B mu G@Sbase-a microbial gene expression and comparative genomic database

The reducing cost of high-throughput functional genomic technologies is creating a deluge of high volume, complex data, placing the burden on bioinformatics resources and tool development. The Bacterial Microarray Group at St George's (BμG@S) has been at the forefront of bacterial microarray design and analysis for over a decade and while serving as a hub of a global network of microbial research groups has developed BμG@Sbase, a microbial gene expression and comparative genomic database. BμG@Sbase (http://bugs.sgul.ac.uk/bugsbase/) is a web-browsable, expertly curated, MIAME-compliant database that stores comprehensive experimental annotation and multiple raw and analysed data formats. Consistent annotation is enabled through a structured set of web forms, which guide the user through the process following a set of best practices and controlled vocabulary. The database currently contains 86 expertly curated publicly available data sets (with a further 124 not yet published) and full annotation information for 59 bacterial microarray designs. The data can be browsed and queried using an explorer-like interface; integrating intuitive tree diagrams to present complex experimental details clearly and concisely. Furthermore the modular design of the database will provide a robust platform for integrating other data types beyond microarrays into a more Systems analysis based future

Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle.

BACKGROUND: The aim of the present study was to determine the influence of age and habitual activity level, at rest and following a single bout of high-intensity exercise, on the levels of three proteins poly(ADP-ribose) polymerase-1 (PARP-1), cleaved-PARP-1 and poly(ADP-ribose) glycohydrolase (PARG), involved in the DNA repair and cell death responses to stress and genotoxic insults. Muscle biopsies were obtained from the vastus lateralis of young trained (22 ± 3 years, n = 6), young untrained (24 ± 4 years, n = 6), old trained (64 ± 3 years, n = 6) and old untrained (65 ± 6 years, n = 6) healthy males before, immediately after and three days following a high-intensity interval exercise bout. RESULTS: PARP-1, which catalyzes poly(ADP-ribosyl)ation of proteins and DNA in response to a range of intrinsic and extrinsic stresses, was increased at baseline in old trained and old untrained compared with young trained and young untrained participants (P ≤ 0.05). Following exercise, PARP-1 levels remained unchanged in young trained participants, in contrast to old trained and old untrained where levels decreased and young untrained where levels increased (P ≤ 0.05). Interestingly, baseline levels of the cleaved PARP-1, a marker of apoptosis, and PARG, responsible for polymer degradation, were both significantly elevated in old untrained compared with old trained, young trained and young untrained (P ≤ 0.05). Despite this baseline difference in PARG, there was no change in any group following exercise. There was a non-significant statistical trend (P = 0.072) towards increased cleaved-PARP-1 expression post-exercise in younger but not old persons, regardless of training status. CONCLUSIONS: Collectively, these results show that exercise slows the progression towards a chronically stressed state but has no impact on the age-related attenuated response to acute exercise. Our findings provide valuable insight into how habitual exercise training could protect skeletal muscle from chronic damage to macromolecules and may reduce sarcopenia in older people

Diet management, lifestyle factors and education needs by target attainment in Italian youth with type 1 diabetes from the Global TEENs study

Background and aims: TEENs is an international, cross-sectional observational study, conducted in 20 countries in order to assess T1D management and psychosocial parameters in 8-25-year-olds (y/o). Data on diet management, lifestyle factors and education needs by target HbA1c attainment from the Italian cohort are reported. Materials and methods: Data were collected at 23 centres by participant interview, medical record review and participant/parent survey from 1,009 Italian youth (46% female) in three age groups: 8-12 y/o (n=330), 13-18 y/o (n=490), and 19-25 y/o (n=189). HbA1c was measured uniformly using A1cNow™ with target HbA1c defined as <7.5% (58 mmol/mol) for ≤18 y/o (ISPAD) and <7% (53 mmol/mol) for >18 y/o (ADA). Results: Overall, 40% of participants met HbA1c targets. Measuring food intake based on experience was the most common method used by all age groups, followed by carbohydrate counting (Table). Of the participants who used carbohydrate counting, a higher percentage met target HbA1c than did not in all age groups, with a significant effect on target attainment due to carbohydrate counting compared with other methods observed in 13-18 y/o (p=0.035). Avoiding sugars was the least common method used in all age groups. Across all age groups, participants who did not undertake any exercise were numerically less likely to reach HbA1c target; on the contrary, participants who exercised 1-2 days/week were numerically more likely to reach HbA1c target. Performing exercise had a significant effect on target HbA1c attainment in 8-12 y/o (p=0.012). The majority of participants were in the underweight/normal body mass index (BMI) category in all age groups, with no clear pattern between BMI class and the proportion of patients reaching HbA1c target. Participants of all ages commonly requested education on diet, carbohydrate counting, how to manage T1D during illness, and how to manage blood glucose levels with exercise. Conclusion: Carbohydrate counting and exercising at least twice per week help to attain HbA1c target across all age groups. Assessment of lifestyle factors suggests that efforts targeting carbohydrate counting and exercise could promote successful health outcomes and help more patients with T1D to reach the recommended HbA1c target. Supported by: Sanof

Development of minimal fermentation media supplementation for ethanol production using two Saccharomyces cerevisiae strains

Ethanol production by fermentation is strongly dependent on media composition. Specific nutrients, such as trace elements, vitamins and nitrogen will affect the physiological state and, consequently, the fermentation performance of the micro-organism employed. The purpose of this study has been to assess the highest ethanol production by a minimal medium, instead of the more complex nutrients supplementation used during alcoholic fermentation. All fermentation tests were carried out using a microwell plate reader to monitor the processes. Two Saccharomyces cerevisiae strains (NCYC 2826 and NCYC 3445) were tested using three nitrogen sources, supplied with different vitamin and salts. The results show that solutions made of urea phosphate, KCl, MgSO4·7H2O, Ca-panthothenate, biotin allowed an ethanol yield of 22.9 and 23.4 g/L for strain NCYC 2826 and NCYC 3445, respectively, representing 90 and 92% of the theoretical yield. All tests were carried out using glucose as common reference carbon source

Interpretation and application of carbon isotope ratios in freshwater diatom silica

Carbon incorporated into diatom frustule walls is protected from degradation enabling analysis for carbon isotope composition (δ13Cdiatom). This presents potential for tracing carbon cycles via a single photosynthetic host with well-constrained ecophysiology. Improved understanding of environmental processes controlling carbon delivery and assimilation is essential to interpret changes in freshwater δ13Cdiatom. Here relationships between water chemistry and δ13Cdiatom from contemporary regional data sets are investigated. Modern diatom and water samples were collected from river catchments within England and lake sediments from across Europe. The data suggest dissolved, biogenically produced carbon supplied proportionately to catchment productivity was critical in the rivers and soft water lakes. However, dissolved carbon from calcareous geology overwhelmed the carbon signature in hard water catchments. Both results demonstrate carbon source characteristics were the most important control on δ13Cdiatom, with a greater impact than productivity. Application of these principles was made to a sediment record from Lake Tanganyika. δ13Cdiatom co-varied with δ13Cbulk through the last glacial and Holocene. This suggests carbon supply was again dominant and exceeded authigenic demand. This first systematic evaluation of contemporary δ13Cdiatom controls demonstrates that diatoms have the potential to supply a record of carbon cycling through lake catchments from sediment records over millennial timescales

Does non-employment contribute to the health disadvantage among lone mothers in Britain, Italy and Sweden? Synergy effects and the meaning of family policy.

This study analyses self-rated health and non-employment and potential synergy effects among lone and couple mothers aged 25–59 in Britain, Sweden and Italy, representing different family policy categories using data from national surveys (2000–2005). Synergy effects on health were calculated by synergy index. Non-employment only marginally contributed to the excess risk of poor health among lone mothers but there were synergy effects between lone motherhood and non-employment in all three countries, producing a higher risk of poor health than would be expected from a simple addition of these exposures. Results are discussed in relation to the different family policy and living contexts

Impact of age on outcome after colorectal cancer surgery in the elderly - a developing country perspective

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is a major source of morbidity and mortality in the elderly population and surgery is often the only definitive management option. The suitability of surgical candidates based on age alone has traditionally been a source of controversy. Surgical resection may be considered detrimental in the elderly solely on the basis of advanced age. Based on recent evidence suggesting that age alone is not a predictor of outcomes, Western societies are increasingly performing definitive procedures on the elderly. Such evidence is not available from our region. We aimed to determine whether age has an independent effect on complications after surgery for colorectal cancer in our population.</p> <p>Methods</p> <p>A retrospective review of all patients who underwent surgery for pathologically confirmed colorectal cancer at Aga Khan University Hospital, Karachi between January 1999 and December 2008 was conducted. Using a cut-off of 70 years, patients were divided into two groups. Patient demographics, tumor characteristics and postoperative complications and 30-day mortality were compared. Multivariate logistic regression analysis was performed with clinically relevant variables to determine whether age had an independent and significant association with the outcome.</p> <p>Results</p> <p>A total of 271 files were reviewed, of which 56 belonged to elderly patients (≥ 70 years). The gender ratio was equal in both groups. Elderly patients had a significantly higher comorbidity status, Charlson score and American society of anesthesiologists (ASA) class (all p < 0.001). Upon multivariate analysis, factors associated with more complications were ASA status (95% CI = 1.30-6.25), preoperative perforation (95% CI = 1.94-48.0) and rectal tumors (95% CI = 1.21-5.34). Old age was significantly associated with systemic complications upon univariate analysis (p = 0.05), however, this association vanished upon multivariate analysis (p = 0.36).</p> <p>Conclusion</p> <p>Older patients have more co-morbid conditions and higher ASA scores, but increasing age itself is not independently associated with complications after surgery for CRC. Therefore patient selection should focus on the clinical status and ASA class of the patient rather than age.</p

MTF-1-Mediated Repression of the Zinc Transporter Zip10 Is Alleviated by Zinc Restriction

The regulation of cellular zinc uptake is a key process in the overall mechanism governing mammalian zinc homeostasis and how zinc participates in cellular functions. We analyzed the zinc transporters of the Zip family in both the brain and liver of zinc-deficient animals and found a large, significant increase in Zip10 expression. Additionally, Zip10 expression decreased in response to zinc repletion. Moreover, isolated mouse hepatocytes, AML12 hepatocytes, and Neuro 2A cells also respond differentially to zinc availability in vitro. Measurement of Zip10 hnRNA and actinomycin D inhibition studies indicate that Zip10 was transcriptionally regulated by zinc deficiency. Through luciferase promoter constructs and ChIP analysis, binding of MTF-1 to a metal response element located 17 bp downstream of the transcription start site was shown to be necessary for zinc-induced repression of Zip10. Furthermore, zinc-activated MTF-1 causes down-regulation of Zip10 transcription by physically blocking Pol II movement through the gene. Lastly, ZIP10 is localized to the plasma membrane of hepatocytes and neuro 2A cells. Collectively, these results reveal a novel repressive role for MTF-1 in the regulation of the Zip10 zinc transporter expression by pausing Pol II transcription. ZIP10 may have roles in control of zinc homeostasis in specific sites particularly those of the brain and liver. Within that context ZIP10 may act as an important survival mechanism during periods of zinc inadequacy

A qualitative evaluation of the impact of a palliative care course on preregistration nursing students' practice in Cameroon

Background Current evidence suggests that palliative care education can improve preregistration nursing students’ competencies in palliative care. However, it is not known whether these competencies are translated into students’ practice in the care of patients who are approaching the end of life. This paper seeks to contribute to the palliative care evidence base by examining how nursing students in receipt of education report transfer of learning to practice, and what the barriers and facilitators may be, in a resource-poor country. Methods We utilised focus groups and individual critical incident interviews to explore nursing students’ palliative care learning transfer. Three focus groups, consisting of 23 participants and 10 individual critical incident interviews were conducted with preregistration nursing student who had attended a palliative care course in Cameroon and had experience caring for a patient approaching the end of life. Data was analysed thematically, using the framework approach. Results The results suggest that nursing students in receipt of palliative care education can transfer their learning to practice. Students reported recognizing patients with palliative care needs, providing patients with physical, psychosocial and spiritual support and communicating patient information to the wider care team. They did however perceive some barriers to this transfer which were either related to themselves, qualified nurses, the practice setting or family caregivers and patients. Conclusion The findings from this study suggest that nursing student in receipt of palliative care education can use their learning in practice to provide care to patients and their families approaching the end of life. Nevertheless, these findings need to be treated with some caution given the self-reported nature of the data. Demonstrating the link between preregistration palliative care education and patient care is vital to ensuring that newly acquired knowledge and skills are translated and embedded into clinical practice. This study also has implications for advocating for palliative care policies and adequately preparing clinical placement sites for students’ learning and transfer of learning

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure