Oct-4 expression maintained stem cell properties in prostate cancer-derived CD133+MDR1+ cells

Purpose: CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered an important marker that represents the subset population of cancer stem-like cells. The purpose of the present study is to isolate cancerous stem-like cells from normal healthy volunteers and prostate cancer patients (CD133+) which also express MDR1 and to ascertain the influence of Oct-4 on ‘stem-ness' and differentiation of these CD133+ cells towards epithelium. Methods: CD133+ cells were isolated using magnetic beads from normal healthy volunteers and prostate cancer patients (NV-CD133+and PC-CD133+). The isolated cells were analyzed using flow cytometry and Western blot technique for CD133, MDR1 and Oct-4. CD133+MDR1+ cells were cultured in presence and absence of antihuman Oct-4 blocking antibody. Results: PC-CD133+ cells displayed higher Oct-4 expression with the ability to self-renew and may represent a reservoir with differentiation potential for generating prostate cancer cells. Furthermore, PCCD133 + cells highly co-expressed the multiple drug-resistant marker MDR1. The treatment with Oct-4 blocking antibody can specifically block the capability of PC-CD133+ cells to differentiate into prostate epithelial cells bearing CD57. Conclusion: PC-CD133+ cells displayed a higher Oct-4 expression with the ability to self-renew and may represent a reservoir with differentiation potentials for progression of prostate cancer. The MDR1 expression of PC-CD133+ cells in vitro and in vivo is partially due to preferential activation of Oct-4 gene expression. Keywords: Prostate cancer, Cancer stem-like cells, Oct-4, CD133, Multi-drug resistance1 (MDR1)Tropical Journal of Pharmaceutical Research Vol. 8 (1) 2009: pp. 3-

Effectiveness of body–mind–spirit intervention on well‐being, functional impairment and quality of life among depressive patients – a randomized controlled trial

Aim The aim of the study was to examine the efficacy of body–mind–spirit Intervention in improving the outcomes (well-being, quality of life and functional impairment) among depressive patients. Background Depressive disorders lead to significant dysfunction, disability and poor quality of life among sufferers. Body–mind–spirit intervention has been associated with improvements in the outcomes; however, few studies have examined this among depressive patients. Design True experimental pre–post equivalent groups design was adopted with longitudinal measurement of outcomes. Methods Participants were 120 adult depressive patients visiting the psychiatric outpatient department in a District Hospital in India. The participants were randomly assigned to either the body–mind–spirit group or the treatment-as-usual group between July 2011–January 2013. The treatment-as-usual group (n = 64) received only routine treatment (antidepressants and structured psycho-education) in the hospital. The body–mind–spirit group (n = 56) received four weekly body–mind–spirit group sessions in addition to the routine treatment. Outcome measures on depression, well-being, functional impairment and quality of life were evaluated for both groups at baseline and at four follow-up assessments in the 1st, 2nd, 3rd and 6th month. Treatment effects of the body–mind–spirit intervention were analysed by repeated-measures analysis of covariance. Findings Compared with the treatment-as-usual group, the body–mind–spirit group showed significant reduction in depression and functional impairment, and significant improvement in the well-being and quality of life scores over the 6-month study period. Conclusion The present findings provided evidence for the effectiveness of integrating a complementary therapy such as the body–mind–spirit intervention with conventional treatment in improving prospective outcomes among the depressive patients.postprin

Knowledge Sources and International Business Activity in a Changing Innovation Ecosystem: A Study of the Indian Pharmaceutical Industry

The Indian pharmaceutical industry has experienced rapid growth, becoming the world's largest provider of generic drugs, based on product and process innovation. The industry has undergone dynamic changes in recent decades, operating in a rapidly evolving environment affected by domestic and global policies; a key example of the latter is the TRIPS agreement. Taking an intellectual property perspective, we describe how changes in the innovation ecosystem have affected companies’ strategies related to international activity and accessing knowledge from both internal and external knowledge sources, during the transitional- and post-TRIPS periods (1995–2004 and 2005–2014, respectively). Combining intellectual property arguments with contextual aspects of the innovation ecosystem, we conjecture that, in the post-TRIPS period, externally-sourced knowledge will be more important than internally-sourced knowledge, for Indian pharmaceutical firms’ international business activity

A case report of recalcitrant non union humerus treated with on lay fibular bone grafting and locking compression plate

Nonunion of diaphyseal fractures of the humerus are frequently seen in clinical practice (incidence of up to 15% in certain studies) and osteosynthesis using dynamic compression plates, intra medullary nails and Ilizarov fixators have been reported previously. Locking compression plates (LCP) are useful in the presence of disuse osteoporosis, segmental bone loss and cortical defects that preclude strong fixation. Fixation using a compression plate and a non-vascularised fibular graft achieves good outcome for infected non-union of the humerus despite prior multiple failed surgeries. We report a failed case of fracture shaft humerus which was operated three times, first with DCP and next two times with DCP and autologous cancellous bone graft from iliac crest. The patient is now treated with LCP and on lay fibular bone grafting

Expression of biopterin transporter (BT1) protein in Leishmania

The present work focuses on the growth phase regulated expression of biopterin transporter gene (BT1) from the LD1 locus on chromosome 35 of Leishmania donovani. Antiserum against recombinant BT1 detected a polypeptide of 45 kDa of equal intensity at lag, log and stationary phases of promastigote growth, both in L. donovani strain LSB-7.1 (MHOM/BL/67/ITMAP263), and strain LSB-146.1 (HOM/IR/95/X81), a natural isolate from Isfehan, Iran that caused cutaneous leishmaniasis. However, in both these strains an additional polypeptide of higher molecular mass (50 kDa) was also observed during lag phase only. In addition, polypeptides of 40, 20, 18 and 16 kDa were seen only during the lag and log phases of both strains. Analysis of L. donovani single, double and triple (null) BT1 knockout mutants confirmed that the 45-kDa polypeptide was the BT1 gene product, as it was absent in the null mutant. These results indicate that 45-kDa BT1 protein in Leishmania is consistently and constitutively expressed in all the growth stages of the parasite

Supersymmetry Breaking Triggered by Monopoles

We investigate N = 1 supersymmetric gauge theories where monopole condensation triggers supersymmetry breaking in a metastable vacuum. The low-energy effective theory is an O'Raifeartaigh-like model of the kind investigated recently by Shih where the R-symmetry can be spontaneously broken. We examine several implementations with varying degrees of phenomenological interest.Comment: 20 pages, 4 figures (v2: minor clarifications and typos fixed

Role of biopterin transporter (BT1) gene on growth and infectivity of Leishmania

Leishmania are known to be auxotrophic for pteridines that are known to play a critical role in the parasites survival. In the present work the role of biopterin transporter in the growth of the parasite and infectivity in to macrophages has been worked out. The role of biopterin transporter in the susceptibility of Leishmania to antimonial compounds has also been demonstrated. This role has been verified by using attenuated strains of Leishmania with single, double, and triple (null) biopterin (BT1) mutants made by targeted gene replacement with specific antibiotic markers. Growth analysis of these mutants revealed that wild type, single and double knock out cell lines maintained high growth rates in the medium supplemented with biopterin and folate, whereas the triple knock out or null BT1 mutants were unable to grow in the absence of supplemental biopterin. Using wild type and null BT1 mutants, we examined the role of BT1 gene in infectivity and parasite survival. The cell lines with amplified BT1 gene showed increased infectivity and survival in the macrophages where as the cell lines with disrupted BT1 gene showed reduced infectivity and survival in the macrophages. We also examined the interaction between pteridine and antimonial compounds using recombinant Leishmania strains with reduced or absent biopterin transporter gene (BT1) alleles. No difference in susceptibility to Pentostam or Glucantime was observed in both wild type and BT1-knock out strains. However, pterin or folate supplementation resulted in reversal of Glucantime but not Pentostam susceptibility in both wild type and BT1-knock out strains. The reversal of Glucantime susceptibility by pterins in BT1-knock out strains suggests that the effect may be exerted independently of biopterin transporter, possibly by blocking Glucantime uptake

The Leishmania donovani LD1 locus gene ORFG encodes a biopterin transporter (BT1)

We have previously described two genes, ORFF and ORFG, from the LD1 locus near one telomere of chromosome 35, which are frequently amplified in Leishmania isolates. In Leishmania donovani LSB-51.1, gene conversion of the rRNA gene locus on chromosome 27 with these two genes resulted in their over-expression, because of their transcription by the RNA polymerase I-mediated rRNA promoter. The predicted ORFG protein has substantial sequence homology to the ESAG10 gene product from the Trypanosoma brucei VSG expression site and both are putative membrane proteins. Using successive rounds of gene replacement of the three ORFG genes in L. donovani LSB-51.1, ORFG null mutants were obtained. These mutant cell lines show a direct relationship between ORFG mRNA, protein expression levels and active transport of biopterin into the cells. Transformation of the null mutant with a plasmid containing ORFG restores biopterin transport activity. In addition, the null mutants are unable to grow in the absence of supplemental biopterin. Thus, ORFG encodes a biopterin transporter and has been renamed BT1

Simplified Models for LHC New Physics Searches

This document proposes a collection of simplified models relevant to the design of new-physics searches at the LHC and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the "Topologies for Early LHC Searches" workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first ~50-500 pb-1 of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results from "Topologies for Early LHC Searches" workshop (SLAC, September 2010). Supplementary material can be found at http://lhcnewphysics.or