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781.
782.
Rachel Yamin Noa S. Kaynan Ariella Glasner Alon Vitenshtein Pinchas Tsukerman Yoav Bauman Yael Ophir Shlomo Elias Yotam Bar-On Chamutal Gur Ofer Mandelboim 《PLoS pathogens》2013,9(8)
Natural killer (NK) cells are innate immune cells able to rapidly kill virus-infected and tumor cells. Two NK cell populations are found in the blood; the majority (90%) expresses the CD16 receptor and also express the CD56 protein in intermediate levels (CD56Dim CD16Pos) while the remaining 10% are CD16 negative and express CD56 in high levels (CD56Bright CD16Neg). NK cells also reside in some tissues and traffic to various infected organs through the usage of different chemokines and chemokine receptors. Kaposi''s sarcoma-associated herpesvirus (KSHV) is a human virus that has developed numerous sophisticated and versatile strategies to escape the attack of immune cells such as NK cells. Here, we investigate whether the KSHV derived cytokine (vIL-6) and chemokines (vMIP-I, vMIP-II, vMIP-III) affect NK cell activity. Using transwell migration assays, KSHV infected cells, as well as fusion and recombinant proteins, we show that out of the four cytokine/chemokines encoded by KSHV, vMIP-II is the only one that binds to the majority of NK cells, affecting their migration. We demonstrate that vMIP-II binds to two different receptors, CX3CR1 and CCR5, expressed by naïve CD56Dim CD16Pos NK cells and activated NK cells, respectively. Furthermore, we show that the binding of vMIP-II to CX3CR1 and CCR5 blocks the binding of the natural ligands of these receptors, Fractalkine (Fck) and RANTES, respectively. Finally, we show that vMIP-II inhibits the migration of naïve and activated NK cells towards Fck and RANTES. Thus, we present here a novel mechanism in which KSHV uses a unique protein that antagonizes the activity of two distinct chemokine receptors to inhibit the migration of naïve and activated NK cells. 相似文献
783.
Awareness of the problem of antimicrobial resistance (AMR) has escalated and drug-resistant infections are named among the most urgent problems facing clinicians today. Our experiments here identify a transporter interactome and portray its essential function in acquisition of antimicrobial resistance. By exposing E. coli cells to consecutive increasing concentrations of the fluoroquinolone norfloxacin we generated in the laboratory highly resistant strains that carry multiple mutations, most of them identical to those identified in clinical isolates. With this experimental paradigm, we show that the MDTs function in a coordinated mode to provide an essential first-line defense mechanism, preventing the drug reaching lethal concentrations, until a number of stable efficient alterations occur that allow survival. Single-component efflux transporters remove the toxic compounds from the cytoplasm to the periplasmic space where TolC-dependent transporters expel them from the cell. We postulate a close interaction between the two types of transporters to prevent rapid leak of the hydrophobic substrates back into the cell. The findings change the prevalent concept that in Gram-negative bacteria a single multidrug transporter, AcrAB-TolC type, is responsible for the resistance. The concept of a functional interactome, the process of identification of its members, the elucidation of the nature of the interactions and its role in cell physiology will change the existing paradigms in the field. We anticipate that our work will have an impact on the present strategy searching for inhibitors of AcrAB-TolC as adjuvants of existing antibiotics and provide novel targets for this urgent undertaking. 相似文献
784.
Avraham Zeharia Avraham Shaag Orit Pappo Ann Saada Olga Karicheva Noa Ofek Daphna Marom Ivan Tarassov 《American journal of human genetics》2009,85(3):401-407
Acute liver failure in infancy accompanied by lactic acidemia was previously shown to result from mtDNA depletion. We report on 13 unrelated infants who presented with acute liver failure and lactic acidemia with normal mtDNA content. Four died during the acute episodes, and the survivors never had a recurrence. The longest follow-up period was 14 years. Using homozygosity mapping, we identified mutations in the TRMU gene, which encodes a mitochondria-specific tRNA-modifying enzyme, tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase. Accordingly, the 2-thiouridylation levels of the mitochondrial tRNAs were markedly reduced. Given that sulfur is a TRMU substrate and its availability is limited during the neonatal period, we propose that there is a window of time whereby patients with TRMU mutations are at increased risk of developing liver failure. 相似文献
785.
The effect of angiotensin II on myosin heavy chain expression in cultured myocardial cells 总被引:1,自引:0,他引:1
Noa Shalitin Menahem Friedman Hadassa Schlesinger Yael Barhum Maurice J. Levy Wolfgang Schaper Gania Kessler-Icekson 《In vitro cellular & developmental biology. Animal》1996,32(9):573-578
Summary Angiotensin II (AII), the principal mediator of the renin-angiotensin system, is an important regulator of vascular and cardiac
homeostasis. AII has also been shown to be a regulator of cardiac hypertrophy and of the corresponding changes in amount and
composition of certain tissue proteins. We examined the trophic effects of AII on cultured myocytes derived from neonatal
rat ventricles and followed, by Northern blot analysis and polyacrylamide gel electrophoresis, the expression of α- and β-myosin
heavy chain iso-mRNAs and isoproteins. Our findings show that a single administration of AII is sufficient to induce a trophic
response in cultured beating myocytes and to enhance the expression of β-myosin heavy chain iso-mRNA and isoprotein, having
no effect on α-myosin heavy chain. Induction of α-myosin heavy chain expression by thyroid hormone before AII was administered
showed that AII could not potentiate a shift from α- to β-myosin heavy chain predominance. We suggest that the potency of
AII to regulate the expression of myosin heavy chain isogenes is restricted to the β isoform and is overridden by thyroid
hormone. 相似文献
786.
Yael Grunwald Noa Wigoda Nir Sade Adi Yaaran Tanmayee Torne Sanbon Chaka Gosa Nava Moran Menachem Moshelion 《The Plant journal : for cell and molecular biology》2021,106(2):301-313
The leaf vascular bundle sheath cells (BSCs) that tightly envelop the leaf veins, are a selective and dynamic barrier to xylem sap water and solutes radially entering the mesophyll cells. Under normal conditions, xylem sap pH below 6 is presumably important for driving and regulating the transmembranal solute transport. Having discovered recently a differentially high expression of a BSC proton pump, AHA2, we now test the hypothesis that it regulates the xylem sap pH and leaf radial water fluxes. We monitored the xylem sap pH in the veins of detached leaves of wild-type Arabidopsis, AHA mutants and aha2 mutants complemented with AHA2 gene solely in BSCs. We tested an AHA inhibitor (vanadate) and stimulator (fusicoccin), and different pH buffers. We monitored their impact on the xylem sap pH and the leaf hydraulic conductance (Kleaf), and the effect of pH on the water osmotic permeability (Pf) of isolated BSCs protoplasts. We found that AHA2 is necessary for xylem sap acidification, and in turn, for elevating Kleaf. Conversely, AHA2 knockdown, which alkalinized the xylem sap, or, buffering its pH to 7.5, reduced Kleaf, and elevating external pH to 7.5 decreased the BSCs Pf. All these showed a causative link between AHA2 activity in BSCs and leaf radial hydraulic water conductance. 相似文献
787.
Elizabeth A. Hobson Matthew J. Silk Nina H. Fefferman Daniel B. Larremore Puck Rombach Saray Shai Noa Pinter-Wollman 《Biological reviews of the Cambridge Philosophical Society》2021,96(6):2716-2734
Analysing social networks is challenging. Key features of relational data require the use of non-standard statistical methods such as developing system-specific null, or reference, models that randomize one or more components of the observed data. Here we review a variety of randomization procedures that generate reference models for social network analysis. Reference models provide an expectation for hypothesis testing when analysing network data. We outline the key stages in producing an effective reference model and detail four approaches for generating reference distributions: permutation, resampling, sampling from a distribution, and generative models. We highlight when each type of approach would be appropriate and note potential pitfalls for researchers to avoid. Throughout, we illustrate our points with examples from a simulated social system. Our aim is to provide social network researchers with a deeper understanding of analytical approaches to enhance their confidence when tailoring reference models to specific research questions. 相似文献
788.
Noa Betzalel Paul Ben Ishai Sharon Einav Yuri Feldman 《Journal of biophotonics》2021,14(7):e202100027
The helical nature of human sweat ducts, combined with the morphological and dielectric properties of skin, suggests electromagnetic activity in the sub-THz frequency band. A detailed electromagnetic simulation model of the skin, with embedded sweat ducts, was created. The model includes realistic dielectric properties based on the measured water content of each layer of skin, derived from Raman Spectroscopy. The model was verified by comparing it to measurements of the reflection coefficient of the palms of 13 volunteers in the frequency band 350–410 GHz. They were subjected to a measurement protocol intended to induce mental stress, thereby also activating the sweat glands. The Galvanic Skin Response was concurrently measured. Using the simulation model the optimal ac-conductivity for each measurement was found. The range of variation for all subjects was found to be from 100 S/m to a maximum value of 6000 S/m with averages of 1000 S/m. These are one order of magnitude increase from the accepted values for water at these frequencies (~100 s/m at 100 GHz). Considering the known biochemical mechanism for inducing perspiration, we conclude that these ac-conductivity levels are probably valid, even though the real time measurements of sweat ac-conductivity levels inside the duct are inaccessible. 相似文献
789.
790.