A new approach to sequence comparison: normalized sequence alignment

The Smith-Waterman algorithm for local sequence alignment is one of the most important techniques in computational molecular biology. This ingenious dynamic programming approach was designed to reveal the highly conserved fragments by discarding poorly conserved initial and terminal segments. However, the existing notion of local similarity has a serious flaw: it does not discard poorly conserved intermediate segments. The Smith-Waterman algorithm finds the local alignment with maximal score but it is unable to find local alignment with maximum degree of similarity (e.g. maximal percent of matches). Moreover, there is still no efficient algorithm that answers the following natural question: do two sequences share a (sufficiently long) fragment with more than 70% of similarity? As a result, the local alignment sometimes produces a mosaic of well-conserved fragments artificially connected by poorly-conserved or even unrelated fragments. This may lead to problems in comparison of long genomic sequences and comparative gene prediction as recently pointed out by Zhang et al. (Bioinformatics, 15, 1012-1019, 1999). In this paper we propose a new sequence comparison algorithm (normalized local alignment ) that reports the regions with maximum degree of similarity. The algorithm is based on fractional programming and its running time is O(n2log n). In practice, normalized local alignment is only 3-5 times slower than the standard Smith-Waterman algorithm.     

Synthesis of new sulfonamide inhibitors of carbonic anhydrase

Four different derivatives of aromatic sulfonamides have been synthesized: 1,2-bis[(4-sulfonamidobenzamide)ethoxy]ethane (SBAM), 1,2-bis[(4-sulfonamidobenzoate)ethoxy]ethane, 1,2-bis[(2,4-dichloro-5-sulfonamidobenzamide)ethoxy]ethane, and 1,2-bis[(2,4-dichloro-5-sulfonamidobenzoate)ethoxy]ethane. SBAM is a most potent inhibitor on ciliary epithelium carbonic anhydrase and is approximately 13 times more active against carbonic anhydrase isoform II than against isoform I.     

AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation

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Workshops Without Walls: broadening access to science around the world

The National Aeronautics and Space Administration (NASA) Astrobiology Institute (NAI) conducted two "Workshops Without Walls" during 2010 that enabled global scientific exchange--with no travel required. The second of these was on the topic "Molecular Paleontology and Resurrection: Rewinding the Tape of Life." Scientists from diverse disciplines and locations around the world were joined through an integrated suite of collaborative technologies to exchange information on the latest developments in this area of origin of life research. Through social media outlets and popular science blogs, participation in the workshop was broadened to include educators, science writers, and members of the general public. In total, over 560 people from 31 US states and 30 other nations were registered. Among the scientific disciplines represented were geochemistry, biochemistry, molecular biology and evolution, and microbial ecology. We present this workshop as a case study in how interdisciplinary collaborative research may be fostered, with substantial public engagement, without sustaining the deleterious environmental and economic impacts of travel.     

The effects of dietary boric acid and borax supplementation on lipid peroxidation,antioxidant activity,and DNA damage in rats

The aims of this study were to clarify the effects of high dietary supplementation with boric acid and borax, called boron (B) compounds, on lipid peroxidation (LPO), antioxidant activity, some vitamin levels, and DNA damage in rats. Thirty Sprague Dawley male rats were divided into three equal groups: the animals in the first group (control) were fed with a standard rodent diet containing 6.4 mg B/kg, and the animals in the experimental group were fed with a standard rodent diet added with a supra-nutritional amount of boric acid and borax (100 mg B/kg) throughout the experimental period of 28 days. The B compounds decreased malondialdehyde (MDA), DNA damage, the protein carbonyl content (PCO) level in blood, and glutathione (GSH) concentration in the liver, Cu–Zn superoxide dismutase (SOD), and catalase (CAT) activity in the kidney. The B compounds increased GSH concentration in blood and the vitamin C level in plasma. Consequently, our results demonstrate that B supplementation (100 mg/kg) in diet decreases LPO, and enhances the antioxidant defense mechanism and vitamin status. There are no differences in oxidant/antioxidant balance and biochemical parameters except for serum vitamin A and liver GSH concentration, between the boron compounds used in this study.     

Antimicrobial and biological effects of ipemphos and amphos on bacterial and yeast strains

In this study, the antimicrobial effects of monophosphazenes such as SM ipemphos and amphos were examined on bacterial and yeast strains. In addition, the biological effects of these compounds were tested on the lipid level of Saccharomyces cerevisiae and Candida albicans cells. The SM has an antimicrobial effect on the bacterial and yeast strains within the range of 100 and 1500 microg. When the concentration was increased, the inhibition zone expanded on the growth media ( p < 0.01; p < 0.001). The ipemphos did not affect the bacterial and yeast cells in the 100 and 600 microg range. In addition, the amphos did not show an antimicrobial effect on the bacterial cells between 100 and 300 microg or on yeast cells at any of the administered concentrations. In vitro media, the biological effects of these molecules were compared with vitamin E, melatonin and fish oil on the yeast cells. We have found that monophosphazenes have growth effects on the cells in vitro media. The lipid level of S. cerevisiae cells was decreased by 300 microg doses of vitamin E, fish oil, and ipemphos (respectively; p < 0.05, p < 0.01, and p < 0. 001). In addition, the lipid levels of the same yeast cells were depressed by 1000-microg doses in all supplemented groups. However, it was observed that the highest decrease in lipid level of S. cerevisiae cells occurred in the amphos group ( p < 0.001). The lipid levels of the C. albicans cells were significantly reduced ( p < 0.01) by 300 microg of amphos and melatonin. In contrast, the vitamin E and fish oil significantly raised ( p < 0.01; p < 0.001) the lipid level of the same yeast cell, as compared with the control. In addition, the lipid level of these cells was increased by administration of 1000 microg vitamin E, and melatonin ( p < 0.01). In conclusion, while high concentrations of ipemphos and amphos have an antimicrobial effect on bacterial and yeast cells, amphos did not affect the yeast cells. While ipemphos and amphos increased cell growth in media, they reduced the lipid level of C. albicans and S. cerevisiae. In addition, the antioxidants such as vitamin E, melatonin, and fish oils affected the lipid level of yeast cells.     

Evidence for M?ssbauer spectroscopy for different forms of iron core in Pseudomonas aeruginosa bacterial ferritin.

Mössbauer spectroscopic studies of whole cells of Pseudomonas aeruginosa, grown under different conditions, indicate that the predominant form of iron in the cells varies significantly. These differences are interpreted in terms of differences in the nature of the iron cores of the bacterial ferritin, which result from different growth conditions.     

Diverse effects of three furocoumarins on human lymphocyte proliferation

The biological effects of three furocoumarins on the proliferation of human normal peripheral blood lymphocytes have been investigated. Mitogen-stimulated human lymphocytes were assayed "in vitro" by measuring 3H-thymidine (3H-TdR) incorporation in the presence and in the absence of 15-30 microM 3-carbethoxypsoralen (3-CPs), trimethylangelicin (TMA) and psoralen (PSR) with and without UV-A irradiation (365 nm). The three furocoumarins differ in their ability to form mono- and bi-functional adducts with DNA pyrimidine bases and in producing reactive species of oxygen. At low furocoumarin doses and short times of UV-A irradiation (15-30 sec) used in the present study, 3-CPs did not affect 3H-TdR incorporation in PHA-stimulated human lymphocytes, TMA strongly inhibited 3H-TdR incorporation, while, unexpectedly, PSR increased 3H-TdR incorporation in the absence of irradiation, likely acting, under these experimental conditions, as a co-mitogen.     

Comparative bioinformatics analysis and abiotic stress responses of expansin proteins in Cucurbitaceae members: watermelon and melon

Protoplasma - Watermelon and melon are members of the Cucurbitaceae family including economically significant crops in the world. The expansin protein family, which is one of the members of the...