CWRML: representing crop wild relative conservation and use data in XML

Background Crop wild relatives are wild species that are closely related to crops. They are valuable as potential gene donors for crop improvement and may help to ensure food security for the future. However, they are becoming increasingly threatened in the wild and are inadequately conserved, both in situ and ex situ. Information about the conservation status and utilisation potential of crop wild relatives is diverse and dispersed, and no single agreed standard exists for representing such information; yet, this information is vital to ensure these species are effectively conserved and utilised. The European Community-funded project, European Crop Wild Relative Diversity Assessment and Conservation Forum, determined the minimum information requirements for the conservation and utilisation of crop wild relatives and created the Crop Wild Relative Information System, incorporating an eXtensible Markup Language (XML) schema to aid data sharing and exchange. Results Crop Wild Relative Markup Language (CWRML) was developed to represent the data necessary for crop wild relative conservation and ensure that they can be effectively utilised for crop improvement. The schema partitions data into taxon-, site-, and population-specific elements, to allow for integration with other more general conservation biology schemata which may emerge as accepted standards in the future. These elements are composed of sub-elements, which are structured in order to facilitate the use of the schema in a variety of crop wild relative conservation and use contexts. Pre-existing standards for data representation in conservation biology were reviewed and incorporated into the schema as restrictions on element data contents, where appropriate. Conclusion CWRML provides a flexible data communication format for representing in situ and ex situ conservation status of individual taxa as well as their utilisation potential. The development of the schema highlights a number of instances where additional standards-development may be valuable, particularly with regard to the representation of population-specific data and utilisation potential. As crop wild relatives are intrinsically no different to other wild plant species there is potential for the inclusion of CWRML data elements in the emerging standards for representation of biodiversity data

Healthcare resource utilisation and related costs of patients with CKD from the UK: a report from the DISCOVER CKD retrospective cohort

Background Chronic kidney disease (CKD) is widely reported to decrease quality of life, increase morbidity and mortality and cause increased healthcare resource utilisation (HCRU) as the disease progresses. However, there is a relative paucity of accurate and recent estimates of HCRU in this patient population. Our aim was to address this evidence gap by reporting HCRU and related costs in patients with CKD from the UK primary and secondary care settings. Methods HCRU and cost estimates of CKD were derived for UK patients included in the DISCOVER CKD cohort study using clinical records from the Clinical Practice Research Datalink linked to external databases. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using the urinary albumin:creatinine ratio (UACR) and estimated glomerular filtration rate. Results Hospitalisation rates more than tripled between low (A1) and high (A3) UACR categories and the mean annual per-patient costs ranged from £4966 (A1) to £9196 (A3) and from £4997 (G2) to £7595 (G5), demonstrating that a large healthcare burden can be attributed to a relatively small number of patients with later stage CKD, including those with kidney failure and/or albuminuria. Conclusions HCRU and costs associated with CKD impose a substantial burden on the healthcare system, particularly in the more advanced stages of CKD. New interventions that can delay the progression of CKD to kidney failure may not only prolong the patient’s life, but would also provide significant resource and cost savings to healthcare providers

Characterization of peri-infarct zone by CMR is a robust predictor of major adverse events and is strongly associated with systemic inflammatory response post-myocardial infarction

[No abstract available

Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis

Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes.

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Attachment of HeLa cells during early G1 phase

Both growth factor directed and integrin dependent signal transduction were shown to take place directly after completion of mitosis. The local activation of these signal transduction cascades was investigated in early G1 cells. Interestingly, various key signal transduction proteins were found in blebs at the cell membrane within 30 min after mitosis. These membrane blebs appeared in round, mitotic-like cells and disappeared rapidly during spreading of the cells in G1 phase. In addition to tyrosine-phosphorylated proteins, the blebs contained also phosphorylated FAK and phosphorylated MAP kinase. The formation of membrane blebs in round, mitotic cells before cell spreading is not specific for mitotic cells, because similar features were observed in trypsinized cells. Just before cell spreading also these cells exhibited membrane blebs containing active signal transduction proteins. Inhibition of signal transduction did not affect membrane bleb formation, suggesting that the membrane blebs were formed independent of signal transduction

A framework for the integration of green and lean six sigma for superior sustainability performance

Evidence suggests that Lean, Six Sigma and Green approaches make a positive contribution to the economic, social and environmental (i.e. sustainability) performance of organizations. However, evidence also suggests that organizations have found their integration and implementation challenging. The purpose of this research is therefore to present a framework that methodically guides companies through a five stages and sixteen steps process to effectively integrate and implement the Green, Lean and Six Sigma approaches to improve their sustainability performance. To achieve this, a critical review of the existing literature in the subject area was conducted to build a research gap, and subsequently develop the methodological framework proposed. The paper presents the results from the application of the proposed framework in four organizations with different sizes and operating in a diverse range of industries. The results showed that the integration of Lean Six Sigma and Green helped the organizations to averagely reduce their resources consumption from 20% to 40% and minimize the cost of energy and mass streams by 7-12%. The application of the framework should be gradual, the companies should assess their weaknesses and strengths, set priorities, and identify goals for successful implementation. This paper is one of the very first researches that presents a framework to integrate Green and Lean Six Sigma at a factory level, and hence offers the potential to be expanded to multiple factories or even supply chains

Validation of the Tetracycline Regulatable Gene Expression System for the Study of the Pathogenesis of Infectious Disease

Understanding the pathogenesis of infectious disease requires the examination and successful integration of parameters related to both microbial virulence and host responses. As a practical and powerful method to control microbial gene expression, including in vivo, the tetracycline-regulatable system has recently gained the favor of many investigative groups. However, some immunomodulatory effects of the tetracyclines, including doxycycline, could potentially limit its use to evaluate host responses during infection. Here we have used a well-established murine model of disseminated candidiasis, which is highly dependent on both the virulence displayed by the fungal cells and on the host immune status, to validate the use of this system. We demonstrate that the pathogenesis of the wild type C. albicans CAF2-1 strain, which does not contain any tet-regulatable element, is not affected by the presence of doxycycline. Moreover levels of key cytokines, chemokines and many other biomarkers, as determined by multi-analyte profiling, remain essentially unaltered by the presence of the antibiotic during infection. Our results indicate that the levels of doxycycline needed to control the tetracycline regulatable promoter gene expression system have no detectable effect on global host responses during candidiasis. Because tet-regulatable systems are now being increasingly used in a variety of pathogenic microorganisms, these observations have wide implications in the field of infectious diseases

Serum interleukin-5 levels are elevated in mild and moderate persistent asthma irrespective of regular inhaled glucocorticoid therapy

BACKGROUND: Interleukin-5 (IL-5) is thought to play a pivotal role in the pathogenesis of asthma. High levels of circulating IL-5 have been documented in acute asthma. However, serum IL-5 levels in mild to moderate asthmatics and the influence of regular use of inhaled glucocorticoids, is not known. METHODS: Fifty-six asthmatics and 56 age and sex matched controls were recruited prospectively from an outpatient department. Information on asthma severity and treatment was gathered by a questionnaire. Serum IL-5, total IgE and specific IgE levels were measured in a blinded fashion. RESULTS: There were 32 atopic and 24 non-atopic mild-to-moderate asthmatics. The median serum IL-5 levels in atopic asthmatics (9.5 pg/ml) and in non-atopic asthmatics (8.1 pg/ml) were significantly higher than in normal controls (4.4 pg/ml, both p < 0.003). However, median serum IL-5 levels in atopic and non-atopic asthmatics were not significantly different. The median serum IL-5 level was insignificantly higher in fourteen moderate persistent asthmatics (10.6 pg/ml) compared to forty-two mild persistent asthmatics (7.3 pg/ml) (p = 0.13). The median serum IL-5 levels in asthmatics using regular inhaled steroids (7.8 pg/ml) was not significantly different from those not using inhaled steroids (10.2 pg/ml). Furthermore, serum total IgE levels and eosinophil counts were not significantly different in those using versus those not using inhaled glucocorticoids. CONCLUSION: Serum IL-5 levels are elevated in mild and moderate persistent atopic and non-atopic asthmatics. Regular use of inhaled glucocorticoids may not abrogate the systemic Th2 type of inflammatory response in mild-moderate persistent asthma