Further developments towards a genome-scale metabolic model of yeast

Background

To date, several genome-scale network reconstructions have been used to describe the metabolism of the yeast Saccharomyces cerevisiae, each differing in scope and content. The recent community-driven reconstruction, while rigorously evidenced and well annotated, under-represented metabolite transport, lipid metabolism and other pathways, and was not amenable to constraint-based analyses because of lack of pathway connectivity.

Results

We have expanded the yeast network reconstruction to incorporate many new reactions from the literature and represented these in a well-annotated and standards-compliant manner. The new reconstruction comprises 1102 unique metabolic reactions involving 924 unique metabolites - significantly larger in scope than any previous reconstruction. The representation of lipid metabolism in particular has improved, with 234 out of 268 enzymes linked to lipid metabolism now present in at least one reaction. Connectivity is emphatically improved, with more than 90% of metabolites now reachable from the growth medium constituents. The present updates allow constraint-based analyses to be performed; viability predictions of single knockouts are comparable to results from in vivo experiments and to those of previous reconstructions.

Conclusions

We report the development of the most complete reconstruction of yeast metabolism to date that is based upon reliable literature evidence and richly annotated according to MIRIAM standards. The reconstruction is available in the Systems Biology Markup Language (SBML) and via a publicly accessible database http://www.comp-sys-bio.org/yeastnet/.     

Investigation on the potential application of biological agents in the extension of shelf life of fresh beef in Nigeria

The objective of this study was to evaluate the ability of lactic acid bacteria (LAB) cultures to preserve fresh beef at room temperature, with a view to promoting safety and availability of the product in Nigeria. Two LAB strains, Pediococcus pentosaceus LIV 01 and P. acidilactici FLE 01, were applied as starters (10⁶ cfu/g) on sliced fresh beef samples, and were stored for 7 days at 30°C. Analyses of microbiological, thiobarbituric acid (TBA) and free fatty acids (FFA) were carried out during storage. Results indicated reduction in the Enterobacteriaceae, Staphylococcus and coliforms in starter inoculated samples. TBA and FFA were lower in starter culture inoculated samples compared to controls during storage. In a challenge experiment against the LAB cultures during a 7-day storage, two sets of meat were inoculated separately with 10⁶ cfu/g each of pathogenic organisms Listeria monocytogenes and Salmonella Typhimurium. There was about 1 log reduction in the L. monocytogenes on day 1 while counts were below detection limit (<2 log) on day 2 in meat samples inoculated with P. pentosaceus alone and in combination with P. acidilactici. Counts of S. Typhimurium showed about 2 log reduction in starter inoculated samples during storage while an increase by about 3 log was observed in control samples. The protective ability of the LAB strains could be exploited in shelf life extension and control of foodborne pathogens in fresh beef; their use as biological preservatives may help in promoting public health, safety and availability of the product in Nigeria.     

Hydration State of Goats Transported by Road for 12 Hours During the Hot-Dry Conditions and the Modulating Role of Ascorbic Acid

This study investigated the effects of 12 hr of road transportation during the hot-dry conditions and the modulating role of ascorbic acid (AA) on the hydration state of goats. Twenty goats who served as treatment goats received oral administration of 100 mg/kg body weight of AA, whereas another 20 control goats received sterile water; thereafter, the goats were loaded and transported. The study determined changes in skin thickness; albumin (Alb); total protein (TP); elimination of the gut content; fecal water; urine specific gravity (SG); and pH before, during, and after the transportation. The result obtained in the control goats showed significant (p < .05) increases in the values of TP, Alb, urine SG, and pH; elimination; and drinking behavior, whereas skin thickness decreased over transportation. In the treatment goats who were administered AA, the changes observed in the values were insignificant (p > .05). In conclusion, 12-hr road transportation of goats induced dehydration, which may affect the welfare and health status of the goats. The administration of AA ameliorated the risk of adverse effects of handling, loading, transportation, and hot-dry conditions on hydration state of goats.     

Stand dynamics and spatial patterns across varying sites in the invasive Lantana camara L. (Verbenaceae)

As with many invasive plant species, little is known of the population spatial patterns and stand dynamics of Lantana camara L. (Verbenaceae)??a thicket-forming weed of worldwide significance in managed and conservation lands, including coastal and inland habitats of Eastern Australia. Consequently, we mapped and followed annually for 3?years the demographic fate of more than 2000 Lantana individuals at sites with four land-uses (hoop pine plantation, cattle farm, and two eucalyptus forests with occasional grazing and periodic burning regime, respectively) in Queensland, SE Australia. Populations exhibited plant size distributions that were continuous (i.e., of L or symmetric type) and unimodal, except the farm population where bimodality was observed. Newly established plants could be reproductive within one growing season at ~50?cm in height, especially where environmental resources were not limiting. Density had an appreciable effect on the weed??s reproductive capacity and growth, but not on survival. Established and newly recruited individuals were aggregated but the degree of aggregation decreased with plant size. However, in the sites that had experienced burning or mechanical clearing, Lantana seedling/juvenile recruitment assumed negative association (spatial displacement) in relation to established individuals. The findings of this study agree with the notion that ecological processes often leave characteristic spatial signatures, which if interpreted using appropriate hypotheses can help to ascertain factors responsible for the observed spatial patterns and stand dynamics.     

Biosynthesis of chiral α- and β-pinenes in pinus species

C-3 of (+) and (?)-α-pinene and of (?)-β-pinene biosynthesized in several Pinus species was derived from C-2 of mevalonate; and the hydrogen at C-5 in all the isomers was derived from that at C-6 in nerol. This pattern is consistent with two routes for bicyclization of the acyclic biosynthetic precursor: one leads to (?)-β-pinene and the other to (+)-α-pinene of opposite absolute configuration. (?)-α-Pinene probably results from subsequent isomerisation of the (?)-β-isomer, and (very small) amounts of (+)-β-pinene result from similar (unfavoured thermodynamically) isomerisation of the (+)-α-isomer.     

Erratum to: Lead Exposure: A Contributing Cause of the Current Breast Cancer Epidemic in Nigerian Women

Breast cancer incidence in Nigerian women has significantly increased during the past three decades in parallel with the rapid industrialization of that country. This suggested that the associated widespread contamination of the soil and of the water supplies by lead (Pb) and other industrial metals was a major contributing cause. Because of its many domestic, industrial, and automotive uses, Pb is of particular concern as it has been shown to promote the development of mammary tumors in murine mammary tumor virus-infected female C3H mice at levels as low of 0.5 ppm Pb in the drinking water. Lead belongs to the group of selenium-antagonistic elements that interact with selenium (Se), abolishing its anti-carcinogenic effect. Lead on chronic, low-level exposure in addition also accelerates tumor growth rates. Higher levels of Pb were found in blood and head hair samples of newly diagnosed patients with breast cancer, all with infiltrating ductal carcinoma, the most common form of breast cancer in Nigeria, seen at Obafemi Awolowo University, than in cancer-free controls from the same area. Evidence for interactions between Pb and Se was obtained from blood, hair, and tumor biopsy tissue analyses. Furthermore, the Pb levels in hair samples of the patients were directly correlated with the volumes of their tumors, in accord with the tumor growth-promoting effects of Pb. Conversely, Se levels in hair and blood were inversely correlated with the tumor volumes, consistent with the anti-proliferative effects of Se. Several other elements, e.g., Cd, Hg, Cr, Sn, and As, were detected in the scalp hair of the patients and the controls, although at significantly lower levels than those of Pb. However, correlation calculations revealed them also to interact with Se, suggesting that only a fraction of the Se in organs and tissues is actually present in bioactive forms. In metal-exposed subjects, a state of latent Se deficiency may exist, resulting in depressed immune functions and increased cancer susceptibility. Evidence is presented to show that Pb and other metals also interact with iodine, another vitally important essential trace element believed to protect against breast cancer development. Public health programs aiming at lowering the breast cancer risk of Nigerian women thus will have to include effective measures to protect the population from exposures to Pb and other industrial metals that are presently contaminating the environment and the water supplies.     

Evaluation of Current Knowledge, Awareness and Practice of Spirometry among Hospital -based Nigerian Doctors

Background

The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis.

Methods

Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography.

Results

Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and D_LCO were independent predictors of systolic pulmonary artery pressure.

Conclusion

Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.     

Structures of glyceraldehyde 3‐phosphate dehydrogenase in Neisseria gonorrhoeae and Chlamydia trachomatis

Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct) are the most commonly reported sexually transmitted bacteria worldwide and usually present as co‐infections. Increasing resistance of Ng to currently recommended dual therapy of azithromycin and ceftriaxone presents therapeutic challenges for syndromic management of Ng‐Ct co‐infections. Development of a safe, effective, and inexpensive dual therapy for Ng‐Ct co‐infections is an effective strategy for the global control and prevention of these two most prevalent bacterial sexually transmitted infections. Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) is a validated drug target with two approved drugs for indications other than antibacterials. Nonetheless, any new drugs targeting GAPDH in Ng and Ct must be specific inhibitors of bacterial GAPDH that do not inhibit human GAPDH, and structural information of Ng and Ct GAPDH will aid in finding such selective inhibitors. Here, we report the X‐ray crystal structures of Ng and Ct GAPDH. Analysis of the structures demonstrates significant differences in amino acid residues in the active sites of human GAPDH from those of the two bacterial enzymes suggesting design of compounds to selectively inhibit Ng and Ct is possible. We also describe an efficient in vitro assay of recombinant GAPDH enzyme activity amenable to high‐throughput drug screening to aid in identifying inhibitory compounds and begin to address selectivity.     

Tracking the Quality of Care for Sick Children Using Lot Quality Assurance Sampling: Targeting Improvements of Health Services in Jigawa,Nigeria

Background

In Nigeria, 30% of child deaths are due to malaria. The National Malaria Control Program of Nigeria (NMCP) during 2009 initiated a program to improve the quality of paediatric malaria services delivered in health facilities (HF). This study reports a rapid approach used to assess the existing quality of services in Jigawa state at decentralised levels of the health system.

Methods

NMCP selected Lot Quality Assurance Sampling (LQAS) to identify the variation in HF service quality among Senatorial Districts (SD). LQAS was selected because it was affordable and could be used by local health workers (HW) in a population-based survey. NMCP applied a 2-stage LQAS using a structured Rapid Health Facility Assessment (R-HFA) tool to identify high and low performing SD for specified indicators.

Findings

LQAS identified variations in HF performance (n = 21) and enabled resources to be targeted to address priorities. All SD exhibited deficient essential services, supplies and equipment. Only 9.7% of HF had Artemisinin-based Combination Therapies and other first-line treatments for childhood illnesses. No SD and few HF exhibited adequate HW performance for the assessment, treatment or counselling of sick children. Using the IMCI algorithm, 17.5% of HW assessed the child’s vaccination status, 46.8% assessed nutritional status, and 65.1% assessed children for dehydration. Only 5.1% of HW treatments were appropriate for the assessment. Exit interviews revealed that 5.1% of caregivers knew their children’s illness, and only 19.9% could accurately describe how to administer the prescribed drug.

Conclusion

This R-HFA, using LQAS principles, is a rapid, simple tool for assessing malaria services and can be used at scale. It identified technical deficiencies that could be corrected by improved continuing medical education, targeted supervision, and recurrent R-HFA assessments of the quality of services.