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Functional characterisation of vigilin, a highly conserved multi-KH-domain protein that binds RNA and ssDNA, remains elusive and, to some extent, controversial. Studies performed in Saccharomyces cerevisiae and human cells indicate that vigilin localises to the cytoplasm, binds ribosomes, associates to RER and regulates mRNA translation. On the other hand, we and others reported a contribution to heterochromatin-mediated gene silencing (PEV) and chromosome segregation in S. cerevisiae, Drosophila and human cells. Whether this contribution is direct remains, however, unclear. Here, we report that Drosophila vigilin, DDP1, vastly localises to the cytoplasm, being largely excluded from the nucleus. We also show that DDP1 preferentially associates to RER and co-purifies with several ribosomal proteins, suggesting a contribution to mRNA translation. In light of these results, the contribution of DDP1 to PEV was re-examined. Here, we show that a newly generated null ddp1(Δ) mutation is only a weak suppressor of PEV, which is in contrast with our own previous results showing dominant suppression in the presence of a strong hypomorphic ddp1(15.1) mutation. Similar results were obtained in the fission yeast Schizosaccharomyces pombe, where vigilin (Vgl1) also associates to RER, having no significant contribution to PEV at centromeres, telomeres and the mating-type locus. Altogether, these results indicate that cytoplasmic localisation and association to RER, but not contribution to heterochromatin organisation, are evolutionarily conserved features of vigilin, favouring a model by which vigilin acts in the cytoplasm, regulating RNA metabolism, and affects nuclear functions only indirectly. 相似文献
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Recently government ministers have set out their vision of the future of purchasing. Ineffective treatments will be discarded and purchasing will be based on guidelines or protocols rather than activity. But have the advocates of this approach considered all the issues? This paper examines the challenges of balancing the desire for protocol based uniformity with the needs of individual patients, explores the extent to which existing purchasing structures can support this process, and questions whether such moves will actually lead to reduced costs. In each case it is concluded that oversimplistic analyses are likely to be misleading and that much of the current debate fails to recognise the complexity of health care. 相似文献
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Energetics, body size, and the limits to endothermy 总被引:1,自引:0,他引:1
BRIAN K. MCNAB 《Journal of Zoology》1983,199(1):1-29
The scaling rate of metabolism with respect to body mass is analysed. Scaling of heat production implies that scaling also exists between temperature regulation and body mass. Most vertebrates follow a Kleiber relation down to a "critical mass, below which the scaling of metabolism must be changed to ensure the maintenance of endothermy. Such an adjustment is found interspecifically in birds and mammals, and is found intraspecifically in mammals during post-natal growth. If the Kleiber scaling relation is maintained below the critical mass, mammals and birds shiR from endothermic temperature regulation (above critical mass) to endothermy with obligatory torpor (below critical mass). If the Kleiber relation is followed to masses far below the critical mass, ectothermy results. Critical mass varies inversely with the level of energy expenditure, which therefore accounts for the fact that most mammals and birds are endotherms and most reptiles and fish are ectotherms. The same relationship permits the facultative endothermy found in some insects and plants.
The scaling relations existing among rate of metabolism, endothermy, and body mass can be written as a modification of the Kleiber relation. This analysis suggests that any organism, irrespective of phylogenetic position, can be endothermic at any body size, if its rate of metabolism is high enough, or can be endothermic with any rate of metabolism, if it is large enough. Consequently, it is difficult to distinguish minimal endothermy from inertial homoiothermy in animals having a large mass. The boundary conditions for effective endothermy are similar to the relationship described between metabolism and mass in the evolution of endothermy through a decrease in mass in the phylogeny of mammals. Even though endothermy may evolve with an increase in mass, its perfection may always require an evolutionary decrease in mass. 相似文献
The scaling relations existing among rate of metabolism, endothermy, and body mass can be written as a modification of the Kleiber relation. This analysis suggests that any organism, irrespective of phylogenetic position, can be endothermic at any body size, if its rate of metabolism is high enough, or can be endothermic with any rate of metabolism, if it is large enough. Consequently, it is difficult to distinguish minimal endothermy from inertial homoiothermy in animals having a large mass. The boundary conditions for effective endothermy are similar to the relationship described between metabolism and mass in the evolution of endothermy through a decrease in mass in the phylogeny of mammals. Even though endothermy may evolve with an increase in mass, its perfection may always require an evolutionary decrease in mass. 相似文献
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Yvette E. Pearson 《Journal of bioethical inquiry》2007,4(2):105-115
In this paper I examine the prevailing assumption that there is a right to procreate and question whether there exists a coherent
notion of such a right. I argue that we should question any and all procreative activities, not just alternative procreative
means and contexts. I suggest that clinging to the assumption of a right to procreate prevents serious scrutiny of reproductive behavior and that, instead of continuing to embrace this assumption,
attempts should be made to provide a proper foundation for it. I argue that the focus of procreative activities and discourse
on reproductive ethics should be on obligations instead of rights, as rights talk tends to obfuscate recognition of obligations
toward others, particularly those who bear the most significant burdens of the procreative process. I examine some possible
foundations of a right to procreate as well as John Robertson’s thoughtful account of “procreative liberty” but conclude that
at the present time there exists no compelling account of a right to procreate. Finally, I conclude that in the absence of
a satisfactory account of a right to procreate, we should refrain from grounding practices or polices on the assumption that
there is such a right.
相似文献
Yvette E. PearsonEmail: URL: http://al.odu.edu/iepa/ |
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Robert E. Furrow 《PloS one》2014,9(7)
There has been minimal theoretical exploration of the role of epigenetic variation in the response to natural selection. Using a population genetic model, I derive formulae that characterize the response of epigenetic variation to selection over multiple generations. Unlike genetic models in which mutation rates are assumed to be low relative to the strength of selection, the response to selection decays quickly due to a rapid lowering of parent-offspring epiallelic correlation. This effect is separate from the slowing response caused by a reduction in epigenetic variation. These results suggest that epigenetic variation may be less responsive to natural selection than is genetic variation, even in cases where levels of heritability appear similar. 相似文献
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Tu JM Kupka M Böhm S Plöscher M Eichacker L Zhao KH Scheer H 《Photosynthesis research》2008,95(2-3):163-168
The phycobilin: Cysteine-84-phycobiliprotein lyase, CpeS1, catalyzes phycocyanobilin (PCB) and phycoerythrobilin attachment
to nearly all cysteine-84 (consensus sequence) binding sites of phycoerythrin, phycoerythrocyanin, phycocyanin and allophycocyanin
(Zhao et al. (2007) Proc Natl Acad Sci 104:14300–14305). We now show that CpeS1 can bind PCB, as assayed by Ni2+ chelating affinity chromatography. Binding is rapid, and the chromophore is bound in an extended conformation similar to
that in phycobiliproteins but only poorly fluorescent. Upon addition of apo-biliproteins, the chromophore is transferred to
the latter much slower (∼1 h), indicating that chromophorylated CpeS1 is an intermediate in the enzymatic reaction. In addition,
imidazole is bound to PCB, as shown by mass spectroscopy of tryptic digests of the intermediate CpeS1–PCB complex. 相似文献
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Johnson JM Yen TC Zhao K Kosiba WA 《American journal of physiology. Heart and circulatory physiology》2005,288(4):H1573-H1579
Previous work indicates that sympathetic nerves participate in the vascular responses to direct cooling of the skin in humans. We evaluated this hypothesis further in a four-part series by measuring changes in cutaneous vascular conductance (CVC) from forearm skin locally cooled from 34 to 29 degrees C for 30 min. In part 1, bretylium tosylate reversed the initial vasoconstriction (-14 +/- 6.6% control CVC, first 5 min) to one of vasodilation (+19.7 +/- 7.7%) but did not affect the response at 30 min (-30.6 +/- 9% control, -38.9 +/- 6.9% bretylium; both P < 0.05, P > 0.05 between treatments). In part 2, yohimbine and propranolol (YP) also reversed the initial vasoconstriction (-14.3 +/- 4.2% control) to vasodilation (+26.3 +/- 12.1% YP), without a significant effect on the 30-min response (-26.7 +/- 6.1% YP, -43.2 +/- 6.5% control; both P < 0.05, P > 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no significant effect on either phase of vasoconstriction (P > 0.05 between sites both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also reversed the initial vasoconstriction (-20.1 +/- 6.4% control) to one of vasodilation (+213.4 +/- 87.0% Emla), whereas the final levels did not differ significantly (-37.7 +/- 10.1% control, -37.2 +/- 8.7% Emla; both P < 0.05, P > 0.05 between treatments). These results indicate that local cooling causes cold-sensitive afferents to activate sympathetic nerves to release norepinephrine, leading to a local cutaneous vasoconstriction that masks a nonneurogenic vasodilation. Later, a vasoconstriction develops with or without functional sensory or sympathetic nerves. 相似文献
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Some RGD-type integrins rely on a synergistic site in addition to the canonical RGD site for ligand binding. However, the precise involvement of each of these recognition sites during cell adhesion is still unclear. Here we review recent investigations on integrin alphaIIbbeta3-mediated cell adhesion to immobilized fibrinogen providing evidence that the fibrinogen synergy gamma(400-411) sequence by itself promotes cell attachment by initiating alphaIIbbeta3 clustering and recruitment of intracellular proteins to focal complexes, while the RGD motif subsequently acts as a molecular switch on the beta3 subunit to induce a conformational change necessary for RhoA activation and full cell spreading. 相似文献
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Antibodies to the codons ApApAp, ApApC, and ApUpG 总被引:6,自引:0,他引:6
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Mongolism, parental desires, and the right to life 总被引:4,自引:0,他引:4
J M Gustafson 《Perspectives in biology and medicine》1973,16(4):529-557
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Only ∼10% of replication origins that are licensed by loading minichromosome maintenance 2-7 (MCM2-7) complexes are normally used, with the majority remaining dormant. If replication fork progression is inhibited, nearby dormant origins initiate to ensure that all of the chromosomal DNA is replicated. At the same time, DNA damage-response kinases are activated, which preferentially suppress the assembly of new replication factories. This diverts initiation events away from completely new areas of the genome toward regions experiencing replicative stress. Mice hypomorphic for MCM2-7, which activate fewer dormant origins in response to replication inhibition, are cancer-prone and are genetically unstable. The licensing checkpoint delays entry into S phase if an insufficient number of origins have been licensed. In contrast, humans with Meier-Gorlin syndrome have mutations in pre-RC proteins and show defects in cell proliferation that may be a consequence of chronic activation of the licensing checkpoint.Replicating the large amount of DNA in eukaryotic cells is a complex task, requiring the activation of hundreds or thousands of origins spread throughout the genome. To maintain genetic stability, it is essential that during S phase genomic DNA is precisely duplicated, with no sections of DNA left unreplicated and no section of DNA replicated more than once. To prevent re-replication, cells divide the process of DNA replication into two non-overlapping phases. Prior to S phase, origins are licensed by the binding of minichromosome maintenance 2-7 (MCM2-7) double hexamers (Gillespie et al. 2001; Blow and Dutta 2005; Arias and Walter 2007). During S phase, these are activated as the core of the CMG (Cdc45-MCM-GINS) replicative helicase (Moyer et al. 2006; Ilves et al. 2010). Prior to the onset of S phase, licensing proteins are down-regulated or inhibited, so that no more origins can be licensed (Wohlschlegel et al. 2000; Tada et al. 2001; Li et al. 2003; Li and Blow 2005). One consequence of using this mechanism for preventing re-replication of DNA is that it is imperative that enough origins are licensed prior to S-phase entry, so that no regions of the genome remain unreplicated, even if some replication forks stall or some origins fail to initiate (Blow et al. 2011). Metazoan cells employ a licensing checkpoint to monitor that sufficient origins are licensed, inhibiting S-phase entry until this is established (Shreeram et al. 2002; Blow and Gillespie 2008).Here we review recent research showing how cells ensure complete genome duplication by licensing more replication origins in G1 than are normally used during S phase. The otherwise dormant replication origins become important for ensuring the completion of DNA replication if replication forks stall or are inhibited during S phase. We also review research showing how the licensing checkpoint ensures that a large enough number of origins are licensed before cells embark on S phase. 相似文献
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K. Tukamoto 《Journal of fish biology》1990,36(5):659-671
A total of 149 Anguilla japonica elvers collected at 10 locations along the Japanese coast were aged according to otolith daily increments. The interrelationships among age, birth date, body size, pigmentation stage, sampling location and the timing of recruitment were examined in order to determine the recruitment mechanism of elvers to coastal waters.
First catches of eels were earlier in the locations at lower latitudes. Age at recruitment was roughly constant, 218 ± 29 (mean ± s.d.) days old, disregarding the localities, but a weak positive correlation was obtained between age and sampling date or timing of recruitment. Body length at recruitment was also constant, 56.3 ± 2.3 mm s.l., and showed no significant correlation with either locality or recruitment timing. Estimated birth date ranged from April to November, the mean ± s.d. being 22 July 1982 ± 42 days, suggesting a peak season spawning in summer. Birth date was closely related with both the latitude of location and sampling time. Pigmentation developed more at lower latitude. Recruitment mechanism of the Japanese eel was summarized as follows: the earlier-born individual recruits earlier at lower latitude and at younger age, but at a constant body size. 相似文献
First catches of eels were earlier in the locations at lower latitudes. Age at recruitment was roughly constant, 218 ± 29 (mean ± s.d.) days old, disregarding the localities, but a weak positive correlation was obtained between age and sampling date or timing of recruitment. Body length at recruitment was also constant, 56.3 ± 2.3 mm s.l., and showed no significant correlation with either locality or recruitment timing. Estimated birth date ranged from April to November, the mean ± s.d. being 22 July 1982 ± 42 days, suggesting a peak season spawning in summer. Birth date was closely related with both the latitude of location and sampling time. Pigmentation developed more at lower latitude. Recruitment mechanism of the Japanese eel was summarized as follows: the earlier-born individual recruits earlier at lower latitude and at younger age, but at a constant body size. 相似文献
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Immature gerbils (4 weeks of age or less) proved to be more resistant to Babesia divergens infections than did mature animals (greater than 8 weeks old). Nutritional studies showed that a milk diet contributes little to this innate resistance. Similarly, the apparent predilection of B. divergens for mature erythrocytes, and also in vitro serum incubation studies, suggested that blood factors do not contribute to any major degree. Splenectomy of immature gerbils abolished their nonspecific resistance and studies with splenocyte incubations with the piroplasm imply that splenic integrity is necessary for the maintenance of this, apparently antibody-independent, resistance to infection with B. divergens. 相似文献
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Bruno C Carocci A Catalano A Cavalluzzi MM Corbo F Franchini C Lentini G Tortorella V 《Chirality》2006,18(4):227-231
Lubeluzole [(S)-9] has been synthesized by a convergent synthesis, alkylation of N-methyl-N-piperidin-4-yl-1,3-benzothiazol-2-amine (4) with (+)-(R)-1-chloro-3-(3,4-difluorophenoxy)propan-2-ol [(+)-(R)-8] being the key step. Alcohol (+)-(R)-8 was obtained from commercially available (R)-epichlorohydrin [(R)-6], while the thiazole derivative 4 was easily obtained starting from N-protected piperidin-4-one (1) in a three-step procedure. The same method was used in order to obtain both the (R)-stereoisomer of lubeluzole [(R)-9] and its racemate [(RS)-9]. Overall yields ranged from 20% to 35%. The enantiomeric excess values for (S)-9 and (R)-9 were 97% and 94% respectively, as analyzed by chiral HPLC. 相似文献