Brca2 and Trp53 deficiency cooperate in the progression of mouse prostate tumourigenesis.

Epidemiological studies have shown that one of the strongest risk factors for prostate cancer is a family history of the disease, suggesting that inherited factors play a major role in prostate cancer susceptibility. Germline mutations in BRCA2 predispose to breast and ovarian cancer with its predominant tumour suppressor function thought to be the repair of DNA double-strand breaks. BRCA2 has also been implicated in prostate cancer etiology, but it is unclear the impact that mutations in this gene have on prostate tumourigenesis. Here we have undertaken a genetic analysis in the mouse to determine the role of Brca2 in the adult prostate. We show that deletion of Brca2 specifically in prostate epithelia results in focal hyperplasia and low-grade prostate intraepithelial neoplasia (PIN) in animals over 12 months of age. Simultaneous deletion of Brca2 and the tumour suppressor Trp53 in prostate epithelia gave rise to focal hyperplasia and atypical cells at 6 months, leading to high-grade PIN in animals from 12 months. Epithelial cells in these lesions show an increase in DNA damage and have higher levels of proliferation, but also elevated apoptosis. Castration of Brca2;Trp53 mutant animals led to regression of PIN lesions, but atypical cells persisted that continued to proliferate and express nuclear androgen receptor. This study provides evidence that Brca2 can act as a tumour suppressor in the prostate, and the model we describe should prove useful in the development of new therapeutic approaches

Canola-Wheat Rotation versus Continuous Wheat for the Southern Plains

Crop rotations are not common in the wheat belt of the Southern Plains. After years of continuous wheat, weeds have become increasingly difficult and expensive to manage. Yield data were elicited from farmers and used to determine if canola-wheat-wheat rotations are economically competitive with continuous wheat in the region.crop rotation, wheat, canola, elicited yield distributions, Crop Production/Industries, Farm Management, Q10, Q12,

Matrix modification for enhancing the transport properties of the human cartilage endplate to improve disc nutrition.

Poor solute transport through the cartilage endplate (CEP) impairs disc nutrition and could be a key factor that limits the success of intradiscal biologic therapies. Here we demonstrate that treating the CEP with matrix metalloproteinase-8 (MMP-8) reduces the matrix constituents that impede solute uptake and thereby improves nutrient diffusion. Human CEP tissues harvested from four fresh cadaveric lumbar spines (age range: 38-66 years old) were treated with MMP-8. Treatment caused a dose-dependent reduction in sGAG, localized reductions to the amount of collagen, and alterations to collagen structure. These matrix modifications corresponded with 16-24% increases in the uptake of a small solute (376 Da). Interestingly, the effects of MMP-8 treatment depended on the extent of non-enzymatic glycation: treated CEPs with high concentrations of advanced glycation end products (AGEs) exhibited the lowest uptake compared to treated CEPs with low concentrations of AGEs. Moreover, AGE concentrations were donor-specific, and the donor tissues with the highest AGE concentrations appeared to have lower uptake than would be expected based on the initial amounts of collagen and sGAG. Finally, increasing solute uptake in the CEP improved cell viability inside diffusion chambers, which supports the nutritional relevance of enhancing the transport properties of the CEP. Taken together, our results provide new insights and in vitro proof-of-concept for a treatment approach that could improve disc nutrition for biologic therapy: specifically, matrix reduction by MMP-8 can enhance solute uptake and nutrient diffusion through the CEP, and AGE concentration appears to be an important, patient-specific factor that influences the efficacy of this approach

Absolute Properties of the Eclipsing Binary Star BF Draconis

BF Dra is now known to be an eccentric double-lined F6+F6 binary star with relatively deep (0.7 mag) partial eclipses. Previous studies of the system are improved with 7494 differential photometric observations from the URSA WebScope and 9700 from the NFO WebScope, 106 high-resolution spectroscopic observations from the Tennessee State University 2 m automatic spectroscopic telescope and the 1 m coudé-feed spectrometer at Kitt Peak National Observatory, and 31 accurate radial velocities from the CfA. Very accurate (better than 0.6%) masses and radii are determined from analysis of the two new light curves and four radial velocity curves. Theoretical models match the absolute properties of the stars at an age of about 2.72 Gyr and [Fe/H] = −0.17, and tidal theory correctly confirms that the orbit should still be eccentric. Our observations of BF Dra constrain the convective core overshooting parameter to be larger than about 0.13 Hp. We find, however, that standard tidal theory is unable to match the observed slow rotation rates of the components\u27 surface layers

Embryopathic Effects of Waterborne and Sediment-Accumulated Cadmium, Mercury and Zinc on Reproduction and Survival of Fish and Amphibian Populations in Kentucky

Fish and amphibian egg cultures were used to determine the embryopathic effects of cadmium, mercury, and zinc released from natural and metal-enriched sediments, and to develop egg culture bioassay procedures suitable for monitoring bottom sediments for hazardous contaminants. Eggs of the narrow-mouthed toad (Gastrophryne carolinensis), goldfish (Carassius auratus), and rainbow trout (Salmo gairdnei) were cultured in contaminant-free water added to natural and metal-enriched sediments. Exposure was initiated after fertilization (toad, goldfish) or at 10 days prehatching (trout) and maintained continuously through 4-10 days posthatching. Sediments were enriched with 0.1-100 ppm cadmium and mercury and 1.0-1000 ppm zinc. Natural control sediments contained average concentrations of 0.052 ppm mercury, 1.0 ppm cadmium, and 108.2 ppm zinc. Substantial frequencies of mortality and teratogenesis occurred for all 3 animal species when eggs were cultured over natural elements further enriched with as little as 0.1-1.0 ppm cadmium or mercury and 1-10ppm zinc. Survival of trout embryos and alevins closely paralleled sediment test concentrations. The sediment TL50 concentrations for trout stages cultured from 10 days prehatching through 10 days posthatching were approximately 1ppm for mercury, 2.15 ppm for cadmium, and 210.6 ppm for zinc. Sediment metals were substantially more lethal to eggs and embryos than to free-living larvae or fry

Arctic system on trajectory to new state

The Arctic system is moving toward a new state that falls outside the envelope of glacial-interglacial fluctuations that prevailed during recent Earth history. This future Arctic is likely to have dramatically less permanent ice than exists at present. At the present rate of change, a summer ice-free Arctic Ocean within a century is a real possibility, a state not witnessed for at least a million years. The change appears to be driven largely by feedback-enhanced global climate warming, and there seem to be few, if any processes or feedbacks within the Arctic system that are capable of altering the trajectory toward this “super interglacial” state

B843: The Ecology, Economics, and Management of Potato Cropping Systems: A Report of the First Four Years of the Maine Potato Ecosystem Project

The bulletin reports on the first four years of the Maine Potato Ecosystem Project, a long-term, multidisciplinary study of alternative crop management strategies. The study site is a 15-acre tract on the northern boundary of the University of Maine\u27s Aroostook Farm in Presque Isle, Maine, divided into 96 main plots that are grouped into four blocks. Each block is an area where soil survey data show similar soil characteristics. Thus, given the same production inputs, the crop output is expected to be the same on each plot within a block. Within each block there are 24 plots to which the different treatments have been randomly assigned. A treatment is a particular combination of the following factors: (1) pest management—conventiorial, reduced input, or biological; (2) potato variety—Atlantic or Superior; and (3) soil management—amended or unamended.https://digitalcommons.library.umaine.edu/aes_bulletin/1025/thumbnail.jp

Can endoscopic ultrasound or magnetic resonance cholangiopancreatography replace ERCP in patients with suspected biliary disease? A prospective trial and cost analysis

ERCP is the gold standard for pancreaticobiliary evaluation but is associated with complications. Less invasive diagnostic alternatives with similar capabilities may be cost-effective, particularly in situations involving low prevalence of disease. The aim of this study was to compare the performance of endoscopic ultrasound (EUS) with magnetic resonance cholangiopancreatography (MRCP) and ERCP in the same patients with suspected extrahepatic biliary disease. The economic outcomes of EUS-, MRCP-, and ERCP-based diagnostic strategies were evaluated. METHODS : Prospective cohort study of patients referred for ERCP with suspected biliary disease. MRCP and EUS were performed within 24 h before ERCP. The investigators were blinded to the results of the alternative imaging studies. A cost-utility analysis was performed for initial ERCP, MRCP, and EUS strategies for these patients. RESULTS : A total of 30 patients were studied. ERCP cholangiogram failed in one patient, and another patient did not complete MRCP because of claustrophobia. The final diagnoses ( n = 28 ) were CBD stone (mean = 4 mm; range = 3–6 mm) in five patients; biliary stricture in three patients, and normal biliary tree in 20. Two patients had pancreatitis after therapeutic ERCP, one after precut sphincterotomy followed by a normal cholangiogram. EUS was more sensitive than MRCP in the detection of choledocolithiasis (80% vs 40%), with similar specificity. MRCP had a poor specificity and positive predictive value for the diagnosis of biliary stricture (76%/25%) compared to EUS (100%/100%), with similar sensitivity. The overall accuracy of MRCP for any abnormality was 61% (95% CI = 0.41–0.78) compared to 89% (CI = 0.72–0.98) for EUS. Among those patients with a normal biliary tree, the proportion correctly identified with each test was 95% for EUS and 65% for MRCP ( p < 0.02 ). The cost for each strategy per patient evaluated was $1346 for ERCP,$1111 for EUS, and $1145 for MRCP. CONCLUSIONS : In this patient population with a low disease prevalence, EUS was superior to MRCP for choledocholithiasis. EUS was most useful for confirming a normal biliary tree and should be considered a low-risk alternative to ERCP. Although MRCP had the lowest procedural reimbursement, the initial EUS strategy had the greatest cost-utility by avoiding unnecessary ERCP examinations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73885/1/j.1572-0241.2001.04245.x.pd

The Passing of Print

This paper argues that ephemera is a key instrument of cultural memory, marking the things intended to be forgotten. This important role means that when ephemera survives, whether accidentally or deliberately, it does so despite itself. These survivals, because they evoke all those other objects that have necessarily been forgotten, can be described as uncanny. The paper is divided into three main sections. The first situates ephemera within an uncanny economy of memory and forgetting. The second focuses on ephemera at a particular historical moment, the industrialization of print in the nineteenth century. This section considers the liminal place of newspapers and periodicals in this period, positioned as both provisional media for information as well as objects of record. The third section introduces a new configuration of technologies – scanners, computers, hard disks, monitors, the various connections between them – and considers the conditions under which born-digital ephemera can linger and return. Through this analysis, the paper concludes by considering digital technologies as an apparatus of memory, setting out what is required if we are not to be doubly haunted by the printed ephemera within the digital archive

Estimating the abundance of marine mammal populations

Support for this project was provided by the Lenfest Ocean Program.Motivated by the need to estimate the abundance of marine mammal populations to inform conservation assessments, especially relating to fishery bycatch, this paper provides background on abundance estimation and reviews the various methods available for pinnipeds, cetaceans and sirenians. We first give an “entry-level” introduction to abundance estimation, including fundamental concepts and the importance of recognizing sources of bias and obtaining a measure of precision. Each of the primary methods available to estimate abundance of marine mammals is then described, including data collection and analysis, common challenges in implementation, and the assumptions made, violation of which can lead to bias. The main method for estimating pinniped abundance is extrapolation of counts of animals (pups or all-ages) on land or ice to the whole population. Cetacean and sirenian abundance is primarily estimated from transect surveys conducted from ships, small boats or aircraft. If individuals of a species can be recognized from natural markings, mark-recapture analysis of photo-identification data can be used to estimate the number of animals using the study area. Throughout, we cite example studies that illustrate the methods described. To estimate the abundance of a marine mammal population, key issues include: defining the population to be estimated, considering candidate methods based on strengths and weaknesses in relation to a range of logistical and practical issues, being aware of the resources required to collect and analyze the data, and understanding the assumptions made. We conclude with a discussion of some practical issues, given the various challenges that arise during implementation.Publisher PDFPeer reviewe