Dimerization of a flocculent protein from Moringa oleifera: experimental evidence and in silico interpretation

Many proteins exist in dimeric and other oligomeric forms to gain stability and functional advantages. In this study, the dimerization property of a coagulant protein (MO_2.1) from Moringa oleifera seeds was addressed through laboratory experiments, protein–protein docking studies and binding free energy calculations. The structure of MO_2.1 was predicted by homology modelling, while binding free energy and residues-distance profile analyses provided insight into the energetics and structural factors for dimer formation. Since the coagulation activities of the monomeric and dimeric forms of MO_2.1 were comparable, it was concluded that oligomerization does not affect the biological activity of the protein.     

Effects of vitamin C supplementation on the growth of Heterobranchus longifilis fingerlings

A 12-week growth experiment was conducted to establish the necessity of vitamin C in the nutrition of Heterobranchus longifilis fingerlings. Vitamin C was supplemented at levels of 0 and 50 mg x kg(-1) to a basal diet (42.5% CP), which was fed to triplicate groups of H. longifilis fingerlings. Fish receiving the vitamin C-supplemented diet had significantly improved weight gain (20.7 vs. 16.7 g per fish), feed efficiency ratio (1.03 vs. 1.42), specific growth rate (3.00 vs. 2.74%), protein efficiency ratio (2.26 vs. 1.64), and survival rate (90% vs. 50%). There was a significant decrease in haematocrit and haemoglobin levels in the blood of fish fed no supplemental vitamin C. Furthermore, this group exhibited retarded growth and pathological changes such as vertebral curvature, condensation associated with fragility of the spinal bones. Supplementation of 50 mg vitamin C per kg diet was adequate to prevent the occurrence of vitamin C deficiency in H. longifilis and it was concluded that vitamin C is essential in the nutrition of these fishes.     

Dynamic regulation of the cerebral cavernous malformation pathway controls vascular stability and growth

Cardiovascular growth must balance stabilizing signals required to maintain endothelial connections and network integrity with destabilizing signals that?enable individual endothelial cells to migrate and proliferate. The cerebral cavernous malformation (CCM) signaling pathway utilizes the adaptor protein CCM2 to strengthen endothelial cell junctions and stabilize vessels. Here we identify a CCM2 paralog, CCM2L, that is expressed selectively in endothelial cells during periods of active cardiovascular growth. CCM2L competitively blocks CCM2-mediated stabilizing signals biochemically, in cultured endothelial cells, and in developing mice. Loss of CCM2L reduces endocardial growth factor expression and impairs tumor growth and wound healing. Our studies identify CCM2L as a molecular mechanism by which endothelial cells coordinately regulate vessel stability and growth during cardiovascular development, as well as postnatal vessel growth.     

Performance of the tsetse, Glossina morsitans morsitans reared under various feeding regimens in Zambia

Groups of Glossina morsitans morsitans Westwood fed at emergence and thereafter daily, every second or third day respectively, up to the end of their first pregnancy cycle, survived well (73–79%) and produced virtually the same number of puparia/ (0.83–0.85) in the same puparial weight class (23–24 mg). However, adult survival (29%), number of puparia/ (0.30) and puparial weight (19 mg) were much lower in the group consistently fed every 4th day after the initial meal at emergence. It is proposed that tsetse colonies could be fed on Mondays, Wednesdays and Fridays without jeopardising adult survival, puparial production/ and the size (weight) of puparia produced.

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Performances en Zambie de la mouche Tsé-Tsé (Glossina morsitans morsitans) élevée en utilisant différents régimes alimentaires

Résumé Afin d'estimer si une alimentation quotidienne de G. morsitans morsitans présente un avantage sur une alimentation moins fréquente, nous avons enrigestré la survie des adultes, la production et le poids des pupes chez des individus nourris à l'émergence et, ensuite, tous les jours ou tous les 2, 3 ou 4 jours. Les femelles alimentées quotidiennement, ou tous les 2 ou 3 jours, ont produit le même nombre de pupes (0,83–0,85), avec des poids de même ordre (23–24 mg), et avec une aussi bonne survie (73 à 79%). Alimentées tous les 4 jours, elles ont produit 0,30 pupe/femelle, pesant 19 mg/pupe et avec une plus faible survie (29%). Ces résultats montrent qu'il est inutile de nourrir les mouches chaque jour au lieu de tous les 2 ou 3 jours. Cependant une alimentation à des intervalles supérieurs à 3 jours, a eu des conséquences clairement défavorables. Ainsi, peuvent être considérablement réduits et le travail et le coût des élevages, sans porter préjudice à la production, en alimentant les mouches 3 fois par semaine, par ex. les lundis, mercredis et vendredis.

     

Differentiating Coeliac Disease from Irritable Bowel Syndrome by Urinary Volatile Organic Compound Analysis – A Pilot Study

Coeliac disease (CD), a T-cell-mediated gluten sensitive enteropathy, affects ∼1% of the UK population and can present with wide ranging clinical features, often being mistaken for Irritable Bowel Syndrome (IBS). Heightened clinical awareness and serological screening identifies those with potential coeliac disease; the diagnosis is confirmed with duodenal biopsies, and symptom improvement with a gluten-free diet. Limitations to diagnosis are false negative serology and reluctance to undergo biopsy. The gut microbiome is altered in several gastrointestinal disorders, causing altered gut fermentation patterns recognisable by volatile organic compounds (VOC) analysis in urine, breath and faeces. We aimed to determine if CD alters the urinary VOC pattern, distinguishing it from IBS. 47 patients were recruited, 27 with established CD, on gluten free diets, and 20 with diarrhoea-predominant IBS (D-IBS). Collected urine was stored frozen in 10 ml aliquots. For assay, the specimens were heated to 40±0.1°C and the headspace analysed by Field Asymmetric Ion Mobility Spectrometry (FAIMS). Machine learning algorithms were used for statistical evaluation. Samples were also analysed using Gas chromatography and mass spectroscopy (GC-MS). Sparse logistic regression showed that FAIMS distinguishes VOCs in CD vs D-IBS with ROC curve AUC of 0.91 (0.83–0.99), sensitivity and specificity of 85% respectively. GCMS showed a unique peak at 4′67 found only in CD, not D-IBS, which correlated with the compound 1,3,5,7 cyclooctatetraene. This study suggests that FAIMS offers a novel, non-invasive approach to identify those with possible CD, and distinguishes from D-IBS. It offers the potential for monitoring compliance with a gluten-free diet at home. The presence of cyclooctatetraene in CD specimens will need further validation.     

Transmitted/Founder and Chronic HIV-1 Envelope Proteins Are Distinguished by Differential Utilization of CCR5

Infection by HIV-1 most often results from the successful transmission and propagation of a single virus variant, termed the transmitted/founder (T/F) virus. Here, we compared the attachment and entry properties of envelope (Env) glycoproteins from T/F and chronic control (CC) viruses. Using a panel of 40 T/F and 47 CC Envs, all derived by single genome amplification, we found that 52% of clade C and B CC Envs exhibited partial resistance to the CCR5 antagonist maraviroc (MVC) on cells expressing high levels of CCR5, while only 15% of T/F Envs exhibited this same property. Moreover, subtle differences in the magnitude with which MVC inhibited infection on cells expressing low levels of CCR5, including primary CD4⁺ T cells, were highly predictive of MVC resistance when CCR5 expression levels were high. These results are consistent with previous observations showing a greater sensitivity of T/F Envs to MVC inhibition on cells expressing very high levels of CCR5 and indicate that CC Envs are often capable of recognizing MVC-bound CCR5, albeit inefficiently on cells expressing physiologic levels of CCR5. When CCR5 expression levels are high, this phenotype becomes readily detectable. The utilization of drug-bound CCR5 conformations by many CC Envs was seen with other CCR5 antagonists, with replication-competent viruses, and did not obviously correlate with other phenotypic traits. The striking ability of clade C and B CC Envs to use MVC-bound CCR5 relative to T/F Envs argues that the more promiscuous use of CCR5 by these Env proteins is selected against at the level of virus transmission and is selected for during chronic infection.     

Antiretroviral therapy in the Malawi defence force: access, treatment outcomes and impact on mortality

Background

HIV/AIDS affects all sectors of the population and the defence forces are not exempt. A national survey was conducted in all public and private sectors in Malawi that provide antiretroviral therapy (ART) to determine the uptake of ART by army personnel, their outcomes while on treatment, and the impact of ART on mortality in the Malawi Defence Force.

Methodology/Principal Findings

A retrospective cohort analysis was carried out, collecting data on access and retention on treatment from all 103 public and 38 private sector ART clinics in Malawi, using standardised patient master cards and clinic registers. Observations were censored on December 31^st 2006. Independent data on mortality trends in army personnel from all causes between 2002 and 2006 were available from army records. By December 31^st 2006, there were 85,168 patients ever started on ART in both public and private sectors, of whom 547 (0.7%) were army personnel. Of these, 22% started ART in WHO clinical stage 1 or 2 with a CD4-lymphocyte count of ≤250/mm³ and 78% started in stage 3 or 4. Treatment outcomes of army personnel by December 31^st 2006 were:−365 (67%) alive and on ART at their registration facility, 98 (18%) transferred out to another facility, 71 (13%) dead, 9 (2%) lost to follow-up, and 4 (<1%) stopped treatment. The probability of being alive on ART at 6-, 12- and 18-months was 89.8%, 83.4% and 78.8% respectively. All-cause mortality in army personnel declined dramatically over the five year period from 2002–2006.

Conclusion/Significance

There has been a good access of army personnel to ART during the last five years with excellent outcomes, and this should serve as an example for other defence forces and large companies in the region.