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961.
Harrington AW St Hillaire C Zweifel LS Glebova NO Philippidou P Halegoua S Ginty DD 《Cell》2011,146(3):421-434
The neurotrophins NGF and NT3 collaborate to support development of sympathetic neurons. Although both promote axonal extension via the TrkA receptor, only NGF activates retrograde transport of TrkA endosomes to support neuronal survival. Here, we report that actin depolymerization is essential for initiation of NGF/TrkA endosome trafficking and that?a Rac1-cofilin signaling module associated with TrkA early endosomes supports their maturation to retrograde transport-competent endosomes. These actin-regulatory endosomal components are absent from NT3/TrkA endosomes, explaining the failure of NT3 to support retrograde TrkA transport and survival. The inability of NT3 to activate Rac1-GTP-cofilin signaling is likely due to the labile nature of NT3/TrkA complexes within the acidic environment of TrkA early endosomes. Thus, TrkA endosomes associate with actin-modulatory proteins to promote F-actin disassembly, enabling their maturation into transport-competent signaling endosomes. Differential control of this process explains how NGF but not NT3 supports retrograde survival of sympathetic neurons. 相似文献
962.
TRP channels form a superfamily of channel proteins exhibiting versatile regulatory characteristics with many channels participating in the regulation of Ca2+ homeostasis and influencing the cell fate. Multitude of evidence is emerging that the colocalization of TRP channels with Ca2+-sensing elements of specific regulatory pathways leading to either proliferation or apoptosis is what makes these channels participate in cell fate regulation and, in turn, determines the final effect of Ca2+ entry via the particular channel. This review focuses on the aspects of TRP channel localization and function that affect the balance between cell survival and death and how various dysregulations of these channels may lead to perturbed balance and onset of cancer. 相似文献
963.
Ogawa J Kodera T Smirnov SV Hibi M Samsonova NN Koyama R Yamanaka H Mano J Kawashima T Yokozeki K Shimizu S 《Applied microbiology and biotechnology》2011,89(6):1929-1938
4-Hydroxyisoleucine (HIL) found in fenugreek seeds has insulinotropic and anti-obesity effects and is expected to be a novel orally active drug for insulin-independent diabetes. Here, we show that the newly isolated strain Bacillus thuringiensis 2e2 and the closely related strain B. thuringiensis ATCC 35646 operate a novel metabolic pathway for L-isoleucine (L-Ile) via HIL and 2-amino-3-methyl-4-ketopentanoic acid (AMKP). The HIL synthesis was catalyzed stereoselectively by an α-ketoglutaric acid-dependent dioxygenase and to be useful for efficient production of a naturally occurring HIL isomer, (2S,3R,4S)-HIL. The (2S,3R,4S)-HIL was oxidized to (2S,3R)-AMKP by a NAD(+)-dependent dehydrogenase. The metabolic pathway functions as an effective bypass pathway that compensates for the incomplete tricarboxylic acid (TCA) cycle in Bacillus species and also explains how AMKP, a vitamin B(12) antimetabolite with antibiotic activity, is synthesized. These novel findings pave a new way for the commercial production of HIL and also for AMKP. 相似文献
964.
López-Morales M Gómez-Pérez N Ruedas T 《Origins of life and evolution of the biosphere》2011,41(6):533-537
We present estimations of dipolar magnetic moments for terrestrial exoplanets using the Olson & Christiansen (EPS Lett 250:561–571,
2006) scaling law and assuming their interior structure is similar to Earth. We find that the dipolar moment of fast rotating
planets (where the Coriolis force dominates convection in the core), may amount up to ~80 times the magnetic moment of Earth,
M
⊕
, for at least part of the planets’ lifetime. For slow rotating planets (where the force of inertia dominates), the dipolar
magnetic moment only reaches up to ~1.5 M
⊕
. Applying our calculations to confirmed rocky exoplanets, we find that CoRoT-7b, Kepler-10b and 55 Cnc e can sustain dynamos
up to ~18, 15 and 13 M
⊕
, respectively. Our results also indicate that the magnetic moment of rocky exoplanets not only depends on rotation rate,
but also on their formation history, thermal state, age, composition, and the geometry of the field. These results apply to
all rocky planets, but have important implications for the particular case of planets in the Habitable Zone of M-dwarfs. 相似文献
965.
Human-mediated translocations of species beyond their native ranges can enhance evolutionary processes in populations introduced
to novel environments. We studied such processes in several generations of pink salmon Oncorhynchus gorbuscha introduced to the European North of Russia using a set of morphological and life-history traits as well as molecular genetic
markers with different selective values: protein-coding loci, mtDNA, microsatellites, and MHC. The introduction of reproductively
isolated pink salmon broodlines of odd and even years yielded different results. The odd-year broodline established self-reproducing
local populations in many rivers of new range, but sustainable changes in external morphology, reproduction, and life-history,
as well as the impoverishment of the gene pool occurred. Their successful colonisation of the new range resulted in specialisation
manifested in the rapid directional shifts in some highly heritable phenotypic traits accompanied by increased homozygosity
at molecular markers as a consequence of genetic drift and selective processes. The returns of transplanted pink salmon of
even-year broodline decreased sharply already in the second generation, but there was no marked reduction of genetic diversity.
Our data, as well as the analysis of the history of all pink salmon transplantations beyond the species range, demonstrate
comparatively greater success of introduced odd-year broodline and permit to assume different adaptive plasticity of the even-
and odd-year broodlines in pink salmon, what is most likely determined by differences in their evolutionary histories. Population
genetic data suggest that the even-year broodline probably diverged from the odd-year broodline relatively recently and, due
to the founder effect, may have lost a part of its genetic variation with which adaptive plasticity potential is associated. 相似文献
966.
Alfaro C Perez-Gracia JL Suarez N Rodriguez J Fernandez de Sanmamed M Sangro B Martin-Algarra S Calvo A Redrado M Agliano A Gonzalez A Rodriguez I Bolaños E Hervás-Stubbs S Perez-Calvo J Benito A Peñuelas I Vigil C Richter J Martinez-Forero I Melero I 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(11):6130-6142
Twenty-four patients with metastatic cancer received two cycles of four daily immunizations with monocyte-derived dendritic cells (DC). DC were incubated with preheated autologous tumor lysate and subsequently with IFN-α, TNF-α, and polyinosinic:polycytidylic acid to attain type 1 maturation. One DC dose was delivered intranodally, under ultrasound control, and the rest intradermally in the opposite thigh. Cyclophosphamide (day -7), GM-CSF (days 1-4), and pegIFN alpha-2a (days 1 and 8) completed each treatment cycle. Pretreatment with cyclophosphamide decreased regulatory T cells to levels observed in healthy subjects both in terms of percentage and in absolute counts in peripheral blood. Treatment induced sustained elevations of IL-12 in serum that correlated with the output of IL-12p70 from cultured DC from each individual. NK activity in peripheral blood was increased and also correlated with the serum concentration of IL-12p70 in each patient. Circulating endothelial cells decreased in 17 of 18 patients, and circulating tumor cells markedly dropped in 6 of 19 cases. IFN-γ-ELISPOT responses to DC plus tumor lysate were observed in 4 of 11 evaluated cases. Tracing DC migration with [(111)In] scintigraphy showed that intranodal injections reached deeper lymphatic chains in 61% of patients, whereas with intradermal injections a small fraction of injected DC was almost constantly shown to reach draining inguinal lymph nodes. Five patients experienced disease stabilization, but no objective responses were documented. This combinatorial immunotherapy strategy is safe and feasible, and its immunobiological effects suggest potential activity in patients with minimal residual disease. A randomized trial exploring this hypothesis is currently ongoing. 相似文献
967.
968.
969.
El Fangour S Balas L Rossi JC Fedenyuk A Gretskaya N Bobrov M Bezuglov V Hillard CJ Durand T 《Bioorganic & medicinal chemistry letters》2003,13(12):1977-1980
Three new endocannabinoid analogues in which amide moiety was replaced either by oxomethylene group or ester moiety with simultaneous substitution of both alpha-hydrogens with methyl groups were synthesized and their abilities to interact with CB1-receptor and FAAH were investigated. 相似文献
970.
Root phosphoenolpyruvate carboxylase and NAD-malic enzymes activity increase the ammonium-assimilating capacity in tomato 总被引:1,自引:0,他引:1