Transcriptional regulation of the human ALDH1A1 promoter by the oncogenic homeoprotein TLX1/HOX11

The homeoprotein TLX1, which is essential to spleen organogenesis and oncogenic when aberrantly expressed in immature T cells, functions as a bifunctional transcriptional regulator, being capable of activation or repression depending on cell type and/or promoter context. However, the detailed mechanisms by which it regulates the transcription of target genes such as ALDH1A1 remains to be elucidated. We therefore functionally assessed the ability of TLX1 to regulate ALDH1A1 expression in two hematopoietic cell lines, PER-117 T-leukemic cells and human erythroleukemic (HEL) cells, by use of luciferase reporter and mobility shift assays. We showed that TLX1 physically interacts with the general transcription factor TFIIB via its homeodomain, and identified two activities in respect to TLX1-mediated regulation of the CCAAT box-containing ALDH1A1 promoter. The first involved CCAAT-dependent transcriptional repression via perturbation of GATA factor-containing protein complexes assembled at a non-canonical TATA (GATA) box. A structurally intact homeodomain was essential for repression by TLX1 although direct DNA binding was not required. The second activity, which involved CCAAT-independent transcriptional activation did not require an intact homeodomain, indicating that the activation and repression functions of TLX1 are distinct. These findings confirm ALDH1A1 gene regulation by TLX1 and support an indirect model for TLX1 function, in which protein-protein interactions, rather than DNA binding at specific sites, are crucial for its transcriptional activity

The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 1: modifications to the androgen receptor

Prostate cancer is the second most common male malignancy in the western world an increasing incidence in an ageing population. Treatment of advanced prostate cancer relies on androgen deprivation. Although the majority of patients initially respond favourably to androgen deprivation therapy, the mean time to relapse is 12-18 months. Currently there are few treatments available for men who have developed resistance to hormone therapy, due to the lack of understanding of the molecular mechanisms underlying development of this disease. Recently, however, major advances have been made in understanding both androgen receptor (AR) dependent and independent pathways which promote development of hormone resistant prostate cancer. This review will focus on modifications to the AR and associated pathways. Molecular modifications to the androgen receptor itself, e.g. mutations and/or amplification, although involved in the development of hormone resistance cannot explain all cases. Phosphorylation of AR, via either Ras/MAP kinase or PI3K/Akt signal transduction pathways, have been shown to activate AR in both a ligand (androgen) dependent and independent fashion. During this review we will discuss the clinical evidence to support AR dependent pathways as mediators of hormone resistance

Osmoregulation of the Australian freshwater crocodile, Crocodylus johnstoni, in fresh and saline waters

An unusual saltwater population of the "freshwater" crocodilian, Crocodylus johnstoni, was studied in the estuary of the Limmen Bight River in Australia's Northern Territory and compared with populations in permanently freshwater habitats. Crocodiles in the river were found across a large salinity gradient, from fresh water to a salinity of 24 mg.ml-1, more than twice the body fluid concentration. Plasma osmolarity, concentrations of plasma Na+, Cl-, and K+, and exchangeable Na+ pools were all remarkably constant across the salinity spectrum and were not substantially higher or more variable than those in crocodiles from permanently freshwater habitats. Body fluid volumes did not vary; condition factor and hydration status of crocodiles were not correlated with salinity and were not different from those of crocodiles from permanently fresh water. C. johnstoni clearly has considerable powers of osmoregulation in waters of low to medium salinity. Whether this osmoregulatory competence, extends to continuously hyperosmotic environments is not known, but distributional data suggest that C. johnstoni in hyperosmotic conditions may require periodic access to hypoosmotic water. The study demonstrates a physiological capacity for colonisation of at least some estuarine waters by this normally stenohaline freshwater crocodilian

A beta-alpha coincidence counting system for measurement of trace quantities of 238U and 232Th in aqueous samples at the Sudbury Neutrino Observatory

The Sudbury Neutrino Observatory experiment was built to measure the total flux of 8B solar neutrinos via the neutral current disintegration deuterium nuclei. This process can be mimicked by daughter isotopes of 232Th and 238U which can photo-disintegrate the deuterium nucleus. Measurement of the concentration of such radioisotopes in the heavy water was critical to the success of the experiment. A radium assay technique using Hydrous Titanium Oxide coated filters was developed for this purpose and it was used in conjunction with a delayed beta-alpha coincidence counting system. The design, calibration and operation of this counting system are described in this paper. The counting efficiency for 232Th (224Ra) and 238U (226Ra) were measured to be 50 +/- 5% and 62 +/- 7

Sodium and Water Fluxes in Free-Living Crocodylus Porosus in Marine and Brackish Conditions

Radioactive sodium and water were used to determine total body water (TBW), exchangeable sodium (ExNa) and water and sodium fluxes in free-living Crocodylus porosus in marine (hyperosmotic; salinity = 250/00-350/00) and brackish (hypoosmotic; salinity = 20/00-7.50/00) sections of the Tomkinson River in northern Australia. At capture, size-corrected TBW and ExNa pools in 62 crocodiles (hatchlings, juveniles, and subadults; weight, 0.108-54.4 kg) were independent of salinity history. To determine fluxes, all animals were released at their capture sites and left undisturbed until recapture. Thirty-seven were recaptured after 7-18 days. Fifteen of the 17 hatchlings recaptured from both salinity categories grew and maintained their condition and hydration status. In contrast, all 20 juveniles and subadults lost weight in the same period, and juveniles in hyperosmotic conditions showed significantly lower hydration and condition factors. Water effluxes in hatchlings were ~80 and ~160 ml kg-0.63 day-1 in marine and brackish conditions, respectively. Comparable sodium effluxes were 7.5 and 4.4 mmol kg-0.63 day1. All crocodiles in hyperosmotic conditions had consistently lower water effluxes (~ X0.5) and higher sodium effluxes (~ X 1.6) than did crocodiles in brackish water. In both salinity categories, hatchlings had greater water turnover (~ X 1.3, X 1.6) and sodium turnover (~ X 1.5, X 1.25) than did juveniles and subadults. Interpretation of the field data is complicated by integumentary exchange of sodium and water, a size-related aphagia apparently induced by disturbance, and difficulties of adjusting for allometric differences across a wide range of sizes. Nevertheless, it is clear that C. porosus is able to effect considerable economies of water turnover in hyperosmotic salt water and that the secretory capacity of the lingual glands, as measured in the laboratory, is more than enough to account for the highest sodium effluxes that we measured in C. porosus in the field

KContact, an enhanced intervention for contact between children in out-of-home care and their parents: protocol for a cluster randomised controlled trial

BACKGROUND: When children are unable to safely live at home with their parents, contact between these children and their parents is considered, in most cases, important for maintaining children's sense of identity and relationships with their parents. However, the research evidence on contact is weak and provides little guidance on how to manage contact and when it is beneficial or potentially harmful. The evidence in relation to contact interventions with parents and their children who are to remain in long-term care is the most limited. A small number of studies have been identified where interventions which were therapeutic, child-focused and with clear goals, particularly aimed at preparing and supporting parents, showed some promising results. This trial aims to build on the existing evidence by trialling an enhanced model of contact in multiple sites in Australia. METHODS/DESIGN: This study is a cluster randomised controlled trial of an enhanced contact intervention with children in long-term care who are having supervised contact with their parents. Intervention sites will implement the kContact intervention that increases the preparation and support provided to parents in relation to contact. Baseline and follow-up interviews are being conducted with parents, carers and agency workers at intervention and control sites. Follow-ups interviews will assess whether there has been an increase in children's emotional safety and a reduction in distress in response to contact visits with their parents (the primary outcome variable as measured using the Strength and Difficulties Questionnaire), improved relationships between children and their parents, improved parental ability to support contact, and fewer contact visits cancelled. DISCUSSION: By increasing the evidence base in this area, the study aims to better guide the management and supervision of contact visits in the out-of-home care context and improve outcomes for the children and their families. TRIAL REGISTRATION: Trial registered on 7 April 2015 with the Australian New Zealand Clinical Trials Registry ACTRN12615000313538

Osmoregulation by the Broad-Snouted Caiman, "Caiman latirostris", in Estuarine Habitat in Southern Brazil

The broad-snouted caiman Caiman latirostris, of South America mostly frequents freshwater but occurs also in estuaries. Nothing of substance is known of its osmoregulatory physiology but, in the light of accumulating evidence that alligatorids lack specialised adaptations for life in hyperosmotic waters, we anticipated its physiology would be more similar to that of Alligator mississippiensis than the euryhaline Crocodylus porosus, which has both lingual salt glands and a more complex renal:cloacal system. This proved to be the case. Caiman captured in estuaries of the Ilha do Cardoso in southern Brazil were effective hypoosmotic osmoregulators in salinities of 0-24 ppt (seawater = 35 ppt). Plasma osmolarity, sodium and chloride were similar to those in other crocodilians and not influenced by salinity. Plasma urea was low and did not vary with salinity. We found no evidence of lingual or other salt glands. Urinary electrolyte concentrations varied considerably with salinity and in ways reminiscent of A. mississippiensis but very different from C. porosus. Ca. latirostris dehydrated in seawater more rapidly than C. porosus and had substantially higher integumental permeability to water. Caiman did not drink seawater but rehydrated rapidly when returned to freshwater (FW). We found small caiman (< 500 g) only in very low salinities (< 3 ppt) and larger caiman closer to the sea. We postulate that medium to large Ca. latirostris can take advantage of the feeding opportunities presented by the estuarine mangal despite lacking the physiological specialisations of crocodylids. Two individuals which we re-sighted by chance had traveled at least 600m in 2-3 days, showing that every caiman we captured or saw was within easy reach of FW. Most likely their habitation of the estuary and its mangal is achieved through a combination of low surface area:volume ratio, relatively impermeable skin, and periodic access to FW

What is the Value of Group Nutrition Education for Older Adults with Diabetes?

Background: • 23.6 million people or 7.8% of the US population have diabetes • Type 2 diabetes can cause many serious problems that affect the heart, nerves, eyes, and kidneys • Lifestyle choices, including dietmanagement, can be used to control or help supplement medical care used in minimizing the risk factors associated with diabeteshttps://scholarworks.uvm.edu/comphp_gallery/1009/thumbnail.jp