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PubMed1996

A small amount of wheel running facilitates eating in nondeprived rats.

A high level of dopaminergic activation such as that produced by a high dose of amphetamine suppresses eating, whereas a low level such as that produced by a low dose can have the opposite effect. Like a high dose of amphetamine, a high level of wheel running also suppresses eating. It was hypothesized that this suppression is due to dopaminergic activation produced by wheel running. If so, a relatively small amount of wheel running should produce a low level of dopaminergic activation and thus have the same effect as a low dose of amphetamine: facilitation of eating. In the present experiment, nondeprived rats were allowed to run in a wheel for 30 min before a feeding test. As predicted, a little wheel running facilitated eating in these rats relative to appropriate controls. The present results may be relevant to an understanding of eating disorders in humans.

Animals↗

PubMed2003

Different domains of synaptotagmin control the choice between kiss-and-run and full fusion.

Exocytosis-the release of the contents of a vesicle--proceeds by two mechanisms. Full fusion occurs when the vesicle and plasma membranes merge. Alternatively, in what is termed kiss-and-run, vesicles can release transmitter during transient contacts with the plasma membrane. Little is known at the molecular level about how the choice between these two pathways is regulated. Here we report amperometric recordings of catecholamine efflux through individual fusion pores. Transfection with synaptotagmin (Syt) IV increased the frequency and duration of kiss-and-run events, but left their amplitude unchanged. Endogenous Syt IV, induced by forskolin treatment, had a similar effect. Full fusion was inhibited by mutation of a Ca2+ ligand in the C2A domain of Syt I; kiss-and-run was inhibited by mutation of a homologous Ca2+ ligand in the C2B domain of Syt IV. The Ca2+ sensitivity for full fusion was 5-fold higher with Syt I than Syt IV, but for kiss-and-run the Ca2+ sensitivities differed by a factor of only two. Syt thus regulates the choice between full fusion and kiss-and-run, with Ca2+ binding to the C2A and C2B domains playing an important role in this choice.

Animals↗

PubMed1999

Sustained activation of hippocampal pyramidal cells by 'space clamping' in a running wheel.

In contrast to sensory cortical areas of the brain, the relevant physiological inputs to the hippocampus, leading to selective activation of pyramidal cells, are largely unknown. Pyramidal cells are thought to be phasically activated by spatial cues and a variety of sensory and motor stimuli. Here, we used a behavioural 'space clamp' method, which involved the confinement of the actively running animal in a defined position in space (running wheel) and kept sensory inputs constant. Twelve percent of the recorded CA1 pyramidal cells were selectively active while the rat was running in the wheel. Cell firing was specific to the direction of running and disappeared after rotating the recording apparatus. The discharge frequency of pyramidal cells and interneurons was sustained as long as the rat ran continuously in the wheel. Furthermore, the discharge frequency of pyramidal cells and interneurons increased with increasing running velocity, even though the frequency of hippocampal theta waves remained constant. The discharge frequency of some 'wheel-related' pyramidal cells could increase more than 10-fold between 10 and 100 cm/s, whereas the firing rate of 'non-wheel' cells remained constantly low. We hypothesize that: (i) a necessary condition for place-specific discharge of hippocampal pyramidal cells is the presence of theta oscillation; and (ii) relevant stimuli can tonically and selectively activate hippocampal pyramidal cells as long as theta activity is present.

Action Potentials↗

PubMed2003

The evaluation of run-off prior to infra-inguinal bypass reconstruction - a modified scoring system based on flow measurement.

OBJECTIVES: To compare angiographic scoring and flow measurements in the assessment of run-off prior infra-inguinal bypass. PATIENTS AND METHODS: In a series of 108 consecutive infra-inguinal bypasses, run-off was scored on the basis of pre- and post-operative angiograms and related to intra- and post-operative flow rates as determined by Doppler ultrasonography. RESULTS: There was a highly significant correlation between the angiographic score and flow (p = 0.0000), as well as between angiographic score (p = 0.0000), flow (p = 0.0000) and the level of distal anastomosis. Flow determined per crural vessel (quotient of flow to angiographic score) proved to be independent of the level of distal bypass anastomosis (p = 0.20). CONCLUSION: In this study, angiographic scoring and Doppler flow measurements were equally valid means for the assessment of run-off. Our system allows an objective assessment of run-off independently of the distal bypass anastomosis level and provides a functional estimation of run-off.

Adult↗

PubMed2004

Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain.

The properties of gamma-aminobutyric acid (GABA) type A receptors (GABA(A) receptors) microtransplanted from the human epileptic brain to the plasma membrane of Xenopus oocytes were compared with those recorded directly from neurons, or glial cells, in human brains slices. Cell membranes isolated from brain specimens, surgically obtained from six patients afflicted with drug-resistant temporal lobe epilepsy (TLE) were injected into frog oocytes. Within a few hours, these oocytes acquired GABA(A) receptors that generated GABA currents with an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, receptors derived from membranes of a nonepileptic hippocampal uncus, membranes from mouse brain, or recombinant rat alpha 1 beta 2 gamma 2-GABA receptors exhibited a much less pronounced GABA-current run-down. Moreover, the GABA(A) receptors of pyramidal neurons in temporal neocortex slices from the same six epileptic patients exhibited a stronger run-down than the receptors of rat pyramidal neurons. Interestingly, the GABA(A) receptors of neighboring glial cells remained substantially stable after repetitive activation. Therefore, the excessive GABA-current run-down observed in the membrane-injected oocytes recapitulates essentially what occurs in neurons, rather than in glial cells. Quantitative RT-PCR analyses from the same TLE neocortex specimens revealed that GABA(A)-receptor beta 1, beta 2, beta 3, and gamma 2 subunit mRNAs were significantly overexpressed (8- to 33-fold) compared with control autopsy tissues. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE brain leads to the expression of run-down-enhanced GABA(A) receptors. Blockage of phosphatases stabilizes the TLE GABA(A) receptors and strengthens GABAergic inhibition. It may be that this process can be targeted to develop new treatments for intractable epilepsy.

Adult↗

PubMedDate not supplied

Automotive exhaust and mouse activity: relationships between pollutant concentrations and decreases in wheel running.

Groups of male and female mice inhaled either clean air, 100 ppm carbon monoxide, or light-irradiated and nonirradiated automotive exhaust containing nominally 25, 50, 75, or 100 ppm carbon monoxide in three tests with exposure lasting from 4 to 7 days. Exhaust from a factory or lean-tuned engine in the first and third tests reversibly suppressed activity wheel running during exposure in mice of both sexes by as much as 78.3 and 83.1%, respectively. Light-irradiated exhaust suppressed running more than nonirradiated exhaust. For the second test, when the engine was tuned to be low in pollutants other than carbon monoxide, exhaust did not suppress running. Exposure to carbon monoxide alone only slightly decreased running in male mice, but increased running in female mice.

Air Pollutants↗

PubMed2000

Comparison of the phenolic composition of fruit juices by single step gradient HPLC analysis of multiple components versus multiple chromatographic runs optimised for individual families.

After minimal sample preparation, two different HPLC methodologies, one based on a single gradient reversed-phase HPLC step, the other on multiple HPLC runs each optimised for specific components, were used to investigate the composition of flavonoids and phenolic acids in apple and tomato juices. The principal components in apple juice were identified as chlorogenic acid, phloridzin, caffeic acid and p-coumaric acid. Tomato juice was found to contain chlorogenic acid, caffeic acid, p-coumaric acid, naringenin and rutin. The quantitative estimates of the levels of these compounds, obtained with the two HPLC procedures, were very similar, demonstrating that either method can be used to analyse accurately the phenolic components of apple and tomato juices. Chlorogenic acid in tomato juice was the only component not fully resolved in the single run study and the multiple run analysis prior to enzyme treatment. The single run system of analysis is recommended for the initial investigation of plant phenolics and the multiple run approach for analyses where chromatographic resolution requires improvement.

Beverages↗

PubMed2000

Engineering the processive run length of the kinesin motor.

Conventional kinesin is a highly processive molecular motor that takes several hundred steps per encounter with a microtubule. Processive motility is believed to result from the coordinated, hand-over-hand motion of the two heads of the kinesin dimer, but the specific factors that determine kinesin's run length (distance traveled per microtubule encounter) are not known. Here, we show that the neck coiled-coil, a structure adjacent to the motor domain, plays an important role in governing the run length. By adding positive charge to the neck coiled-coil, we have created ultra-processive kinesin mutants that have fourfold longer run lengths than the wild-type motor, but that have normal ATPase activity and motor velocity. Conversely, adding negative charge on the neck coiled-coil decreases the run length. The gain in processivity can be suppressed by either proteolytic cleavage of tubulin's negatively charged COOH terminus or by high salt concentrations. Therefore, modulation of processivity by the neck coiled-coil appears to involve an electrostatic tethering interaction with the COOH terminus of tubulin. The ability to readily increase kinesin processivity by mutation, taken together with the strong sequence conservation of the neck coiled-coil, suggests that evolutionary pressures may limit kinesin's run length to optimize its in vivo function.

Amino Acid Sequence↗

PubMed2000

Running suturing: the ideal length facilitates this task.

BACKGROUND AND PURPOSE: Laparoscopic intracorporeal suturing is difficult, a complex task involving several integrated skills such as needle handling, suturing, and knotting. Running suturing is even more complex in the closed environment secondary to the angles of the suture lines, the tension maintained on the suture line, and the need to secure the ends, including tying a knot from the tail of the suture to the loop of the preceding stitch. We have hypothesized that the ideal suture length facilitates this process, and this study was specifically designed to determine the ideal suture length for an intracorporeal running suture. MATERIALS AND METHODS: Latex phantoms were incised for 1 or 2 cm, and each was marked with black points to indicate suture entrance and exit sites. These marks were placed 2 mm from the incision, starting 2 mm proximally and ending 2 mm distally. Suture lengths could then be varied in direct proportion to the length of the incision, keeping all of these points as constants. The ratios of suture length:incision length were 9:1, 10:1, and 11:1. One surgeon performed all of the running suturing utilizing dry 3-0 coated polyglactin with a tapered SH needle. The times needed to create running suture lines were recorded (seconds), the number of ideal entrance and exit points tabulated, and the number of technical errors (missed movements resulting in prolonged suturing) recorded. RESULTS: The lengths of both the incision and the suture affect the ability to perform laparoscopic intracorporeal running suturing. As the incision increased, the suture:incision ratio of 9:1 resulted in the most efficient results (quickest suturing and fewest errors). In smaller suture lines (1 cm), the ratios 10:1 and 11:1 appeared better. CONCLUSIONS: A suture:incision ratio of 9:1 is best for longer suture lines and 10:1 is better for short suture lines.

Evaluation Studies as Topic↗

PubMed2000

A DNA polymerase epsilon mutant that specifically causes +1 frameshift mutations within homonucleotide runs in yeast.

The DNA polymerases delta and epsilon are the major replicative polymerases in the yeast Saccharomyces cerevisiae that possess 3' --> 5' exonuclease proofreading activity. Many errors arising during replication are corrected by these exonuclease activities. We have investigated the contributions of regions of Polepsilon other than the proofreading motifs to replication accuracy. An allele, pol2-C1089Y, was identified in a screen of Polepsilon mutants that in combination with an exonuclease I (exo1) mutation could cause a synergistic increase in mutations within homonucleotide runs. In contrast to other polymerase mutators, this allele specifically results in insertion frameshifts. When pol2-C1089Y was combined with deletions of EXO1 or RAD27 (homologue of human FEN1), mutation rates were increased for +1 frameshifts while there was almost no effect on -1 frameshifts. On the basis of genetic analysis, the pol2-C1089Y mutation did not cause a defect in proofreading. In combination with a deletion of the mismatch repair gene MSH2, the +1 frameshift mutation rate for a short homonucleotide run was increased nearly 100-fold whereas the -1 frameshift rate was unchanged. This suggests that the Pol2-C1089Y protein makes +1 frameshift errors during replication of homonucleotide runs and that these errors can be corrected by either mismatch repair (MMR) or proofreading (in short runs). This is the first report of a +1-specific mutator for homonucleotide runs in vivo. The pol2-C1089Y mutation defines a functionally important residue in Polepsilon.

Alleles↗

PubMed2004

The effects of aging and treadmill running on soleus and gastrocnemius muscle morphology in the senescence-accelerated mouse (SAMP1).

We investigated the effects of aging on the soleus and gastrocnemius muscles in male SAMP1 (senescence-accelerated mouse prone 1). Body mass, muscle wet weight, fiber size, and the percent of type II fibers declined from 50 weeks of age. Voluntary motor behavior also significantly declined with age. Furthermore, we examined the effects of high (twice daily) and low (once daily) frequency treadmill running, for 6 weeks at 5 days per week, beginning when the mice were 50 weeks old. Muscle fiber size for the high frequency running significantly increased. Pathological fiber alterations in these mice were increased by running, especially by high frequency running. This suggests that age-related muscle morphological changes in SAMP1 occurs from 50 weeks of age, and that the decline in voluntary motor behavior is an important factor in aging muscle atrophy. In addition, high frequency running is more beneficial for aged muscle hypertrophy. This model is useful for studying the acceleration of the aging process in skeletal muscle of the SAM.

Aging↗

PubMed1990

Transcriptional slippage occurs during elongation at runs of adenine or thymine in Escherichia coli.

A run of 11 adenine or thymine residues at the 5' end of an out-of-frame lacZ gene causes a high level of beta-galactosidase expression in E. coli. This effect was not observed for a run of guanine residues. Reverse transcription of mRNA isolated from E. coli containing the run of 11 A's reveals heterogeneity of transcript length while reverse transcription of mRNA isolated from S. cerevisiae containing the same gene shows no heterogeneity. Protein sequencing of the beta-galactosidase molecules derived from the out-of-frame construct containing a run of adenines reveals the addition of a lysine at the run. A new method was developed where messages small enough to allow resolution of single nucleotide differences on an acrylamide gel are electrophoresed, electroblotted onto nylon and probed. This confirmed the reverse transcription results and showed that additional residues can be added to transcripts derived from DNA containing 10 or 11 thymine residues. A mechanism for slippage is discussed where the A-U rich RNA-DNA hybrid can denature during elongation and rehybridize in an offset position, causing the addition of extra residues to the transcript.

Adenine↗

PubMed1997

Effects of creatine loading and training on running performance and biochemical properties of rat skeletal muscle.

Several reports have shown that the use of oral creatine (Cr) supplementation can increase performance during brief high intensity exercise in humans. The purpose of this study was to examine the separate and combined effects of Cr supplementation and high intensity run training on the performance capacity and biochemical properties of rodent skeletal muscle. Running performance was assessed following acute (10-d) and chronic (4-wk) Cr supplementation. Results indicate that Cr supplementation alone has ergogenic effects and the combination of run training plus Cr results in a more pronounced enhancement of performance than either intervention alone. The benefits of Cr supplementation were seen most clearly during repetitive bouts of high intensity interval running. Cr concentrations increased in both the slow soleus and fast plantaris muscles (P < 0.05) in response to Cr supplementation. Increased creatine concentrations appeared to be reflected in increased phosphorylated creatine (PCr). Citrate synthase (CS) activity was increased in both the soleus and plantaris muscles following training (P < 0.05). CS activity of the untrained soleus but not the plantaris responded to the dietary stimulus. There were no significant changes in either creatine phosphokinase activity or myosin heavy chain isoform distribution following training or supplementation. These results indicate that the gains in high intensity running performance seen following Cr loading are a combined result of increased aerobic (CS) and anaerobic (Cr and PCr) energy buffering capacity of the muscle.

Animals↗

PubMed1998

Immune system activation and fatigue during treadmill running: role of interferon.

UNLABELLED: Extreme fatigue often accompanies infection and other diseases, but the causal mechanisms are unknown. Recent research has focused on various cytokines as potential immune system mediators of fatigue during illness. Interferon-alpha/beta (IFN-alpha/beta) has attracted the most interest in this regard. PURPOSE: The purpose of this research was to study the effect of IFN-alpha/beta on fatigue during treadmill running in mice. METHODS: Mice (male CD-1) were acclimated to treadmill running for 4 d before experimental sessions. In experiment 1 (EXP 1), mice were injected with either polyI:C (pI:C) (5 mg.kg-1 body weight) or saline (CON) 12 or 24 h before the exercise session. These sessions consisted of treadmill running to fatigue (approximately 3 h, 19-24 m.min-1, 5% grade, no shock). In experiment 2 (EXP 2), mice were injected 24 h before exercise with normal rabbit serum (CON), pI:C, or pI:C + anti-IFN-alpha/beta antibody (pI:C + Ab). RESULTS: The results of EXP 1 showed that the plasma IFN-alpha/beta titer was much higher at 24 h than at 12 h after pI:C injection (P < 0.001) and that run time to fatigue was significantly reduced only when the exercise occurred 24 h after injection (P < 0.05). In EXP 2, administration of the anti-IFN-alpha/beta antibody attenuated both the pI:C-induced increase in plasma IFN-alpha/beta (P < 0.001) and the decrease in run time to fatigue (r = -0.81, P < 0.001). CONCLUSIONS: These results suggest that immune system activation by pI:C was associated with early fatigue during prolonged treadmill exercise and that this effect may, at least partially, result from increased IFN-alpha/beta.

Animals↗

PubMed2006

Frequencies of hydrophobic and hydrophilic runs and alternations in proteins of known structure.

Patterns of alternation of hydrophobic and polar residues are a profound aspect of amino acid sequences, but a feature not easily interpreted for soluble proteins. Here we report statistics of hydrophobicity patterns in proteins of known structure in a current protein database as compared with results from earlier, more limited structure sets. Previous studies indicated that long hydrophobic runs, common in membrane proteins, are underrepresented in soluble proteins. Long runs of hydrophobic residues remain significantly underrepresented in soluble proteins, with none longer than 16 residues observed. These long runs most commonly occur as buried alpha helices, with extended hydrophobic strands less common. Avoiding aggregation of partially folded intermediates during intracellular folding remains a viable explanation for the rarity of long hydrophobic runs in soluble proteins. Comparison between database editions reveals robustness of statistics on aqueous proteins despite an approximately twofold increase in nonredundant sequences. The expanded database does now allow us to explain several deviations of hydrophobicity statistics from models of random sequence in terms of requirements of specific secondary structure elements. Comparison to prior membrane-bound protein sequences, however, shows significant qualitative changes, with the average hydrophobicity and frequency of long runs of hydrophobic residues noticeably increasing between the database editions. These results suggest that the aqueous proteins of solved structure may represent an essentially complete sample of the universe of aqueous sequences, while the membrane proteins of known structure are not yet representative of the universe of membrane-associated proteins, even by relatively simple measures of hydrophobic patterns.

Computational Biology↗

PubMed2006

Effects of running exercise on fibre-type distribution of soleus and plantaris muscles in diabetic Otsuka Long-Evans Tokushima fatty rats.

AIM: Effect of running exercise on fibre-type distributions of the slow soleus and fast plantaris muscles was investigated in male Otsuka Long-Evans Tokushima fatty rats (OLETF) as an animal model of spontaneous type 2 diabetes mellitus. METHODS: Five-week-old OLETF rats were allowed to exercise voluntarily in running wheels for 32 days and the data were compared with those of age-matched non-exercised OLETF and non-diabetic Long-Evans Tokushima Otsuka rats (LETO). RESULTS: In the soleus muscle, a higher percentage of type I fibres was observed in non-exercised OLETF rats compared with LETO rats, and there were no type IIA fibres in non-exercised OLETF rats. In the plantaris muscle, a higher percentage of type IIB fibres and a lower percentage of type I and type IIA fibres were observed in non-exercised OLETF rats compared with LETO rats. In contrast, there were no differences in the fibre-type distribution of soleus and plantaris muscles between exercised OLETF and LETO rats. The body weight and type I fibre percentage of the soleus muscle were related to the running distance in exercised OLETF rats. White adipose tissue weight, HbA(1c) and blood insulin and glucose concentrations were lower in exercised OLETF rats than in non-exercised OLETF rats, irrespective of the running distance. There was a difference in the gene-expression pattern of the soleus muscle among LETO rats, non-exercised OLETF and exercised OLETF rats. CONCLUSION: Running exercise can inhibit diabetes-associated type shifting of fibres, which is more apparent with postnatal growth, in skeletal muscles of diabetic OLETF rats, as a result of mRNA expression change in muscle.

Adipose Tissue↗

PubMed1992

Long-run impacts of AIDS.

"Over the next century, the impact of the AIDS epidemic on the supply of and returns to factors of production may be significant. Public policies might offset some of the long run impacts, especially if initiated early in the epidemic. History suggests the types of economic effects that can occur in the long run and the limits of public policies' effectiveness in controlling diseases of this type. The models developed here to show possible long run time paths for the epidemic also imply a long-run equilibrium, a concept not appreciated in most disciplines. Because data deficiencies make long run numerical forecasting highly controversial, this paper uses history and modeling to emphasize qualitative understanding of the epidemic."

Acquired Immunodeficiency Syndrome↗

PubMed1999

A cytoplasmic factor, calpastatin and ATP together reverse run-down of Ca2+ channel activity in guinea-pig heart.

1. The cytoplasmic extract of bovine heart was separated into four fractions by gel filtration: H (molecular mass > 300 kDa), P (250-300 kDa), L1 (180-250 kDa) and L2 (< 180 kDa). The effects of these fractions on the run-down of L-type Ca2+ channel activity were investigated in guinea-pig ventricular myocytes. 2. After run-down induced by inside-out patch formation, Ca2+ channel activity was restored by P or H (+ 3 mM ATP) to 7.5 and 5.8 % of that in the cell-attached mode, respectively, but to as high as 86 % by P + H + ATP. 3. The reversal of run-down brought about by the P fraction was mimicked by calpastatin. 4. The restorative effect of calpastatin + ATP showed a biphasic time course: 38 % in the early transient phase and 11 % in the late phase. However, calpastatin + H + ATP showed a sustained effect: 66 % in the early transient phase, and 87 % in the late phase. 5. The effective component of the H fraction showed a protein-like nature: heat and trypsin sensitivity. 6. The activities of cAMP-dependent protein kinase, casein kinase I, casein kinase II, protein tyrosine kinase, protein serine/threonine or tyrosine phosphatases were measured. However, these kinases and phosphatases were not confirmed as the effective component of cytoplasm or the H fraction. 7. Run-down was not prevented by 2 microM phalloidin or 2 microM paclitaxel, suggesting that neither actin filaments nor microtubules are directly involved in the run-down. 8. Our results support the view that the basal activity of the Ca2+ channel is maintained by at least three factors: a protein-like factor in the H fraction, calpastatin, and ATP.

Adenosine Triphosphate↗