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11.
Bloom's syndrome (BS) is a genetic disorder characterized cellularly by increases in sister chromatid exchanges (SCEs) and numbers of micronuclei. BS is caused by mutation in the BLM DNA helicase gene and involves a greatly enhanced risk of developing the range of malignancies seen in the general population. With a mouse model for the disease, we set out to determine the relationship between genomic instability and neoplasia. We used a novel two-step analysis to investigate a panel of eight cell lines developed from mammary tumors that appeared in Blm conditional knockout mice. First, the panel of cell lines was examined for instability. High numbers of SCEs were uniformly seen in members of the panel, and several lines produced chromosomal instability (CIN) manifested by high numbers of chromosomal structural aberrations (CAs) and chromosome missegregation events. Second, to see if Blm mutation was responsible for the CIN, time-dependent analysis was conducted on a tumor line harboring a functional floxed Blm allele. The floxed allele was deleted in vitro, and mutant as well as control subclones were cultured for 100 passages. By passage 100, six of nine mutant subclones had acquired high CIN. Nine mutant subclones produced 50-fold more CAs than did nine control subclones. Finally, chromosome loss preceded the appearance of CIN, suggesting that this loss provides a potential mechanism for the induction of instability in mutant subclones. Such aneuploidy or CIN is a universal feature of neoplasia but has an uncertain function in oncogenesis. Our results show that Blm gene mutation produces this instability, strengthening a role for CIN in the development of human cancer. 相似文献
12.
Shelly Adi‐Harel Shlomit Erlich Eran Schmukler Sarit Cohen‐Kedar Oshik Segev Liat Mizrachy Joel A. Hirsch Ronit Pinkas‐Kramarski 《Journal of cellular biochemistry》2010,110(5):1262-1271
Autophagy, a process of self‐digestion of cellular constituents, regulates the balance between protein synthesis and protein degradation. Beclin 1 represents an important component of the autophagic machinery. It interacts with proteins that positively regulate autophagy, such as Vps34, UVRAG, and Ambra1, as well as with anti‐apoptotic proteins such as Bcl‐2 via its BH3‐like domain to negatively regulate autophagy. Thus, Beclin 1 interactions with several proteins may regulate autophagy. To identify novel Beclin 1 interacting proteins, we utilized a GST‐Beclin 1 fusion protein. Using mass spectroscopic analysis, we identified Beclin 1 as a protein that interacts with GST‐Beclin 1. Further examination by cross linking and co‐immunoprecipitation experiments confirmed that Beclin 1 self‐interacts and that the coiled coil and the N‐terminal region of Beclin 1 contribute to its oligomerization. Importantly, overexpression of vps34, UVRAG, or Bcl‐xL, had no effect on Beclin 1 self‐interaction. Moreover, this self‐interaction was independent of autophagy induction by amino acid deprivation or rapamycin treatment. These results suggest that full‐length Beclin 1 is a stable oligomer under various conditions. Such an oligomer may provide a platform for further protein–protein interactions. J. Cell. Biochem. 110: 1262–1271, 2010. Published 2010 Wiley‐Liss, Inc. 相似文献
13.
Yuval Nash Eran Schmukler Dorit Trudler Ronit Pinkas‐Kramarski Dan Frenkel 《Journal of neurochemistry》2017,143(5):584-594
14.
Melissa Motew Xi Chen Eric G. Booth Stephen R. Carpenter Pavel Pinkas Samuel C. Zipper Steven P. LoheideII Simon D. Donner Kai Tsuruta Peter A. Vadas Christopher J. Kucharik 《Ecosystems》2017,20(8):1468-1482
Decades of fertilizer and manure applications have led to a buildup of phosphorus (P) in agricultural soils and sediments, commonly referred to as legacy P. Legacy P can provide a long-term source of P to surface waters where it causes eutrophication. Using a suite of numerical models, we investigated the influence of legacy P on water quality in the Yahara Watershed of southern Wisconsin, USA. The suite included Agro-IBIS, a terrestrial ecosystem model; THMB, a hydrologic and nutrient routing model; and the Yahara Water Quality Model which estimates water quality indicators in the Yahara chain of lakes. Using five alternative scenarios of antecedent P storage (legacy P) in soils and channels under historical climate conditions, we simulated outcomes of P yield from the landscape, lake P loading, and three lake water quality indicators. Legacy P had a significant effect on lake loads and water quality. Across the five scenarios for Lake Mendota, the largest and most upstream lake, average P yield (kg ha?1) varied by ?41 to +22%, P load (kg y?1) by ?35 to +14%, summer total P (TP) concentration (mg l?1) by ?25 to +12%, Secchi depth (m) by ?7 to +3%, and the probability of hypereutrophy by ?67 to +34%, relative to baseline conditions. The minimum storage scenario showed that a 35% reduction in present-day loads to Lake Mendota corresponded with a 25% reduction in summer TP and smaller reductions in the downstream lakes. Water quality was more vulnerable to heavy rainfall events at higher amounts of P storage and less so at lower amounts. Increases in heavy precipitation are expected with climate change; therefore, water quality could be protected by decreasing P reserves. 相似文献
15.
Pavla Angelisová Ondřej Ballek Jan Sýkora Oldřich Benada Tomáš Čajka Jana Pokorná Dominik Pinkas Václav Hořejší 《生物化学与生物物理学报:生物膜》2019,1861(1):130-141
An emerging alternative to the use of detergents in biochemical studies on membrane proteins is apparently the use styrene-maleic acid (SMA) amphipathic copolymers. These cut the membrane into nanodiscs (SMA-lipid particles, SMALPs), which contain membrane proteins possibly surrounded by their native lipid environment. We examined this approach for studies on several types of T cell membrane proteins, previously defined as raft or non-raft associated, to see whether the properties of the raft derived SMALPs differ from non-raft SMALPs. Our results indicate that two types of raft proteins, GPI-anchored proteins and two Src family kinases, are markedly present in membrane fragments much larger (>250?nm) than those containing non-raft proteins (<20?nm). Lipid probes sensitive to membrane fluidity (membrane order) indicate that the lipid environment in the large SMALPs is less fluid (more ordered) than in the small ones which may indicate the presence of a more ordered lipid Lo phase which is characteristic of membrane rafts. Also the lipid composition of the small vs. large SMALPs is markedly different – the large ones are enriched in cholesterol and lipids containing saturated fatty acids. In addition, we confirm that T cell membrane proteins present in SMALPs can be readily immunoisolated. Our results support the use of SMA as a potentially better (less artifact prone) alternative to detergents for studies on membrane proteins and their complexes, including membrane rafts. 相似文献
16.
The effect of detrital addition on the development of nanoflagellates and bacteria in Lake Kinneret 总被引:1,自引:0,他引:1
Hadas O.; Pinkas R.; Albert-Diez C.; Bloem J.; Cappenberg T.; Berman T. 《Journal of plankton research》1990,12(1):185-199
The effect of adding dissolved substrates derived from algalcells on the patterns of nutrient cycling and growth of bacteria,heterotrophic nanoflagellates (HNAN) and photoautotrophs wasdetermined in samples of near-surface waters from Lake Kinneret.Supplementation of substrates always resulted in an increasedpeak of HNAN numbers and had little effect on bacterial numbers.HNAN-mediated nutrient remineralization of nitrogen and phosphoruswas also stimulated. In light-incubated samples the remineralizednutrients were taken up by photoautotrophic cells. Maximum growthrates observed for HNAN ranged from 0.03 to 0.11 h1,clearance rates for bacteria 1.17.3 nl HNAN1 h1and remineralization rates 6.48.4 µg N mg dry wt1h1 and 0.370.99 µg P mg dry wt1 h1. 相似文献
17.
Einat Zalckvar Hanna Berissi Liat Mizrachy Yulia Idelchuk Itay Koren Miriam Eisenstein Helena Sabanay Ronit Pinkas‐Kramarski Adi Kimchi 《EMBO reports》2009,10(3):285-292
Autophagy, an evolutionarily conserved process, has functions both in cytoprotective and programmed cell death mechanisms. Beclin 1, an essential autophagic protein, was recently identified as a BH3‐domain‐only protein that binds to Bcl‐2 anti‐apoptotic family members. The dissociation of beclin 1 from its Bcl‐2 inhibitors is essential for its autophagic activity, and therefore should be tightly controlled. Here, we show that death‐associated protein kinase (DAPK) regulates this process. The activated form of DAPK triggers autophagy in a beclin‐1‐dependent manner. DAPK phosphorylates beclin 1 on Thr 119 located at a crucial position within its BH3 domain, and thus promotes the dissociation of beclin 1 from Bcl‐XL and the induction of autophagy. These results reveal a substrate for DAPK that acts as one of the core proteins of the autophagic machinery, and they provide a new phosphorylation‐based mechanism that reduces the interaction of beclin 1 with its inhibitors to activate the autophagic machinery. 相似文献
18.
O. Hadas R. Pinkas N. Malinsky-Rushansky G. Shalev-Alon E. Delphine T. Berner 《欧洲藻类学杂志》2013,48(2):259-267
Response of Aphanizomenon ovalisporum to certain environmental parameters was studied to gain a better understanding of the conditions which may have stimulated its autumnal bloom in Lake Kinneret. Optimal temperature for A. ovalisporum growth was 26–30?°C, resulting in growth rates of 0.2–0.3?day?1, similar to those observed in the lake. Maximal rate of CO2 fixation (assimilation numbers of 6–8?μg?C?μg?1?Chl?h?1) was obtained at low irradiances (I k of 40–100?μmol?photons?m?2?s?1), 200?μM Pi and low N:Pi ratios. Growth was strongly affected by phosphorus availability, reaching a maximum at Pi concentrations above 40?μM. The high demand for phosphorus was indicated by an increase in alkaline phosphatase activity. The relative abundance of Pi in the cells increased by 4-fold in Pi-rich compared with Pi-limited cultures. Uptake of Pi was faster in Pi-depleted compared with Pi-sufficient cells. Maximal photosynthetic rates and K1/2(HCO3 ?) were 140–220?μmol?O2?mg?1?Chl?h?1 and 10–24?μM, respectively. At pH 7.0 the K 1/2(CO2) was 2.2 and fell to 0.04?μM at pH 9.0. These data indicated that A. ovalisporum is a HCO3 ? user, and can explain its high photosynthetic rates during the bloom, under high pH and low dissolved CO2 conditions. Na+ concentrations of about 5?mM were essential for A. ovalisporum growth at high pH approaching values in the lake. 相似文献
19.
Thompson LP Aguan K Pinkas G Weiner CP 《American journal of physiology. Regulatory, integrative and comparative physiology》2000,279(5):R1813-R1820
To investigate the effect of chronic hypoxia (HPX) on vasodilation of the fetal heart, we exposed pregnant guinea pigs to room air or 12% O(2) for 4, 7, or 10 days. We excised hearts from anesthetized fetuses (60 +/- 3 days; 65-day gestation = term) and measured changes in both the coronary artery pressure of the isolated constant-flow preparation and endothelial nitric oxide synthase (eNOS) mRNA of fetal ventricles. Dilator responses to cumulative addition (10(-9)-10(-5) M) of acetylcholine and sodium nitroprusside in prostaglandin F(2alpha) (5 x 10(-6) M)-constricted hearts were similar among normoxia (NMX), 4-, 7-, and 10-day HPX (control). Nitro-L-arginine (L-NA, 10(-4)M), a NOS inhibitor, inhibited maximal acetylcholine dilation of hearts exposed to 10-day HPX greater than NMX, 4-, and 7-day HPX. Hypoxia (after 7 and 10 days) increased eNOS mRNA of fetal ventricles compared with NMX and 4-day HPX. 4-Aminopyridine (3 mM), a voltage-dependent K(+)-channel inhibitor, inhibited acetylcholine- but not sodium nitroprusside-induced dilation of NMX and 10-day HPX hearts to a similar magnitude. Glibenclamide (10(-5) M), an ATP-sensitive K(+)-channel inhibitor, had no effect on vasodilation. We conclude that chronic HPX increases the contribution of NO but does not alter K(+)-channel activation in response to acetylcholine-stimulated coronary dilation. Thus increases in NO production via upregulation of eNOS gene expression may be an adaptive response to chronic HPX in the fetal coronary circulation. 相似文献
20.
Ronit Pinkas Dr. Daniel Zamir Dr. Gideon Ladizinsky 《Plant Systematics and Evolution》1985,151(1-2):131-140
The genusLens includes 5 taxonomic species:L. culinaris is cultivated andL. orientalis, L. odemensis, L. ervoides, andL. nigricans are wild. All the species are annual and almost exlusively selfers. The wild lentils are distributed over a large geographical
area and form small disjunct populations which are composed of a small number of plants. 67Lens populations were assayed electrophoretically for 9 enzyme systems; 15 enzymic genes with 37 alleles were identified. The
genetic distances (D) measured between the pairs of populations indicated a significantly greater similarity between populations
belonging to the same taxonomic species. Assuming the populations represent a random sample of the variability in each of
the species the genetic distances (D) between the 5 taxa were calculated. The shortest genetic distance was found betweenL. orientalis andL. culinaris. Another significant feature of the data is the apparent isolation ofL. nigricans from the other 4 species. The genetic distances between theLens species are compared to the patterns of crossability barriers between them. 相似文献