Book Review: The Dressed Society: Clothing, the Body and Some Meanings of the World

Review of The Dressed Society: Clothing, the Body and Some Meanings of the World by Peter Corriga

DNA Damage Recognition Proteins and Their Involvement in Cisplatin Resistance

cis-Diamminedichloroplatinum(II) (CDDP) is a chemotherapeutic agent widely used in the treatment of various types of cancer. Its mechanism of cytotoxicity is unclear although it is believed that DNA is the critical target. CDDP binds to DNA forming a variety of adducts including intrastrand adducts, interstrand adducts, monofunctional adducts and DNA-protein crosslinks. This thesis presents evidence that there are protein(s) present in mammalian cells which recognise CDDP-damaged DNA, To assay for these DNA damage recognition proteins (DDRPs) conditions for two very separate assays were developed. The gel mobility shift assay, which detects protein complexes under non-denaturing conditions, identified two retardation complexes which bound to CDDP damaged DNA in human, murine and feline tumour cell extracts. Binding of these complexes is shown to CDDP treated oligonucleotide of 54 base pairs but not to a CDDP treated oligonucleotide of 27 base pairs, therefore suggesting binding is dependent on having normal DNA duplex. The other system used in the detection of the DDRPs is the South-Western assay. This allowed the detection of proteins of sizes 25, 50, 100KD binding to CDDP treated DNA. The proteins in the South-Western system are run under denaturing conditions. It is not entirely clear as to whether the proteins detected in both systems are the same or whether they represent entirely different species. CDDP has been reported to bind to DNA and cause areas of singlestrandedness around the adducts. The results presented in this thesis demonstrate that the 50KD and 100KD DDRP which bind to CDDP treated double-stranded DNA may also have an affinity for single-stranded DNA. The 25KD DDRP, however, only recognises double-stranded DNA treated with CDDP suggesting that it is recognising the CDDP adducts and not the areas of single-strandedness generated around the adducts. Resistance to CDDP proves a major problem area in treatment regimes. Many cell lines resistant to CDDP have been derived in vitro by multiple exposures to the drug. Many mechanisms of resistance to CDDP have been suggested from these lines. If a role of the DDRPs was to process damage in the DNA then cell lines resistant to CDDP may show an increase in expression of the DDRPs. This thesis presents evidence that an ovarian tumour cell line resistant to CDDP in comparison to its parental line shows an increase in the binding to the 50KD and 100KD DDRPs. Work in chapter 5 presents the isolation of CDDP resistant cell lines, by acute exposure to the drug, with an increase of up to seven fold resistance levels. Evidence is presented for the resistant clones being of a mutational origin. Resistant variants occur at a frequency of 3.2x10e-6 per viable cell. This frequency can be increased to 3.4x10e-5 by treatment of the cells with the chemical mutagen ethyl methane sulphonate, EMS. The CDDP resistant phenotype is maintained after six months growth in drug free medium. This single step selection may provide clones which are more clinically relevant than the lines isolated by multiple exposures to CDDP. They may therefore provide a superior model for the study of drug resistance mechanisms to CDDP. However examination of the DDRPs showed no detectable difference in the resistant clones derived from the A2780 human ovarian tumour cell line. The thesis therefore presents evidence of the existence of DDRPs in mammalian cells. The role of these damage recognition proteins will be discussed

Irrigation and water resources in the 1990's

Presented at Irrigation and water resources in the 1990's: proceedings from the 1992 national conference held on October 5-7, 1992 in Phoenix, Arizona.An interceptor canal will be constructed near the end of eight laterals to collect and transport operational discharge and returned farm deliveries to a reservoir for temporary storage. The water will then be pumped over to an adjacent canal system for delivery. This project is being funded by the Imperial Irrigation District - Metropolitan Water District of Southern California (IID-MWD) Water Conservation Agreement. This paper describes the planning process for the project

Alternative Strategies for the Treatment of Classical Congenital Adrenal Hyperplasia: Pitfalls and Promises

Despite decades of different treatment algorithms, the management of congenital adrenal hyperplasia (CAH) remains clinically challenging. This is due to the inherent difficulty of suppressing adrenal androgen production using near physiological dosing of glucocorticoids (GC). As a result, alternating cycles of androgen versus GC excess can occur and may lead to short stature, obesity, virilization, and alterations in puberty. Novel therapeutic alternatives, including new and more physiological means of GC delivery, inhibitors at the level of CRH or ACTH secretion and/or action, as well as “rescue strategies”, such as GnRH analogs, anti-androgens, aromatase inhibitors, and estrogen receptor blockers, are available; many of these agents, however, still require active investigation in CAH. Bilateral adrenalectomy is effective but it is also still an experimental approach. Gene therapy and stem cells, to provide functional adrenal cortical tissue, are at preclinical stage but provide exciting avenues for a potential cure for CAH

Fuller, richer feedback, more easily delivered, using tablet PCs

We have developed a method to use tablet PCs to enable markers more efficiently to give written feedback on students’ work. Comments may either be made in handwriting, or may be typed, or may be presented in type following handwriting recognition. Additionally, any comments so made can be stored and reused, allowing for editing. Importantly, feedback can be made richer by including forward links for students to follow up on common mistakes that they have made so that their engagement with feedback is more constructive. Such feedback would otherwise be very tedious to provide if marking on paper was used exclusively. We have run this system successfully for two years to mark essays in a large class of 450+ students, using twenty markers. This volume of work was efficiently handled and involved no paper. Checking of marks and assuring consistent standards was much more easily done than with paper. We consulted students and markers. Students take the system in their stride. They are well able to provide essays, with diagrams and figures. Markers fell into a number of groups. We have learned that there are a variety of marking styles and developed the software to accommodate these. The only software required is Microsoft Word and Excel

Land application of sewage sludge (biosolids) in Australia: risks to the environment and food crops

Australia is a large exporter of agricultural products, with producers responsible for a range of quality assurance programs to ensure that food crops are free from various contaminants of detriment to human health. Large volumes of treated sewage sludge (biosolids), although low by world standards, are increasingly being recycled to land, primarily to replace plant nutrients and to improve soil properties; they are used in agriculture, forestry, and composted. The Australian National Biosolids Research Program (NBRP) has linked researchers to a collective goal to investigate nutrients and benchmark safe concentrations of metals nationally using a common methodology, with various other research programs conducted in a number of states specific to regional problems and priorities. The use of biosolids in Australia is strictly regulated by state guidelines, some of which are under review following recent research outcomes. Communication and research between the water industry, regulators and researchers specific to the regulation of biosolids is further enhanced by the Australian and New Zealand Biosolids Partnership (ANZBP).This paper summarises the major issues and constraints related to biosolids use in Australia using specific case examples from Western Australia, a member of the Australian NBRP, and highlights several research projects conducted over the last decade to ensure that biosolids are used beneficially and safely in the environment. Attention is given to research relating to plant nutrient uptake, particularly nitrogen and phosphorus (including that of reduced phosphorus uptake in alum sludge-amended soil); the risk of heavy metal uptake by plants, specifically cadmium, copper and zinc; the risk of pathogen contamination in soil and grain products; change to soil pH (particularly following lime-amended biosolids); and the monitoring of faecal contamination by biosolids in waterbodies using DNA techniques. Examples of products that are currently produced in Western Australia from sewage sludge include mesophilic anaerobically digested and dewatered biosolids cake, lime-amended biosolids, alum sludge and compost

Family attitudes, actions, decisions and experiences following implementation of deemed consent and the Human Transplantation (Wales) Act 2013:mixed-method study protocol

IntroductionThe Human Transplantation (Wales) Act 2013 (the Act) introduced a ‘soft opt-out’ system of organ donation on 1 December 2015. Citizens are encouraged to make their organ donation decision known during their lifetime. In order to work, the Act and media campaign need to create a context, whereby organ donation becomes the norm, and create a mechanism for people to behave as intended (formally register their decision; consider appointing a representative; convey their donation decision to their families and friends or do nothing—deemed consent). In addition, family members/appointed representatives need to be able to put their own views aside to support the decision of their loved one. The aim of this study is to evaluate initial implementation, outcomes and impact on families and appointed representatives who were approached about organ donation during the first 18 months.Methods and analysisProspective mixed-method coproductive study undertaken with National Health Service Blood and Transplant (NHSBT), and multiple patient/public representatives. The study is designed to collect information on all cases who meet specified criteria (≥18 years, deceased person voluntarily resident in Wales and died in Wales or England) whose family were approached between 1 December 2015 and 31 June 2017). Data for analysis include: NHSBT routinely collected anonymised audit data on all cases; Specialist Nurse in Organ Donation (SNOD) completed anonymised form for all cases documenting their perception of the families’ understanding of the Act, media campaign and outcome of the donation approach; questionnaires and depth interviews with any family member or appointed representative (minimum 50 cases). Additional focus groups and interviews with SNODs. Anonymised donation outcomes and registration activity reports for Wales provide additional context.Ethics and disseminationApproved by NHSBT Research, Innovation and Technology Advisory Group on 23 October 2015; Wales Research Ethics Committee 5 (IRAS190066; Rec Reference 15/WA/0414) on 25 November 2015 and NHSBT R&amp;D Committee (NHSBT ID: AP-15–02) on 24 November 2015.RegistrationThe protocol is registered on the Health and Care Research Wales Clinical Research Portfolio. Study ID number 34396, www.ukctg.nihr.ac.uk</jats:sec

Cell Cycle-Dependent Localization of Voltage-Dependent Calcium Channels and the Mitotic Apparatus in a Neuroendocrine Cell Line(AtT-20)

Changes in intracellular calcium are necessary for the successful progression of mitosis in many cells. Both elevation and reduction in intracellular calcium can disrupt mitosis by mechanisms that remain ill defined. In this study we explore the role of transmembrane voltage-gated calcium channels (CaV channels) as regulators of mitosis in the mouse corticotroph cell line (AtT-20). We report that the nifedipine-sensitive isoform CaV1.2 is localized to the “poleward side” of kinetechores during metaphase and at the midbody during cytokinesis. A second nifedipine-sensitive isoform, CaV1.3, is present at the mid-spindle zone in telophase, but is also seen at the midbody. Nifedipine reduces the rate of cell proliferation, and, utilizing time-lapse microscopy, we show that this is due to a block at the prometaphase stage of the cell cycle. Using Fluo-4 we detect calcium fluxes at sites corresponding to the mid-spindle zone and the midbody region. Another calcium dye, Fura PE3/AM, causes an inhibition of mitosis prior to anaphase that we attribute to a chelation of intracellular calcium. Our results demonstrate a novel, isoform-specific localization of CaV1 channels during cell division and suggest a possible role for these channels in the calcium-dependent events underlying mitotic progression in pituitary corticotrophs

A Longitudinal Study of Rural Youth Involvement in Outdoor Activities throughout Adolescence: Exploring Social Capital as a Factor in Community-Level Outcomes

This study examined youth participation in both organized and unstructured outdoor activities throughout adolescence, in a rural region in the northeastern United States. Survey data were collected at 7th, 8th, 10th, and 12th grade from 186 respondents across the region and was analyzed explore the relationship between antecedent predictors, outdoor activity participation, and outcomes related to developmental and educational achievement. Higher outdoor activity involvement was linked with positive outcomes but was also associated with other known predictors of development success including parents\u27 educational level, marital status, and involvement in future planning. The concept of social capital helps to explain overall patterns in the data, to broaden understanding of social dimensions of outdoor activity involvement, and to suggest directions for future research on positive youth development through outdoor activity

Phosphorus Cycling in the Sargasso Sea: Investigation Using the Oxygen Isotopic Composition of Phosphate, Enzyme-Labeled Fluorescence, and Turnover Times

Dissolved inorganic phosphorus (DIP) concentrations in surface water of vast areas of the ocean are extremely low (\u3c10 nM) and phosphorus (P) availability could limit primary productivity in these regions. We explore the use of oxygen isotopic signature of dissolved phosphate (δ18OPO4) to investigate biogeochemical cycling of P in the Sargasso Sea, Atlantic Ocean. Additional techniques for studying P dynamics including 33P-based DIP turnover time estimates and percent of cells expressing alkaline phosphatase (AP) activity as measured by enzyme-labeling fluorescence are also used. In surface waters, δ18OPO4 values were lower than equilibrium by 3–6%, indicative of dissolved organic phosphorous (DOP) remineralization by extracellular enzymes. An isotope mass balance model using a variety of possible combinations of enzymatic pathways and substrates indicates that DOP remineralization in the euphotic zone can account for a large proportion on P utilized by phytoplankton (as much as 82%). Relatively short DIP turnover times (4–8 h) and high expression of AP (38–77% of the cells labeled) are consistent with extensive DOP utilization and low DIP availability in the euphotic zone. In deep water where DOP utilization rates are lower, δ18OPO4 values approach isotopic equilibrium and DIP turnover times are longer. Our data suggests that in the euphotic zone of the Sargasso Sea, DOP may be appreciably remineralized and utilized by phytoplankton and bacteria to supplement cellular requirements. A substantial fraction of photosynthesis in this region is supported by DOP uptake