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61.
Kalaivani Batumalaie Mohamed Faraj Edbeib Naji Arafat Mahat Fahrul Huyop 《Journal of biomolecular structure & dynamics》2013,31(12):3077-3093
Interests in Acinetobacter haemolyticus lipases are showing an increasing trend concomitant with growth of the enzyme industry and the widening search for novel enzymes and applications. Here, we present a structural model that reveals the key catalytic residues of lipase KV1 from A. haemolyticus. Homology modeling of the lipase structure was based on the structure of a carboxylesterase from the archaeon Archaeoglobus fulgidus as the template, which has a sequence that is 58% identical to that of lipase KV1. The lipase KV1 model is comprised of a single compact domain consisting of seven parallel and one anti-parallel β-strand surrounded by nine α-helices. Three structurally conserved active-site residues, Ser165, Asp259, and His289, and a tunnel through which substrates access the binding site were identified. Docking of the substrates tributyrin and palmitic acid into the pH 8 modeled lipase KV1 active sites revealed an aromatic platform responsible for the substrate recognition and preference toward tributyrin. The resulting binding modes from the docking simulation correlated well with the experimentally determined hydrolysis pattern, for which pH 8 and tributyrin being the optimum pH and preferred substrate. The results reported herein provide useful insights into future structure-based tailoring of lipase KV1 to modulate its catalytic activity. 相似文献
62.
Ravikanth Danda Gopinath Krishnan Kalaivani Ganapathy Uma Maheswari Krishnan Khetan Vikas Sailaja Elchuri Nivedita Chatterjee Subramanian Krishnakumar 《PloS one》2013,8(12)
In order to realise the full potential of cancer suicide gene therapy that allows the precise expression of suicide gene in cancer cells, we used a tissue specific Epithelial cell adhesion molecule (EpCAM) promoter (EGP-2) that directs transgene Herpes simplex virus–thymidine kinase (HSV-TK) expression preferentially in EpCAM over expressing cancer cells. EpCAM levels are considerably higher in retinoblastoma (RB), a childhood eye cancer with limited expression in normal cells. Use of miRNA regulation, adjacent to the use of the tissue-specific promoter, would provide the second layer of control to the transgene expression only in the tumor cells while sparing the normal cells. To test this hypothesis we cloned let-7b miRNA targets in the 3’UTR region of HSV-TK suicide gene driven by EpCAM promoter because let-7 family miRNAs, including let-7b, were found to be down regulated in the RB tumors and cell lines. We used EpCAM over expressing and let-7 down regulated RB cell lines Y79, WERI-Rb1 (EpCAM +ve/let-7bdown-regulated), EpCAM down regulated, let-7 over expressing normal retinal Müller glial cell line MIO-M1(EpCAM −ve/let-7bup-regulated), and EpCAM up regulated, let-7b up-regulated normal thyroid cell line N-Thy-Ori-3.1(EpCAM +ve/let-7bup-regulated) in the study. The cell proliferation was measured by MTT assay, apoptosis was measured by probing cleaved Caspase3, EpCAM and TK expression were quantified by Western blot. Our results showed that the EGP2-promoter HSV-TK (EGP2-TK) construct with 2 or 4 copies of let-7b miRNA targets expressed TK gene only in Y79, WERI-Rb-1, while the TK gene did not express in MIO-M1. In summary, we have developed a tissue-specific, miRNA-regulated dual control vector, which selectively expresses the suicide gene in EpCAM over expressing cells. 相似文献
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64.
This study elucidates the reduction of organics from textile effluents through electrochemical oxidation technique. Effect of pH and current intensity were investigated in this system. It was found that degradation was maximum at the current intensity of 0.6 A and at a pH of 1.3. Under the same experimental conditions the removal of chemical oxygen demand (COD), total solids, total dissolved solids and total organic carbon were found to be approximately 68%, 49.2%, 50.7% and 96.8%, respectively. Effect of current intensity on color removal was also investigated as a function of electrolysis time (30-210 minutes) and it showed that maximum removal efficiency (96%) was reached within 60 minutes at 0.6 A. While studying the effect of pH on COD removal, it was observed that a decrease in pH to an optimum of 1.3 showed maximum COD reduction of 68%. These results suggest an important role of these parameters in electrochemical process for removing organic pollutants. 相似文献
65.
The decoction (D) of the bark of Ficus racemosa Linn (Family: Moraceae) is claimed as an antidiuretic by some Sri Lankan traditional practitioners. However, the validity of this claim has not been scientifically proven or refuted. The aim of this study was to evaluate the antidiuretic potential of D of the bark of F. racemosa (made as specified in traditional use) in rats using three doses (250, 500 or 1000 mg/kg) following oral administration. The reference drug used was ADH. The results demonstrated both the low- and high-doses of D and ADH significantly impaired the total urine output. The D-induced antidiuresis had a rapid onset (within 1 h), peaked at 3 h and lasted throughout the study period (5 h). However, antidiuretic potential of D was about 50% lower than that of ADH. The D was well tolerated even with subchronic administration. The D caused a reduction in urinary Na+ level and Na+/K+ ratio, and an increase in urinary osmolarity indicating multiple mechanisms of action. The results provide scientific support for its claimed antidiuretic action and deserve intensive scrutiny. 相似文献
66.
Tiwari M Hemalatha T Ganesan K Nayeem M Murali Manohar B Balachandran C Vairamuthu S Subramaniam S Puvanakrishnan R 《Molecular and cellular biochemistry》2008,312(1-2):81-91
The aim of this study was to evaluate the time course events of cellular damage during myocardial ischemia and reperfusion
injury in rats and to find out a correlation between the structural alterations with respect to the biochemical changes. Cardiac
biomarkers and lysosomal enzymes viz. cathepsin D, acid phosphatase and β-glucuronidase and matrix metalloproteinases (MMPs)
were evaluated at different time points, in response to ischemia-reperfusion induced oxidative stress in an isolated rat heart
model perfused in Langendorff mode. Microscopically, changes in myocardial architecture, myofibrillar degradation, and collagen
(COL) integrity were studied using hematoxylin-eosin, Masson’s trichrome and toluidine blue staining techniques. A three-fold
increase in the level of myoglobin was observed after 30 min of ischemia followed by 120 min of reperfusion as compared to
15 min ischemia, 120 min reperfusion. Similarly, a significant increase (P < 0.05) in the levels of lipid peroxides and superoxide anion coupled with a decrease in enzymatic and nonenzymatic antioxidant
levels were observed. A concomitant increase in the activity of cathepsin D (24.07 ± 0.95) and a higher expression of MMPs
after 120 min of reperfusion following 30 min ischemia were shown to correlate with the myocardial damage as shown by histopathology,
suggesting that free radical induced activation of cathepsin D and MMPs could mediate early damage during myocardial ischemia
and reperfusion. 相似文献
67.
Preeti Bharaj Wayne M Sullender Sushil K Kabra Kalaivani Mani John Cherian Vikas Tyagi Harendra S Chahar Samander Kaushik Lalit Dar Shobha Broor 《Virology journal》2009,6(1):1-11
Background
Proventricular dilatation disease (PDD) is a fatal disorder of psittacine birds worldwide. The disease is characterized by lymphoplasmacytic infiltration of the central and peripheral nervous systems, leading to gastrointestinal motility and/or central nervous system dysfunction. Recently, we detected a significant association between avian bornavirus (ABV) infection and clinical signs of PDD in psittacines. However, it remains unclear whether ABV infection actually causes PDD. To address this question, we examined the impact of ABV inoculation on the cockatiel (Nymphicus hollandicus).Results
Five cockatiels were inoculated via multiple routes (intramuscular, intraocular, intranasal, and oral) with a brain homogenate derived from either a PDD(+) avian bornavirus 4 (ABV4) (+) case (n = 3 inoculees) or from a PDD(-) ABV(-) control (n = 2 inoculees). The control birds remained free of clinical or pathological signs of PDD, and tested ABV(-) by RT-PCR and immunohistochemistry (IHC). In contrast, all three cockatiels inoculated with ABV4(+) brain homogenate developed gross and microscopic PDD lesions, and two exhibited overt clinical signs. In numerous tissues, ABV RT-PCR and sequence analysis demonstrated the presence of ABV4 RNA nearly identical to that in the inoculum. ABV was detected in the central nervous system of the three ABV-inoculees by IHC. Pyrosequencing to investigate the viral flora in the ABV4(+) inoculum uncovered 7 unique reads sharing 73–100% nucleotide sequence identity with previously identified ABV sequences and 24 reads sharing 40–89% amino acid sequence identity with viruses in the Retroviridae and Astroviridae families. Of these candidate viral species, only ABV RNA was recovered from tissues of the inoculated birds.Conclusion
In this study, the clinical and pathological manifestations of PDD were induced by inoculation of cockatiels with brain homogenates containing avian bornavirus 4. By using high throughput pyrosequencing an in-depth view of the viral content of the inoculum was achieved, revealing that of 3 candidate virus families detected, only the presence of ABV RNA correlated with the development of PDD. This study provides evidence of a causal association between ABV4 infection and PDD in cockatiels. 相似文献68.
A growing number of innovative mAb therapeutics are on the global market, and biosimilar versions have now also been approved, including in India. Although efficacy and safety is demonstrated prior to approval, targeted pharmacovigilance is essential for the identification and assessment of risk for any mAb products. We analyzed the ADR data related to mAbs reported to the NCC-PvPI through the spontaneous reporting system Vigiflow during April 2011 to February 2014 to identify mAbs with the highest number of ADR including fatal/serious ADR. Only 0.72% reports were related to mAbs. Although 15 mAbs are approved in the country, only 6 mAbs were reported through Vigiflow. Rituximab was highly reported, and no fatal/serious ADR related to any mAbs were reported during the study period. Our study shows that PvPI is effective and robust system in the detection and assessment of risks associated with the use of mAbs. 相似文献
69.
Emergence of carbapenem non‐susceptible multidrug resistant Acinetobacter baumannii strains of clonal complexes 103B and 92B harboring OXA‐type carbapenemases and metallo‐β‐lactamases in Southern India 下载免费PDF全文
Rajagopalan Saranathan P. Shashikala Chandrakesan Sheela Devi Ramakrishnan Kalaivani Johny Asir Pagal Sudhakar K Prashanth 《Microbiology and immunology》2015,59(5):277-284
The molecular epidemiology and carbapenem resistance mechanisms of clinical isolates of Acinetobacter baumannii obtained from a south Indian tertiary care hospital were investigated by repetitive extragenic palindromic sequence PCR (REP‐PCR) and multi‐locus sequence typing (MLST). Analysis of resistant determinants was achieved by PCR screening for the presence of genes encoding OXA‐carbapenemases, metallo‐β‐lactamases (MBLs) and efflux pumps. REP‐PCR generated around eight clusters of high heterogeneity; of these, two major clusters (I and V) appeared to be clonal in origin. Analysis of representative isolates from different clusters by MLST revealed that most of the isolates belonged to sequence type 103 of CC103B. Second most prevalent ST belonged to clonal complex (CC) 92B which is also referred to as international clone II. Most of the isolates were multi‐drug resistant, being susceptible only to polymyxin‐B and newer quinolones. Class D β‐lactamases such as blaOXA‐51‐like (100%), blaOXA‐23‐like (56.8%) and blaOXA‐24‐like (14.8%) were found to be predominant, followed by a class B β‐lactamase, namely blaIMP‐1 (40.7%); none of the isolates had blaOXA‐58 like, blaNDM‐1 or blaSIM‐1. Genes of efflux‐pump adeABC were predominant, most of isolates being biofilm producers that were PCR‐positive for autoinducer synthase gene (>94%). Carbapenem non‐susceptible isolates were highly diverse and present throughout the hospital irrespective of type of ward or intensive care unit. Although previous reports have documented diverse resistant mechanisms in A. baumannii, production of MBL and OXA‐type of carbapenamases were found to be the predominant mechanism(s) of carbapenem resistance identified in strains isolated from Southern India. 相似文献
70.
Nagaraj NS Vigneswaran N Zacharias W 《Apoptosis : an international journal on programmed cell death》2007,12(1):125-139
Tumor hypoxia interferes with the efficacy of chemotherapy, radiotherapy, and tumor necrosis factor-α. TRAIL (tumor necrosis
factor-related apoptosis inducing ligand) is a potent apoptosis inducer that limits tumor growth without damaging normal cells
and tissues in vivo. We present evidence for a central role of lysosomal cathepsins in hypoxia and/or TRAIL-induced cell death in oral squamous
cell carcinoma (OSCC) cells. Hypoxia or TRAIL-induced activation of cathepsins (B, D and L), caspases (-3 and -9), Bid cleavage,
release of Bax and cytochrome c, and DNA fragmentation were blocked independently by zVAD-fmk, CA074Me or pepstatin A, consistent
with the involvement of lysosomal cathepsin B and D in cell death. Lysosome stability and mitochondrial membrane potential
were reduced in hypoxia and TRAIL-induced apoptosis. However, TRAIL treatment under hypoxic condition resulted in diminished
apoptosis rates compared to treatment under normoxia. This inhibitory effect of hypoxia on TRAIL-induced apoptosis may be
based on preventing Bax activation and thus protecting mitochondria stability. Our data show that TRAIL or hypoxia independently
triggered activation of cathepsin B and D leading to apoptosis through Bid and Bax, and suggest that hypoxic tissue regions
provide a selective environment for highly apoptosis-resistant clonal cells. Molecular therapy approaches based on cathepsin
inhibitors need to address this novel tumor-preventing function of cathepsins in OSCC. 相似文献