Immunotherapeutic efficacy of Mycobacterium indicus pranii in eliciting anti-tumor T cell responses: Critical roles of IFN gamma

Mycobacterium indicus pranii (MIP) is approved for use as an adjuvant (Immuvac/Cadi-05) in the treatment of leprosy. In addition, its efficacy is being investigated in clinical trials on patients with tuberculosis and different tumors. To evaluate and delineate the mechanisms by which autoclaved MIP enhances anti-tumor responses, the growth of solid tumors consisting of Sp2/0 (myeloma) and EL4 (thymoma) cells was studied in BALB/c and C57BL/6 mice, respectively. Treatment of mice with a single intra-dermal (i.d.) injection of MIP 3 days after Sp2/0 implantation greatly suppresses tumor growth. MIP treatment of tumor bearing mice lowers Interleukin (IL)6 but increases IL12p70 and IFN? amounts in sera. Also, increase in CD8+ T cell mediated lysis of specific tumor targets and production of high amounts of IL2 and IFN? by CD4+ T cells upon stimulation with specific tumor antigens in MIP treated mice is observed. Furthermore, MIP is also effective in reducing the growth of EL4 tumors; however, this efficacy is reduced in Ifn?-/- mice. In fact, several MIP mediated anti-tumor responses are greatly abrogated in Ifn?-/- mice: increase in serum Interleukin (IL)12p70 amounts, induction of IL2 and lysis of EL4 targets by splenocytes upon stimulation with specific tumor antigens. Interestingly, tumor-induced increase in serum IL12p70 and IFN? and reduction in growth of Sp2/0 and EL4 tumors by MIP are not observed in nonobese diabetic severe combined immunodeficiency mice. Overall, our study clearly demonstrates the importance of a functional immune network, in particular endogenous CD4+ and CD8+ T cells and IFN?, in mediating the anti-tumor responses by MIP.

A unified view of the Apriori-based algorithms for frequent episode discovery

Frequent episode discovery framework is a popular framework in temporal data mining with many applications. Over the years, many different notions of frequencies of episodes have been proposed along with different algorithms for episode discovery. In this paper, we present a unified view of all the apriori-based discoverymethods for serial episodes under these different notions of frequencies. Specifically, we present a unified view of the various frequency counting algorithms. We propose a generic counting algorithm such that all current algorithms are special cases of it. This unified view allows one to gain insights into different frequencies, and we present quantitative relationships among different frequencies.Our unified view also helps in obtaining correctness proofs for various counting algorithms as we show here. It also aids in understanding and obtaining the anti-monotonicity properties satisfied by the various frequencies, the properties exploited by the candidate generation step of any apriori-based method. We also point out how our unified view of counting helps to consider generalization of the algorithm to count episodes with general partial orders.

A unified view of the apriori-based algorithms for frequent episode discovery

Frequent episode discovery framework is a popular framework in temporal data mining with many applications. Over the years, many different notions of frequencies of episodes have been proposed along with different algorithms for episode discovery. In this paper, we present a unified view of all the apriori-based discovery methods for serial episodes under these different notions of frequencies. Specifically, we present a unified view of the various frequency counting algorithms. We propose a generic counting algorithm such that all current algorithms are special cases of it. This unified view allows one to gain insights into different frequencies, and we present quantitative relationships among different frequencies. Our unified view also helps in obtaining correctness proofs for various counting algorithms as we show here. It also aids in understanding and obtaining the anti-monotonicity properties satisfied by the various frequencies, the properties exploited by the candidate generation step of any apriori-based method. We also point out how our unified view of counting helps to consider generalization of the algorithm to count episodes with general partial orders.

Progress in tuberculosis vaccine development and host-directed therapies-a state of the art review

Tuberculosis continues to kill 1.4 million people annually. During the past 5 years, an alarming increase in the number of patients with multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis has been noted, particularly in eastern Europe, Asia, and southern Africa. Treatment outcomes with available treatment regimens for drug-resistant tuberculosis are poor. Although substantial progress in drug development for tuberculosis has been made, scientific progress towards development of interventions for prevention and improvement of drug treatment outcomes have lagged behind. Innovative interventions are therefore needed to combat the growing pandemic of multidrug-resistant and extensively drug-resistant tuberculosis. Novel adjunct treatments are needed to accomplish improved cure rates for multidrug-resistant and extensively drug-resistant tuberculosis. A novel, safe, widely applicable, and more effective vaccine against tuberculosis is also desperately sought to achieve disease control. The quest to develop a universally protective vaccine for tuberculosis continues. So far, research and development of tuberculosis vaccines has resulted in almost 20 candidates at different stages of the clinical trial pipeline. Host-directed therapies are now being developed to refocus the anti-Mycobacterium tuberculosis-directed immune responses towards the host; a strategy that could be especially beneficial for patients with multidrug-resistant tuberculosis or extensively drug-resistant tuberculosis. As we are running short of canonical tuberculosis drugs, more attention should be given to host-directed preventive and therapeutic intervention measures.

Phytoplankton size structure in the southern Bay of Bengal modified by the Summer Monsoon Current and associated eddies: Implications on the vertical biogenic flux

The present study combines field and satellite observations to investigate how hydrographical transformations influence phytoplankton size structure in the southern Bay of Bengal during the peak Southwest Monsoon/Summer Monsoon (July-August). The intrusion of the Summer Monsoon Current (SMC) into the Bay of Bengal and associated changes in sea surface chemistry, traceable eastward up to 90 degrees E along 8 degrees N, seems to influence biology of the region significantly. Both in situ and satellite (MODIS) data revealed low surface chlorophyll except in the area influenced by the SMC During the study period, two well-developed cydonic eddies (north) and an anti-cyclonic eddy (south), closely linked to the main eastward flow of the SMC, were sampled. Considering the capping effect of the low-saline surface water that is characteristic of the Bay of Bengal, the impact of the cyclonic eddy, estimated in terms of enhanced nutrients and chlorophyll, was mostly restricted to the subsurface waters (below 20 m depth). Conversely, the anti-cyclonic eddy aided by the SMC was characterized by considerably higher nutrient concentration and chlorophyll in the upper water column (upper 60 m), which was contrary to the general characteristic of such eddies. Albeit smaller phytoplankton predominated the southern Bay of Bengal (60-95% of the total chlorophyll), the contribution of large phytoplankton was double in the regions influenced by the SMC and associated eddies. Multivariate analysis revealed the extent to which SMC-associated eddies spatially influence phytoplankton community structure. The study presents the first direct quantification of the size structure of phytoplankton from the southern Bay of Bengal and demonstrates that the SMC-associated hydrographical ramifications significantly increase the phytoplankton biomass contributed by larger phytoplankton and thereby influence the vertical opal and organic carbon flux in the region. (C) 2014 Elsevier B.V. All rights reserved.

Evaluation of anti-obesity activities of ethanolic extract of Terminalia paniculata bark on high fat diet-induced obese rats

Background: The prevalence and severity of obesity and associated co-morbidities are rapidly increasing across the world. Natural products-based drug intervention has been proposed as one of the crucial strategies for management of obesity ailments. This study was designed to investigate the anti-obesity activities of ethanolic extract of Terminalia paniculata bark (TPEE) on high fat diet-induced obese rats. Methods: LC-MS/MS analysis was done for ethanolic extract of T. paniculata bark. Male Sprague-Dawley (SD) rats were randomly divided into six groups of six each, normal diet fed (NC), high fat diet-fed (HFD), HFD+ orlistat (standard drug control) administered, and remaining three groups were fed with HFD + TPEE in different doses (100,150 and 200 mg/kg b. wt). For induction of obesity rats were initially fed with HFD for 9 weeks, then, (TPEE) was supplemented along with HFD for 42 days. Changes in body weight, body composition, blood glucose, insulin, tissue and serum lipid profiles, atherogenic index, liver markers, and expression of adipogenesis-related genes such as leptin, adiponectin, FAS, PPARgamma, AMPK-1alpha and SREBP-1c, were studied in experimental rats. Also, histopathological examination of adipose tissue was carried out. Results: Supplementation of TPEE reduced significantly (P < 0.05) body weight, total fat, fat percentage, atherogenic index, blood glucose, insulin, lipid profiles and liver markers in HFD-fed groups, in a dose-dependent manner. The expression of adipogenesis-related genes such as Leptin, FAS, PPARgamma, and SREBP-1c were down regulated while Adiponectin and AMPK-1alpha were up regulated in TPEE + HFD-fed rats. Furthermore, histopathological examination of adipose tissue revealed the alleviating effect of TPEE which is evident by reduced size of adipocytes. Conclusions: Together, the biochemical, histological and molecular studies unambiguously demonstrate the potential anti adipogenic and anti obesity activities of TPEE promoting it as a formidable candidate to develop anti obesity drug.

Synthesis, electron microscopy and anti-microbial properties of Fe3O4-Ag nanotubes

Electrodeposition was used for synthesizing 200 nm diameter Fe3O4-Ag nanotubes. Compositional analysis at the single nanotube level revealed a fairly uniform distribution of component elements in the nanotube microstructure. As-synthesized Fe3O4-Ag nanotubes were superparamagnetic in nature. Electron diffraction revealed the ultrafine nanocrystalline microstructure of the nanotubes. The effect of Ag on the anti-microbial response of the nanotubes was investigated by comparing the effect of sulphate reducing bacteria (SRB) on Fe3O4-Ag and Fe3O4 nanotubes. Fe3O4 nanotubes were also electro-deposited in the present study. It was observed that the Fe3O4-Ag nanotubes exhibited good resistance to sulphate reducing bacteria which revealed the anti-microbial nature of the Fe3O4-Ag nanotubes.