Crystal Structures and Electronic Properties of Haloform-Intercalated C60

Using density functional methods we calculated structural and electronic properties of bulk chloroform and bromoform intercalated C60, C60 2CHX3 (X=Cl,Br). Both compounds are narrow band insulator materials with a gap between valence and conduction bands larger than 1 eV. The calculated widths of the valence and conduction bands are 0.4-0.6 eV and 0.3-0.4 eV, respectively. The orbitals of the haloform molecules overlap with the $\pi$ orbitals of the fullerene molecules and the p-type orbitals of halogen atoms significantly contribute to the valence and conduction bands of C60 2CHX3. Charging with electrons and holes turns the systems to metals. Contrary to expectation, 10 to 20 % of the charge is on the haloform molecules and is thus not completely localized on the fullerene molecules. Calculations on different crystal structures of C60 2CHCl3 and C60 2CHBr3 revealed that the density of states at the Fermi energy are sensitive to the orientation of the haloform and C60 molecules. At a charging of three holes, which corresponds to the superconducting phase of pure C60 and C60 2CHX3, the calculated density of states (DOS) at the Fermi energy increases in the sequence DOS(C60) < DOS(C60 2CHCl3) < DOS(C60 2CHBr3).Comment: 11 pages, 7 figures, 4 table

Association between the p27 rs2066827 variant and tumor multiplicity in patients harboring MEN1 germline mutations.

Objetive: To date, no evidence of robust genotype-phenotype correlation or disease modifiers for Multiple endocrine neoplasia type 1 (MEN1) syndrome have been described, leaving the highly variable clinical presentation of the patients unaccounted for. Design: Because the CDKN1B (p27) gene causes MEN4 syndrome and it is transcriptionally regulated by the product of the MEN1 gene (Menin), we sought to analyze whether p27 influences the phenotype of MEN1-mutated patients. The cohort consisted of one hundred patients carrying germline MEN1 gene mutations and 855 population-matched control individuals. Methods: Genotyping of the coding p27 c.326T&gt;G (V109G) variant was performed by sequencing and restriction site digestion, and the genotypes were associated with clinical parameters by calculating odds ratios (ORs) and their 95% confidence intervals (CIs) using logistic regression. Results: There were significant differences in p27 V109G allele frequencies between controls and MEN1-mutated patients (OR= 2.55, p= 0.019, C.I.= 1.013-5.76). Among patients &ge;30 y old carrying truncating MEN1 mutations, the T allele was strongly associated with susceptibility to tumors in multiple glands (3-4 glands affected vs. 1-2 glands affected; OR=18.33; p=0.002, C.I.=2.88-16.41). This finding remained significant after Bonferroni multiple testing correction, indicating a robust association. No correlations were observed with the development of MEN1-related tumors such as hyperparathyroidism, pituitary adenomas, enteropancreatic and adrenocortical tumors. Conclusions: Our study suggests that the p27 tumor suppressor gene acts as a disease modifier for the MEN1 syndrome associated with MEN1 germline mutations. If confirmed in independent patient cohorts, this finding could facilitate the management of this clinically complex disease

Tyrosine hydroxylase in the brain and its regulation by glucocorticoids

Early life stress events can produce long-lasting changes in neurochemistry and behaviors related to monoamine systems, with increased risks of cardiovascular, metabolic, neuroendocrine, psychiatric disorders, generalized anxiety and depression in adulthood. Tyrosine hydroxylase (TH), the key enzyme for catecholamine synthesis, also plays an important role in the activity of the noradrenergic system and may be a target for glucocorticoids during the perinatal programming of physiological functions and behavior. Administration of hydrocortisone or dexamethasone to female rats on day 20 of pregnancy and to 3-day-old neonatal pups significantly increased TH mRNA levels (real-time PCR) and enzyme activity as well as protein levels determined by ICH in the locus coeruleus. Moreover, our treatment led to increase in TH mRNA levels in 25- and 70-day-old animals, as well as an increase in enzyme activity in the brainstem and cerebral cortex of adult rats. The long-term changes in TH expression are limited by the perinatal period of development. Administration of hormones on day 8 of life was not accompanied by changes in TH mRNA levels or enzyme activity. Glucocorticoids use several mechanisms to bring about transactivation or transrepression of genes. The main mechanism includes direct binding of the hormone-activated GRs to glucocorticoid responsive elements (GREs) in the promoter region of genes. However, despite optimistic claims made the classical GRE was not found in the TH gene promoter. Protein – protein interactions between hormone-activated GR and other transcription factors, for example, AP-1, provide an additional mechanism for the effects of glucocorticoids on gene expression. An important feature of this mechanism is its dependence on the composition of proteins formed by AP-1. Hormone-activated GRs are able to enhance gene expression when AP-1 consists of the Jun / Jun homodimer, but do not do that when AP-1 appears as the Jun / Fos heterodimer. Furthermore, as has been shown recently, the GRE / AP-1 composite site is the major site of interaction of glucocorticoids with  the TH gene in the pheochromocytoma cell line. Ontogenetic variation in the expression of Fos and Jun family proteins, which affects their ratio, can be one of the reasons for the TH gene regulation by glucocorticoids at near-term fetuses and neonates. However, to date this hypothesis has been supported only by in vitro data, and the existence of this mechanism in in vivo conditions needs to be explored in further studies