A Phenomenological Model for Predicting Melting Temperatures of DNA Sequences

We report here a novel method for predicting melting temperatures of DNA sequences based on a molecular-level hypothesis on the phenomena underlying the thermal denaturation of DNA. The model presented here attempts to quantify the energetic components stabilizing the structure of DNA such as base pairing, stacking, and ionic environment which are partially disrupted during the process of thermal denaturation. The model gives a Pearson product-moment correlation coefficient (r) of ∼0.98 between experimental and predicted melting temperatures for over 300 sequences of varying lengths ranging from 15-mers to genomic level and at different salt concentrations. The approach is implemented as a web tool (www.scfbio-iitd.res.in/chemgenome/Tm_predictor.jsp) for the prediction of melting temperatures of DNA sequences

Cervical Pap smear study and detection of abnormal epithelial lesions and determination of its accuracy by cytohistological correlation in patients of tertiary care teaching hospital in central India

Background: Cervical cancer is the second most common cancer in females and is a major cause of morbidity and mortality. Pap smear is simple, cost effective and sensitive tool for screening of various non-neoplastic and neoplastic lesions of cervix. The objective of this study was to determine the pattern of various cervical smear abnormalities in our center, to study the prevalence of epithelial cell abnormalities in our study population and to determine the accuracy of Pap test by correlating with histopathology.Methods: This was a retrospective study of 7127 cervical pap smears screened and reported at department of pathology, Sri Aurobindo institute of medical sciences Indore, Madhya Pradesh, India during the period of January 2013 to December 2015. Pap smear was done by the conventional method and reporting was done based on the Bethesda system .Emphasis was put on epithelial cell abnormalities and the findings of abnormal epithelial lesions were correlated with histopathology.Results: In this study, the epithelial cell abnormalities constituted 2% of all cases. Low grade squamous intraepithelial lesion was the most common epithelial cell abnormality found in our study group followed by HSIL and then squamous cell carcinoma. About two thirds of the abnormal epithelial lesions were found in the age group above 40 years. Our cytological diagnosis correlated well with histopathology.Conclusions: Pap smear is a cost effective and sensitive screening method for detection of cancerous, pre-cancerous and non-cancerous lesions of cervix

JAZF1-SUZ12 dysregulates PRC2 function and gene expression during cell differentiation

Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain gene repression and is essential for cell differentiation. In low-grade endometrial stromal sarcoma (LG-ESS), the PRC2 subunit SUZ12 is often fused with the NuA4/TIP60 subunit JAZF1. We show that JAZF1-SUZ12 dysregulates PRC2 composition, genome occupancy, histone modification, gene expression, and cell differentiation. Loss of the SUZ12 N terminus in the fusion protein abrogates interaction with specific PRC2 accessory factors, reduces occupancy at PRC2 target genes, and diminishes H3K27me3. Fusion to JAZF1 increases H4Kac at PRC2 target genes and triggers recruitment to JAZF1 binding sites during cell differentiation. In human endometrial stromal cells, JAZF1-SUZ12 upregulated PRC2 target genes normally activated during decidualization while repressing genes associated with immune clearance, and JAZF1-SUZ12-induced genes were also overexpressed in LG-ESS. These results reveal defects in chromatin regulation, gene expression, and cell differentiation caused by JAZF1-SUZ12 that may underlie its role in oncogenesis

How Can Health, Agriculture and Economic Policy Actors Work Together to Enhance the External Food Environment for Fruit and Vegetables? A Qualitative Policy Analysis in India

The benefits of fruit and vegetables are well established, particularly their role in preventing general micronutrient-deficiencies and chronic diseases. However, global food systems are not delivering diverse and high quality diets: healthy food is unavailable and too expensive for many. Creating food environments that foster consumer access to fruit and vegetables will require coordinated policy action across sectors, mostly outside of the health sector. The aim of this paper is to identify opportunities to strengthen food system policy for nutrition, through an analysis of the policies relevant to the external food environment for fruit and vegetables in India. We conducted interviews based on policy theory with 55 stakeholders from national and state level, from within government, research, private sector and non-government agencies, and from health, agriculture and economic sectors. Specific strategies identified in this study to improve consumers’ external food environment for fruit and vegetables in India were: development of strategic Public-Private Partnerships to increase access to diverse expertise across the supply chain; linking health and economic/agricultural policy agendas; and strengthening surveillance of policy impacts on consumer access to fruit and vegetables. We also found that public health actors can play an important role in advocating for ‘consumer oriented’ fruit and vegetable supply policy. This study demonstrates the usefulness of ‘policy learning’-oriented qualitative policy analysis in identifying ‘points of entry’ for food policy change, and extends understanding of political dynamics in engendering agricultural policy change for nutrition. Improving access to affordable fruit and vegetables is a global priority, and given common global food supply challenges, the findings from this study are also likely to be relevant for other low and middle income countries

Strengthening fruit and vegetable supply-chain policies and programmes in India

India currently has one of the highest numbers of malnourished children in the world – 8% stunted, 43% underweight, and 20% overweight and obese. This distressing public health scenario is further exacerbated by a high prevalence of multiple micronutrient deficiencies among these children – such as iron deficiency anaemia and Vitamin A deficiency. Evidence shows linkages between early life malnourishment (either underweight or overweight-obesity) and predisposition to developing chronic diseases in adult life. Consuming 400g/day of fresh fruits and vegetables can help prevent micronutrient deficiencies while promoting overall growth and development. However, national averages indicate that children do not consume even 40% of the daily recommended amounts. Public Health Foundation of India (PHFI) undertook a study titled ‘Leveraging fruit and vegetable supply policies to tackle the dual burden of malnutrition in India’ supported by the Leveraging Agriculture for Nutrition in South Asia (LANSA) consortium at the M S Swaminathan Research Foundation (MSSRF). The study, discussed in this Brief aimed to analyse the policy environment related with fruit and vegetable (FV) supply in India to identify opportunities for policy to increase access to, and thus intakes of FV, especially among children.Department for International Development (DFID)UKAI

Exhausted CD4+ T Cells during Malaria Exhibit Reduced mTORc1 Activity Correlated with Loss of T-bet Expression

CD4<sup>+</sup> T cell functional inhibition (exhaustion) is a hallmark of malaria and correlates with impaired parasite control and infection chronicity. However, the mechanisms of CD4<sup>+</sup> T cell exhaustion are still poorly understood. In this study, we show that Ag-experienced (<i>Ag-exp</i>) CD4<sup>+</sup> T cell exhaustion during <i>Plasmodium yoelii</i> nonlethal infection occurs alongside the reduction in mammalian target of rapamycin (mTOR) activity and restriction in CD4<sup>+</sup> T cell glycolytic capacity. We demonstrate that the loss of glycolytic metabolism and mTOR activity within the exhausted <i>Ag-exp</i>CD4<sup>+</sup> T cell population during infection coincides with reduction in T-bet expression. T-bet was found to directly bind to and control the transcription of various mTOR and metabolism-related genes within effector CD4<sup>+</sup> T cells. Consistent with this, <i>Ag-exp</i>Th1 cells exhibited significantly higher and sustained mTOR activity than effector T-bet- (non-Th1) <i>Ag-exp</i>T cells throughout the course of malaria. We identified mTOR to be redundant for sustaining T-bet expression in activated Th1 cells, whereas mTOR was necessary but not sufficient for maintaining IFN-γ production by Th1 cells. Immunotherapy targeting PD-1, CTLA-4, and IL-27 blocked CD4<sup>+</sup> T cell exhaustion during malaria infection and was associated with elevated T-bet expression and a concomitant increased CD4<sup>+</sup> T cell glycolytic metabolism. Collectively, our data suggest that mTOR activity is linked to T-bet in <i>Ag-exp</i>CD4<sup>+</sup> T cells but that reduction in mTOR activity may not directly underpin <i>Ag-exp</i>Th1 cell loss and exhaustion during malaria infection. These data have implications for therapeutic reactivation of exhausted CD4<sup>+</sup> T cells during malaria infection and other chronic conditions

DNA–Water Interactions Distinguish Messenger RNA Genes from Transfer RNA Genes

Physicochemical properties of DNA sequences as a guide to developing insights into genome organization has received little attention. Here, we utilize the energetics of DNA to further advance the knowledge on its language at a molecular level. Specifically, we ask the question whether physicochemical properties of different functional units on genomes differ. We extract intramolecular and solvation energies of different DNA base pair steps from a comprehensive set of molecular dynamics simulations. We then investigate the solvation behavior of DNA sequences coding for mRNAs and tRNAs. Distinguishing mRNA genes from tRNA genes is a tricky problem in genome annotation without assumptions on length of DNA and secondary structure of the product of transcription. We find that solvation energetics of DNA behaves as an extremely efficient property in discriminating 2 063 537 genes coding for mRNAs from 56 251 genes coding for tRNAs in all (∼1500) completely sequenced prokaryotic genomes

Longitudinal surveillance of serum titanium ion levels in patients with indigenous 3D printed total temporomandibular joint replacement

Abstract The purpose of this longitudinal study was to surveil the serum titanium ion levels at various time intervals in patients with indigenous 3D-printed total temporomandibular joint replacement (TMJ TJR). The study was conducted on 11 patients (male: 8; female: 3) who had undergone unilateral or bilateral TMJ TJR. Blood samples were drawn preoperatively (T0), 3 months (T1), 6 months (T2), and 1 year (T3) postoperatively. Data were analyzed and a p value of < 0.05 was considered statistically significant. The mean serum titanium ion levels at T0, T1, T2, and T3 was 9.34 ± 8.70 µg/L (mcg/L), 35.97 ± 20.27 mcg/L, 31.68 ± 17.03 mcg/L, and 47.91 ± 15.47 mcg/L respectively. The mean serum titanium ion levels increased significantly at T1 (p = 0.009), T2 (p = 0.032), and T3 (p = 0.00) interval. There was no significant difference between unilateral and bilateral groups. Serum titanium ion continued to show increased levels till the last follow-up of 1 year. These initial serum titanium ion levels increase is due to the initial wear phase of the prosthesis which manifests over 1 year. Further studies with large sample sizes and long-term follow-ups are required to see the deleterious effect if any on the TMJ TJR

JAZF1-SUZ12 dysregulates PRC2 function and gene expression during cell differentiation

Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain gene repression and is essential for cell differentiation. In low-grade endometrial stromal sarcoma (LG-ESS), the PRC2 subunit SUZ12 is often fused with the NuA4/TIP60 subunit JAZF1. We show that JAZF1-SUZ12 dysregulates PRC2 composition, genome occupancy, histone modification, gene expression, and cell differentiation. Loss of the SUZ12 N terminus in the fusion protein abrogates interaction with specific PRC2 accessory factors, reduces occupancy at PRC2 target genes, and diminishes H3K27me3. Fusion to JAZF1 increases H4Kac at PRC2 target genes and triggers recruitment to JAZF1 binding sites during cell differentiation. In human endometrial stromal cells, JAZF1-SUZ12 upregulated PRC2 target genes normally activated during decidualization while repressing genes associated with immune clearance, and JAZF1-SUZ12-induced genes were also overexpressed in LG-ESS. These results reveal defects in chromatin regulation, gene expression, and cell differentiation caused by JAZF1-SUZ12 that may underlie its role in oncogenesis