The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila

Human neurodegenerative diseases have the temporal hallmark of afflicting the elderly population. Ageing is one of the most prominent factors to influence disease onset and progression, yet little is known about the molecular pathways that connect these processes. To understand this connection it is necessary to identify the pathways that functionally integrate ageing, chronic maintenance of the brain and modulation of neurodegenerative disease. MicroRNAs (miRNA) are emerging as critical factors in gene regulation during development; however, their role in adult-onset, age-associated processes is only beginning to be revealed. Here we report that the conserved miRNA miR-34 regulates age-associated events and long-term brain integrity in Drosophila, providing a molecular link between ageing and neurodegeneration. Fly mir-34 expression exhibits adult-onset, brain-enriched and age-modulated characteristics. Whereas mir-34 loss triggers a gene profile of accelerated brain ageing, late-onset brain degeneration and a catastrophic decline in survival, mir-34 upregulation extends median lifespan and mitigates neurodegeneration induced by human pathogenic polyglutamine disease protein. Some of the age-associated effects of miR-34 require adult-onset translational repression of Eip74EF, an essential ETS domain transcription factor involved in steroid hormone pathways. Our studies indicate that miRNA-dependent pathways may have an impact on adult-onset, age-associated events by silencing developmental genes that later have a deleterious influence on adult life cycle and disease, and highlight fly miR-34 as a key miRNA with a role in this process

Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder that displays both sporadic and inherited forms [1]. Exposure to several common environmental toxins acting through oxidative stress has been shown to be associated with PD [2]. One recently identified inherited PD gene, DJ-1, may have a role in protection from oxidative stress [3-10], thus potentially linking a genetic cause with critical environmental risk factors. To develop an animal model that would allow integrative study of genetic and environmental influences, we have generated Drosophila lacking DJ-1 function. Fly DJ-1 homologs exhibit differential expression: DJ-1β is ubiquitous, while DJ-1α is predominantly expressed in the male germline. DJ-1α and DJ-1β double knockout flies are viable, fertile, and have a normal lifespan; however, they display a striking selective sensitivity to those environmental agents, including paraquat and rotenone, linked to PD in humans. This sensitivity results primarily from loss of DJ-1β protein, which also becomes modified upon oxidative stress. These studies demonstrate that fly DJ-1 activity is selectively involved in protection from environmental oxidative insult in vivo and that the DJ-1β protein is biochemically responsive to oxidative stress. Study of these flies will provide insight into the critical interplay of genetics and environment in PD. ©2005 Elsevier Ltd. All rights reserved

Dinâmica estrutural da comunidade lenhosa em Floresta Estacional Semidecidual na transição Cerrado-Floresta Amazônica, Mato Grosso, Brasil Structural dynamics of the woody community in a semideciduous forest in the Cerrado-Amazon Forest transition of Mato Grosso, Brazil

O entendimento de processos ecológicos, especialmente das modificações estruturais e florísticas em ecossistemas naturais, é fundamental para embasar ações visando à sua conservação e/ou restauração. O objetivo do estudo foi avaliar mudanças ocorridas na estrutura da comunidade lenhosa na transição Cerrado-Floresta Amazônica, no período de 2003 a 2008. Foram estabelecidas 60 parcelas permanentes de 10 x 10 m onde foram amostrados todos os indivíduos com diâmetro à altura do peito > 5 cm. Em 2003 foram registrados 1.140 ind. ha-1 e área basal de 24,35 m² ha-1, enquanto em 2008 foram 1.071 ind. ha-1 e área basal de 22,04 m² ha-1. O recrutamento (2,76% ano-1) não compensou a mortalidade (3,95% ano-1) e o ganho em área basal (0,54% ano-1) não superou a perda (3,77% ano-1). Em função dessa diferença, a meia vida (17,3 anos) foi menor que o tempo de duplicação (29,9 anos), resultando em baixa estabilidade (12,6 anos) e reposição (23,6 anos) em relação a outras florestas estacionais. Os parâmetros de dinâmica da comunidade e das principais espécies sugerem que a floresta está passando por mudanças caracterizadas principalmente pela retração da densidade e biomassa dos indivíduos arbóreos, que podem estar relacionadas ao aumento das lianas, a uma fase de início de reconstrução do ciclo silvigenético da floresta ou ainda à forte seca que ocorreu na região no ano de 2005.<br>Understanding ecological processes, especially the structural and floristic changes in natural ecosystems, is essential before conserving and/or restoring these areas. The aim of this study was to assess the changes that occurred in the woody plant community from 2003 to 2008. Sixty permanent plots of 10 x 10 m were established, in which all individuals with diameter at breast height > 5 cm were sampled. A total of 1,140 ind. ha-1 were recorded in 2003 (basal area 24.35 m² ha-1) and 1,071 ind. ha-1 in 2008 (basal area of 22.04 m² ha-1). The recruitment (2.76% year-1) did not compensate mortality (3.95% year-1) and the basal area gain (0.54% year-1) did not exceed the loss (3.77% year-1). Because of this unbalance, the half-life (17.3 years) was lower than the doubling time (29.9 years), resulting in low stability (12.6 yrs) and replacement (23.6 yrs) in relation to other seasonal forests. The parameters of community and species dynamics suggest that the forest is undergoing changes characterized mainly by the density and biomass reduction of trees, which may be related to an increase in lianas, an early rebuilding phase of the forest silvigenetic cycle or even the severe drought that occurred in the region in 2005

Characterization of an A-Kinase Anchoring Protein in Human Ciliary Axonemes

Although protein kinase A (PKA) activation is known to increase ciliary beat frequency in humans the molecular mechanisms involved are unknown. We demonstrate that PKA is associated with ciliary axonemes where it specifically phosphorylates a 23-kDa protein. Because PKA is often localized to subcellular compartments in proximity to its substrate(s) via interactions with A-kinase–anchoring proteins (AKAPs), we investigated whether an AKAP was also associated with ciliary axonemes. This study has identified a novel 28 kDa AKAP (AKAP28)that is highly enriched in airway axonemes. The mRNA for AKAP28 is up-regulated as primary airway cells differentiate and is specifically expressed in tissues containing cilia and/or flagella. Additionally, both Western blot and immunostaining data show that AKAP28 is enriched in airway cilia. These data demonstrate that we have identified the first human axonemal AKAP, a protein that likely plays a role in the signaling necessary for efficient modulation of ciliary beat frequency