Life in the Fas lane: differential outcomes of Fas signalling

Fas, also known as CD95 or APO-1, is a member of the tumor necrosis factor/nerve growth factor superfamily. Although best characterized in terms of its apoptotic function, recent studies have identified several other cellular responses emanating from Fas. These responses include migration, invasion, inflammation, and proliferation. In this review, we focus on the diverse cellular outcomes of Fas signaling and the molecular switches identified to date that regulate its pro- and anti-apoptotic functions. Such switches occur at different levels of signal transduction, ranging from the receptor through to cross-talk with other signaling pathways. Factors identified to date including other extracellular signals, proteins recruited to the death-inducing signaling complex, and the availability of different intracellular components of signal transduction pathways. The success of therapeutically targeting Fas will require a better understanding of these pathways, as well as the regulatory mechanisms that determine cellular outcome following receptor activation

Review of standards for biodegradable plastic bags.

The Single Use Carrier Bags Charges (England) Order 2015 requires retailers to charge at least 5p for each single use carrier bag, except where exempted. Under section 18 of that order, the Secretary of State must— (a) complete a review of industry standards for the biodegradability of lightweight plastic material; and (b) lay a copy of a report before Parliament setting out the conclusions of the review, in particular— (i) whether it appears to the Secretary of State that there exists an industry standard appropriate for the purposes of an exclusion from the obligations specified in Part 2 on grounds of biodegradability; and (ii) if so, how that exclusion would be implemented. That review has now been completed. It found that there are a number of standards for plastic bag biodegradability. We will need to conduct further work before any of these could be used to exempt certain types of carrier bags on grounds of biodegradability. By the end of May 2016 retailers are required to report the number of bags that have been supplied, and the uses to which the proceeds of the charge have been put, after reasonable costs are deducted. The Government will use that opportunity to consider the early impacts of the charge. The Government will continue to consider the technical specification for a genuinely biodegradable bag, and will at that point further report on how an exemption for such a biodegradable bag can be implemented

Differences in the epidemiology of theileriosis on smallholder dairy farms in contrasting agro-ecological and grazing strata of highland Kenya

A prospective cohort study was conducted in five purposively-sampled agro-ecological zone (AEZ)-grazing system strata in Murang’a District, Kenya, between March 1995 and June 1996. The study strata were selected based on a preliminary characterization study to represent the widest range of risks to East Coast fever (ECF) in the District and included zero-grazing and open-grazing farms. In total, 225 calves from 188 smallholder farms were examined from birth to 6 months of age and visited within the first 2 weeks of life and thereafter at bi-weekly intervals for up to 14 visits. The purpose of the study was to characterize the differences in epidemiology (risks of infection, morbidity and mortality) and potential control of ECF between the selected strata. Evidence of Theileria parva infection was assessed by increased antibody levels as measured in an indirect ELISA assay by the percent positivity (PP) of serum samples relative to a strong positive reference serum. Sero-conversion risks of T. parva were highest in the open-grazing strata. Antibody prevalence in adult cattle and ECF morbidity and mortality risks were also highest in open-grazing strata. While different, all five AEZ-grazing strata were considered to be endemically unstable for ECF. East Coast fever challenge was low in all zero-grazing strata and this challenge is likely to remain low due to continuing intensification of smallholder farming in the central highlands. In the open-grazing strata, there was higher challenge and a greater impact of ECF. ILRI publication no.: 99017

High speed video capture for mobile phone cameras

We consider an electromechanical model for the operation of a voice coil motor in a mobile phone camera, with the aim of optimizing how a lens can be moved to a desired focusing motion. Although a methodology is developed for optimizing lens shift, there is some concern about the experimentally-determined model parameters that are at our disposal. Central to the model is the value of the estimated magnetic force constant, Kf: its value determines how far it is actually possible to move lens, but it appears that, from the value given, it would not be possible to shift the lens through the displacements desired. Furthermore, earlier experiments have also estimated the value of the back EMF constant, Kg , to be roughly five times greater than Kf, even though we present two theoretical arguments that show that Kf = Kg: a conclusion supported by readily-available manufacturers’ data

The effect of extra dimensions on gravity wave bursts from cosmic string cusps

We explore the kinematical effect of having extra dimensions on the gravity wave emission from cosmic strings. Additional dimensions both round off cusps, and reduce the probability of their formation. We recompute the gravity wave burst, taking into account these two factors, and find a potentially significant damping on the gravity waves of the strings.Comment: 33 pages, 8 figures, published versio

An appraisal of analytical tools used in predicting clinical outcomes following radiation therapy treatment of men with prostate cancer: a systematic review

Background: Prostate cancer can be treated with several different modalities, including radiation treatment. Various prognostic tools have been developed to aid decision making by providing estimates of the probability of different outcomes. Such tools have been demonstrated to have better prognostic accuracy than clinical judgment alone. Methods: A systematic review was undertaken to identify papers relating to the prediction of clinical outcomes (biochemical failure, metastasis, survival) in patients with prostate cancer who received radiation treatment, with the particular aim of identifying whether published tools are adequately developed, validated, and provide accurate predictions. PubMed and EMBASE were searched from July 2007. Title and abstract screening, full text review, and critical appraisal were conducted by two reviewers. A review protocol was published in advance of commencing literature searches. Results: The search strategy resulted in 165 potential articles, of which 72 were selected for full text review and 47 ultimately included. These papers described 66 models which were newly developed and 31 which were external validations of already published predictive tools. The included studies represented a total of 60,457 patients, recruited between 1984 and 2009. Sixty five percent of models were not externally validated, 57% did not report accuracy and 31% included variables which are not readily accessible in existing datasets. Most models (72, 74%) related to external beam radiation therapy with the remainder relating to brachytherapy (alone or in combination with external beam radiation therapy). Conclusions: A large number of prognostic models (97) have been described in the recent literature, representing a rapid increase since previous reviews (17 papers, 1966–2007). Most models described were not validated and a third utilised variables which are not readily accessible in existing data collections. Where validation had occurred, it was often limited to data taken from single institutes in the US. While validated and accurate models are available to predict prostate cancer specific mortality following external beam radiation therapy, there is a scarcity of such tools relating to brachytherapy. This review provides an accessible catalogue of predictive tools for current use and which should be prioritised for future validation.Elspeth Raymond, Michael E. O’Callaghan, Jared Campbell, Andrew D. Vincent, Kerri Beckmann, David Roder, Sue Evans, John McNeil, Jeremy Millar, John Zalcberg, Martin Borg and Kim Morett

Gadolinium-Enhanced Magnetic Susceptibility Contrast Is Reduced in the Corpus Callosum of a Mouse Model of Tauopathy

Alterations to white matter have been implicated in a number of neurodegenerative diseases. In this work we investigate the sensitivity of MRI magnetic susceptibility mapping to these changes using a mouse model of Tauopathy. A non-rigid registration of contrast enhanced, high resolution ex vivo mouse brain images is used to transform susceptibility maps into a common space and a voxel-wise group comparison is performed. Significant differences were observed that may indicate disruption to the tissue of the corpus callosum

Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease

Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with lifethreatening cerebral oedema and dysmyelination in affected individuals. Treatment requires life-long dietary restriction and monitoring of branched-chain amino acids to avoid brain injury. Despite careful management, children commonly suffer metabolic decompensation in the context of catabolic stress associated with non-specific illness. The mechanisms underlying this decompensation and brain injury are poorly understood. Using recently developed mouse models of classic and intermediate maple syrup urine disease, we assessed biochemical, behavioural and neuropathological changes that occurred during encephalopathy in these mice. Here, we show that rapid brain leucine accumulation displaces other essential amino acids resulting in neurotransmitter depletion and disruption of normal brain growth and development. A novel approach of administering norleucine to heterozygous mothers of classic maple syrup urine disease pups reduced branched-chain amino acid accumulation in milk as well as blood and brain of these pups to enhance survival. Similarly, norleucine substantially delayed encephalopathy in intermediate maple syrup urine disease mice placed on a high protein diet that mimics the catabolic stress shown to cause encephalopathy in human maple syrup urine disease. Current findings suggest two converging mechanisms of brain injury in maple syrup urine disease including: (i) neurotransmitter deficiencies and growth restriction associated with branchedchain amino acid accumulation and (ii) energy deprivation through Krebs cycle disruption associated with branched-chain ketoacid accumulation. Both classic and intermediate models appear to be useful to study the mechanism of brain injury and potential treatment strategies for maple syrup urine disease. Norleucine should be further tested as a potential treatment to prevent encephalopathy in children with maple syrup urine disease during catabolic stress

Differential narrow focusing of immunodominant human immunodeficiency virus Gag-specific cytotoxic T-Lymphocyte responses in infected African and Caucasoid adults and children

Cytotoxic T-lymphocyte (CTL) activity plays a central role in control of viral replication and in determining outcome in cases of human immunodeficiency virus type 1 (HIV-1) infection. Incorporation of important CTL epitope sequences into candidate vaccines is, therefore, vital. Most CTL studies have focused upon small numbers of adult Caucasoid subjects infected with clade-B virus, whereas the global epidemic is most severe in sub-Saharan African populations and predominantly involves clade-C infection in both adults and children. In this study, sensitive enzyme-linked immunospot (elispot) assays have been utilized to identify the dominant Gag-specific CTL epitopes targeted by adults and children infected with clade-B or -C virus. Cohorts evaluated included 44 B-clade-infected Caucasoid American and African American adults and children and 37 C-clade-infected African adults and children from Durban, South Africa. The results show that 3 out of 46 peptides spanning p17Gag and p24Gag sequences tested contain two-thirds of the dominant Gag-specific epitopes, irrespective of the clade, ethnicity, or age group studied. However, there were distinctive differences between the dominant responses made by Caucasoids and Africans. Dominant responses in Caucasoids were more often within p17Gag peptide residues 16 to 30 (38 versus 12%; P 30% of the total infected population in Durban. This epitope is closely homologous with dominant HIV-2 and simian immunodeficiency virus Gag-specific CTL epitopes. The fine focusing of dominant CTL responses to these few regions of high immunogenicity is of significance to vaccine design

The association of hypertensive disorders of pregnancy with weight gain over the subsequent 21 years: Findings from a prospective cohort study

Obesity is an important risk factor for hypertensive disorders of pregnancy, but most cases of hypertensive disorders of pregnancy occur in women of normal weight. There may be predisposing factors to both hypertensive disorders of pregnancy and obesity. To test this hypothesis, the authors compared changes in body mass index (weight (kg)/height (m)(2)) overtime in women with and without hypertensive disorders of pregnancy. They used data from 3,572 women who received antenatal care at a major public hospital in Brisbane, Australia, between 1981 and 1984 and who were followed up for 21 years. A total of 318 women (8.9%) had experienced hypertensive disorders in the index pregnancy, and 233 of them (73.3%) had a baseline body mass index of = 5 kg/m(2) were 59% greater for women who experienced hypertensive disorders of pregnancy compared with those who did not (odds ratio = 1.59, 95% confidence interval: 1.24, 2.04). The authors concluded that hypertensive disorders of pregnancy are associated with increased weight gain over 21 years