Possible role of metal ionophore against zinc induced cognitive dysfunction in <Emphasis Type="SmallCaps">d-</Emphasis>galactose senescent mice

Metal ionophores are considered as potential anti-dementia agents, and some are currently undergoing clinical trials. Many metals are known to accumulate and distribute abnormally in the aging brain. Alterations in zinc metal homeostasis in the glutaminergic synapse could contribute to ageing and the pathophysiology of Alzheimer’s disease (AD). The present study was designed to investigate the effect of metal ionophores on long term administration of zinc in D-galactose induced senescent mice. The ageing model was established by combined administration of zinc and D-galactose to mice for 6 weeks. A novel metal ionophore, PBT-2 was given daily to zinc-induced d-galactose senescent mice. The cognitive behaviour of mice was monitored using the Morris Water Maze. The anti-oxidant status and amyloidogenic activity in the ageing mouse was measured by determining mito-oxidative parameters and deposition of amyloid β (Aβ) in the brain. Systemic administration of both zinc and D-galactose significantly produced memory deficits, mito-oxidative damage, heightened acetylcholinesterase enzymatic activity and deposition of amyloid-β. Treatment with PBT-2 significantly improved behavioural deficits, biochemical profiles, cellular damage, and curbed the deposition of APP in zinc-induced senescent mice. These findings suggest that PBT-2, acting as a metal protein attenuating compound, may be helpful in the prevention of AD or alleviation of ageing.     

Characterization and partial purification of <Emphasis Type="Italic">Candida albicans</Emphasis> Secretory IL-12 Inhibitory Factor

Background  

We have previously shown that supernatant from Candida albicans (CA) culture contains a Secretory Interleukin (IL)-12 Inhibitory Factor (CA-SIIF), which inhibits IL-12 production by human monocytes. However, the effect of CA-SIIF on secretion of other cytokines by monocytes is unknown, and detailed characterization of this factor has not been performed.     

Intracellular regulation of cell signaling cascades: how location makes a difference

Organelles such as endosomes and the Golgi apparatus play a critical role in regulating signal transmission to the nucleus. Recent experiments have shown that appropriate positioning of these organelles within the intracellular space is critical for effective signal regulation. To understand the mechanism behind this observation, we consider a reaction-diffusion model of an intracellular signaling cascade and investigate the effect on the signaling of intracellular regulation in the form of a small release of phosphorylated signaling protein, kinase, and/or phosphatase. Variational analysis is applied to characterize the most effective regions for the localization of this intracellular regulation. The results demonstrate that signals reaching the nucleus are most effectively regulated by localizing the release of phosphorylated substrate protein and kinase near the nucleus. Phosphatase release, on the other hand, is nearly equally effective throughout the intracellular space. The effectiveness of the intracellular regulation is affected strongly by the characteristics of signal propagation through the cascade. For signals that are amplified as they propagate through the cascade, reactions in the upstream levels of the cascade exhibit much larger sensitivities to regulation by release of phosphorylated substrate protein and kinase than downstream reactions. On the other hand, for signals that decay through the cascade, downstream reactions exhibit larger sensitivity than upstream reactions. For regulation by phosphatase release, all reactions within the cascade show large sensitivity for amplified signals but lose this sensitivity for decaying signals. We use the analysis to develop a simple model of endosome-mediated regulation of cell signaling. The results demonstrate that signal regulation by the modeled endosome is most effective when the endosome is positioned in the vicinity of the nucleus. The present findings may explain at least in part why endosomes in many cell types localize near the nucleus.     

Signal processing, glycosylation, and secretion of mutant hemagglutinins of a human influenza virus by Saccharomyces cerevisiae.

We investigated the nature of signal recognition, transport, and secretion of mutant hemagglutinins (HAs) of a human influenza virus by the yeast Saccharomyces cerevisiae. The cDNA sequences encoding variant forms of influenza HA were expressed in S. cerevisiae. The HA polypeptides (HA500 and HA325) that were synthesized with their N-terminal signal peptides were correctly targeted to the membrane compartment where they were glycosylated. In contrast, the HA polypeptides (HA484 and HA308) lacking the signal peptide were expressed in the cytoplasm and did not undergo any glycosidic modification, demonstrating the importance of the heterologous signal sequence in the early steps of translocation in S. cerevisiae. The analysis of the N-terminal amino acid sequence of HA500 and HA325 polypeptides demonstrated the correct cleavage of the signal peptide, indicating the structural compatibility of a heterologous signal peptide for efficient recognition and processing by the yeast translocation machinery. The membrane-sequestered and glycosylated HA polypeptides were relatively stable in S. cerevisiae compared with the signal-minus, nonglycosylated HA molecules. Although both the anchor-minus HA (HA500) and HA1 (HA325) polypeptides were targeted efficiently to the membrane, their glycosylation and transport patterns were shown to be different. During pulse-chase, the HA500 remained cell-associated with no detectable secretion into the extracellular medium, whereas the HA325 secreted into the medium. Furthermore, only the cell-associated and secreted forms of HA325 and not HA500 appeared to have undergone hyperglycosylation with the extensive addition of high-molecular-weight outer-chain mannans. Possible reasons for the observed phenotypic behavior of these two mutant HAs are discussed.     

Compatability of Metarhizium anisopliae var. anisopliae with chemical pesticides

The effects of various insecticides on the mycelial growth, sporulation and conidial germination of Metarhizium anisopliae var. anisopliae isolate E₉ were studied in the laboratory. Chlorpyrifos was the most toxic organophosphate to mycelial growth and sporulation at all concentrations. Temephos, malathion and leptophos were highly toxic to sporulation while malathion was the most inhibitory to germination. The carbamates, carbofuran, methomyl and oxamyl were moderately toxic to mycelial growth and sporulation while oxamyl had an adverse effect on germination. The pyrethroids (pyrethrin, permethrin and resmethrin) and the insect growth regulators (diflubenzuron and methoprene) were not inhibitory to the various developmental stages of isolate E₉. The chlorinated hydrocarbons (chlordane, lindane and toxaphene) were more deleterious than all other insecticide groups tested. Among the fungicides, benomyl and maneb produced the greatest inhibition.     

Does the MRCGP examination discriminate against Asian doctors?

OBJECTIVE--To ascertain whether the membership examination for the Royal College of General Practitioners (MRCGP) discriminates against doctors of Indian subcontinent ethnic origin ("Asian doctors"). DESIGN--Retrospective analysis of data from five administrations of the MRCGP examination (December 1988-December 1990). SETTING--United Kingdom national examination body. SUBJECTS--3686 doctors taking the examination for the first time, 244 of whom were classified as Asian, the remainder as non-Asian. MAIN OUTCOME MEASURES--Comparison of performance in each of the written and oral components of the examination between Asian doctors, identified by their names and classified into subgroups by countries of birth and primary medical training from data provided at registration, and non-Asian doctors. RESULTS--On written components of the examination (multiple choice paper mean score Asians versus non-Asians 42.3 v 48.6, modified essay paper 40.9 v 48.9, practice topic/critical reading paper 41.5 v 48.7, all p less than 0.001 by t testing). But analysis by countries of birth and primary training showed that these differences were due largely to poor performance by certain groups of Asian doctors, especially those born and trained in the Indian subcontinent or elsewhere outside the United Kingdom. Asian doctors born and trained in the United Kingdom and those born in Africa or the West Indies and trained in the United Kingdom performed similarly to the non-Asian doctors. CONCLUSIONS--The examination does not systematically discriminate against Asian doctors, but the poor performance of the two subgroups of Asians is cause for serious concern and requires investigation.     

Ecology of deepwater rice-fields in Bangladesh 3. Associated algae and macrophytes

1. Aquatic macrophytes formed dense beds in fallow areas during the four and a half months of the flood season in all but one deepwater rice-growing location in Bangladesh; these included several types of life-form, but the fine-leaved species, Myriophyllum sp., Najas indica, Utricularia stellaris were often especially abundant. The same species grew inside deepwater rice fields, but at much lower densities. A similar contrast occurred for the algae, although deepwater rice often developed dense masses of epiphytes on aquatic roots, stems and leaf sheaths, when plants were growing in isolated, well-illuminated situations.
2. Two widespread algae, Aulosira fertilissima and Scytonema mirabile, were equally successful on soil in the period prior to the arrival of floodwaters and floating on the surface of the water during the flood season. Other species common during the flood season differed from those common on soil.
3. Most blue-green algae inside deepwater rice fields were heterocystous; the only species not so, but forming distinct colonies, was Aphanothece stagnina. However only non-heterocystous forms were found at one location in south Bangladesh (Phaltita) and a change from heterocystous to non-heterocystous forms was noted at the main research site (near Sonargaon) during late September in at least one year. The water column at the former was almost entirely anoxic, while the change at the latter occurred at a time when the water sometimes became anoxic during the night. It is suggested that differences in ability to tolerate anoxic periods may be a key factor in determining the success of the algal and vascular plant species in the different micro-habitats within these DWR-growing areas.
4. Although diatoms were quantitatively only a minor component of the algal biomass, they became more frequent later in the season when the water became microaerobic or anoxic for part of the day. Navicula confervacea was overall the most abundant species at the two main research locations.

     

Ecology of deepwater rice-fields in Bangladesh 4. Nitrogen fixation by blue-green algal communities

1. Aquatic macrophytes formed dense beds in fallow areas during the four and a half months of the flood season in all but one deepwater rice-growing location in Bangladesh; these included several types of life-form, but the fine-leaved species, Myriophyllum sp., Najas indica, Utricularia stellaris were often especially abundant. The same species grew inside deepwater rice fields, but at much lower densities. A similar contrast occurred for the algae, although deepwater rice often developed dense masses of epiphytes on aquatic roots, stems and leaf sheaths, when plants were growing in isolated, well-illuminated situations.
2. Two widespread algae, Aulosira fertilissima and Scytonema mirabile, were equally successful on soil in the period prior to the arrival of floodwaters and floating on the surface of the water during the flood season. Other species common during the flood season differed from those common on soil.
3. Most blue-green algae inside deepwater rice fields were heterocystous; the only species not so, but forming distinct colonies, was Aphanothece stagnina. However only non-heterocystous forms were found at one location in south Bangladesh (Phaltita) and a change from heterocystous to non-heterocystous forms was noted at the main research site (near Sonargaon) during late September in at least one year. The water column at the former was almost entirely anoxic, while the change at the latter occurred at a time when the water sometimes became anoxic during the night. It is suggested that differences in ability to tolerate anoxic periods may be a key factor in determining the success of the algal and vascular plant species in the different micro-habitats within these DWR-growing areas.
4. Although diatoms were quantitatively only a minor component of the algal biomass, they became more frequent later in the season when the water became microaerobic or anoxic for part of the day. Navicula confervacea was overall the most abundant species at the two main research locations.