Studying the role of integrin αVβ6 in pancreatic cancer

PhDPancreatic cancer is often referred to as the “silent killer“ due to the asymptomatic nature of the disease in the early stages and the extremely poor prognosis overall. The average one-year survival rate for PDAC patients is 24% (American Cancer Society, facts and figures, 2010), decreasing to 5%-6% over 5 years (WHO report, Pancreatic cancer, 2010). Only 20% of patients are suitable for surgical resection at the time of diagnosis and treatment options available to PDAC patients have not improved significantly over the past few decades. Thus novel therapeutic approaches are essential to treat this disease. Our experimental, clinical and pre-clinical data suggest integrin αvβ6 may be a suitable target. Bioinformatics studies using the Pancreatic Expression Database revealed that the β6 gene (ITGB6) was highly up regulated in pancreatic ductal carcinoma (PDAC) compared with normal pancreas. Further analysis carried out showed that there was a significant correlation between ITGB6 expression at the mRNA level and survival in a cohort of 292 PDAC patients. Immunohistochemistry analysis on two separate patient cohorts (n=118 and n=147) showed that normal pancreas lacked αvβ6 expression whereas 91% of PDAC tissues expressed αvβ6 at the protein level. There was no significant correlation between αvβ6 expression and survival at the protein level in both cohorts of patients tested. Flow cytometry and Western blotting analyses on a panel of PDAC cell lines confirmed expression of αvβ6 in PDAC cell lines. This study investigated the functional role of αvβ6 in PDAC cell lines. Antibody mediated function blockade of αvβ6 significantly inhibited proliferation in a dose dependent manner, specifically in αvβ6 positive PDAC cell lines. A significant reduction in migration and invasion was also observed in a panel of αvβ6 positive PDAC cell lines when treated with an αvβ6 function-blocking antibody. αvβ6 targeted antibody mediated therapy in combination with gemcitabine significantly inhibited tumour growth in a physiologically relevant pre-clinical subcutaneous xenograft model of PDAC. These data reaffirms that αvβ6 is a potential novel therapeutic target and an αvβ6 specific function-blocking antibody can be used as a novel agent to treat pancreatic adenocarcinoma patients.Pancreatic Cancer Research Fund (PCRF); Howard-Kerr scholarship; ORSAS scholarship from Queen Mary University of London

Dose–Sensitivity, Conserved Non-Coding Sequences, and Duplicate Gene Retention through Multiple Tetraploidies in the Grasses

Whole genome duplications, or tetraploidies, are an important source of increased gene content. Following whole genome duplication, duplicate copies of many genes are lost from the genome. This loss of genes is biased both in the classes of genes deleted and the subgenome from which they are lost. Many or all classes are genes preferentially retained as duplicate copies are engaged in dose sensitive protein–protein interactions, such that deletion of any one duplicate upsets the status quo of subunit concentrations, and presumably lowers fitness as a result. Transcription factors are also preferentially retained following every whole genome duplications studied. This has been explained as a consequence of protein–protein interactions, just as for other highly retained classes of genes. We show that the quantity of conserved noncoding sequences (CNSs) associated with genes predicts the likelihood of their retention as duplicate pairs following whole genome duplication. As many CNSs likely represent binding sites for transcriptional regulators, we propose that the likelihood of gene retention following tetraploidy may also be influenced by dose–sensitive protein–DNA interactions between the regulatory regions of CNS-rich genes – nicknamed bigfoot genes – and the proteins that bind to them. Using grass genomes, we show that differential loss of CNSs from one member of a pair following the pre-grass tetraploidy reduces its chance of retention in the subsequent maize lineage tetraploidy

Transplant ineligible multiple myeloma patients presenting as paraplegia/paraparesis a prospective single institution study

Background: Multiple myeloma a plasma cell neoplasm characterized by heterogeneous myriad of presentation with paraparesis or paraplegia in 20% cases due to spinal cord compression by vertebral collapse, compression or fracture.Methods: This is a prospective observational study of thirty transplant ineligible multiple myeloma patients with paraplegia/paraparesis. Pretreatment evaluation done as per standard protocol including MRI whole spine. Involved spine XRT 8Gy single fraction followed by BLD (Bortezomib 1.3mg/m2 weekly once, Lenalidomide 10mg/m2 for 21 days, oral dexamethasone 40 mg weekly once). Neurological parameters, time to neurological and tumor response at 6 months assessed. Patients in very good partial response or complete response were maintained on Lenalidomide and bisphosphonate therapy for a period of two years. The duration of symptoms and time to response were analyzed with Mann Whitney Cox test.Results: 15 patients were grade 0 power and others grade 1 or 2. Median time to any neurological response was 2.97 weeks. 63.3% of patients achieved power of grade 5, 30% grade 4 and 6.7% grade 3 powers. 23.3% patients received complete response while 63.3% patient’s very good partial response.Conclusions: Bedridden myeloma patients had an excellent improvement in quality of life and tumor control with this treatment schedule.

Facile Green Synthesis of Cinnamomum tamala Extract Capped Silver Nanoparticles and its Biological Applications

The plant mediated biogenic synthesis of nanoparticles is of magnificent concern due to its eco-benign and single pot nature. Here, Cinnamomum tamala (C. tamala) aqueous leaf extract was utilised for the silver nanoparticles’ (Ag NPs) synthesis. The phytoconstituents in the leaf extract were analysed by standard methods. These metabolites, especially carbohydrate polymers reduce Ag ions to Ag NPs accompanied by a reddish-brown coloration of the reaction mixture. The visual observation of intense brown colour is the first indication of the formation of Ag NPs. Various spectro-analytical techniques further characterise the Ag NPs. The green synthesised spherical Ag NPs were crystalline with an average size of 38 nm. The Ag NPs were scrutinised for antioxidant, antimicrobial and cytotoxic activity and obtained good results. The free radical scavenging was studied by 2, 2-Diphenyl-l-picrylhydrazyl (DPPH) assay. The antibacterial activity of Ag NPs was assessed against human pathogens, and it shown to have good antibacterial potency against a wide spectrum of bacteria. The cytotoxic activity against HEK-293T (human embryonic kidney) cell line was evaluated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. These potent biological activities enable C. tamala capped Ag NPs to be suitable candidates for the future applications in various fields, predominantly clinical and biomedical

A Bayesian Analysis of the Correlations Among Sunspot Cycles

Sunspot numbers form a comprehensive, long-duration proxy of solar activity and have been used numerous times to empirically investigate the properties of the solar cycle. A number of correlations have been discovered over the 24 cycles for which observational records are available. Here we carry out a sophisticated statistical analysis of the sunspot record that reaffirms these correlations, and sets up an empirical predictive framework for future cycles. An advantage of our approach is that it allows for rigorous assessment of both the statistical significance of various cycle features and the uncertainty associated with predictions. We summarize the data into three sequential relations that estimate the amplitude, duration, and time of rise to maximum for any cycle, given the values from the previous cycle. We find that there is no indication of a persistence in predictive power beyond one cycle, and conclude that the dynamo does not retain memory beyond one cycle. Based on sunspot records up to October 2011, we obtain, for Cycle 24, an estimated maximum smoothed monthly sunspot number of 97 +- 15, to occur in January--February 2014 +- 6 months.Comment: Accepted for publication in Solar Physic

AgBioData consortium recommendations for sustainable genomics and genetics databases for agriculture

The future of agricultural research depends on data. The sheer volume of agricultural biological data being produced today makes excellent data management essential. Governmental agencies, publishers and science funders require datamanagement plans for publicly funded research. Furthermore, the value of data increases exponentially when they are properly stored, described, integrated and shared, so that they can be easily utilized in future analyses. AgBioData (https://www.agbiodata.org) is a consortium of people working at agricultural biological databases, data archives and knowledgbases who strive to identify common issues in database development, curation and management, with the goal of creating database products that are more Findable, Accessible, Interoperable and Reusable. We strive to promote authentic, detailed, accurate and explicit communication between all parties involved in scientific data. As a step toward this goal, we present the current state of biocuration, ontologies, metadata and persistence, database platforms, programmatic (machine) access to data, communication and sustainability with regard to data curation. Each section describes challenges and opportunities for these topics, along with recommendations and best practices

An observational study to evaluate the efficacy of Saha Ashwagandhadi Taila Nasya and Balashatavaryadi Ghrita Tarpana in Prathama Patalagata Timira with special reference to Simple Myopia

Introduction: Prathama Patalagata Timira is one of the stages of Timira which is a Drishtigata Roga and can be correlated to Simple Myopia with the characteristic symptom of blurred vision for distant objects. This disease is said to be physiological and become the major health concern. It is the common cause of ocular morbidity that may ultimately lead to blindness as explained by Vagbhatacharya. Objectives: The objectives of the study are to evaluate efficacy of Nasya and Tarpana in relieving Myopia & Asthenopic symptoms such as head ache, eye strain, watering of the eyes. Methods: 30 patients fulfilling the inclusion criteria of simple myopia were randomly selected. Nasya with Saha Ashwagandhadi taila for 7 days then from 8th day Tarpana with Balashatavaryadi Ghrita was done for 7 days, followed by 2 follow-ups. Results: The overall assessment was done before treatment, on 15th day, 30th day and 44th day. Conclusion: Nasya has role in improving vision where as Tarpana relieves asthenopic symptoms as well as improves vision

Comparison of conventional smear cytology and manual liquid based cytology based on smears from normal oral exfoliated cells

<p>Liquid-based cytology (LBC), since its inception in the 1990s, has shown significant advantages over conventional exfoliative cytology. LBC gives better results than conventional method as it not only enhances both sensitivity and specificity, but also provides material for further investigations. However, LBC requires expensive automated devices and materials, which might not be affordable for many cytopathology laboratories in countries with poor resources. In order to formulate an economic cytological procedure with the accuracy of LBC, smears made out of manual liquid based cytology (MLBC) technique was followed in this study and the results were compared with respective conventional cytology smears. To the authors’ knowledge, this is the first comparative study between MLBC and conventional method done for oral cavity in normal buccal mucosa. One hundred apparently normal subjects who reported to the outpatient department were selected after obtaining informed consent from all the subjects. Two Scrapings were made in each patient from the clinically normal appearing buccal mucosa. Both conventional and MLBC smears were stained by routine Papanicolaou technique and evaluated by three independent observers for specimen adequacy, thickness of the smear, uniformity of cell distribution, clarity or resolution of the cells, presence of background artifacts, and staining characteristics of the cells. Each parameter was graded as satisfactory; satisfactory but limited; or unsatisfactory. Number of satisfactory results obtained in MLBC smears was significantly higher than that by conventional smears. After comparison of smears prepared from conventional cytology and manual liquid-based cytology, we conclude that manual liquid-based cytology is both cost effective and also technically sound method with specific and clear results.</p