Biallelic inactivation of BRCA2 in Fanconi anemia

Fanconi anemia (FA) is a rare autosomal recessive cancer susceptibility disorder characterized by cellular hypersensitivity to mitomycin C (MMC). Six FA genes have been cloned, but the gene or genes corresponding to FA subtypes B and D1 remain unidentified. Here we show that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins. Functional complementation of FA-D1 fibroblasts with wild-type BRCA2 complementary DNA restores MMC resistance. Our results link the six cloned FA genes with BRCA1 and BRCA2 in a common pathway. Germ-line mutation of genes in this pathway may result in cancer risks similar to those observed in families with BRCA1 or BRCA2 mutations.     

Receptor-coupled activation of phosphoinositide-specific phospholipase C by an N protein

Cleavage of phosphatidylinositol 4,5-bisphosphate by phospholipase C results in the production of two important second messengers: inositol-1,4,5-trisphosphate and 1,2-diacylglycerol. Although several receptors promote this cleavage, the molecular details of phospholipase C activation have remained unresolved. In this study, occupancy of a Ca2+-mobilizing receptor, the oligopeptide chemoattractant receptor on human polymorphonuclear leukocyte plasma membranes, was found to lead to the activation of a guanine nucleotide regulatory (N) protein by guanosine 5'-triphosphate. The activated N protein then stimulated a polyphosphoinositide-specific phospholipase C by reducing the Ca2+ requirement for expression of this activity from superphysiological to normal intracellular concentrations. Therefore, the N protein-mediated activation of phospholipase C may be a key step in the pathway of cellular activation by chemoattractants and certain other hormones.     

Antigen presentation requires transport of MHC class I molecules from the endoplasmic reticulum

The role of exocytosis of major histocompatibility complex (MHC) class I molecules in the presentation of antigens to mouse cytotoxic T lymphocytes (CTLs) was examined by use of a recombinant vaccinia virus that expresses the E19 glycoprotein from adenovirus. E19 blocked the presentation of vaccinia and influenza virus proteins to CTLs in a MHC class I allele-specific manner identical to its inhibition of MHC class I transport from the endoplasmic reticulum. This finding indicates that (i) the relevant parameter for antigen presentation is the rate of MHC class I molecule exocytosis, not the level of class I cell surface expression, and (ii) association of class I molecules with antigen is likely to occur within the endoplasmic reticulum.     

Early biochemical effects of an organic mercury fungicide on infants: "dose makes the poison"

Phenylmercury absorbed through the skin from contaminated diapers affected urinary excretion in infants in Buenos Aires. The effects were reversible and quantitatively related to the concentration of urinary mercury. Excretion of gamma-glutamyl transpeptidase, an enzyme in the brush borders of renal tubular cells, increased in a dose-dependent manner when mercury excretion exceeded a "threshold" value. Urine volume also increased but at a higher threshold with respect to mercury. The results support the threshold concept of the systemic toxicity of metals. gamma-Glutamyl transpeptidase is a useful and sensitive marker for preclinical effects of toxic metals.     

East pacific rise: hot springs and geophysical experiments

Hydrothermal vents jetting out water at 380 degrees +/- 30 degrees C have been discovered on the axis of the East Pacific Rise. The hottest waters issue from mineralized chimneys and are blackened by sulfide precipitates. These hydrothermal springs are the sites of actively forming massive sulfide mineral deposits. Cooler springs are clear to milky and support exotic benthic communities of giant tube worms, clams, and crabs similar to those found at the Galápagos spreading center. Four prototype geophysical experiments were successfully conducted in and near the vent area: seismic refraction measurements with both source (thumper) and receivers on the sea floor, on-bottom gravity measurements, in situ magnetic gradiometer measurements from the submersible Alvin over a sea-floor magnetic reversal boundary, and an active electrical sounding experiment. These high-resolution determinations of crustal properties along the spreading center were made to gain knowledge of the source of new oceanic crust and marine magnetic anomalies, the nature of the axial magma chamber, and the depth of hydrothermal circulation.     

Experimental evaluation of foot-and-mouth disease vaccines for emergency use in ruminants and pigs: a review

Changes to foot-and-mouth disease (FMD) control policies since 2001 mean that emergency vaccination must be considered more readily as a control measure in the future. Since field application of vaccine for emergency use has only rarely been applied, the effectiveness of single dose administration, as a control measure in an outbreak situation, is poorly understood. In this review we consider all the available experimental data from studies utilizing either experimental or readily available, commercially produced vaccines, in order to assess their likely effectiveness as an additional means of controlling FMD transmission and spread in an emergency. Overall it is concluded that such vaccines offer an additional and valuable means of FMD control for both ruminants and pigs. They are able to reduce clinical disease, sub-clinical infection and excretion and onward transmission of virus. However, to be most effective, vaccination should be rapidly applied to give maximum opportunity for immunity to develop. We also identify areas for future research and emphasize the importance of vaccine efficacy studies in providing data for models that can help to predict the efficacy of differing FMD control strategies.     

Modelling soil water and salt dynamics under pulsed and continuous surface drip irrigation of almond and implications of system design

The HYDRUS-2D model was experimentally verified for water and salinity distribution during the profile establishment stage (33?days) of almond under pulsed and continuous drip irrigation. The model simulated values of water content obtained at different lateral distances (0, 20, 40, 60, 100?cm) from a dripper at 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140 and 160?cm soil depths at different times (5, 12, 19, 26 and 33?days of profile establishment) were compared with neutron probe measured values under both irrigation scenarios. The model closely predicted water content distribution at all distances, times and soil depths as RMSE values ranged between 0.017 and 0.049. The measured mean soil water salinity (ECsw) at 25?cm from the dripper at 30, 60, 90 and 150?cm soil depth also matched well with the predicted values. A correlation of 0.97 in pulsed and 0.98 in continuous drip systems with measured values indicated the model closely predicted total salts in the root zone. Thus, HYDRUS-2D successfully simulated the change in soil water content and soil water salinity in both the wetting pattern and in the flow domain. The initial mean ECsw below the dripper in pulsed (5.25?dSm^?1) and continuous (6.07?dSm^?1) irrigations decreased to 1.31 and 1.36?dSm^?1, respectively, showing a respective 75.1 and 77.6% decrease in the initial salinity. The power function [y?=?ax ^?b ] best described the mathematical relationship between salt removal from the soil profile as a function of irrigation time under both irrigation scenarios. Contrary to other studies, higher leaching fraction (6.4–43.1%) was recorded in pulsed than continuous (1.1–35.1%) irrigation with the same amount of applied water which was brought about by the variation in initial soil water content and time of irrigation application. It was pertinent to note that a small (0.012) increase in mean antecedent water content (θ _i ) brought about 8.25–9.06% increase in the leaching fraction during the profile establishment irrespective of the emitter geometry, discharge rate, and irrigation scenario. Under similar θ _i , water applied at a higher discharge rate (3.876?Lh^?1) has resulted in slightly higher leaching fraction than at a low discharge rate (1.91?Lh^?1) under pulsing only owing to the variation in time of irrigation application. The influence of pulsing on soil water content, salinity distribution, and drainage flux vanished completely when irrigation was applied daily on the basis of crop evapotranspiration (ETc) with a suitable leaching fraction. Therefore, antecedent soil water content and scheduling or duration of water application play a significant role in the design of drip irrigation systems for light textured soils. These factors are the major driving force to move water and solutes within the soil profile and may influence the off-site impacts such as drainage flux and pollution of the groundwater.