Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

The influence of family history of hypertension on disease prevalence and associated metabolic risk factors among Sri Lankan adults

Background Hypertension is a major contributor to the global non-communicable disease burden. Family history is an important non-modifiable risk factor for hypertension. The present study aims to describe the influence of family history (FH) on hypertension prevalence and associated metabolic risk factors in a large cohort of South Asian adults, from a nationally representative sample from Sri Lanka. Methods A cross-sectional survey among 5,000 Sri Lankan adults, evaluating FH at the levels of parents, grandparents, siblings and children. A binary logistic regression analysis was performed in all patients with ‘presence of hypertension’ as dichotomous dependent variable and using family history in parents, grandparents, siblings and children as binary independent variables. The adjusted odds ratio controlling for confounders (age, gender, body mass index, diabetes, hyperlipidemia and physical activity) are presented below. Results In all adults the prevalence of hypertension was significantly higher in patients with a FH (29.3 %, n = 572/1951) than those without (24.4 %, n = 616/2530) (p < 0.001). Presence of a FH significantly increased the risk of hypertension (OR:1.29; 95 % CI:1.13-1.47), obesity (OR:1.36; 95 % CI: 1.27–1.45), central obesity (OR:1.30; 95 % CI 1.22–1.40) and metabolic syndrome (OR:1.19; 95 % CI: 1.08–1.30). In all adults presence of family history in parents (OR:1.28; 95 % CI: 1.12–1.48), grandparents (OR:1.34; 95 % CI: 1.20–1.50) and siblings (OR:1.27; 95 % CI: 1.21–1.33) all were associated with significantly increased risk of developing hypertension. Conclusions Our results show that the prevalence of hypertension was significantly higher in those with a FH of hypertension. FH of hypertension was also associated with the prevalence of obesity, central obesity and metabolic syndrome. Individuals with a FH of hypertension form an easily identifiable group who may benefit from targeted interventions.

Projecting excess emergency department visits and associated costs in Brisbane, Australia, under population growth and climate change scenarios

The direct and indirect health effects of increasingly warmer temperatures are likely to further burden the already overcrowded hospital emergency departments (EDs). Using current trends and estimates in conjunction with future population growth and climate change scenarios, we show that the increased number of hot days in the future can have a considerable impact on EDs, adding to their workload and costs. The excess number of visits in 2030 is projected to range between 98–336 and 42–127 for younger and older groups, respectively. The excess costs in 2012–13 prices are estimated to range between AU$51,000–184,000 (0–64) and AU$27,000–84,000 (65+). By 2060, these estimates will increase to 229–2300 and 145–1188 at a cost of between AU$120,000–1,200,000 and AU$96,000–786,000 for the respective age groups. Improvements in climate change mitigation and adaptation measures are likely to generate synergistic health co-benefits and reduce the impact on frontline health services.

IgE-Associated IGHV Genes from Venom and Peanut Allergic Individuals Lack Mutational Evidence of Antigen Selection

Antigen selection of B cells within the germinal center reaction generally leads to the accumulation of replacement mutations in the complementarity-determining regions (CDRs) of immunoglobulin genes. Studies of mutations in IgE-associated VDJ gene sequences have cast doubt on the role of antigen selection in the evolution of the human IgE response, and it may be that selection for high affinity antibodies is a feature of some but not all allergic diseases. The severity of IgE-mediated anaphylaxis is such that it could result from higher affinity IgE antibodies. We therefore investigated IGHV mutations in IgE-associated sequences derived from ten individuals with a history of anaphylactic reactions to bee or wasp venom or peanut allergens. IgG sequences, which more certainly experience antigen selection, served as a control dataset. A total of 6025 unique IgE and 5396 unique IgG sequences were generated using high throughput 454 pyrosequencing. The proportion of replacement mutations seen in the CDRs of the IgG dataset was significantly higher than that of the IgE dataset, and the IgE sequences showed little evidence of antigen selection. To exclude the possibility that 454 errors had compromised analysis, rigorous filtering of the datasets led to datasets of 90 core IgE sequences and 411 IgG sequences. These sequences were present as both forward and reverse reads, and so were most unlikely to include sequencing errors. The filtered datasets confirmed that antigen selection plays a greater role in the evolution of IgG sequences than of IgE sequences derived from the study participants.

Geochronological (U–Pb, U–Th–total Pb, Sm–Nd) and geochemical (REE, 87Sr/86Sr, δ18O, δ13C) tracing of intraplate tectonism and associated fluid flow in the Warburton Basin, Australia

The Warburton Basin of central Australia has experienced a complex tectonic and fluid-flow history, resulting in the formation of various authigenic minerals. Geochemical and geochronological analyses were undertaken on vein carbonates from core samples of clastic sediments. Results were then integrated with zircon U–Pb dating and uraninite U–Th–total Pb dating from the underlying granite. Stable and radiogenic isotopes (δ18O, Sr and εNd), as well as trace element data of carbonate veins indicate that >200 °C basinal fluids of evolved meteoric origin circulated through the Warburton Basin. Almost coincidental ages of these carbonates (Sm–Nd; 432 ± 12 Ma) with primary zircon (421 ± 3.8 Ma) and uraninite (407 ± 16 Ma) ages from the granitic intrusion point towards a substantial period of active tectonism and an elevated thermal regime during the mid Silurian. We hypothesise that such a thermal regime may have resulted from extensional tectonism and concomitant magmatic activity following regional orogenesis. This study shows that the combined application of geochemical and geochronological analyses of both primary and secondary species may constrain the timing of tectonomagmatic events and associated fluid flow in intraplate sedimentary basins. Furthermore, this work suggests that the Sm–Nd-isotopic system is surprisingly robust and can record geologically meaningful age data from hydrothermal mineral species.

Characterization of an Evolutionarily Conserved Metallophosphoesterase That Is Expressed in the Fetal Brain and Associated with the WAGR Syndrome

Among the human diseases that result from chromosomal aberrations, a de novo deletion in chromosome 11p13 is clinically associated with a syndrome characterized by Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR). Not all genes in the deleted region have been characterized biochemically or functionally. We have recently identified the first Class III cyclic nucleotide phosphodiesterase, Rv0805, from Mycobacterium tuberculosis, which biochemically and structurally belongs to the superfamily of metallophosphoesterases. We performed a large scale bioinformatic analysis to identify orthologs of the Rv0805 protein and identified many eukaryotic genes that included the human 239FB gene present in the region deleted in the WAGR syndrome. We report here the first detailed biochemical characterization of the rat 239FB protein and show that it possesses metallophosphodiesterase activity. Extensive mutational analysis identified residues that are involved in metal interaction at the binuclear metal center. Generation of a rat 239FB protein with a mutation corresponding to a single nucleotide polymorphism seen in human 239FB led to complete inactivation of the protein. A close ortholog of 239FB is found in adult tissues, and biochemical characterization of the 239AB protein demonstrated significant hydrolytic activity against 2',3'-cAMP, thus representing the first evidence for a Class III cyclic nucleotide phosphodiesterase in mammals. Highly conserved orthologs of the 239FB protein are found in Caenorhabditis elegans and Drosophila and, coupled with available evidence suggesting that 239FB is a tumor suppressor, indicate the important role this protein must play in diverse cellular events.

Current CAPE-15: A measure of recent psychotic-like experiences and associated distress

Aim Psychotic-like experiences (PLEs) are common in young people and are associated with both distress and adverse outcomes. The Community Assessment of Psychic Experiences-Positive Scale (CAPE-P) provides a 20-item measure of lifetime PLEs. A 15-item revision of this scale was recently published (CAPE-P15). Although the CAPE-P has been used to assess PLEs in the last 12 months, there is no version of the CAPE for assessing more recent PLEs (e.g. 3 months). This study aimed to determine the reliability and validity of the current CAPE-P15 and assess its relationship with current distress. Method A cross-sectional online survey of 489 university students (17–25 years) assessed lifetime and current substance use, current distress, and lifetime and 3-month PLEs on the CAPE-P15. Results Confirmatory factor analysis indicated that the current CAPE-P15 retained the same three-factor structure as the lifetime version consisting of persecutory ideation, bizarre experiences and perceptual abnormalities. The total score of the current version was lower than the lifetime version, but the two were strongly correlated (r = .64). The current version was highly predictive of generalized distress (r = .52) and indices that combined symptom frequency with associated distress did not confer greater predictive power than frequency alone. Conclusion This study provided preliminary data that the current CAPE-P15 provides a valid and reliable measure of current PLEs. The current CAPE-P15 is likely to have substantial practical utility if it is later shown to be sensitive to change, especially in prevention and early intervention for mental disorders in young people.

Anisotropic Gaussian Schell-model beams: Passage through optical systems and associated invariants

Anisotropic Gaussian Schell-model (AGSM) fields and their transformation by first-order optical systems (FOS’s) forming Sp(4,R) are studied using the generalized pencils of rays. The fact that Sp(4,R), rather than the larger group SL(4,R), is the relevant group is emphasized. A convenient geometrical picture wherein AGSM fields and FOS’s are represented, respectively, by antisymmetric second-rank tensors and de Sitter transformations in a (3+2)-dimensional space is developed. These fields are shown to separate into two qualitatively different families of orbits and the invariants over each orbit, two in number, are worked out. We also develop another geometrical picture in a (2+1)-dimensional Minkowski space suitable for the description of the action of axially symmetric FOS’s on AGSM fields, and the invariants, now seven in number, are derived. Interesting limiting cases forming coherent and quasihomogeneous fields are analyzed.

Controlling Pythium and associated pests in ginger

This project is to identify treatments that ginger growers can use to control two serious soil-borne pathogens that have emerged and threaten the viability of the ginger industry. Pythium myriotylum, responsible for a severe rhizome rot, is the more serious of the two. It was first identified by ginger growers in the 2007/08 growing season, with some producers reporting total crop losses in some blocks. Symphylids are wingless soil-inhabiting arthropods that feed on the ginger plant's root tips and impair the plants´ ability to absorb nutrients, seriously restricting plant growth and development. Damage caused by symphylids to ginger roots is also expected to facilitate entry of Pythium into the plant.

Compression use during an exercise intervention and associated changes in breast cancer-related lymphoedema

Aim This study assessed the association between compression use and changes in lymphoedema observed in women with breast cancer-related lymphoedema who completed a 12 week exercise intervention. Methods This work uses data collected from a 12 week exercise trial, whereby women were randomly allocated into either aerobic-based only (n=21) or resistance-based only (n=20) exercise. Compression use during the trial was at the participant’s discretion. Differences in lymphoedema (measured by L-Dex score and inter-limb circumference difference [%]) and associated symptoms between those who wore, and did not wear compression during the 12 week intervention were assessed. We also explored participants’ reasons surrounding compression during exercise. Results No significant interaction effect between time and compression use for lymphoedema was observed. There was no difference between groups over time in the number or severity of lymphoedema symptoms. Irrespective of compression use, there were trends for reductions in the proportion of women reporting severe symptoms, but lymphoedema status did not change. Individual reasons for the use of compression, or lack thereof, varied markedly. Conclusion Our findings demonstrated an absence of a positive or negative effect from compression use during exercise on lymphoedema. Current and previous findings suggest the clinical recommendation that garments must be worn during exercise is questionable, and its application requires an individualised approach.

World War I military portraits of Arthur Neustadt.

Digital Image

Military portraits of Erich Gustav Baum as a solider during World War I Portraits Men

Includes photographs of Erich Gustav Baum with a bicycle, with other unidentified soliders, and wearing an Iron Cross

Board of Delegates of American Israelites records 1859-1881, 1887, 1932

Contains printed copies of the 1860 constitution and by-laws, copies of proceedings and annual reports, 1859-1877, of the Board of Delegates; report on Jews in Roumania, an 1874 annual report of the Hebrew Benevolent and Orphan Asylum Society, manuscript minute books and minutes of meetings, 1859-1876, resolutions, executive, financial, ritual slaughtering and other special committee reports, newspaper clippings and correspondence with synagogues and organizations in the U.S. who constitute the membership of the Board of Delegates, with the Union of American Hebrew Congregations with whom they later merged, the Union's Board of Delegates of Civil and Religious Rights, and with individuals and organizations in foreign countries including the Alliance Israelite Universelle, the Anglo-Jewish Association, the Board of Deputies of British Jews, the Committee for the Roumanian Jews (Berlin), the Koenigsberg Committee, and the London Roumanian Committee.