A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability.

Two major isoforms of aquaporin-4 (AQP4) have been described in human tissue. Here we report the identification and functional analysis of an alternatively spliced transcript of human AQP4, AQP4-Δ4, that lacks exon 4. In transfected cells AQP4-Δ4 is mainly retained in the endoplasmic reticulum and shows no water transport properties. When AQP4-Δ4 is transfected into cells stably expressing functional AQP4, the surface expression of the full-length protein is reduced. Furthermore, the water transport activity of the cotransfectants is diminished in comparison to transfectants expressing only AQP4. The observed down-regulation of both the expression and water channel activity of AQP4 is likely to originate from a dominant-negative effect caused by heterodimerization between AQP4 and AQP4-Δ4, which was detected in coimmunoprecipitation studies. In skeletal muscles, AQP4-Δ4 mRNA expression inversely correlates with the level of AQP4 protein and is physiologically associated with different types of skeletal muscles. The expression of AQP4-Δ4 may represent a new regulatory mechanism through which the cell-surface expression and therefore the activity of AQP4 can be physiologically modulated

Alternate Solutions to Water Resource Development -- A Case Study

This study was undertaken in an effort to develop procedural methodology for the consideration of alternative solutions for water resources development in a short period of time with a view toward reduction of total costs involved in prefeasibility studies. A review of related literature was made to reveal the status of the need for the development of a comprehensive method to evaluate possible alternatives. Three techniques were developed in this research effort to estimate the investment costs of a reservoir project, a levee project, and a basin conservation reservoir project in an economic region. The application of the methodologies were illustrated by a case study. The cost of a reservoir project in the case study area determined by the method developed in this investigation was in excellent agreement with the Corps of Engineers' estimate using conventional methods. In general, the dependability of all the three methodologies were considered good for use in order-ofmagnitude estimates. Selected solutions for water resources development problems in the Navasota River watershed were analyzed. The cost of water supply by desalination in the service area of the proposed Millican reservoir was computed following the procedure recommended by the Office of Saline Water. The investment costs of the alternatives were compared. The multipurpose reservoir project for flood control, water supply and recreation was found to be the least costly project. However, levees for flood protection in the lower Brazos River basin and desalting for water supply appeared to possess more intangible environmental benefits although the estimated cost of this multipurpose alternative was somewhat higher in comparison to the multipurpose reservoir project. Evaluation of intangible cost factors (environmental, aesthetic, etc.) was not possible in want of scientifically amenable procedures. Total costs (combined tangible and intangible factors) of all alternative plans could not be estimated. As a result, no attempt was made to recommend any specific alternative to the proposed action in the case study area

General Statistical properties of the CMB Polarization field

The distribution of the polarization of the Cosmic Microwave Background (CMB) in the sky is determined by the hypothesis of random Gaussian distribution of the primordial density perturbations. This hypotheses is well motivated by the inflationary cosmology. Therefore, the test of consistency of the statistical properties of the CMB polarization field with the Gaussianity of primordial density fluctuations is a realistic way to study the nature of primordial inhomogeneities in the Universe. This paper contains the theoretical predictions of the general statistical properties of the CMB polarization field. All results obtained under assumption of the Gaussian nature of the signal. We pay the special attention to the following two problems. First, the classification and statistics of the singular points of the polarization field where polarization is equal to zero. Second, the topology of contours of the value of the degree of polarization. We have investigated the percolation properties for the zones of ``strong'' and ``weak'' polarization. We also have calculated Minkowski functionals for the CMB polarization field. All results are analytical.Comment: Latex, 22 pages, including 5 figure

Klf6 protects β-cells against insulin resistance-induced dedifferentiation.

In the pathogenesis of type 2 diabetes, development of insulin resistance triggers an increase in pancreatic β-cell insulin secretion capacity and β-cell number. Failure of this compensatory mechanism is caused by a dedifferentiation of β-cells, which leads to insufficient insulin secretion and diabetic hyperglycemia. The β-cell factors that normally protect against dedifferentiation remain poorly defined. Here, through a systems biology approach, we identify the transcription factor Klf6 as a regulator of β-cell adaptation to metabolic stress. We used a β-cell specific Klf6 knockout mouse model to investigate whether Klf6 may be a potential regulator of β-cell adaptation to a metabolic stress. We show that inactivation of Klf6 in β-cells blunts their proliferation induced by the insulin resistance of pregnancy, high-fat high-sucrose feeding, and insulin receptor antagonism. Transcriptomic analysis showed that Klf6 controls the expression of β-cell proliferation genes and, in the presence of insulin resistance, it prevents the down-expression of genes controlling mature β-cell identity and the induction of disallowed genes that impair insulin secretion. Its expression also limits the transdifferentiation of β-cells into α-cells. Our study identifies a new transcription factor that protects β-cells against dedifferentiation, and which may be targeted to prevent diabetes development

World Antimalarial Resistance Network (WARN) II: In vitro antimalarial drug susceptibility

Intrinsic resistance of Plasmodium falciparum is clearly a major determinant of the clinical failure of antimalarial drugs. However, complex interactions between the host, the parasite and the drug obscure the ability to define parasite drug resistance in vivo. The in vitro antimalarial drug susceptibility assay determines ex-vivo growth of parasite in the presence of serial drug concentrations and, thus, eliminates host effects, such as drug metabolism and immunity. Although the sensitivity of the parasite to various antimalarials provided by such a test provides an important indicator of intrinsic parasite susceptibility, there are fundamental methodological issues that undermine comparison of in vitro susceptibility both between laboratories and within a single laboratory over time. A network of laboratories is proposed that will agree on the basic parameters of the in vitro test and associated measures of quality control. The aim of the network would be to establish baseline values of sensitivity to commonly used antimalarial agents from key regions of the world, and create a global database, linked to clinical, molecular and pharmacology databases, to support active surveillance to monitor temporal trends in parasite susceptibility. Such a network would facilitate the rapid detection of strains with novel antimalarial resistance profiles and investigate suitable alternative treatments with retained efficacy

The Role of Trait and State Perfectionism in Psychological Detachment From Daily Job Demands

Psychological detachment has been proposed to be a mediator of the relations between an individual's responses to stressful work-related experiences and mid- and long-term health. However, the number of studies that have specifically examined the role that personal characteristics play in these associations is considerably small. One personal characteristic that might specifically interfere with psychological detachment is perfectionism, which has been considered an important vulnerability factor for the development of psychological disorders. Hence, the goal of this registered report was to extend research on psychological detachment by introducing trait and state perfectionism as moderators of the aforementioned relations. We conducted an experience sampling study with three measurement occasions per day over the course of 3 working weeks (N = 158 employees; Mage = 41.6; 67% women). Multilevel path models showed that perfectionistic concerns consistently determined strain responses at between- and within-levels of analyses even after the effects of job demands (i.e., unfinished tasks and role ambiguity) and detachment were accounted for. However, we found no evidence for the proposed moderation effects. The theoretical implications for the understanding of the processes proposed in the stressor-detachment model are discussed

The feasibility of milkfish (Chanos chanos) aquaculture in Solomon Islands

Fish is crucial to food and nutrition security in Solomon Islands, and demand is expected to increase due to a growing population. However, it is projected that current capture fisheries production will not meet this growing demand. Aquaculture has the potential to mitigate the capture fishery shortfall, and the Government of Solomon Islands is prioritizing aquaculture as a solution to meet future food and income needs. Aquaculture in Solomon Islands is still in early development. Mozambique tilapia (Oreochromis mossambicus) is farmed for household consumption, but its prolific reproductive rate and resulting slow growth limit its potential as a commercial aquaculture species. More productive fish species that are not indigenous to Solomon Islands but are successfully farmed overseas could be introduced; however, such a decision needs to take into account the potential ecological or social impacts. For land-based pond aquaculture, the only indigenous species that has been farmed extensively elsewhere is milkfish (Chanos chanos). This report presents a feasibility assessment for milkfish farming in Solomon Islands. It synthesizes the current knowledge about milkfish farming and presents results of a 4-year study on the potential for milkfish aquaculture in Solomon Islands

Absence of Aquaporin-4 in Skeletal Muscle Alters Proteins Involved in Bioenergetic Pathways and Calcium Handling

Aquaporin-4 (AQP4) is a water channel expressed at the sarcolemma of fast-twitch skeletal muscle fibers, whose expression is altered in several forms of muscular dystrophies. However, little is known concerning the physiological role of AQP4 in skeletal muscle and its functional and structural interaction with skeletal muscle proteome. Using AQP4-null mice, we analyzed the effect of the absence of AQP4 on the morphology and protein composition of sarcolemma as well as on the whole skeletal muscle proteome. Immunofluorescence analysis showed that the absence of AQP4 did not perturb the expression and cellular localization of the dystrophin-glycoprotein complex proteins, aside from those belonging to the extracellular matrix, and no alteration was found in sarcolemma integrity by dye extravasation assay. With the use of a 2DE-approach (BN/SDS-PAGE), protein maps revealed that in quadriceps, out of 300 Coomassie-blue detected and matched spots, 19 proteins exhibited changed expression in AQP4−/− compared to WT mice. In particular, comparison of the protein profiles revealed 12 up- and 7 down-regulated protein spots in AQP4−/− muscle. Protein identification by MS revealed that the perturbed expression pattern belongs to proteins involved in energy metabolism (i.e. GAPDH, creatine kinase), as well as in Ca2+ handling (i.e. parvalbumin, SERCA1). Western blot analysis, performed on some significantly changed proteins, validated the 2D results. Together these findings suggest AQP4 as a novel determinant in the regulation of skeletal muscle metabolism and better define the role of this water channel in skeletal muscle physiology