Dynamics of the formation of a hydrogel by a pathogenic amyloid peptide: islet amyloid polypeptide

Many chronic degenerative diseases result from aggregation of misfolded polypeptides to form amyloids. Many amyloidogenic polypeptides are surfactants and their assembly can be catalysed by hydrophobic-hydrophilic interfaces (an air-water interface in-vitro or membranes in-vivo). We recently demonstrated the specificity of surface-induced amyloidogenesis but the mechanisms of amyloidogenesis and more specifically of adsorption at hydrophobic-hydrophilic interfaces remain poorly understood. Thus, it is critical to determine how amyloidogenic polypeptides behave at interfaces. Here we used surface tensiometry, rheology and electron microscopy to demonstrate the complex dynamics of gelation by full-length human islet amyloid polypeptide (involved in type II diabetes) both in the bulk solution and at hydrophobic-hydrophilic interfaces (air-water interface and phospholipids). We show that the hydrogel consists of a 3D supramolecular network of fibrils. We also assessed the role of solvation and dissected the evolution over time of the assembly processes. Amyloid gelation could have important pathological consequences for membrane integrity and cellular functions

The feeding behaviour and Plasmodium infection of Anopheles mosquitoes in southern Ethiopia in relation to use of insecticide-treated livestock for malaria control.

Anopheles arabiensis and An. quadriannulatus species B mosquitoes were collected at sites of human and livestock housing and analysed for blood feeding patterns and infection with malaria sporozoites. A low percentage of human blood meals at some sites suggested that zooprophylaxis could be effective in reducing challenge from Plasmodium falciparum

The evaluation of aspects of the chain of survival at gymnasiums in the Pretoria area

Background Sudden cardiac death related to exercise is an uncommon problem, but is perhaps the single biggest challenge to sports medicine practitioners. Although the overall risk of death due to cardiac causes is substantially reduced in those who exercise regularly, the risk is temporarily increased during exercise. The causes of sudden cardiac death related to exercise vary according to age and are divided into two groups. Firstly, those under 35 years, where structural abnormalities of the heart pose a risk. The most common congenital abnormality is hypertrophic cardiomyopathy (HOCM), which occurs in up to two per 1 000 births. Secondly, those above 35 years, where coronary artery disease is the leading cause of sudden cardiac deaths.The most frequent initial rhythm documented in witnessed cardiac arrest is ventricular fibrillation (VF). The most effective treatment for VF is defibrillation. The probability of successful defibrillation decreases by approximately seven to 10 percent for every minute that defibrillation is delayed. VF tends to convert to asystole within a few minutes if left untreated. No matter what the setting – home, community or hospital – the majority of successful adult resuscitations depend on early defibrillation.5Public education and training are crucial aspects of any effort to reduce cardiac death. Because the majority of sudden cardiac deaths occur outside the hospital, it is clear that the community must be recognised as the ‘ultimate coronary care unit'. Communities with a high number of lay persons trained in life-saving techniques such as cardiopulmonary resuscitation (CPR) and the use of automated external defibrillators (AEDs) may achieve resuscitation rates as high as 49% for patients with a documented out-of-hospital VF.CPR is a critical component of BLS (basic life support). Prompt bystander CPR is crucial to all resuscitation efforts. In the absence of prompt bystander CPR, successful resuscitation of out-of-hospital cardiac arrest victims is unlikely, despite the availability of trained paramedics with a rapid response time. CPR performed while waiting for defibrillation appears to prolong VF and contribute to the preservation of heart and brain function.The purpose of the study was to evaluate aspects of the chain of survival in gymnasiums in the Pretoria area. This chain of survival was evaluated against the Basic Life Support (BLS) system known in cardiac resuscitation.Methods Twelve gymnasiums in the Pretoria area were included in the study. A structured questionnaire was given to a staff member of each gymnasium after explanation of the purpose of the study.Results Of the gymnasiums visited, 83% had emergency telephone numbers at hand, while 100% of the staff had CPR training (75% in the last year). Half of the gymnasiums visited had automated external defibrillators (AEDs) available and the staff members at the respective gymnasiums had been trained in the use thereof.Conclusion The partaking gymnasiums in the Pretoria area are well prepared for cardiac emergencies. It is recommended that fitness instructors, medical practitioners and the general public working out in gymnasiums be familiar with the chain of survival, especially how to operate an AED.For full text, click here: SA Fam Pract 2006;48(5):15-15

Statistical analysis driven optimized deep learning system for intrusion detection

Attackers have developed ever more sophisticated and intelligent ways to hack information and communication technology systems. The extent of damage an individual hacker can carry out upon infiltrating a system is well understood. A potentially catastrophic scenario can be envisaged where a nation-state intercepting encrypted financial data gets hacked. Thus, intelligent cybersecurity systems have become inevitably important for improved protection against malicious threats. However, as malware attacks continue to dramatically increase in volume and complexity, it has become ever more challenging for traditional analytic tools to detect and mitigate threat. Furthermore, a huge amount of data produced by large networks has made the recognition task even more complicated and challenging. In this work, we propose an innovative statistical analysis driven optimized deep learning system for intrusion detection. The proposed intrusion detection system (IDS) extracts optimized and more correlated features using big data visualization and statistical analysis methods (human-in-the-loop), followed by a deep autoencoder for potential threat detection. Specifically, a pre-processing module eliminates the outliers and converts categorical variables into one-hot-encoded vectors. The feature extraction module discard features with null values and selects the most significant features as input to the deep autoencoder model (trained in a greedy-wise manner). The NSL-KDD dataset from the Canadian Institute for Cybersecurity is used as a benchmark to evaluate the feasibility and effectiveness of the proposed architecture. Simulation results demonstrate the potential of our proposed system and its outperformance as compared to existing state-of-the-art methods and recently published novel approaches. Ongoing work includes further optimization and real-time evaluation of our proposed IDS.Comment: To appear in the 9th International Conference on Brain Inspired Cognitive Systems (BICS 2018

Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis

Copyright @ 2012 Nature Publishing GroupThis article has been made available through the Brunel Open Access Publishing Fund.Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity.This work was supported in part by The Vidal Sassoon Foundation USA. This article is made available through the Brunel Open Access Publishing Fund

A Trial of a 7-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults.

BACKGROUND: Streptococcus pneumoniae is a leading and serious coinfection in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. Prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed. METHODS: In this double-blind, randomized, placebo-controlled clinical efficacy trial, we studied the efficacy of a 7-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adolescents and adults who had recovered from documented invasive pneumococcal disease. Two doses of vaccine were given 4 weeks apart. The primary end point was a further episode of pneumococcal infection caused by vaccine serotypes or serotype 6A. RESULTS: From February 2003 through October 2007, we followed 496 patients (of whom 44% were male and 88% were HIV-seropositive) for 798 person-years of observation. There were 67 episodes of pneumococcal disease in 52 patients, all in the HIV-infected subgroup. In 24 patients, there were 19 episodes that were caused by vaccine serotypes and 5 episodes that were caused by the 6A serotype. Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95% confidence interval [CI], 30 to 90). There were 73 deaths from any cause in the vaccine group and 63 in the placebo group (hazard ratio in the vaccine group, 1.18; 95% CI, 0.84 to 1.66). The number of serious adverse events within 14 days after vaccination was significantly lower in the vaccine group than in the placebo group (3 vs. 17, P=0.002), and the number of minor adverse events was significantly higher in the vaccine group (41 vs. 13, P=0.003). CONCLUSIONS: The 7-valent pneumococcal conjugate vaccine protected HIV-infected adults from recurrent pneumococcal infection caused by vaccine serotypes or serotype 6A. (Current Controlled Trials number, ISRCTN54494731.) Copyright 2010 Massachusetts Medical Society

Paraovarian tumor of borderline malignancy: a case report

A case of a 23-year-old woman with a paraovarian tumor is presented. The patient complained of pelvic pain and abdominal swelling. Cystectomy was the initial surgical treatment, but after the histological diagnosis, a staging surgery was carried out. The clinical aspects and subsequent management of related cases are discussed, and a literature review is made

Control of crosslinking for tailoring collagen-based scaffolds stability and mechanics.

UNLABELLED: We provide evidence to show that the standard reactant concentrations used in tissue engineering to cross-link collagen-based scaffolds are up to 100 times higher than required for mechanical integrity in service, and stability against degradation in an aqueous environment. We demonstrate this with a detailed and systematic study by comparing scaffolds made from (a) collagen from two different suppliers, (b) gelatin (a partially denatured collagen) and (c) 50% collagen-50% gelatin mixtures. The materials were processed, using lyophilisation, to produce homogeneous, highly porous scaffolds with isotropic architectures and pore diameters ranging from 130 to 260 μm. Scaffolds were cross-linked using a carbodiimide treatment, to establish the effect of the variations in crosslinking conditions (down to very low concentrations) on the morphology, swelling, degradation and mechanical properties of the scaffolds. Carbodiimide concentration of 11.5mg/ml was defined as the standard (100%) and was progressively diluted down to 0.1%. It was found that 10-fold reduction in the carbodiimide content led to the significant increase (almost 4-fold) in the amount of free amine groups (primarily on collagen lysine residues) without compromising mechanics and stability in water of all resultant scaffolds. The importance of this finding is that, by reducing cross-linking, the corresponding cell-reactive carboxylate anions (collagen glutamate or aspartate residues) that are essential for integrin-mediated binding remain intact. Indeed, a 10-fold reduction in carbodiimide crosslinking resulted in near native-like cell attachment to collagen scaffolds. We have demonstrated that controlling the degree of cross-linking, and hence retaining native scaffold chemistry, offers a major step forward in the biological performance of collagen- and gelatin-based tissue engineering scaffolds. STATEMENT OF SIGNIFICANCE: This work developed collagen and gelatine-based scaffolds with structural, material and biological properties suitable for use in myocardial tissue regeneration. The novelty and significance of this research consist in elucidating the effect of the composition, origin of collagen and crosslinking concentration on the scaffold physical and cell-binding characteristics. We demonstrate that the standard carbodiimide concentrations used to crosslink collagenous scaffolds are up to 100 times higher than required for mechanical integrity in service, and stability against dissolution. The importance of this finding is that, by reducing crosslinking, the corresponding cell-reactive carboxylate anions (essential for integrin-mediated binding) remain intact and the native scaffold chemistry is retained. This offers a major step forward in the biological performance of tissue engineered scaffolds.The authors would like to thank the British Heart Foundation (Grants NH/11/1/28922 and RG/09/003/27122) and the ERC Advanced Grant 320598 3D-E for providing financial support for this project. D. V. Bax is funded by the Peoples Programme of the EU 7th Framework Programme (RAE no: PIIF-GA-2013-624904) and also supported by an EPSRC IKC Proof of Concept Award.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.actbio.2015.07.03