排序方式: 共有56条查询结果,搜索用时 15 毫秒
1.
The capsaicin receptor TRPV1, a member of the transient receptor potential family of non-selective cation channels is a polymodal nociceptor. Noxious thermal stimuli, protons, and the alkaloid irritant capsaicin open the channel. The mechanisms of heat and capsaicin activation have been linked to voltage-dependent gating in TRPV1. However, until now it was unclear whether proton activation or potentiation or both are linked to a similar voltage-dependent mechanism and which molecular determinants underlie the proton gating. Using the whole-cell patch-clamp technique, we show that protons activate and potentiate TRPV1 by shifting the voltage dependence of the activation curves towards more physiological membrane potentials. We further identified a key residue within the pore region of TRPV1, F660, to be critical for voltage-dependent proton activation and potentiation. We conclude that proton activation and potentiation of TRPV1 are both voltage dependent and that amino acid 660 is essential for proton-mediated gating of TRPV1. 相似文献
2.
Tribolium castaneum is a well-characterised model insect, whose short germ-band mode of embryonic development is characteristic of many insect species and differs from the exhaustively studied Drosophila. Mechanisms of early neurogenesis, however, show significant conservation with Drosophila, as a characteristic pattern of neuroblasts arises from neuroectoderm proneural clusters in response to the bHLH activator Ash, a homologue of Achaete–Scute. Here we study the expression and function of two other bHLH proteins, the bHLH-O repressors E(spl)1 and E(spl)3. Their Drosophila homologues are expressed in response to Notch signalling and antagonize the activity of Achaete–Scute proteins, thus restricting the number of nascent neuroblasts. E(spl)1 and 3 are the only E(spl) homologues in Tribolium and both show expression in the cephalic and ventral neuroectoderm during embryonic neurogenesis, as well as a dynamic pattern of expression in other tissues. Their expression starts early, soon after Ash expression and is dependent on both Ash and Notch activities. They act redundantly, since a double E(spl) knockdown (but not single knockdowns) results in neurogenesis defects similar to those caused by Notch loss-of-function. A number of other activities have been evolutionarily conserved, most notably their ability to interact with proneural proteins Scute and Daughterless. 相似文献
3.
Alexandra V. Stavropoulou Florentia Fostira Maroulio Pertesi Marianthi Tsitlaidou Gerassimos E. Voutsinas Olga Triantafyllidou Aristotelis Bamias Meletios A. Dimopoulos Eleni Timotheadou Dimitrios Pectasides Christos Christodoulou George Klouvas Christos Papadimitriou Thomas Makatsoris George Pentheroudakis Gerasimos Aravantinos Vassilis Karydakis Drakoulis Yannoukakos George Fountzilas Irene Konstantopoulou 《PloS one》2013,8(3)
Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18% of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to 50%. A variable incidence of mutations has been reported for these genes in ovarian cancer cases from different populations. In Greece, six mutations in BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes. This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort of 106 familial ovarian cancer patients that had strong family history or metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698 patients were screened for the six recurrent Greek mutations (including founder mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23–24 and exon 24). In familial cases, the BRCA1 gene was consequently screened for exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in 43/106 (40.6%) of familial cancer cases and in 27/592 (4.6%) of sporadic cases. The variant of unknown clinical significance p.V1833M was identified in 9/698 patients (1.3%). The majority of BRCA1 carriers (71.2%) presented a high-grade serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or ovarian cancer families is important, as it enables carriers to take preventive measures. All ovarian cancer patients with a serous phenotype should be considered for genetic testing. Further studies are warranted to determine the prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and other novel predisposing genes for breast and ovarian cancer. 相似文献
4.
Akhtar S Shamotienko O Papakosta M Ali F Dolly JO 《The Journal of biological chemistry》2002,277(19):16376-16382
Most neuronal Kv1 channels contain Kv1.1, Kv1.2 alpha, and Kvbeta2.1 subunits, yet the influences of their stoichiometries on properties of the (alpha)(4)(beta)(4) variants remain undefined. cDNAs were engineered to contain 0, 1, 2, or 4 copies of Kv1.1 with the requisite number of Kv1.2 and co-expressed in mammalian cells with Kvbeta2.1 to achieve "native-like" hetero-oligomers. The monomeric (Kv1.1 or 1.2), dimeric (Kv1.1-1.2 or 1.2-1.2), and tetrameric (Kv1.1-(1.2)(3)) constructs produced proteins of M(r) approximately 62,000, 120,000, and 240,000, which assembled into (alpha)(4)(beta)(4) complexes. Each alpha cRNA yielded a distinct K(+) current in oocytes, with voltage dependence of activation being shifted negatively as the Kv1.1 content in tetramers was increased. Channels containing 1, 2, or 4 copies of Kv1.1 were blocked by dendrotoxin k (DTX)(k) with similarly high potencies, whereas Kv(1.2)(4) proved nonsusceptible. Accordingly, Kv1.2/beta2.1 expressed in baby hamster kidney cells failed to bind DTX(k); in contrast, oligomers containing only one Kv1.1 subunit in a tetramer exhibited high affinity, with additional copies causing modest increases. Thus, one Kv1.1 subunit largely confers high affinity for DTX(k), whereas channel electrophysiological properties are tailored by the content of Kv1.1 relative to Kv1.2. This notable advance could explain the diversity of symptoms of human episodic ataxia I, which is often accompanied by myokymia, due to mutated Kv1.1 being assembled in different combinations with wild-type and Kv1.2. 相似文献
5.
6.
Dubey A Boukouvala F Keyvan G Hsia R Saranteas K Brone D Misra T Ierapetritou MG Muzzio FJ 《AAPS PharmSciTech》2012,13(1):231-246
A combination of analytical and statistical methods is used to improve a tablet coating process guided by quality by design
(QbD) principles. A solid dosage form product was found to intermittently exhibit bad taste. A suspected cause was the variability
in coating thickness which could lead to the subject tasting the active ingredient in some tablets. A number of samples were
analyzed using a laser-induced breakdown spectroscopy (LIBS)-based analytical method, and it was found that the main variability
component was the tablet-to-tablet variability within a lot. Hence, it was inferred that the coating process (performed in
a perforated rotating pan) required optimization. A set of designed experiments along with response surface modeling and kriging
method were used to arrive at an optimal set of operating conditions. Effects of the amount of coating imparted, spray rate,
pan rotation speed, and spray temperature were characterized. The results were quantified in terms of the relative standard
deviation of tablet-averaged LIBS score and a coating variability index which was the ratio of the standard deviation of the
tablet-averaged LIBS score and the weight gain of the tablets. The data-driven models developed based on the designed experiments
predicted that the minimum value of this index would be obtained for a 6% weight gain for a pan operating at the highest speed
at the maximum fill level while using the lowest spraying rate and temperature from the chosen parametric space. This systematic
application of the QbD-based method resulted in an enhanced process understanding and reducing the coating variability by
more than half. 相似文献
7.
8.
9.
10.
A comparison of root architecture and shoot morphology between naturally regenerated and container-grown seedlings of Quercus ilex 总被引:1,自引:0,他引:1
Marianthi Tsakaldimi Thekla Tsitsoni Petros Ganatsas Theocharis Zagas 《Plant and Soil》2009,324(1-2):103-113
We explored the different mechanisms developed by naturally regenerated seedlings of Quercus ilex L. (Holm oak) under Mediterranean conditions compared to container-seedlings commonly used in plantations. We examined the differences in root architecture (including topology and morphology) and shoot parameters. The results showed that there are many differences in the architecture of the root system as well as in the shoot morphology between the two types of seedlings. The naturally regenerated seedlings were smaller with regard to most of the shoot and root parameters, but they developed a longer taproot, only first order lateral roots, and presented a more herringbone-like root system compared to the container seedlings. Conversely, all types of container seedlings, were larger and had a more extended root system with many orders of lateral roots, while their taproot length was restricted within the container’s depth. The quotient log (α)/ log (μ) for all seedlings, showed a tendency to decrease with plant size. A strict herringbone root system with an elongated taproot may be the optimal root architecture for Quercus ilex L. seedlings in order to survive under Mediterranean conditions. 相似文献