Stem cell biology in thyroid cancer: Insights for novel therapies

Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.     

SHW1, a common regulator of abscisic acid (ABA) and light signaling pathways

In our recent paper in Plant Physiology, we have reported the identification and functional characterization of a unique regulator, SHW1, a serine-arginine-aspartate rich protein in Arabidopsis seedling development.¹ Genetic and molecular analyses have revealed that SHW1 functions in an independent and interdependent manner with COP1, and differentially regulates photomorphogenic growth and light regulated gene expression. Here, we show the involvement of photoreceptors in the function of SHW1. Our results have further revealed that SHW1 is a common regulator of light and ABA signaling pathways. These results along with some data described in Plant Physiology paper have been discussed here in a broader perspective.Key words: light signaling, photomorphogenesis, SHW1, COP1, ABA responsePlants are exposed to various intensities and wavelengths of light with a specific wavelength of light being predominant at a particular daytime. For example, plants are exposed to varied intensities of light in the morning and noon, or far-red light being predominant in the twilight. However, plants have also evolved to respond to and subsequently tackle such variations in light quality or quantity by multiple modes of actions. One such mode of action might be to employ multiple negative regulatory proteins that function as filtering units to light intensity. These negative regulators could be operative in a specific wavelength of light or in a broad spectrum of light². Identification and functional characterization of several negative regulators, including SHW1, of photomorphogenic growth support such notion. SHW1 does not seem to have a homologue in animal system or in lower eukaryotes, and thereby has evolved as a plant specific gene. When seedlings are exposed to light after reaching the soil surface, it is important to protect the emerging cotyledons from high intensity light that otherwise might get bleached and subsequently die. SHW1 is expressed in germinating seeds to flowering plants, and it is predominantly expressed in the photosynthetically active tissues.¹ Therefore, SHW1 might function as a filtering unit not only in the case of emerging seedlings in the soil but also in the adult plants during dark to light transition.     

Cold chain monitoring of OPV at transit levels in India: correlation of VVM and potency status

We have conducted a study to analyze monitoring of the cold chain of 674 OPV field samples collected at four different levels of vaccine distribution viz., immunization clinics, district stores, hospitals and Primary Health Centers (PHC) from states of Uttar Pradesh, Madhya Pradesh, and Delhi. The study design included: collection and scoring of vaccine vial monitor (VVM) status of the samples and testing for total oral polio virus concentration (TOPV) by standard WHO protocol. Ten samples each were exposed to 25 degrees C and 37 degrees C, and 10 samples as controls were kept at -20 degrees C. VVM were scored daily till they attained grade 4 and each sample was subsequently subjected to potency testing for individual polio serotypes 1, 2 and 3, and TOPV.Of the 674 samples tested it was observed that: samples from immunization clinics and district stores had an acceptable VVM score of grade 1 and 2; however the probable risk that a sub potent vaccine could have been administered was 2.15%. In 2.5% samples received from district stores vaccine had a VVM score of grade 3 (i.e., discard point), although vaccine when tested was found to be potent (i.e., leading to the vaccine wastage). With exposure to higher temperatures, VVM changed score to grade 2 and 3 when the vaccine was kept at 25 degrees C/37 degrees C, and the titres of individual serotypes 1, 2 and 3 and TOPV were beyond the acceptable limits.Important observations at the different levels of vaccine distribution network and correlation of VVM and potency status of OPV are discussed in the paper which will be of help to the EPI program managers at different transit levels.     

Spatial and Temporal Variability in Growing-Season Net Ecosystem Carbon Dioxide Exchange at a Large Peatland in Ontario,Canada

We measured net ecosystem exchange of carbon dioxide (CO2) (NEE) during wet and dry summers (2000 and 2001) across a range of plant communities at Mer Bleue, a large peatland near Ottawa, southern Ontario, Canada. Wetland types included ombrotrophic bog hummocks and hollows, mineral-poor fen, and beaver pond margins. NEE was significantly different among the sites in both years, but rates of gross photosynthesis did not vary spatially even though species composition at the sites was variable. Soil respiration rates were very different across sites and dominated interannual variability in summer NEE within sites. During the dry summer of 2001, net CO2 uptake was significantly smaller, and most locations switched from a net sink to a source of CO2 under a range of levels of photosynthetically active radiation (PAR). The wetter areas--poor fen and beaver pond margin--had the largest rates of CO2 uptake and smallest rates of respiratory loss during the dry summer. Communities dominated by ericaceous shrubs (bog sites) maintained similar rates of gross photosynthesis between years; by contrast, the sedge-dominated areas (fen sites) showed signs of early senescence under drought conditions. Water table position was the strongest control on respiration in the drier summer, whereas surface peat temperature explained most of the variability in the wetter summer. Q 10 temperature-respiration quotients averaged 1.6 to 2.2. The ratio between maximum photosynthesis and respiration ranged from 3.7:1 in the poor fen to 1.2:1 at some bog sites; it declined at all sites in the drier summer owing to greater respiration rates relative to photosynthesis in evergreen shrub sites and a change in both processes in sedge sites. Our ability to predict ecosystem responses to changing climate depends on a more complete understanding of the factors that control NEE across a range of peatland plant communities.     

Trypanosoma cruzi infection disturbs mitochondrial membrane potential and ROS production rate in cardiomyocytes

In this study, we investigated the role of Trypanosoma cruzi invasion and inflammatory processes in reactive oxygen species (ROS) production in a mouse atrial cardiomyocyte line (HL-1) and primary adult rat ventricular cardiomyocytes. Cardiomyocytes were incubated with T. cruzi (Tc) trypomastigotes, Tc lysate (TcTL), or Tc secreted proteins (TcSP) for 0–72 h, and ROS were measured by amplex red assay. Cardiomyocytes infected by T. cruzi (but not those incubated with TcTL or TcSP) exhibited a linear increase in ROS production for 2–48 h postinfection (max 18-fold increase), which was further enhanced by recombinant cytokines (IL-1β, TNF-α, and IFN-γ). We observed no increase in NADPH oxidase, xanthine oxidase, or myeloperoxidase activity, and specific inhibitors of these enzymes did not block the increased rate of ROS production in infected cardiomyocytes. Instead, the mitochondrial membrane potential was perturbed and resulted in inefficient electron transport chain (ETC) activity and enhanced electron leakage and ROS formation in infected cardiomyocytes. HL-1 rho (ρ) cardiomyocytes lacked a functional ETC and exhibited no increase in ROS formation in response to T. cruzi. Together, these results demonstrate that invasion by T. cruzi and an inflammatory milieu affect mitochondrial integrity and contribute to electron transport chain inefficiency and ROS production in cardiomyocytes.     

Studies on tamoxifen encapsulated in lipid vesicles: effect on the growth of human breast cancer MCF-7 cells

Tamoxifen is a nonsteroidal estrogen-receptor modulator widely used in the treatment of breast cancer. Apoptosis has been reported to be a major mechanism for its antitumor effect. In the current studies, an endeavor was made to investigate the efficacy of vesicularly encapsulated tamoxifen on human breast cancer MCF-7 cells. Phospholipid-based vesicular systems viz. conventional liposomes and elastic-membrane liposomes were employed to encapsulate the drug. The MTT colorimetric assay was used to determine the efficacy of the tested formulations. The results demonstrated composition-dependent strong inhibition in the viability of MCF-7 cells with encapsulated tamoxifen vis-à-vis free drug. The encouraging findings from the current work construe immense potential of the lipid-based vesicular systems in the treatment of breast cancer.     

Optimization of microporous palm shell activated carbon production for flue gas desulphurization: experimental and statistical studies

Optimizing the production of microporous activated carbon from waste palm shell was done by applying experimental design methodology. The product, palm shell activated carbon was tested for removal of SO2 gas from flue gas. The activated carbon production was mathematically described as a function of parameters such as flow rate, activation time and activation temperature of carbonization. These parameters were modeled using response surface methodology. The experiments were carried out as a central composite design consisting of 32 experiments. Quadratic models were developed for surface area, total pore volume, and microporosity in term of micropore fraction. The models were used to obtain the optimum process condition for the production of microporous palm shell activated carbon useful for SO2 removal. The optimized palm shell activated carbon with surface area of 973 m(2)/g, total pore volume of 0.78 cc/g and micropore fraction of 70.5% showed an excellent agreement with the amount predicted by the statistical analysis. Palm shell activated carbon with higher surface area and microporosity fraction showed good adsorption affinity for SO2 removal.     

Effect of catalyst additives on the production of biofuels from palm oil cracking in a transport riser reactor

Catalytic cracking of crude palm oil (CPO) and used palm oil (UPO) were studied in a transport riser reactor for the production of biofuels at a reaction temperature of 450 °C, with residence time of 20 s and catalyst-to-oil ratio (CTO) of 5 g g^?1. The effect of HZSM-5 (differrent Si/Al ratios), beta zeolite, SBA-15 and AlSBA-15 were studied as physically mixed additives with cracking catalyst Rare earth-Y (REY). REY catalyst alone gave 75.8 wt% conversion with 34.5 wt% of gasoline fraction yield using CPO, whereas with UPO, the conversion was 70.9 wt% with gasoline fraction yield of 33.0 wt%. HZSM-5, beta zeolite, SBA-15 and AlSBA-15 as additives with REY increased the conversion and the yield of organic liquid product. The transport riser reactor can be used for the continuous production of biofuels from cracking of CPO and UPO over REY catalyst.     

Syntheses and evaluation of glucosyl aryl thiosemicarbazide and glucosyl thiosemicarbazone derivatives as antioxidant and anti-dyslipidemic agents

A series of N-per-O-acetyl-glucosyl arylthiosemicarbazide and thiosemicarbazone derivatives have been synthesized and evaluated for their in vivo anti-dyslipidemic and in vitro antioxidant activities. Among 16 compounds tested, 3 compounds showed potent anti-dyslipidemic activity and 6 compounds showed potent antioxidant and scavenger of oxygen free radicals activity.     

SSR and AFLP based genetic diversity of soybean germplasm differing in photoperiod sensitivity

Forty-four soybean genotypes with different photoperiod response were selected after screening of 1000 soybean accessions under artificial condition and were profiled using 40 SSR and 5 AFLP primer pairs. The average polymorphism information content (PIC) for SSR and AFLP marker systems was 0.507 and 0.120, respectively. Clustering of genotypes was done using UPGMA method for SSR and AFLP and correlation was 0.337 and 0.504, respectively. Mantel's correlation coefficients between Jaccard's similarity coefficient and the cophenetic values were fairly high in both the marker systems (SSR = 0.924; AFLP = 0.958) indicating very good fit for the clustering pattern. UPGMA based cluster analysis classified soybean genotypes into four major groups with fairly moderate bootstrap support. These major clusters corresponded with the photoperiod response and place of origin. The results indicate that the photoperiod insensitive genotypes, 11/2/1939 (EC 325097) and MACS 330 would be better choice for broadening the genetic base of soybean for this trait.