Involvement of PL-D in the alternate signal tranduction pathway of macrophages induced by an exernal stimulus

The alternate pathway of signal transduction via hydrolysis of phosphatidylcholine, the major cellular phospholipid, has been investigated in murine peritoneal macrophages. A sustained formation of diacylglycerol, is preceded by an enhanced production of phosphatidic acid, when the macrophages were given a stimulus with 12-O-tetradecanoyl phorbol-13-acetate for sixty minutes. Production of choline and choline metabolites are significantly increased too. Propranolol, which inhibits phosphatidate phosphohydrolase, the enzyme responsible for conversion of phosphatidic acid to diacylglycerol, can effectively block the formation of diacylglycerol. Inhibition of protein kinase C either by its inhibitors, staurosporine and H-7 or by depletion, apparently affect the generation of the lipid products. Moreover, based on the results of transphosphatidylation reaction, involvement of a phospholipase D in the phosphatidylcholine-hydrolytic pathway in macrophages is predicted. These observations support the view that probably the phorbol ester acting directly on protein kinase C of the macrophages activate their phosphatidylcholine-specific phospholipase D to allow a steady generation of second messengers, to enable them to participate in the cell signalling process in a more efficient manner than those generated in the phosphoinositide pathway of signal transduction. (Mol Cell Biochem 000: 000-000,1999)     

Embryogenesis and plant regeneration from callus cultures derived from unpollinated ovaries of Hyoscyamus muticus L.

Unpollinated ovaries of Hyoscyamus muticus L. (commonly known as Egyptian henbane) were cultured on Murashige and Skoog and Bourgin and Nitsch media supplemented with various growth hormones to study the organogenesis, embryogenesis and regeneration of plantlets. Embryogenesis was reported for callus grown on both media containing 0.05 mg/l α-naphthaleneacetic acid and 0.5 mg/l 6-benzylaminopurine. Differentiation of roots and shoots from the calli also occurred in these media. Albinism or chlorophyll deficiency and variation in ploidy level were observed among the ovary-derived plantlets. Received: 7 April 1997 / Revised received: 2 August 1997 / Accepted: 2 September 1997     

The Des-1 protein, required for central spindle assembly and cytokinesis, is associated with mitochondria along the meiotic spindle apparatus and with the contractile ring during male meiosis in Drosophila melanogaster

Spermatogenesis in Drosophila melanogaster serves as an excellent model system for the isolation and analysis of genes required in the control of chromosome segregation and cytokinesis. We report here the isolation and molecular characterization of a novel P-element induced allele of the des-1 gene, which leads to male sterility as a consequence of the failure of central spindle assembly in meiotic spermatocytes and the formation of aberrant meiotic end products characteristic of cytokinesis failure. We have raised affinity-purified antibodies against a Des-1 fusion protein, and localized the Des-1 protein in Drosophila spermatocytes. We show that the Des-1 protein is colocalized with mitochondria throughout male meiosis, becoming intimately associated with mitochondria along the spindle apparatus during anaphase and telophase, and with the Nebenkern, or mitochondrial derivative, of the meiotic end products. In addition, a significant association of Des-1 with the contractile ring is observed during anaphase and telophase of meiosis. These observations, together with the presence of six potential transmembrane domains in the Des-1 protein, raise the possibility that Des-1 may act as part of an anchoring mechanism that links membrane-bounded cellular compartments to components of the cytoskeleton.     

Catchment Legacies and Time Lags: A Parsimonious Watershed Model to Predict the Effects of Legacy Storage on Nitrogen Export

Nutrient legacies in anthropogenic landscapes, accumulated over decades of fertilizer application, lead to time lags between implementation of conservation measures and improvements in water quality. Quantification of such time lags has remained difficult, however, due to an incomplete understanding of controls on nutrient depletion trajectories after changes in land-use or management practices. In this study, we have developed a parsimonious watershed model for quantifying catchment-scale time lags based on both soil nutrient accumulations (biogeochemical legacy) and groundwater travel time distributions (hydrologic legacy). The model accurately predicted the time lags observed in an Iowa watershed that had undergone a 41% conversion of area from row crop to native prairie. We explored the time scales of change for stream nutrient concentrations as a function of both natural and anthropogenic controls, from topography to spatial patterns of land-use change. Our results demonstrate that the existence of biogeochemical nutrient legacies increases time lags beyond those due to hydrologic legacy alone. In addition, we show that the maximum concentration reduction benefits vary according to the spatial pattern of intervention, with preferential conversion of land parcels having the shortest catchment-scale travel times providing proportionally greater concentration reductions as well as faster response times. In contrast, a random pattern of conversion results in a 1:1 relationship between percent land conversion and percent concentration reduction, irrespective of denitrification rates within the landscape. Our modeling framework allows for the quantification of tradeoffs between costs associated with implementation of conservation measures and the time needed to see the desired concentration reductions, making it of great value to decision makers regarding optimal implementation of watershed conservation measures.     

Mechanisms of Basin-Scale Nitrogen Load Reductions under Intensified Irrigated Agriculture

Irrigated agriculture can modify the cycling and transport of nitrogen (N), due to associated water diversions, water losses, and changes in transport flow-paths. We investigate dominant processes behind observed long-term changes in dissolved inorganic nitrogen (DIN) concentrations and loads of the extensive (465,000 km2) semi-arid Amu Darya River basin (ADRB) in Central Asia. We specifically considered a 40-year period (1960–2000) of large irrigation expansion, reduced river water flows, increased fertilizer application and net increase of N input into the soil-water system. Results showed that observed decreases in riverine DIN concentration near the Aral Sea outlet of ADRB primarily were due to increased recirculation of irrigation water, which extends the flow-path lengths and enhances N attenuation. The observed DIN concentrations matched a developed analytical relation between concentration attenuation and recirculation ratio, showing that a fourfold increase in basin-scale recirculation can increase DIN attenuation from 85 to 99%. Such effects have previously only been observed at small scales, in laboratory experiments and at individual agricultural plots. These results imply that increased recirculation can have contributed to observed increases in N attenuation in agriculturally dominated drainage basins in different parts of the world. Additionally, it can be important for basin scale attenuation of other pollutants, including phosphorous, metals and organic matter. A six-fold lower DIN export from ADRB during the period 1981–2000, compared to the period 1960–1980, was due to the combined result of drastic river flow reduction of almost 70%, and decreased DIN concentrations at the basin outlet. Several arid and semi-arid regions around the world are projected to undergo similar reductions in discharge as the ADRB due to climate change and agricultural intensification, and may therefore undergo comparable shifts in DIN export as shown here for the ADRB. For example, projected future increases of irrigation water withdrawals between 2005 and 2050 may decrease the DIN export from arid world regions by 40%.     

The Health System and Population Health Implications of Large-Scale Diabetes Screening in India: A Microsimulation Model of Alternative Approaches

Background

Like a growing number of rapidly developing countries, India has begun to develop a system for large-scale community-based screening for diabetes. We sought to identify the implications of using alternative screening instruments to detect people with undiagnosed type 2 diabetes among diverse populations across India.

Methods and Findings

We developed and validated a microsimulation model that incorporated data from 58 studies from across the country into a nationally representative sample of Indians aged 25–65 y old. We estimated the diagnostic and health system implications of three major survey-based screening instruments and random glucometer-based screening. Of the 567 million Indians eligible for screening, depending on which of four screening approaches is utilized, between 158 and 306 million would be expected to screen as “high risk” for type 2 diabetes, and be referred for confirmatory testing. Between 26 million and 37 million of these people would be expected to meet international diagnostic criteria for diabetes, but between 126 million and 273 million would be “false positives.” The ratio of false positives to true positives varied from 3.9 (when using random glucose screening) to 8.2 (when using a survey-based screening instrument) in our model. The cost per case found would be expected to be from US$5.28 (when using random glucose screening) to US$17.06 (when using a survey-based screening instrument), presenting a total cost of between US$169 and US$567 million. The major limitation of our analysis is its dependence on published cohort studies that are unlikely fully to capture the poorest and most rural areas of the country. Because these areas are thought to have the lowest diabetes prevalence, this may result in overestimation of the efficacy and health benefits of screening.

Conclusions

Large-scale community-based screening is anticipated to produce a large number of false-positive results, particularly if using currently available survey-based screening instruments. Resource allocators should consider the health system burden of screening and confirmatory testing when instituting large-scale community-based screening for diabetes.     

Neurons under viral attack: Victims or warriors?

When the central nervous system (CNS) is under viral attack, defensive antiviral responses must necessarily arise from the CNS itself to rapidly and efficiently curb infections with minimal collateral damage to the sensitive, specialized and non-regenerating neural tissue. This presents a unique challenge because an intact blood–brain barrier (BBB) and lack of proper lymphatic drainage keeps the CNS virtually outside the radar of circulating immune cells that are at constant vigilance for antigens in peripheral tissues. Limited antigen presentation skills of CNS cells in comparison to peripheral tissues is because of a total lack of dendritic cells and feeble expression of major histocompatibility complex (MHC) proteins in neurons and glia. However, research over the past two decades has identified immune effector mechanisms intrinsic to the CNS for immediate tackling, attenuating and clearing of viral infections, with assistance pouring in from peripheral circulation in the form of neutralizing antibodies and cytotoxic T cells at a later stage. Specialized CNS cells, microglia and astrocytes, were regarded as sole sentinels of the brain for containing a viral onslaught but neurons held little recognition as a potential candidate for protecting itself from the proliferation and pathogenesis of neurotropic viruses. Accumulating evidence however indicates that extracellular insult causes neurons to express immune factors characteristic of lymphoid tissues. This article aims to comprehensively analyze current research on this conditional alteration in the protein expression repertoire of neurons and the role it plays in CNS innate immune response to counter viral infections.     

Epigenetic modulation of host: new insights into immune evasion by viruses

Viruses have evolved with their hosts, which include all living species. This has been partly responsible for the development of highly advanced immune systems in the hosts. However, viruses too have evolved ways to regulate and evade the host’s immune defence. In addition to mutational mechanisms that viruses employ to mimic the host genome and undergo latency to evade the host’s recognition of the pathogen, they have also developed epigenetic mechanisms by which they can render the host’s immune responses inactive to their antigens. The epigenetic regulation of gene expression is intrinsically active inside the host and is involved in regulating gene expression and cellular differentiation. Viral immune evasion strategies are an area of major concern in modern biomedical research. Immune evasion strategies may involve interference with the host antigen presentation machinery or host immune gene expression capabilities, and viruses, in these manners, introduce and propagate infection. The aim of this review is to elucidate the various epigenetic changes that viruses are capable of bringing about in their host in order to enhance their own survivability and pathogenesis.