Structural and biochemical characterization of interactions centered on RNA decay factors: MTR4 and SMG1

The nuclear exosome is the central 3'-5' RNA degradation machinery that performs a myriad roles critical for the health of a cell. The exosome associates with the MTR4 helicase, which binds and unwinds RNA substrates that are threaded through the exosome barrel for degradation. In several cases, MTR4 is targeted to specific RNA substrates via its association with adaptor proteins. Since MTR4 is a component of several exosome adaptor complexes, it was hypothesized that it might be recognizing the adaptor proteins via a common motif. The first results section of this thesis presents a study in which I identified and characterized the interactions of the MTR4 helicase with a pre-ribosome processing adaptor, NVL and the scaffolding and MTR4 activating component of the nuclear exosome targeting complex, ZCCHC8. I identified that the N-terminal regions of NVL and ZCCHC8 contain conserved sequences resembling the arch interacting motif (AIM) of the yeast rRNA processing factors. The structural and biochemical analysis indicate that these AIM-like motifs bind the MTR4 arch domain in a manner similar to that of the AIMs described earlier in the literature. Overall, the results suggest that nuclear exosome adaptors have evolved canonical and non- canonical AIM sequences to bind to human MTR4 and demonstrate the versatility and specificity with which the MTR4 arch domain can recruit a repertoire of different RNA- binding proteins. Recognizing RNA substrates for degradation is not only important in the nucleus but also in the cytoplasm. Nonsense mediated decay (NMD) is a cytoplasmic RNA decay mechanism which recognizes and degrades aberrant mRNA containing premature stop codons. It has also been shown to function in the regulation of physiological gene expression. SMG1, a 410 kDa PI3K related kinase, plays a crucial role in metazoan NMD by phosphorylating the UPF1 helicase. The phosphorylation of UPF1 was shown to be essential for the execution of NMD and represents the committed step of the NMD pathway. Although earlier low-resolution electron microscopic structures of human SMG1 along with some of its interacting partners were useful in gaining insight into the domain architecture of SMG1, the mechanism and regulation of SMG1 phosphorylation activity by SMG8-SMG9 remain poorly understood and are a subject of current research. The second results section presents a study, where I contributed to the characterization the C. elegans SMG8-SMG9 structurally and biochemically in an attempt to gain insights into the architecture of the complex and its possible biochemical role in NMD. The structure of the SMG8-SMG9 complex revealed that the complex exists as G-domain heterodimer with nucleotide binding capabilities. In a later study, presented as the third part of the results section, I contributed to understanding of the architecture of the SMG1-SMG8-SMG9 complex. The results not only recapitulate the findings of the SMG8-SMG9 complex but also provide structural basis for the SMG8-SMG9 interaction with SMG1. The structure also revealed that inositol-6-phosphate is a constitutive component of SMG1 and seems to play a role as a critical structural co-factor. The high- resolution structure of SMG1-SMG8-SMG9 provides a basis for several follow-up structural and biochemical studies centered on the early steps of NMD

Single coronary artery with origin of right coronary artery from left circumflex in a patient with ventricular tachycardia: a case report

Only a few cases of a single coronary artery (CA) have been described. Almost all cases reported so far also had associated atherosclerotic coronary artery or valvular heart disease. We present a 48 years old male with atypical chest pain with an episode of Ventricular Tachycardia (VT) on treadmill test (TMT). Coronary angiography (CAG) showed a single Left coronary artery (LCA) with Right coronary artery (RCA) arising from left circumflex artery (LCX) without any atherosclerotic disease

Hall Effect in the Viscous Incompressible Flow Through a Rotating Channel Between Two Porous Walls

Exact solutions for the velocity and induced magnetic field distributions, accounting for Hall currents have been obtained for the flow of a conducting porous walls under the action of a constant pressure gradient and in the presence of a uniform magnetic field transversely applied to the flow. Further, the channel is rotated with constant angular velocity about an axis perpendicular to the walls. For the purpose of mathematical simplicity, the magnetic prandtl number is assumed to be negligible. An expression for the boundary layer thickness dependent on Taylor, Hartmann, suction Reynolds numbers and Hall parameter has been obtained

Analysis of Non-motorised Transport and Public Transport Facilities Using Bicycle Compatibility Index and Stop Coverage Ratio, in Vijayanagar, Bengaluru

Transportation development is one of the parameters indicating the development of any country. Due to improper maintenance of infrastructure, non-eco-friendly designs and practices etc. have led to congestion, accidents and environmental depletion. These problems can be addressed by developing a structured transportation system integrated with sustainability and safety. The aim of this study is to analyze the existing facilities in the study area and to suggest integration of non-motorised transport and public transport through questionnaire survey. The bicycle compatibility index is calculated to find the bicycle level of service of the study area. The bus stop coverage analysis was done by calculating the ideal stop accessibility index, actual stop accessibility index and stop coverage ratio index. From bicycle compatibility index, it can be concluded that the compatibity of the surveyed region was moderately high for bicyclists. Based on bus-stop coverage analysis, Kalyan nagar bus stop is said to have good accessibility whereas ITI layout has poor accessibility

A novel weather parameters prediction scheme and their effects on crops

Weather forecast is significantly imperative in today’s smart technological world. A precise forecast model entails a plentiful data in order to attain the most accurate predictions. However, a forecast of future rainfall from historical data samples has always been challenging and key area of research. Hence, in modern weather forecasting a combo of computer models, observation, and knowledge of trends and patterns are introduced. This research work has presented a fitness function based adaptive artificial neural network scheme in order to forecast rainfall and temperature for upcoming decade (2021-2030) using historical weather data of 20 different districts of Karnataka state. Furthermore, effects of these forecasted weather parameters are realized over five major crops of Karnataka namely rice, wheat, jowar, maize, and ragi with the intention of evaluation for efficient crop management in terms of the passing relevant messages to the farmers and alternate measures such as suggesting other geographical locations to grow the same crop or growing other suitable crops at same geographical location. A graphical user interface (GUI) application has been developed for the proposed work in order to ease out the flow of work

A study of incidence and pattern of coronary artery anomalies in Western Rajasthan, India

Background: Coronary artery anomalies (CAAs) are a diverse group of congenital disorders whose manifestations and pathophysiological mechanisms are highly variable. Among patients undergoing coronary angiography, the incidence depends on the population studied and the criteria used to define an anomaly. This is the first ever study conducted in western Rajasthan to detect the incidence and pattern of coronary anomalies.Methods: We retrospectively studied 8500 coronary angiographies (CAG) done in the institution over a period of 12 years from 2004 to 2015 for detection of incidence and pattern of coronary anomalies. Patients with ischemic heart disease and valvular heart disease who underwent CAG were included in the study.Results: Out of the 8500 angiograms screened a total of 108 coronary anomalies were detected (incidence of 1.27%). Anomalies of origin and course was the most common anomaly (106 out of 108 patients) followed by anomalies of  coronary termination (fistulas) which was seen in just two patients. Most common anomaly was absent left main artery with separate origin of the left anterior descending (LAD) artery and left circumflex artery (LCx) (n=36, 33.3%), followed closely by anomalous origin of right coronary artery (RCA) from left sinus (n=34, 31.48%). Anomalous origin of LCx from right sinus/ RCA was the third most common anomaly (n=22, 20.37%). Other rare anomalies include anomalous origin of left coronary artery from right coronary sinus (n=6, 5.55%), RCA from posterior sinus (n=4, 3.7%). Single coronary artery, LAD from RCA and coronary artery fistula were seen in two patients each (n=2, 1.85%).Conclusions: In present study though the total incidence of coronary anomalies was similar to that in other studies, the pattern of coronary anomalies was slightly different from that reported from different parts of the world.

Understanding the Status of Important Criteria Air Pollutants and Its Health Effects – A Review

In India, airborne pollutant is serious, and a growing illness cause of concern, adding considerably to the country\u27s disease burden. Atmospheric effects are generally known to have several harmful health implications. India\u27s air pollution has risen significantly because of population expansion, rising vehicle numbers, fuel usage, inefficient transit networks, poor land use patterns, industrialisation, and most importantly, insufficient environmental legislation. Because air pollution is a major factor, this has an impact on human health. People gradually understood that contaminated outdoor air had detrimental consequences on human health. Hypercholesterolemia, breathing problems, chronic obstructive pulmonary disease (COPD), and asthma are all connected to ambient air pollution on a global scale. The purpose of this research is to review the literature on air quality and how it impacts population livelihoods

Correlational study of self-concept, social self-perception, academic self-concept and behavior problems among elementary school children

The purpose of this study was to examine the relationships, if any, between General Self-Concept, Social Self-Perception, Academic Self-Concept, and Behavior Problems among elementary school children. Twenty-two third grade students participated in this study. The Coopersmith Self-Esteem Inventory was used to measure self-concept. Social Self-Perception and Academic Self-Concept were measured by subscales of the Coopersmith Inventory. The Connors\u27 Teacher Rating Scales-39 was used to measure the general dimension of behavior problems. Findings from these two measures indicated a significant positive correlation between General Self-Concept and Social Self-Perception; General Self-Concept and Academic Self-Concept, and Social Self-Perception and Academic Self-Concept. There was, however, an insignificant negative correlation between General Self-Concept and Behavior Problems, Social Self-Perception and Behavior Problems, and Academic Self-Concept and Behavior Problems