Nuclear Progesterone Receptors Are Up-Regulated by Estrogens in Neurons and Radial Glial Progenitors in the Brain of Zebrafish

In rodents, there is increasing evidence that nuclear progesterone receptors are transiently expressed in many regions of the developing brain, notably outside the hypothalamus. This suggests that progesterone and/or its metabolites could be involved in functions not related to reproduction, particularly in neurodevelopment. In this context, the adult fish brain is of particular interest, as it exhibits constant growth and high neurogenic activity that is supported by radial glia progenitors. However, although synthesis of neuroprogestagens has been documented recently in the brain of zebrafish, information on the presence of progesterone receptors is very limited. In zebrafish, a single nuclear progesterone receptor (pgr) has been cloned and characterized. Here, we demonstrate that this pgr is widely distributed in all regions of the zebrafish brain. Interestingly, we show that Pgr is strongly expressed in radial glial cells and more weakly in neurons. Finally, we present evidence, based on quantitative PCR and immunohistochemistry, that nuclear progesterone receptor mRNA and proteins are upregulated by estrogens in the brain of adult zebrafish. These data document for the first time the finding that radial glial cells are preferential targets for peripheral progestagens and/or neuroprogestagens. Given the crucial roles of radial glial cells in adult neurogenesis, the potential effects of progestagens on their activity and the fate of daughter cells require thorough investigation

Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings

Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of “accelerated aging” in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex.The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of “accelerated cell aging.” Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05).These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure

Decompressive craniotomy: prognostic factors and complications in 89 patients Craniotomia descompressiva: análise de fatores prognósticos e complicações em 89 pacientes

Decompressive craniotomy (DC) is applied to treat post-traumatic intracranial hypertension (ICH). The purpose of this study is to identify prognostic factors and complications of unilateral DC. Eighty-nine patients submited to unilateral DC were retrospectively analyzed over a period of 30 months. Qui square independent test and Fisher test were used to identify prognostic factors. The majority of patients were male (87%). Traffic accidents had occurred in 47% of the cases. 64% of the patients had suffered severe head injury, while pupillary abnormalities were already present in 34%. Brain swelling plus acute subdural hematoma were the most common tomographic findings (64%). Complications occurred in 34.8% of the patients: subdural effusions in 10 (11.2%), hydrocephalus in 7 (7.9%) and infection in 14 (15.7%). The admittance Glasgow coma scale was a statistically significant predictor of outcome ( p=0.0309).<br>A craniotomia descompressiva (CD) é técnica utilizada para tratamento da hipertensão intracraniana (HIC) pós-traumática. O objetivo do estudo foi determinar fatores prognósticos e complicações nos pacientes submetidos a esta técnica. Realizou-se estudo retrospectivo de 89 pacientes submetidos à CD unilateral para tratamento da HIC pós-traumática durante 30 meses. Utilizou-se testes do Qui-quadrado de independência e teste exato de Fisher para análise de fatores independentes de prognóstico. A maioria dos pacientes era do sexo masculino (87%). A causa mais comum foi o acidente de trânsito (47%). A maioria apresentava traumatismo cranioencefálico grave (64%), 34% já apresentavam anisocoria. O achado tomográfico mais comum foi a associação entre tumefação cerebral e hematoma subdural agudo (64%). Em 34,8% dos pacientes houve complicações inerentes à técnica: coleção subdural (11,2%), hidrocefalia (7,9%) e infecção (15,7%). A escala de coma de Glasgow à admissão correlacionou-se estatisticamente como fator prognóstico (p=0,0309)

Functional roles for evolutionarily conserved Spt4p at centromeres and heterochromatin in Saccharomyces cerevisiae

The kinetochore (centromeric DNA and associated proteins) mediates the attachment of chromosomes to the mitotic spindle apparatus and is required for faithful chromosome transmission. We established that evolutionarily conserved Saccharomyces cerevisiae SPT4, previously identified in genetic screens for defects in chromosome transmission fidelity (ctf), encodes a new structural component of specialized chromatin at kinetochores and heterochromatic loci, with roles in kinetochore function and gene silencing. Using chromatin immunoprecipitation assays (ChIP), we determined that kinetochore proteins Ndc10p, Cac1p, and Hir1p are required for the association of Spt4p to centromeric (CEN) loci. Absence of functional Spt4p leads to altered chromatin structure at the CEN DNA and mislocalization of the mammalian CENP-A homolog Cse4p to noncentromeric loci. Spt4p associates with telomeres (TEL) and HMRa loci in a Sir3p-dependent manner and is required for transcriptional gene silencing. We show that a human homolog of SPT4 (HsSPT4) complements Scspt4-silencing defects and associates with ScCEN DNA in an Ndc10p-dependent manner. Our results highlight the evolutionary conservation of pathways required for genome stability in yeast and humans