Genome variations in commensal and pathogenic E.coli

Comparative genomics of the four E.coli strains MG1655, CFT073 and O157-EDL933 and Sakai has provided a wealth of information in understanding the continual expansion and retraction of E.coli genomes in detail. In this study, a systematic analysis was performed to assess the DNA polymorphisms at the region of bgl/Z5211-Z5214 island encoded systems, c1955-c1960 island encoded system and lac region in 25 septicemic, 32 uropathogenic, 1 asysmptomatic bacteriuria, 81 human commensals and 32 animal commensal E.coli strains and were compared to that seen in the four sequenced E.coli strains. Based on the observations E.coli strains were typed at the bgl/Z5211-Z5214 locus into five main types and one sub type: MG1655 type, CFT073 type, O157 type, fourth type, fifth type and mixed type. Approximately, 20% of the strains have bgl region like MG1655, 26% have bgl region like CFT073, 20% have Z5211-Z5214 region like O157, 20% have upstream sequence like O157 followed by bgl and downstream like MG1655 (with hybrid yieI gene) and 11% of the strains with the exception of downstream yieI gene have MG1655 sequence in the upstream, bgl and in the downstream region. Mixed type strains have mixture of sequences from MG1655, CFT073 and O157 in the bgl/Z5211-Z5214 region. In addition, three different types of beta-glucoside utilization phenotypes were seen. 35% of the strains papillate like MG1655, 16% of the strains papillate more frequently than MG1655 and 15% showed weak Bgl+ (relaxed) phenotype. All the strains that showed relaxed phenotype carried CFT073 type bgl operon, indicating CFT073 bgl sequence is important for relaxed phenotype and not vice versa. Mutations in the genes that are necessary for general cellular metabolism like amino acid biosynthesis and nucleotide biosynthesis abolished the relaxed phenotype. The analysis also demonstrated that the sequence variations seen at the bgl promoter region in the CFT073 bgl/Z type strains does not significantly influence the bgl expression in E.coli K-12 background. Furthermore, an additional beta-glucoside system was identified. This system corresponds to c1955-c1960 region of the CFT073 chromosome. The analysis of c1955-c1960 region revealed that 97 out of 171 strains carried c1955-c1960 system. The presence of c1955-c1960 was observed to be predominant in the strains that carry CFT073 type bgl. In a second line of investigation, it was demonstrated that c1955-c1960 system encodes genes for beta-glucoside utilization. It carries a CAP dependent promoter and is catabolically repressed in the presence of glucose. In order to analyze whether the typing at the bgl/Z5211-Z5214 locus has any correlations with the other sugar utilizing systems, the lactose utilization phenotypes were determined. Nine out of 171 strains showed Lac- phenotype, in which six of them belong to O157 type (at bgl/Z5211-Z5214). Taken together, the analysis demonstrates the genetic diversity among the E.coli strains. Moreover, it may provide an insight in considering bgl/Z5211-Z5214 island region as a marker for devising a novel strain-typing method for E.coli isolates

Modelling Studies for a \u2018Whole of Society (WoS)\u2019 Framework to monitor Cardio-Metabolic Risk among Children (6 to 18 years)

In the World Health Assembly (WHA) 2013, India was among the first country to adapt global framework for monitoring non-communicable diseases (NCD) - Government of India (GOI) has set targets to halt the prevalence of diabetes and obesity by 2025. To halt the prevalence of major NCDs it is necessary to protect children from becoming obese or overweight. Childhood obesity is a precursor of adulthood obesity and attendant cardio-metabolic risk. In last 15 years the prevalence of overweight and obesity increased almost four times (4 to 15%). This translates in to approximately 58 million obese and 122 million overweight children in the country. Studies have reported at least one cardiovascular risk factor among 70 per cent of these children. It is frightening to know that, unit percentage rise in its prevalence in India shall add at least another five million children into the cardiovascular risk pool. Body Mass Index (BMI) [Weight (kg)/Height (m2)] is the most widely used definition for monitoring overweight and obesity; among children BMI-for-age based growth curves (centile values) are used. There are number of BMI-for age based guidelines with varying cut offs (like IOTF, WHO, CDC etc.) \u2013 in India, the growth curves published Indian Association of Pediatrics (IAP), 2015 is considered as the standard. Despite BMI\u2019s large scale application in clinical and public health programs it has many inherent problems. Firstly, BMI cannot distinguish between fat and fat free mass. Excess body fat is an independent risk factor for cardio vascular and metabolic diseases. In an individual with BMI of 20, body fat may range from 5%-40% whereas for body fat content of 20% BMI may vary from 15-30 points. Validity studies using BMI to identify children with excess adiposity have generally documented low to moderate sensitivities (6-46%). Secondly, BMI is not independent on height of the individuals. BMI may not be a sensitive measure in children at the extremes of the height due to unusual fat distribution or highly developed muscles. BMI preferentially classifies taller children and adolescents as overweight. Finally, the definition of childhood overweight and obesity is arbitrary as it is extrapolated from adult reference data and not based on its association with health outcomes. Considering these variations, there has been a growing concern about using single standard to define overweight and obesity which may be appropriate for many sub-populations in the world. Methods: Overall aim of this study was to develop a monitoring mechanism that correlates with cardio-metabolic risk factors among Indian children aged 6-18 yrs. Primary objective of the study was to relate health outcomes, i.e. measures of cardio-metabolic risk, to body fatness and to 4 measure its distribution. Under this overarching goal specific objectives were finalized as mentioned in section 1.4 (Page no.40). Quantitative data was collected from schools in 3 regions (New Delhi, Shillong and Hyderabad) from a representative sample of 3242 children between 6 to 18 years of age. Detailed assessments were done on; a) anthropometry; b) pubertal staging; c) blood biochemistry (fasting plasma insulin, fasting plasma glucose, lipid profile and sub-fractions uric acid) using semi-automated analyzer), d) body composition by bio impedance (BIA) (InBody 720, body composition analyzer, Biospace\ua9), e) body composition using DEXA (Hologic QDR 4500A) on selected sub samples, f) socio-economic status (standard of living index), g) media and market exposures, h) food frequency and dietary recalls, and i) physical activity recalls. The results are presented as: \uf0b7 Study 1: Assessment of whole-body composition using bioelectrical impedance analysis (BIA) among children 6 to 18 years: Validation with Dual X-Ray Absorptiometry (DEXA) \uf0b7 Study 2: Reference values and Percentile curves for cardio-metabolic risk factors among Indian children (6 to 18 years) \uf0b7 Study 3: Clustering of Bio-chemical Markers of Cardio-metabolic Risk among Indian Children: An Imperative for Continuous Monitoring of Risk Factors \uf0b7 Study 4: A multi-level framework for monitoring cardio-metabolic risk: proximal & distal factors associated with clustering of bio-chemical marker

Predictions and Constraints of Cosmological Correlators

In this dissertation, we study the role of correlation functions in Cosmology. The study is bidirectional: We explore the constraints that correlation functions gathered from data impose on different theories; we also analyze the constraints that get imposed on correlation functions given symmetries of theories. For the former analysis, we use structure formation data like the CMB and matter power spectrum to set limits on the temperature of cold dark matter particles, basically only assuming that the particles were nonrelativistic when they decoupled and have interacted negligibly since. In another study, we use the same data to constrain how much Sommerfeld enhancement of dark matter annihilation could have occurred, with the analysis being insensitive to the details of the annihilation. Finally, we propose a new method to detect the so-called CMB anomalies in a more general manner than is usually considered. For the latter type of analysis, we consider the role of gauge symmetry in constraining relations between $n$- and $(n+1)$-point correlation functions for gravity coupled to a scalar field. Using certain assumptions, we show how novel consistency relations between fields can be derived, that arise only out of the symmetry of the action, and are independent of its particular form

Lattice Quantum Gravity and Asymptotic Safety

We study the nonperturbative formulation of quantum gravity defined via Euclidean dynamical triangulations (EDT) in an attempt to make contact with Weinberg's asymptotic safety scenario. We find that a fine-tuning is necessary in order to recover semiclassical behavior. Such a fine-tuning is generally associated with the breaking of a target symmetry by the lattice regulator; in this case we argue that the target symmetry is the general coordinate invariance of the theory. After introducing and fine-tuning a nontrivial local measure term, we find no barrier to taking a continuum limit, and we find evidence that four-dimensional, semiclassical geometries are recovered at long distance scales in the continuum limit. We also find that the spectral dimension at short distance scales is consistent with 3/2, a value that could resolve the tension between asymptotic safety and the holographic entropy scaling of black holes. We argue that the number of relevant couplings in the continuum theory is one, once symmetry breaking by the lattice regulator is accounted for. Such a theory is maximally predictive, with no adjustable parameters. The cosmological constant in Planck units is the only relevant parameter, which serves to set the lattice scale. The cosmological constant in Planck units is of order 1 in the ultraviolet and undergoes renormalization group running to small values in the infrared. If these findings hold up under further scrutiny, the lattice may provide a nonperturbative definition of a renormalizable quantum field theory of general relativity with no adjustable parameters and a cosmological constant that is naturally small in the infrared.Comment: 69 pages, 25 figures. Revised discussion of target symmetry throughout paper. Numerical results unchanged and main conclusions largely unchanged. Added references and corrected typos. Conforms with version published in Phys. Rev.

Recent results in Euclidean dynamical triangulations

We study a formulation of lattice gravity defined via Euclidean dynamical triangulations (EDT). After fine-tuning a non-trivial local measure term we find evidence that four-dimensional, semi-classical geometries are recovered at long distance scales in the continuum limit. Furthermore, we find that the spectral dimension at short distance scales is consistent with 3/2, a value that is also observed in the causal dynamical triangulation (CDT) approach to quantum gravity.Comment: 7 pages, 3 figures. Proceedings for the 3rd conference of the Polish society on relativit

Tetraspanins as Potential Therapeutic Candidates for Targeting Flaviviruses

Tetraspanin family of proteins participates in numerous fundamental signaling pathways involved in viral transmission, virus-specific immunity, and virus-mediated vesicular trafficking. Studies in the identification of novel therapeutic candidates and strategies to target West Nile virus, dengue and Zika viruses are highly warranted due to the failure in development of vaccines. Recent evidences have shown that the widely distributed tetraspanin proteins may provide a platform for the development of novel therapeutic approaches. In this review, we discuss the diversified and important functions of tetraspanins in exosome/extracellular vesicle biology, virus-host interactions, virus-mediated vesicular trafficking, modulation of immune mechanism(s), and their possible role(s) in host antiviral defense mechanism(s) through interactions with noncoding RNAs. We also highlight the role of tetraspanins in the development of novel therapeutics to target arthropod-borne flaviviral diseases

A Clinical Evaluation of Management of Amavata with Rasonadi kwatha, w.s.r. to Rheumatoid Arthritis

Purpose: To evaluate the role of Rasonadi kwatha, a classical medicament in the management of Amavata, w.s.r. to Rheumatoid Arthrits, which is attributed with best Amavatahara property, considering a trend of progressively increasing incidence of the condition.Methods: The trial drug Rasonadi kwatha was prepared as per the classical method of Kashaya kalpana. Total of 47 patients of Amavata fulfilling the inclusion criteria were registered, of which 30 completed the course of intervention, in a single armed, prospective, open label, cohort study, with pre and postintervention analysis design. Descriptive data including Mean, Standard Deviation (SD), Standard Error (SE), t-value and percentages were calculated for all variables in the trial group. The post treatment changes were assessed by paired Student t-test, taking 0.05 as the level of significance.Results: Effect of the intervention on Subjective criteria including Signs and symptoms of Amavata and objective criteria including Disease Activity Score 28, Grip strength, Foot Pressure and Range of Movement was statistically significant with P value 0.001 after completion of treatment. The trial drug showed 36.67% of Moderate improvement and 53.33% of mild improvement in subjects of Amavata in the present study.Conclusion: The formulation Rasonadi kwatha is efficacious in management of the disease Amavata w.s.r. to Rheumatoid Arthritis. The formulation is Ruksha (Dry) and Ushna (Hot potency) and thus it is a potent Amapachaka (digesting the Ama), breaking the primary pathogenesis of the disease. It showed statistically significant improvements in Samanya lakshanas and good results in Pradhana lakshanas of Amavata