Drinking and Flying: Does Alcohol Consumption Affect the Flight and Echolocation Performance of Phyllostomid Bats?

In the wild, frugivorous and nectarivorous bats often eat fermenting fruits and nectar, and thus may consume levels of ethanol that could induce inebriation. To understand if consumption of ethanol by bats alters their access to food and general survival requires examination of behavioural responses to its ingestion, as well as assessment of interspecific variation in those responses. We predicted that bats fed ethanol would show impaired flight and echolocation behaviour compared to bats fed control sugar water, and that there would be behavioural differences among species. (Chiroptera, Phyllostomidae) sugar water (44 g of table sugar in 500 ml of water) or sugar water with ethanol before challenging them to fly through an obstacle course while we simultaneously recorded their echolocation calls. We used bat saliva, a non-invasive proxy, to measure blood ethanol concentrations ranging from 0 to >0.3% immediately before flight trials. Flight performance and echolocation behaviour were not significantly affected by consumption of ethanol, but species differed in their blood alcohol concentrations after consuming it.The bats we studied display a tolerance for ethanol that could have ramifications for the adaptive radiation of frugivorous and nectarivorous bats by allowing them to use ephemeral food resources over a wide span of time. By sampling across phyllostomid genera, we show that patterns of apparent ethanol tolerance in New World bats are broad, and thus may have been an important early step in the evolution of frugivory and nectarivory in these animals

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Minority education in transition : ethnicity, poverty and education in rural China

Marketization of the Chinese economy has created wealth and economic opportunities. But it has also created barriers preventing vulnerable gTOUpS from accessing quality education and escaping poverty. This thesis examines the causes of low educational investment by minority ethnic groups in rural China between 1988 and 2002. Information about conditions facing minority groups, including the financing and administration of education, motivates a theoretical model of investment. Characteristics of minority households, such as remote, rural location and low parental education play a role in explaining disadvantage. Low income is both a cause and effect of disadvantage for credit-constrained households. Furthermore, low education has a negative externality on the rewards for education facing other households. Poor 'ethnic capital' and cultural norms regarding enrolment can perpetuate a poverty trap generated by differences in the ways groups form expectations about the behaviour of other group members. The remaining chapters test these hypotheses using rural household data from 1988, 1995 and 2002, and a data-set on academic achievement of children in the final year of compulsory education, collected by the author in a remote minority prefecture. Descriptive regression analysis and decomposition of the differences in educational outcomes between minority and Han groups suggest that low income, relatively high fertility, and low parental education are among the factors driving minority disadvantage. lVIore careful analysis of the effect of income, attempting to control for potential endogeneity, finds the effect to be robust, although differences in income explain far les of the gap in investment than differences in community resources, although it was not possible to control for all potential sources of bias. Higher fertility of minority households may be an important cause of their lower investment. More careful examination of the impacts of fertility finds a significant negative impact of siblings in school and siblings in work, although suitable instrumental variables were not available. Fixed effects regressions, con- trolling for all observed and unobserved household characteristics, revealed that households spend significantly more on more able children and that younger and middle children often lose out. The final chapter reveals that minority students are segregated into lower quality schools, partly because of the high costs of traveling to school from remote locations. This reduces their academic achieve- ment. However, poor achievement of minority students is not fully explained by school choice and observable household characteristics. It is plausible that cul- tural barriers or disengagement from the education system reduce the benefits of education for these children. 2EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Polychlorinated Biphenyls (PCBs): Impact on Bat Activity and Foraging Behaviour along the Upper Hudson River, New York

Sediments of the upper Hudson River, New York, contain polychlorinated biphenyls (PCBs). Consequently, elevated levels of PCBs have been found in the tissues of bats and their insect prey along this region. However, it is not clear whether bat activity and foraging behaviour have been affected. To assess possible effects of PCBs on bat activity and foraging behaviour, we measured Myotis lucifugus (little brown bat; LeConte, 1831) and Lasiurus cinereus (hoary bat; Beauvois, 1796) activity along the upper Hudson River, as well as abundance of insect prey at the same locations. We also measured foraging duration and distances travelled by radio-tagged M. lucifugus. We found that bat activity and insect abundance did not differ with PCB concentration. We did, however, find that foraging behaviour along the Hudson River differed from a control site. Specifically, M. lucifugus foraging along PCB contaminated areas of the Hudson River traveled shorter distances from their roosts, and spent less time foraging than bats at an uncontaminated site. Our results show that while bats roost and forage in areas historically exposed to PCBs, this exposure has not adversely affected bat activity, foraging behaviour, or abundance of insect prey.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

The role of microRNAs as predictors of response to tamoxifen treatment in breast cancer patients

This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. However, resistance to endocrine therapy leads to breast cancer relapse. The recent extension of adjuvant tamoxifen treatment up to 10 years actualizes the need for identifying biological markers that may be used to monitor predictors of treatment response. MicroRNAs are promising biomarkers that may fill the gap between preclinical knowledge and clinical observations regarding endocrine resistance. MicroRNAs regulate gene expression by posttranscriptional repression or degradation of mRNA, most often leading to gene silencing. MicroRNAs have been identified directly in the primary tumor, but also in the circulation of breast cancer patients. The few available studies investigating microRNA in patients suggest that seven microRNAs (miR-10a, miR-26, miR-30c, miR-126a, miR-210, miR-342 and miR-519a) play a role in tamoxifen resistance. Ingenuity Pathway Analysis (IPA) reveals that these seven microRNAs interact more readily with estrogen receptor (ER)-independent pathways than ER-related signaling pathways. Some of these pathways are targetable (e.g., PIK3CA), suggesting that microRNAs as biomarkers of endocrine resistance may have clinical value. Validation of the role of these candidate microRNAs in large prospective studies is warranted

MiR-18a and miR-18b are expressed in the stroma of oestrogen receptor alpha negative breast cancers

Background Previously, we have shown that miR-18a and miR-18b gene expression strongly correlates with high proliferation, oestrogen receptor -negativity (ER−), cytokeratin 5/6 positivity and basal-like features of breast cancer. Methods We investigated the expression and localization of miR-18a and -18b in formalin fixed paraffin embedded (FFPE) tissue from lymph node negative breast cancers (n = 40), by chromogenic in situ hybridization (CISH). The expression level and in situ localization of miR-18a and -18b was assessed with respect to the presence of tumour infiltrating lymphocytes (TILs) and immunohistochemical markers for ER, CD4, CD8, CD20, CD68, CD138, PAX5 and actin. Furthermore, in two independent breast cancer cohorts (94 and 377 patients) the correlation between miR-18a and -18b expression and the relative quantification of 22 immune cell types obtained from the CIBERSORT tool was assessed. Results CISH demonstrated distinct and specific cytoplasmic staining for both miR-18a and miR-18b, particularly in the intratumoural stroma and the stroma surrounding the tumour margin. Staining by immunohistochemistry revealed some degree of overlap of miR-18a and -18b with CD68 (monocytes/macrophages), CD138 (plasma cells) and the presence of high percentages of TILs. CIBERSORT analysis showed a strong correlation between M1-macrophages and CD4+ memory activated T-cells with mir-18a and -18b. Conclusions Our study demonstrates that miR-18a and miR-18b expression is associated with ER- breast tumours that display a high degree of inflammation. This expression is potentially associated specifically with macrophages. These results suggest that miR-18a and miR-18b may play a role in the systemic immunological response in ER− tumourspublishedVersio

Digital Image Analysis of Ki-67 Stained Tissue Microarrays and Recurrence in Tamoxifen-Treated Breast Cancer Patients

Purpose: The proliferation marker Ki-67 has been used as a prognostic marker to separate low- and high-risk breast cancer subtypes and guide treatment decisions for adjuvant chemotherapy. The association of Ki-67 with response to tamoxifen therapy is unclear. High-throughput automated scoring of Ki-67 might enable standardization of quantification and definition of clinical cut-off values. We hypothesized that digital image analysis (DIA) of Ki-67 can be used to evaluate proliferation in breast cancer tumors, and that Ki-67 may be associated with tamoxifen resistance in early-stage breast cancer. Patients and Methods: Here, we apply DIA technology from Visiopharm using a custom designed algorithm for quantifying the expression of Ki-67, in a case–control study nested in the Danish Breast Cancer Group clinical database, consisting of stages I, II, or III breast cancer patients of 35– 69 years of age, diagnosed during 1985– 2001, in the Jutland peninsula, Denmark. We assessed DIA-Ki-67 score on tissue microarrays (TMAs) from breast cancer patients in a case–control study including 541 ER-positive and 300 ER-negative recurrent cases and their non-recurrent controls, matched on ER-status, cancer stage, menopausal status, year of diagnosis, and county of residence. We used logistic regression to estimate odds ratios and associated 95% confidence intervals to determine the association of Ki-67 expression with recurrence risk, adjusting for matching factors, chemotherapy, type of surgery, receipt of radiation therapy, age category, and comorbidity. Results: Ki-67 was not associated with increased risk of recurrence in tamoxifen-treated patients (ORadj =0.72, 95% CI 0.54, 0.96) or ER-negative patients (ORadj =0.85, 95% CI 0.54, 1.34). Conclusion: Our findings suggest that Ki-67 digital image analysis in TMAs is not associated with increased risk of recurrence among tamoxifen-treated ER-positive breast cancer or ER-negative breast cancer patients. Overall, our findings do not support an increased risk of recurrence associated with Ki-67 expression.publishedVersio