Assessment of heavy metals bioavailability in dumpsites of Zaria Metropolis, Nigeria

The objectives of this study was to investigate the chemical fractionation, mobility and bioavailability of Cd, Cu, Mn, Pb and Zn in refuse waste soils of some dumpsites in Zaria metropolis. The heavy metals in the waste soils samples were sequentially extracted and measured using atomic absorption spectrometry. Mean of total extractable metals in the samples analysed for Cd, Cu, Mn, Pb and Zn ranged from 25.86 – 95.71, 1.70 – 446.43, 141.92 – 423.22, 39.9 – 739.10, and 122.45 – 511.57 mgKg-1 dry weight, respectively. Cd and Pb were mostly found to be in the mobile phase of the samples indicating that the metals are potentially more bioavailable to the environment than the other metals studied. Overall, the order of mobility and bioavailability of the metals is Cd > Pb > Zn > Mn > Cu

A potential new, stable state of the E-cadherin strand-swapped dimer in solution

E-cadherin is a transmembrane glycoprotein that facilitates inter-cellular adhesion in the epithelium. The ectodomain of the native structure is comprised of five repeated immunoglobulin-like domains. All E-cadherin crystal structures show the protein in one of three alternative conformations: a monomer, a strand-swapped trans homodimer and the so-called X-dimer, which is proposed to be a kinetic intermediate to forming the strand-swapped trans homodimer. However, previous studies have indicated that even once the trans strand-swapped dimer is formed, the complex is highly dynamic and the E-cadherin monomers may reorient relative to each other. Here, molecular dynamics simulations have been used to investigate the stability and conformational flexibility of the human E-cadherin trans strand-swapped dimer. In four independent, 100 ns simulations, the dimer moved away from the starting structure and converged to a previously unreported structure, which we call the Y-dimer. The Y-dimer was present for over 90% of the combined simulation time, suggesting that it represents a stable conformation of the E-cadherin dimer in solution. The Y-dimer conformation is stabilised by interactions present in both the trans strand-swapped dimer and X-dimer crystal structures, as well as additional interactions not found in any E-cadherin dimer crystal structures. The Y-dimer represents a previously unreported, stable conformation of the human E-cadherin trans strand-swapped dimer and suggests that the available crystal structures do not fully capture the conformations that the human E-cadherin trans homodimer adopts in solution

Ecological implications of a flower size/number trade-off in tropical forest trees

Peer reviewedPublisher PD

A human cancer-associated truncation of MBD4 causes dominant negative impairment of DNA repair in colon cancer cells

MBD4 binds to methylated DNA and acts as a thymine DNA glycosylase in base excision repair. Deficiency of MBD4 in mice enhances mutation at CpG sites and alters apoptosis in response to DNA damage, but does not increase tumorigenesis in mismatch repair-deficient mice. However, in humans, frameshift mutation of MBD4, rather than deletion, is what occurs in up to 43% of microsatellite unstable colon cancers. There is no murine equivalent of this mutation. We now show that recombinant truncated MBD4 (MBD4tru) inhibits glycosylase activities of normal MBD4 or Uracil DNA glycosylase in cell-free assays as a dominant negative effect. Furthermore, overexpression of MBD4tru in Big Blue (lacI)-transfected, MSI human colorectal carcinoma cells doubled mutation frequency, indicating that the modest dominant negative effect on DNA repair can occur in living cells in short-term experiments. Intriguingly, the whole mutation spectrum was increased, not only at CpG sites, suggesting that truncated MBD4 has a more widespread effect on genomic stability. This demonstration of a dominant negative effect may be of significance in tumour progression and acquisition of drug resistance

Availability and quality of anti-malarials among private sector outlets in Myanmar in 2012: results from a large, community-based, cross-sectional survey before a large-scale intervention

BACKGROUND: Global malaria control efforts are threatened by the spread and emergence of artemisinin-resistant Plasmodium falciparum parasites. In 2012, the widespread sale of partial courses of artemisinin-based monotherapy was suspected to take place in the highly accessed, weakly regulated private sector in Myanmar, posing potentially major threats to drug resistance. This study investigated the presence of artemisinin-based monotherapies in the Myanmar private sector, particularly as partial courses of therapy, to inform the targeting of future interventions to stop artemisinin resistance. METHODS: A large cross-sectional survey comprised of a screening questionnaire was conducted across 26 townships in Myanmar between March and May, 2012. For outlets that stocked anti-malarials at the time of survey, a stock audit was conducted, and for outlets that stocked anti-malarials within 3 months of the survey, a provider survey was conducted. RESULTS: A total of 3,658 outlets were screened, 83% were retailers (pharmacies, itinerant drug vendors and general retailers) and 17% were healthcare providers (private facilities and health workers). Of the 3,658 outlets screened, 1,359 outlets (32%) stocked at least one anti-malarial at the time of study. Oral artemisinin-based monotherapy comprised of 33% of self-reported anti-malarials dispensing volumes found. The vast majority of artemisinin-based monotherapy was sold by retailers, where 63% confirmed that they sold partial courses of therapy by cutting blister packets. Very few retailers (5%) had malaria rapid diagnostic tests available, and quality-assured artemisinin-based combination therapy was virtually nonexistent among retailers. CONCLUSION: Informal private pharmacies, itinerant drug vendors and general retailers should be targeted for interventions to improve malaria treatment practices in Myanmar, particularly those that threaten the emergence and spread of artemisinin resistance

Purification and functional characterisation of rhiminopeptidase A, a novel aminopeptidase from the venom of Bitis gabonica rhinoceros

This study describes the discovery and characterisation of a novel aminopeptidase A from the venom of B. g. rhinoceros and highlights its potential biological importance. Similar to mammalian aminopeptidases, rhiminopeptidase A might be capable of playing roles in altering the blood pressure and brain function of victims. Furthermore, it could have additional effects on the biological functions of other host proteins by cleaving their N-terminal amino acids. This study points towards the importance of complete analysis of individual components of snake venom in order to develop effective therapies for snake bites

Associations between the time of conception and the shape of the lactation curve in early lactation in Norwegian dairy cattle

<p>Abstract</p> <p>Background</p> <p>This study was carried out to determine if an association exists between the shape of the lactation curve before it is influenced by the event of conception and the time from calving to conception in Norwegian dairy cattle. Lactation curves of Norwegian Red cows during 5 to 42 days in milk (DIM) were compared between cows conceiving between 43 and 93 DIM and cows conceiving after 93 DIM.</p> <p>Methods</p> <p>Data from 23,049 cows, represented by one lactation each, with 219,538 monthly test days were extracted from the Norwegian Dairy Herd Recording System, which represents 97% of all Norwegian dairy cows. Besides veterinary treatments, these records also included information on daily milk yield at monthly test days. The data were stratified by parity groups (1, 2, and 3 and higher) and time to conception periods (43-93 DIM and >93 DIM). The sample was selected using the following selection criteria: conception later than 42 DIM, calving season July to September, no records of veterinary treatment and the level of energy fed as concentrates between 8.69 and 12.83 MJ. The shape of the lactation curves were parameterized using a modified Wilmink-model in a mixed model analysis. Differences in the parameters of the lactation curves with different conception times were evaluated using confidence intervals.</p> <p>Results</p> <p>Lactation curves characterized by a low intercept and a steep ascending slope and a steep descending slope were associated with early conception across all parities. The peak milk yield was not associated with time of conception.</p> <p>Conclusions</p> <p>A practical application of the study results is the use of the shape of the lactation curve in future herd management. Groups of cows with impaired reproductive performance may be identified due to an unfavorable shape of the lactation curve. Monitoring lactation curves and adjusting the feeding strategy to adjust yield therefore may be useful for the improvement of reproductive performance at herd level.</p

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty