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At least 775 records · Page 43Linked to original sources

PubMed1996

Nitric oxide-induced mobilization of intracellular calcium via the cyclic ADP-ribose signaling pathway.

Cyclic adenosine diphosphate ribose (cADPR) is a potent endogenous calcium-mobilizing agent synthesized from beta-NAD+ by ADP-ribosyl cyclases in sea urchin eggs and in several mammalian cells (Galione, A., and White, A. (1994) Trends Cell Biol. 4, 431 436). Pharmacological studies suggest that cADPR is an endogenous modulator of Ca2+-induced Ca2+ release mediated by ryanodine-sensitive Ca2+ release channels. An unresolved question is whether cADPR can act as a Ca2+-mobilizing intracellular messenger. We show that exogenous application of nitric oxide (NO) mobilizes Ca2+ from intracellular stores in intact sea urchin eggs and that it releases Ca2+ and elevates cADPR levels in egg homogenates. 8-Amino-cADPR, a selective competitive antagonist of cADPR-mediated Ca2+ release, and nicotinamide, an inhibitor of ADP-ribosyl cyclase, inhibit the Ca2+-mobilizing actions of NO, while, heparin, a competitive antagonist of the inositol 1,4,5-trisphosphate receptor, did not affect NO-induced Ca2+ release. Since the Ca2+-mobilizing effects of NO can be mimicked by cGMP, are inhibited by the cGMP-dependent-protein kinase inhibitor, Rp-8-pCPT-cGMPS, and in egg homogenates show a requirement for the guanylyl cyclase substrate, GTP, we suggest a novel action of NO in mobilizing intracellular calcium from microsomal stores via a signaling pathway involving cGMP and cADPR. These results suggest that cADPR has the capacity to act as a Ca2+-mobilizing intracellular messenger.

ADP-ribosyl Cyclase↗

PubMed1997

Sequential modification of serines 621 and 624 in the Raf-1 carboxyl terminus produces alterations in its electrophoretic mobility.

The Raf-1 serine/threonine protein kinase plays a central role in many of the mitogenic signaling pathways regulating cell growth and differentiation. The regulation of Raf-1 is complex, and involves protein-protein interactions as well as changes in the phosphorylation state of Raf-1 that are accompanied by alterations in its electrophoretic mobility. We have previously shown that a 33-kDa COOH-terminal, kinase-inactive fragment of Raf-1 underwent a mobility shift in response to the stimulation of cells with serum or phorbol esters. Here we demonstrate that treatment of NIH 3T3 cells or Sf9 cells with hydrogen peroxide (H2O2) also induces the mobility shift of the kinase-inactive Raf-1 fragment. A series of deletion mutants of the Raf-1 COOH terminus were analyzed, and the region required for the mobility shift was localized to a 78-amino acid fragment (residues 566-643). Metabolic labeling revealed that the slower migrating forms of the 33-kDa and of the smaller fragment contained phosphorus. Mutation of a previously characterized phosphorylation site, serine 621, to alanine prevented the mobility shift as well as phosphate incorporation or Src and Ras-dependent kinase activation in Sf9 cells when this mutation was engineered into the full-length Raf-1. Mutation of 621 to aspartate yielded a protein that existed in both the shifted and unshifted forms, demonstrating that a negative charge at 621 was necessary, but not sufficient, for the mobility shift to occur; however, its full-length form was still resistant to activation in the Sf9 system. Additional mutation of nearby serine 624 to alanine blocked the shift, implicating this residue as the site of the second of a two-step modification process leading to the slower migrating form. Co-expression of the 33-kDa fragment with an activated form of mitogen-activated protein kinase kinase in NIH 3T3 led to the appearance of the shifted form in a serum-independent manner. These results demonstrate that a mitogen-activated protein kinase kinase-induced event involving modification of serines 621 and 624 leads to the mobility shift of Raf-1.

3T3 Cells↗

PubMed2002

Dynamic shuttling and intranuclear mobility of nuclear hormone receptors.

We expressed green fluorescent protein (GFP) chimeras of estrogen, retinoic acid, and thyroid hormone receptors (ERs, RARs, and TRs, respectively) in HeLa cells to examine nucleocytoplasmic shuttling and intranuclear mobility of nuclear hormone receptors (NRs) by confocal microscopy. These receptors were predominantly in the nucleus and, interestingly, underwent intranuclear reorganization after ligand treatment. Nucleocytoplasmic shuttling was demonstrated by heterokaryon experiments and energy-dependent blockade of nuclear import and leptomycin-dependent blockade of nuclear export. Ligand addition decreased shuttling by GFP-ER, whereas heterodimerization with retinoid X receptor helped maintain TR and RAR within the nucleus. Intranuclear mobility of the GFP-NRs was studied by fluorescence recovery after photo-bleaching +/- cognate ligands. Both GFP-TR and GFP-RAR moved rapidly in the nucleus, and ligand binding did not significantly affect their mobility. In contrast, estrogen binding decreased the mobility of GFP-ER and also increased the fraction of GFP-ER that was unable to diffuse. These effects were even more pronounced with tamoxifen. Co-transfection of the co-activator, SRC-1, further slowed the mobility of liganded GFP-ER. Our findings suggest estradiol and tamoxifen exert differential effects on the intranuclear mobility of GFP-ER. They also show that ligand-binding and protein-protein interactions can affect the intracellular mobility of some NRs and thereby may contribute to their biological activity.

Cell Nucleus↗

PubMed2002

Anthropometric indices predict physical function and mobility in older Australians: the Australian Longitudinal Study of Ageing.

OBJECTIVE: To evaluate, in terms of function and mobility, the predictive value of commonly adopted anthropometric 'definitions' used in the nutritional assessment of older adults, in a cohort of older Australians. DESIGN: Prospective cohort study - Australian Longitudinal Study of Ageing (ALSA). SETTING: Adelaide, South Australia (1992-1994). SUBJECTS: Data were analysed from 1272 non-institutionalised (685 males, 587 females) older adults > or =70 years old in South Australia. Seven 'definitions' commonly used in the anthropometric assessment of both under- and overnutrition (including four using body mass index (BMI), waist-to-hip ratio, waist circumference and percentage weight change) were evaluated at baseline, for their ability to predict functional and mobility limitation assessed (by self-report questionnaire) at two years follow-up. All questionnaires were administered and anthropometry performed by trained investigators. The associations between the definitions and decline in mobility and physical function were evaluated over two years using multiple logistic regression. RESULTS: A BMI >85th percentile or >30 kg m-2 or a waist circumference of >102 cm in males and >88 cm in females increased risk of functional and mobility limitations. Over two years, a loss of 10% body weight significantly increased the risk of functional and mobility limitations. CONCLUSION: Maintaining weight within older adults, irrespective of initial body weight, may be important in preventing functional and mobility limitations. Excessive weight is associated with an increased risk of limitation in function and mobility, both key components of health-related quality of life.

Aged↗

PubMed2003

Field testing the influence of sperm competition based on sperm mobility in breeder turkey toms.

1. Commercial reproduction of turkeys relies on pooling of semen from multiple males for inseminations. Understanding how sperm characteristics influence paternity under commercial breeding conditions is important to improving production efficiency. 2. The objective of this study was to evaluate progeny production of individual toms following commercial practices of pooling semen to determine if sperm mobility influences progeny production in field conditions. 3. A total of 104 toms were evaluated for sperm mobility. A subset of 10 toms were housed together and semen was collected, pooled and used to inseminate hens (n = 28). Hens were inseminated at 30 weeks of age and weekly thereafter. 4. Ejaculates from each tom were evaluated on two separate days for sperm mobility. Semen from each tom was diluted and layered upon 6% (wt/vol) Accudenz solution. The sperm suspension was incubated at 41 degrees C for 5 min and absorbance was measured with a spectrophotometer. 5. Toms were ranked by absorbance and categorised as high or low if mobility score was +/- 1 SD from the flock mean (average). 6. For parentage determination, DNA was extracted from tom, hen and poult blood. Poult parentage (n = 276) was determined at one day of age or at 14 weeks by analysis of marker genotypes that were generated by polymerase chain reaction (PCR) amplification of genomic DNA with selected microsatellite markers. 7. Sperm mobility differed across males with absorbance values ranging from 0.147 to 0.366. 8. Findings demonstrate differences in poult production among individual toms when semen from multiple males was pooled and inseminated. Toms classified as high, average and low produced 55, 41 and 4% of the offspring, respectively. 9. It appears that sperm mobility is a trait that influences sperm competition among toms under field conditions where sperm numbers inseminated from individual toms are not controlled or constant and that toms with low sperm mobility produce few offspring.

Animals↗

PubMed1998

Clinical symptoms related to musculoskeletal neck-shoulder pain and mobility in the cervico-thoracic spine.

In a cross-sectional study 142 male and 139 female workers participated in a self-report questionnaire and a clinical examination. The aim of this study was to use the cervico-thoracic ratio (CTR), a clinical method for measuring segmental mobility between C7 and T5, to evaluate the influence of segmental mobility in neck-shoulder pain and different subjectively experienced symptoms. The study showed that reduced relative mobility at levels C7-T1 and T1-T2 significantly predicted neck-shoulder pain and the symptom weakness in the hands. The strongest relationship between segmental mobility and symptoms was found among subjects classified as having an inverse C7-T1 function, defined as equal or less mobility in motion segment C7-T1 compared to T1-T2. Reduced mobility explained 14% of neck-shoulder pain and 15% of weakness in the hands. It is suggested that deviation from synchronous distribution of mobility between motion segments C7-T1 and T1-T2 might be a factor provoking joint mechano receptors.

Adult↗

PubMed1998

Associations of sensory-motor functions with poor mobility in 75- and 80-year-old people.

This study investigated the associations of sensory-motor functions with mobility in elderly people. All 75- and 80-year-old residents of the city of Jyväskylä, Finland, were invited to take part in the study. A total of 617 (93%) persons were interviewed, and 500 (75%) took part in laboratory examinations. Self-reported mobility was recorded during the interview. Basic mobility functions (maximal walking speed and stair-mounting ability) and sensory-motor functions (maximal isometric muscle strength, standing balance, reaction time and visual acuity) were measured in the laboratory. Multivariate analyses showed that poor sensory-motor functions were significantly associated with poor performance in basic mobility functions and that poor performance in basic mobility functions was associated with self-reported disability in mobility. The associations discovered were consistent with models of the disablement process. Muscle strength, balance, reaction time and vision all have individual significance for mobility, underlining the need for multifactorial approaches in prevention and rehabilitation.

Activities of Daily Living↗

PubMed2003

The SIGAM mobility grades: a new population-specific measure for lower limb amputees.

PURPOSE: To develop a valid measure of lower limb amputee mobility suitable for routine clinical use, including monitoring change. METHODS: The Special Interest Group in Amputee Medicine (SIGAM) described a single-item scale comprising six clinical grades (A-F) of amputee mobility. A self-report questionnaire was developed and algorithm designed to facilitate grade assignment. Reproducibility of the questionnaire and grades were assessed in 62 amputees. Concurrent validity and sensitivity to change were investigated using the timed walking test (TWT). The mobility construct was examined in 200 amputees, using item response theory, by co-calibration with the Rivermead Mobility Index (RMI) on the same patients. RESULTS: Patients included 144 males and 66 females, aged 13-90. Intraclass correlation coefficients and reproducibility kappa values were satisfactory. Observers agreed 100% in using the algorithm. TWT improved as SIGAM grade increased. Examination of psychometric properties revealed the SIGAM item fitted within the RMI mobility matrix. Average measures for the six grades were ordered correctly. There was no local dependency or differential item functioning for clinically relevant patient subgroups. The SIGAM scale showed an effect size of 10.66. CONCLUSIONS: The SIGAM mobility grades represent a novel, valid, clinically useful measure of amputee mobility which is also sensitive to change.

Activities of Daily Living↗

PubMed2003

Experiencing the loss of mobility: perspectives of older adults with MS.

PURPOSE: The purpose of this study was to develop an understanding the experience and meaning of mobility loss among older adults with multiple sclerosis (MS). This work is part of a larger study on the health concerns and service needs of older adults with MS. METHODS: Twenty-seven people with MS (mean age = 62 years, range = 55-82) were interviewed using a phenomenological approach. RESULTS: Thematic analysis found that three factors contributed to participants' experience of mobility as a person with MS: reality of having MS, mobility needs, and contextual factors. Participants discussed how the reality of MS meant variability in their ability to get around and the importance of trying to remain in control over their mobility experiences. The experience of mobility lead participants to mourn losses, take action, and contemplate their futures. They expressed concerns about the continual declines in their mobility, losing independence, becoming a burden on caregivers, and the potential for having to move into a nursing home. CONCLUSIONS: Findings provide insight into the experience of mobility loss among older adults with MS, and point to potential strategies that can be used to help people cope with and adapt to these losses.

Activities of Daily Living↗

PubMed1966

Cellular electrophoretic mobility and the mitotic cycle.

The electrophoretic mobility of RPMI No. 41 cells grown in suspension, parasynchronized by double thymidine blocking and cold shock, is reported. No. 41 cells have a higher electrophoretic mobility during the mitotic peak phase than at other times in the mitotic cycle. Treatment of parasynchronous cells by neuraminidase reduces the mobility to the same value irrespective of the stage of the cells in the mitotic cycle. The higher electrophoretic mobility of cells in mitotic peak phase is probably due to a higher surface charge density at this time, possibly caused by a higher concentration of ionized neuraminic acid carboxyl groups at the hydrodynamic shear layer. The mobility of nonsynchronous rapidly and slowly growing cells differs; neuraminidase reduces their mobility by proportionately similar amounts. The results suggest that the differences in mobility between rapidly and slowly growing cells cannot be accounted for exclusively by differences in the amount of neuraminic acid groups at the shear layer.

Cell Division↗

PubMed1986

Mobility of voltage-dependent ion channels and lectin receptors in the sarcolemma of frog skeletal muscle.

The mobility of lectin receptors and of two types of ion channels was studied in skeletal muscles of the frog Rana temporaria. Lectin receptors were labeled with fluorescent derivatives of succinyl-concanavalin A (Con A) or wheat germ agglutinin (WGA), and their mobility was measured by fluorescence recovery after photobleaching. Of the receptors for WGA, approximately 53% were free to diffuse in the plane of the membrane, with an average diffusion coefficient as found in other preparations (D = 6.4 X 10(-11) cm2/s). Con A receptors were not measurably mobile. The mobility of voltage-dependent Na and K (delayed rectifier) channels was investigated with the loose-patch clamp method, coupled with through-the-pipette photodestruction of channels by ultraviolet (UV) light. Na channels were not measurably mobile (D less than or equal to 10(-12) cm2/s). With K channels, photodestruction was followed by a small but consistent recovery of K current, which suggested that some K channels diffused in the plane of the membrane. Our results with K currents are best fit if 25% of the K channels diffuse with D = 5 X 10(-11) cm2/s, with the remainder being immobile. For both Na and K channels, photodestruction by UV was most effective at a wavelength of approximately 289 nm. At this wavelength, the energy density required for an e-fold reduction in the number of functional channels was 0.40 J/cm2 for Na channels and 0.94 J/cm2 for K channels. Irradiation at this wavelength and dose did not measurably diminish the mobility of WGA receptors; hence, the immobility of Na and most K channels is not due to UV irradiation. It is concluded that mobile and immobile membrane proteins coexist in the sarcolemma of frog skeletal muscle, and that voltage-dependent Na and K channels are singled out for immobilization.

Animals↗

PubMed2004

Adaptive evolution of social traits: origin, trajectories, and correlations of altruism and mobility.

Social behavior involves "staying and helping," two individual attributes that vary considerably among organisms. Investigating the ultimate causes of such variation, this study integrates previously separate lines of research by analyzing the joint evolution of altruism and mobility. We unfold the network of selective pressures and derive how these depend on physiological costs, eco-evolutionary feedbacks, and a complex interaction between the evolving traits. Our analysis highlights habitat saturation, both around individuals (local aggregation) and around unoccupied space (local contention), as the key mediator of altruism and mobility evolution. Once altruism and mobility are allowed to evolve jointly, three general insights emerge. First, the cost of mobility affects the origin of altruism, determining whether and how quickly selfishness is overcome. Second, the cost of altruism determines which of two qualitatively different routes to sociality are taken: an evolutionary reduction of mobility, resulting in higher habitat saturation, is either preceded or followed by the adaptive rise of altruism. Third, contrary to conventional expectations, a positive correlation between evolutionarily stable levels of altruism and mobility can arise; this is expected when comparing populations that evolved under different constraints on mobility or that differ in other life-history traits.

Adaptation, Physiological↗

PubMed2005

Characterization of human immunodeficiency virus (HIV)-2 vector mobilization by HIV-1.

Conditionally replicating human immunodeficiency virus type 2 (crHIV-2) vectors can compete with HIV-1 for packaging in HIV-1-infected cells, indicating that the mobilization of vectors could selectively target as well as protect reservoirs susceptible to HIV-1 infection. The incorporation of HIV-1-specific antiviral transgenes in crHIV-2 vectors, although increasing the direct antiviral effect, may decrease mobilization and transmission to surrounding cells. To investigate how HIV-1-specific catalytic RNA cassettes (ribozymes) affect this balance between antiviral activity and mobilization, crHIV-2 vectors shown to display anti-HIV-1 activity were packaged by HIV-2 and used to transduce cells previously infected with HIV-1 or to transduce uninfected cells that were subsequently challenged with HIV-1. Vector mobilization was greater when HIV-1-infected cells were transduced with vector than when transduced cells were infected with HIV-1, and approximately 3-fold lower vector production was observed in cultures transduced with vectors expressing anti-HIV-1 ribozymes. Vector and antiviral effects could be transferred to new cultures by passaging supernatants to fresh cultures. No evidence of recombination with HIV-1 was observed. Vector mobilization and protection from HIV-1 infection were also demonstrated in human peripheral blood mononuclear cells. These data suggest that strategies employing vector mobilization for HIV-1 gene therapy should use vectors with maximal antiviral potency, despite resulting reductions in mobilization of the vector.

Base Sequence↗

PubMed2005

High mobility of flap endonuclease 1 and DNA polymerase eta associated with replication foci in mammalian S-phase nucleus.

Originally detected in fixed cells, DNA replication foci (RFi) were later visualized in living cells by using green fluorescent protein (GFP)-tagged proliferating cell nuclear antigen (PCNA) and DNA ligase I. It was shown using fluorescence redistribution after photobleaching (FRAP) assay that focal GFP-PCNA slowly exchanged, suggesting the existence of a stable replication holocomplex. Here, we used the FRAP assay to study the dynamics of the GFP-tagged PCNA-binding proteins: Flap endonuclease 1 (Fen1) and DNA polymerase eta (Pol eta). We also used the GFP-Cockayne syndrome group A (CSA) protein, which does associate with transcription foci after DNA damage. In normal cells, GFP-Pol eta and GFP-Fen1 are mobile with residence times at RFi (t(m)) approximately 2 and approximately 0.8 s, respectively. GFP-CSA is also mobile but does not concentrate at discrete foci. After methyl methanesulfonate (MMS) damage, the mobile fraction of focal GFP-Fen1 decreased and t(m) increased, but it then recovered. The mobilities of focal GFP-Pol eta and GFP-PCNA did not change after MMS. The mobility of GFP-CSA did not change after UV-irradiation. These data indicate that the normal replication complex contains at least two mobile subunits. The decrease of the mobile fraction of focal GFP-Fen1 after DNA damage suggests that Fen1 exchange depends on the rate of movement of replication forks.

Animals↗

PubMed2003

Onset of mobility disability among community-dwelling old men and women. The role of tiredness in daily activities.

BACKGROUND: in the primary prevention of disability among older adults it might be useful to identify individuals at high risk for functional decline before it occurs. OBJECTIVE: to examine whether tiredness in daily activities is an independent determinant of onset of mobility disability at 1 1/2-year follow-up among non-disabled older men and women. DESIGN: a prospective study with 1 1/2-year follow-up. SETTING: 34 communities in four counties in Denmark. SUBJECTS: 1396 older non-disabled adults (74-75 and 80 years old) living in 17 of the participating communities. METHODS: questionnaire surveys at baseline and at 1 1/2-year follow-up. Tiredness in daily activities was measured by questions about tiredness in six mobility activities. Onset of mobility disability was measured as onset of need for help in one to six mobility activities. RESULTS: men and women who felt tired in their daily activities at baseline had a higher risk of onset of mobility disability at 1 1/2-year follow-up, when adjusted by the covariates. In addition, low social participation, poor psychological function, and physical inactivity were independent risk factors of onset of mobility disability among men, and home help, low sense of coherence and physical inactivity were independent risk factors of onset of mobility disability among women. CONCLUSION: older people who complain about tiredness are at higher risk of becoming disabled than others. This highlights the need for alertness and management of this early sign of functional decline in a preventive perspective.

Activities of Daily Living↗

PubMed2005

Long-term mobile phone use and brain tumor risk.

Handheld mobile phones were introduced in Sweden during the late 1980s. The purpose of this population-based, case-control study was to test the hypothesis that long-term mobile phone use increases the risk of brain tumors. The authors identified all cases aged 20-69 years who were diagnosed with glioma or meningioma during 2000-2002 in certain parts of Sweden. Randomly selected controls were stratified on age, gender, and residential area. Detailed information about mobile phone use was collected from 371 (74%) glioma and 273 (85%) meningioma cases and 674 (71%) controls. For regular mobile phone use, the odds ratio was 0.8 (95% confidence interval: 0.6, 1.0) for glioma and 0.7 (95% confidence interval: 0.5, 0.9) for meningioma. Similar results were found for more than 10 years' duration of mobile phone use. No risk increase was found for ipsilateral phone use for tumors located in the temporal and parietal lobes. Furthermore, the odds ratio did not increase, regardless of tumor histology, type of phone, and amount of use. This study includes a large number of long-term mobile phone users, and the authors conclude that the data do not support the hypothesis that mobile phone use is related to an increased risk of glioma or meningioma.

Adult↗

PubMed1996

Reduced germline mobility of a mariner vector containing exogenous DNA: effect of size or site?

Germline mobilization of the transposable element mariner is severely inhibited by the insertion of a 4.5- to 11.9-kb fragment of exogenous DNA into a unique SacI site approximately in the middle of the 1286-bp element. In the presence of transposase driven by the germline-specific hsp26-sgs3 promoter, mobilization of the MlwB construct (containing a 11.9-kb insertion) is detected at low frequency. Analysis of a mobilized MlwB element indicated that mobilization is mediated by the mariner transposase. However, transposed MlwB elements are also defective in germline mobilization. Rare, transposase-induced germline excision events were also recovered for such vectors. The estimated rate of excision is < 0.1% per chromosome per generation. Excision appears to be accompanied by gap repair if a suitable template is available. The data imply that the reduced mobility of mariner vectors with exogenous DNA in the SacI site results from disruption of sequences necessary for efficient mobilization. The relative stability may be a valuable property in the uses of mariner-like elements in genetic engineering of insects of economic importance.

Animals↗

PubMed2000

Change in muscle mass and muscle strength after a hip fracture: relationship to mobility recovery.

BACKGROUND: Hip fracture in elderly persons has a serious impact on long-term physical function. This study determines the change in muscle strength and muscle mass after a hip fracture, and the associations between these changes and mobility recovery. METHODS: Ninety community-dwelling women aged 65 years and older who had recently experienced a fracture of the proximal femur were included in the study. At 2 to 10 days after hospital admission, the women's grip strength, ankle dorsiflexion strength, and regional muscle mass (by dual-energy x-ray absorptiometry) were measured, and the prefracture level of independence for five mobility function items was assessed. All measurements were repeated at 12 months. RESULTS: At follow-up, only 17.8% of the women had returned to their prefracture level of mobility function for all five items. Mobility function recovery was not related to change in skeletal muscle mass of the nonfractured leg or the arms. However, women who lost grip strength (mean loss of -28.7%, SD = 16.9%), or who lost ankle strength of the nonfractured leg (mean loss of -21.5%, SD = 14.7%), had a worse mobility recovery compared with those who gained strength (p = .04 and p = .09, respectively). In addition, chronic disease (p = .03), days hospitalized (p = .04), and self-reported hip pain (p = .07) were independent predictors of decline in mobility function. CONCLUSIONS: The results suggest that loss of muscle strength, but not loss of muscle mass, is an independent predictor of poorer mobility recovery 12 months after a hip fracture. When confirmed by other studies, these findings may have implications for rehabilitation strategies after a hip fracture.

Aged↗