Hydrogeological typologies of the Indo-Gangetic basin alluvial aquifer, South Asia.

The Indo-Gangetic aquifer is one of the world's most important transboundary water resources, and the most heavily exploited aquifer in the world. To better understand the aquifer system, typologies have been characterized for the aquifer, which integrate existing datasets across the Indo-Gangetic catchment basin at a transboundary scale for the first time, and provide an alternative conceptualization of this aquifer system. Traditionally considered and mapped as a single homogenous aquifer of comparable aquifer properties and groundwater resource at a transboundary scale, the typologies illuminate significant spatial differences in recharge, permeability, storage, and groundwater chemistry across the aquifer system at this transboundary scale. These changes are shown to be systematic, concurrent with large-scale changes in sedimentology of the Pleistocene and Holocene alluvial aquifer, climate, and recent irrigation practices. Seven typologies of the aquifer are presented, each having a distinct set of challenges and opportunities for groundwater development and a different resilience to abstraction and climate change. The seven typologies are: (1) the piedmont margin, (2) the Upper Indus and Upper-Mid Ganges, (3) the Lower Ganges and Mid Brahmaputra, (4) the fluvially influenced deltaic area of the Bengal Basin, (5) the Middle Indus and Upper Ganges, (6) the Lower Indus, and (7) the marine-influenced deltaic areas.

L'aquifère de l'Indus et du Gange est une des ressources en eau transfrontalière la plus importante au monde et un des aquifères le plus exploité au monde. Pour mieux comprendre le système aquifère, des typologies ont été caractérisées pour cet aquifère ; elles intègrent pour la première fois un jeu de données disponibles sur l'ensemble du bassin de l'Indus et du Gange à une échelle transfrontalière, et apportent une conceptualisation alternative de ce système aquifère. Traditionnellement considéré et cartographié comme un simple aquifère homogène aux propriétés aquifères similaires et comme une ressource d'eau souterraine à l'échelle transfrontalière, les typologies mettent en évidence des différences significatives spatiales de la recharge, de la perméabilité, de la capacité de stockage et de la chimie des eaux souterraines sur l'ensemble du système aquifère à une échelle transfrontalière. Ces changements sont systématiques coïncidant aux changements à large échelle de la sédimentologie de l'aquifère alluvial du Pléistocène et de l'Holocène, du climat et des pratiques récentes d'irrigation. Sept typologies de l'aquifère sont présentées, chacune ayant un ensemble distinct de défis et d'opportunités pour le développement des eaux souterraines et une résilience différente à l'exploitation et au changement climatique. Les sept typologies sont: (1) la marge de piedmont, (2) Le haut Indus et le Ganges moyen supérieur, (3) le Ganges inférieur et le Brahmapoutre moyen, (4) la zone deltaïque du bassin du Bengale sous influence fluviale, (5) l'Indus moyen et le Ganges supérieur, (6) l'Indus inférieur, et (7) la zone deltaïque sous influence marine.

El acuífero Indo-Gangético es uno de los recursos hídricos transfronterizos más importantes y el acuífero más explotado del mundo. Para comprender mejor el sistema acuífero, por primera vez se han caracterizado tipologías para el acuífero, integrando los conjuntos de datos existentes a través de la cuenca hidrográfica Indo-Ganges a una escala transfronteriza, y proporcionando una conceptualización alternativa de este sistema acuífero. Tradicionalmente consideradas y cartografiadas como un solo acuífero homogéneo de propiedades acuíferas y recursos de agua subterránea comparables a escala transfronteriza, las tipologías iluminan diferencias espaciales significativas en la recarga, permeabilidad, almacenamiento y química del agua subterránea a través del sistema acuífero a esta escala transfronteriza. Estos cambios son mostrados por ser sistemáticos, coincidentes con cambios en gran escala en la sedimentología del acuífero aluvial del Pleistoceno y del Holoceno, en el clima y en las prácticas recientes de riego. Se presentan siete tipologías del acuífero, cada una con un conjunto distinto de desafíos y oportunidades para el desarrollo del agua subterránea y una diferente resiliencia a la extracción y al cambio climático. Las siete tipologías son: (1) el margen del piedemonte, (2) el Indus superior y el Ganges superior-medio, (3) el Ganges inferior y el Brahmaputra medio, (4) el área deltaica fluvialmente influenciada de la cuenca de Bengala, (5) el Ganges superior, (6) el Indo Inferior, y (7) las áreas deltaicas con influencia marina.

O aquífero do Indo-Gangético é um dos recursos hídricos transfronteiriços mais importantes do mundo, e o mais explorado. Para melhor entender o sistema aquífero, tipologias foram caracterizadas para o aquífero, que integram pela primeira vez bancos de dados existentes sobre a bacia de abastecimento Indo-Gangética em uma escala transfornteiriça, e fornecem uma conceptualização alternativa desse sistema aquífero. Tradicionalmente considerado e mapeado como um aquífero homogêneo de propriedades aquíferas comparáveis e recursos subterrâneos em escala transfronteiriça, as tipologias elucidam diferenças espaciais significantes na recarga, permeabilidade, armazenamento, e química das águas subterrâneas pelo aquífero nessa escala transfronteiriça. Essas mudanças aparentam ser sistemáticas, concorrentes com mudanças em larga escala na sedimentologia do aquífero aluvial do Pleistoceno e Holoceno, clima e práticas recentes de irrigação. Sete tipologias do aquífero são apresentadas, cada uma tendo conjuntos de desafios e oportunidades distintos para o desenvolvimento das águas subterrâneas e uma resiliência diferente nas mudanças de extração e clima. As sete tipologias são: (1) a margem piemonte, (2) O Alto Indo e o Alto-médio Ganges, (3) O Baixo Ganges e o Médio Brahmaputra, (4) a área deltaica influenciada fluvialmente da Bacia de Bengala, (5) o Médio Indo e o Alto Ganges, (6) o Baixo Indo, e (7) as áreas deltaicas com influencia marinha.

Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair.

Histone deacetylase inhibitors (HDACi) developed as anti-cancer agents have a high degree of selectivity for killing cancer cells. HDACi induce acetylation of histones and nonhistone proteins, which affect gene expression, cell cycle progression, cell migration, and cell death. The mechanism of the tumor selective action of HDACi is unclear. Here, we show that the HDACi, vorinostat (Suberoylanilide hydroxamic acid, SAHA), induces DNA double-strand breaks (DSBs) in normal (HFS) and cancer (LNCaP, A549) cells. Normal cells in contrast to cancer cells repair the DSBs despite continued culture with vorinostat. In transformed cells, phosphorylated H2AX (gammaH2AX), a marker of DNA DSBs, levels increased with continued culture with vorinostat, whereas in normal cells, this marker decreased with time. Vorinostat induced the accumulation of acetylated histones within 30 min, which could alter chromatin structure-exposing DNA to damage. After a 24-h culture of cells with vorinostat, and reculture without the HDACi, gammaH2AX was undetectable by 2 h in normal cells, while persisting in transformed cells for the duration of culture. Further, we found that vorinostat suppressed DNA DSB repair proteins, e.g., RAD50, MRE11, in cancer but not normal cells. Thus, the HDACi, vorinostat, induces DNA damage which normal but not cancer cells can repair. This DNA damage is associated with cancer cell death. These findings can explain, in part, the selectivity of vorinostat in causing cancer cell death at concentrations that cause little or no normal cell death.

Neuron-glia interactions underlie ALS-like axonal cytoskeletal pathology.

Amyotrophic lateral sclerosis (ALS) is a devastating disorder involving loss of movement due to degeneration of motor neurons. Studies suggest that in ALS axonal dysfunction precedes the death of motor neurons. Pathologically, ALS is characterized by neurofilamentous swellings (spheroids) within the axons of motor neurons. However, the causes of this axonopathy and possible resulting axonal dysfunction are not known. Using a novel model of cultured mouse motor neurons, we have determined that these neurons are susceptible to proximal axonopathy, which is related to the glial environment. This axonopathy showed remarkable similarity, both morphologically and neurochemically, to spheroids that develop over months in SOD1(G93A) transgenic mice. Focal ubiquitination, as well as perturbations of neurofilaments and microtubules, occurred in the axonal spheroid-like swellings in vitro, and visualization of mitochondrial dynamics demonstrated that axonopathy resulted in impaired axonal transport. These data provide strong evidence for the involvement of non-neuronal cells in axonal dysfunction in ALS. This cell culture model may be of benefit for the development of therapeutic interventions directed at axonal preservation.

Excitotoxicity mediated by non-NMDA receptors causes distal axonopathy in long-term cultured spinal motor neurons.

Excitotoxicity has been implicated as a potential cause of neuronal degeneration in amyotrophic lateral sclerosis (ALS). It has not been clear how excitotoxic injury leads to the hallmark pathological changes of ALS, such as the abnormal accumulation of filamentous proteins in axons. We have investigated the effects of overactivation of excitatory receptors in rodent neurons maintained in long-term culture. Excitotoxicity, mediated principally via non-N-methyl-D-aspartate (NMDA) receptors, caused axonal swelling and accumulation of cytoskeletal proteins in the distal segments of the axons of cultured spinal, but not cortical, neurons. Axonopathy only occurred in spinal neurons maintained for 3 weeks in vitro, indicating that susceptibility to axonal pathology may be related to relative maturity of the neuron. Excitotoxic axonopathy was associated with the aberrant colocalization of phosphorylated and dephosphorylated neurofilament proteins, indicating that disruption to the regulation of phosphorylation of neurofilaments may lead to their abnormal accumulation. These data provide a strong link between excitotoxicity and the selective pattern of axonopathy of lower motor neurons that underlies neuronal dysfunction in ALS.

Groundwater: the processes and global significance of aquifer degradation.

The exploitation of groundwater resources for human use dates from the earliest civilizations, but massive resource development has been largely restricted to the past 50 years. Although global in scope, the emphasis of this paper is on groundwater-based economies in a developing nation context, where accelerated resource development has brought major social and economic benefits over the past 20 years. This results from groundwater's significant role in urban water supply and in rural livelihoods, including irrigated agriculture. However, little of the economic benefit of resource development has been reinvested in groundwater management, and concerns about aquifer degradation and resource sustainability began to arise. A general review, for a broad-based audience, is given of the mechanisms and significance of three semi-independent facets of aquifer degradation. These are (i) depletion of aquifer storage and its effects on groundwater availability, terrestrial and aquatic ecosystems; (ii) groundwater salinization arising from various different processes of induced hydraulic disturbance and soil fractionation; and (iii) vulnerability of aquifers to pollution from land-use and effluent discharge practices related to both urban development and agricultural intensification. Globally, data with which to assess the status of aquifer degradation are of questionable reliability, inadequate coverage and poor compilation. Recourse has to be made to 'type examples' and assumptions about the extension of similar hydrogeological settings likely to be experiencing similar conditions of groundwater demand and subsurface contaminant load. It is concluded that (i) aquifer degradation is much more than a localized problem because the sustainability of the resource base for much of the rapid socio-economic development of the second half of the twentieth century is threatened on quite a widespread geographical basis; and (ii) major (and long overdue) investments in groundwater resource and quality protection are urgently needed. These investments include appropriate institutional provisions, demand-side management, supply-side enhancement and pollution control.