Natural streamflow regime alterations: Damming of the Piave river basin (Italy)

A novel approach is proposed to estimate the natural streamflow regime of a river and to assess the extent of the alterations induced by dam operation related to anthropogenic (e.g., agricultural, hydropower) water uses in engineered river basins. The method consists in the comparison between the seasonal probability density function (pdf) of observed streamflows and the purportedly natural streamflow pdf obtained by a recently proposed and validated probabilistic model. The model employs a minimum of landscape and climate parameters and unequivocally separates the effects of anthropogenic regulations from those produced by hydroclimatic fluctuations. The approach is applied to evaluate the extent of the alterations of intra-annual streamflow variability in a highly engineered alpine catchment of north-eastern Italy, the Piave river. Streamflows observed downstream of the regulation devices in the Piave catchment are found to exhibit smaller means/modes, larger coefficients of variation, and more pronounced peaks than the flows that would be observed in the absence of anthropogenic regulation, suggesting that the anthropogenic disturbance leads to remarkable reductions of river flows, with an increase of the streamflow variability and of the frequency of preferential states far from the mean. Some structural limitations of management approaches based on minimum streamflow requirements (widely used to guide water policies) as opposed to criteria based on whole distributions are also discussed. Copyright © 2010 by the American Geophysical Union.

Morphological characteristics of urban water bodies: mechanisms of change and implications for ecosystem function.

The size, shape, and connectivity of water bodies (lakes, ponds, and wetlands) can have important effects on ecological communities and ecosystem processes, but how these characteristics are influenced by land use and land cover change over broad spatial scales is not known. Intensive alteration of water bodies during urban development, including construction, burial, drainage, and reshaping, may select for certain morphometric characteristics and influence the types of water bodies present in cities. We used a database of over one million water bodies in 100 cities across the conterminous United States to compare the size distributions, connectivity (as intersection with surface flow lines), and shape (as measured by shoreline development factor) of water bodies in different land cover classes. Water bodies in all urban land covers were dominated by lakes and ponds, while reservoirs and wetlands comprised only a small fraction of the sample. In urban land covers, as compared to surrounding undeveloped land, water body size distributions converged on moderate sizes, shapes toward less tortuous shorelines, and the number and area of water bodies that intersected surface flow lines (i.e., streams and rivers) decreased. Potential mechanisms responsible for changing the characteristics of urban water bodies include: preferential removal, physical reshaping or addition of water bodies, and selection of locations for development. The relative contributions of each mechanism likely change as cities grow. The larger size and reduced surface connectivity of urban water bodies may affect the role of internal dynamics and sensitivity to catchment processes. More broadly, these results illustrate the complex nature of urban watersheds and highlight the need to develop a conceptual framework for urban water bodies.

Enhanced de novo alloantibody and antibody-mediated injury in rhesus macaques.

Chronic allograft rejection is a major impediment to long-term transplant success. Humoral immune responses to alloantigens are a growing clinical problem in transplantation, with mounting evidence associating alloantibodies with the development of chronic rejection. Nearly a third of transplant recipients develop de novo antibodies, for which no established therapies are effective at preventing or eliminating, highlighting the need for a nonhuman primate model of antibody-mediated rejection. In this report, we demonstrate that depletion using anti-CD3 immunotoxin (IT) combined with maintenance immunosuppression that included tacrolimus with or without alefacept reliably prolonged renal allograft survival in rhesus monkeys. In these animals, a preferential skewing toward CD4 repopulation and proliferation was observed, particularly with the addition of alefacept. Furthermore, alefacept-treated animals demonstrated increased alloantibody production (100%) and morphologic features of antibody-mediated injury. In vitro, alefacept was found to enhance CD4 effector memory T cell proliferation. In conclusion, alefacept administration after depletion and with tacrolimus promotes a CD4+memory T cell and alloantibody response, with morphologic changes reflecting antibody-mediated allograft injury. Early and consistent de novo alloantibody production with associated histological changes makes this nonhuman primate model an attractive candidate for evaluating targeted therapeutics.

Release of outer membrane vesicles by Gram-negative bacteria is a novel envelope stress response.

Conditions that impair protein folding in the Gram-negative bacterial envelope cause stress. The destabilizing effects of stress in this compartment are recognized and countered by a number of signal transduction mechanisms. Data presented here reveal another facet of the complex bacterial stress response, release of outer membrane vesicles. Native vesicles are composed of outer membrane and periplasmic material, and they are released from the bacterial surface without loss of membrane integrity. Here we demonstrate that the quantity of vesicle release correlates directly with the level of protein accumulation in the cell envelope. Accumulation of material occurs under stress, and is exacerbated upon impairment of the normal housekeeping and stress-responsive mechanisms of the cell. Mutations that cause increased vesiculation enhance bacterial survival upon challenge with stressing agents or accumulation of toxic misfolded proteins. Preferential packaging of a misfolded protein mimic into vesicles for removal indicates that the vesiculation process can act to selectively eliminate unwanted material. Our results demonstrate that production of bacterial outer membrane vesicles is a fully independent, general envelope stress response. In addition to identifying a novel mechanism for alleviating stress, this work provides physiological relevance for vesicle production as a protective mechanism.

Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery.

Intratumoral B lymphocytes are an integral part of the lung tumor microenvironment. Interrogation of the antibodies they express may improve our understanding of the host response to cancer and could be useful in elucidating novel molecular targets. We used two strategies to explore the repertoire of intratumoral B cell antibodies. First, we cloned VH and VL genes from single intratumoral B lymphocytes isolated from one lung tumor, expressed the genes as recombinant mAbs, and used the mAbs to identify the cognate tumor antigens. The Igs derived from intratumoral B cells demonstrated class switching, with a mean VH mutation frequency of 4%. Although there was no evidence for clonal expansion, these data are consistent with antigen-driven somatic hypermutation. Individual recombinant antibodies were polyreactive, although one clone demonstrated preferential immunoreactivity with tropomyosin 4 (TPM4). We found that higher levels of TPM4 antibodies were more common in cancer patients, but measurement of TPM4 antibody levels was not a sensitive test for detecting cancer. Second, in an effort to focus our recombinant antibody expression efforts on those B cells that displayed evidence of clonal expansion driven by antigen stimulation, we performed deep sequencing of the Ig genes of B cells collected from seven different tumors. Deep sequencing demonstrated somatic hypermutation but no dominant clones. These strategies may be useful for the study of B cell antibody expression, although identification of a dominant clone and unique therapeutic targets may require extensive investigation.