Publications by authors named "Mehul Makwana"

Proteins are responsible for most intracellular functions, which they perform as part of higher-order molecular complexes, located within defined subcellular niches. Localization is both dynamic and context specific and mislocalization underlies a multitude of diseases. It is thus vital to be able to measure the components of higher-order protein complexes and their subcellular location dynamically in order to fully understand cell biological processes.

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Article Synopsis
  • Researchers developed stable analogues of two types of phosphohistidine, τ-pHis and π-pHis, to create antibodies for use in various immunological techniques.
  • These analogues were synthesized and characterized using techniques like P NMR spectroscopy, and were effectively used to produce polyclonal antibodies through conjugation with BSA-glutaraldehyde.
  • The study demonstrated that the antibodies generated via different haptens (phosphopyrazole and pyridyl amino amide) had selectivity for their respective analogues and were effective in assays such as ELISA, western blot, and immunofluorescence.
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There is growing evidence to suggest that phosphohistidines are present at significant levels in mammalian cells and play a part in regulating cellular activity, in particular signaling pathways related to cancer. Because of the chemical instability of phosphohistidine at neutral or acid pH, it remains unclear how much phosphohistidine is present in cells. Here we describe a protocol for extracting proteins from mammalian cells in a way that avoids loss of covalent phosphates from proteins, and use it to measure phosphohistidine concentrations in human bronchial epithelial cell (16HBE14o-) lysate using 31P NMR spectroscopic analysis.

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The ESCRT machinery, comprising of multiple proteins and subcomplexes, is crucial for membrane remodelling in eukaryotic cells, in processes that include ubiquitin-mediated multivesicular body formation, membrane repair, cytokinetic abscission, and virus exit from host cells. This ESCRT system appears to have simpler, ancient origins, since many archaeal species possess homologues of ESCRT-III and Vps4, the components that execute the final membrane scission reaction, where they have been shown to play roles in cytokinesis, extracellular vesicle formation and viral egress. Remarkably, metagenome assemblies of Asgard archaea, the closest known living relatives of eukaryotes, were recently shown to encode homologues of the entire cascade involved in ubiquitin-mediated membrane remodelling, including ubiquitin itself, components of the ESCRT-I and ESCRT-II subcomplexes, and ESCRT-III and Vps4.

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We create hybrid topological-photonic localisation of light by introducing concepts from the field of topological matter to that of photonic crystal fiber arrays. S-polarized obliquely propagating electromagnetic waves are guided by hexagonal, and square, lattice topological systems along an array of infinitely conducting fibers. The theory utilises perfectly periodic arrays that, in frequency space, have gapped Dirac cones producing band gaps demarcated by pronounced valleys locally imbued with a nonzero local topological quantity.

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Strategically combining four structured domains creates the first ever three-way topological energy-splitter; remarkably, this is only possible using a square, or rectangular, lattice, and not the graphene-like structures more commonly used in valleytronics. To achieve this effect, the two mirror symmetries, present within all fully-symmetric square structures, are broken; this leads to two nondistinct interfaces upon which valley-Hall states reside. These interfaces are related to each other via the time-reversal operator and it is this subtlety that allows us to ignite the third outgoing lead.

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We create a passive wave splitter, created purely by geometry, to engineer three-way beam splitting in electromagnetism in transverse electric and magnetic polarisation. We do so by considering arrangements of Indium Phosphide dielectric pillars in air, in particular we place several inclusions within a cell that is then extended periodically upon a square lattice. Hexagonal lattice structures are more commonly used in topological valleytronics but, as we discuss, three-way splitting is only possible using a square, or rectangular, lattice.

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Since the publication of the paper the authors have noted some errors in the text (please read the full correction for more information). These errors have now been corrected in both the HTML and PDF versions of the paper.

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Protein phosphorylation is an important post-translational modification that is an integral part of cellular function. The O-phosphorylated amino-acid residues, such as phosphoserine (pSer), phosphothreonine (pThr) and phosphotyrosine (pTyr), have dominated the literature while the acid labile N-linked phosphorylated amino acids, such as phosphohistidine (pHis), have largely been historically overlooked because of the acidic conditions routinely used in amino-acid detection and analysis. This review highlights some misinterpretations that have arisen in the existing literature, pinpoints outstanding questions and potential future directions to clarify the role of pHis in mammalian signalling systems.

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