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51.
Hagar Gelbard-Sagiv Efrat Magidov Haggai Sharon Talma Hendler Yuval Nir 《Current biology : CB》2018,28(14):2239-2249.e6
52.
Effects of Combined Water Potential and Temperature Stresses on Cryptosporidium parvum Oocysts 总被引:1,自引:0,他引:1 下载免费PDF全文
Hosts infected with the parasite Cryptosporidium parvum may excrete oocysts on soils in watersheds that supply public drinking water. Environmental stresses decrease the numbers of oocysts after deposition on soils. However, the rates and effects of combined stresses have not been well characterized, especially for the purposes of estimating decrease in numbers. We subjected oocysts to combined stresses of water potential (−4, −12, and −33 bars), above-freezing temperatures (4 and 30°C), and a subfreezing temperature (−14°C) for 1, 14, and 29 days and one to six freeze-thaw cycles (−14 to 10°C) to estimate coefficients to characterize population degradation using multiplicative error and exponential decay models. The experiments were carried out in NaCl solutions with water potentials of −4, −12, and −33 bars, in combination with temperature stresses at levels that could be expected in natural soils. Increased water potential increased the rate of population degradation for all temperature conditions investigated. Enhanced degradation leads to estimated rates of population degradation that are greater than those that have been reported and used in previous studies conducted to assess risk of water supply contamination from sources of C. parvum. 相似文献
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54.
Grim JE Knoblaugh SE Guthrie KA Hagar A Swanger J Hespelt J Delrow JJ Small T Grady WM Nakayama KI Clurman BE 《Molecular and cellular biology》2012,32(11):2160-2167
Colorectal cancer (CRC) remains a major cause of cancer mortality worldwide. Murine models have yielded critical insights into CRC pathogenesis, but they often fail to recapitulate advanced-disease phenotypes, notably metastasis and chromosomal instability (CIN). New models are thus needed to understand disease progression and to develop therapies. We sought to model advanced CRC by inactivating two tumor suppressors that are mutated in human CRCs, the Fbw7 ubiquitin ligase and p53. Here we report that Fbw7 deletion alters differentiation and proliferation in the gut epithelium and stabilizes oncogenic Fbw7 substrates, such as cyclin E and Myc. However, Fbw7 deletion does not cause tumorigenesis in the gut. In contrast, codeletion of both Fbw7 and p53 causes highly penetrant, aggressive, and metastatic adenocarcinomas, and allografts derived from these tumors form highly malignant adenocarcinomas. In vitro evidence indicates that Fbw7 ablation promotes genetic instability that is suppressed by p53, and we show that most Fbw7−/−; p53−/− carcinomas exhibit a CIN+ phenotype. We conclude that Fbw7 and p53 synergistically suppress adenocarcinomas that mimic advanced human CRC with respect to histopathology, metastasis, and CIN. This model thus represents a novel tool for studies of advanced CRC as well as carcinogenesis associated with ubiquitin pathway mutations. 相似文献
55.
Cyanobacteria are globally important primary producers and nitrogen fixers. They are frequently limited by iron bioavailability in natural environments that often fluctuate due to rapid consumption and irregular influx of external Fe. Here we identify a succession of physiological changes in Synechocystis sp. PCC 6803 occurring over 14–16 days of iron deprivation and subsequent recovery. We observe several adaptive strategies that allow cells to push their metabolic limits under the restriction of declining intracellular Fe quotas. Interestingly, cyanobacterial populations exposed to prolonged iron deprivation showed discernible heterogeneity in cellular auto-fluorescence during the recovery process. Using FACS and microscopy techniques we revealed that only cells with high auto-fluorescence were able to grow and reconstitute thylakoid membranes. We propose that ROS-mediated damage is likely to be associated with the emergence of the two subpopulations, and, indeed, a rapid increase in intracellular ROS content was observed during the first hours following iron addition to Fe-starved cultures. These results suggest that an increasing iron supply is a double-edged sword - posing both an opportunity and a risk. Therefore, phenotypic heterogeneity within populations is crucial for the survival and proliferation of organisms facing iron fluctuations within natural environments. 相似文献
56.
Streptozotocin and Alloxan-based Selection Improves Toxin Resistance of Insulin-Producing RINm Cells
Konstantin O. Bloch Romy Zemel Olga V. Bloch Hagar Grief Pnina Vardi 《Experimental diabetes research》2000,1(3):211-219
The aim of our study was to develop a method for
selection of subpopulations of insulin producing
RINm cells with higher resistance to beta cell toxins.
Cells, resistant to streptozotocin (RINmS) and
alloxan (RINmA), were obtained by repeated exposure
of parental RINm cells to these two toxins,
while the defense capacity, was estimated by the
MTT colorimetric method, and [3H]-thymidine incorporation
assay. We found that RINmS and
RINmA displayed higher resistance to both streptozotocin
(STZ) and alloxan (AL) when compared to
the parental RINm cells. In contrast, no differences
in sensitivity to hydrogen peroxide were found
between toxin selected and parental cells. Partial
protection from the toxic effect of STZ and AL was
obtained only in the parental RINm cells after
preincubation of cells with the unmetabolizable 3-
O-methyl-glucose. The possibility that GLUT-2 is
involved in cell sensitivity to toxins was confirmed
by Western blot analysis, which showed higher
expression of GLUT-2 in parental RINm compared
to RINmS and RINmA cells. In addition to the
higher cell defense property evidenced in the
selected cells, we also found higher insulin content
and insulin secretion in both RINmS and RINmA
cells when compared to the parental RINm cells. In
conclusion, STZ and AL treatment can be used for
selection of cell sub-populations with higher cell defense properties and hormone production. The
different GLUT-2 expression in parental and re
sistant cells suggest involvement of GLUT-2 in
mechanisms of cell response to different toxins. 相似文献
57.
Bavat Bornstein Hagar Meltzer Ruth Adler Idan Alyagor Victoria Berkun Gideon Cummings Fabienne Reh Hadas KerenShaul Eyal David Thomas Riemensperger Oren Schuldiner 《The EMBO journal》2021,40(12)
The mechanisms controlling wiring of neuronal networks are not completely understood. The stereotypic architecture of the Drosophila mushroom body (MB) offers a unique system to study circuit assembly. The adult medial MB γ‐lobe is comprised of a long bundle of axons that wire with specific modulatory and output neurons in a tiled manner, defining five distinct zones. We found that the immunoglobulin superfamily protein Dpr12 is cell‐autonomously required in γ‐neurons for their developmental regrowth into the distal γ4/5 zones, where both Dpr12 and its interacting protein, DIP‐δ, are enriched. DIP‐δ functions in a subset of dopaminergic neurons that wire with γ‐neurons within the γ4/5 zone. During metamorphosis, these dopaminergic projections arrive to the γ4/5 zone prior to γ‐axons, suggesting that γ‐axons extend through a prepatterned region. Thus, Dpr12/DIP‐δ transneuronal interaction is required for γ4/5 zone formation. Our study sheds light onto molecular and cellular mechanisms underlying circuit formation within subcellular resolution. 相似文献