A new species of cosmocerca (Nematoda, ascaridomorpha) from the marine toad rhinella marina (linnaeus) (anura, bufonidae) in Australia

The marine toad Rhinella marina (Linnaeus) (Anura, Bufonidae) is a notorious, exotic amphibian species in Australia. However, our present knowledge of the composition of the nematode fauna of R. marina is still not complete. In the present study, a new cosmocercid nematode, Cosmocerca multipapillata sp. nov., was described using both light and scanning electron microscopy, based on specimens collected from R. marina in Australia. Cosmocerca multipapillata sp. nov. can be easily distinguished from its congeners by the body size, the presence of lateral alae and well sclerotized gubernaculum, the number and arrangement of plectanes and rosettes and the length of spicules, oesophagus and tail

Native species Maxvachonia chabaudi Mawson, 1972 (Nematoda: Cosmocercoidea) found in the invasive marine toad Rhinella marina (Linnaeus) (Anura: Bufonidae) in Australia

The genus Maxvachonia Chabaud et Brygoo, 1960 (Ascaridomorpha: Cosmocercidae) is a poorly known group of parasitic nematodes. Species of Maxvachonia are native to Madagascar-Australo-Papuan Region, where they are known to parasitise frogs, snakes and skinks. Unfortunately, most of Maxvachonia species have been inadequately described. In the present study, we report the native species Maxvachonia chabaudi Mawson, 1972 from the intestine of the invasive marine toad Rhinella marina (Linnaeus) in Australia for the first time. We speculate that the marine toads infected with M. chabaudi are likely related to their eating skinks or the similarity in diet/habitat/ecology between the toad and the skinks. The detailed morphology of M. chabaudi was studied using light microscopy and, for the first time, scanning electron microscopy, based on the newly collected specimens. Some characters important for the specific diagnosis of M. chabaudi are reported for the first time, including each lip with distinct inner flanges, the location of vulva varying from anterior to posterior of the oesophageal bulb and the presence of single medio-ventral precloacal papilla. An identification key to the species of Maxvachonia is provided

Explorations, Vol. 4, No. 2

Articles include: Cover: Maya—painted clay figure from Jaina Island, Campeche, Mexico, 500-700A. D., approximately 100 percent. The clay figure is from a superb assemblage of pre-Hispanic materials from Mexico and Central America donated to the University of Maine’s Hudson Museum from the estate of William P Palmer III. In addition to this fine collection, Palmer donated an extensive array of objects from the Northwest Coast. Palmer earned his undergraduate degree in history and government from the University of Maine, and remained a strong, active supporter of the institution throughout his lifetime. More examples of objects from the Palmer Collection, including some pre-Columbian goldwork from Central America, may be found on page 10. Editorial Reflections, by Carole J. Bombard A Living Educational Experience: The Hudson Museum, by Richard G. Emerick Molly in the Museum Other Wonders, Other Ways From Classroom Walls to High Tech Museum Sharing Our Strengths: the development of youth conservation clubs in Pakistan, by James A. Sherburne Up Close and Personal Objects, Signs, and Symbols from Scafell to Chamonix: Visions of Mont Blanc, by Robert Brinkley Public Service in Special Places: Music Education as Empowerment, by Susan Grindel Cosset Lambs, Floods and Stars, by Roberta Chester Tuning the Immune System Fighting AIDS, Cancer and Other Diseases, by Anne P. Sherblom and Charles E. Moody Why do they do it? One Graduate Student Explains, by Diane Carroll Nutrition and Reproduction in Cows, by Barbara Barton and Diane Carroll Diane Carroll: former graduate student Research News Research New

Strong population structure deduced from genetics, otolith chemistry and parasite abundances explains vulnerability to localized fishery collapse in a large Sciaenid fish, Protonibea diacanthus

As pressure on coastal marine resources is increasing globally, the need to quantitatively assess vulnerable fish stocks is crucial in order to avoid the ecological consequences of stock depletions. Species of Sciaenidae (croakers, drums) are important components of tropical and temperate fisheries and are especially vulnerable to exploitation. The black-spotted croaker, Protonibea diacanthus, is the only large sciaenid in coastal waters of northern Australia where it is targeted by commercial, recreational and indigenous fishers due to its food value and predictable aggregating behaviour. Localised declines in the abundance of this species have been observed, highlighting the urgent requirement by managers for information on fine and broad-scale population connectivity. This study examined the population structure of P. diacanthus across northwestern Australia using three complementary methods: genetic variation in microsatellite markers, otolith elemental composition and parasite assemblage composition. The genetic analyses demonstrated that there were at least five genetically distinct populations across the study region, with gene flow most likely restricted by inshore biogeographic barriers such as the Dampier Peninsula. The otolith chemistry and parasite analyses also revealed strong spatial variation among locations within broad-scale regions, suggesting fine-scale location fidelity within the lifetimes of individual fish. The complementarity of the three techniques elucidated patterns of connectivity over a range of spatial and temporal scales. We conclude that fisheries stock assessments and management are required at fine scales (100's km) to account for the restricted exchange among populations (stocks) and to prevent localised extirpations of this species. Realistic management arrangements may involve the successive closure and opening of fishing areas to reduce fishing pressure

Efficacy and safety of bempedoic acid in patients not receiving statins in phase 3 clinical trials

BACKGROUND: Despite the high incidence of patients with statin tolerance problems, randomized evaluations of nonstatin oral treatment options for lowering of low-density lipoprotein cholesterol (LDL-C) in this population are sparse. OBJECTIVE: To assess the LDL-C lowering effect of bempedoic acid in patients not taking statins. METHODS: This was a pooled analysis of data from patients enrolled in four phase 3 bempedoic acid studies (12 to 52 weeks in duration) who were not taking concomitant statins (Phase 3 No Statin Cohort) and a phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (BA+EZE FDC No Statin Cohort). The primary endpoint for all studies was the percent change from baseline to week 12 in LDL-C levels. Safety and tolerability were assessed by laboratory values and adverse events. RESULTS: In the Phase 3 No Statin Cohort, bempedoic acid (n = 394) lowered LDL-C levels at week 12 significantly more than placebo (n = 192; -26.5% [95% CI, -29.7%, -23.2%]; P\u3c0.001). The fixed-dose combination of bempedoic acid with ezetimibe lowered LDL-C by 39.2% (95% CI, -51.7% to -26.7%; P\u3c0.001). Muscle-related disorders occurred at a rate of 26.4 and 28.6 per 100 person-years with bempedoic acid and placebo, respectively. CONCLUSIONS: In patients with hypercholesterolemia unable to take statins, bempedoic acid lowered LDL-C levels by a mean of 26.5% vs placebo and bempedoic acid + ezetimibe fixed-dose combination lowered LDL-C by 39.2%. The treatments were generally well tolerated, suggesting that bempedoic acid may be efficacious and well tolerated in this challenging-to-treat patient population

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Mineralogical characterization of protolith and fault rocks from the SAFOD Main Hole

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94865/1/grl22060.pd

Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells

<p>Abstract</p> <p>Background</p> <p>Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (<it>PLK1</it>) is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy.</p> <p>Methods</p> <p>We examined the expression of <it>PLK1 </it>mRNA in medulloblastoma tumor samples using microarray analysis. The impact of PLK1 on cell proliferation was evaluated by depleting expression with RNA interference (RNAi) or by inhibiting function with the small molecule inhibitor BI 2536. Colony formation studies were performed to examine the impact of BI 2536 on medulloblastoma cell radiosensitivity. In addition, the impact of depleting <it>PLK1 </it>mRNA on tumor-initiating cells was evaluated using tumor sphere assays.</p> <p>Results</p> <p>Analysis of gene expression in two independent cohorts revealed that <it>PLK1 </it>mRNA is overexpressed in some, but not all, medulloblastoma patient samples when compared to normal cerebellum. Inhibition of PLK1 by RNAi significantly decreased medulloblastoma cell proliferation and clonogenic potential and increased cell apoptosis. Similarly, a low nanomolar concentration of BI 2536, a small molecule inhibitor of PLK1, potently inhibited cell growth, strongly suppressed the colony-forming ability, and increased cellular apoptosis of medulloblastoma cells. Furthermore, BI 2536 pretreatment sensitized medulloblastoma cells to ionizing radiation. Inhibition of PLK1 impaired tumor sphere formation of medulloblastoma cells and decreased the expression of SRY (sex determining region Y)-box 2 (<it>SOX2</it>) mRNA in tumor spheres indicating a possible role in targeting tumor inititiating cells.</p> <p>Conclusions</p> <p>Our data suggest that targeting PLK1 with small molecule inhibitors, in combination with radiation therapy, is a novel strategy in the treatment of medulloblastoma that warrants further investigation.</p

A practical drug discovery project at the undergraduate level

A practical drug discovery project for third-year undergraduates is described. No previous knowledge of medicinal chemistry is assumed. Initial lecture-workshops cover the basic principles; then students are asked to improve the profile of a weakly potent, poorly soluble PI3K inhibitor (1). Compound array design, molecular modelling and screening data analysis are followed by laboratory work in which each student, as part of a team, attempts to synthesise at least two target compounds. The project benefits from significant industrial support, including lectures, student mentoring and consumables. The aim is to make the learning experience as close as possible to real-life industrial situations. Forty-eight target compounds have been prepared, the best of which (5b, 5j, 6b and 6ap) improved the potency and aqueous solubility of the lead compound (1) by 100-1000 fold and 10-fold, respectively

Enhanced Discrimination of Malignant from Benign Pancreatic Disease by Measuring the CA 19-9 Antigen on Specific Protein Carriers

The CA 19-9 assay detects a carbohydrate antigen on multiple protein carriers, some of which may be preferential carriers of the antigen in cancer. We tested the hypothesis that the measurement of the CA 19-9 antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenocarcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage cancer), owing to diversity among patients in their CA 19-9 protein carriers. However, a subset of cancer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 antigen specifically on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of cancer detection was improved relative to CA 19-9 alone in each sample set, achieving 67–80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glycans on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic cancer could have important applications for improving the treatment and management of patients suffering from this disease