Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity

<p>Abstract</p> <p>Background</p> <p>Previous reports have shown that peptides derived from the apolipoprotein E receptor binding region and the amphipathic α-helical domains of apolipoprotein AI have broad anti-infective activity and antiviral activity respectively. Lipoproteins and viruses share a similar cell biological niche, being of overlapping size and displaying similar interactions with mammalian cells and receptors, which may have led to other antiviral sequences arising within apolipoproteins, in addition to those previously reported. We therefore designed a series of peptides based around either apolipoprotein receptor binding regions, or amphipathic α-helical domains, and tested these for antiviral and antibacterial activity.</p> <p>Results</p> <p>Of the nineteen new peptides tested, seven showed some anti-infective activity, with two of these being derived from two apolipoproteins not previously used to derive anti-infective sequences. Apolipoprotein J (151-170) - based on a predicted amphipathic alpha-helical domain from apolipoprotein J - had measurable anti-HSV1 activity, as did apolipoprotein B (3359-3367) dp (apoBdp), the latter being derived from the LDL receptor binding domain B of apolipoprotein B. The more active peptide - apoBdp - showed similarity to the previously reported apoE derived anti-infective peptide, and further modification of the apoBdp sequence to align the charge distribution more closely to that of apoEdp or to introduce aromatic residues resulted in increased breadth and potency of activity. The most active peptide of this type showed similar potent anti-HIV activity, comparable to that we previously reported for the apoE derived peptide apoEdpL-W.</p> <p>Conclusions</p> <p>These data suggest that further antimicrobial peptides may be obtained using human apolipoprotein sequences, selecting regions with either amphipathic α-helical structure, or those linked to receptor-binding regions. The finding that an amphipathic α-helical region of apolipoprotein J has antiviral activity comparable with that for the previously reported apolipoprotein AI derived peptide 18A, suggests that full-length apolipoprotein J may also have such activity, as has been reported for full-length apolipoprotein AI. Although the strength of the anti-infective activity of the sequences identified was limited, this could be increased substantially by developing related mutant peptides. Indeed the apolipoprotein B-derived peptide mutants uncovered by the present study may have utility as HIV therapeutics or microbicides.</p

Crystal polymorphs and transformations of 2-iodo-4-nitroaniline

Full crystal structural characterization of three crystal polymorphs of 2-iodo-4-nitroaniline was carried out: the triclinic, orthorhombic, and a new monoclinic form. Powder X-ray diffraction, differential scanning calorimetry, and infrared data on the three of these are reported. Solvent-mediated transformations were observed on the basis of changes in crystal morphology and data from an in situ laser probe. Transformation to the monoclinic form was observed in all cases. [Published as part of a virtual special issue of selected papers presented in celebration of the 40th Anniversary Conference of the British Association for Crystal Growth (BACG), which was held at Wills Hall, Bristol, UK, September 6-8, 2009

Assessment Of The Impact Of Potential Tetracycline Exposure On The Phenotype Of Aedes Aegypti Ox513a: Implications For Field Use

Background Aedes aegypti is the primary vector of dengue fever, a viral disease which has an estimated incidence of 390 million infections annually. Conventional vector control methods have been unable to curb the transmission of the disease. We have previously reported a novel method of vector control using a tetracycline repressible self-limiting strain of Ae. aegypti OX513A which has achieved > 90% suppression of wild populations. Methodology/Principal Findings We investigated the impact of tetracycline and its analogues on the phenotype of OX513A from the perspective of possible routes and levels of environmental exposure. We determined the minimum concentration of tetracycline and its analogues that will allow an increased survivorship and found these to be greater than the maximum concentration of tetracyclines found in known Ae. aegypti breeding sites and their surrounding areas. Furthermore, we determined that OX513A parents fed tetracycline are unable to pre-load their progeny with sufficient antidote to increase their survivorship. Finally, we studied the changes in concentration of tetracycline in the mass production rearing water of OX513A and the developing insect. Conclusion/Significance Together, these studies demonstrate that potential routes of exposure of OX513A individuals to tetracycline and its analogues in the environment are not expected to increase the survivorship of OX513A.98Oxitec's core investmen

Motor vehicle accidents in patients with an implantable cardioverter-defibrillator

Objectives.This study was designed to examine driving safety in patients at risk for sudden death after implantation of a cardioverter-defibrillator.Background.Cardioverter-defibrillators are frequently implanted in patients at high risk for sudden death. Despite concern about the safety of driving in these patients, little is known about their actual motor vehicle accident rates.Methods.Surveys were sent to all 742 physicians in the United States involved in cardioverter-defibrillator implantation and follow-up. Physicians were questioned about numbers of patients followed up, numbers of fatal and nonfatal accidents, physician recommendations to patients about driving and knowledge of state driving laws.Results.Surveys were returned by 452 physicians (61%). A total of 30 motor vehicle accidents related to shocks from implantable defibrillators were reported by 25 physicians over a 12-year period from 1980 to 1992. Of these, nine were fatal accidents involving eight patients with a defibrillator and one passenger in a car driven by a patient. No bystanders were fatally injured. There were 21 nonfatal accidents involving 15 patients, 3 passengers and 3 bystanders. The estimated fatality rate for patients with a defibrillator, 7.5/100,000 patient-years, is significantly lower than that for the general population (18.4/100,000 patient-years, p < 0.05). The estimated injury rate, 17.6/100,000 patient-years, is also significantly lower than that for the general public (2,224/100,000 patient-years, p < 0.05). Only 10.5% (30 of 286) of all defibrillator discharges during driving resulted in accidents. Regarding physician recommendations, most physicians (58.1%) ask their patients to wait a mean (± SD) of 7.3 ± 3.4 months after implantation or a shock before driving again.Conclusions.The motor vehicle accident rate caused by discharge from an implantable cardioverter-defibrillator is low. Although restricting driving for a short period of time after implantation may be appropriate, excessive restrictions or a total ban on driving appears to be unwarranted

Carbon­yl[tris­(3,5-diphenyl­pyrazol-1-yl-κN 2)methane]copper(I) hexa­fluorido­phosphate–dichloro­methane–diethyl ether (4/3/1)

In the title compound, [Cu(C46H34N6)(CO)]PF6·0.75CH2Cl2·0.25C4H10O, the CuI atom is coordinated by three N atoms from the tridentate chelating tris­(3,5-diphenyl­pyrazol-1-yl)methane ligand (average Cu—N distance = 2.055 Å) and the C atom from a carbon monoxide ligand in a distorted tetra­hedral coordination geometry. The average N—Cu—N angle between adjacent pyrazole-ring-coordinated N atoms is 88.6°, while the average N—Cu—C angle between the pyrazole-bound N atom and the C atom of carbon monoxide is 126.3°. One of the 3-phenyl rings of the tris­(pyrazol­yl)methane ligand is disordered over two sites each with an occupancy factor of 0.50. The structure also exhibits disorder of the monosolvate that has been modeled with 0.75 CH2Cl2 and 0.25 Et2O occupancy

BIM : a methodology to transform business processes into software systems

This manuscript proposes a guiding methodology to obtain a software system that supports the execution of the business processes existing within an organization. The methodology promotes the usage of business process reference models and intends to reduce the implementation time of the software systems. The methodology assumes four distinct phases and several abstraction levels and is applicable both when developing systems from scratch or in re-engineering contexts. The methodology embodies a special phase to handle the diversity of the business processes of an organization. By tailoring process reference models and by considering the characteristics of a specific organization, a proper set of business processes is derived for that organization. Then, we can obtain a suitable information system and implement its automatable parts in a software solution that can run on top of open source software frameworks. We also present four new supporting concepts to the methodology, and a summarized execution of it

A novel use of honey's aggregation approach to the analysis of repertory grids

This paper examines and appraises a novel approach to generating shared group constructs through aggregative analysis: the application of Honey’s aggregation procedure to repertory grid technique (RGT) data. Revisiting Personal Construct Theory’s underlying premises and adopting a social constructivist epistemology, we argue that, whilst “implicit theories” of the world, elicited via RGT, are unique to individuals, the constructs on which they are founded may be shared collectively. Drawing on a study of workplace performance, we outline a protocol for this novel use of Honey’s (1979a; 1979b) approach demonstrating how it can be utilized to generate shared constructs inductively to facilitate theory building. We argue that, unlike other grid aggregation processes, the approach does not compromise data granularity, offering a useful augmentation to traditional idiographic approaches examining individual-level constructs only. This approach appears especially suited to addressing complex and implicit topics, where individuals struggle to convey thoughts and ideas

Crew factors in flight operations 9: Effects of planned cockpit rest on crew performance and alertness in long-haul operations

This study examined the effectiveness of a planned cockpit rest period to improve alertness and performance in long-haul flight operations. The Rest Group (12 crew members) was allowed a planned 40 minute rest period during the low workload, cruise portion of the flight, while the No-Rest Group (9 crew members) had a 40 minute planned control period when they maintained usual flight activities. Measures used in the study included continuous ambulatory recordings of brain wave and eye movement activity, a reaction time/vigilance task, a wrist activity monitor, in-flight fatigue and alertness ratings, a daily log for noting sleep periods, meals, exercise, flight and duty periods, and the NASA Background Questionnaire. The Rest Group pilots slept on 93 percent of the opportunities, falling asleep in 5.6 minutes and sleeping for 25.8 minutes. This nap was associated with improved physiological alertness and performance compared to the No-Rest Group. The benefits of the nap were observed through the critical descent and landing phases of flight. The nap did not affect layover sleep or the cumulative sleep debt. The nap procedures were implemented with minimal disruption to usual flight operations and there were no reported or identified concerns regarding safety

Violent and victimized bodies: sexual violence policy in England and Wales

This paper uses the notion of the body to frame an archaeology of sexual violence policy in England and Wales, applying and developing Pillow’s ideas. It argues that the dominant construction is of sexual violence as an individualized crime, with the solution being for a survivor to report, and with support often instrumentalized in relation to criminal justice objectives. However, criminal justice proceedings can intensify or create further trauma for sexual violence survivors. Furthermore, in addition to criminalizing the violent body and supporting the victimized one, there is a need for policy to produce alternative types of bodies through preventative interventions. Much sexual violence is situated within (hetero) sexual dynamics constructing a masculine aggressor and a feminine body which eventually yields. Prevention must therefore focus on developing embodied boundaries, and narratives at the margins of policy could underpin such efforts