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31.
Lasry I Seo YA Ityel H Shalva N Pode-Shakked B Glaser F Berman B Berezovsky I Goncearenco A Klar A Levy J Anikster Y Kelleher SL Assaraf YG 《The Journal of biological chemistry》2012,287(35):29348-29361
Zinc is an essential mineral, and infants are particularly vulnerable to zinc deficiency as they require large amounts of zinc for their normal growth and development. We have recently described the first loss-of-function mutation (H54R) in the zinc transporter ZnT-2 (SLC30A2) in mothers with infants harboring transient neonatal zinc deficiency (TNZD). Here we identified and characterized a novel heterozygous G87R ZnT-2 mutation in two unrelated Ashkenazi Jewish mothers with infants displaying TNZD. Transient transfection of G87R ZnT-2 resulted in endoplasmic reticulum-Golgi retention, whereas the WT transporter properly localized to intracellular secretory vesicles in HC11 and MCF-7 cells. Consequently, G87R ZnT-2 showed decreased stability compared with WT ZnT-2 as revealed by Western blot analysis. Three-dimensional homology modeling based on the crystal structure of YiiP, a close zinc transporter homologue from Escherichia coli, revealed that the basic arginine residue of the mutant G87R points toward the membrane lipid core, suggesting misfolding and possible loss-of-function. Indeed, functional assays including vesicular zinc accumulation, zinc secretion, and cytoplasmic zinc pool assessment revealed markedly impaired zinc transport in G87R ZnT-2 transfectants. Moreover, co-transfection experiments with both mutant and WT transporters revealed a dominant negative effect of G87R ZnT-2 over the WT ZnT-2; this was associated with mislocalization, decreased stability, and loss of zinc transport activity of the WT ZnT-2 due to homodimerization observed upon immunoprecipitation experiments. These findings establish that inactivating ZnT-2 mutations are an underlying basis of TNZD and provide the first evidence for the dominant inheritance of heterozygous ZnT-2 mutations via negative dominance due to homodimer formation. 相似文献
32.
Culicoides oxystoma (Diptera: Ceratopogonidae) is an important vector species, reported mainly from Asia, with high potential to transmit viral diseases affecting livestock. In Japan, many arboviruses have been isolated from C. oxystoma, suggesting it as a key player in the epidemiology of several Culicoides-borne diseases. Over the years, C. oxystoma has also been reported in the Middle East region, including Israel. In this region, however, C. oxystoma cannot be easily distinguished morphologically from its sibling species included in the Culicoides schultzei complex. We therefore used genomic data for species identification and phylogeny resolution. Phylogenetic analyses based on internal transcribed spacer 1 (ITS-1) of ribosomal DNA and the mitochondrial gene encoding cytochrome oxidase subunit I (COI) showed that C. oxystoma from Israel is closely related to C. oxystoma from Japan. Using differential probing PCR, we showed that C. oxystoma is distributed all over the country, especially in Mediterranean climate regions. Culicoides oxystoma is less common or even absent in arid regions, while the other genetic cluster of C. schultzei complex was found only in the east of the country (mostly arid and semiarid regions). The molecular finding of C. oxystoma in wide geographical regions, together with its high proportion in the general Culicoides population and its vectoring potential, imply that it may be an important vector species in the Middle East. 相似文献
33.
Nesher M Vachutinsky Y Fridkin G Schwarz Y Sasson K Fridkin M Shechter Y Lichtstein D 《Bioconjugate chemistry》2008,19(1):342-348
Natriuretic peptides (NP), including atrial natriuretic peptide (ANP), induce potent natriuresis and vasodilation and thereby generate hypotension in vivo. Despite intensive efforts, clinical application of NP as an antihypertensive agent is limited because of their short biological half-life and poor bioavailability. Recently, we have developed a strategy that facilitates slow release of peptides from PEG-peptide inactive conjugates, based on reversible pegylation. Peptides prepared by this approach undergo slow, spontaneous chemical hydrolysis at physiological conditions, releasing the native active peptide/protein drug from the inactive conjugates over prolonged periods. A PEG chain of 30 kDa was linked covalently to the alpha-amino side chain of the hormone via a MAL-Fmoc-NHS spacer, yielding PEG 30-Fmoc-ANP, a prodrug that releases the native hormone upon incubation at physiological conditions. Bolus administration of native ANP to Wistar rats receiving adrenaline yields a short, transitory effect in lowering blood pressure (BP), reaching a maximum at 2 min, and then returning to control values after 12 to 25 min. In contrast, administration of PEG 30-Fmoc-ANP lowered BP following a lag period of 50 min, and maintained low BP for a period exceeding 60 min. Saline or PEG 30-Fmoc-Alanine were not effective in lowering BP in Wistar rats. These results show that the novel compound, PEG 30-Fmoc-ANP, is a reversible pegylated prodrug derivative that facilitates a prolonged BP lowering effect in rats and may be considered as a candidate for development into an antihypertensive drug. 相似文献
34.
Sherman E Itkin A Kuttner YY Rhoades E Amir D Haas E Haran G 《Biophysical journal》2008,94(12):4819-4827
Fluorescence correlation spectroscopy (FCS) is a sensitive analytical tool that allows dynamics and hydrodynamics of biomolecules to be studied under a broad range of experimental conditions. One application of FCS of current interest is the determination of the size of protein molecules in the various states they sample along their folding reaction coordinate, which can be accessed through the measurement of diffusion coefficients. It has been pointed out that the analysis of FCS curves is prone to artifacts that may lead to erroneous size determination. To set the stage for FCS studies of unfolded proteins, we first show that the diffusion coefficients of small molecules as well as proteins can be determined accurately even in the presence of high concentrations of co-solutes that change the solution refractive index significantly. Indeed, it is found that the Stokes-Einstein relation between the measured diffusion coefficient and solution viscosity holds even in highly concentrated glycerol or guanidinium hydrochloride (GuHCl) solutions. These measurements form the basis for an investigation of the structure of the denatured state of two proteins, the small protein L and the larger, three-domain protein adenylate kinase (AK). FCS is found useful for probing expansion in the denatured state beyond the unfolding transition. It is shown that the denatured state of protein L expands as the denaturant concentration increases, in a process akin to the transition from a globule to a coil in polymers. This process continues at least up to 5 M GuHCl. On the other hand, the denatured state of AK does not seem to expand much beyond 2 M GuHCl, a result that is in qualitative accord with single-molecule fluorescence histograms. Because both the unfolding transition and the coil-globule transition of AK occur at a much lower denaturant concentration than those of protein L, a possible correlation between the two phenomena is suggested. 相似文献
35.
Accelerated Biodegradation of Cement by Sulfur-Oxidizing Bacteria as a Bioassay for Evaluating Immobilization of Low-Level Radioactive Waste 总被引:2,自引:0,他引:2 下载免费PDF全文
Disposal of low-level radioactive waste by immobilization in cement is being evaluated worldwide. The stability of cement in the environment may be impaired by sulfur-oxidizing bacteria that corrode the cement by producing sulfuric acid. Since this process is so slow that it is not possible to perform studies of the degradation kinetics and to test cement mixtures with increased durability, procedures that accelerate the biodegradation are required. Semicontinuous cultures of Halothiobacillus neapolitanus and Thiomonas intermedia containing thiosulfate as the sole energy source were employed to accelerate the biodegradation of cement samples. This resulted in a weight loss of up to 16% after 39 days, compared with a weight loss of 0.8% in noninoculated controls. Scanning electron microscopy of the degraded cement samples revealed deep cracks, which could be associated with the formation of low-density corrosion products in the interior of the cement. Accelerated biodegradation was also evident from the leaching rates of Ca2+ and Si2+, the major constituents of the cement matrix, and Ca exhibited the highest rate (up to 20 times greater than the control rate) due to the reaction between free lime and the biogenic sulfuric acid. Leaching of Sr2+ and Cs+, which were added to the cement to simulate immobilization of the corresponding radioisotopes, was also monitored. In contrast to the linear leaching kinetics of calcium, silicon, and strontium, the leaching pattern of cesium produced a saturation curve similar to the control curve. Presumably, the leaching of cesium is governed by the diffusion process, whereas the leaching kinetics of the other three ions seems to governed by dissolution of the cement. 相似文献
36.
By comparing versions of mental illness narratives – told by Haredi (Utraorthodox Jews) male patients of a mental health clinic in Israel and by their rabbis – this paper relates to two distinct, yet interrelated, theoretical questions: the place and agency of narrators, and the tension between experience and representation. A pair of narratives exemplifies a pattern in which the patients (Talmudic students) tell a narrative of a sudden breakdown related to a dramatic meeting with a non-human figure (often, a woman) or force. Their rabbis, by contrast, tell a narrative that emphasizes their students' mundane symptoms, ``abnormal' and ``immoral' behavior, and use a local adaptation of a Western psychological explanatory model. A dynamic of inclusion and exclusion emerges as students are seeking legitimization and avoidance of stigma, while their rabbis are silencing themes that challenge social and cultural orders. The different narratives are further interpreted in the context of the micropolitics of the interviews and of identity politics between the Haredim and secular Israelis. This social dynamics shows how differently placed social actors-narrators-interpreters construct differently contested and diverse cultural narratives of a seemingly shared reality. 相似文献
37.
Increasing anthropogenic pCO2 alters seawater chemistry, with potentially severe consequences for coral reef growth and health. Octocorals are the second most important faunistic component in many reefs, often occupying 50% or more of the available substrate. Three species of octocorals from two families were studied in Eilat (Gulf of Aqaba), comprising the zooxanthellate Ovabunda macrospiculata and Heteroxenia fuscescens (family Xeniidae), and Sarcophyton sp. (family Alcyoniidae). They were maintained under normal (8.2) and reduced (7.6 and 7.3) pH conditions for up to 5 months. Their biolological features, including protein concentration, polyp weight, density of zooxanthellae, and their chlorophyll concentration per cell, as well as polyp pulsation rate, were examined under conditions more acidic than normal, in order to test the hypothesis that rising pCO2 would affect octocorals. The results indicate no statistically significant difference between the octocorals exposed to reduced pH values compared to the control. It is therefore suggested that the octocorals' tissue may act as a protective barrier against adverse pH conditions, thus maintaining them unharmed at high levels of pCO2. 相似文献
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40.
Daniel Krekeler Pavel Sigalevich A. Teske H. Cypionka Yehuda Cohen 《Archives of microbiology》1997,167(6):369-375
In an investigation on the oxygen tolerance of sulfate-reducing bacteria, a strain was isolated from a 107-fold dilution of the upper 3-mm layer of a hypersaline cyanobacterial mat (transferred from Solar Lake, Sinai). The isolate,
designated P1B, appeared to be well-adapted to the varying concentrations of oxygen and sulfide that occur in this environment.
In the presence of oxygen strain P1B respired aerobically with the highest rates [260 nmol O2 min–1 (mg protein)–1] found so far among marine sulfate-reducing bacteria. Besides H2 and lactate, even sulfide or sulfite could be oxidized with oxygen. The sulfur compounds were completely oxidized to sulfate.
Under anoxic conditions, it grew with sulfate, sulfite, or thiosulfate as the electron acceptor using H2, lactate, pyruvate, ethanol, propanol, or butanol as the electron donor. Furthermore, in the absence of electron donors the
isolate grew by disproportionation of sulfite or thiosulfate to sulfate and sulfide. The highest respiration rates with oxygen
were obtained with H2 at low oxygen concentrations. Aerobic growth of homogeneous suspensions was not obtained. Additions of 1% oxygen to the gas
phase of a continuous culture resulted in the formation of cell clumps wherein the cells remained viable for at least 200
h. It is concluded that strain P1B is oxygen-tolerant but does not carry out sulfate reduction in the presence of oxygen under
the conditions tested. Analysis of the 16S rDNA sequence indicated that strain P1B belongs to the genus Desulfovibrio, with Desulfovibrio halophilus as its closest relative. Based on physiological properties strain P1B could not be assigned to this species. Therefore, a
new species, Desulfovibrio oxyclinae, is proposed.
Received: 7 August 1996 / Accepted: 29 January 1997 相似文献