Measurements of diffusion and clustering of integrin receptors in the plasma membrane of live cells using fluorescence-based techniques

Cell membranes display a complex, dynamic organization of lipids, proteins and other small molecules. This organization may arise from varied protein-protein interactions including interactions between receptors, effectors and ligand molecules or from formation of specialized domains within the plasma membrane such as lipid rafts. The involvement of integrin cell surface receptors in membrane complexes is intensively known. Integrins\u27 interactions with other components in these complexes can alter many signal transduction cascades, thus modulating integrins\u27 own functions and affecting various cellular processes. Integrins are heterodimers formed by the non-covalent association of an α and a β subunit. Each subunit consists of a single transmembrane domain, a large extracellular domain and a short cytoplasmic domain. While ligand binding to integrin extracellular domains allows transmission of signals into the cell (outside-in signaling), binding of cytoskeletal proteins to integrin cytoplasmic domains permits inside-out signaling. In this way, integrins mediate bidirectional signaling across the plasma membrane and control a variety of cellular processes including cell adhesion, mobility, growth, survival, proliferation, and differentiation. The work described in this dissertation aims to achieve a better understanding of membrane organization by identifying the factors that affect integrin dynamics. Using molecular biology and fluorescence microscopy techniques, we have measured integrin clustering and diffusion properties under altered environments such as reduced membrane cholesterol levels, reduced cytoplasmic protein concentrations and reduced membrane protein concentrations. Additionally, we have also studied the effects of post-translational modifications on integrin dynamics. The fluorescence techniques used in this work include fluorescence resonance energy transfer (FRET) to study integrin clustering, fluorescence recovery after photobleaching (FRAP) and single particle tracking (SPT) to study integrin diffusion. A number of cytoplasmic and membrane proteins were identified that alter integrin diffusion and clustering. Reducing the levels of cholesterol from the cell membrane resulted in more mobile integrins and affected diffusion of integrins in confined domains. Removing a potential palmitoylation site in αPS2CβPS integrins resulted in more mobile integrins. The role of other proteins, cholesterol and palmitoylation in altering integrin diffusion and clustering may be the result of partitioning of integrins into lipid nanodomains, which are heterogeneous regions in the cell membrane containing higher concentration of lipids and proteins as compared to the bulk membrane and play a very important role in cell signaling

Redrawing the Contours of Nationalist Discourse through the Voices of Courtesans-Turned-Warriors

The last quarter of the twentieth century has seen the emergence of a “cult of pluralism” (Chakrabarty) in the writing of Indian history, thus challenging the standardized narrative of the nation. The hegemonic accounts of India’s struggle for independence, which have failed to acknowledge the involvement of many significant warriors, make the inextricable links between power, history, and representation quite apparent. One such exclusion is that of the tawaifs2 of Awadh.3 This hypocrisy combined with the facade of respectability has eclipsed the contribution of tawaifs, demoting them to singing and dancing girls merely. By looking at the role of Begum Hazrat Mahal in the Revolt of 1857, this paper intends to add another dimension to both the understanding of tawaifs and the historiography of the revolt. It also seeks to question the inclination of historians to focus on the participation of men and ignore women, especially those women from marginalized demographics. The study foregrounds the role of tawaifs in the changing discourses of colonialism and nationalism, with the goal to problematize their invisibility in academic discourse. Kenizé Mourad’s biographical fiction, The City of Gold and Silver, is taken as a case study to focus on the production of counter- narratives. A thorough examination of the various aspects of Begum’s personality calls into question history’s selective representations. Furthermore, by focusing on the Begum’s political life, the paper seeks to correct the false image of Awadh’s tawaifs and kothas4 and to restore the lost voices of the unsung heroines

Thermodynamic study of nanometals for different shapes and sizes

Thermodynamic analytic model has been discussed to study the size as well as shape effect on thermodynamic parameters of nanometals. Thermodynamic properties like melting temperature, cohesive energy, vacancy formation energy and Debye temperature of Al, Ag, Au, In and Sn nano metals for spherical and non spherical nanoparticles (i.e. tetrahedral, hexahedral, octahedral and disc like) with different size have been studied. Present study shows that spherical and nonspherical nanoparticles behave in different manner due to the difference in their shape factor. It has been found that these thermal properties show decreasing trend with decrement in size of the nanomaterial due to the change in surface to volume ratio. The obtained results also reveal that shape of the nanoparticle plays a vital role to affect the thermodynamic properties of small sized nanoparticles because of change in surface area with shape for fixed volume. Theoretical results obtained for melting temperature, cohesive energy, vacancy formation energy and Debye temperature have been discussed in the light of available simulated and experimental data which supports the validity of present model

Observational study of vaginal culture in symptomatic and asymptomatic non pregnant female patient in tertiary care hospital

Background: Vaginal miroflora plays an important role in maintaining healthy microenvironment. Lactobacilli are the dominant flora responsible for this. Any disturbance in balance of normal and abnormal flora leads to different types of vaginal infections like, vulvo-vaginal candidiasis, and bacterial vaginosis. Most common organisms causing vaginitis is Gardnerella vaginalis which causes bacterial vaginosis. Other organisms responsible for infections are, candida, trichomonas, and viruses. Abnormal growth of pathogenic bacteria during pregnancy can lead to various adverse pregnancy outcomes. Methods: This is an observational study conducted in a tertiary care hospital over a period of 6 months (January 2023 to June 2023). Overall, out of 135 women, sample of 120 women were taken and treated accordingly. Results: Among 120 women, 52 (43.3%) women had no growth on culture, while 20 patients (16.6%) showed growth of Klebsiella and 20 (16.6%) patient shows Candida and rest shows growth of other pathogen. Conclusions: In our study, half of the women were found to be with positive culture report, who shown improvement after treatment

On How Traffic Signals Impact the Fundamental Diagrams of Urban Roads

Being widely adopted by the transportation and planning practitioners, the fundamental diagram (FD) is the primary tool used to relate the key macroscopic traffic variables of speed, flow, and density. We empirically analyze the relation between vehicular space-mean speeds and flows given different signal settings and postulate a parsimonious parametric function form of the traditional FD where its function parameters are explicitly modeled as a function of the signal plan factors. We validate the proposed formulation using data from signalized urban road segments in Salt Lake City, Utah, USA. The proposed formulation builds our understanding of how changes to signal settings impact the FDs, and more generally the congestion patterns, of signalized urban segments

The role of a conserved membrane proximal cysteine in altering αPS2CβPS integrin diffusion

Cysteine residues (Cys) in the membrane proximal region are common post-translational modification (PTM) sites in transmembrane proteins. Herein, the effects of a highly conserved membrane proximal α-subunit Cys1368 on the diffusion properties of αPS2CβPS integrins are reported. Sequence alignment shows that this cysteine is palmitoylated in human α3 and α6 integrin subunits. Replacing Cys1368 in wild-type integrins with valine (Val1368) putatively blocks a PTM site and alters integrins\u27 ligand binding and diffusion characteristics. Both fluorescence recovery after photobleaching (FRAP) and single particle tracking (SPT) diffusion measurements show Val1368 integrins are more mobile compared to wild-type integrins. Approximately 33% and 8% more Val1368 integrins are mobile as measured by FRAP and SPT, respectively. The mobile Val1368 integrins also exhibit less time-dependent diffusion, as measured by FRAP. Tandem mass spectrometry data suggest that Cys1368 contains a redox or palmitoylation PTM in αPS2CβPS integrins. This membrane proximal Cys may play an important role in the diffusion of other alpha subunits that contain this conserved residue

Restoring the Esthetics in Hemiparalytic Patient with Detachable Prosthesis

Emphasis on facial esthetics has become an integral part of dental treatment. Restoring and improving facial appearance of a complete edentulous patient with hollow cheeks is achallenge to the prosthodontist. Thus, to improve patient’s lower lip contour that was paralyzed and to improve patient’s oral competency, a detachable prosthesis was fabricated. This clinical report describes the procedure for making a lip plumper prosthesis to improve patient esthetics, oral function

Global impact of tobacco control policies on smokeless tobacco use: A systematic review protocol

Introduction Smokeless tobacco (ST) was consumed by 356 million people globally in 2017. Recent evidence shows that ST consumption is responsible for an estimated 652 494 all-cause deaths across the globe annually. The WHO Framework Convention on Tobacco Control (FCTC) was negotiated in 2003 and ratified in 2005 to implement effective tobacco control measures. While the policy measures enacted through various tobacco control laws have been effective in reducing the incidence and prevalence of smoking, the impact of ST-related policies (within WHO FCTC and beyond) on ST use is under-researched and not collated. Methods and analysis A systematic review will be conducted to collate all available ST-related policies implemented across various countries and assess their impact on ST use. The following databases will be searched: Medline, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Scopus, EconLit, ISI Web of Science, Cochrane Library (CENTRAL), African Index Medicus, LILACS, Scientific Electronic Library Online, Index Medicus for the Eastern Mediterranean Region, Index Medicus for South-East Asia Region, Western Pacific Region Index Medicus and WHO Library Database, as well as Google search engine and country-specific government websites. All ST-related policy documents (FCTC and non-FCTC) will be included. Results will be limited to literature published since 2005 in English and regional languages (Bengali, Hindi and Urdu). Two reviewers will independently employ two-stage screening to determine inclusion. The Effective Public Health Practice Project's 'Quality Assessment Tool for Quantitative Studies' will be used to record ratings of quality and risk of bias among studies selected for inclusion. Data will be extracted using a standardised form. Meta-analysis and narrative synthesis will be used. Ethics and dissemination Permission for ethics exemption of the review was obtained from the Centre for Chronic Disease Control's Institutional Ethics Committee, India (CCDC-IEC-06-2020; dated 16 April 2020). The results will be disseminated through publications in a peer-reviewed journal and will be presented in national and international conferences. PROSPERO registration number CRD42020191946. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Muhammad Aziz Rahman” is provided in this record*

Anti-ulcer activity of the methanolic extract of Nothapodytes foetida in wistar rats

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