A family of amphiphilic dioxidovanadium(V) hydrazone complexes as potent carbonic anhydrase inhibitors along with anti-diabetic and cytotoxic activities

BioMetals - A family of dioxidovanadium(V) complexes (1–4) of the type [Na(H2O)x]+[VVO2(HL1?4)]? (x?=?4, 4.5 and 7) where HL2? represents the dianionic form of...     

Degradation of bacterial DNA by a natural antimicrobial agent with the help of biomimetic membrane system

The antimicrobial efficacy of methylglyoxal (MG) against several gram-negative bacteria including Escherichia coli has been reported. To determine the mechanism of action of MG, molecular interactions between lipid and MG within the liposomal membrane were also investigated. Multilamellar and unilamellar vesicles were prepared from 1, 2-dipalmitoyl-snglycero-3-phosphocholine (DPPC). The effect of MG on DPPC liposomal membrane was studied by fluorescence spectroscopy and differential scanning calorimetry. The results indicate that MG interacts mainly with the DPPC head group that produces a significant increase in the fluidity of liposomal vesicles, which could be the cause of a fusion/aggregation effect in microbial cells. The agarose gel electrophoresis study with the genomic DNA extracted from E. coli ATCC 25922 revealed that addition of MG could completely degrade this DNA within 1 h, pointing out to their distinctly high degree of sensitivity towards MG. Further, the drug was able to cross the cell membranes, penetrating into the interior of the cell and interacting with DNA for demonstrating antibacterial activity of MG.     

Identification and optimization of small molecule antagonists of vasoactive intestinal peptide receptor-1 (VIPR1)

Identification, synthesis and structure-activity relationship of small-molecule VIPR1 antagonists encompassing two chemical series are described.     

Distinct synergistic action of piperacillin and methylglyoxal against Pseudomonas aeruginosa

The dicarbonyl compound methylglyoxal is a natural constituent of Manuka honey produced from Manuka flowers in New Zealand. It is known to possess both anticancer and antibacterial activity. Such observations prompted to investigate the ability of methylglyoxal as a potent drug against multidrug resistant Pseudomonas aeruginosa. A total of 12 test P. aeruginosa strains isolated from various hospitals were tested for their resistances against many antibiotics, most of which are applied in the treatment of P. aeruginosa infections. Results revealed that the strains were resistant to many drugs at high levels, only piperacillin, carbenicillin, amikacin and ciprofloxacin showed resistances at comparatively lower levels. Following multiple experimentations it was observed that methylglyoxal was also antimicrobic against all the strains at comparable levels. Distinct and statistically significant synergism was observed between methylglyoxal and piperacillin by disc diffusion tests when compared with their individual effects. The fractional inhibitory concentration index of this combination evaluated by checkerboard analysis, was 0.5, which confirmed synergism between the pair. Synergism was also noted when methylglyoxal was combined with carbenicillin and amikacin.     

N,N-dimethylsphingosine-coumarin: synthesis, chemical characterization, and biological evaluation

Coumarin derivatives of N,N-dimethylsphingosine (DMSP) were prepared and chemically characterized. They were apparently biologically equivalent to DMSP in terms of tumor cell cytotoxicity and were used to establish the rapid mitochondrial localization of this sphingolipid in tumor cells, followed closely by its marked reduction of mitochondrial membrane potential.     

不同桑树基因型的遗传多样性研究

调查了印度 25 个不同农业气候条件下的桑树(Morus spp.)基因型的 14 个形态测量性状, 以研究它们的遗传多样性分布特点。研究发现在 14 个性状中存在广泛的遗传变异。25 个不同基因型的桑树被分为 10 个簇。实验结果表明 7 种基因型桑树 Baragura-2, Gorabandha-2, Kalimpong, Herbertpur, Kollegal, Resham majri-7 和 UP-14 的遗传资源是重要的。对不同基因型桑树性状的关联分析显示, 对桑树叶片长度、新鲜叶的总量、叶片面积和单个叶的重量这些性状的直接筛选将有助于提高桑树叶片的产量。     

PluriPred: A Web server for predicting proteins involved in pluripotent network

Pluripotency is a unique property of stem cells that allows them to differentiate into all types of adult cells or maintain the self-renewal property. PluriPred predicts whether a protein is involved in pluripotency from primary protein sequence using manually curated pluripotent proteins as training datasets. Machine learning techniques (MLTs) such as Support Vector Machine (SVM), Naïve Base (NB), Random Forest (RF), and sequence alignment technique BLAST were used in our study. The combination of SVM and PSI-BLAST was our proposed best model, which obtained a sensitivity of 77.40%, specificity of 79.72%, accuracy of 79.2%, and area under the ROC curve was 0.82 using 5-fold cross-validation. Furthermore, PluriPred gives the confidence of the prediction from training dataset’s SVM score distribution and p-value from BLAST. We validated our proposed model with the other existing high-throughput studies using blind/independent datasets. Using PluriPred, 233 novel core and 323 novel extended core pluripotent proteins from mouse proteome, and 167 novel core and 385 extended core pluripotent proteins from human proteome, were predicted with high confidence. The Web application of PluriPred is available from bicresources.jcbose.ac.in/ssaha4/pluripred/. Many pluripotent genes/proteins take part in protein-protein networks associated with stem cell, cancer, and developmental biology, and we believe that PluriPred will help in these research.     

Repair of DNA damage induced by methylating agents in human uterine cervical cells with or without cancer precursor lesions

Experiments were carried out to study the repair capabilities of normal human cervical fibroblasts and fibroblasts derived from human uterine cervical dysplasia, carcinoma in situ and invasive carcinoma. Sedimentation analysis of DNA in alkaline sucrose density gradient was carried out to monitor the DNA damage induced by a methylating carcinogen, methylnitrosourea (MNU). The results indicate that none of the cell lines, namely, fibroblasts either derived from normal human uterine cervix (T₃₀-11) or from cervical cells of cancer precursor lesions (T₄-3F; T₂₃-3; T₁₈) exhibited any significant repair in 72 h. In contrast fibroblasts derived from normal human skin (GM105) exhibited 38% repair of their DNA damaged by MNU. Epithelial-like cells (T₄-3E) obtained from cervical dysplasia exhibited only 18% repair of MNU-induced DNA damage in 72 h.When the damage was induced by another methylating agent, methyl methanesulfonate (MMS), fibroblasts from normal human skin (GM105) exhibited 40% repair of the damaged DNA whereas fibroblasts from normal human uterine cervix (T₃₀-11) exhibited only a 16% repair, in 72 h.These results suggest that fibroblasts derived from either normal human uterine cervix or from cervix with cancer precursor or cancer lesions exhibit low levels of repair of DNA damged by methylating agents.