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321.
Hanna Segev Ayeleth Reshef Vèronique Clavey Christiane Delbart Gustave Routier Eran Leitersdorf 《Human genetics》1995,95(2):238-240
Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid-storage disease caused by mutations in the sterol 27-hydroxylase gene (CYP27). So far several mutations causing CTX have been identified and characterized. A new mutation creating an insertion of cytosine at position 6 in the cDNA, which is expected to result in a frameshift and a premature termination codon at codon 179, has been identified in a French family. The mutation creates a new site for the restriction endonuclease HaeIII. 相似文献
322.
Einat Segev Isla S. Castañeda Elisabeth L. Sikes Hera Vlamakis Roberto Kolter 《Journal of phycology》2016,52(1):125-130
The microalga Emiliania huxleyi produces alkenone lipids that are important proxies for estimating past sea surface temperatures. Field calibrations of this proxy are robust but highly variable results are obtained in culture. Here, we present results suggesting that algal‐bacterial interactions may be responsible for some of this variability. Co‐cultures of E. huxleyi and the bacterium Phaeobacter inhibens resulted in a 2.5‐fold decrease in algal alkenone‐containing lipid bodies. In addition levels of unsaturated alkenones increase in co‐cultures. These changes result in an increase in the reconstructed growth temperature of up to 2°C relative to axenic algal cultures. 相似文献
323.
Kurnvir Singh Rose Tanui Armanda Gameiro Gilad Eisenberg Claire Colas Avner Schlessinger Christof Grewer 《Bioorganic & medicinal chemistry letters》2017,27(3):398-402
The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl ring resulted in compounds with characteristics of ASCT2 inhibitors. Apparent binding affinity increased with increasing hydrophobicity of the side chain. In contrast, interaction of the ASCT2 binding site with specific positions on the phenyl ring was not observed. The most potent compound inhibits the ASCT2 anion conductance with a Ki of 3 μM, which is in the same range as that of more bulky and higher molecular weight inhibitors recently reported by others. The experimental results are consistent with computational analysis based on docking of the inhibitors against an ASCT2 homology model. The benzylproline scaffold provides a valuable tool for further improving binding potency of future ASCT2 inhibitors. 相似文献
324.
Bourguignon LY Gilad E Brightman A Diedrich F Singleton P 《The Journal of biological chemistry》2006,281(20):14026-14040
In this study we have examined the interaction of CD44 (a major hyaluronan (HA) receptor) with a RhoA-specific guanine nucleotide exchange factor (leukemia-associated RhoGEF (LARG)) in human head and neck squamous carcinoma cells (HNSCC-HSC-3 cell line). Immunoprecipitation and immunoblot analyses indicate that CD44 and the LARG protein are expressed in HSC-3 cells and that these two proteins are physically associated as a complex. HA-CD44 binding induces LARG-specific RhoA signaling and phospholipase C epsilon (PLC epsilon) activity. In particular, the activation of RhoA-PLC epsilon by HA stimulates inositol 1,4,5-triphosphate production, intracellular Ca2+ mobilization, and the up-regulation of Ca2+/calmodulin-dependent kinase II (CaMKII), leading to phosphorylation of the cytoskeletal protein, filamin. The phosphorylation of filamin reduces its interaction with filamentous actin, promoting tumor cell migration. The CD44-LARG complex also interacts with the EGF receptor (EGFR). Most importantly, the binding of HA to the CD44-LARG-EGFR complex activates the EGFR receptor kinase, which in turn promotes Ras-mediated stimulation of a downstream kinase cascade including the Raf-1 and ERK pathways leading to HNSCC cell growth. Using a recombinant fragment of LARG (the LARG-PDZ domain) and a binding assay, we have determined that the LARG-PDZ domain serves as a direct linker between CD44 and EGFR. Transfection of the HSC-3 cells with LARG-PDZcDNA significantly reduces LARG association with CD44 and EGFR. Overexpression of the LARG-PDZ domain also functions as a dominant-negative mutant (similar to the PLC/Ca2+-calmodulin-dependent kinase II (CaMKII) and EGFR/MAPK inhibitor effects) to block HA/CD44-mediated signaling events (e.g. EGFR kinase activation, Ras/RhoA co-activation, Raf-ERK signaling, PLC epsilon-mediated inositol 1,4,5-triphosphate production, intracellular Ca2+ mobilization, CaMKII activity, filamin phosphorylation, and filamin-actin binding) and to abrogate tumor cell growth/migration. Taken together, our findings suggest that CD44 interaction with LARG and EGFR plays a pivotal role in Rho/Ras co-activation, PLC epsilon-Ca2+ signaling, and Raf/ERK up-regulation required for CaMKII-mediated cytoskeleton function and in head and neck squamous cell carcinoma progression. 相似文献
325.
Elishai Ezra-Tsur Oren Amsalem Lea Ankri Pritish Patil Idan Segev Michal Rivlin-Etzion 《PLoS computational biology》2021,17(12)
Retinal direction-selectivity originates in starburst amacrine cells (SACs), which display a centrifugal preference, responding with greater depolarization to a stimulus expanding from soma to dendrites than to a collapsing stimulus. Various mechanisms were hypothesized to underlie SAC centrifugal preference, but dissociating them is experimentally challenging and the mechanisms remain debatable. To address this issue, we developed the Retinal Stimulation Modeling Environment (RSME), a multifaceted data-driven retinal model that encompasses detailed neuronal morphology and biophysical properties, retina-tailored connectivity scheme and visual input. Using a genetic algorithm, we demonstrated that spatiotemporally diverse excitatory inputs–sustained in the proximal and transient in the distal processes–are sufficient to generate experimentally validated centrifugal preference in a single SAC. Reversing these input kinetics did not produce any centrifugal-preferring SAC. We then explored the contribution of SAC-SAC inhibitory connections in establishing the centrifugal preference. SAC inhibitory network enhanced the centrifugal preference, but failed to generate it in its absence. Embedding a direction selective ganglion cell (DSGC) in a SAC network showed that the known SAC-DSGC asymmetric connectivity by itself produces direction selectivity. Still, this selectivity is sharpened in a centrifugal-preferring SAC network. Finally, we use RSME to demonstrate the contribution of SAC-SAC inhibitory connections in mediating direction selectivity and recapitulate recent experimental findings. Thus, using RSME, we obtained a mechanistic understanding of SACs’ centrifugal preference and its contribution to direction selectivity. 相似文献
326.
Rolls A Shechter R London A Segev Y Jacob-Hirsch J Amariglio N Rechavi G Schwartz M 《PLoS medicine》2008,5(8):e171
Background
Chondroitin sulfate proteoglycan (CSPG) is a major component of the glial scar. It is considered to be a major obstacle for central nervous system (CNS) recovery after injury, especially in light of its well-known activity in limiting axonal growth. Therefore, its degradation has become a key therapeutic goal in the field of CNS regeneration. Yet, the abundant de novo synthesis of CSPG in response to CNS injury is puzzling. This apparent dichotomy led us to hypothesize that CSPG plays a beneficial role in the repair process, which might have been previously overlooked because of nonoptimal regulation of its levels. This hypothesis is tested in the present study.Methods and Findings
We inflicted spinal cord injury in adult mice and examined the effects of CSPG on the recovery process. We used xyloside to inhibit CSPG formation at different time points after the injury and analyzed the phenotype acquired by the microglia/macrophages in the lesion site. To distinguish between the resident microglia and infiltrating monocytes, we used chimeric mice whose bone marrow-derived myeloid cells expressed GFP. We found that CSPG plays a key role during the acute recovery stage after spinal cord injury in mice. Inhibition of CSPG synthesis immediately after injury impaired functional motor recovery and increased tissue loss. Using the chimeric mice we found that the immediate inhibition of CSPG production caused a dramatic effect on the spatial organization of the infiltrating myeloid cells around the lesion site, decreased insulin-like growth factor 1 (IGF-1) production by microglia/macrophages, and increased tumor necrosis factor alpha (TNF-α) levels. In contrast, delayed inhibition, allowing CSPG synthesis during the first 2 d following injury, with subsequent inhibition, improved recovery. Using in vitro studies, we showed that CSPG directly activated microglia/macrophages via the CD44 receptor and modulated neurotrophic factor secretion by these cells.Conclusions
Our results show that CSPG plays a pivotal role in the repair of injured spinal cord and in the recovery of motor function during the acute phase after the injury; CSPG spatially and temporally controls activity of infiltrating blood-borne monocytes and resident microglia. The distinction made in this study between the beneficial role of CSPG during the acute stage and its deleterious effect at later stages emphasizes the need to retain the endogenous potential of this molecule in repair by controlling its levels at different stages of post-injury repair. 相似文献327.
328.
Peter B. Johansen Yael Segev Daniel Landau Moshe Phillip Allan Flyvbjerg 《Experimental diabetes research》2003,4(2):73-81
The growth hormone (GH) and insulin-like growth factor
I (IGF-I) axis were studied in streptozotocin (STZ) diabetic
and nondiabetic female mice following intravenous
(IV) injection of the GH secretagogue (GHS) ipamorelin or
saline. On day 14, blood samples were obtained before and
10 minutes after the injection. Livers were removed and
frozen for determination of the mRNA expressions of the
GH receptor, GH-binding protein, and IGF-I, and hepatic
IGF-I peptide. Serum samples were analyzed for GH and
IGF-I. Following ipamorelin injection, the GH levels were
found to be 150 ± 35 μg/L and 62 ± 11 μg/L in the diabetic
compared to the nondiabetic mice (P < .05). Serum IGF-I
levels were lower in diabetic than in nondiabetic animals,
and rose after stimulation only in the nondiabetic animals.
Furthermore, hepatic GH resistance and IGF-I mRNA levels
and IGF-I peptide were increased in nondiabetic animals
in response to GH stimulation, whereas the low levels per se
of all these parameters in diabetic mice were unaffected. The study shows that STZ diabetic mice demonstrate a substantial
part of the clinical features of type 1 diabetes in humans,
including GH hypersecretion and GH resistance. Accordingly,
it is proposed that STZ diabetic mice may be a better
model of the perturbations of the GH/IGF-I axis in diabetes
than STZ diabetic rats. 相似文献
329.
330.
Recovery of Streptococcus iniae from Diseased Fish Previously Vaccinated with a Streptococcus Vaccine 总被引:1,自引:0,他引:1 下载免费PDF全文
Gilad Bachrach Amir Zlotkin Avshalom Hurvitz Donald L. Evans Avi Eldar 《Applied microbiology》2001,67(8):3756-3758
Streptococcus iniae was recovered from diseased rainbow trout (Oncorhynchus mykiss, Walbaum) previously vaccinated against streptococcosis. PCR and serological methods indicate the presence of a new serotype in the diseased fish. 相似文献