抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

Gold nanoparticles (GNPs) with controlled geometrical, optical, and surface chemical properties are the subject of intensive studies and applications in biology and medicine. To date, the ever increasing diversity of published examples has included genomics and biosensorics, immunoassays and clinical chemistry, photothermolysis of cancer cells and tumors, targeted delivery of drugs and antigens, and optical bioimaging of cells and tissues with state-of-the-art nanophotonic detection systems. This critical review is focused on the application of GNP conjugates to biomedical diagnostics and analytics, photothermal and photodynamic therapies, and delivery of target molecules. Distinct from other published reviews, we present a summary of the immunological properties of GNPs. For each of the above topics, the basic principles, recent advances, and current challenges are discussed (508 references).

Gold nanoparticles in biomedical applications: recent advances and perspectives

The immune system has evolved to protect the host from a universe of pathogenic microbes that are themselves constantly evolving. The immune system also helps the host eliminate toxic or allergenic substances that enter through mucosal surfaces. Central to the immune system's ability to mobilize a response to an invading pathogen, toxin, or allergen is its ability to distinguish self from nonself. The host uses both innate and adaptive mechanisms to detect and eliminate pathogenic microbes, and both of these mechanisms include self-nonself discrimination. This overview identifies key mechanisms used by the immune system to respond to invading microbes and other exogenous threats and identifies settings in which disturbed immune function exacerbates tissue injury.

/pdf/overview-of-the-immune-response-2is735zjhy.pdf

Overview of the Immune Response

Two new polyoxygenated flavonoids from Blumea eriantha DC, methanol extract and their anti-proliferative activity.

Traditional Chinese medicine (TCM) and Ayurveda have been used in humans for thousands of years [1]. While the link to a particular indication has been established in man, the mode-of-action (MOA) of the formulations is relatively unknown. In this study, we aim to understand the MOA of formulations used in traditional medicine using in silico target prediction tools, which predicts protein targets (hence, MOAs) given the chemical structure of a compound. We were able to establish several links between suggested MOAs and experimental evidence. In particular, compounds from the 'tonifying and replenishing medicinal' class exhibit a hypoglycemic effect [2] which can be connected to SGLT 1 and 2 [3] and PTP1B [4]. Similar results were obtained with Ayurvedic anti-cancer drugs. Here, both primary anti-cancer targets, which directly participate in cancer pathogenesis, i.e. steroid-5-alpha-reductase 1 and 2 were predicted, as well as synergistic targets, i.e. P-glycoprotein (blocking this efflux pump increases intracellular concentration of the primary active ingredient) [5]. In addition, some targets may point us to possible novel MOA and side effects. Most notably, GPBAR1 which was predicted as a target for both 'tonifying and replenishing medicinal' and anti-cancer classes, suggest an influence of the compounds on metabolism [6]. Understanding the MOA of these compounds is beneficial as it can provide new resources for NME, with higher efficacies in the clinic than in the current drug discovery setting. This can be a promising endeavor as the phenotypes of these compounds are well known which indicates both the therapeutic impact and efficacy against a certain disease.

/pdf/chemogenomics-approaches-to-rationalising-compound-action-of-xj53ach19n.pdf

Chemogenomics approaches to rationalising compound action of traditional Chinese and Ayurvedic medicines

Malted barley waste is a rich source of different fungi. Hydrophobin like surface active proteins can be isolated from these fungal species and can be studied for industrial applications. In this study total 50 fungal strains were isolated from malt waste and screened for production of hydrophobin like protein (HYD-LP). Fungi producing highly hydrophobic spores were selected for fermentative growth. Ten such strains have shown good foam stability with half decay time more than foam of 0.1% SDS. Fungal strain S7-5 (Penicillium species close to P. islandicum) was selected for isolation of HYD-LPs which had lowered the surface tension of fermentation media to 31.046 mN/m with high half decay time of foam and good emulsification capacity. SDS-insoluble HYD-LP was purified using trifluroacetic acid. SDS-PAGE confirmed presence of low molecular weight protein (15 kDa) isolated from spore walls and fermentation broth. This protein was partially characterized as HYD-LP by performing RP-HPLC and studying its amphipathic nature as it has made low contact angle with Teflon surface. It also formed stable layer on Teflon surface and spore wall HYD-LP decreased hydrophobicity of Teflon by lowering contact angle (CA) of water by 21.63% and HYD-LP isolated from fermentation broth lowered water CA by 37.62%. This study is first to report the bio prospecting of fungi isolated from malted barley waste for biosurfactant characteristics and subsequent isolation of HYD-LP from strain close to Penicllium islandicum.

/pdf/exploring-malted-barley-waste-for-fungi-producing-surface-4ce6yguq9w.pdf

Exploring malted barley waste for fungi producing surface active proteins like hydrophobins

The deregulated activity of the Bcr-Abl tyrosine
kinase provides a rational basis for the development
therapeutics in all phases of Chronic Myelogenous
Leukemia (CML). Although a well studied imatinib
therapy has clinical success against CML, resistance to
imatinib due to mutations in the kinase domain, especially
T315I poses a major problem for the ultimate success of
CML therapy by this agent. Herein we describe an
NPB001-05, derived from extract of Piper betle leafs,
which is highly active in specifically inhibiting Bcr-Abl
expressing cells. NPB001-05 inhibited the proliferation of
BaF3 cells ectopically expressing wild type Bcr-Abl
phenotype and 12 different imatinib-resistant mutations of
clinical relevance (average IC50 5.7 μg/ml). Moreover,
NPB001-05 was highly inhibitory to wild type P210Bcr-Abl
and P210Bcr-Abl-T315I kinase activity and abrogated the
autophosphorylating enzyme in time- and dose- dependent
manner. NPB001-05 was non-toxic on normal cells, but
was inhibitory to CML patient derived peripheral blood
mononuclear cells. Treatment with NPB001-05 caused
apoptosis induction and G0G1 cell cycle arrest in both Bcr-
Abl wild type and T315I mutant cell lines

NPB001-05 inhibits Bcr-Abl kinase leading to apoptosis of imatinib-resistant cells.

Among the PCR-based markers that are most widely used in molecular genetic studies, SCARs (sequence characterized amplified regions) have the advantage of being less sensitive to the conditions of a standard PCR due to its primer size when compared to RAPD (random amplified polymorphic DNA) and hence are more specific and reproducible. Moreover, SCARs require no radioactive isotopes and detect only a single locus. Here, we describe the development of SCAR from RAPD amplicons.

Kalpana Joshi

Papers

Two new polyoxygenated flavonoids from Blumea eriantha DC, methanol extract and their anti-proliferative activity.

Chemogenomics approaches to rationalising compound action of traditional Chinese and Ayurvedic medicines

Exploring malted barley waste for fungi producing surface active proteins like hydrophobins

NPB001-05 inhibits Bcr-Abl kinase leading to apoptosis of imatinib-resistant cells.

Development of sequence characterized amplified region from random amplified polymorphic DNA amplicons.