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11.
12.
Gerard H. Thomas Adam J. Babbs Rosemary E. Chatfield Thomas M. Krülle Peter S. Widdowson Daniel Provost James G. McCormack 《Obesity (Silver Spring, Md.)》2009,17(3):467-473
The noradrenaline (NA) and serotonin reuptake inhibitor, sibutramine, gives effective weight loss, but full efficacy cannot be attained at approved doses due to cardiovascular side effects. We assessed in rats the contributions of NA and serotonin transporters to sibutramine's hypophagic and cardiovascular effects, and whether selective 5‐hydroxytryptamine (5‐HT1A) receptor activation could counteract the latter without affecting the former. Food intake was assessed in freely feeding rats and cardiovascular parameters in conscious telemetered rats. Ex vivo radioligand binding was used to estimate brain monoamine transporter occupancy. Sibutramine (1–10 mg/kg p.o.) dose‐dependently reduced food intake; however, 10 mg/kg p.o. markedly elevated blood pressure and heart rate. Sibutramine gave greater occupancy of NA than serotonin reuptake sites. Coadministration of the selective 5‐HT1A agonist F‐11440 (2.5 mg/kg p.o.) attenuated sibutramine‐induced hypertension and tachycardia without altering its food intake effects. The selective NA reuptake inhibitors, nisoxetine or reboxetine, did not alter food intake alone, but each reduced food intake when combined with F‐11440. These results suggest that sibutramine‐induced hypophagic and cardiovascular effects are largely due to increased brain synaptic NA via NA reuptake inhibition, and that 5‐HT1A activation can counter the undesirable cardiovascular effects resulting from increased sympathetic activity. Selective NA reuptake inhibitors did not reduce food intake alone but did when combined with 5‐HT1A activation. Hence increased synaptic serotonin, via serotonin reuptake inhibition or 5‐HT1A activation, together with increased NA, would appear to produce hypophagia. Thus weight loss with minimal cardiovascular risk could be achieved by 5‐HT1A activation combined with NA transporter blockade. 相似文献
13.
Sara L Goodacre Oliver Y Martin Dries Bonte Linda Hutchings Chris Woolley Kamal Ibrahim CF George Thomas Godfrey M Hewitt 《BMC biology》2009,7(1):32-8
Background
Dispersal plays a key role in shaping biological and ecological processes such as the distribution of spatially-structured populations or the pace and scale of invasion. Here we have studied the relationship between long-distance dispersal behaviour of a pest-controlling money spider,Erigone atra, and the distribution of maternally acquired endosymbionts within the wider meta-population. This spider persists in heterogeneous environments because of its ability to recolonise areas through active long-distance airborne dispersal using silk as a sail, in a process termed 'ballooning'. 相似文献14.
15.
European Working Group on CF Genetics 《Human genetics》1990,85(4):436-445
Summary In this collaborative European study, a total of 4871 cystic fibrosis (CF) chromosomes and 3539 normal chromosomes have been
characterized for the haplotypes defined by the 2 extragenic polymorphic sequences revealed by XV2c and KM19. The association
between one of these haplotypes (B haplotype) and the most frequent CF mutation, ΔF508, suggests for the latter a single origin
and a subsequent diffusion according to a South East-North West gradient. The linkage disequilibrium data between CF and the
B haplotype in different European populations are compatible with a relatively more recent appearance of the mutation in Northern
Europe whereas in Southern Europe a longer history of the same mutation would have allowed time for recombination with other
haplotypes. This model is also compatible with a selective advantage of carriers but does not account for (1) the excess of
B haplotypes observed among both normal and non-ΔF508 CF chromosomes; (2) the correlation between the B haplotype and the
severity of the phenotypic effect caused by CF mutations, as measured by pancreatic insufficiency and meconium ileus. 相似文献
16.
17.
Jain RK; Piskorz CF; Huang BG; Locke RD; Han HL; Koenig A; Varki A; Matta KL 《Glycobiology》1998,8(7):707-717
The selectins interact in important normal and pathological situations with
certain sialylated, fucosylated glycoconjugate ligands containing sialyl
Lewisx(Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcN Ac). Much effort has gone
into the synthesis of sialylated and sulfated Lewisxanalogs as competitive
ligands for the selectins. Since the natural selectin ligands GlyCAM-1 and
PSGL-1 carry sialyl Lewisxas part of a branched Core 2 O-linked structure,
we recently synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(SE-3Galbeta1++
+-3)GalNAc1alphaOMe and found it to be a moderately superior ligand for L
and P-selectin (Koenig et al. , Glycobiology 7, 79-93, 1997). Other studies
have shown that sulfate esters can replace sialic acid in some selectin
ligands (Yeun et al. , Biochemistry, 31, 9126-9131, 1992; Imai et al. ,
Nature, 361, 555, 1993). Based upon these observations, we hypothesized
that Neu5Acalpha2-3Galbeta1-3GalNAc might have the capability of
interacting with L- and P-selectin. To examine this hypothesis, we
synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Neu5Acalpha2++
+-3Galbeta1-3)- GalNAc alpha1-OB, which was found to be 2- to 3-fold better
than sialyl Lexfor P and L selectin, respectively. We also report the
synthesis of an unusual structure GalNAcbeta1-4(Fucalpha1-
3)GlcNAcbeta1-OMe (GalNAc- Lewisx-O-methyl glycoside), which also proved to
be a better inhibitor of L- and P-selectin than sialyl Lewisx-OMe.
Combining this with our knowledge of Core 2 branched structures, we have
synthesized a molecule that is 5- to 6-fold better at inhibiting L- and
P-selectin than sialyl Lewisx-OMe, By contrast to unbranched structures,
substitution of a sulfate ester group for a sialic acid residue in such a
molecule resulted in a considerable loss of inhibition ability. Thus, the
combination of a sialic acid residue on the primary (beta1-3) arm, and a
modified Lexunit on the branched (beta1-6) arm on an O-linked Core 2
structure generated a monovalent synthetic oliogosaccharide inhibitor
superior to SLexfor both L- and P-selectin.
相似文献
18.
Haug Marion F Biehlmaier Oliver Mueller Kaspar P Neuhauss Stephan CF 《Frontiers in zoology》2010,7(1):1-7
Background
Mating plugs that males place onto the female genital tract are generally assumed to prevent remating with other males. Mating plugs are usually explained as a consequence of male-male competition in multiply mating species. Here, we investigated whether mating plugs also have collateral effects on female fitness. These effects are negative when plugging reduces female mating rate below an optimum. However, plugging may also be positive when plugging prevents excessive forced mating and keeps mating rate closer to a females' optimum. Here, we studied these consequences in the gonochoristic nematode Caenorhabditis remanei. We employed a new CO2-sedation technique to interrupt matings before or after the production of a plug. We then measured mating rate, attractiveness and offspring number.Results
The presence of a mating plug did not affect mating rate or attractiveness to roving males. Instead, females with mating plugs produced more offspring than females without copulatory plugs.Conclusions
Our experiment suggests that plugging might have evolved under male-male competition but represents a poor protection against competing males in our experiment. Even if plugging does not reduce mating rate, our results indicate that females may benefit from being plugged in a different sense than remating prevention. 相似文献19.
20.
Charles F Babbs 《Biomedical engineering online》2010,9(1):42