Human guanylate binding proteins: Generation of tools, and their role during Toxoplasma gondii infection

Guanylate binding proteins (GBPs) are large GTPases that are substantially upregulated by interferons during infection. The human genome consists of seven GBP family members with high sequence identity. GBPs have been implicated to confer host resistance to a number of pathogens across several species. In mice, specific GBP family members are responsible for host defence mechanisms, including the induction of inflammasome responses during bacterial infections, and the disruption of pathogen vacuoles leading to effective protection against the parasite Toxoplasma gondii, and the bacteria Salmonella enterica typhimurium and Chlamydia trachomatis. Toxoplasma is an apicomplexan intracellular parasite that resides within a parasitophorous vacuole (PV), and can cause severe complications and even death in humans and other animals. The aim of this project was to analyse the characteristics and roles of individual human GBP family members in cells at steady state and in Toxoplasma infected cells. The first step was to develop tools to study the proteins, including producing and characterising specific antibodies, establishing cell overexpression systems and characterising cells deficient in certain GBPs. Using these tools, the subcellular localisations of GBP1 and GBP4 were determined to the cytoplasm and nucleus respectively. It was concluded that during type I and II Toxoplasma infection GBP1 and 4 are not recruited to the PV like in the mouse. Despite this, in human epithelial cells, GBP1 plays an important and specific role in the restriction of Toxoplasma replication. It was deduced that GBP4 protein levels are dramatically reduced during infection with the type I, but not the type II strain of Toxoplasma. GBP4 protein levels could be stabilised during type I Toxoplasma infection with an inhibitor of cysteine, serine and threonine proteases. Using an antibody specific for GBP1 and 2, a large dataset of potential interaction partners in a Toxoplasma strain-specific fashion was generated. The tools produced, specifically the GBP-specific antibodies, provide a valuable resource that can be used by other lab members and collaborators to more fully understand the functions of these interesting and important large GTPases

The Royal College of Ophthalmologists' National Ophthalmology Database study of cataract surgery: report 1, visual outcomes and complications.

Aim To describe the outcomes of cataract surgery in the United Kingdom. Methods Anonymised data on 180 114 eyes from 127 685 patients undergoing cataract surgery between August 2006 and November 2010 were collected prospectively from 28 sites. Outcome measures included intraoperative and postoperative complication rates, and preoperative and postoperative visual acuities. Results Median age at first eye surgery was 77.1 years, 36.9% cases had ocular co-pathology and 41.0% patients underwent cataract surgery on both eyes. Preoperative visual acuity was 0.30 logMAR or better in 32.0% first eyes and 47.7% second eyes. Postoperative best-measured visual acuity was 0.00 and 0.30 logMAR or better in 50.8 and 94.6% eyes without ocular co-pathology, and 32.5 and 79.9% in eyes with co-pathology. For eyes without co-pathology, postoperative uncorrected distance visual acuity was 0.00 and 0.30 logMAR or better in 27.3 and 80.9% eyes. Posterior capsule rupture or vitreous loss or both occurred in 1.95% cases, and was associated with a 42 times higher risk of retinal detachment surgery within 3 months and an eight times higher risk of endophthalmitis. Conclusion These results provide updated data for the benchmarking of cataract surgery. Visual outcomes, and the rate of posterior capsule rupture or vitreous loss or both appear stable over the past decade

Teacher perceptions on the delivery and implementation of movement integration strategies: the CLASS PAL (Physically Active Learning) Programme

Children sit for extended periods in the school classroom. Movement integration (MI) methods (e.g. active breaks, physically active lessons) could be used to break/reduce sitting time and improve classroom behaviour and engagement. Limited evidence is available on teacher perceptions of what influences the implementation of MI. Interviewed primary school teachers reported factors perceived to influence implementation at a variety of levels including individual (e.g. teacher and pupil characteristics, time, behavioural management) and school (e.g. whole school approach; and external to school expectations). In addition suggestions for increasing adoption and implementation of MI (e.g. communicating MI initiatives to schools) were identified

Reproductive Care of Childhood and Adolescent Cancer Survivors: A 12-Year Evaluation

Background: Reproductive complications for cancer survivors are identified as one of the top unmet needs in the survivorship period. However, current models of cancer care do not routinely incorporate reproductive follow-up for pediatric or adolescent cancer patients. The Kids Cancer Centre has had a one-stop survivorship clinic that includes the attendance of a gynecologist and fertility specialist for the last 12 years. Methodology: To inform the future development of our reproductive survivorship care, we reviewed the reproductive care our survivorship clinic has provided over a 12-year period, specifically reviewing the electronic and patient records to collect information on the demographics of the patients who used the service and their gonadotoxic risk and associated fertility treatment, their documented reproductive needs and concerns, and information provided on preventative reproductive advice and screening. Main Results: Two hundred seventy-eight patients were seen (397 consultations) for advice and management of reproductive issues, including 189 female patients (68.0%). Survivors' median age at follow-up was 25.0 years (range = 6-50), on average 19.2 years from their primary diagnosis (range = 3-46). The reviewed data had five overarching themes (fertility care, hormone dysfunction, sexual dysfunction, fertility-related psychological distress due to reproductive concerns, and preventative health care), although each theme had a number of components. Patients had on average 2.5 reproductive concerns documented per consultation (range 1-5). The three most commonly documented symptoms or concerns at the initial consultation related to fertility status (43.9%), endocrine dysfunction (35.3%), and contraception advice (32.4%). In patients younger than 25 years, documented discussions were predominately about endocrine dysfunction, fertility status, and contraception, while dominant themes for 26-35-year olds were fertility status, reproductive-related health prevention strategies, contraception, and endocrine dysfunction. Survivors 36-45 years of age prioritized fertility status, pregnancy, and contraception. Fertility preservation (FP) (p = 0.05), preventative health strategies (p = 0.001), and contraception advice (p < 0.001) were more commonly discussed by females than males. Conclusion: Young cancer survivors have multiple ongoing reproductive concerns that change over time. Assessing survivors' reproductive potential following cancer treatment is important as it gives patients who have not completed their family planning an opportunity to explore a possible window to FP or Assisted Reproductive Treatment. Our data can assist in informing the model of care for a reproductive survivorship clinic

Investing in Prevention or Paying for Recovery - Attitudes to Cyber Risk

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Broadly speaking an individual can invest time and effort to avoid becoming victim to a cyber attack and/or they can invest resource in recovering from any attack. We introduce a new game called the pre-vention and recovery game to study this trade-off. We report results from the experimental lab that allow us to categorize different approaches to risk taking. We show that many individuals appear relatively risk loving in that they invest in recovery rather than prevention. We find little difference in behavior between a gain and loss framing

Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

A prospective study of a normal childhood population identified 44 islet cell antibody positive individuals. These subjects were typed for HLA DR and DQ alleles and investigated for the presence of antibodies to the Mr 64,000 (64K) islet cell antigen, complement-fixing islet cell antibodies and radiobinding insulin autoantibodies to determine their potency in detecting subjects with impaired Beta-cell function. At initial testing 64K antibodies were found in six of 44 islet cell antibody positive subjects (13.6%). The same sera were also positive for complement-fixing islet cell antibodies and five of them had insulin autoantibodies. During the follow-up at 18 months, islet cell antibodies remained detectable in 50% of the subjects studied. In all six cases who were originally positive, 64K antibodies were persistently detectable, whereas complement-fixing islet cell antibodies became negative in two of six and insulin autoantibodies in one of five individuals. HLA DR4 (p < 0.005) and absence of asparic acid (Asp) at position 57 of the HLA DQ chain (p < 0.05) were significantly increased in subjects with 64K antibodies compared with control subjects. Of 40 individuals tested in the intravenous glucose tolerance test, three had a first phase insulin response below the first percentile of normal control subjects. Two children developed Type 1 (insulin-dependent) diabetes mellitus after 18 and 26 months, respectively. Each of these subjects was non-Asp homozygous and had persistent islet cell and 64K antibodies. We conclude that 64K antibodies, complement-fixing islet cell antibodies and insulin autoantibodies represent sensitive serological markers in assessing high risk for a progression to Type 1 diabetes in islet cell antibody positive non-diabetic individuals

A momentum-dependent perspective on quasiparticle interference in Bi_{2}Sr_{2}CaCu_{2}O_{8+\delta}

Angle Resolved Photoemission Spectroscopy (ARPES) probes the momentum-space electronic structure of materials, and provides invaluable information about the high-temperature superconducting cuprates. Likewise, the cuprate real-space, inhomogeneous electronic structure is elucidated by Scanning Tunneling Spectroscopy (STS). Recently, STS has exploited quasiparticle interference (QPI) - wave-like electrons scattering off impurities to produce periodic interference patterns - to infer properties of the QP in momentum-space. Surprisingly, some interference peaks in Bi_{2}Sr_{2}CaCu_{2}O_{8+\delta} (Bi-2212) are absent beyond the antiferromagnetic (AF) zone boundary, implying the dominance of particular scattering process. Here, we show that ARPES sees no evidence of quasiparticle (QP) extinction: QP-like peaks are measured everywhere on the Fermi surface, evolving smoothly across the AF zone boundary. This apparent contradiction stems from different natures of single-particle (ARPES) and two-particle (STS) processes underlying these probes. Using a simple model, we demonstrate extinction of QPI without implying the loss of QP beyond the AF zone boundary

The function of the alula in avian flight

The alula is a small structure located at the joint between the hand-wing and arm-wing of birds and is known to be used in slow flight with high angles of attack such as landing. It is assumed to function similarly to a leading-edge slat that increases lift and delays stall. However, in spite of its universal presence in flying birds and the wide acceptance of stall delay as its main function, how the alula delays the stall and aids the flight of birds remains unclear. Here, we investigated the function of alula on the aerodynamic performance of avian wings based on data from flight tasks and wind-tunnel experiments. With the alula, the birds performed steeper descending flights with greater changes in body orientation. Force measurements revealed that the alula increases the lift and often delays the stall. Digital particle image velocimetry showed that these effects are caused by the streamwise vortex, formed at the tip of the alula, that induces strong downwash and suppresses the flow separation over the wing surface. This is the first experimental evidence that the alula functions as a vortex generator that increases the lift force and enhances manoeuvrability in flights at high angles of attack.open1

The process of developing a management system for subsistence fisheries in South Africa: recognizing and formalizing a marginalized fishing sector in South Africa

Subsistence fishers were first recognized as a formal fishing sector in South Africa when new fishing legislation, aimed at redressing past inequalities, was enacted in 1998. Little information was available about these fishers, their activities, and the resources upon which they rely. Recognizing the imperative to gain an understanding of the fishers and to consult broadly, the national agency responsible for the management of marine living resources, Marine and Coastal Management (MCM) of the Department of Environmental Affairs and Tourism, appointed a Subsistence Fisheries Task Group (SFTG) in December 1998 to provide advice on the implementation of appropriate management systems for subsistence fisheries. This paper describes the process followed to formulate recommendations that were presented by the SFTG to MCM in February 2000. The activities of the SFTG fell into two categories: research aimed at identifying subsistence fishers and gaining an understanding of their activities and socio-economic profiles; and consultation aimed at ensuring that the needs and aspirations of fishers and the experience of local managers were incorporated. Research included both field-based studies and synthesis of information about comparative fisheries elsewhere. Consultation took the form of local interviews and focusgroup discussions, meetings with fishers and a national workshop. A pivotal activity was the development of a clear definition and qualifying criteria for subsistence fishers. A significant outcome was the identification of a separate small-scale commercial sector, previously erroneously lumped with subsistence fishers. Needs of fishers and problems identified during the process provided the basis for recommendations in the following areas: definitions, assessment and categorization of resources, management systems, communication mechanisms, application and allocation procedures, capacity building, compliance, research and monitoring, and funding and staff required for the management of this new sector. An evaluation is made of the opportunities presented by the SFTG process, constraints experienced and lessons learnt, giving important insights that are applicable to other similar processes, yet seldom documented in formal literature. Keywords: management of fisheries, subsistence fisheriesAfrican Journal of Marine Science 2002, 24: 405–42