Griscelli Syndrome Type 3: Two New Cases and Review of the Literature

A 3‐year‐old Arab boy with a history of hypoplastic left heart syndrome was referred to the pediatric dermatology clinic at Sheba Medical Center for evaluation of hypomelanosis, manifested by fair skin pigmentation and silvery‐grey hair, eyebrows, and eyelashes. The child had one older brother with similar hypopigmentation and another older brother who had died of congenital heart disease. The child had no history of neurologic deficits or immunodeficiency and no additional findings on clinical evaluation.     

The effect of bacterial melanin on electrical activity of neurons of the substantia nigra under conditions of GABA generation

The changes in spike activity of single neurons of the compact part of the substantia nigra, evoked by nucleus caudatus stimulation under conditions of long-term registration of the single and multiple, isolated and combined actions of GABA, GABA-amide, glutamine, and ethanolamine-O-sulfate (EOS) were studied in albino rats. Inhibition of poststimulus activity under GABA action was recorded and the inhibitory effect of GABA-amide was revealed. Primary excitatory and subsequent inhibitory effects of glutamine in combination with EOS were shown. The subsequent administration of bacterial melanin, synthesized by a mutant culture of Bacillus thuringiensis (BT-M) evoked a clear-cut and prolonged excitatory reaction during all the combined actions of GABA, GABA-amide, glutamine, and EOS. Preliminary administration of BT-M abolished the inhibitory poststimulus effects of GABA, GABA-amide, and EOS, as well as glutamine-induced excitation.     

Progesterone and insulin stimulation of CPEB-dependent polyadenylation is regulated by Aurora A and glycogen synthase kinase-3

Progesterone stimulation of Xenopus oocyte maturation requires the cytoplasmic polyadenylation-induced translation of mos and cyclin B mRNAs. One cis element that drives polyadenylation is the CPE, which is bound by the protein CPEB. Polyadenylation is stimulated by Aurora A (Eg2)-catalyzed CPEB serine 174 phosphorylation, which occurs soon after oocytes are exposed to progesterone. Here, we show that insulin also stimulates Aurora A-catalyzed CPEB S174 phosphorylation, cytoplasmic polyadenylation, translation, and oocyte maturation. However, these insulin-induced events are uniquely controlled by PI3 kinase and PKC-zeta, which act upstream of Aurora A. The intersection of the progesterone and insulin signaling pathways occurs at glycogen synthase kinase 3 (GSK-3), which regulates the activity of Aurora A. GSK-3 and Aurora A interact in vivo, and overexpressed GSK-3 inhibits Aurora A-catalyzed CPEB phosphorylation. In vitro, GSK-3 phosphorylates Aurora A on S290/291, the result of which is an autophosphorylation of serine 349. GSK-3 phosphorylated Aurora A, or Aurora A proteins with S290/291D or S349D mutations, have reduced or no capacity to phosphorylate CPEB. Conversely, Aurora A proteins with S290/291A or S349A mutations are constitutively active. These results suggest that the progesterone and insulin stimulate maturation by inhibiting GSK-3, which allows Aurora A activation and CPEB-mediated translation.     

Regulated CPEB phosphorylation during meiotic progression suggests a mechanism for temporal control of maternal mRNA translation

CPEB is an mRNA-binding protein that stimulates polyadenylation-induced translation of maternal mRNA once it is phosphorylated on Ser 174 or Thr 171 (species-dependent). Disruption of the CPEB gene in mice causes an arrest of oogenesis at embryonic day 16.5 (E16.5), when most oocytes are in pachytene of prophase I. Here, we show that CPEB undergoes Thr 171 phosphorylation at E16.5, but dephosphorylation at the E18.5, when most oocytes are entering diplotene. Although phosphorylation is mediated by the kinase aurora, the dephosphorylation is due to the phosphatase PP1. The temporal control of CPEB phosphorylation suggests a mechanism in which CPE-containing mRNA translation is stimulated at pachytene and metaphase I.     

The product of gene P of coliphage λ

The product of gene P of phage λ was identified. The P protein has an apparent molecular weight of 23,000 as estimated by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. The phage λimmP22c2ts 30 which carries gene 12 of phage P22 in place of the λ P gene, is unable to synthesize the 23,000-molecular weight protein band. This phage synthesizes a protein of molecular weight 50,000.     

21-gene recurrence score testing in the older population with estrogen receptor-positive breast cancer

Introduction

The 21-gene recurrence score (RS) (Oncotype Dx, Genomic Health, Redwood City Ca) has not been validated in an older cohort with estrogen receptor (ER)-positive breast cancer. The objective of this study was to evaluate RS validity in a group of older women with ER-positive breast cancer.