An Effective Chemical Deterrent for Invasive Cuban Treefrogs

Introduced vertebrates have a variety of impacts on ecosystems and economies, and many cause problems for humans. One such problem is the loss of electrical power when invasive animals cause short circuits in power-transmission equipment. Cuban treefrogs (Osteopilus septentrionalis) are known to cause power outages and are a nuisance to humans when they invade homes and defecate on doors and windows. These large, slightly toxic treefrogs were introduced into Florida from the Caribbean. They now occur throughout the peninsula of Florida and are spreading to other states in the Southeast. We used refuge choice experiments to test the effectiveness of Sniff ’n’ StopTM animal deterrent to exclude Cuban treefrogs from enclosed spaces, such as utility switchgear boxes. We found that the deterrent was effective and showed potential as a low-cost means to prevent frog-related power outages and reduce conflicts with residents in the urbanized areas preferred by these invasive frog

Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of O6-Methylguanine-DNA-methyltransferase, DNA Mismatch Repair and p53.

The antitumor prodrug Temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (EC 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilinoethyl)-substituted imidazotetrazines are reported that have activity independent of MGMT, MMR and p53. This is achieved through a switch of mechanism so that bioactivity derives from imidazotetrazine-generated arylaziridinium ions that principally modify guanine-N7 sites on DNA. Mono- and bi-functional analogs are reported and a quantitative structure-activity relationship (QSAR) study identified the p-tolyl-substituted bi-functional congener as optimized for potency, MGMT-independence and MMR-independence. NCI60 data show the tumor cell response is distinct from other imidazotetrazines and DNA-guanine-N7 active agents such as nitrogen mustards and cisplatin. The new imidazotetrazine compounds are promising agents for further development and their improved in vitro activity validates the principles on which they were designed

Pity for economically disadvantaged groups motivates donation and ally collective action intentions

We argue that pity can motivate collective action intentions toward groups that are both politically and economically deprived. We tested this connection in four online surveys and an experiment. In Study 1 (N = 1,007), pity for the Roma in Hungary predicted collective action intentions, which was replicated in Study 2 in connection with refugees in Germany (N = 191) and in Hungary (N = 563). Study 3 (N = 475) demonstrated that for not economically but politically disadvantaged groups (e.g., sexual minorities), pity was not a predictor of ally action. In an experiment (Study 4, N = 447), pity was just as strong a predictor of collective action intentions as outrage on behalf of an economically and politically disadvantaged outgroup. Pity can be a mobilizing emotion when it comes to groups that are both economically and politically disadvantaged; however, outrage remains more important in the absence of economic hardship

Mutations in STK11 gene in Czech Peutz-Jeghers patients

<p>Abstract</p> <p>Background</p> <p>Peutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary disease characterized by mucocutaneous pigmentation and gastrointestinal hamartomatous polyposis. The germline mutations in the serine/threonine kinase 11 (<it>STK11</it>) gene have been shown to be associated with the disease. Individuals with PJS are at increased risk for development of various neoplasms. The aim of the present study was to characterize the genotype and phenotype of Czech patients with PJS.</p> <p>Methods</p> <p>We examined genomic DNA of 8 individuals from five Czech families by sequencing analysis of <it>STK11 </it>gene, covering its promotor region, the entire coding region and the splice-site boundaries, and by multiplex ligation-dependent probe amplification (MLPA) assay designed for the identification of large exonic deletions or duplications of <it>STK11 </it>gene.</p> <p>Results</p> <p>We found pathogenic mutations in <it>STK11 </it>gene in two families fulfilling the diagnostic criteria of PJS and in one of three sporadic cases not complying with the criteria. The patient with the frameshift mutation in <it>STK11 </it>gene developed aggressive gastric cancer. No other studied proband has developed a carcinoma so far.</p> <p>Conclusion</p> <p>Our results showed that a germline mutation of <it>STK11 </it>gene can be found not only in probands fulfilling the PJS diagnostic criteria, but also in some sporadic cases not complying with the criteria. Moreover, we observed a new case of aggressive gastric cancer in a young patient with a frameshift mutation of <it>STK11 </it>gene.</p

Risk of Malignant Progression in Barrett’s Esophagus Patients: Results from a Large Population-Based Study

BACKGROUND: Barrett’s esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett’s esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005. SUBJECTS AND METHODS: We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General’s Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests. RESULTS: After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P < .001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P < .001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P < .001). CONCLUSION: We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective

LKB1 as the ghostwriter of crypt history

Familial cancer syndromes present rare insights into malignant tumor development. The molecular background of polyp formation and the cancer prone state in Peutz-Jeghers syndrome remain enigmatic to this day. Previously, we proposed that Peutz-Jeghers polyps are not pre-malignant lesions, but an epiphenomenon to the malignant condition. However, Peutz-Jeghers polyp formation and the cancer-prone state must both be accounted for by the same molecular mechanism. Our contribution focuses on the histopathology of the characteristic Peutz-Jeghers polyp and recent research on stem cell dynamics and how these concepts relate to Peutz-Jeghers polyposis. We discuss a protracted clonal evolution scenario in Peutz-Jeghers syndrome due to a germline LKB1 mutation. Peutz-Jeghers polyp formation and malignant transformation are separately mediated through the same molecular mechanism played out on different timescales. Thus, a single mechanism accounts for the development of benign Peutz-Jeghers polyps and for malignant transformation in Peutz-Jeghers syndrome

An evidence-based decision assistance model for predicting training outcome in juvenile guide dogs

Working dog organisations, such as Guide Dogs, need to regularly assess the behaviour of the dogs they train. In this study we developed a questionnaire-style behaviour assessment completed by training supervisors of juvenile guide dogs aged 5, 8 and 12 months old (n = 1,401), and evaluated aspects of its reliability and validity. Specifically, internal reliability, temporal consistency, construct validity, predictive criterion validity (comparing against later training outcome) and concurrent criterion validity (comparing against a standardised behaviour test) were evaluated. Thirty-nine questions were sourced either from previously published literature or created to meet requirements identified via Guide Dogs staff surveys and staff feedback. Internal reliability analyses revealed seven reliable and interpretable trait scales named according to the questions within them as: Adaptability; Body Sensitivity; Distractibility; Excitability; General Anxiety; Trainability and Stair Anxiety. Intra-individual temporal consistency of the scale scores between 5±8, 8±12 and 5±12 months was high. All scales excepting Body Sensitivity showed some degree of concurrent criterion validity. Predictive criterion validity was supported for all seven scales, since associations were found with training outcome, at at-least one age. Thresholds of z-scores on the scales were identified that were able to distinguish later training outcome by identifying 8.4% of all dogs withdrawn for behaviour and 8.5% of all qualified dogs, with 84% and 85% specificity. The questionnaire assessment was reliable and could detect traits that are consistent within individuals over time, despite juvenile dogs undergoing development during the study period. By applying thresholds to scores produced from the questionnaire this assessment could prove to be a highly valuable decision-making tool for Guide Dogs. This is the first questionnaire-style assessment of juvenile dogs that has shown value in predicting the training outcome of individual working dogs

Role of LKB1 in lung cancer development

Three phenotypically related genetic syndromes and their lesions (LKB1, PTEN, and TSC1/2) are identified as frequently altered in lung cancer. LKB1, a kinase inactivated in 30% of lung cancers, is discussed in this review. Loss of LKB1 regulation often coincident with KRAS activation allows for unchecked growth and the metabolic capacity to accommodate the proliferation