A new species of Eriocaulon (Eriocaulaceae) from Madhya Pradesh, India

Eriocaulon raipurense (Eriocaulaceae) is described and illustrated as a new species from Madhya Pradesh, India. The species is closely allied to E. hamiltonianum but differs in the size and apex of involucral bancts, white-pilose nature of floral bracts and colour of female petals.     

BaTiO3-Graphene-Affinity Layer–Based Surface Plasmon Resonance (SPR) Biosensor for Pseudomonas Bacterial Detection

Plasmonics - In the present work, a highly sensitive SPR biosensor based on silver (Ag), barium titanate (BaTiO3), graphene, and affinity layer is proposed for the detection of Pseudomonas...     

Synthesis of functionalized amino acid derivatives as new pharmacophores for designing anticancer agents

A new series of functionalized amino acid derivatives N-substituted 1-N-(tert-butoxycarbonyl)-2,2-dimethyl-4-phenyl-5-oxazolidine carboxamide (1-17) and 1-N-substituted-3-amino-2-hydroxy-3-phenylpropane-1-carboxamide (18-34) were synthesized and evaluated for their in vitro cytotoxicity against human cancer cell lines. Compound 6 has shown interesting cytotoxicity (IC₅₀ = 5.67 μm) in ovarian cancer, while compound 10 exhibited promising cytotoxicity in ovarian (IC₅₀ = 6.1 μm) and oral (IC₅₀ = 4.17 μm) cancers. These compounds could be of use in designing new anti-cancer agents.     

Effect of Organic Selenium Supplementation on Growth, Se Uptake, and Nutrient Utilization in Guinea Pigs

Forty weaned male guinea pigs (Cavia porcellus) of 152.6?±?7.96 g mean body weight were divided into four equal groups and fed a common basal diet comprised of 25% ground cowpea (Vigna unguiculata) hay, 30% ground maize (Zea mays) grain, 22% ground gram (Cicer arietinum) grain, 9.5% deoiled rice (Oryza sativa) bran, 6% soybean (Glycine max) meal, 6% fish meal, 1.5% mineral mixture (without Se), and ascorbic acid at 200 mg/kg to meet their nutrient requirements along with 0, 0.1, 0.2, and 0.3 ppm of organic selenium (Se) in groups I, II, III, and IV, respectively. Experimental feeding lasted for a period of 10 weeks, during which, daily feed intake and weekly body weights were recorded. Intake and digestibility of dry matter, organic matter, ether extract, crude fiber, and nitrogen-free extract as well as uptake of calcium and phosphorus were similar (P?>?0.05) among the four groups. Feed:gain ratio was also similar (P?>?0.05) in the four groups. However, digestibility of crude protein was significantly (P?<?0.001) higher in group II supplemented with 0.1 ppm organic Se as compared to other three group. Intake and absorption of Se was significantly (P?<?0.001) higher in all the Se supplemented groups as compared to control group. Average daily gain (ADG) was significantly (P?<?0.05) higher in group II (3.16 g/day) and III (3.38 g/day) as compared to group I (2.88 g/day). However, ADG in group IV (supplemented 0.3 ppm organic Se) was significantly (P?<?0.05) lower (2.83 g/day) than group II and III, but comparable (P?>?0.05) to group I. Findings of the present experiment suggests that Se requirements of guinea pigs are ≥0.2 ppm, as supplementation of 0.1 ppm organic Se in the diet (having 0.1 ppm Se) not only enhanced their growth rate but also improved the protein utilization.     

Quantifying the significance of phage attack on starter cultures: a mechanistic model for population dynamics of phage and their hosts isolated from fermenting sauerkraut

We investigated the possibility of using starter cultures in sauerkraut fermentation and thereby reducing the quantity of salt used in the process. This, in turn, would reduce the amount of waste salt that would enter in our water resources. Phage, naturally present in sauerkraut fermentation, could potentially affect the starter cultures introduced. Thus, a mechanistic mathematical model was developed to quantify the growth kinetics of the phage and starter cultures. The model was validated by independent experiments with two Leuconostoc mesenteroides strains isolated from sauerkraut and their corresponding phage. Model simulations and experimental evidence showed the presence of phage-resistant cell populations in starter cultures which replaced phage-sensitive cells, even when the initial phage density (P(0)) and multiplicity of infection (MOI) were low (P(0) < 1 x 10(3) PFU/ml; MOI < 10(-4)) in the MRS media. Based on the results of model simulation and parameter optimization, it was suggested that the kinetic parameters of phage-host interaction, especially the adsorption rate, vary with the initial phage and host densities and with time. The model was validated in MRS broth. Therefore, the effects of heterogeneity and other environmental factors, such as temperature and pH, should be considered to make the model applicable to commercial fermentations.     

Effect of different levels of selenium supplementation on growth rate, nutrient utilization, blood metabolic profile, and immune response in lambs

Eighteen male lambs (8-9 months of age, 25.00 +/- 0.90 kg body weight) were divided into three groups of six animals in each and fed a total mixed ration (TMR) containing concentrate mixture (30% maize grain, 27% soybean meal, 40% wheat bran, 2% mineral mixture, and 1% common salt) and wheat straw in 65:35 ratio and supplemented with selenium (Se) as sodium selenite at 0 (T1, control), 0.15 (T2), and 0.30 ppm (T3) levels. Experimental feeding was done for a period of 90 days including a 6-day metabolism trial. To assess the growth performance, lambs were weighed every 15 days throughout the experimental period. All the lambs were intramuscularly inoculated with a single dose (2 ml) of haemorrhagic septicaemia oil adjuvant vaccine on 0 day to evaluate the humoral immune response. Blood samples were collected on 0 day and thereafter at 30 days interval. Results revealed that supplementation of Se both at 0.15 and 0.30 ppm levels had no significant (P > 0.05) effect on intake and digestibility of dry matter, organic matter, crude protein (CP), ether extract, neutral detergent fiber, acid detergent fiber, and hemicellulose; balances of calcium and phosphorus; and level and intake of digestible CP and total digestible nutrients. Se supplementation also had no significant (P > 0.05) effect on the levels of serum total cholesterol, total protein, albumin, globulin, albumin/globulin ratio, tri-iodothyronine (T(3)), thyroxine (T(4)), and T(4)/T(3) ratio; and serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase enzyme activity in the lambs. However, there was a significant (P < 0.05) increase in the plasma Se levels, red blood cell glutathione peroxidase enzyme activity, and humoral immune response in both the Se-supplemented groups. Feed (TMR) required per kilogram gain was less by 11.1% and 16.5% in groups T2 and T3, respectively, as compared to control (T1) group. Average daily gain was highest (108.5 g) in group T3, followed by group T2 (98.2 g), and lowest (89.06 g) in the control group (T1). These results indicated that supplementation of 0.15 and 0.3 ppm Se in the diet (having 0.19 ppm Se) of lambs significantly improves their immune response and antioxidant status.     

Selenium supplementation influences growth performance, antioxidant status and immune response in lambs

To investigate and compare the effect of inorganic and organic Se supplementation, 18 male lambs (24.68 ± 2.89 kg mean body weight, about 8–9 months of age) were divided into three groups of six animals in each, following randomized block design. While animals in the control group (Gr I) were fed a standard TMR containing 195 g/kg crushed maize grain, 175.5 g/kg soybean meal, 260 g/kg wheat bran, 13 g/kg mineral mixture (without Se), 6.5 g/kg common salt and 350 g/kg wheat straw, animals in Gr II and Gr III were additionally supplemented with 0.15 mg Se/kg of diet through sodium selenite (inorganic Se) and Jevsel-101 (organic Se), respectively. Experimental feeding was done for a period of 90 days. To assess the humoral immune response, all the lambs were intramuscularly inoculated with a single dose (2 mL) of Haemorrhagic septicaemia oil adjuvant vaccine on day 0; and blood samples were collected on day 0, 30, 60 and 90. Supplementation of Se had no effect on serum total cholesterol, total protein, albumin, globulin, albumin:globulin ratio, T₃, T₄, T₄:T₃ ratio; serum Ca and P levels and SGOT and SGPT activity. However, there was a significant increase in the serum Se level, RBC GSH-Px activity and humoral immune response in both the Se supplemented groups as compared to control group. Average daily gain (g) was highest (110) in Gr III, followed by Gr II (98.2) and lowest in Gr I (89.1). Thus, supplementation of organic as well as inorganic Se was found to improve the growth rate, humoral immune response and antioxidant status of the lambs; and between two sources, organic Se was more effective than inorganic Se.     

Synthesis of functionalized amino acid derivatives as new pharmacophores for designing anticancer agents

A new series of functionalized amino acid derivatives N-substituted 1-N-(tert-butoxycarbonyl)-2,2-dimethyl-4-phenyl-5-oxazolidine carboxamide (1-17) and 1-N-substituted-3-amino-2-hydroxy-3-phenylpropane-1-carboxamide (18-34) were synthesized and evaluated for their in vitro cytotoxicity against human cancer cell lines. Compound 6 has shown interesting cytotoxicity (IC(50) = 5.67 microm) in ovarian cancer, while compound 10 exhibited promising cytotoxicity in ovarian (IC(50) = 6.1 microm) and oral (IC(50) = 4.17 microm) cancers. These compounds could be of use in designing new anti-cancer agents.     

Heterogeneity of Pancreatic Cancer Metastases in a Single Patient Revealed by Quantitative Proteomics

Many patients with pancreatic cancer have metastases to distant organs at the time of initial presentation. Recent studies examining the evolution of pancreatic cancer at the genetic level have shown that clonal complexity of metastatic pancreatic cancer is already initiated within primary tumors, and organ-specific metastases are derived from different subclones. However, we do not yet understand to what extent the evolution of pancreatic cancer contributes to proteomic and signaling alterations. We hypothesized that genetic heterogeneity of metastatic pancreatic cancer results in heterogeneity at the proteome level. To address this, we employed a model system in which cells isolated from three sites of metastasis (liver, lung, and peritoneum) from a single patient were compared. We used a SILAC-based accurate quantitative proteomic strategy combined with high-resolution mass spectrometry to analyze the total proteome and tyrosine phosphoproteome of each of the distal metastases. Our data revealed distinct patterns of both overall proteome expression and tyrosine kinase activities across the three different metastatic lesions. This heterogeneity was significant because it led to differential sensitivity of the neoplastic cells to small molecule inhibitors targeting various kinases and other pathways. For example, R428, a tyrosine kinase inhibitor that targets Axl receptor tyrosine kinase, was able to inhibit cells derived from lung and liver metastases much more effectively than cells from the peritoneal metastasis. Finally, we confirmed that administration of R428 in mice bearing xenografts of cells derived from the three different metastatic sites significantly diminished tumors formed from liver- and lung-metastasis-derived cell lines as compared with tumors derived from the peritoneal metastasis cell line. Overall, our data provide proof-of-principle support that personalized therapy of multiple organ metastases in a single patient should involve the administration of a combination of agents, with each agent targeted to the features of different subclones.Approximately half of the patients with pancreatic cancer are initially diagnosed with metastases to distal sites, with the commonest sites being the liver, lung, and peritoneum (1). Therapeutic strategies against metastases could help reduce the high mortality rates associated with this cancer (2). Understanding the nature of metastatic pancreatic cancer at a systems level can enable the discovery of potential targets for the development of targeted therapies.Pancreatic cancer has been shown to be a genetically evolving and heterogeneous disease (3–5). Clonal diversity and evolution of cancer genomes have also been demonstrated based on the isolation of distinct clonal populations purified directly from patient biopsies by means of flow cytometry followed by genomic characterization (6). A number of reports have documented the adoption of a proteomic approach for the discovery of potential biomarkers in pancreatic cancer (7, 8). However, these studies generally assume pancreatic cancers to be homogeneous, and the emphasis is placed on identifying molecules that are common across a broad array of tumors. There is a lack of studies systematically examining the proteomic changes or signaling pathways across pancreatic cancers to dissect the nature of the heterogeneity of each clone. An excellent setting in which the heterogeneity of tumors can be studied systematically is in a patient harboring metastases to several distant sites. To this end, we chose cells isolated from three metastatic pancreatic lesions of a single patient. The exomes of each tumor site were previously sequenced to study the progression of pancreatic cancer, and the results showed that all cell lines were identical for the genetic status of driver mutations (e.g. KRAS, TP53, and SMAD4) (9). Our hypothesis was that a better understanding of the proteomic consequences of the heterogeneity derived from genetic changes, and possibly other types of alterations, might provide additional opportunities to identify therapeutic targets.In order to precisely quantify differences across the proteomes of multiple metastatic pancreatic cancer lesions, we employed a SILAC-based¹ quantitative proteomics strategy combined with high-resolution mass spectrometry (10, 11). Based on changes observed at the whole-proteome level, we found that a class of cell surface receptors showed significant enrichment with the highest alteration of their expression among the three metastatic pancreatic cancer cell lines examined (i.e. peritoneum, lung, and liver). Because the total protein levels provide information about the static levels of proteins and not their activity per se, we decided to examine the activation of phosphorylation-driven pathways, many of which are activated by cell surface receptors. To globally examine tyrosine phosphorylation-based signaling pathways, we carried out mass spectrometric analysis of purified tyrosine phosphorylated peptides enriched using anti-phosphotyrosine antibodies. As a result, we observed differential activation of tyrosine kinases in the three different sites of metastases. For example, Axl receptor tyrosine kinase was found to be hyperphosphorylated in lung and liver metastases relative to peritoneal metastasis. Expression of Axl receptor tyrosine kinase in primary and matched pancreatic cancers on tissue microarrays was validated by immunohistochemistry. Given such unique patterns of activation of pathways, it was possible that tumors derived from different sites could show differences in their sensitivity to pathway inhibitors. To test this, we performed experiments in which we screened cell lines derived from each metastatic site against a panel of small molecule inhibitors. We observed that the three metastatic pancreatic cancers had differential sensitivities to different inhibitors. For example, cells derived from the peritoneal metastasis were highly sensitive to lapatinib, whereas greater sensitivity to the Axl inhibitor R428 was observed in the lung metastasis cell line. Finally, we showed that treatment of mice bearing xenografts from these different pancreatic cancer cell lines with R428, an inhibitor of Axl receptor tyrosine kinase, led to reduction of tumors with evidence of activation of Axl.