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991.
The mechanism of yeast mitochondrial F1-ATPase inhibition by its regulatory peptide IF1 was investigated with the noncatalytic sites frozen by pyrophosphate pretreatment that mimics filling by ATP. This allowed for confirmation of the mismatch between catalytic site occupancy and IF1 binding rate without the kinetic restriction due to slow ATP binding to the noncatalytic sites. These data strengthen the previously proposed two-step mechanism, where IF1 loose binding is determined by the catalytic state and IF1 locking is turnover-dependent and competes with IF1 release (Corvest, V., Sigalat, C., Venard, R., Falson, P., Mueller, D. M., and Haraux, F. (2005) J. Biol. Chem. 280, 9927-9936). They also demonstrate that noncatalytic sites, which slightly modulate IF1 access to the enzyme, play a minor role in its binding. It is also shown that loose binding of IF1 to MgADP-loaded F1-ATPase is very slow and that IF1 binding to ATP-hydrolyzing F1-ATPase decreases nucleotide binding severely in the micromolar range and moderately in the submillimolar range. Taken together, these observations suggest an outline of the total inhibition process. During the first catalytic cycle, IF1 loosely binds to a catalytic site with newly bound ATP and is locked when ATP is hydrolyzed at a second site. During the second cycle, blocking of ATP hydrolysis by IF1 inhibits ATP from becoming entrapped on the third site and, at high ATP concentrations, also inhibits ADP release from the second site. This model also provides a clue for understanding why IF1 does not bind ATP synthase during ATP synthesis. 相似文献
992.
Claude Meisch 《Hydrobiologia》2007,585(1):181-200
The posterior end of body of the extant ostracods exhibits a pair of variously shaped appendages, commonly designated as furca(e),
uropods or caudal rami, used for feeding and/or locomotion. It is here shown that the so-called furca of all extant ostracods
has evolved from the (probably epipodal) vibratory plates of a pair of uropods.
The transformation comprised the following steps: (a) complete reduction of the uropodal protopodite and endopodite; (b) sclerotisation
of the lateral walls of the vibratory plates; (c) transformation of the branchial filaments into spines and/or claws; (d)
re-orientation of the plates from posterodorsal to posteroventral. These modifications are suggested to have evolved in parallel
with a change in function, from respiratory to locomotory and/or feeding.
The most primitive condition, reminiscent of the ancestral state of character, is seen in the Platycopida: the ‘furca’ still
appears similar in shape to the vibratory plates of the pair of sixth limbs. In the Podocopida the uropodal plates have been
modified into plate-like, more often into rod-shaped rami mainly used for locomotion. In both the Platycopida and Podocopida
the anus has remained in its original place, posterior to the ‘furcal’ plates or rami.
In the Myodocopida and Halocyprida the uropodal vibratory plates are transformed into heavily developed lamellae bearing sturdy
spines. They are activated by a complex apparatus of muscles and sclerites, the development of which necessitated the displacement
of the anus from the end of the body towards its present place, anterior to the ‘furca’.
The furca of the Ostracoda being not a ‘true’ furca, a change in terminology is proposed: uropodal plates or lamellae in the
Platycopida, Palaeocopida and Myodocopida/Halocyprida; uropodal rami in the Podocopida. The so-called furcae of the Ostracoda
being homologous structures, it is concluded that all extant ostracods belong to a monophyletic lineage. 相似文献
993.
Caroline Geeraerts Michaël Ovidio Hilde Verbiest David Buysse Johan Coeck Claude Belpaire Jean-Claude Philippart 《Hydrobiologia》2007,582(1):143-153
Adult roach Rutilus rutilus (L.) (N = 24; 19.9–36.1 cm FL) from three highly fragmented Belgian rivers were tagged with surgically implanted radio transmitters.
Their seasonal movements were observed from March to August 2004 (circum reproduction period) in river stretches delimited
by two physical barriers. In the three rivers, roach displayed similar patterns of movements which were mainly influenced
by the date of observation (movements increased in late April–May) and water temperature (travel distances were more important
when water temperature ranged between 10°C and 14°C). Roach sometimes cleared physical obstacles. The mean distances travelled
in each river were relatively short (max. 2.5 km) and mainly influenced by the length of the study reach, which was delimited
by physical barriers. 相似文献
994.
Froyen G Bauters M Boyle J Van Esch H Govaerts K van Bokhoven H Ropers HH Moraine C Chelly J Fryns JP Marynen P Gecz J Turner G 《Human genetics》2007,121(5):539-547
Using high resolution X chromosome array-CGH we identified an interstitial microdeletion at Xp11.23 in three brothers with
moderate to severe mental retardation (MR) without dysmorphic features. The extent of the deletion was subsequently delineated
to about 50 kb by regular PCR and included only the SLC38A5 and FTSJ1 genes. The loss of the FTSJ1 MR gene in males is expected to result in the observed phenotype but the contribution of the deletion of the solute carrier
SLC38A5 gene is less clear. Their mother also carries the deletion and completely inactivates the aberrant X chromosome. Interestingly,
the distal breakpoint is situated within a 200 kb SSX repeat region that appears to stimulate recombination since subtle copy
number changes often occur at this location and it is frequently involved in translocations in tumours. Since this apparent
SSX unstable structure is flanked proximally by FTSJ1 and PQBP1, subtle deletions or duplications at this location would be expected to cause MR, as in our family. So far, we have screened
a cohort of 300 patients but did not find additional aberrations at the FTSJ1 locus indicating that the frequency is likely to be low. 相似文献
995.
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic compound of cigarette smoke that generates electrophilic
intermediates capable of damaging DNA. Recently, we have shown that NNK can modulate mediator production by alveolar macrophages
(AM) and bronchial and alveolar epithelial cells, suggesting that cigarette smoke can alter lung immune response. Thus, we
investigated the effect of NNK and cigarette smoke extract (CSE) on AM capacity to eliminate tumoral cells. Rat AM cell line,
NR8383, was treated with NNK (500 μM) or CSE (3%) and stimulated with lipopolysaccharide (10 ng/ml). The release of cytotoxic
mediators, tumor necrosis factor (TNF) and reactive oxygen species (ROS), was measured in cell-free supernatants using ELISA
and superoxide anion production. TNF- and ROS-dependent cytotoxicity were studied using a 51Chromium-release assay and WEHI-164 and P-815 cell lines. Treatment of AM with NNK and CSE for 18 h significantly inhibited
AM TNF release. CSE exposure resulted in a significant increase of ROS production, whereas NNK did not. TNF-dependent cytotoxic
activity of NR8383 and freshly isolated rat AM was significantly inhibited after treatment with NNK and CSE. Interestingly,
although ROS production was stimulated by CSE and not affected by NNK, CSE inhibited AM ROS-dependent cytotoxicity. These
results suggest that NNK may be one of the cigarette smoke components responsible for the reduction of pulmonary cytotoxicity.
Thus, NNK may have a double pro-carcinogenic effect by contributing to DNA adduct formation and inhibiting AM cytotoxicity
against tumoral cells. 相似文献
996.
Stature (adult height) is one of the most heritable human traits, yet few genes, if any, have been convincingly associated
with adult height variation in the general population. Here, we selected 150 tag SNPs from eight candidate genes in the growth
hormone (GH)/insulin-like growth factor-1 (IGF1) axis (GHR, GHRH, GHRHR, IGF1, IGFALS, IGFBP3, JAK2, STAT5B), and genotyped them in ∼2,200 individuals ascertained for short or tall stature. Nominally significant tag SNPs were then
tested in three additional replication cohorts, including a family-based panel to rule out spurious associations owing to
population stratification. Across the four height cohorts (N = 6,075 individuals), we did not observe any consistent associations between stature and common variants (≥5% minor allele
frequency) in these eight genes, including a common deletion of the growth hormone receptor gene exon 3. Tests of epistatic
interactions between these genes did not yield any results beyond those expected by chance. Although we have not tested all
genes in the GH/IGF1 axis, our results indicate that common variation in these GH/IGF1 axis genes is not a major determinant of stature, and suggest that if common variation contributes to adult height variation
in the general population, the variants are in other, possibly unanticipated genes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
997.
Kanbar R Oréa V Barrès C Julien C 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,292(1):R362-R367
The effects of acute emotional stress on the sympathetic component of the arterial baroreceptor reflex have not yet been described in conscious animals and humans. Arterial pressure (AP) and renal sympathetic nerve activity (RSNA) were simultaneously recorded in 11 conscious rats before and during exposure to a mild environmental stressor (jet of air). Baroreflex function curves relating AP and RSNA were constructed by fitting a sigmoid function to RSNA and AP measured during sequential nitroprusside and phenylephrine administrations. Stress increased mean AP from 112 +/- 2 to 124 +/- 2 mmHg, heart rate from 381 +/- 10 to 438 +/- 18 beats/min, and RSNA from 0.80 +/- 0.14 to 1.49 +/- 0.23 microV. The RSNA-AP relationship was shifted toward higher AP values, and its maximum gain was significantly (P < 0.01) increased from 9.0 +/- 1.3 to 16.2 +/- 2.1 normalized units (NU)/mmHg. The latter effect was secondary to an increase (P < 0.01) in the range of the RSNA variation from 285 +/- 33 to 619 +/- 59 NU. In addition, the operating range of the reflex was increased (P < 0.01) from 34 +/- 2 to 41 +/- 3 mmHg. The present study indicates that in rats, the baroreflex control of RSNA is sensitized and operates over a larger range during emotional stress, which suggests that renal vascular tone, and possibly AP, are very efficiently controlled by the sympathetic nervous system under this condition. 相似文献
998.
Kanbar R Oréa V Chapuis B Barrès C Julien C 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,293(5):R1938-R1946
The present study examined whether the gain of the transfer function relating cardiac-related rhythm of renal sympathetic nerve activity (RSNA) to arterial pressure (AP) pulse might serve as a spontaneous index of sympathetic baroreflex sensitivity (BRS). AP and RSNA were simultaneously recorded in conscious rats, either baroreceptor-intact (control, n = 11) or with partial denervation of baroreflex afferents [aortic baroreceptor denervated (ABD; n = 10)] during 1-h periods of spontaneous activity. Transfer gain was calculated over 58 adjacent 61.4-s periods (segmented into 10.2-s periods). Coherence between AP and RSNA was statistically (P < 0.05) significant in 90 +/- 3% and 56 +/- 10% of cases in control and ABD rats, respectively. Transfer gain was higher (P = 0.0049) in control [2.39 +/- 0.13 normalized units (NU)/mmHg] than in ABD (1.48 +/- 0.22 NU/mmHg) rats. In the pooled study sample, transfer gain correlated with sympathetic BRS estimated by the vasoactive drug injection technique (R = 0.75; P < 0.0001) and was inversely related to both time- (standard deviation; R = -0.74; P = 0.0001) and frequency-domain [total spectral power (0.00028-2.5 Hz); R = -0.82; P < 0.0001] indices of AP variability. In control rats, transfer gain exhibited large fluctuations (coefficient of variation: 34 +/- 3%) that were not consistently related to changes in the mean level of AP, heart rate, or RSNA. In conclusion, the transfer function method provides a continuous, functionally relevant index of sympathetic BRS and reveals that the latter fluctuates widely over time. 相似文献
999.
Gauthier JY Black WC Courchesne I Cromlish W Desmarais S Houle R Lamontagne S Li CS Massé F McKay DJ Ouellet M Robichaud J Truchon JF Truong VL Wang Q Percival MD 《Bioorganic & medicinal chemistry letters》2007,17(17):4929-4933
Highly potent, selective, and bioavailable inhibitors of human, mouse, or rat cathepsin S are described. The key structural features combine a sulfonyl moiety attached to a large group in P2 and a small substituent in P3. 相似文献
1000.