F-box protein FBXO31 directs degradation of MDM2 to facilitate p53-mediated growth arrest following genotoxic stress

The tumor suppressor p53 plays a critical role in maintaining genomic stability. In response to genotoxic stress, p53 levels increase and induce cell-cycle arrest, senescence, or apoptosis, thereby preventing replication of damaged DNA. In unstressed cells, p53 is maintained at a low level. The major negative regulator of p53 is MDM2, an E3 ubiquitin ligase that directly interacts with p53 and promotes its polyubiquitination, leading to the subsequent destruction of p53 by the 26S proteasome. Following DNA damage, MDM2 is degraded rapidly, resulting in increased p53 stability. Because of the important role of MDM2 in modulating p53 function, it is critical to understand how MDM2 levels are regulated. Here we show that the F-box protein FBXO31, a candidate tumor suppressor encoded in 16q24.3 for which there is loss of heterozygosity in various solid tumors, is responsible for promoting MDM2 degradation. Following genotoxic stress, FBXO31 is phosphorylated by the DNA damage serine/threonine kinase ATM, resulting in increased levels of FBXO31. FBXO31 then interacts with and directs the degradation of MDM2, which is dependent on phosphorylation of MDM2 by ATM. FBXO31-mediated loss of MDM2 leads to elevated levels of p53, resulting in growth arrest. In cells depleted of FBXO31, MDM2 is not degraded and p53 levels do not increase following genotoxic stress. Thus, FBXO31 is essential for the classic robust increase in p53 levels following DNA damage

Lepton Flavor Violation within a realistic SO(10)/G(224) Framework

Lepton flavor violation (LFV) is studied within a realistic unified framework, based on supersymmetric SO(10) or an effective G(224) = SU(2)_L\times SU(2)_R\times SU(4)^c symmetry, that successfully describes (i) fermion masses and mixings, (ii) neutrino oscillations, as well as (iii) CP violation. LFV emerges as an important prediction of this framework, bringing no new parameters, barring the few SUSY parameters, which are assumed to be flavor-universal at M^*>= M_{GUT}. We study LFV (i.e. \mu -> e\gamma, \tau -> \mu\gamma, \tau -> e\gamma and \mu N -> e N) within this framework by including contributions both from the presence of the right handed neutrinos as well as those arising from renormalization group running in the post-GUT regime (M^* to M_{GUT}). Typically the latter, though commonly omitted in the literature, is found to dominate. Our predicted rates for \mu -> e\gamma show that while some choices of (m_o, m_{1/2}) are clearly excluded by the current empirical limit, this decay should be seen with an improvement of the current sensitivity by a factor of 10--100, even if sleptons are moderately heavy (<= 800 GeV, say). For the same reason, \mu-e conversion (\mu N -> e N) should show in the planned MECO experiment. Implications of WMAP and (g-2)_{\mu}-measurements are noted, as also the significance of the measurement of parity-odd asymmetry in the decay of polarized \mu^+ into e^+ \gamma.Comment: 17 pages, 1 figur

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

Studies of the Melting of a 2D Solid

We have made a detailed numerical analysis of neutron diffraction lineshapes across the constant -coverage melting transition of incommensurate monolayers of methane structure factor. We find that in the liquid phase the liquid lineshapes is well fitted with a lorentzian structure factor. While the exact nature of the transition very close to Tm cannot be commented upon, the 'freezing' of the liquid appears to be initially continuous, with an increase in correlation length to hundreds of Angstroms before the appearance of a solid phase

Back to the basics: Study of portable chest radiographic findings in 116 COVID-19 positive patients in an Indian tertiary care hospital

Context: Paucity of literature of portable CXR findings in COVID-19. Aims: Evaluate radiographic findings in COVID-19 patients and calculate sensitivity of radiographs with RT-PCR as gold standard. Subjects and Methods: Total 116 COVID-19 patients underwent portable CXR between April-June, 2020. Two radiologists reviewed radiographs with respect to laterality, craniocaudal, mediolateral distribution, shape, density, unifocality/multifocality and number of lung zones. Sensitivity of radiography was calculated with RT-PCR as gold standard. Statistical Analysis Used: IBM SPSS Statistics Subscription software (IBM, New York, USA). Results: Many patients 67.2% (78/116) were asymptomatic. Cough (21.5%, 25/116) and fever (17.6%, 20/116) were the most frequent symptoms. 36.2% (42/116) patients revealed COVID-19 pneumonia-like abnormalities on CXR. Sensitivity of CXR with RT-PCR as gold standard was 36.2% (CI: Confidence interval = 27.46% - 44.95%). More patients in symptomatic group (68.4%, 26/38) had abnormal CXR compared to asymptomatic group (20.5%, 16/78) [P < 0.0001]. Radiographs revealed both unilateral (57.1%, 24/42), bilateral (42.8%, 18/42), GGO (80.9%, 34/42), or consolidation (11/42, 26.1%) in a middle (57.1%, 24/42), lower zone (83.3%, 35/42) and peripheral distribution (78.5%, 33/42). Lesions were commonly patchy (88%, 37/42) and multifocal (59.5%, 25/42). Majority had single (40.4%, 17/42) or two zone (35.7%, 15/42) involvement. Conclusions: Significant number of COVID-19 patients were asymptomatic. Over 1/3rd of patients showed radiographic abnormalities. Symptomatic patients were more likely to show radiographic findings than asymptomatic patients. If radiographs identify pneumonia in appropriate clinical setting, CT can be avoided. Common radiographic abnormalities among COVID 19 patients were bilateral/unilateral, patchy, multifocal, ground glass opacity or consolidation in peripheral and middle/lower zone distribution

Developmental and eruption disturbances of teeth and associated complications in Indian children from birth to 12 years of age: A cross-sectional survey

Introduction: This study evaluated the prevalence of developmental and eruption disturbances of teeth in both primary and mixed dentition of the patients along with the associations between the variables such as child's age, gender, jaw, and teeth. Materials and Methods: A total of 9235 children visiting the Outpatient Department of Pedodontics and Preventive Dentistry, Postgraduate Institute of Dental Sciences, Rohtak, Haryana, India, were examined during a period of 1 year from January 2014 to January 2015. Clinical examination was carried out to identify the presence of developmental and eruption disturbances. Data management and statistical analysis were carried out using software Statistical Package for Social Sciences version 19. Results: A total of 223 (2.41%) patients were affected by the developmental dental and eruption disturbances. The prevalence of developmental dental anomalies was 1.62 and of eruption disturbances was 1.06. Enamel hypoplasia was the most prevalent anomaly (0.77) whereas the most prevalent eruption disturbance was ectopic eruption (0.80). Conclusion: The early detection and diagnosis of dental anomalies is important to prevent further disturbances and related complications

Social and Behavioral Determinants for Early Childhood Caries among Preschool Children in India

Background and aims. Early Childhood Caries (ECC) is a public health problem with biological, social and behavioural determinants and the notion that the principal etiology is inappropriate feeding modalities is no longer tenable. Hence this study was undertaken to assess the relationship between ECC and socio-demographic factors, dietary habits, oral hygiene habits and parental characteristics. Materials and methods. The study involved a dental examination of 1400 children aged 0‒71 months, recording caries using Gruebbel’s deft index and a structured questionnaire to interview parents or caretakers. The tabulated data was statis-tically analyzed using t-test and ANOVA at 5% level of significance. Results. The variables significantly associated with ECC were age (P<0.001), geographical location (P<0.05), duration of breast/bottle feeding (P<0.001), use of sweetened pacifiers (P<0.001), frequency of snacking (P<0.05), frequency of tooth brushing (P<0.001), the person responsible for child’s oral health care (P<0.05) and education level of parents (P<0.05). However, other variables like child’s gender, number of siblings, types of snack the child preferred and age at which tooth brushing was instituted did not have statistically significant relationship with ECC (P>0.05). Conclusion. ECC is preventable and manageable with proper information and skills. It is important for healthcare profes-sionals, family physicians and parents to be cognizant of the involved risk factors as their preventive efforts represent the first line of defense