Accelerated Age-Related Cognitive Decline and Neurodegeneration, Caused by Deficient DNA Repair

Age-related cognitive decline and neurodegenerative diseases are a growing challenge for our societies with their aging populations. Accumulation of DNA damage has been proposed to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. Here we take advantage of Ercc1(Delta/-) mutant mice, which are impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. We show that these mice exhibit an age-dependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype is observed in mice where the mutation is restricted to excitatory forebrain neurons. Moreover, these neuron-specific mutants develop a learning impairment. Together, these results suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration. Hence, accumulated DNA damage could therefore be an important factor in the onset and progression of age-related cognitive decline and neurodegenerative diseases

Effects of 59Fe, 65Zn and of three soil types on dry matter yield, chemical composition and nitrogen fixation in Phaseolus vulgaris L. cv. carioca

The aim of this work was to study in greenhouse conditions the effects of two levels of iron and zinc on yield and chemical composition of common bean (Phaseolus vulgaris L.) and on atmospheric nitrogen fixation, in three soils, classified as Terra Roxa Estruturada (TRE), Latossol Vermelho Escuro (LVE), and Podzolico Vermelho Amarelo (PVA). The coefficient of utilization of these micronutrients by this crop and its distribution in above-ground parts and roots were also assessed. The rates for iron were 1.5 and 3.0 ppm, and for zinc, 2.5 and 5.0 ppm. It was applied 7.5 µCi of 59Fe/kg of soil with the lower rate of the stable iron, and 5.0 and 10.0 µCi of Zn/kg of soil in the pots corresponding to the lower and higher rate of the stable zinc, respectively. The plants were harveste at the age of 60 days and nitrogen, phosphorus, potassium, iron and zinc contents were determined. Immediately after harvest, symbiotic nitrogen fixation was assessed, using the acetylene reduction method. The detection of 59Fe and 65zn radioactivity were carried out on nitric percloric extract, by gamma ray spectrometry. The behavior of common bean presented high variation among the three soils, for all the variables. There was no influence of treatments of iron and zinc on dry matter of above ground part and root and also on the weight and number of nodules. The rate of 3.0 ppm of iron decreased the capacity of nodules to fix atmospheric nitrogen in relation to rate of 1.5 ppm, while the rate of 5.0 ppm of zinc increased this capacity, in relation to the rate of 2.5 ppm. There was significative effect of treatments on nitrogen, potassium and zinc contents in above ground part and on nitrogen and zinc contents in the root. The absorption of zinc from the fertilizer and the percentagem of zinc in the plant derived from fertilizer were diretly influenced by rate of zinc The higher coefficient of utilization of zinc from the fertilizer was 4.0%.No presente trabalho, conduzido em casa de vegetação, procuramos estudar os efeitos dos micronutrientes ferro e zinco na produção de materia seca, composição química do feijoeiro (Phaseolus vulgaris L.) e na fixação do nitrogênio atmosférico, em três solos, classificados como Terra Roxa Estruturada (TRE), Latossol Vermelho Escuro (LVE) e Podzólico Vermelho Amarelo (PVA). Procuramos também determinar os índices de aproveitamento destes micronutrientes pelo feijoeiro e sua distribuição na parte aérea e na raiz. O delineamento experimental foi um fatorial 3x7, sendo três solos e sete tratamentos por solo, com três repetições. Nos tratamentos, foram utilizados duas doses de ferro e duas doses de zinco em separado ou combinando as doses menores e maiores destes micronutrientes (Fe1Zn1, Fe2Zn2). As doses de ferro foram 1,5 e 3,0 ppm e as de zinco foram 2,5 e 5,0 ppm. Foram aplicados 7,5 µCi de 59Fe/kg de solo nos vasos correspondentes à dose menor de ferro e 5,0 e 10,0 µCi de 65Zn/kg de solo nos vasos correspondentes respectivamente à dose menor e maior de zinco. Todos os tratamentos receberam uma adubação básica. O comportamento do feijoeiro apresentou grande variação entre os três tipos de solos, para todas as variáveis. Não houve influência dos tratamentos de ferro e zinco na produção de parte aérea e raiz e nem no peso e numero dos nodulos. A dose de 3,0 ppm de ferro diminuiu a capacidade dos nódulos de fixarem nitrogênio atmosférico em relação à dose de 1,5 ppm enquanto que a dose de 5,0 ppm de zinco aumentou esta capacidade, em relação à dose de 2,5 ppm. Houve um efeito significativo dos tratamentos na concentração de nitrogênio, potássio, ferro e zinco na parte aérea e na concentração de nitrogênio, e zinco na raiz. A absorção de zinco dos fertilizantes e a percentagem do zinco na planta proveniente do adubo foram influenciadas diretamente pelas doses de zinco. O maior coeficiente de aproveitamento do zinco do adubo foi de 4,0%

DNA repair gene polymorphisms and genetic predisposition to cutaneous melanoma

The incidence of cutaneous melanoma is rising rapidly in a number of countries. The key environmental risk factor is exposure to the ultraviolet (UV) component in sunlight. The nucleotide excision repair (NER) pathway deals with the main forms of UV-induced DNA damage. We have investigated the hypothesis that polymorphisms in NER genes constitute genetic susceptibility factors for melanoma. However, not all melanomas arise on sun-exposed sites and so we investigated the hypothesis that genes involved in other pathways for the repair of oxidative DNA damage may also be involved in susceptibility to melanoma. Scotland, with its high incidence of melanoma and stable homogeneous population, was ideal for this case-control study, involving 596 Scottish melanoma patients and 441 population-based controls. Significant associations were found for the NER genes ERCC1 and XPF, with the strongest associations for melanoma cases aged 50 and under [ERCC1 odds ratio (OR) 1.59, P = 0.008; XPF OR 1.69, P = 0.003]. Although an XPD haplotype was associated with melanoma, it did not contain the variant 751 Gln allele, which has been associated with melanoma in some previous studies. No associations were found for the base excision repair and DNA damage response genes investigated. An association was also found for a polymorphism in the promoter of the vitamin D receptor gene, VDR (OR 1.88, P = 0.005). The products of the two NER genes, ERCC1 and XPF, where associations with melanoma were found, act together in a rate-limiting step in the repair pathwa

Geomorphology and earth system science

Earth system science is an approach to obtain a scientific understanding of the entire Earth system on a global scale by describing how its component parts and their interactions have evolved, how they function, and how they may be expected to continue to evolve on all time-scales. The aim of this review is to introduce some key examples showing the role of earth surface processes, the traditional subject of geomorphology, within the interacting Earth system. The paper considers three examples of environmental systems in which geomorphology plays a key role: (i) links between topography, tectonics, and atmospheric circulation; (ii) links between geomorphic processes and biogeochemical cycles; and (iii) links between biological processes and the earth’s surface. Key research needs are discussed, including the requirement for better opportunities for interdisciplinary collaboration, clearer mathematical frameworks for earth system models, and more sophisticated interaction between natural and social scientists