Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2

Risks of breast and ovarian cancer were determined for Ashkenazi Jewish women with inherited mutations in the tumor suppressor genes BRCA1 and BRCA2. We selected 1008 index cases, regardless of family history of cancer, and carried out molecular analysis across entire families. The lifetime risk of breast cancer among female mutation carriers was 82%, similar to risks in families with many cases. Risks appear to be increasing with time: Breast cancer risk by age 50 among mutation carriers born before 1940 was 24%, but among those born after 1940 it was 67%. Lifetime risks of ovarian cancer were 54% for BRCA1 and 23% for BRCA2 mutation carriers. Physical exercise and lack of obesity in adolescence were associated with significantly delayed breast cancer onset.     

Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast

Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.     

A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila

One proposed strategy for controlling the transmission of insect-borne pathogens uses a drive mechanism to ensure the rapid spread of transgenes conferring disease refractoriness throughout wild populations. Here, we report the creation of maternal-effect selfish genetic elements in Drosophila that drive population replacement and are resistant to recombination-mediated dissociation of drive and disease refractoriness functions. These selfish elements use microRNA-mediated silencing of a maternally expressed gene essential for embryogenesis, which is coupled with early zygotic expression of a rescuing transgene.     

Comparative influence of isolation,landscape, and wetland characteristics on egg-mass abundance of two pool-breeding amphibian species

The distribution and abundance of species are shaped by local and landscape processes, but the dominant processes may differ with scale and increasing human disturbance. We investigated population responses of two pool-breeding amphibian species to differences in local and landscape characteristics in suburbanizing, southeastern New Hampshire, USA. In 2003 and 2004, we sampled 49 vernal pools for spotted salamander (Ambystoma maculatum) and wood frog (Lithobates sylvaticus) egg masses. Using egg masses as a proxy for breeding-female population size, we examined the relative influence of five land-use and three isolation variables at two scales (300 and 1000 m) and five wetland variables on egg-mass abundance. For both species, road density at the landscape scale (1000 m) and hydroperiod most strongly predicted egg-mass abundance, with abundance decreasing as roads became denser and hydroperiods shortened. Wetland isolation was also an important predictor, with abundance greatest at more isolated pools, suggesting that both species concentrate at isolated pools when alternative breeding sites are scarce. Surprisingly, no 300-m parameters were strongly associated with salamander egg-mass abundance, whereas several landscape parameters were. In suburbanizing areas, it is at least as important to consider landscape-scale road density as to consider hydroperiod when designing conservation plans for these species. Furthermore, both isolated and clustered pools provide these species important habitat and may require protection. Finally, the conceptual framework for spotted-salamander management must be expanded so that spatial configuration at the landscape scale becomes a regular, integrated component of conservation planning for this species.     

Rice bran fermented with saccharomyces boulardii generates novel metabolite profiles with bioactivity

Emerging evidence supporting chronic disease fighting properties of rice bran has advanced the development of stabilized rice bran for human use as a functional food and dietary supplement. A global and targeted metabolomic investigation of stabilized rice bran fermented with Saccharomyces boulardii was performed in three rice varieties. Metabolites from S. boulardii-fermented rice bran were detected by gas chromatography-mass spectrometry (GC-MS) and assessed for bioactivity compared to nonfermented rice bran in normal and malignant lymphocytes. Global metabolite profiling revealed significant differences in the metabolome that led to discovery of candidate compounds modulated by S. boulardii fermentation. Fermented rice bran extracts from three rice varieties reduced growth of human B lymphomas compared to each variety's nonfermented control and revealed that fermentation differentially altered bioactive compounds. These data support that integration of global and targeted metabolite analysis can be utilized for assessing health properties of rice bran phytochemicals that are enhanced by yeast fermentation and that differ across rice varieties.     

Evaluation of intrarenal mesenchymal stem cell injection for treatment of chronic kidney disease in cats: a pilot study

The feasibility of autologous intrarenal mesenchymal stem cell (MSC) therapy in cats with chronic kidney disease (CKD) was investigated. Six cats (two healthy, four with CKD) received a single unilateral intrarenal injection of autologous bone marrow-derived or adipose tissue-derived MSC (bmMSC or aMSC) via ultrasound guidance. Minimum database and glomerular filtration rate (GFR) via nuclear scintigraphy were determined pre-injection, at 7 days and at 30 days post-injection. Intrarenal injection did not induce immediate or long-term adverse effects. Two cats with CKD that received aMSC experienced modest improvement in GFR and a mild decrease in serum creatinine concentration. Despite the possible benefits of intrarenal MSC injections for CKD cats, the number of sedations and interventions required to implement this approach would likely preclude widespread clinical application. We concluded that MSC could be transferred safely by ultrasound-guided intrarenal injection in cats, but that alternative sources and routes of MSC therapy should be investigated.     

Antioxidants, low molecular weight carbohydrates, and total antioxidant capacity in strawberries (Fragaria x ananassa): effects of cultivar, ripening, and storage

Four cultivars of strawberries (Senga Sengana, BFr77111, Elsanta, and Honeoye) were studied for their content of antioxidants, total antioxidant capacity, and low molecular weight carbohydrates in relation to harvest year, ripening stage, and cold storage. For ascorbic acid, chlorogenic acid, ellagic acid, and total antioxidative capacity, measured in both water-soluble and water-insoluble extracts, there was a 2-5-fold variation among cultivars. Unripe berries contained lower concentrations of chlorogenic acid and p-coumaric acid and also quercetin and kaempferol compared with riper berries. During cold storage for up to 3 days, relatively few changes in the concentration of the different antioxidants occurred. The concentrations of several investigated parameters were interrelated, for example, for ascorbic acid and water-soluble antioxidant capacity and for ellagic acid and water-insoluble antioxidant capacity. The dominating sugars in strawberries were fructose and glucose, but considerable amounts of sucrose were also present, and their contents varied among cultivars, giving a predicted glycemic index of approximately 81. Verbascose, raffinose, and stachyose were found in only minor amounts. The study shows that the concentration of a number of bioactive compounds in strawberries varied according to cultivar, ripening stage, and storage. This information should make it possible to select strawberries with an optimal content of bioactive compounds.     

Ex vivo investigation of the use of hydrothermal energy to induce chondrocyte necrosis in articular cartilage of the metacarpophalangeal and metatarsophalangeal joints of horses

OBJECTIVE: To evaluate the use of hydrothermal ablation of articular cartilage for arthrodesis in horses through investigation of the effects of joint lavage with physiologic saline (0.9% NaCI) solution (80 degrees C) for various treatment times on chondrocyte viability in the articular cartilage of the metacarpophalangeal and metatarsophalangeal joints of cadaveric horse limbs. Sample Population-7 pairs of metacarpophalangeal and 8 pairs of metatarsophalangeal joints from 8 Thoroughbreds. PROCEDURE: The horses were euthanatized for reasons unrelated to musculoskeletal disease. On a random basis, 1 joint of each pair underwent intra-articular lavage for 5, 10, or 15 minutes with heated saline solution (80 degrees C); the other joint underwent sham treatment of similar duration with saline solution at 22 degrees C (control). Cartilage samples from the distal articular surface of metacarpus III (or metatarsus III), the proximal surface of the proximal phalanx, and the lateral and medial proximal sesamoid bones were assessed for chondrocyte viability via confocal microscopy and viability staining following enzymatic digestion. RESULTS: Compared with the control joints, findings of both viability assays indicated that the percentage of sites containing viable chondrocytes in heat-treated joints was decreased.Treatment hazard ratios of 0.048 (confocal microscopy) and 0.2 (digestion assay) were estimated. Histologically, periarticular soft tissues had minimal detrimental effects after heat treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Ex vivo intra-articular lavage with saline solution at 80 degrees C resulted in the death of almost all articular chondrocytes in the joint. This technique may be a satisfactory method for extensive cartilage ablation when performing arthrodesis by minimally invasive techniques.     

Central nervous system dysfunction associated with Rocky Mountain spotted fever infection in five dogs

Five dogs from the northeastern United States were presented with clinical signs of neurological disease associated with Rocky Mountain spotted fever (RMSF) infection. Four of the five dogs had vestibular system dysfunction. Other neurological signs included paresis, tremors, and changes in mentation. All of the dogs had an elevated indirect fluorescent antibody titer or a positive semiquantitative enzyme screening immunoassay titer for Rickettsia rickettsii at the time of presentation. Although a higher mortality rate has been reported for dogs with neurological symptoms and RMSF infection, all of the dogs in this study improved with appropriate medical therapy and supportive care.