Structural polymorphism exhibited by a homopurine.homopyrimidine sequence found at the right end of human c-jun protooncogene

Homopurine·homopyrimidine (Pu·Py) tracts are likely to play important biological role in eukaryotes. Using circular dichroism, UV-thermal denaturation and gel electrophoresis, we have analyzed the structural polymorphism of a 21-bp Pu·Py DNA segment within human c-jun protooncogene 3′-region, a potential target for triplex formation. Results show that below physiological pH and in the presence of Na⁺/K⁺ with Mg²⁺ the duplex is destabilized/disproportionated, resulting in strand mediated structural transitions to the self-associated structures of G- and C-rich strands separately, identified as G-quadruplex and i-motif species. A significant differential behavior of the monovalent cations was observed, accordingly the presence of Na⁺ in acidic as well as neutral pH facilitated the duplex formation, while K⁺ favored the formation of self-associated structures. In Na⁺ and Mg²⁺, under acidic and neutral pH conditions, the duplex displayed triphasic and biphasic melting profiles, respectively. This self-association property of oligonucleotides might limit their use as duplex targets in triplex formation. Study is also relevant for understanding structural and biological properties of DNA sequence containing homopurine tracts.     

Synergistic blends of monoterpenes for aggregation pheromones of the mountain pine beetle (Coleoptera: Curculionidae)

The superiority of the host monoterpene myrcene as a synergist for trans-verbenol and exo-brevicomin, aggregation pheromone components of the mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae), suggests that the ancestral host of the mountain pine beetle is a pine rich in myrcene. A field trapping experiment in British Columbia testing reconstituted bole oleoresin of whitebark pine, Pinus albicaulis Engelmann, composed of mainly myrcene (20.7%), terpinolene (6.8%), and 3-carene (61.9%) showed it to be a better pheromone synergist than reconstituted bole oleoresin of lodgepole pine, Pinus contorta variety latifolia Engelmann, which contained only 2.7, 1.0, and 6.0%, respectively, of the above-mentioned three compounds. In the same experiment myrcene alone was the best synergist. In subsequent experiments, testing myrcene, terpinolene and 3-carene alone and in all possible binary and ternary combinations, a 50:50 blend of myrcene and terpinolene released at the same rate as either compound alone generally resulted in trap catches approximately 3 times higher than with myrcene as a synergist. This result held as long as the terpinolene was free of contaminants, and the traps were in the open, well away from potential interference of semiochemicals emitted by newly attacked trees. 3-Carene seemed to be inert or slightly inhibitory. No single monoterpene tested alone or in binary or ternary combination in the absence of pheromones was attractive. There was no effect of doubling or tripling the release rate of myrcene or terpinolene. In five of nine experiments, adding terpinolene to myrcene caused a significant increase in the percentage of female mountain pine beetles captured. Among host pines, the presence of highly synergistic monoterpenes at various levels in combination with other monoterpenes that are apparently either inert or inhibitory could account for different degrees of pheromone synergism, and thus host preference. The highly synergistic effect of combining myrcene plus terpinolene with the mountain pine beetle aggregation pheromone components opens up the potential for suppression of populations through semiochemical-based mass trapping.     

Dual roles of immunoregulatory cytokine TGF-beta in the pathogenesis of autoimmunity-mediated organ damage

Ample evidence suggests a role of TGF-beta in preventing autoimmunity. Multiorgan inflammatory disease, spontaneous activation of self-reactive T cells, and autoantibody production are hallmarks of autoimmune diseases, such as lupus. These features are reminiscent of the immunopathology manifest in TGF-beta1-deficient mice. In this study, we show that lupus-prone (New Zealand Black and White)F(1) mice have reduced expression of TGF-beta1 in lymphoid tissues, and TGF-beta1 or TGF-beta1-producing T cells suppress autoantibody production. In contrast, the expression of TGF-beta1 protein and mRNA and TGF-beta signaling proteins (TGF-beta receptor type II and phosphorylated SMAD3) increases in the target organs, i.e., kidneys, of these mice as they age and develop progressive organ damage. In fact, the levels of TGF-beta1 in kidney tissue and urine correlate with the extent of chronic lesions that represent local tissue fibrosis. In vivo TGF-beta blockade by treatment of these mice with an anti-TGF-beta Ab selectively inhibits chronic fibrotic lesions without affecting autoantibody production and the inflammatory component of tissue injury. Thus, TGF-beta plays a dual, seemingly paradoxical, role in the development of organ damage in multiorgan autoimmune diseases. According to our working model, reduced TGF-beta in immune cells predisposes to immune dysregulation and autoantibody production, which causes tissue inflammation that triggers the production of anti-inflammatory cytokines such as TGF-beta in target organs to counter inflammation. Enhanced TGF-beta in target organs, in turn, can lead to dysregulated tissue repair, progressive fibrogenesis, and eventual end-organ damage.     

Fermentation waste of Aspergillus terreus: a potential copper biosorbent

Aspergillus terreus mycelial waste produced during lipase production showed good copper biosorption capacity (160–180 mg Cu²⁺ biosorbed/g dry biomass). The sorption process followed fast kinetics and the absorption behaviour could be explained by a Freundlich isotherm model. The process was temperature independent and unaffected by the presence of many competing ions in a multi-ion situation. Maximum biosorption occurred between pH 4 and 5. The biomass could efficiently remove copper from mine effluents. Moreover the loaded biomass could easily be desorbed by a simple acid wash and could be reused a number of times without a decline in its biosorbing potential, thus making the process cost-effective.     

Socioeconomic and ethnic group differences in self reported health status and use of health services by children and young people in England: cross sectional study

ObjectivesTo examine whether self reported health status and use of health services varies in children of different social class and ethnic group.DesignCross sectional study from the 1999 health survey for England.Subjects6648 children and young adults aged 2-20 years.SettingPrivate households in England.ResultsLarge socioeconomic differences were observed between ethnic subgroups; a higher proportion of Afro-Caribbean, Indian, Pakistani, and Bangladeshi children belonged to lower social classes than the general population. The proportion of children and young adults reporting acute illnesses in the preceding two weeks was lower in Bangladeshi and Chinese subgroups (odds ratio 0.41, 95% confidence interval 0.27 to 0.61 and 0.46, 0.28 to 0.77, respectively) than in the general population. Longstanding illnesses was less common in Bangladeshi and Pakistani children (0.52, 0.40 to 0.67 and 0.57, 0.46 to 0.70) than in the general population. Irish and Afro-Caribbean children reported the highest prevalence of asthma (19.5% and 17.7%) and Bangladeshi children the lowest (8.2%). A higher proportion of Afro-Caribbean children reported major injuiries than the general population (11.0% v 10.0%), and children from all Asian subgroups reported fewer major and minor injuries than the general population. Indian and Pakistani children were more likely to have consulted their general practitioner in the preceding fortnight than the general population (1.86, 1.35 to 2.57 and 1.51, 1.13 to 2.01, respectively). Indian, Pakistani, Bangladeshi, and Chinese children were less likely to have attended outpatient departments in the preceding three months. No significant differences were found between ethnic groups in the admission of inpatients to hospitals. Acute and chronic illness were the best predictors of children''s use of health services. Social classes did not differ in self reported prevalence of treated infections, major injuries, or minor injuries, and no socioeconomic differences were seen in the use of primary and secondary healthcare services.ConclusionsChildren''s use of health services reflected health status rather than ethnic group or socioeconomic status, implying that equity of access has been partly achieved, although reasons why children from ethnic minority groups are able to access primary care but receive less secondary care need to be investigated.

What is already known on this topic

Children from lower socioeconomic classes and from Indian ethnic subgroups may make more use of general practitioners'' services than other childrenAfro-Caribbean, Indian, Pakistani, and Bangladeshi children are less likely to be referred to outpatient and inpatient services at hospitals than white children

What this study adds

Indian, Pakistani, and Bangladeshi children reported less acute and chronic illness, asthma, and injuries than the general population, whereas Afro-Caribbean children reported moreChildren''s self reported health status and use of health services did not vary by social classIndian and Pakistani children make more use of general practitioners'' services, but Indian, Pakistani, Bangladeshi, and Chinese children are less likely to be referred to outpatient clinicsSelf reported health status rather than socioeconomic status or ethnicity is the best predictor of use of primary and secondary services     

The Role of Olfactory Cues in Short-Range Mate Finding by the Emerald Ash Borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae)

We investigated the relative importance of olfaction versus vision in the mate-finding behavior of Agrilus planipennis. When coupled in male–female, male–male and female–female pairs, attempts to mate occurred only in the male–female pairs, suggesting that beetles can identify the opposite sex before attempting to mate. In a set of sensory deprivation experiments with male–female pairs, we evaluated whether males could find females when deprived of their sense of olfaction, vision or both. Males whose antennae were blocked with model paint took significantly longer to find females and spent less time in copula compared to untreated males. Males whose eyes were similarly blocked did not differ in their mate finding capacity compared to untreated males. In a third experiment that compared both olfaction and vision, olfactorily impaired beetles never mated whereas the mate finding potential of visually impaired beetles did not differ from that of untreated beetles. Our results indicate that males can identify females before coming into physical contact with them, and that at short range (≤5 cm), volatile cues detected by olfaction are involved in mate finding by A. planipennis.     

In vivo genotoxicity evaluation of a plant based antiarthritic and anticancer therapeutic agent Boswelic acids in rodents

The genotoxic potential of anti-inflammatory/anti-arthritic and anticancer plant based drug molecule Boswelic acids (BA) was studied by in vivo system. Systematic literature survey revealed that studies on the genotoxicity of BA are not available. Although reports on genotoxicity of Boswellia serrata dry extract and modified 3-O-acetyl-11-keto-β-boswelic acid are available and these studies were conducted in in vitro systems. The earlier general toxicity study of BA has been conducted by us, revealed it to be non toxic. The genotoxicity was carried out in Wistar rats using different cytogenetic assay system-abnormalities viz. chromosomal aberrations; sperm morphology, micronuclei and comet assays. Six groups of animals, each comprised of five rats, were taken for each study. Group1-4 received BA at 125, 250, 500 and 1000 mg/kg p.o., respectively prepared as 2% gum acacia suspension, fifth group received a positive control cyclophosphamide (CP) 40 mg/kg p.o. or metronedazole (MTZ) 130 mg/kg p.o. or mercuric chloride (HgCl₂) 0.864 mg/kg p.o. (as per the experiment requirement) whereas the sixth group kept as vehicle control. The results on the bases of the data obtained revealed that BA is quite safe as it did not show any genotoxicity at any dose level up to 1000 mg/kg. The positive controls used in different experiments showed highly significant abnormal cytogenetic changes in comparison to the control group.     

Microwave-assisted synthesis of N-substituted cyclic imides and their evaluation for anticancer and anti-inflammatory activities

A number of N-substituted cyclic imides 3a–e, 5a–e, 7a–d, and 9a–e have been synthesized in very high yields, by condensation of various diacids 2, 4, 6, and 8 with different amines under microwave irradiation. These compounds were screened for anticancer and anti-inflammatory activities, and compounds 3c, 3e, 5c, 9c, and 9d exhibited anticancer activity against colon (COLO 205) cancer better than 5-fluorouracil and mitomycin-C, and compound 9b exhibited anti-inflammatory activity better than standard drug phenyl butazone.     

Synthesis of oxalamide and triazine derivatives as a novel class of hybrid 4-aminoquinoline with potent antiplasmodial activity

Frequency of malaria and its resistance to chemotherapeutic options are emerging rapidly. To counter this problem, a series of 4-aminoquinolines having oxalamide and triazine functionalities in the side chain were synthesized and screened for their antimalarial activities. Triazine derivative 48 found to be the most active against CQ sensitive strain 3D7 of Plasmodium falciparum in an in vitro assay with an IC₅₀ of 5.23 ng/mL and oxalamide derivative 13 showed an in vivo suppression of 70.45% on day 4 against CQ resistant strain N-67 of Plasmodium yoelii.