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Results for “Functional potential”

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PubMed1988

The organisation and expression of histone genes from Xenopus borealis.

We have isolated genomic clones from Xenopus borealis representing 3 different types of histone gene cluster. We show that the major type (H1, H2B, H2A, H4, H3), present at about 60-70 copies per haploid genome (1), is tandemly reiterated with a repeat length of 15 kb. In situ hybridization to mitotic chromosomes shows that the majority of histone genes in Xenopus borealis are at one locus. This locus is on the long arm of one of the small sub-metacentric chromosomes. A minor cluster type with the gene order H1, H3, H4, H2A is present at about 10-15 copies. The genome also contains rare or unique cluster types present at less than 5 copies having other types of organisation. An isolate of this type had the gene order H1, H4, H2B, H2A, H1 (no H3 cloned). Microinjection of all of the clones into Xenopus laevis oocyte nuclei shows that most of the genes present are functional or potentially functional and a number of variant histone proteins have been observed. S1 mapping experiments confirm that the genes of the major cluster are expressed in all tissues and at all developmental stages examined.

Animals↗

PubMed2005

Representation and modeling of protein surface determinants.

Surface characterization of peptides may provide useful information about functionality and potential interactions with other molecules. A description of a protein site through a surface that models the shape conferred by the exposed residues is an effective tool for the analysis and the modeling of proteins that may highlight similarities and relationships not detectable through comparisons at level of primary, secondary, and tertiary structure. This study concerns the development of a tool that extracts the residues that concur to the shape modeling of the surface of a protein or a portion of it. This task is accomplished without taking into account the order of the amino acids in the primary structure, but only according to the selection of a portion of the protein indicated through geometric parameters or an explicit list of amino acids belonging to the site of interest. Both in the case of an entire protein and in the case of a portion of it, the method provides the mesh that models the surface described by the exposed residues that constitute the external envelope. The developed tool which allows the extraction of the exposed residues, and thus of the potential function determinants, is applied to identify the amino acids that concur to the structural interaction in several protein complexes.

Amino Acid Sequence↗

PubMed1997

Why does Staphylococcus aureus secrete an Enterococcus faecalis-specific pheromone?

The long known fact that Staphylococcus aureus can secrete a peptide (staph-cAM373) which acts as a sex pheromone for strains of E. faecalis carrying the sex pheromone plasmid pAM373 was studied in detail. 85 of 100 independent isolates of S. aureus produced an activity inducing the pAM373 encoded adhesin resulting in a clumping reaction of E. faecalis (i.e. secreted staph-cAM373), but not a single one of 100 independent isolates of coagulase-negative Staphylococci possessed this activity. The production of peptides acting as sex pheromone for E. faecalis was observed only for sex pheromone plasmid pAM373, but not for sex pheromone plasmids pAD1 and pPD1. It was shown that the amount of staph-pAM373 produced during growth paralleled cell mass, therefore this peptide should not be used as a cell density indicator by S. aureus (i.e. has no quorum sensing function). The potential function of staph-cAM373 to trigger gene transfer from Escherichia faecalis to S. aureus is discussed.

Bacterial Adhesion↗

PubMed2002

Genetic redundancy in evolving populations of simulated robots.

A number of authors have argued that redundancy in biological organisms contributes to their evolvability. We investigate this hypothesis via the experimental manipulation of genetic redundancy in evolving populations of simulated robots controlled by artificial neural networks. A genetic algorithm is used to simulate the evolution of robots with the ability to perform a previously studied task. Redundancy is measured using systematic lesioning. In our experiments, populations of robots with larger genotypes achieve systematically higher fitness than populations whose genotypes are smaller. It is shown that, in principle, robots with smaller genotypes have enough computational power to achieve optimal fitness. Populations with larger (redundant) genotypes appear, however, to be more evolvable and display significantly higher diversity. It is argued that this enhanced evolvability is a direct effect of genetic redundancy, which allows populations of redundant robots to explore neutral networks spanning large areas of genotype space. We conjecture that, where cost considerations allow, redundancy in functional or potentially functional components of the genome may make a valuable contribution to evolution in artificial and perhaps in biological systems. The methods described in the article provide a practical way of testing this hypothesis for the artificial case.

Models, Genetic↗

PubMed1993

Functional domains of the human C1q A-chain.

This brief review was inspired by discussions relating to the IIIrd. International C1 Workshop (this volume) and the realization that certain functional properties of the C1q molecule are limited exclusively to the A-chain. The collagen-like region of the A-chain contains a major binding site for non-immunoglobulin substances, which include C-reactive protein, serum amyloid P, LPS and DNA. This binding site is immediately adjacent to, and partially overlapping with, an arthritis-modulating epitope common to the C1q A-chain and various types of collagen, including cartilage type II collagen. At the N-terminal end of the C1q A-chain is a leader peptide sequence that anchors the intact C1q molecule firmly in the membrane of macrophages, the C1q molecule can thus be classified as a type II membrane protein, functioning as an additional receptor for molecules known to react with C1q in fluid phase such as the Fc region of IgG, LPS and polyanionic molecules (e.g. chondroitin sulphate, heparin, dextran sulphate etc.). The various domains within the A-chain, and their respective functions (or potential functions), are presented and discussed in the context of the intact C1 molecule and with regard to any wider functional relevance.

Amino Acid Sequence↗

PubMed1993

Surgery for chronic lower extremity ischemia in patients eighty or more years of age: operative results and assessment of postoperative independence.

PURPOSE: Revascularization for chronic lower extremity ischemia (CLEI) in patients 80 or more years of age is controversial. High operative mortality, short remaining life span, and nonambulatory nursing home existence are cited as frequent outcomes in this patient group. Despite these considerations we have maintained an aggressive policy of lower extremity revascularization in functional and potentially functional patients 80 or more years of age with limb-threatening ischemia or claudication sufficient to threaten their independence. METHODS: The records of all patients 80 or more years of age who underwent lower extremity revascularization for CLEI from 1981 through 1991 were reviewed. Patients were evaluated for surgical indication, perioperative mortality, late survival, graft patency, and limb salvage. In addition, the patient's preoperative and postoperative independence determined by living situation (home versus nursing home) and ambulatory status were examined. RESULTS: During the period reviewed 88 patients 80 or more years of age underwent 95 arterial reconstructions for CLEI; 95% for limb salvage and 5% for short-distance claudication. There were 81 (85%) infrainguinal bypasses and 14 (15%) extra-anatomic bypasses, 5 of which also included a simultaneously placed infrainguinal bypass. The perioperative mortality rate was 6%. Mean hospitalization was 18 days (range 6 to 62). The 1- and 3-year primary graft patency rates were 88% and 66%, limb salvage rates 94% and 91%, and patient survival rates 73% and 51%, respectively. One year after operation 88% of patients were ambulatory, 85% were living at home, and 80% were both living at home and ambulatory. At 3 years these results were 86%, 76%, and 71%, respectively. Of the patients living at home and ambulatory before operation, 100% and 84% of survivors were still living at home and ambulatory 1 and 3 years after operation. Of patients living at home who had late graft occlusions, 67% required amputation and subsequent nursing home placement. CONCLUSION: Although survival in this group is predictably lower than that of age-matched control subjects, octogenarians have satisfactory 1- and 3-year graft patency, limb salvage, and functional results. Revascularization for CLEI in patients 80 or more years of age is appropriate and results in maintenance of independent living in a large majority.

Activities of Daily Living↗

PubMedDate not supplied

Nursing in the NHS: the executive nurse director.

The advent of trusts within the NHS brought a new dimension to the role of nurses in management, in that each trust must appoint an executive nurse director to sit on the trust board. The function and potential function of this role is, I believe, pivotal to the development of clinical services within the NHS.

Education, Nursing↗

PubMed2006

A physically meaningful method for the comparison of potential energy functions.

In the study of the conformational behavior of complex systems, such as proteins, several related statistical measures are commonly used to compare two different potential energy functions. Among them, the Pearson's correlation coefficient r has no units and allows only semiquantitative statements to be made. Those that do have units of energy and whose value may be compared to a physically relevant scale, such as the root-mean-square deviation (RMSD), the mean error of the energies (ER), the standard deviation of the error (SDER) or the mean absolute error (AER), overestimate the distance between potentials. Moreover, their precise statistical meaning is far from clear. In this article, a new measure of the distance between potential energy functions is defined that overcomes the aforementioned difficulties. In addition, its precise physical meaning is discussed, the important issue of its additivity is investigated, and some possible applications are proposed. Finally, two of these applications are illustrated with practical examples: the study of the van der Waals energy, as implemented in CHARMM, in the Trp-Cage protein (PDB code 1L2Y) and the comparison of different levels of the theory in the ab initio study of the Ramachandran map of the model peptide HCO-L-Ala-NH2.

Chemistry, Physical↗

PubMed2001

Evaluation of renal function in potential living kidney donors.

BACKGROUND: Most transplant centers in the United States, including our own, use creatinine clearance (Ccr) to estimate glomerular filtration rate (GFR) in potential living kidney donors. The purpose of this study was to evaluate our experience with estimation of donor GFR by Ccr and to explore other potential strategies for evaluation of renal function in donors. METHODS: Potential donors performed one to three outpatient urine collections for Ccr measurement. Those with low or inconsistent results underwent measurement of GFR by a radionuclide method not dependent upon urine collection (rGFR). The ability to determine adequacy of urine volume by creatinine excretion rate (UVcr) was examined. GFR was also predicted from serum creatinine (Scr) by using two prediction equations [Cockcroft-Gault and that from the Modification of Diet in Renal Disease Study (MDRD)]. The effect of indexing GFR by height, as opposed to body surface area (BSA) was explored. RESULTS: Over a 5-year period, 22 potential donors (approximately 10% of total evaluated) had inconsistent or low Ccr. Most had normal rGFR and, presumably, undercollected their urine. However, several female donors had truly low GFR by rGFR. The accuracy of Ccr (compared with rGFR) was not predicted by UVcr in a clinically useful way. The prediction equations did not have sufficient accuracy or precision to replace rGFR in this population. Indexing GFR estimates by BSA introduced a bias toward lower values in females; this was largely overcome by indexing GFR by height. CONCLUSIONS: Evaluation of GFR in potential living donors by Ccr is not very useful. A more promising strategy could be developed predicting GFR from Scr and indexing the results by height rather than BSA. The optimum method for evaluation of renal function in kidney donors deserves further study.

Adult↗

PubMed1999

Calculation of protein conformation by global optimization of a potential energy function.

A novel hierarchical approach to protein folding has been applied to compute the unknown structures of seven target proteins provided by CASP3. The approach is based exclusively on the global optimization of a potential energy function for a united-residue model by conformational space annealing, followed by energy refinement using an all-atom potential. Comparison of the submitted models for five globular proteins with the experimental structures shows that the conformations of large fragments (approximately 60 aa) were predicted with rmsds of 4.2-6.8 A for the C alpha atoms. Our lowest-energy models for targets T0056 and T0061 were particularly successful, producing the correct fold of approximately 52% and 80% of the structures, respectively. These results support the thermodynamic hypothesis that protein structure can be computed solely by global optimization of a potential energy function for a given amino acid sequence.

Algorithms↗

PubMed1997

Fourfold Clusters of Rovibrational Energies in H2Po Studied with an ab Initio Potential Energy Function

We report here an ab initio investigation of the cluster effect (i.e., the formation of four-member groups of nearly degenerate rotation-vibration energy levels at higher J and Ka values) in the H2Po molecule. The potential energy function has been calculated ab initio for a total of 143 molecular geometries by means of the CCSD(T) method, using an averaged relativistic effective potential for Po in conjunction with a newly optimized basis set. The values of the potential energy function obtained cover the region up to around 5000 cm-1 above the equilibrium energy. On the basis of the ab initio potential, the rotation-vibration energies of H2209Po have been calculated with the MORBID (Morse oscillator rigid bender internal dynamics) Hamiltonian and computer program. In particular, we have calculated the rotational energy manifolds for J </= 40 in the vibrational ground state. We find that the formation of fourfold clusters in H2Po is very similar to that in H2Te. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗

PubMed2000

5-HT(3) receptor function and potentiation by alcohols in frontal cortex neurons from transgenic mice overexpressing the receptor.

The function of 5-hydroxytryptamine (5-HT)(3) receptors was examined by whole-cell patch-clamp recording in dissociated frontal cortex neurons from 5-HT(3) receptor overexpressing transgenic, and wild-type mice. The effect of acute exposure to alcohols on the 5-HT(3) receptor-mediated ion current was also investigated. The 5-HT(3) receptors expressed on frontal cortex neurons in transgenic mice were activated by 5-HT and a selective 5-HT(3) receptor agonist, 2-methyl-5-HT. This current was blocked by zacopride, a specific 5-HT(3) receptor antagonist. Dissociated frontal cortex neurons from wild-type mice exhibited little or no 5-HT(3) receptor-mediated current. Ethanol (EtOH) and trichloroethanol (TCEt) potentiated the function of 5-HT(3) receptors overexpressed in transgenic mice. This is the first evidence that 5-HT(3) receptors exhibit sensitivity to alcohols when expressed by a central neuron.

Alcohols↗

PubMed2005

Assessing the potential for functional improvement of stroke patients attending a geriatric day hospital.

In the present study the potential for functional improvement in 103 stroke patients attending a geriatric day hospital was evaluated using the Orpington Prognostic Scale (OPS). This information may assist in coordinating the patients' and caregivers' expectations, allocating resources efficiently, and advance care planning. The Spearman correlation was used to calculate the association between OPS score and Functional Independent Measure (FIM), the Nottingham Extended ADL Index (NEAI), and the timed Get Up and Go test (TUG). The studied population was divided into two groups: patients with mild neurological impairment (OPS score<3.2) and those with moderate to severe neurological impairment (OPS score> or =3.2) and their performance on the above outcome measure were compared. The OPS score significantly correlated (p<0.001) with discharge scores of FIM (r=-0.730), NEAI (r=-0.675), and TUG (r=0.448). Patients with OPS score <3.2 achieved significantly higher discharge scores (p<0.001) in all three measures (FIM, TUG, and NEAI) compared to patients with OPS score > or =3.2. Nevertheless, patients with moderate to severe neurological impairment achieved greater score changes in FIM and TUG than patients with mild neurological impairment, although their discharge scores were less favorable. These results indicate that stroke patients even the more impaired, may continually recover and should be exposed to a prolonged rehabilitation program.

Aged↗

PubMed2004

Effects of antithrombin III on spinal cord-evoked potentials and functional recovery after spinal cord injury in rats.

STUDY DESIGN: From the view of motor function, spinal cord-evoked potentials, and histology, we evaluated the effects of antithrombin III on a spinal cord injury resulting in incomplete paraplegia. OBJECTIVES: To investigate the effect of antithrombin III on the recovery process after acute incomplete rat spinal cord injury. SUMMARY OF BACKGROUND DATA: Antithrombin III is used for treating disseminated intravascular coagulation by its anticoagulant effect and is also reported to reduce organ damage by the release of prostaglandin I2 from endothelial cells, induced by antithrombin III. Therefore, antithrombin III has potential as a therapeutic agent for spinal cord damage. METHODS: The spinal cord injury was induced by placing a 25 g weight on the dorsal surface of the spinal cord at the 10th thoracic spine level for 20 minutes. Antithrombin III (250 U/kg) was administered intravenously 5 minutes before the compression, whereas 2 mL of physiologic saline solution was administered to the control group. We recorded the spinal cord-evoked potentials at the T13 level after stimulation of the brain and C7 level. For 12 weeks after the injury, we observed the recovery course of waveform and motor function. The recovery of motor function was evaluated by using inclined table and modified Tarlov scores. We also examined the histology of the compressed site in the spinal cord. RESULTS: There were statistically significant differences in the motor recovery process between the two groups. Evoked potentials of the antithrombin III group recovered earlier than those of the control group. Histologically, hemorrhage and tissue defects in the spinal cord were less in the antithrombin III group. CONCLUSION: Because antithrombin III facilitated the recovery of behavior and evoked potentials, these findings suggest that antithrombin III may have a positive effect on the recovery of incomplete spinal cord injury.

Animals↗

PubMed2006

Nutritional approach for designing meat-based functional food products with nuts.

Meat and meat products are essential components of diets in developed countries and despite the convincing evidence that relate them to an increased risk for CVD, a growing consumption of meat products is foreseen. Epidemiological studies show that regular consumption of nuts, in general, and walnuts in particular, correlates inversely with myocardial infarction and ischaemic vascular disease. We assess the nutritional basis for and technological approach to the development of functional meat-based products potentially relevant in cardiovascular disease (CVD) risk reduction. Using the available strategies in the meat industry (reformulation processes) and a food-based approach, we address the design and development of restructured beef steak with added walnuts, potentially functional for CVD risk reduction. Its adequacy as a vehicle for active nutrients is confirmed by a pharmacokinetic pilot study in humans using gamma-tocopherol as an exposure biomarker in chylomicrons during the post-prandial state. Effect and potential "functionality" is being assessed by a dietary intervention study in subjects at risk and markers and indicators related to CVD are being evaluated. Within the conceptual framework of evidence-based medicine, development of meat-based functional products may become a useful approach for specific applications, with a potential market and health benefits of great importance at a population level.

Animals↗

PubMed2004

Effects of exercise training and detraining on oxidized low-density lipoprotein-potentiated platelet function in men.

OBJECTIVE: To investigate how exercise training and detraining affect oxidized low-density lipoprotein (Ox-LDL)-potentiated platelet function in men. DESIGN: Cohort study. SETTING: Department of physical medicine and rehabilitation. PARTICIPANTS: Ten sedentary men (mean age +/- standard error of the mean, 21.6+/-0.2 y) who did not engage in any regular physical activity for at least 1 year before the study. INTERVENTIONS: Subjects cycled on an ergometer at about 50% of maximal oxygen consumption for 30 minutes daily, 5 days a week, for 8 weeks, then detrained for 12 weeks. MAIN OUTCOME MEASURES: During the experimental period, blood samples from the subjects were collected before and immediately after a progressive exercise test (ie, strenuous, acute exercise) every 4 weeks. The following measurements were taken when the subjects were at rest and immediately after exercise: plasma lipid profile, plasma Ox-LDL level, and platelet aggregation and intracellular calcium concentration ([Ca2+]i) elevation induced by adenosine disphosphate (ADP) alone or simultaneous ADP and Ox-LDL addition. RESULTS: Analytical results indicated that: (1) plasma total cholesterol and LDL levels were reduced after exercise training from 151+/-7 mg/dL and 58+/-2 mg/dL to 133+/-6 mg/dL and 46+/-2 mg/dL (P<.05), respectively, whereas the plasma Ox-LDL level remained unchanged; (2) platelet aggregation and [Ca2+]i elevation promoted by 100 microg/mL of Ox-LDL were significantly increased from 70%+/-5% and 91%+/-7% of resting level to 108%+/-4% and 125%+/-3% after strenuous, acute exercise (P<.05); (3) exercise training decreased resting and postexercise 100 microg/mL Ox-LDL-potentiated platelet aggregation (ie, 31%+/-4% and 82%+/-4%, respectively; P<.05) and [Ca2+]i elevation (ie, 35%+/-6% and 71%+/-4%, respectively; P<.05); (4) detraining reversed the training effects on lipid profile and platelet function; and (5) treating the platelet with L-arginine-inhibited Ox-LDL-potentiated platelet activation during the experimental period. CONCLUSIONS: Our results suggest that 8 weeks of exercise training decreased the plasma LDL level, but failed to influence production of plasma Ox-LDL. Importantly, resting and exercise-induced Ox-LDL-potentiated platelet activation was decreased by exercise training. However, this was reversed by detraining to the pretraining level.

Adenosine Diphosphate↗

PubMed1965

Thermodynamics of terrestrial evolution.

The causal element of biological evolution and development can be understood in terms of a potential function which is generalized from the variational principles of irreversible thermodynamics. This potential function is approximated by the rate of entropy production in a configuration space which admits of macroscopic excursions by fluctuation and regression as well as microscopic ones. Analogously to Onsager's dissipation function, the potential takes the form of a saddle surface in this configuration space. The path of evolution following from an initial high dissipation state within the fixed constraint provided by the invariant energy flux from the sun tends toward the stable saddle point by a series of spontaneous regressions which lower the entropy production rate and by an alternating series of spontaneous fluctuations which introduce new internal constraints and lead to a higher entropy production rate. The potential thus rationalizes the system's observed tendency toward "chemical imperialism" (high dissipation) while simultaneously accommodating the development of "dynamic efficiency" and complication (low dissipation).

Biological Evolution↗

PubMed2001

Consequences of Hox gene duplication in the vertebrates: an investigation of the zebrafish Hox paralogue group 1 genes.

As a result of a whole genome duplication event in the lineage leading to teleosts, the zebrafish has seven clusters of Hox patterning genes, rather than four, as described for tetrapod vertebrates. To investigate the consequences of this genome duplication, we have carried out a detailed comparison of genes from a single Hox paralogue group, paralogue group (PG) 1. We have analyzed the sequences, expression patterns and potential functions of all four of the zebrafish PG1 Hox genes, and compared our data with that available for the three mouse genes. As the basic functions of Hox genes appear to be tightly constrained, comparison with mouse data has allowed us to identify specific changes in the developmental roles of Hox genes that have occurred during vertebrate evolution. We have found variation in expression patterns, amino acid sequences within functional domains, and potential gene functions both within the PG1 genes of zebrafish, and in comparison to mouse PG1 genes. We observed novel expression patterns in the midbrain, such that zebrafish hoxa1a and hoxc1a are expressed anterior to the domain traditionally thought to be under Hox patterning control. The hoxc1a gene shows significant coding sequence changes in known functional domains, which correlate with a reduced capacity to cause posteriorizing transformations. Moreover, the hoxb1 duplicate genes have differing functional capacities, suggesting divergence after duplication. We also find that an intriguing function 'shuffling' between paralogues has occurred, such that one of the zebrafish hoxb1 duplicates, hoxb1b, performs the role in hindbrain patterning played in mouse by the non-orthologous Hoxa1 gene.

Amino Acid Sequence↗