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Resultados filtrados por Publicador: The National Academy of Sciences

‣ Measures of degeneracy and redundancy in biological networks

Tononi, Giulio; Sporns, Olaf; Edelman, Gerald M.
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
Publicado em 16/03/1999 Português
Relevância na Pesquisa
553.33094%
Degeneracy, the ability of elements that are structurally different to perform the same function, is a prominent property of many biological systems ranging from genes to neural networks to evolution itself. Because structurally different elements may produce different outputs in different contexts, degeneracy should be distinguished from redundancy, which occurs when the same function is performed by identical elements. However, because of ambiguities in the distinction between structure and function and because of the lack of a theoretical treatment, these two notions often are conflated. By using information theoretical concepts, we develop here functional measures of the degeneracy and redundancy of a system with respect to a set of outputs. These measures help to distinguish the concept of degeneracy from that of redundancy and make it operationally useful. Through computer simulations of neural systems differing in connectivity, we show that degeneracy is low both for systems in which each element affects the output independently and for redundant systems in which many elements can affect the output in a similar way but do not have independent effects. By contrast, degeneracy is high for systems in which many different elements can affect the output in a similar way and at the same time can have independent effects. We demonstrate that networks that have been selected for degeneracy have high values of complexity...

‣ Separation of phylogenetic and functional associations in biological sequences by using the parametric bootstrap

Wollenberg, Kurt R.; Atchley, William R.
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
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553.33094%
Quantitative analyses of biological sequences generally proceed under the assumption that individual DNA or protein sequence elements vary independently. However, this assumption is not biologically realistic because sequence elements often vary in a concerted manner resulting from common ancestry and structural or functional constraints. We calculated intersite associations among aligned protein sequences by using mutual information. To discriminate associations resulting from common ancestry from those resulting from structural or functional constraints, we used a parametric bootstrap algorithm to construct replicate data sets. These data are expected to have intersite associations resulting solely from phylogeny. By comparing the distribution of our association statistic for the replicate data against that calculated for empirical data, we were able to assign a probability that two sites covaried resulting from structural or functional constraint rather than phylogeny. We tested our method by using an alignment of 237 basic helix–loop–helix (bHLH) protein domains. Comparison of our results against a solved three-dimensional structure confirmed the identification of several sites important to function and structure of the bHLH domain. This analytical procedure has broad utility as a first step in the identification of sites that are important to biological macromolecular structure and function when a solved structure is unavailable.

‣ A biological function for cadmium in marine diatoms

Lane, Todd W.; Morel, François M. M.
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
553.33094%
The oceanic distribution of cadmium follows closely that of major algal nutrients such as phosphate. The reasons for this “nutrient-like” distribution are unclear, however, because cadmium is not generally believed to have a biological function. Herein, we provide evidence of a biological role for Cd in the marine diatom Thalassiosira weissflogii under conditions of low zinc, typical of the marine environment. Addition of Cd to Zn-limited cultures enhances the growth rate of T. weissflogii, particularly at low pCO2. This increase in growth rate is reflected in increased levels of cellular carbonic anhydrase (CA) activity, although the levels of TWCA1, the major intracellular Zn-requiring isoform of CA in T. weissflogii, remain low. 109Cd label comigrates with a protein band that shows CA activity and is distinct from TWCA1 on native PAGE of radiolabeled T. weissflogii cell lysates. The levels of the Cd protein are modulated by CO2 in a manner that is consistent with a role for this enzyme in carbon acquisition. Purification of the CA-active fraction leads to the isolation of a Cd-containing protein of 43 kDa. It is now clear that T. weissflogii expresses a Cd-specific CA, which, particularly under conditions of Zn limitation, can replace the Zn enzyme TWCA1 in its carbon-concentrating mechanism.

‣ Accelerated reaction of nitric oxide with O2 within the hydrophobic interior of biological membranes

Liu, Xiaoping; Miller, Mark J. S.; Joshi, Mahesh S.; Thomas, Douglas D.; Lancaster, Jack R.
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
Publicado em 03/03/1998 Português
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553.33094%
We demonstrate herein dramatic acceleration of aqueous nitric oxide (NO) reaction with O2 within the hydrophobic region of either phospholipid or biological membranes or detergent micelles and demonstrate that the presence of a distinct hydrophobic phase is required. Per unit volume, at low amounts of hydrophobic phase, the reaction of NO with O2 within the membranes is approximately 300 times more rapid than in the surrounding aqueous medium. In tissue, even though the membrane represents only 3% of the total volume, we calculate that 90% of NO reaction with O2 will occur there. We conclude that biological membranes and other tissue hydrophobic compartments are important sites for disappearance of NO and for formation of NO-derived reactive species and that attenuation of these potentially damaging reactions is an important protective action of lipid-soluble antioxidants such as vitamin E.

‣ Susceptibility to the biological effects of polyaromatic hydrocarbons is influenced by genes of the major histocompatibility complex

Elmets, Craig A.; Athar, Mohammad; Tubesing, Karen A.; Rothaupt, Dinah; Xu, Hui; Mukhtar, Hasan
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
Publicado em 08/12/1998 Português
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Polyaromatic hydrocarbons are ubiquitous environmental chemicals that are important mutagens and carcinogens. The purpose of this study was to determine whether genes within the major histocompatibility complex (MHC) influence their biological activities. Cell-mediated immunity to dimethylbenz(a)anthracene (DMBA) was investigated in congenic strains of mice. On three different backgrounds, H-2k and H-2a haplotype mice developed significantly greater contact-hypersensitivity responses to DMBA than H-2b, H-2d, and H-2s mice. In B10.A(R1) mice, which are Kk and Id, a vigorous contact-hypersensitivity response was present, indicating that the response was governed by class I, rather than class II, MHC genes. C3H/HeN (H-2k) and C3H.SW (H-2s) strains were also compared for the development of skin tumors and the persistence of DMBA–DNA adducts. When subjected to a DMBA initiation, phorbol 12-tetradecanoate 13-acetate (TPA)-promotion skin-tumorigenesis protocol, C3H/HeN mice, (which develop cell-mediated immunity to DMBA) were found to have significantly fewer tumors than C3H.SW mice (a strain that failed to develop a cell-mediated immune response to DMBA). DMBA–DNA adducts were removed more rapidly in C3H/HeN than in C3H.SW mice. The results indicate that genes within the MHC play an important role in several of the biological activities of carcinogenic polyaromatic hydrocarbons. The observations are consistent with the hypothesis that cell-mediated immunity to chemical carcinogens serves to protect individuals by removing mutant cells before they can evolve into clinically apparent neoplasms.

‣ Digital in-line holography for biological applications

Xu, Wenbo; Jericho, M. H.; Meinertzhagen, I. A.; Kreuzer, H. J.
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
Publicado em 25/09/2001 Português
Relevância na Pesquisa
553.33094%
Digital in-line holography with numerical reconstruction has been developed into a new tool, specifically for biological applications, that routinely achieves both lateral and depth resolution, at least at the micron level, in three-dimensional imaging. The experimental and numerical procedures have been incorporated into a program package with a very fast reconstruction algorithm that is now capable of real-time reconstruction. This capability is demonstrated for diverse objects, such as suspension of microspheres and biological samples (diatom, the head of Drosophila melanogaster), and the advantages are discussed by comparing holographic reconstructions with images taken by using conventional compound light microscopy.

‣ Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori

Björkholm, Britta; Sjölund, Maria; Falk, Per G.; Berg, Otto G.; Engstrand, Lars; Andersson, Dan I.
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
553.33094%
Among the several factors that affect the appearance and spread of acquired antibiotic resistance, the mutation frequency and the biological cost of resistance are of special importance. Measurements of the mutation frequency to rifampicin resistance in Helicobacter pylori strains isolated from dyspeptic patients showed that ≈1/4 of the isolates had higher mutation frequencies than Enterobacteriaceae mismatch-repair defective mutants. This high mutation frequency could explain why resistance is so frequently acquired during antibiotic treatment of H. pylori infections. Inactivation of the mutS gene had no substantial effect on the mutation frequency, suggesting that MutS-dependent mismatch repair is absent in this bacterium. Furthermore, clarithromycin resistance conferred a biological cost, as measured by a decreased competitive ability of the resistant mutants in mice. In clinical isolates this cost could be reduced, indicating that compensation is a clinically relevant phenomenon that could act to stabilize resistant bacteria in a population.

‣ ADP ribosylation of human neutrophil peptide-1 regulates its biological properties

Paone, Gregorino; Wada, Akihiro; Stevens, Linda A.; Matin, Abul; Hirayama, Toshiya; Levine, Rodney L.; Moss, Joel
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
Publicado em 11/06/2002 Português
Relevância na Pesquisa
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In human airways, epithelial cells lining the lumen and intraluminal cells (e.g., polymorphonuclear cells) participate in the innate immune response. These cells secrete or express on their surfaces arginine-specific ADP ribosyltransferases. Defensins, antimicrobial proteins secreted by immune cells, are arginine-rich, leading us to hypothesize that ADP ribosylation could modify their biological activities. We found that an arginine-specific ADP ribosyltransferase-1 present on airway epithelial cells modifies Arg-14 of α defensin-1. ADP-ribosylated defensin-1 had decreased antimicrobial and cytotoxic activities but still stimulated T cell chemotaxis and IL-8 release from A549 cells. Further, ADP-ribosylated defensin-1 inhibited cytotoxic and antimicrobial activities of unmodified defensin-1. We identified ADP-ribosylated defensin-1 in bronchoalveolar lavage fluid from smokers but not from nonsmokers, confirming its existence in vivo. Thus, airway mono-ADP-ribosyltransferases could have an important regulatory role in the innate immune response through modification of α defensin-1 and perhaps other basic molecules, with alteration of their biological properties.