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At least 775 records · Page 43Linked to original sources
PubMed2003

Influence of executive function on locomotor function: divided attention increases gait variability in Alzheimer's disease.

OBJECTIVES: To evaluate how cognitive function and divided attention affect gait in Alzheimer's disease (AD). DESIGN: Cross-sectional intervention study with subjects serving as their own controls. SETTING: Inpatient unit and outpatient clinic for patients with dementia located at a Veterans Affairs Medical Center. PARTICIPANTS: Twenty-eight patients diagnosed with probable AD. INTERVENTION: Performance of a cognitive task (repeating random digits) while walking. MEASUREMENTS: Neuropsychological measures including clock drawing, verbal fluency, and digit span were obtained along with the Clinical Dementia Rating and Mini-Mental State Examination, the measures of dementia severity. Gait speed and stride-to-stride variability of gait rhythm were measured, once during normal walking and once during dual-task walking. RESULTS: During usual walking, subjects walked slowly and with greater gait variability than older adults without AD. Gait speed was significantly reduced (P<.012) and gait variability increased with dual-task walking (P<.007). The effect on gait variability was larger than the effect on gait speed (P<.015). Executive and neuropsychological function were significantly (P<.02) associated with the increased gait variability that occurred when walking with divided attention but not with gait speed or usual, single-task walking measures of gait. CONCLUSION: Divided attention markedly impairs the ability of patients with AD to regulate the stride-to-stride variations in gait timing. This susceptibility to distraction and its effect on stride time variability, a measure of gait unsteadiness, could partially explain the predilection to falling observed in patients with dementia. The results also support the concept that persons with AD have significant impairments in the cognitive domain of attention and that locomotor function relies upon cognitive, especially executive, function.

Aged↗
PubMed2002

Functional electric stimulation-assisted rowing: Increasing cardiovascular fitness through functional electric stimulation rowing training in persons with spinal cord injury.

OBJECTIVES: To assess changes in peak functional aerobic power after a 36-session, progressive functional electric stimulation (FES) rowing hybrid training program for persons with spinal cord injury (SCI) and to examine the safety and acceptability of the ROWSTIM II device as well as the integrity of technical modifications to it. DESIGN: Repeated-measures training study, quasi-experimental design, within-person data comparison. SETTING: A university-based recreational physical activity facility for persons with physical disabilities. PARTICIPANTS: Six persons with level C7-T12 SCI (American Spinal Injury Association classes A-C). INTERVENTION: Progressive rowing training program, 30 minutes per session, 3 times a week for 12 weeks at 70% to 75% of pretest peak functional aerobic power during FES rowing on an open loop control, FES-assisted rowing machine. MAIN OUTCOME MEASURES: Total rowing distance, peak functional oxygen consumption, and peak oxygen pulse. RESULTS: Subjects completed between 22 to 36 sessions. After 3 months of training, rowing distance increased by 25% (P<.02), peak oxygen consumption by 11.2% (P<.001), and peak oxygen pulse by 11.4% (P<.01). Heart rate response to hybrid training did not change at the end of training, although peak heart rate with FES lower-extremity exercise increased significantly from pre- to posttraining (P<.01). CONCLUSIONS: Pre- and posttraining peak aerobic power values for ROWSTIM II training were comparable to previously reported values for hybrid cycle and upper-extremity exercise. We conclude that FES-assisted rowing is an effective, safe, and well-tolerated training system for persons with SCI.

Adult↗
PubMed2005

[Voice function and quality of life--patients with laryngeal carcinoma following minimal-invasive laser surgery and function voice rehabilitation].

BACKGROUND: Quality of life is a relevant criterion for therapeutical outcome in laryngeal carcinoma patients. The aim of this study was to assess the self-related complaints in quality of life and functional outcome of voice among persons who had undergone laryngeal cancer surgery. METHODS: The examination took place 67 months (SD 34.8) after the last surgery, on average and finishing of 60 therapy sessions (median). First a measurement with the Goettinger Hoarseness Diagram (GHD) was carried out. Next the subjects answered self-reported standardized questionnaires for life quality in oncological patients on the same day: EORTC-QLQ-C30 and 3 scales of the German Fragebogen zur Lebenszufriedenheit (health-related fulfillment, fulfillment with work/occupation, fulfillment with social environment). For disease-related symptoms of different head and neck domains the EORTC-HandN35 was administered. SUBJECTS: Forty-four patients (37 males, 7 females) who were treated primarily with minimal invasive laser surgery followed by functional voice rehabilitation (Goettinger Konzept). Mean age: 60.1 (SD 9.7) years. RESULTS: The acoustic voice quality according to the GHD showed a significant correlation with self-reported "Somatic Functioning" (- 0.32, p = 0.04) and "Social Functioning" (- 0.38, p = 0.01) in the EORTC-QLQ-C30 as well as with the symptom scales "Speech" (0.45, p < 0.0024) resp. "Social Contact" (0.45, p = 0.0021) in the EORTC-HandN35. Also hoarseness and health-related fulfillment (- 0.36, p = 0.02) as well as fulfillment with work/occupation (- 0.33, p = 0.03) correlated significantly. On the other hand, there was no significant association between the GHD and the assessment of global quality of life. CONCLUSION: Postoperative phonatory reductions in patients with laser surgically treated laryngeal carcinoma have only a slight influence on overall quality of life. The same is true for the GHD. Assessment of self-reported quality of life in recommendation of oncologic treatment may not be able to replace the objective findings, but may be useful to detect other problems, e.g. psychosocial.

Aged↗
PubMed2005

Applications of a time correlation function theory for the fifth-order Raman response function I: atomic liquids.

Multidimensional spectroscopy has the ability to provide great insight into the complex dynamics and time-resolved structure of liquids. Theoretically describing these experiments requires calculating the nonlinear-response function, which is a combination of quantum-mechanical time correlation functions R5(t1,t2) was expressed with a two-time, computationally tractable, classical TCF. Writing the response function in terms of classical TCFs brings the full power of atomistically detailed molecular dynamics to the problem. In this paper, the new TCF theory is employed to calculate the fifth-order Raman response function for liquid xenon and investigate several of the polarization conditions for which experiments can be performed on an isotropic system. The theory is shown to reproduce line-shape characteristics predicted by earlier theoretical work.

Journal Article↗
PubMed2005

Calculation of spin-densities within the context of density functional theory. The crucial role of the correlation functional.

It is demonstrated that the LYP correlation functional is not suited to be used for the calculation of electron spin resonance hyperfine structure (HFS) constants, nuclear magnetic resonance spin-spin coupling constants, magnetic, shieldings and other properties that require a balanced account of opposite- and equal-spin correlation, especially in the core region. In the case of the HFS constants of alkali atoms, LYP exaggerates opposite-spin correlation effects thus invoking too strong in-out correlation effects, an exaggerated spin-polarization pattern in the core shells of the atoms, and, consequently, too large HFS constants. Any correlation functional that provides a balanced account of opposite- and equal-spin correlation leads to improved HFS constants, which is proven by comparing results obtained with the LYP and the PW91 correlation functional. It is suggested that specific response properties are calculated with the PW91 rather than the LYP correlation functional.

Journal Article↗
PubMed2006

Screened exchange hybrid density-functional study of the work function of pristine and doped single-walled carbon nanotubes.

We present a detailed study of the work function of pristine and doped single-walled carbon nanotubes (SWCNTs) using a novel screened exchange hybrid density functional. We find that SWCNTs with diameters larger than 0.9 nm tend asymptotically and smoothly to the graphene limit of 4.6 eV. On the other hand, the work function of narrow tubes exhibits a strong dependence on their diameter and chiral angle. Boron or nitrogen doping, with concentrations from 1% to 2%, not only changes the electronic behavior by introducing new states around the Fermi level, but also produces a significant change of the work function that can vary between 3.9 (N doping) and 5.2 eV (B doping).

Journal Article↗
PubMed2002

Identification of gene function and functional pathways by systemic plasmid-based ribozyme targeting in adult mice.

To date, functional genomic studies have been confined to either cell-based assays or germline mutations, using transgenic or knockout animals. However, these approaches are often unable either to recapitulate complex biologic phenotypes, such as tumor metastasis, or to identify the specific genes and functional pathways that produce serious diseases in adult animals. Although the transcription factor NF-kappaB transactivates many metastasis-related genes in cells, the precise genes and functional-pathways through which NF-kappaB regulates metastasis in tumor-bearing hosts are poorly understood. Here, we show that the systemic delivery of plasmid-based ribozymes targeting NF-kappaB in adult, tumor-bearing mice suppressed NF-kappaB expression in metastatic melanoma cells, as well as in normal cell types, and significantly reduced metastatic spread. Plasmid-based ribozymes suppressed target-gene expression with sequence specificity not achievable by using synthetic oligonucleotide-based approaches. NF-kappaB seemed to regulate tumor metastasis through invasion-related, rather than angiogenesis-, cell-cycle- or apoptosis-related pathways in tumor-bearing mice. Furthermore, ribozymes targeting either of the NF-kappaB-regulated genes, integrin beta(3) or PECAM-1 (a ligand-receptor pair linked to cell adhesion), reduced tumor metastasis at a level comparable to NF-kappaB. These studies demonstrate the utility of gene targeting by means of systemic, plasmid-based ribozymes to dissect out the functional genomics of complex biologic phenotypes, including tumor metastasis.

Aging↗
PubMed2003

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Inactivation of the tumor suppressor p53 by missense mutations is the most frequent genetic alteration in human cancers. The common missense mutations in the TP53 gene disrupt the ability of p53 to bind to DNA and consequently to transactivate downstream genes. However, it is still not fully understood how a large number of the remaining mutations affect p53 structure and function. Here, we used a comprehensive site-directed mutagenesis technique and a yeast-based functional assay to construct, express, and evaluate 2,314 p53 mutants representing all possible amino acid substitutions caused by a point mutation throughout the protein (5.9 substitutions per residue), and correlated p53 function with structure- and tumor-derived mutations. This high-resolution mutation analysis allows evaluation of previous predictions and hypotheses through interrelation of function, structure and mutation.

Amino Acid Substitution↗
PubMed2003

CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly.

Age-related declines in immune function have an impact on both primary and memory responses. In this study, we have examined the ability of naive CD4 T cells from young and aged T cell receptor transgenic mice to establish functional memory. We found that memory cells generated from young CD4 T cells responded well to antigen, even a year after generation, whereas memory cells derived from CD4 T cells from aged mice responded poorly both ex vivo and in vivo. Memory cells generated from aged naive cells proliferate less, produce reduced levels of cytokines, and exhibit reduced cognate helper function, compared with memory cells generated by using young naive cells. These results indicate that it is the age of the naive T cell when it first encounters antigen, rather than the age when it reencounters antigen, that is critical for good memory CD4 T cell function.

Aging↗
PubMed1971

Similar idiotypic specificities in immunoglobulin fractions with different antibody functions or even without detectable antibody function.

IDIOTYPY HAS BEEN STUDIED IN ANTIBODIES AGAINST A PROTEIN ANTIGEN: hen ovalbumin. Various fractions of antisera to hen ovalbumin have been compared from the standpoint of the idiotypic specificities found on the immunoglobulins that they contain. Idiotypic specificities were found to be common to (a) antibodies that were not eluted from the same immunoadsorbent by the same MgCl(2) concentration, but by four different concentrations. (b) Antibodies that were precipitable only by hen ovalbumin, only by hen and turkey ovalbumin, or also by duck ovalbumin. (c) Antibodies that were precipitated or not precipitated by the homologous ovalbumin, and proteins apparently devoid of antiovalbumin antibody function. These findings are discussed from the standpoint of (i) the differences in function between the various fractions with the same idiotypic specificities, and (ii) what may be common in the cellular origin of immunoglobulins with a common idiotypic specificity, and what may be different in immunoglobulins with different antibody functions or without antibody function. The same idiotypic specificities have been found in certain IgG and IgM antiovalbumin antibodies.

Animals↗
PubMed1990

Functions of replication factor C and proliferating-cell nuclear antigen: functional similarity of DNA polymerase accessory proteins from human cells and bacteriophage T4.

The proliferating-cell nuclear antigen (PCNA) and the replication factors A and C (RF-A and RF-C) are cellular proteins essential for complete elongation of DNA during synthesis from the simian virus 40 origin of DNA replication in vitro. All three cooperate to stimulate processive DNA synthesis by DNA polymerase delta on a primed single-stranded M13 template DNA and as such can be categorized as DNA polymerase accessory proteins. Biochemical analyses with highly purified RF-C and PCNA have demonstrated functions that are completely analogous to the functions of bacteriophage T4 DNA polymerase accessory proteins. A primer-template-specific DNA binding activity and a DNA-dependent ATPase activity copurified with the multisubunit protein RF-C and are similar to the functions of the phage T4 gene 44/62 protein complex. Furthermore, PCNA stimulated the RF-C ATPase activity and is, therefore, analogous to the phage T4 gene 45 protein, which stimulates the ATPase function of the gene 44/62 protein complex. Indeed, some primary sequence similarities between human PCNA and the phage T4 gene 45 protein could be detected. These results demonstrate a striking conservation of the DNA replication apparatus in human cells and bacteriophage T4.

Adenosine Triphosphatases↗
PubMed1993

Essential role of the HMG domain in the function of yeast mitochondrial histone HM: functional complementation of HM by the nuclear nonhistone protein NHP6A.

The yeast mitochondrial histone protein HM is required for maintenance of the mitochondrial genome, and disruption of the gene encoding HM (HIM1/ABF2) results in formation of a respiration-deficient petite mutant phenotype. HM contains two homologous regions, which share sequence similarity with the eukaryotic nuclear nonhistone protein, HMG-1. Experiments with various deletion mutants of HM show that a single HMG domain of HM is functional and can restore respiration competency to cells that lack HM protein (him1 mutant cells). The gene encoding the putative yeast nuclear HMG-1 homolog, the NHP6A protein, can functionally complement the him1 mutation. These results suggest that the HMG domain is the basic unit for the function of HM in mitochondria and that the function of HMG-1 proteins in the nucleus and HM in the mitochondrion may be equivalent.

ATP-Binding Cassette Transporters↗
PubMed1995

Ovulation efficiency is reduced in mice that lack plasminogen activator gene function: functional redundancy among physiological plasminogen activators.

Several lines of indirect evidence suggest that plasminogen activation plays a crucial role in degradation of the follicular wall during ovulation. However, single-deficient mice lacking tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), or PA inhibitor type 1(PAI-1) gene function were recently found to have normal reproduction, although mice with a combined deficiency of tPA and uPA were significantly less fertile. To investigate whether the reduced fertility of mice lacking PA gene function is due to a reduced ovulation mechanism, we have determined the ovulation efficiency in 25-day-old mice during gonadotropin-induced ovulation. Our results reveal that ovulation efficiency is normal in mice with a single deficiency of tPA or uPA but reduced by 26% in mice lacking both physiological PAs. This result suggests that plasminogen activation plays a role in ovulatory response, although neither tPA nor uPA individually or in combination is obligatory for ovulation. The loss of an individual PA seems to be functionally complemented by the remaining PA but this compensation does not appear to involve any compensatory up-regulation. Our data imply that a functionally redundant mechanism for plasmin formation operates during gonadotropin-induced ovulation and that PAs together with other proteases generate the proteolytic activity required for follicular wall degradation.

Animals↗
PubMed1995

Functional degenerin-containing chimeras identify residues essential for amiloride-sensitive Na+ channel function.

The highly selective, amiloride-sensitive Na+ channel is formed of three homologous subunits termed alpha, beta, and gamma. The three subunits exhibit similarities with Caenorhabditis elegans proteins called degenerins involved in sensory touch transduction and, when mutated, in neurodegeneration. Swelling of neurons observed in neurodegeneration suggests an involvement of ion transport, but the channel function of degenerins has not yet been demonstrated. We used chimeras to study the functional relationship between the epithelial sodium channel and the degenerin Mec-4. Exchange of the hydrophobic domains of the Na+ channel alpha subunit by those of Mec-4 results in a functional ion channel with changed pharmacology for amiloride and benzamil and changed selectivity, conductance, gating, and voltage dependence. All of these differences were also obtained by exchanging Ser-589 and Ser-593 in the second transmembrane region by the corresponding residues of Mec-4, suggesting that these two residues are essential for the ionic pore function of the channel.

Amiloride↗
PubMed1995

Isolation of a functional homolog of the cell cycle-specific NIMA protein kinase of Aspergillus nidulans and functional analysis of conserved residues.

To investigate the degree of conservation of the cell cycle-specific NIMA protein kinase of Aspergillus nidulans, and to help direct its functional analysis, we cloned a homolog (designated nim-1) from Neurospora crassa. Over the catalytic domain NIM-1 is 75% identical to NIMA, but overall the identity drops to 52%. nim-1 was able to functionally complement nimA5 in A. nidulans. Mutational analysis of potential activating phosphorylation sites found in NIMA, NIM-1, and related protein kinases was performed on NIMA. Mutation of threonine 199 (conserved in all NIMA-related kinases) inhibited NIMA beta-casein kinase activity and abolished its in vivo function. This site conforms to a minimal consensus phosphorylation site for NIMA (FXXT) and is analogous to the autophosphorylation site of cyclic-AMP-dependent protein kinases. However, mutation of a unique cysteine residue found only in the catalytic site of NIMA and NIM-1 had no effect on NIMA kinase activity or function. Three temperature-sensitive alleles of nimA that cause arrest in G2 were sequenced and shown to generate three different amino acid substitutions. None of the mutations prevented accumulation of NIMA protein during G2 arrest, but all prevented the p34cdc2/cyclin B-dependent phosphorylation of NIMA normally seen during mitotic initiation even though p34cdc2/cyclin B H1 kinase activity was fully activated.

Amino Acid Sequence↗
PubMed1998

Structural and functional effects of pseudo-module substitution in hemoglobin subunits. New structural and functional units in globin structure.

Functional and structural significance of the "module" in proteins has been investigated for globin proteins. Our previous studies have revealed that some modules in globins are responsible for regulating the subunit association and heme environmental structures, whereas the module substitution often induces fatal structural destabilization, resulting in failure of functional regulation. In this paper, to gain further insight into functional and structural significance of the modular structure in globins, we focused upon the "pseudo-module" in globin structure where boundaries are located at the center of modules. Although the pseudo-module has been supposed not to retain a compactness, the betaalpha(PM3)-subunit, in which one of the pseudo-modules, the F1-H6 region, of the alpha-subunit is implanted into the beta-subunit, conserved stable globin structure, and its association property was converted into that of the alpha-subunit, as the case for the module substituted globin, the betaalpha(M4)-subunit. These results suggest that modules are not unique structural and functional units for globins. Interestingly, however, the recent reconsideration of the module boundary indicates that the modules in globins can be further divided into two small modules, and one of the boundaries for the new small modules coincides with that of the pseudo-module we substituted in this study. Although it would be premature to conclude the significance of the modular structure in globins, it can be safely said that we have found new structural units in globin structure, probably new modules.

Amino Acid Sequence↗
PubMed2000

A fully functional rod visual pigment in a blind mammal. A case for adaptive functional reorganization?

In the blind subterranean mole rat Spalax ehrenbergi superspecies complete ablation of the visual image-forming capability has been accompanied by an expansion of the bilateral projection from the retina to the suprachiasmatic nucleus. We have cloned the open reading frame of a visual pigment from Spalax that shows >90% homology with mammalian rod pigments. Baculovirus expression yields a membrane protein with all functional characteristics of a rod visual pigment (lambda(max) = 497 +/- 2 nm; pK(a) of meta I/meta II equilibrium = 6.5; rapid activation of transducin in the light). We not only provide evidence that this Spalax rod pigment is fully functional in vitro but also show that all requirements for a functional pigment are present in vivo. The physiological consequences of this unexpected finding are discussed. One attractive option is that during adaptation to a subterranean lifestyle, the visual system of this mammal has undergone mosaic reorganization, and the visual pigments have adapted to a function in circadian photoreception.

Amino Acid Sequence↗
PubMed2002

Structure-function analysis of yeast Grx5 monothiol glutaredoxin defines essential amino acids for the function of the protein.

Grx5 defines a family of yeast monothiol glutaredoxins that also includes Grx3 and Grx4. All three proteins display significant sequence homology with proteins found from bacteria to humans. Grx5 is involved in iron/sulfur cluster assembly at the mitochondria, but the function of Grx3 and Grx4 is unknown. Three-dimensional modeling based on known dithiol glutaredoxin structures predicted a thioredoxin fold structure for Grx5. Positionally conserved amino acids in this glutaredoxin family were replaced in Grx5, and the effect on the biological function of the protein has been tested. For all changes studied, there was a correlation between the effects on several different phenotypes: sensitivity to oxidants, constitutive protein oxidation, ability for respiratory growth, auxotrophy for a number of amino acids, and iron accumulation. Cys(60) and Gly(61) are essential for Grx5 function, whereas other single or double substitutions in the same region had no phenotypic effects. Gly(115) and Gly(116) could be important for the formation of a glutathione cleft on the Grx5 surface, in contrast to adjacent Cys(117). Substitution of Phe(50) alters the beta-sheet in the thioredoxin fold structure and inhibits Grx5 function. None of the substitutions tested affect the structure at a significant enough level to reduce protein stability.

Amino Acid Sequence↗