Synthesis based on cyclohexadienes. Part 17. Total synthesis of the sesquiterpenes of Eremophila georgei diels

The first stereoselective total synthesis of the novel sesquiterpenes 1 and 2 is described. The preparation of the key intermediate 27 involved a rearrangement of a bicyclo[3.2.1] octane framework to an isomeric bicyclo[3.2.1]octane skeleton via a bicyclo[2.2.2]octane derivative.

Regulation of progesterone biosynthesis in the human placenta by estradiol 17 beta and progesterone

Ex vivo addition of estradiol 17 beta to first trimester or term human placental minces caused a significant increase in the quantity of progesterone produced. Addition of an aromatase inhibitor, CGS 16949 A or the estrogen receptor antagonist, ICI 182780, significantly inhibited progesterone production confirming the role of estradiol 17 beta in the regulation of progesterone synthesis in human placenta. RU 486 and ZK 98299, which are antagonists of progesterone receptor, significantly modulated progesterone synthesis in the human placenta but exhibited paradoxical effects on the first trimester and term placenta We conclude that progesterone synthesis in the human placenta is regulated by estradiol 17 beta and progesterone. This is the first report providing evidence for autoregulation of progesterone synthesis in the human placenta.

The electrical switching and thermal behavior of bulk Ge(15)Te(85-x)Sn(x) and Ge(17)Te(83-x)Sn(x) glasses

Bulk Ge(15)Te(85 - x)Sn(x) and Ge(17)Te(83 - x)Sn(x) glasses, are found to exhibit memory type electrical switching. The switching voltages (V(t)) and thermal stability of Ge(15)Te(85 - x)Sn(x) and Ge(17)Te(83 - x)Sn(x) glasses are found to decrease with Sn content. The composition dependence of v, has been understood on the basis of the decrease in the OFF state resistance and thermal stability of these glasses with tin addition. X-ray diffraction studies reveal that no elemental Sn or Sn compounds with Te or Ge are present in thermally crystallized Ge-Te-Sn samples. This indicates that Sn atoms do not interact with the host matrix and form a phase separated network of its own, which remains in the parent glass matrix as an inclusion. Consequently, there is no enhancement of network connectivity and rigidity. The thickness dependence of switching voltages of Ge(15)Te(85 - x)Sn(x) and Ge(17)Te(83 - x)Sn(x) glasses is found to be linear, in agreement with the memory switching behavior shown by these glasses. (C) 2011 Elsevier B.V. All rights reserved.

Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-gamma and IL-17 production in blood from TB plus patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras

Background: A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Methods: Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-gamma and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). Results: M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-gamma production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. Conclusions: The pattern of immune target recognition is different in regard to IFN-gamma and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras.

Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity

Huntington's disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminal HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK. (C) 2014 Elsevier Inc. All rights reserved.

One-step synthesis of a cyclic 2,17-dioxo3,3](4,4 `)biphenylophane and first preparation of a microporous polymer network from a macrocyclic precursor by cyclotrimerization

One-step synthesis of a cyclic 2,17-dioxo3,3](4,4') biphenylophane (MC) was achieved in high yield; its structure was verified by single crystal X-ray analysis. As a first example, a microporous polymer network was formed from macrocycle MC via acid-catalysed cyclotrimerization yielding a BET surface area of ca. 570 m(2) g(-1).

Neonatal exposure to 17 beta-estradiol down-regulates the expression of synaptogenesis related genes in selected brain regions of adult female rats

Aims: Administration of estradiol or compounds with estrogenic activity to newborn female rats results in irreversible masculinization as well as defeminization in the brain and the animals exhibit altered reproductive behavior as adults. The cellular and molecular mechanism involved in inducing the irreversible changes is largely unknown. In the present study, we have monitored the changes in the expression of selected synaptogenesis related genes in the sexually dimorphic brain regions such as POA, hypothalamus and pituitary following 17 beta-estradiol administration to neonatal female rats. Main methods: Female Wistar rats which were administered 17 beta-estradiol on day 2 and 3 after birth were sacrificed 120 days later and the expression levels of genes implicated in synaptogenesis were monitored by semi-quantitative reverse transcription PCR. Since estradiol induced up-regulation of COX-2 in POA is a marker for estradiol induced masculinization as well as defeminization, in the present study only animals in which the increase in expression of COX-2 gene was observed in POA were included in the study. Key findings: Down-regulation of genes such as NMDA-2B, NETRIN-1, BDNF, MT-5 MMP and TNF-alpha was observed in the pre-optic area of neonatally E2 treated female rat brain but not in hypothalamus and pituitary compared to the vehicle- treated controls as assessed by RT-PCR and Western blot analysis. Significance: Our results suggest a possibility that down-regulation of genes associated with synaptogenesis in POA, may be resulting in disruption of the cyclical regulation of hormone secretion by pituitary the consequence of which could be infertility and altered reproductive behavior. (C) 2015 Elsevier Inc. All rights reserved.