Thiazole Antibiotic Thiostrepton Synergize with Bortezomib to Induce Apoptosis in Cancer Cells

Thiazole antibiotic, thiostrepton was recently identified as proteasome inhibitor. We investigated the therapeutic potential of the combination of thiostrepton and proteasome inhibitor bortezomib (Velcade) on various human tumor cell lines. Combination of sub-lethal concentrations of thiostrepton and bortezomib induced potent apoptosis and inhibition of long-term colony formation in a wide variety of human cancer cell lines. The synergistic relationship between thiostrepton and bortezomib combination was also quantitatively demonstrated by calculating their combination index values that were much lower than 1 in all studied cell lines. The synergy between these drugs was based on their proteasome inhibitory activities, because thiostrepton modification, thiostrepton methyl ester, which did not have intact quinaldic acid ring and did not inhibit proteasome activity failed to demonstrate any synergy in combination with bortezomib

"Nala-ki bata": An edition with translation, grammatical study, and glossary.

The thesis is an edition with a critical apparatus of a Rajasthani MS. Nala-ki bata by Bhangcanda Bhavasa, Royal Asiatic Society, Todd Collection No. 81. The work appears to have been written in the early part of the 19th century, as a date in Samvat corresponding to A.D. 1806 is found written at the end of another story (Dhola Maruji-ki bata) appended to the story of the MS. The thesis consists of four parts. A grammatical study of the language of the MS. Part II Text with critical footnotes. Part III Translation. Part IV Complete glossary of the text with notes on the derivation of most of the words

Ventricular remodelling in rabbits with sustained high‐fat diet

Aim Excess weight gain and obesity are one of the most serious health problems in the western societies. These conditions enhance risk of cardiac disease and have been linked with increased prevalence for cardiac arrhythmias and sudden death. Our goal was to study the ventricular remodelling occurring in rabbits fed with high‐fat diet ( HFD ) and its potential arrhythmogenic mechanisms. Methods We used 15 NZW rabbits that were randomly assigned to a control ( n  = 7) or HFD group ( n  = 8) for 18 weeks. In vivo studies included blood glucose, electrocardiographic, and echocardiographic measurements. Optical mapping was performed in Langendorff‐perfused isolated hearts. Results Body weight (3.69 ± 0.31 vs. 2.94 ± 0.18 kg, P  < 0.001) and blood glucose levels (230 ± 61 vs. 141 ± 14 mg dL −1 , P  < 0.05) were higher in the HFD group vs. controls. The rate‐corrected QT interval and its dispersion were increased in HFD rabbits vs. controls (169 ± 10 vs. 146 ± 13 ms and 37 ± 11 vs. 9 ± 2 ms, respectively; P  < 0.05). Echocardiographic analysis showed morphological and functional alterations in HFD rabbits indicative of left ventricle (LV) hypertrophy. Isolated heart studies revealed no changes in repolarization and propagation properties under conditions of normal extracellular K + , suggesting that extrinsic factors could underlie those electrocardiographic modifications. There were no differences in the dynamics of ventricular fibrillation (frequency, wave breaks) in the presence of isoproterenol. However, HFD rabbits showed a small reduction in action potential duration and an increased incidence of arrhythmias during hyperkalaemia. Conclusion High‐fat feeding during 18 weeks in rabbits induced a type II diabetes phenotype, LV hypertrophy, abnormalities in repolarization and susceptibility to arrhythmias during hyperkalaemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106944/1/apha12185.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106944/2/apha12185-sup-0001-FigS1-S4TableS1-S3.pd

SUPFAM: A database of sequence superfamilies of protein domains

BACKGROUND: SUPFAM database is a compilation of superfamily relationships between protein domain families of either known or unknown 3-D structure. In SUPFAM, sequence families from Pfam and structural families from SCOP are associated, using profile matching, to result in sequence superfamilies of known structure. Subsequently all-against-all family profile matches are made to deduce a list of new potential superfamilies of yet unknown structure. DESCRIPTION: The current version of SUPFAM (release 1.4) corresponds to significant enhancements and major developments compared to the earlier and basic version. In the present version we have used RPS-BLAST, which is robust and sensitive, for profile matching. The reliability of connections between protein families is ensured better than before by use of benchmarked criteria involving strict e-value cut-off and a minimal alignment length condition. An e-value based indication of reliability of connections is now presented in the database. Web access to a RPS-BLAST-based tool to associate a query sequence to one of the family profiles in SUPFAM is available with the current release. In terms of the scientific content the present release of SUPFAM is entirely reorganized with the use of 6190 Pfam families and 2317 structural families derived from SCOP. Due to a steep increase in the number of sequence and structural families used in SUPFAM the details of scientific content in the present release are almost entirely complementary to previous basic version. Of the 2286 families, we could relate 245 Pfam families with apparently no structural information to families of known 3-D structures, thus resulting in the identification of new families in the existing superfamilies. Using the profiles of 3904 Pfam families of yet unknown structure, an all-against-all comparison involving sequence-profile match resulted in clustering of 96 Pfam families into 39 new potential superfamilies. CONCLUSION: SUPFAM presents many non-trivial superfamily relationships of sequence families involved in a variety of functions and hence the information content is of interest to a wide scientific community. The grouping of related proteins without a known structure in SUPFAM is useful in identifying priority targets for structural genomics initiatives and in the assignment of putative functions. Database URL:

Condensation of Silica Nanoparticles on a Phospholipid Membrane

The structure of the transient layer at the interface between air and the aqueous solution of silica nanoparticles with the size distribution of particles that has been determined from small-angle scattering has been studied by the X-ray reflectometry method. The reconstructed depth profile of the polarizability of the substance indicates the presence of a structure consisting of several layers of nanoparticles with the thickness that is more than twice as large as the thickness of the previously described structure. The adsorption of 1,2-distearoyl-sn-glycero-3-phosphocholine molecules at the hydrosol/air interface is accompanied by the condensation of anion silica nanoparticles at the interface. This phenomenon can be qualitatively explained by the formation of the positive surface potential due to the penetration and accumulation of Na+ cations in the phospholipid membrane.Comment: 7 pages, 5 figure

Evidence for Excimer Photoexcitations in an Ordered {\pi}-Conjugated Polymer Film

We report pressure-dependent transient picosecond and continuous-wave photomodulation studies of disordered and ordered films of 2-methoxy-5-(2-ethylhexyloxy) poly(para-phenylenevinylene). Photoinduced absorption (PA) bands in the disordered film exhibit very weak pressure dependence and are assigned to intrachain excitons and polarons. In contrast, the ordered film exhibits two additional transient PA bands in the midinfrared that blueshift dramatically with pressure. Based on high-order configuration interaction calculations we ascribe the PA bands in the ordered film to excimers. Our work brings insight to the exciton binding energy in ordered films versus disordered films and solutions. The reduced exciton binding energy in ordered films is due to new energy states appearing below the continuum band threshold of the single strand.Comment: 5.5 pages, 5 figure

Effect of Different Spacing and Mulching on Growth and Yield of Okra (Abelmoschus Esculentus L.) in Chitwan, Nepal

Okra (Abelmoschus esculentus L.) is one of the most important vegetable crop of Nepal. Its yield and growth parameters are affected by different cultural practices. This study was conducted at Olericulture Farm of Agriculture and Forestry University, Rampur, Chitwan, Nepal during April 29 to July 9 of 2018. The field experiment was carried out in split plot design using three replications. The treatments consisted of three intra row spacing (30, 45 and 60 cm) and four different mulching materials (Silver plastic, Panicum repens, Lantana camara and bare soil). The objective of this experiment was to assess the effects of various intra-row spacings and mulching materials on growth and yield of okra. The effect of mulching materials on okra yield was found significant. The okra yield was highest (8104 kg/ha) under silver plastic mulch followed by control (5161kg/ha), Panicum repens (3901kg/ha) and Lantana camera (3701kg/ha), respectively. Silver plastic mulch enhanced the growth parameters like canopy length, plant height, leaf number, leaf length, girth and yield of okra. The spacings provided non significant effect on okra yield, however the yield of okra was highest (7295 kg/ha) under 30×30 cm spacing followed by 45×30 cm (4660 kg/ha) and 60 cm × 30 cm spacing (3703 kg/ha), respectively. Combination of silver plastic mulch along with 30 cm × 30 cm spacing provided the highest okra yield. This study suggests that farmers of the Chitwan should grow okra at spacing of 30 cm × 30 cm and under silver plastic mulch to produce higher yield

Exact results and scaling properties of small-world networks

We study the distribution function for minimal paths in small-world networks. Using properties of this distribution function, we derive analytic results which greatly simplify the numerical calculation of the average minimal distance, $\bar{\ell}$, and its variance, $\sigma^2$. We also discuss the scaling properties of the distribution function. Finally, we study the limit of large system sizes and obtain some analytic results.Comment: RevTeX, 4 pages, 5 figures included. Minor corrections and addition