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Results for “Functional potential”

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PubMed2004

Recognition of functional sites in protein structures.

Recognition of regions on the surface of one protein, that are similar to a binding site of another is crucial for the prediction of molecular interactions and for functional classifications. We first describe a novel method, SiteEngine, that assumes no sequence or fold similarities and is able to recognize proteins that have similar binding sites and may perform similar functions. We achieve high efficiency and speed by introducing a low-resolution surface representation via chemically important surface points, by hashing triangles of physico-chemical properties and by application of hierarchical scoring schemes for a thorough exploration of global and local similarities. We proceed to rigorously apply this method to functional site recognition in three possible ways: first, we search a given functional site on a large set of complete protein structures. Second, a potential functional site on a protein of interest is compared with known binding sites, to recognize similar features. Third, a complete protein structure is searched for the presence of an a priori unknown functional site, similar to known sites. Our method is robust and efficient enough to allow computationally demanding applications such as the first and the third. From the biological standpoint, the first application may identify secondary binding sites of drugs that may lead to side-effects. The third application finds new potential sites on the protein that may provide targets for drug design. Each of the three applications may aid in assigning a function and in classification of binding patterns. We highlight the advantages and disadvantages of each type of search, provide examples of large-scale searches of the entire Protein Data Base and make functional predictions.

Algorithms↗

PubMed2004

Evidence of thymic reconstitution after highly active antiretroviral therapy in HIV-1 infection.

OBJECTIVES: We aimed to provide evidence of thymic reconstitution after highly active antiretroviral therapy (HAART) in HIV-1 infected patients and to correlate this with the restoration of peripheral naïve T cells. METHODS: Positron emission tomography (PET) enables definitive evidence of thymic activity, indicating functional potential. In this case study, a single patient who initiated HAART demonstrated reconstitution of the naïve T-cell pool and underwent thymic PET scans at baseline and 2 and 6 months following initiation of therapy. Two patients who failed to demonstrate such reconstitution acted as controls. These patients (mean age 27 years) had chronic HIV infection with low CD4 T-cell counts (mean 82, range 9-160 cells/microL blood). Increased function of the thymus visualized by PET was correlated with phenotypic changes in CD4 and CD8 T cells in the periphery measured by flow cytometry, and with numbers of recent thymic emigrants measured by quantification of the numbers of T-cell receptor excision circles (TRECs) in peripheral cells. RESULTS: In one patient, clear correlations could be drawn between visible activity within the thymus, as measured by increased [F18]fluorodeoxyglucose (FDG) uptake, and regeneration of naïve CD4 (CD45RA/CD62L) T cells, increased numbers of CD4 T cells, controlled viraemia and increased numbers of recent thymic emigrants. A second patient displayed no increase in peripheral CD4 count and no increase in thymic activity. The third patient elected to stop therapy following the 2-month time point. CONCLUSIONS: The use of PET suggests that thymic activity may increase after HAART, indicating that the thymus has the potential to be functional even in HIV-1 infected persons with low CD4 T-cell counts.

Adult↗

PubMed1989

Expression of the mammalian mitochondrial genome. Stability of mitochondrial translation products as a function of membrane potential.

Polypeptide decay has been measured as a function of membrane potential. Mitochondrial translation products were pulse-labeled in vitro with [35S]methionine using isolated rat heart mitochondria in the presence of an energy-generating system. The relative rate of protein degradation was estimated from the specific activity (counts/min/mg of protein) of the labeled translation products following the addition of unlabeled methionine (chase). To modulate membrane potential, inhibitors of oxidative phosphorylation were used singly or in combination; their effect was monitored by following uptake of the nonmetabolizable lipophilic cation triphenylmethylphosphonium. When the potential was dissipated, the rate of polypeptide decay increased and vice versa. These results suggest that the stability of mitochondrial translation products is linked to a process(es) that is dependent upon delta psi; likely candidates include synthesis and/or assembly of mitochondrial gene products.

Animals↗

PubMed1990

Senescence of visual function as studied by visually evoked cortical potentials.

Visual functions in senescence were assessed quantitatively by the pattern reversal visually evoked cortical potentials (VECP) in human subjects and animals. The results obtained in the elderly showed an elevation of contrast threshold, ie, lowered sensitivity, for higher spatial frequency, and a rise in the luminance thresholds. There was also an overall suppression in the temporal frequency curves, a sensitivity decrease for the upper half of the visual field, a blue-yellow defect and a decrease in the amplitude of accommodation. Studies of the pseudophakic eye with an intraocular lens verified that the lower transparency and yellowish changes of the crystalline lens and senile miosis do not entirely account for the depressed visual function in the elderly. The delay of P100 peak latency of the VECP in patients with juvenile Parkinson's disease after cessation of L-dopa indicated the deficiency of dopamine in these patients, which in turn was considered as a clinical model of senescence. Optic nerve fiber counts in mice showed a significant decrease in the aged group. It was considered that there is neuronal senescence other than in the eye itself. The results can be illustrated by the following daily life experience. In the evening, an elderly person would have difficulty in identifying a cat as a calico cat if the cat were atop a wall and running quickly through the visual field. It was surprising, however, that the senescence found in the visual function was not as great as that found in the other sensory organs. As further studies, investigation of the feedback mechanism from the brain to the retina and the compensatory mechanism should be made.

Accommodation, Ocular↗

PubMed2006

The evolution of ATPase activity in SMC proteins.

The SMC (structural maintenance of chromosomes) proteins are a highly conserved and ubiquitous family of ATPases, found in nearly all living organisms examined, where they play crucial roles in transmission of the hereditary material. However, the extent to which efficient ATP hydrolysis is required for SMC function has been a matter of some debate. Here we investigate the potential functional significance of ATP binding and hydrolysis in different eukaryotic SMC proteins, both by comparing the conservation of conserved ATPase motifs and by exploring potential coevolution between associated domains. In this way, we have been able to account for the reduced requirement for ATPase activity in cohesin's SMC3 and demonstrate the greater apparent conservation requirements for such activity in condensin SMC proteins. Finally, we explore possible interactions between the SMC and non-SMC components of the condensin complex that are required for full condensin activity and may modulate ATPase activity in the holocomplex.

Adenosine Triphosphatases↗

PubMed2006

Comparative gene expression analysis reveals a characteristic molecular profile of the superior olivary complex.

The superior olivary complex (SOC) is a very conspicuous structure in the mammalian auditory brainstem. It represents the first binaural processing center and is important for sound localization in the azimuth and in feedback regulation of cochlear function. In order to define molecular determinants of the SOC, which are of potential functional relevance, we have performed a comprehensive analysis of its transcriptome by serial analysis of gene expression in adult rats. Here, we performed a detailed analysis of the SOC's gene expression profile compared to that of two other neural tissues, the striatum and the hippocampus, and with extraocular muscle tissue. This tested the hypothesis that SOC-specific or significantly upregulated transcripts provide candidates for the specific function of auditory neurons. Thirty-three genes were significantly upregulated in the SOC when compared to the two other neural tissues. Thirteen encoded proteins involved in neurotransmission, including action potential propagation, exocytosis, and myelination; five genes are important for the energy metabolism, and five transcripts are unknown or poorly characterized and have yet to be described in the nervous system. The comparison of functional gene classes indicates that the SOC has the highest energy demand of the three neural tissues, yet protein turnover is apparently not increased. This suggests a high energy demand for fueling auditory neurotransmission. Such a demand may have implications on auditory-specific tasks and relate to central auditory processing disorders. Ultimately, these data provide new avenues to foster investigations of auditory function and to advance molecular physiology in the central auditory system.

Animals↗

PubMed1996

Helmholtz free energy of peptide hydrogen bonds in proteins.

We estimate the Helmholtz free energy of peptide hydrogen bonds in native protein structures as a function of spatial separation between donor and acceptor atoms. The resulting potential function has a deep narrow well at H-bond contact but bond formation is hindered by a barrier and the net change in free energy is close to zero. The barrier provides a molecular lock mechanism acting as a kinetic trap. Once formed, H-bonds keep protein chains in a precise orientation. However, bond formation requires energy input and opposes protein folding. In contrast, the free energy functions of most side-chain interactions have no energy barriers. They lack spatial precision but free energy differences of contact formation are substantial. These interactions drive folding and stabilize structures but precision is mediated and maintained by H-bonds.

Arginine↗

PubMed2005

Natural antibodies and the autoimmunity of atherosclerosis.

In recent years, the subject of natural antibodies has been revisited and the immunobiological roles of these humoral factors are being better defined. These antibodies are secreted by distinct sets of innate-like B cells, B-1 cells and marginal zone B cells, which arise early in development to become the sources of "natural immune memory". Due to their interactions with a variety of self-determinants, natural antibodies have previously been postulated to play roles in the maintenance of host homeostasis. A central paradigm has recently been developed from the demonstration that oxidation derived epitopes on apoptotic cells and oxidized low-density lipoproteins are recognized by the phosphorylcholine-specific germline encoded B-1 cell natural antibody, T15, which has provided important insights into possible "house-keeping" functions under both normal and pathological conditions. In this review, the potential functions of natural antibodies in the pathogenesis and progression of the chronic inflammatory condition of atherosclerosis are discussed, as well as their capacities for apoptotic cell binding and clearance. These interactions of natural antibodies and oxidation-epitopes from phospholipids appear to provide a dynamic immunobiological connection linking host responses in infection, autoimmunity and atherosclerosis.

Animals↗

PubMed2005

HHR23A, a human homolog of Saccharomyces cerevisiae Rad23, regulates xeroderma pigmentosum C protein and is required for nucleotide excision repair.

HHR23A and hHR23B are the human homologs of Saccharomyces cerevisiae Rad23. hHR23B is associated with the nucleotide excision repair (NER) factor xeroderma pigmentosum C (XPC) protein and is required for global genome repair. The function of hHR23A is not yet clear. In this study, the potential function of the hHR23A protein was investigated using RNA interference techniques. The hHR23A knock-down (KD) construct diminished the RNA level of hHR23A protein by approximately 60%, and it did not interfere with expression of the hHR23B gene. Based on Southwestern immunoblot and host-cell reactivation assays, hHR23A(KD) cells were found to be deficient in DNA repair activity against the DNA damage caused by UVC irradiation. In these hHR23A(KD) cells, the XPC gene was not normally induced by UVC irradiation, indicating that the hHR23A protein is involved in NER through regulation of the DNA damage recognition protein XPC. Co-immunoprecipitation experiments revealed that hHR23A was associated with a small portion of hHR23B and the majority of p53 protein, indicating that hHR23A regulates the function of XPC by its association with the NER activator p53.

Cell Line, Tumor↗

PubMed2005

Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2.

The immunosuppressant FK-506 binding protein 38 (FKBP38) is localized at the mitochondrial membrane and appears to play an important role in apoptosis. Recent reports about the potential functions of FKBP38 in apoptosis appear to be controversial. To further understand the biological function of FKBP38, here, we studied its molecular characteristics and a potential regulatory role on the anti-apoptotic protein Bcl-2. Our results suggest that FKBP38 appears to show chaperone activities in the citrate synthase aggregation assays during thermal denaturation and affect solubility of Bcl-2 when they are co-expressed. The FKBP family proteins bind the immunosuppressive drug FK-506 through the FK-506 binding domain and consequently inhibit the activity of calcineurin. In this study, from our NMR studies and calcineurin assays in vitro, we demonstrate that the N-terminal fragment of FKBP38 which contains the FK-506 binding domain does not bind FK-506 at molecular level. Lastly, to investigate the effect of FKBP38 on Bcl-2, we suppressed FKBP38 by RNA interference (RNAi) of FKBP38. Our results suggest that the suppression of FKBP38 appears to make Bcl-2 unstable or unprotected from degradation in an unknown mechanism.

Apoptosis↗

PubMed2026

Building biofilms for saline hydrogenotrophic denitrification from contrasting origins: Convergent acclimation, divergent performance.

Hydrogenotrophic denitrification is promising for deep nitrogen removal from saline, low-C/N wastewaters, but rapid establishment of stable biofilms at high salinity remains challenging. Here, two saline-adapted inocula from two representative, functionally contrasting habitats-a functionally-diversified inoculum from mangrove sediment and a functionally-focused inoculum from seabed sediment-were acclimated in parallel H2-based membrane biofilm reactors at constant 3.5% salinity. The Diverse-derived biofilm required 80 d to reach steady state and achieved only partial denitrification with 61.1% nitrate removal and considerable nitrite accumulation. In contrast, the Focus-derived biofilm rapidly established complete denitrification within ∼40 d, which was maintained for >50 d, with effluent NOx- below 1 mg-N·L-1 and 98.7% nitrate removal. Microbiome analyses showed that identical operation promoted convergence in community structure and enriched similar community-level functional potentials. However, genome-resolved analysis revealed distinct source-dependent functional organization among dominant microbial populations. Complete denitrifiers co-encoding denitrifying, hydrogenotrophic, and autotrophic functions were preferentially enriched in the Focus-derived biofilm, whereas these functions remained partitioned among different dominant populations in the Diverse-derived biofilm, coinciding with less complete denitrification. These findings indicate that saline hydrogenotrophic denitrification performance depends not only on which functions are enriched at the community level, but also on how key functions become organized among microbial populations, providing a previously overlooked criterion for inoculum selection in saline biological nitrogen control.

Complete denitrification↗

PubMed2000

Marine biodiversity and ecosystem services: an elusive link.

Efforts to test the hypothesised positive link between ecosystem services and functions and biodiversity are increasing in order to forecast the consequences of the present erosion of biodiversity on ecosystem functions and to provide an additional basis for the conservation of biodiversity. These efforts have been, however, modest in marine ecosystems. An examination of seagrass communities, which are simple assemblages with a limited membership of about 50 species worldwide and <12 species in any one community, provides, however, strong evidence for the existence of such positive link between species richness and ecosystem functions. Ecosystem functions are, however, dependent on the particular membership of the community, rather that its number, for the functions are species-specific properties. Yet evidence, is provided, that an increasing species richness should be, on average, linked to an increase in the functional repertoire present in the community, will lead to a more efficient use of resources and a greater capacity to ensure the sustainability of ecosystem functions under disturbance or ecosystem change. Closer examination indicates that the functional variability of mixed-species seagrass assemblages is correlated to the variability in species size, whereas species of similar size tend to show similar functional capacities and, therefore, a greater degree of functional redundancy. In addition, the demonstration of positive interactions in seagrass communities, which are also dependent on the presence of engineering species in the community that facilitate the growth of other species, provides increasing grounds to expect an enhanced functional performance of mixed communities over that expected from a simple additive contribution of the community members. Multispecific communities also hold, within the functional repertoire they contain, many unrealised functional potentials that may prove instrumental to ensure the sustainability of ecosystem functions in the presence of disturbance or a changing environment. The arguments offered, illustrated for the comparatively simple seagrass communities, provide strong reasons to expect a strong - if difficult to test experimentally - positive relationship between species diversity and the functions of marine ecosystems and, thereby, the services they yield to humanity.

Journal Article↗

PubMed1998

Understanding and assessing the motivations of volunteers: a functional approach.

The authors applied functionalist theory to the question of the motivations underlying volunteerism, hypothesized 6 functions potentially served by volunteerism, and designed an instrument to assess these functions (Volunteer Functions Inventory; VFI). Exploratory and confirmatory factor analyses on diverse samples yielded factor solutions consistent with functionalist theorizing; each VFI motivation, loaded on a single factor, possessed substantial internal consistency and temporal stability and correlated only modestly with other VFI motivations (Studies 1, 2, and 3). Evidence for predictive validity is provided by a laboratory study in which VFI motivations predicted the persuasive appeal of messages better when message and motivation were matched than mismatched (Study 4), and by field studies in which the extent to which volunteers' experiences matched their motivations predicted satisfaction (Study 5) and future intentions (Study 6). Theoretical and practical implications are discussed.

Adult↗

PubMed2004

The nuclear magnetic resonance line shapes of Xe in the cages of clathrate hydrates.

We report, for the first time, a prediction of the line shapes that would be observed in the (129)Xe nuclear magnetic resonance (NMR) spectrum of xenon in the cages of clathrate hydrates. We use the dimer tensor model to represent pairwise contributions to the intermolecular magnetic shielding tensor for Xe at a specific location in a clathrate cage. The individual tensor components from quantum mechanical calculations in clathrate hydrate structure I are represented by contributions from parallel and perpendicular tensor components of Xe-O and Xe-H dimers. Subsequently these dimer tensor components are used to reconstruct the full magnetic shielding tensor for Xe at an arbitrary location in a clathrate cage. The reconstructed tensors are employed in canonical Monte Carlo simulations to find the Xe shielding tensor component along a particular magnetic field direction. The shielding tensor component weighted according to the probability of finding a crystal fragment oriented along this direction in a polycrystalline sample leads to a predicted line shape. Using the same set of Xe-O and Xe-H shielding functions and the same Xe-O and Xe-H potential functions we calculate the Xe NMR spectra of Xe atom in 12 distinct cage types in clathrate hydrates structures I, II, H, and bromine hydrate. Agreement with experimental spectra in terms of the number of unique tensor components and their relative magnitudes is excellent. Agreement with absolute magnitudes of chemical shifts relative to free Xe atom is very good. We predict the Xe line shapes in two cages in which Xe has not yet been observed.

Journal Article↗

PubMed1997

Functional electrical stimulation.

In the health-care professions, electrical stimulation is used for three purposes: to aid diagnosis; as a therapeutic tool; and to restore lost or damaged functions. Functional electrical stimulation (FES) and functional neurostimulation (FNS) are terms which are more or less interchangeable, and which encompass the third of these purposes. FES itself can also be conveniently divided into three classes, according to purpose: the restoration of sensor functions; the restoration of skeleto-motor functions; and the restoration of autonomic functions. Potentially, a fourth class would comprise devices restoring cognitive or psychological functions, but no such devices are clinically available as yet. The methods and devices which are currently available for providing FES are reviewed, as are the sorts of result and benefit that may be expected from them. The structure and emphasis of the review is on the clinical applications and the relevant anatomical and neurophysiological considerations and this approach is chosen for two main reasons. Firstly, the clinical, anatomical, and physiological considerations are independent of technological change and development, so they will not become quickly out of date. Secondly, the author is a clinician by profession, and an engineer only by inclination. The functional aims of FES methods will continue to develop as a result of experience gained following the introduction and use of successful devices, and these evolutionary improvements will come from within the FES programme; but the engineering embodiment of those devices may be revolutionized at any time by technological advances coming from elsewhere.

Electric Stimulation↗

PubMed2002

Nox/Duox family of nicotinamide adenine dinucleotide (phosphate) oxidases.

Reactive oxygen species are classically described as occurring as an accidental byproduct of respiration, and are generally thought to be deleterious to biologic systems. The phagocyte nicotinamide adenine dinucleotide phosphate oxidase provides an example of deliberate reactive oxygen species generation, but the function of this enzyme is to oxidatively modify bacteria as part of bactericidal mechanisms. The discovery of a family of nicotinamide adenine dinucleotide (phosphate) oxidases related to the phagocyte oxidase, the Nox/Duox family, provides additional examples of deliberate generation of reactive oxygen species. This article describes this new family of enzymes and considers hypotheses for their function. Potential roles of Nox/Duox in generation of reactive oxygen species that function in cell signaling (related to growth and angiogenesis), immune function, hypoxic response, and oxidative modification of extracellular matrix proteins are discussed.

Animals↗

PubMed2001

Dynamics of kinks in one- and two-dimensional hyperbolic models with quasidiscrete nonlinearities.

We study the evolution of fronts in the Klein-Gordon equation when the nonlinear term is inhomogeneous. Extending previous works on homogeneous nonlinear terms, we describe the derivation of an equation governing the front motion, which is strongly nonlinear, and, for the two-dimensional case, generalizes the damped Born-Infeld equation. We study the motion of one- and two-dimensional fronts finding a much richer dynamics than in the homogeneous system case, leading, in most cases, to the stabilization of one phase inside the other. For a one-dimensional front, the function describing the inhomogeneity of the nonlinear term acts as a "potential function" for the motion of the front, i.e., a front initially placed between two of its local maxima asymptotically approaches the intervening minimum. Two-dimensional fronts, with radial symmetry and without dissipation can either shrink to a point in finite time, grow unboundedly, or their radius can oscillate, depending on the initial conditions. When dissipation effects are present, the oscillations either decay spirally or not depending on the value of the damping dissipation parameter. For fronts with a more general shape, we present numerical simulations showing the same behavior.

Journal Article↗

PubMed1992

Effects of anoxia on mitochondrial biogenesis in rice shoots: modification of in organello translation characteristics.

Shoots of germinating rice (Oryza sativa L.) seedlings are able to grow under anoxia and to withstand long periods of anoxic treatment. Mitochondria were purified from aerobically germinated and anaerobically treated rice shoots by differential and isopycnic centrifugation and were found to consist of two subpopulations. The mitochondrial subpopulation of higher density was used for further characterization. Ultrastructural studies showed anaerobic mitochondria to be significantly different from aerobic mitochondria, with a matrix of lower density and more developed cristae. Aerobic and anaerobic mitochondria also differed in their specific activities for fumarase and succinate dehydrogenase, which were significantly lower after the anoxic treatment. In vivo labeling of seedlings with l-[(35)S]methionine and subsequent isolation of the mitochondria indicated that anoxia induced a drastic decrease, but not a total inactivation, of the synthesis of mitochondrial proteins. In organello protein synthesis showed that anaerobic mitochondria were able to synthesize most of the polypeptides synthesized by aerobic mitochondria, although only in the presence of exogenous ATP, as would occur under anoxia. Anaerobic mitochondria, but not aerobic mitochondria, could carry out protein synthesis without a functional respiratory chain. Thus, mitochondrial protein synthesis was found to be potentially functional in the rice shoot under anoxia.

Journal Article↗