Molecular phylogeny of Himalopsyche (Trichoptera,Rhyacophilidae)

Species of the genus Himalopsyche (Trichoptera, Rhyacophilidae) inhabit alpine to montane environments in Central and East Asia and North America. Diversity of the genus is concentrated primarily in the Himalayas and surrounding mountain ranges. Phylogenetic hypotheses have hitherto been proposed based on morphological data. Here, we present the first molecular phylogeny of Himalopsyche based on six gene fragments, using three methods of phylogenetic inference. Based on the phylogenetic analyses, we re‐evaluated species groups suggested by previous authors based on adult male morphology. We found that the previously defined groups are largely supported by molecular evidence as well as larval and adult morphology. However, we modify the species groups so that Himalopsyche phryganea and Himalopsyche lepcha constitute monotypic groups, and so that the tibetana group and anomala group sensu Schmid & Botosaneanu are merged to a single group, here defined as the tibetana group. Thus, we propose that Himalopsyche can be divided into five groups: kuldschensis group, lepcha group, navasi group, phryganea group, and tibetana group. We also provide a biogeographic synthesis of Himalopsyche distributions.     

Radiosynthesis and evaluation of [11C]CMP,a high affinity GSK3 ligand

Dysfunction of GSK3 is implicated in the etiology of many brain, inflammatory, cardiac diseases, and cancer. PET imaging would enable in vivo detection and quantification of GSK3 and can impact the choice of therapy, allow non-invasive monitoring of disease progression and treatment effects. In this report, the synthesis and evaluation of a high affinity GSK3 ligand, [¹¹C]2-(cyclopropanecarboxamido)-N-(4-methoxypyridin-3-yl)isonicotinamide, ([¹¹C]CMP, (3), (IC₅₀?=?3.4?nM, LogP?=?1.1) is described. [¹¹C]CMP was synthesized in 25?±?5% yield by radiomethylating the corresponding phenolate using [¹¹C]CH₃I. The radioligand exhibited modest uptake in U251 human glioblastoma cell lines with ～50% specific binding. MicroPET studies in rats indicated negligible blood–brain barrier (BBB) penetration of [¹¹C]CMP, despite its high affinity and suitable logP value for BBB penetration. However, administration of cyclosporine prior to [¹¹C]CMP injection showed significant improvement in brain radioactivity uptake and the tracer binding. This finding indicates that [¹¹C]CMP might be a P-gp efflux substrate and therefore has some limitations for routine in vivo PET evaluations in brain.     

Targeting phosphoinositide-3-kinase pathway in biliary tract cancers: A remedial route?

Biliary tract cancers (BTC) are aggressive tumours with a low survival rate. At the advent of the genomic era, various genetic mutations in cell signalling pathways have been incriminated in carcinogenesis. Genomic analysis studies have connected main components of the phosphoinositide-3-kinase (PI3K) signalling pathway to BTC. PI3K pathway playing a central role in cell signalling and being deregulated in various tumours has been studied as a target for chemotherapy. Novel compounds have also been identified in preclinical trials that specifically target the PI3K pathway in BTCs, but these studies have not accelerated to clinical use. These novel compounds can be examined in upcoming studies to validate them as potential therapeutic agents, as further research is required to combat the growing need for adjuvant chemotherapy to successfully battle this tumour type. Furthermore, these molecules could also be used along with gemcitabine, cisplatin and 5-fluorouracil to improve sensitivity of the tumour tissue to chemotherapy. This review focuses on the basics of PI3K signalling, genetic alterations of this pathway in BTCs and current advancement in targeting this pathway in BTCs. It emphasizes the need for gene-based drug screening in BTC. It may reveal various novel targets and drugs for amelioration of survival in patients with BTC and serve as a stepping stone for further research.     

Induction of Heat Shock Proteins and Acquisition of Thermotolerance in Germinating Pigeonpea Seeds

Heat shock proteins (HSPs) ranging in molecular masses from 14 to 110 kDa were induced in embryonic axes of germinating Cajanus cajan (L.) Millspaugh seeds after exposure to 40 °C for 1 or 2 h. At 45 °C, there was a marked decline in synthesis of HSPs. A close relationship was observed between HSPs induced and the growth of the germinating seeds. Pretreatment of germinating seeds at 40 °C for 1 h or 45 °C for 10 min followed by incubation at 28 °C for 3 h led to considerable thermotolerance (45 °C, 2 h) and the recovery of protein synthesis. This revised version was published online in July 2006 with corrections to the Cover Date.     

The function of G-protein coupled receptors and membrane cholesterol: specific or general interaction?

Cholesterol is an essential component of eukaryotic membranes and plays a crucial role in membrane organization, dynamics and function. The G-protein coupled receptors (GPCRs) are the largest class of molecules involved in signal transduction across membranes and constitute ~1–2% of the human genome. GPCRs have emerged as major targets for the development of novel drug candidates in all clinical areas due to their involvement in the generation of multitude of cellular responses. Membrane cholesterol has been reported to have a modulatory role in the function of a number of GPCRs. This effect could either be due to specific molecular interaction between cholesterol and GPCR, or due to alterations in the membrane physical properties induced by cholesterol. Alternatively, membrane cholesterol could modulate receptor function by occupying the ‘nonannular’ sites around the receptor. In this review, we have highlighted the nature of cholesterol dependence of GPCR function taking a few known examples.     

Evaluation of Selected Immunomodulatory Glycoproteins as an Adjunct to Cancer Immunotherapy

Polysaccharopeptide (PSP), from Coriolus versicolor, has been used widely as an adjuvant to chemotherapy with demonstrated anti-tumor and broad immunomodulating effects. While PSP’s mechanism of action still remains unknown, its enhanced immunomodulatory potential with acacia gum is of great interest. Acacia gum, which also contains polysaccharides and glycoproteins, has been demonstrated to be immunopotentiating. To elucidate whether PSP directly activates T-cell-dependent B-cell responses in vivo, we used a well-established hapten carrier system (Nitrophenyl-chicken gamma globulin (NP-CGG)). 6-week C57BL/6 male mice were immunised with 50 μg of NP₂₅-CGG alum precipitate intraperitoneally. Mice were gavaged daily with 50mg/kg PSP in a vehicle containing acacia gum and sacrificed at days 0, 4, 7, 10, 14 and 21. ELISA was used to measure the total and relative hapten-specific anti-NP IgA, IgM and IgG titre levels compared to the controls. It was found that PSP, combined with acacia gum, significantly increased total IgG titre levels at day 4 (P< 0.05), decreased IgM titre levels at days 4 and 21 (P< 0.05) with no alterations observed in the IgA or IgE titre levels at any of the time points measured. Our results suggest that while PSP combined with acacia gum appears to exert weak immunological effects through specific T-cell dependent B-cell responses, they are likely to be broad and non-specific which supports the current literature on PSP. We report for the first time the application of a well-established hapten-carrier system that can be used to characterise and delineate specific T-cell dependent B-cell responses of potential immunomodulatory glycoprotein-based herbal medicines combinations in vivo.     

Symbolic Numerical Magnitude Processing Is as Important to Arithmetic as Phonological Awareness Is to Reading

In this article, we tested, using a 1-year longitudinal design, whether symbolic numerical magnitude processing or children’s numerical representation of Arabic digits, is as important to arithmetic as phonological awareness is to reading. Children completed measures of symbolic comparison, phonological awareness, arithmetic, reading at the start of third grade and the latter two were retested at the start of fourth grade. Cross-sectional and longitudinal correlations indicated that symbolic comparison was a powerful domain-specific predictor of arithmetic and that phonological awareness was a unique predictor of reading. Crucially, the strength of these independent associations was not significantly different. This indicates that symbolic numerical magnitude processing is as important to arithmetic development as phonological awareness is to reading and suggests that symbolic numerical magnitude processing is a good candidate for screening children at risk for developing mathematical difficulties.