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.     

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.     

Silk genes support the single origin of orb webs

The orb web is a spectacular evolutionary innovation that enables spiders to catch flying prey. This elegant, geometric structure is woven with silk fibers that are renowned for their superior mechanical properties. We used silk gland expression libraries to address a long-standing controversy concerning the evolution of the orb-web architecture. Contrary to the view that the orb-web design evolved multiple times, we found that the distribution and phylogeny of silk proteins support a single, ancient origin of the orb web at least 136 million years ago. Furthermore, we substantially expanded the repository of silk sequences that can be used for the synthesis of high-performance biomaterials.     

Systemic Listeria monocytogenes infection and concurrent pleural mesothelioma in a cat

Herein we describe a rare case of systemic Listeria monocytogenes infection with concurrent pleural mesothelioma in a stray cat that was found dead and submitted for autopsy. Gross pathology changes consisted of thoracic clear yellow fluid admixed with suspended fibrin strands; clear-to-tan, variably sized, <3 mm diameter pulmonary nodules; and enlargement of the submandibular, retropharyngeal, and prescapular lymph nodes. Histologic changes consisted of extensive areas of suppurative inflammation and necrosis with mineralization that partially effaced the pulmonary parenchyma and lymph nodes. Random, distinct necrotic foci were present throughout the hepatic parenchyma. Extending from the pleura, within perinecrotic alveolar spaces, and infiltrating the submandibular, retropharyngeal, and prescapular lymph nodes were dense sheets of neoplastic epithelioid cells with moderate pleomorphism and occasional karyomegaly and multinucleation. Neoplastic cells exhibited immunolabeling for pancytokeratin AE1/AE3 and vimentin, consistent with pleural mesothelioma. Aerobic bacterial culture of lung yielded heavy growth of L. monocytogenes. Immunohistochemistry (IHC) for L. monocytogenes revealed clusters of bacteria in the lung, lymph node, and liver. Pathologic changes were consistent with systemic listeriosis, confirmed by bacterial culture and IHC, and concurrent pleural mesothelioma.     

Health of farmed fish: its relation to fish welfare and its utility as welfare indicator

This brief review focuses on health and biological function as cornerstones of fish welfare. From the function-based point of view, good welfare is reflected in the ability of the animal to cope with infectious and non-infectious stressors, thereby maintaining homeostasis and good health, whereas stressful husbandry conditions and protracted suffering will lead to the loss of the coping ability and, thus, to impaired health. In the first part of the review, the physiological processes through which stressful husbandry conditions modulate health of farmed fish are examined. If fish are subjected to unfavourable husbandry conditions, the resulting disruption of internal homeostasis necessitates energy-demanding physiological adjustments (allostasis/acclimation). The ensuing energy drain leads to trade-offs with other energy-demanding processes such as the functioning of the primary epithelial barriers (gut, skin, gills) and the immune system. Understanding of the relation between husbandry conditions, allostatic responses and fish health provides the basis for the second theme developed in this review, the potential use of biological function and health parameters as operational welfare indicators (OWIs). Advantages of function- and health-related parameters are that they are relatively straightforward to recognize and to measure and are routinely monitored in most aquaculture units, thereby providing feasible tools to assess fish welfare under practical farming conditions. As the efforts to improve fish welfare and environmental sustainability lead to increasingly diverse solutions, in particular integrated production, it is imperative that we have objective OWIs to compare with other production forms, such as high-density aquaculture. However, to receive the necessary acceptance for legislation, more robust scientific backing of the health- and function-related OWIs is urgently needed.