time 53.22 s as compared an on placebo 7.5 (p < 0.05). In 6-min walk test, the average distance increased by 106 m ibopamine-treated group 68 > subset treatment no effect plasma...