Assessment of bacteria and SPM in the indoor air of households of urban area of Jammu (J&K), India

The present study was conducted to assess status of bacteria (Gram +ve and Gram –ve) in the indoor air of Households located in Jammu city. The study area was divided into eight Sites. At each site two Households were selected randomly and in each Household sampling of SPM (?g/m3) and bacteria (CFU/m3) was done twice at three sub sites. Total bacterial count and SPM was found to be maximum (9308.24 CFU/m3and1006.12 ?g/m3 respectively) in Households near Water Body and total bacterial count and SPM was minimum (5251.00 CFU/m3and 659.09?g/m3respectively) in Households near Hospital. A significant positive correlation (r) was found between SPM and no. of Gram +ve (+0.18 to +0.78) as well as between SPM and no. of Gram –ve (+0.21 to +0.76) bacteria in the study area

Work Details of Hospitality and Tourism Industry Workers and Impact on their Body

The hotel/restaurant/tourism sector covers a wide range of different businesses. It plays an important role as a job creator in the service sectors. This sector employs more than 7.8 million people in the India and is characterized by high job demands and high physical workload. It was found through a research that there was a change in worker\u27s work capacity or ability due to monotonous work and prolong standing posture during performing the work. The problems in the absence of ergonomically designed equipments, the prolonged standing posture and continuous working hours resulted to problems like lower and upper back problem, headache, swelling on ankles, stiffness in leg and hand joints etc. Besides this there were problems of slips, falls, repetitive body motion, and adoption of awkward posture. Seeing above problem a study was undertaken on 200 workers working in kumaun region of Uttarakhand. Descriptive cum experimental research approach was followed. The result showed that maximum 26 per cent of the workers were having the pain and discomfort at the lower back while doing the activity and 9.5 per cent workers faced problems in the legs and neck respectively

The Development of Peptide Analogues as Potential Fluorescent and PET Imaging Probes.

Molecular imaging is a non-invasive way to diagnose disease. Molecular imaging probes consist of a targeting entity that has a high affinity for a biological target and a signaling source for external detection. Multimodality imaging combines the advantages of different imaging modalities, at the same time eliminating their shortcomings, thereby providing more accurate results. This thesis focuses on the development of novel dual PET/fluorescence imaging agents based on peptides as targeting entities. Porphyrins are suitable for multimodality imaging applications due to their innate characteristics such as an ability to fluoresce and to coordinate metals. A gallium-protoporphyrin IX(PPIX)-ghrelin based analogue was designed as a potential dual PET/fluorescence imaging probe for detection of growth hormone secretagogue receptor 1a (GHS-R1a) and it was found that fluorescence was not quenched upon coordination to Ga. The PPIX-ghrelin analogue was also successfully radiolabeled with 68Ga. The specific uptake of this analogue by the receptor target, GHS-R1a, was demonstrated through confocal fluorescence microscopy using OVCAR-8 cells transfected with GHS-R1a. Thus, these dual modality probes can aid in bridging the gap and extend research from in vitro fluorescence imaging to in vivo PET imaging. 69/71Ga-hematoporphyrin-bombesin analogues were synthesized as potential PET/fluorescence imaging probes for the gastrin releasing peptide receptor (GRP-R), but the reaction yields were low and all the components of the hematoporphyrin-bombesin mixture could not be coordinated with gallium and this mixture of coordinated and the uncoordinated analogues could not be analyzed by optical methods. Nonetheless, the ability of hematoporphyrin to act as a chelator for Ga and to couple to peptides was demonstrated. BODIPY dyes are widely used for fluorescence imaging but suffer from drawbacks such as complicated synthesis and small Stokes shifts. However, novel BF2-formazanate dyes have favourable properties such as convenient synthesis and optical properties that can be tuned by modifying the structure. BF2-formazanate- peptide based analogues were developed as fluorescence imaging agents for GHS-R1a and GRP-R. Use of a modified ghrelin sequence led to an improvement in the IC50 value. Specific uptake of the probes could be visualized through fluorescence microscopy. Keywords Optical imaging, positron emission tomography, protoporphyrin, hematoporphyrin, GHS-R1a, GRP-R, BF2-formazanat

Identification of resistance mechanism to targeting of the ADAM 17/ EGFR axis in triple negative breast cancer in vivo

Triple-negative breast cancers (TNBCs) (ER/PR/HER2 negative) represent 15% of invasive\nbreast cancers and occur at a higher rate in young and African-American women. Exploration of\nnovel therapeutic approaches is critical, since only 30% of woman with metastatic breast cancer\nwill survive and virtually none with metastatic TNBC. The status quo as it pertains to the\ntreatment of TNBCs can be summarized as: no effective therapies available. In part, the lack of\ntherapeutic success is due to high genetic heterogeneity of TNBCs, challenging single drug\napproaches.\nMany targeted strategies to treat TNBC are being explored, including the inhibition of kinase\npathways (e.g. PI3K/Akt, MEK, VEGFR and PDGFR), the inhibition of DNA repair, of survival\npathways and androgen receptor blockade. In most cases, such single-drug targeted therapy is\ncombined with systemic genotoxic chemotherapy. For example, although about 60% of basallike\nTNBCs over express EGFR, EGFR targeted therapy, including kinase inhibition, has been\ndisappointing due to the development of resistance.\nVarious resistance mechanisms allow cancer cells to evade single-drug targeted therapies:\nmutations in the targeted molecules, extensive crosstalk/pathway redundancy and the upregulation\nof alternate growth or survival pathways. Design of combinatorial approaches of\ntherapeutics for TNBC that overcome resistance is therefore critical. The contribution of the\nproposed research is expected to be the identification of signaling network perturbations that\noccur in response to single targeted therapies, in particular in ADAM17/EGFR axis inhibition,\nand confer resistance. Based on published results, inhibition of the ADAM17/EGFR ligand axis\nin TNBC should provide therapeutic benefit with reduced tumor growth and decreased\nmetastasis, if not possibly cure.\nIn our in vitro studies on PKC? and PPP1R14D gene knockout in MDA-MB-231 cells indeed led\nto decreases in cellular growth and migration. However, to our surprise, when the same cells\nwere injected into mice through orthotropic fat pad transplantation, they produced aggressive,\nmetastatic tumors that showed activation of alternate growth signaling pathways, namely of the\nmitogen-activated protein kinase ERK and of the PI3kinase target Akt, also a mitogen activated\nkinase. This suggested that TNBC cells were developing resistance to EGF ligand regulator\nknockdown by rewiring their growth factor signaling pathways. To determine where these\nadditional growth signals come from, we first considered the tumor cells themselves.\nIn this context we discovered that when kept in culture, MDA-MB-231 cells expressing sh-\nRNAs targeting either PKCa or PPP1R14D maintained knockdown of the target for up to 35days\ntested. At the same time EGFR and ERK showed low activity as expected due to a decrease in\nEGF ligand cleavage; Akt activity was undetectable. Since we observed strong reactivation of\nERK and new activation of Akt in tumors in vivo, we considered possible up-regulation of other\ngrowth factor receptors on the cell surface that would be engaged by factors released from the\ntumor stroma once cells are inserted in vivo. Indeed, we found that FGFR2 and Erbb4 were\nupregulated. It is therefore likely that reactivation of ERK and new activation of Akt was due to\nFGFR2 and Erbb4. This would suggest that combination therapy of EGF ligand release regulator\ninhibition and FGFR inhibition would decrease growth of these tumors in vivo.Fil: Sharma, Neha. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaEl cáncer de mama triple negativo (TNCB) es aquel que no expresa el receptor de estrógenos\n(ER), ni el de progesterona (PR) o el HER2. Esta patología representa el 15% de los tumores de\nmama invasivos y tiene una alta incidencia en mujeres jóvenes Afro-Americanas. Es responsable\nde una alta tasa de mortalidad por cáncer de mama ya que generalmente el TNCB causa\nmetástasis; además, responde pobremente a las terapias con quimioterápicos a largo plazo y\ngeneralmente desarrolla resistencia a las terapias dirigidas, incluyendo las que implican al EGFR.\nPor todo ello, es fundamental el desarrollo de terapias alternativas, dado que solo el 30% de las\nmujeres con cáncer de mama metastásico sobrevive pero ninguna de las que presentan TNBC\nmetastásico.\nActualmente, no existe una terapia adecuada y efectiva para el TNBC. En parte, esto se debe a la\nalta heterogeneidad genética que presentan estos tumores, lo cual redunda en la inefectividad de\nterapias basadas en una única droga. Terapias basadas en blancos terapéuticos específicos están\nen investigación y desarrollo, como aquellas basadas en la inhibición de quinasas implicadas en\nseñalización (ejemplo: /Akt, MEK, VEGFR, PDGFR), reparación del DNA, supervivencia\ncelular o acciones androgénicas. Mayormente, estas terapias específicas son combinadas con\nquimioterapia sistémica. Sin embargo, hasta el momento, los beneficios de tales propuestas\nterapéuticas no son claros. Aproximadamente el 60% de los TNBC de tipo basal sobreexpresan\nEGFR; sin embargo, las terapias que implican la inhibición del receptor son mayormente\ninefectivas debido al desarrollo de resistencia. Distintos mecanismos están involucrados en el\ndesarrollo de resistencia a las terapias dirigidas, como ser mutaciones en la proteína blanco o la\nredundancia y sobreactivación de vías de señalización compartidas con otros factores de\ncrecimiento.\nPor lo tanto, es fundamental diseñar terapias combinadas para TNBC que contemplen el posible\ndesarrollo de resistencia. El trabajo de investigación propuesto intenta identificar alteraciones de\nvías de señalización intracelular ocasionadas por las terapias dirigidas, particularmente en lo que\nrespecta al eje ADAM17/EGFR, con el fin de establecer su posible implicancia en el desarrollo\nde resistencia.\nDado que se desconoce como es regulada la actividad y selectividad de ADAM17, se realizó un\namplio estudio mediante shRNA para dilucidar como se regula el clivaje de and PPP1R14D\nregulan el clivaje de TGFa, AREG y HB-EGF sin afectar la actividad proteasa de ADAM17. La\ninhibición del eje ADAM17/EGFR sería beneficioso para el tratamiento del TNBC. Nuestros\nestudios in vitro revelaron que células MDA MB 231 knockout para PKC? and PPP1R14D no\npresentan sobreactivación de RTKs, sugiriendo que en estos modelos podría verse potenciada la\neficacia terapéutica de la inhibición del eje ADAM17/EGFR.\nSin embargo, cuando las mismas células fueron inyectadas a ratones, produjeron un fenotipo de\ntumor agresivo y metastásico, asociado a la reactivación de vías de señalización intracelular\ncomo las mediadas por ERK y PI3K/Akt. Ello se asoció a un aumento de la expresión y\nactivación de distintas RTKs, incluido el EGFR como así también de Akt.\nEstos resultados sugieren la activación alternativa de vías de señalización que permiten que las\ncélulas tumorales proliferen y produzcan metástasis