Prostate screening uptake in Australian BRCA1 and BRCA2 carriers

Men who carry mutations in BRCA1 or BRCA2 are at increased risk for prostate cancer. However the efficacy of prostate screening in this setting is uncertain and limited data exists on the uptake of prostate screening by mutation carriers. This study prospectively evaluated uptake of prostate cancer screening in a multi-institutional cohort of mutation carriers. Subjects were unaffected male BRCA1 and BRCA2 mutation carriers, aged 40–69 years, enrolled in the Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab) and who had completed a mailed, self-report follow-up questionnaire 3 yearly after study entry. Of the 75 male carriers in this study, only 26 (35%) had elected to receive their mutation result. Overall, 51 (68%) did not recall having received a recommendation to have prostate screening because of their family history, but 41 (55%) had undergone a prostate specific antigen (PSA) test and 32 (43%) a digital rectal examination (DRE) in the previous 3 years. Those who were aware of their mutation result were more likely to have received a recommendation for prostate screening (43 vs. 6%, p = 0.0001), and to have had a PSA test (77 vs. 43%, p = 0.005) and a DRE (69 vs. 29%, p = 0.001) in the previous 3 years. The majority of unaffected males enrolled in kConFab with a BRCA1/2 mutation have not sought out their mutation result. However, of those aware of their positive mutation status, most have undergone at least one round of prostate screening in the previous 3 years

Analysis of candidate genes for macular telangiectasia type 2

Purpose: To find the gene(s) responsible for macular telangiectasia type 2 (MacTel) by a candidate-gene screening approach.Methods: Candidate genes were selected based on the following criteria: those known to cause or be associated with diseases with phenotypes similar to MacTel, genes with known function in the retinal vasculature or macular pigment transport, genes that emerged from expression microarray data from mouse models designed to mimic MacTel phenotype characteristics, and genes expressed in the retina that are also related to diabetes or hypertension, which have increased prevalence in MacTel patients. Probands from eight families with at least two affected individuals were screened by direct sequencing of 27 candidate genes. Identified nonsynonymous variants were analyzed to determine whether they cosegregate with the disease in families. Allele frequencies were determined by TaqMan analysis of the large MacTel and control cohorts.Results: We identified 23 nonsynonymous variants in 27 candidate genes in at least one proband. Of these, eight were known single nucleotide polymorphisms (SNPs) with allele frequencies of >0.05; these variants were excluded from further analyses. Three previously unidentified missense variants, three missense variants with reported disease association, and five rare variants were analyzed for segregation and/or allele frequencies. No variant fulfilled the criteria of being causal for MacTel. A missense mutation, p.Pro33Ser in frizzled homolog (Drosophila) 4 (FZD4), previously suggested as a disease-causing variant in familial exudative vitreoretinopathy, was determined to be a rare benign polymorphism.Conclusions: We have ruled out the exons and flanking intronic regions in 27 candidate genes as harboring causal mutations for MacTel

Near-island biological hotspots in barren ocean basins

Phytoplankton production drives marine ecosystem trophic-structure and global fisheries yields. Phytoplankton biomass is particularly influential near coral reef islands and atolls that span the oligotrophic tropical oceans. The paradoxical enhancement in phytoplankton near an island-reef ecosystem—Island Mass Effect (IME)—was first documented 60 years ago, yet much remains unknown about the prevalence and drivers of this ecologically important phenomenon. Here we provide the first basin-scale investigation of IME. We show that IME is a near-ubiquitous feature among a majority (91%) of coral reef ecosystems surveyed, creating near-island ‘hotspots' of phytoplankton biomass throughout the upper water column. Variations in IME strength are governed by geomorphic type (atoll vs island), bathymetric slope, reef area and local human impacts (for example, human-derived nutrient input). These ocean oases increase nearshore phytoplankton biomass by up to 86% over oceanic conditions, providing basal energetic resources to higher trophic levels that support subsistence-based human populations

Women Have Higher Protein Content of β-Oxidation Enzymes in Skeletal Muscle than Men

It is well recognized that compared with men, women have better ultra-endurance capacity, oxidize more fat during endurance exercise, and are more resistant to fat oxidation defects i.e. diet-induced insulin resistance. Several groups have shown that the mRNA and protein transcribed and translated from genes related to transport of fatty acids into the muscle are greater in women than men; however, the mechanism(s) for the observed sex differences in fat oxidation remains to be determined. Muscle biopsies from the vastus lateralis were obtained from moderately active men (N = 12) and women (N = 11) at rest to examine mRNA and protein content of genes involved in lipid oxidation. Our results show that women have significantly higher protein content for tri-functional protein alpha (TFPα), very long chain acyl-CoA dehydrogenase (VLCAD), and medium chain acyl-CoA dehydrogenase (MCAD) (P<0.05). There was no significant sex difference in the expression of short-chain hydroxyacyl-CoA dehydrogenase (SCHAD), or peroxisome proliferator activated receptor alpha (PPARα), or PPARγ, genes potentially involved in the transcriptional regulation of lipid metabolism. In conclusion, women have more protein content of the major enzymes involved in long and medium chain fatty acid oxidation which could account for the observed differences in fat oxidation during exercise

New Zealand blackcurrant extract enhances fat oxidation during prolonged cycling in endurance-trained females.

PURPOSE: New Zealand blackcurrant (NZBC) extract has previously been shown to increase fat oxidation during prolonged exercise, but this observation is limited to males. We examined whether NZBC intake also increases fat oxidation during prolonged exercise in females, and whether this was related to greater concentrations of circulating fatty acids. METHODS: In a randomised, crossover, double-blind design, 16 endurance-trained females (age: 28 ± 8 years, BMI: 21.3 ± 2.1 kg·m-2, VO2max: 43.7 ± 1.1 ml·kg-1·min-1) ingested 600 mg·day-1NZBC extract (CurraNZ™) or placebo (600 mg·day-1microcrystalline cellulose) for 7 days. On day 7, participants performed 120 min cycling at 65% VO2max, using online expired air sampling with blood samples collected at baseline and at 15 min intervals throughout exercise for analysis of glucose, NEFA and glycerol. RESULTS: NZBC extract increased mean fat oxidation by 27% during 120 min moderate-intensity cycling compared to placebo (P = 0.042), and mean carbohydrate oxidation tended to be lower (P = 0.063). Pre-exercise, plasma NEFA (P = 0.034) and glycerol (P = 0.051) concentrations were greater following NZBC intake, although there was no difference between conditions in the exercise-induced increase in plasma NEFA and glycerol concentrations (P > 0.05). Mean fat oxidation during exercise was moderately associated with pre-exercise plasma NEFA concentrations (r = 0.45, P = 0.016). CONCLUSIONS: Intake of NZBC extract for 7 days elevated resting concentrations of plasma NEFA and glycerol, indicative of higher lipolytic rates, and this may underpin the observed increase in fat oxidation during prolonged cycling in endurance-trained females

Cationic polyamines inhibit anthrax lethal factor protease

BACKGROUND: Anthrax is a human disease that results from infection by the bacteria, Bacillus anthracis and has recently been used as a bioterrorist agent. Historically, this disease was associated with Bacillus spore exposure from wool or animal carcasses. While current vaccine approaches (targeted against the protective antigen) are effective for prophylaxis, multiple doses must be injected. Common antibiotics that block the germination process are effective but must be administered early in the infection cycle. In addition, new therapeutics are needed to specifically target the proteolytic activity of lethal factor (LF) associated with this bacterial infection. RESULTS: Using a fluorescence-based assay to identify and characterize inhibitors of anthrax lethal factor protease activity, we identified several chemically-distinct classes of inhibitory molecules including polyamines, aminoglycosides and cationic peptides. In these studies, spermine was demonstrated for the first time to inhibit anthrax LF with a K(i )value of 0.9 ± 0.09 μM (mean ± SEM; n = 3). Additional linear polyamines were also active as LF inhibitors with lower potencies. CONCLUSION: Based upon the studies reported herein, we chose linear polyamines related to spermine as potential lead optimization candidates and additional testing in cell-based models where cell penetration could be studied. During our screening process, we reproducibly demonstrated that the potencies of certain compounds, including neomycin but not neamine or spermine, were different depending upon the presence or absence of nucleic acids. Differential sensitivity to the presence/absence of nucleic acids may be an additional point to consider when comparing various classes of active compounds for lead optimization

Marine Protected Area Networks: Assessing Whether the Whole Is Greater than the Sum of Its Parts

Anthropogenic impacts are increasingly affecting the world’s oceans. Networks of marine protected areas (MPAs) provide an option for increasing the ecological and economic benefits often provided by single MPAs. It is vital to empirically assess the effects of MPA networks and to prioritize the monitoring data necessary to explain those effects. We summarize the types of MPA networks based on their intended management outcomes and illustrate a framework for evaluating whether a connectivity network is providing an outcome greater than the sum of individual MPA effects. We use an analysis of an MPA network in Hawai’i to compare networked MPAs to non-networked MPAs to demonstrate results consistent with a network effect. We assert that planning processes for MPA networks should identify their intended outcomes while also employing coupled field monitoring-simulation modeling approaches, a powerful way to prioritize the most relevant monitoring data for empirically assessing MPA network performance