Conformational Regulation of Membrane Localization and Activation of Talin

Talin is a cytosolic protein which is known to be one of the key players involved in integrin mediated cell adhesion dependent processes, including blood coagulation, and tissue remodeling. It connects the extracellular matrix with the actin cytoskeleton. Talin comprises of a head domain (talin-H) and a rod domain (talin-R). Talin-H is further subdivided in F0, F1, F2 and F3 domains. Talin-R contains 13 contiguous helical bundle domains (R1-R13) followed by an actin binding dimerization domain (DD). The F3 domain contains a key integrin binding site that regulates integrin activation. In our previous studies, we have shown that cytosolic talin exists in an autoinhibited state where the integrin binding site in F3 domain is self-masked by R9 domain. The autoinhibited talin is randomly distributed in the cytosol but upon activation, talin is rapidly localized to membrane and it binds and activates integrin. The main focus of the present study was to understand the mechanism of plasma membrane localization and activation of talin. Since talin has long been known to also bind to actin, we also investigated the actin binding sites in talin and how they are conformationally regulated. The crystal structure of autoinhibited talin F2F3-R9 complex, previously determined in our lab, revealed a stretch of negatively charged residues on R9 which is located on the same side as the positively charged surface on talin H. This leads to two hypotheses: (I) Electrostatic repulsion between the negatively charged talin-R9 surface and membrane promotes the cytosolic retention of autoinhibited talin (II) upon enrichment of membrane with negatively charged phosphatidylinositol-4,5-bisphosphate (PIP2), PIP2 strongly pulls the positively charged surface on talin-H towards membrane and simultaneously repels the negatively charged surface on R9, thus promoting the membrane localization and activation of autoinhibited talin via a pull-push mechanism. To test the hypothesis I, we made a triple mutant (H1711E, T1812E, N1815E) o

Conformational Regulation of Membrane Localization and Activation of Talin

Talin is a cytosolic protein which is known to be one of the key players involved in integrin mediated cell adhesion dependent processes, including blood coagulation, and tissue remodeling. It connects the extracellular matrix with the actin cytoskeleton. Talin comprises of a head domain (talin-H) and a rod domain (talin-R). Talin-H is further subdivided in F0, F1, F2 and F3 domains. Talin-R contains 13 contiguous helical bundle domains (R1-R13) followed by an actin binding dimerization domain (DD). The F3 domain contains a key integrin binding site that regulates integrin activation. In our previous studies, we have shown that cytosolic talin exists in an autoinhibited state where the integrin binding site in F3 domain is self-masked by R9 domain. The autoinhibited talin is randomly distributed in the cytosol but upon activation, talin is rapidly localized to membrane and it binds and activates integrin. The main focus of the present study was to understand the mechanism of plasma membrane localization and activation of talin. Since talin has long been known to also bind to actin, we also investigated the actin binding sites in talin and how they are conformationally regulated. The crystal structure of autoinhibited talin F2F3-R9 complex, previously determined in our lab, revealed a stretch of negatively charged residues on R9 which is located on the same side as the positively charged surface on talin H. This leads to two hypotheses: (I) Electrostatic repulsion between the negatively charged talin-R9 surface and membrane promotes the cytosolic retention of autoinhibited talin (II) upon enrichment of membrane with negatively charged phosphatidylinositol-4,5-bisphosphate (PIP2), PIP2 strongly pulls the positively charged surface on talin-H towards membrane and simultaneously repels the negatively charged surface on R9, thus promoting the membrane localization and activation of autoinhibited talin via a pull-push mechanism. To test the hypothesis I, we made a triple mutant (H1711E, T1812E, N1815E) o

Is it the end of the technology acceptance model in the era of generative artificial intelligence?

PurposeThe technology acceptance model (TAM) is a widely used framework explaining why users accept new technologies. Still, its relevance is questioned because of evolving consumer behavior, demographics and technology. Contrary to a research paper or systematic literature review, the purpose of this critical reflection paper is to discuss TAM's relevance and limitations in hospitality and tourism research.Design/methodology/approachThis paper uses a critical reflective approach, enabling a comprehensive review and synthesis of recent academic literature on TAM. The critical evaluation encompasses its historical trajectory, evolutionary growth, identified limitations and, more specifically, its relevance in the context of hospitality and tourism research.FindingsTAM's limitations within the hospitality and tourism context revolve around its individual-centric perspective, limited scope, static nature, cultural applicability and reliance on self-reported measures.Research limitations/implicationsTo optimize TAM's efficacy, the authors propose several strategic recommendations. These include embedding TAM within the specific context of the industry, delving into TAM-driven artificial intelligence adoption, integrating industry-specific factors, acknowledging cultural nuances and using comprehensive research methods, such as mixed methods approach. It is imperative for researchers to critically assess TAM's suitability for their studies and be open to exploring alternative models or methods that can adeptly navigate the distinctive dynamics of the industry.Originality/valueThis critical reflection paper prompts a profound exploration of technology adoption within the dynamic hospitality and tourism sector, makes insightful inquiries into TAM's future potential and presents recommendations

Health and the built environment in United States cities: measuring associations using Google Street View-derived indicators of the built environment

The built environment is a structural determinant of health and has been shown to influence health expenditures, behaviors, and outcomes. Traditional methods of assessing built environment characteristics are time-consuming and difficult to combine or compare. Google Street View (GSV) images represent a large, publicly available data source that can be used to create indicators of characteristics of the physical environment with machine learning techniques. The aim of this study is to use GSV images to measure the association of built environment features with health-related behaviors and outcomes at the census tract level.https://doi.org/10.1186/s12889-020-8300-

A Determination of gas outflow fluxes and study its transport mechanism by the application of flux chamber technique from the two landfill sites of semiarid region of Rajasthan

The investigation was executed to assess outflows of CO2 and CH4 gases from the two landfill sites of Udaipur using commonly applied multiple methodologies for the field to ascertain the accuracy and reliability of data imparted by each of these. To examine the potentiality of each gas discharge quantum for prospective energy that could be used further in waste-to-energy (WtE) projects, a field study was conducted for a period from January 2018 to December 2019 with the division of these landfill sites into segments. The gas samples were recorded onsite at demarked points in each segment by inverting the open portion of the Static Flux Chambers (SFCs) on the landfill surface to stop the ingress of air. This SFC was separately connected with the CO2 and CH4 gas analysers to record their onsite concentrations. The recorded data was further analysed to observe the annual quantitative spatial and temporal variations in the fluxes of these two gases. The mean CO2 and CH4 fluxes of Balicha Landfill Site (BLS) ranged between 932-1876μg/m2/hr and 359-1173μg/m2/hr, respectively. On the other hand the mean CH4 and CO2 fluxes of Titardi Landfill Site (TLS) ranged between 672 - 1483 μg/m2/hr and 157 - 958 μg/m2/hr, respectively. These fluxes emitted from BLS and TLS generated the carbon footprint (CF) of 180000 and 78000 ton of CO2 equivalent (tCO2 eq.) sequentially. In order to ensure the significance of the method used and to get best energy output for the WtE project the obtained gas flux data of both the sites was analysed and compared. This studied data would provide a guideline for the concerned authorities to plan & execute gas extraction operations at these two sites

Positive Impact of Aachar-Rasayana on Health

The first and foremost aim of Ayurveda - “Swasthasya Swasthya Rakshanam Aaturasya Vikara Prashamanam Cha”  is to maintain a healthy state of life and to remain free from the burden of diseases and sufferings so as to accomplish the ultimate goal of human life. To achieve this objective, Ayurveda has advocated certain percepts and rules which can ensure the normal functioning of human body without any hindrance. Ayurveda has suggested schedules of Swasthvritta including Dincharya, Ratricharya, Ritucharya, Rasayana, and Sadvritta as some of the practices and methods that leads to a happy, healthy and long life. In Ayurveda general principles to prevent psychic disturbances, practices preventing psychosomatic disturbances, practices regarding codes of general ethics in diet, behaviour, study, self-control etc. are explained as parts of Sadvritta. True efforts made for the observation of these schedules and conduct give rise to the effects of rejuvenation therapy called Aachar Rasayana that promotes longevity without any attack of diseases. Rasayana is one of the comprehensive disciplines of Ayurveda, which comprises a specialized use of herbs, herbo-mineral formulations, food articles and lifestyle along with self-discipline with social etiquette to achieve the optimum state of tissues that there is least effect of etiological factors on body. A careful analysis of qualities of Aachar Rasayana reveals that most of them are related to Mana, Dhi, Dhriti, along with good conduct. It inculcates the discipline related to mind, character, social, religious and personal life, so as to accord with the happiness and good of the individual and the society as a whole

Butterfly rash with periodontitis: A diagnostic dilemma

Rashes can occur in any part of the body. But rash which appears on face has got both psychological and cosmetic effect on the patient. Rashes on face can sometimes be very challenging to physicians and dermatologists and those associated with oral manifestations pose a challenge to dentists. Butterfly rash is a red flat facial rash involving the malar region bilaterally and the bridge of the nose. The presence of a butterfly rash is generally a sign of lupus erythematosus (LE), but it can also include a plethora of conditions. The case presented here is of a female with butterfly rash along with typical bright red discoloration of gingiva. The clinical, histopathological and biochemical investigations suggested the presence of rosacea

Neighborhood location and nutritional resources as a risk factor for congenital heart disease in the fetus

BACKGROUND: Congenital heart disease (CHD) is the most common birth defect, influenced by maternal health, environmental conditions, and genetics. Maternal health and nutrition, particularly maternal diabetes, is a modifiable risk factor for development of CHD in the fetus. However, the importance of food access during pregnancy on the development of CHD remains unknown. The objective of this study was to investigate the association between maternal neighborhood characteristics, particularly food access, and occurrence of prenatally diagnosed CHD. METHODS: A retrospective case series studied maternal-fetal dyads with prenatally diagnosed CHD between 2019 and 2021 in Washington, DC. Moran\u27s I of maternal addresses evaluated geographic clustering of disease. Negative binomial regression assessed association between census tract demographics and population-adjusted CHD rate. RESULTS: A total of 307 dyads were analyzed. Global Moran\u27s I showed significant CHD clustering (p-value = .004). However, degree of clustering was not clinically meaningful. After adjusting for neighborhood socioeconomic status, residing in food deserts was not a predictor for CHD. However, neighborhoods with a higher percentage of households receiving Supplemental Nutrition Assistance Program (SNAP) benefits were associated with higher rates of conotruncal heart defects (Incident Rate Ratio [IRR] = 1.04, CI = 1.01-1.08) and aggregate CHD (IRR = 1.03, CI = 1.01-1.05). CONCLUSIONS: Neighborhood location and food access were not associated with CHD. However, increased enrollment in SNAP was associated with higher rates of CHD. The association between CHD and SNAP benefits warrants further exploration. Understanding food access and maternal nutrition may illuminate disparities in the burden of CHD