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2.
Rohit Mittal Sew Yeu Peak-Chew Robert S. Sade Yvonne Vallis Harvey T. McMahon 《The Journal of biological chemistry》2010,285(26):19927-19934
Plague, one of the most devastating diseases in human history, is caused by the bacterium Yersinia pestis. The bacteria use a syringe-like macromolecular assembly to secrete various toxins directly into the host cells they infect. One such Yersinia outer protein, YopJ, performs the task of dampening innate immune responses in the host by simultaneously inhibiting the MAPK and NFκB signaling pathways. YopJ catalyzes the transfer of acetyl groups to serine, threonine, and lysine residues on target proteins. Acetylation of serine and threonine residues prevents them from being phosphorylated thereby preventing the activation of signaling molecules on which they are located. In this study, we describe the requirement of a host-cell factor for full activation of the acetyltransferase activity of YopJ and identify this activating factor to be inositol hexakisphosphate (IP6). We extend the applicability of our results to show that IP6 also stimulates the acetyltransferase activity of AvrA, the YopJ homologue from Salmonella typhimurium. Furthermore, an IP6-induced conformational change in AvrA suggests that IP6 acts as an allosteric activator of enzyme activity. Our results suggest that YopJ-family enzymes are quiescent in the bacterium where they are synthesized, because bacteria lack IP6; once injected into mammalian cells by the pathogen these toxins bind host cell IP6, are activated, and deregulate the MAPK and NFκB signaling pathways thereby subverting innate immunity. 相似文献
3.
Aditya Mittal Anandkumar Madhavjibhai Changani Sakshi Taparia 《Journal of biomolecular structure & dynamics》2020,38(15):4579-4583
AbstractNumber of naturally occurring primary sequences of proteins is an infinitesimally small subset of the possible number of primary sequences that can be synthesized using 20 amino acids. Prevailing views ascribe this to slow and incremental mutational/selection evolutionary mechanisms. However, considering the large number of avenues available in form of diversity of emerging/evolving and/or disappearing living systems for exploring the primary sequence space over the evolutionary time scale of ~3.5 billion years, this remains a conjecture. Therefore, to investigate primary sequence space limitations, we carried out a systematic study for finding primary sequences absent in nature. We report the discovery of the smallest peptide sequence “Cysteine-Glutamine-Tryptophan-Tryptophan” that is not found in over half-a-million curated protein sequences in the Uniprot (Swiss-Prot) database. Additionally, we report a library of 83605 pentapeptides that are not found in any of the known protein sequences. Compositional analyses of these absent primary sequences yield a remarkably strong power relationship between the percentage occurrence of individual amino acids in all known protein sequences and their respective frequency of occurrence in the absent peptides, regardless of their specific position in the sequences. If random evolutionary mechanisms were responsible for limitations to the primary sequence space, then one would not expect any relationship between compositions of available and absent primary sequences. Thus, we conclusively show that stoichiometric constraints on amino acids limit the primary sequence space of proteins in nature. We discuss the possibly profound implications of our findings in both evolutionary and synthetic biology.Communicated by Ramaswamy H. Sarma 相似文献
4.
J. Sherrod DeVerse Keith A. Bailey Greg A. Foster Vaishali Mittal Stuart M. Altman Scott I. Simon Anthony G. Passerini 《Journal of visualized experiments : JoVE》2012,(65)
Atherogenesis is potentiated by metabolic abnormalities that contribute to a heightened state of systemic inflammation resulting in endothelial dysfunction. However, early functional changes in endothelium that signify an individual''s level of risk are not directly assessed clinically to help guide therapeutic strategy. Moreover, the regulation of inflammation by local hemodynamics contributes to the non-random spatial distribution of atherosclerosis, but the mechanisms are difficult to delineate in vivo. We describe a lab-on-a-chip based approach to quantitatively assay metabolic perturbation of inflammatory events in human endothelial cells (EC) and monocytes under precise flow conditions. Standard methods of soft lithography are used to microfabricate vascular mimetic microfluidic chambers (VMMC), which are bound directly to cultured EC monolayers.1 These devices have the advantage of using small volumes of reagents while providing a platform for directly imaging the inflammatory events at the membrane of EC exposed to a well-defined shear field. We have successfully applied these devices to investigate cytokine-,2 lipid-3, 4 and RAGE-induced5 inflammation in human aortic EC (HAEC). Here we document the use of the VMMC to assay monocytic cell (THP-1) rolling and arrest on HAEC monolayers that are conditioned under differential shear characteristics and activated by the inflammatory cytokine TNF-α. Studies such as these are providing mechanistic insight into atherosusceptibility under metabolic risk factors. 相似文献
5.
Despite intense study by physicists and biologists, we do not fully understand the unsteady aerodynamics that relate insect wing morphology and kinematics to lift generation. Here, we formulate a force partitioning method (FPM) and implement it within a computational fluid dynamic model to provide an unambiguous and physically insightful division of aerodynamic force into components associated with wing kinematics, vorticity, and viscosity. Application of the FPM to hawkmoth and fruit fly flight shows that the leading-edge vortex is the dominant mechanism for lift generation for both these insects and contributes between 72–85% of the net lift. However, there is another, previously unidentified mechanism, the centripetal acceleration reaction, which generates up to 17% of the net lift. The centripetal acceleration reaction is similar to the classical inviscid added-mass in that it depends only on the kinematics (i.e. accelerations) of the body, but is different in that it requires the satisfaction of the no-slip condition, and a combination of tangential motion and rotation of the wing surface. Furthermore, the classical added-mass force is identically zero for cyclic motion but this is not true of the centripetal acceleration reaction. Furthermore, unlike the lift due to vorticity, centripetal acceleration reaction lift is insensitive to Reynolds number and to environmental flow perturbations, making it an important contributor to insect flight stability and miniaturization. This force mechanism also has broad implications for flow-induced deformation and vibration, underwater locomotion and flows involving bubbles and droplets. 相似文献
6.
Michael Meinecke Emmanuel Boucrot Gamze Camdere Wai-Ching Hon Rohit Mittal Harvey T. McMahon 《The Journal of biological chemistry》2013,288(9):6651-6661
Dynamin mediates various membrane fission events, including the scission of clathrin-coated vesicles. Here, we provide direct evidence for cooperative membrane recruitment of dynamin with the BIN/amphiphysin/Rvs (BAR) proteins, endophilin and amphiphysin. Surprisingly, endophilin and amphiphysin recruitment to membranes was also dependent on binding to dynamin due to auto-inhibition of BAR-membrane interactions. Consistent with reciprocal recruitment in vitro, dynamin recruitment to the plasma membrane in cells was strongly reduced by concomitant depletion of endophilin and amphiphysin, and conversely, depletion of dynamin dramatically reduced the recruitment of endophilin. In addition, amphiphysin depletion was observed to severely inhibit clathrin-mediated endocytosis. Furthermore, GTP-dependent membrane scission by dynamin was dramatically elevated by BAR domain proteins. Thus, BAR domain proteins and dynamin act in synergy in membrane recruitment and GTP-dependent vesicle scission. 相似文献
7.
Abhishek Sharma Satyawati Sharma Aditya Mittal Satya Narayan Naik 《Annals of microbiology》2014,64(2):515-520
The development of biofriendly and economical alternatives to chemical pesticides is a globally important scientific challenge. In this work, Karanja-based media conditions were optimized for obtaining high production of biomass and spores of a biocontrol agent, the entomopathogenic fungus Paecilomyces lilacinus 6029, using a two-step statistical approach coupled with rigorous experimentation. In the first step, non-edible Karanja cake was screened out as a major substrate from other oil cakes. In the second step, biomass production was maximized by applying response surface methodology to experimental variations in key physico-chemical factors: carbon/nitrogen (C/N) ratio and pH. This approach eventually predicted a maximum biomass production of 10.559 g/l with a medium having a C/N ratio of 35.88 and pH 5.9. An experimental production of 10.529 g/l biomass was obtained. The remarkable agreement between the predicted and the experimentally obtained biomass confirm the validity of the approach utilized to maximize production of P. lilacinus. 相似文献
8.
The distribution of protein and carbohydrate constituents in the epidermis of Barbus sophor is described in order to give a better understanding of its cellular organization and physiology.
Various cytochemical techniques show the keratinized nature of the outer free margins of the polygonal cells in the most-superficial layer. These contain appreciable amounts of cysteine bound sulphydryl groups, basic proteins, protein bound NH2 groups, ribonucleic acid and calcium and give a strong Papanicolaou's reaction. Absence of cystine bound disulphide groups suggests that the cornified layer in B. sophor is probably mechanically weak as adjacent keratin chains remain unbonded. The polygonal cells showing keratinization at the outer free margins remain metabolically active and are not sloughed off at the surface. This is in contrast to the keratinized epidermis of other teleosts so far reported in which the keratinized cells are dead and are sloughed off at the surface.
In addition to keratinization the polygonal cells undergo mucogenesis synthesizing sulphated acid mucopolysaccharides.
The presence of eosinophilic granular cells in the epidermis is interesting. The possible role of these cells in the protection of the epidermis has been discussed. The epidermis on the inner surface of the scale is very thin so it may not have much protective significance in these areas. 相似文献
Various cytochemical techniques show the keratinized nature of the outer free margins of the polygonal cells in the most-superficial layer. These contain appreciable amounts of cysteine bound sulphydryl groups, basic proteins, protein bound NH
In addition to keratinization the polygonal cells undergo mucogenesis synthesizing sulphated acid mucopolysaccharides.
The presence of eosinophilic granular cells in the epidermis is interesting. The possible role of these cells in the protection of the epidermis has been discussed. The epidermis on the inner surface of the scale is very thin so it may not have much protective significance in these areas. 相似文献
9.
A note on cold anaesthesia of poikilotherms 总被引:4,自引:0,他引:4
10.
R L Walford T Gossett G M Troup R A Gatti K K Mittal A Robins G B Ferrara E Zeller 《Journal of immunology (Baltimore, Md. : 1950)》1976,116(6):1704-1710
An analysis of the typing results of a 70-member chronic lymphatic leukemia B cell panel revealed evidence for 13 possible groups of the Merrit alloantigenic system. Six of these appeared possibly allelic and may represent a segregant series. The CLL panel was also fully typed for HLA and some degree of linkage dysequilibrium between Merrit and HLA seemed apparent from the data. Merrit antibodies can be absorbed out with selected surface membrane immunoglobulin (SMIG)-positive normal lymphocytes and less so or not at all with E rosette-forming T cells or Fc-positive SMIG-negative lymphocytes. 相似文献