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91.
The degree of microviscosity,
gh, (fluidity/rigidity behavior) of membrane lipids of normal and transformed mammalian fibroblasts obtained from mice, hamsters and rats was quantitatively monitored by fluorescence polarization, P, analysis of the fluorescent probe 1,6-diphenyl 1,3,5-hexatriene (DPH) when embedded in lipid regions of cellular membranes of intact viable cells. Analysis of membrane microviscosity of six different cell populations and of individual cells in each cell population have indicated that the membrane microviscosity of all cell types, both normal and transformed fibroblasts, changes as a function of the cell density in the growing cultures. The membrane microviscosity was found to be low (high lipid fluidity) in sparse conditions but high (high lipid rigidity) in dense conditions. The induced changes in membrane microviscosity are practically reversible for all cell types and a complete reversion can be obtained within a few hours after changing the cell density conditions from sparse to dense and vice versa.Comparative studies with normal and transformed fibroblasts have shown that transformed fibroblasts have a more rigid lipid layer in their cellular membranes than normal or untransformed fibroblasts. The difference in membrane microviscosity between transformed and normal fibroblasts is higher in confluent conditions as compared with subconfluent cultures. These differences in the degree of fluidity of membrane lipids that are controlled by possible differences in the cellto-cell contact in normal and transformed fibroblasts may play a major role in determining the growth behavior of normal and malignant cells that are growing as a solid tissue and may have a direct effect on the control mechanisms that determine the presence or absence of the “density dependent inhibition” of growth. 相似文献
92.
Gabriel J. Rocklin Sarah E. Boyce Marcus Fischer Inbar Fish David L. Mobley Brian K. Shoichet Ken A. Dill 《Journal of molecular biology》2013
Predicting absolute protein–ligand binding affinities remains a frontier challenge in ligand discovery and design. This becomes more difficult when ionic interactions are involved because of the large opposing solvation and electrostatic attraction energies. In a blind test, we examined whether alchemical free-energy calculations could predict binding affinities of 14 charged and 5 neutral compounds previously untested as ligands for a cavity binding site in cytochrome c peroxidase. In this simplified site, polar and cationic ligands compete with solvent to interact with a buried aspartate. Predictions were tested by calorimetry, spectroscopy, and crystallography. Of the 15 compounds predicted to bind, 13 were experimentally confirmed, while 4 compounds were false negative predictions. Predictions had a root-mean-square error of 1.95 kcal/mol to the experimental affinities, and predicted poses had an average RMSD of 1.7 Å to the crystallographic poses. This test serves as a benchmark for these thermodynamically rigorous calculations at predicting binding affinities for charged compounds and gives insights into the existing sources of error, which are primarily electrostatic interactions inside proteins. Our experiments also provide a useful set of ionic binding affinities in a simplified system for testing new affinity prediction methods. 相似文献
93.
This study focuses on the regulation of synchronization between the life cycle of the oligophagous whitefly, Trialeurodes lauri (Signoret), and its evergreen host tree Arbutus andrachne in Mediterranean chaparral. Whitefly infestations vary considerably among trees. The adults of the univoltine (one generation per year) whitefly emerge en masse during April and May and oviposit on the new spring foliage. Following approximately one month of development to the early fourth instar, the nymphs enter nine-month diapauses, terminating in February. This diapause is induced and maintained by the plant and can be experimentally avoided (in the case of developing young nymphs) or terminated (in the case of diapausing fourth instars), if whitefly-bearing branches are severed from the tree and placed in water under laboratory conditions. This study is the first report of a whitefly diapausing through both summer and winter seasons. The role of the host plant in the process is discussed. 相似文献
94.
Chitlaru T Zaide G Ehrlich S Inbar I Cohen O Shafferman A 《Molecular microbiology》2011,81(6):1542-1559
We demonstrate that disruption of the htrA (high temperature requirement A) gene in either the virulent Bacillus anthracis Vollum (pXO1(+) , pXO2(+) ), or in the ΔVollum (pXO1(-), pXO2(-), nontoxinogenic and noncapsular) strains, affect significantly the ability of the resulting mutants to withstand heat, oxidative, ethanol and osmotic stress. The ΔhtrA mutants manifest altered secretion of several proteins, as well as complete silencing of the abundant extracellular starvation-associated neutral protease A (NprA). VollumΔhtrA bacteria exhibit delayed proliferation in a macrophage infection assay, and despite their ability to synthesize the major B. anthracis toxins LT (lethal toxin) and ET (oedema toxin) as well as the capsule, show a decrease of over six orders of magnitude in virulence (lethal dose 50% = 3 × 10(8) spores, in the guinea pig model of anthrax), as compared with the parental wild-type strain. This unprecedented extent of loss of virulence in B. anthracis, as a consequence of deletion of a single gene, as well as all other phenotypic defects associated with htrA mutation, are restored in their corresponding trans-complemented strains. It is suggested that the loss of virulence is due to increased susceptibility of the ΔhtrA bacteria to stress insults encountered in the host. On a practical note, it is demonstrated that the attenuated Vollum ΔhtrA is highly efficacious in protecting guinea pigs against a lethal anthrax challenge. 相似文献
95.
Ido Keren Ayenachew Bezawork-Geleta Max Kolton Inbar Maayan Eduard Belausov Maggie Levy Anahit Mett David Gidoni Felix Shaya Oren Ostersetzer-Biran 《RNA (New York, N.Y.)》2009,15(12):2299-2311
Mitochondria (mt) in plants house about 20 group-II introns, which lie within protein-coding genes required in both organellar genome expression and respiration activities. While in nonplant systems the splicing of group-II introns is mediated by proteins encoded within the introns themselves (known as “maturases”), only a single maturase ORF (matR) has retained in the mitochondrial genomes in plants; however, its putative role(s) in the splicing of organellar introns is yet to be established. Clues to other proteins are scarce, but these are likely encoded within the nucleus as there are no obvious candidates among the remaining ORFs within the mtDNA. Intriguingly, higher plants genomes contain four maturase-related genes, which exist in the nucleus as self-standing ORFs, out of the context of their evolutionary-related group-II introns “hosts.” These are all predicted to reside within mitochondria and may therefore act “in-trans” in the splicing of organellar-encoded introns. Here, we analyzed the intracellular locations of the four nuclear-encoded maturases in Arabidopsis and established the roles of one of these genes, At5g46920 (AtnMat2), in the splicing of several mitochondrial introns, including the single intron within cox2, nad1 intron2, and nad7 intron2. 相似文献
96.
Noam Nissan Talia Golan Edna Furman-Haran Sara Apter Yael Inbar Arie Ariche Barak Bar-Zakay Yuri Goldes Michael Schvimer Dov Grobgeld Hadassa Degani 《PloS one》2014,9(12)
Purpose
To develop a diffusion-tensor-imaging (DTI) protocol that is sensitive to the complex diffusion and perfusion properties of the healthy and malignant pancreas tissues.Materials and Methods
Twenty-eight healthy volunteers and nine patients with pancreatic-ductal-adenocacinoma (PDAC), were scanned at 3T with T2-weighted and DTI sequences. Healthy volunteers were also scanned with multi-b diffusion-weighted-imaging (DWI), whereas a standard clinical protocol complemented the PDAC patients’ scans. Image processing at pixel resolution yielded parametric maps of three directional diffusion coefficients λ1, λ2, λ3, apparent diffusion coefficient (ADC), and fractional anisotropy (FA), as well as a λ1-vector map, and a main diffusion-direction map.Results
DTI measurements of healthy pancreatic tissue at b-values 0,500 s/mm2yielded: λ1 = (2.65±0.35)×10−3, λ2 = (1.87±0.22)×10−3, λ3 = (1.20±0.18)×10−3, ADC = (1.91±0.22)×10−3 (all in mm2/s units) and FA = 0.38±0.06. Using b-values of 100,500 s/mm2 led to a significant reduction in λ1, λ2, λ3 and ADC (p<.0001) and a significant increase (p<0.0001) in FA. The reduction in the diffusion coefficients suggested a contribution of a fast intra-voxel-incoherent-motion (IVIM) component at b≤100 s/mm2, which was confirmed by the multi-b DWI results. In PDACs, λ1, λ2, λ3 and ADC in both 0,500 s/mm2 and 100,500 s/mm2 b-values sets, as well as the reduction in these diffusion coefficients between the two sets, were significantly lower in comparison to the distal normal pancreatic tissue, suggesting higher cellularity and diminution of the fast-IVIM component in the cancer tissue.Conclusion
DTI using two reference b-values 0 and 100 s/mm2 enabled characterization of the water diffusion and anisotropy of the healthy pancreas, taking into account a contribution of IVIM. The reduction in the diffusion coefficients of PDAC, as compared to normal pancreatic tissue, and the smaller change in these coefficients in PDAC when the reference b-value was modified from 0 to 100 s/mm2, helped identifying the presence of malignancy. 相似文献97.
Marianne Strazza Inbar Azoulay-Alfaguter Ariel Pedoeem Adam Mor 《Journal of visualized experiments : JoVE》2014,(88)
T lymphocyte adhesion is required for multiple T cell functions, including migration to sites of inflammation and formation of immunological synapses with antigen presenting cells. T cells accomplish regulated adhesion by controlling the adhesive properties of integrins, a class of cell adhesion molecules consisting of heterodimeric pairs of transmembrane proteins that interact with target molecules on partner cells or extracellular matrix. The most prominent T cell integrin is lymphocyte function associated antigen (LFA)-1, composed of subunits αL and β2, whose target is the intracellular adhesion molecule (ICAM)-1. The ability of a T cell to control adhesion derives from the ability to regulate the affinity states of individual integrins. Inside-out signaling describes the process whereby signals inside a cell cause the external domains of integrins to assume an activated state. Much of our knowledge of these complex phenomena is based on mechanistic studies performed in simplified in vitro model systems. The T lymphocyte adhesion assay described here is an excellent tool that allows T cells to adhere to target molecules, under static conditions, and then utilizes a fluorescent plate reader to quantify adhesiveness. This assay has been useful in defining adhesion-stimulatory or inhibitory substances that act on lymphocytes, as well as characterizing the signaling events involved. Although described here for LFA-1 - ICAM-1 mediated adhesion; this assay can be readily adapted to allow for the study of other adhesive interactions (e.g. VLA-4 - fibronectin). 相似文献
98.
Ben-Nun IF Montague SC Houck ML Tran HT Garitaonandia I Leonardo TR Wang YC Charter SJ Laurent LC Ryder OA Loring JF 《Nature methods》2011,8(10):829-831
For some highly endangered species there are too few reproductively capable animals to maintain adequate genetic diversity, and extraordinary measures are necessary to prevent extinction. We report generation of induced pluripotent stem cells (iPSCs) from two endangered species: a primate, the drill, Mandrillus leucophaeus and the nearly extinct northern white rhinoceros, Ceratotherium simum cottoni. iPSCs may eventually facilitate reintroduction of genetic material into breeding populations. 相似文献
99.
Cohen-Gihon I Fong JH Sharan R Nussinov R Przytycka TM Panchenko AR 《Molecular bioSystems》2011,7(3):784-792
Most eukaryotic proteins are composed of two or more domains. These assemble in a modular manner to create new proteins usually by the acquisition of one or more domains to an existing protein. Promiscuous domains which are found embedded in a variety of proteins and co-exist with many other domains are of particular interest and were shown to have roles in signaling pathways and mediating network communication. The evolution of domain promiscuity is still an open problem, mostly due to the lack of sequenced ancestral genomes. Here we use inferred domain architectures of ancestral genomes to trace the evolution of domain promiscuity in eukaryotic genomes. We find an increase in average promiscuity along many branches of the eukaryotic tree. Moreover, domain promiscuity can proceed at almost a steady rate over long evolutionary time or exhibit lineage-specific acceleration. We also observe that many signaling and regulatory domains gained domain promiscuity around the Bilateria divergence. In addition we show that those domains that played a role in the creation of two body axes and existed before the divergence of the bilaterians from fungi/metazoan achieve a boost in their promiscuities during the bilaterian evolution. 相似文献
100.
Mammalian herbivores induce changes in the chemical composition, phenology, distribution, and abundance of the plants they feed on. Consequently, invertebrate herbivores (predominantly insects) that depend on those plants, and the predators and parasitoids that are associated with them, may be affected. This plant-mediated indirect interaction between mammals and invertebrates has been extensively studied, but mammalian herbivores may also directly affect plant-dwelling invertebrates (PDI) by incidentally ingesting them while feeding. The ubiquity and small size of PDI render them highly susceptible to incidental ingestion, but as common as this interaction may intuitively seem, very little is known about its prevalence and ecological consequences. Nevertheless, cases of incidental ingestion of PDI and associated adaptations for avoiding it that have been sporadically documented in several invertebrate groups and life stages allow us to carefully extrapolate and conclude that it should be common in nature. Incidental ingestion may, therefore, bear significant consequences for PDI, but it may also affect the mammalian herbivores and the shared plants. Future research on incidental ingestion of PDI would have to overcome several technical difficulties to gain better insight into this understudied ecological interaction. 相似文献