Lack of interaction between ErbB2 and insulin receptor substrate signaling in breast cancer

Background: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbBmediated anti-estrogen resistance in breast cancer. Herein, we examined crosstalk between ErbB2 and IRSs using cancer cell lines and transgenic mouse models. Methods: MMTV-ErbB2 and MMTV-IRS2 transgenic mice were crossed to create hemizygous MMTV-ErbB2/MMTVIRS2 bigenic mice. Signaling crosstalk between ErbB2 and IRSs was examined in vitro by knockdown or overexpression followed by western blot analysis for downstream signaling intermediates and growth assays. Results: A cross between MMTV-ErbB2 and MMTV-IRS2 mice demonstrated no enhancement of ErbB2 mediated mammary tumorigenesis or metastasis by elevated IRS2. Substantiating this, overexpression or knockdown of IRS1 or IRS2 in MMTV-ErbB2 mammary cancer cell lines had little effect upon ErbB2 signaling. Similar results were obtained in human mammary epithelial cells (MCF10A) and breast cancer cell lines. Conclusion: Despite previous evidence suggesting that ErbB receptors can bind and activate IRSs, our findings indicate that ErbB2 does not cooperate with the IRS pathway in these models to promote mammary tumorigenesis

Transmission dynamics of pulmonary tuberculosis between autochthonous and immigrant sub-populations

<p>Abstract</p> <p>Background</p> <p>The overall incidence of tuberculosis (TB) in Western Europe has been declining since the 19^thCentury. However, immigrant sub-groups from high-prevalence countries are slowing down this trend. The aim of this study was to describe how immigration influences TB transmission in Germany. For that we prospectively investigated the dynamics of TB transmission between TB high-prevalence immigrant and TB low-prevalence local populations with molecular epidemiological methods and conventional contact investigations. Besides, we assessed transmission in relation to social mixing using an innovative tool that measures the integration of immigrants into the local social environment.</p> <p>Methods</p> <p>A prospective study of confirmed culture positive cases of pulmonary TB and their contacts was carried out in a German federal state from 2003 to 2005. Data for the study included: 1) case data routinely collected by the local public health staff and transmitted to the state health office and the national surveillance centre, 2) a study questionnaire designed to capture social interactions of relevance for TB transmission and 3) molecular genotyping data (IS<it>6110 </it>DNA fingerprint and spoligotyping). The proportion of German cases caused by foreign-born cases, and vice versa, was estimated and an integration index was computed using a selected set of questions from the study questionnaire.</p> <p>Results</p> <p>A total of 749 cases of culture-positive pulmonary tuberculosis voluntarily enrolled in the study, representing 57.8% of all registered cases diagnosed over the study period. Data that included study questionnaire and DNA fingerprinting were available for 41% (n = 308) of the study participants. Forty-seven clusters, defined as a least two cases infected by the same TB strains, were identified by molecular methods and included 132 (17%) of the study participants. Epidemiological links were identified for 28% of the clusters by conventional epidemiological data. In mixed clusters, defined as clusters including German and foreign-born individuals, the probability of cases to be caused by foreign-born cases was estimated at 18.3%. We observed a trend to mixed clusters with increasing time spent by immigrants in the host country. This group also presented comparatively higher integration indexes than immigrants in immigrant-only clusters.</p> <p>Conclusion</p> <p>Our results confirm the findings of other studies that there is no significant TB transmission from TB high-prevalence immigrant to TB low-prevalence autochthonous population. This may be explained by the good performance of tuberculosis screening programmes for certain groups arriving in Germany from high- prevalence countries, by a low degree of mixing of immigrants with the local population or by a combination of both.</p

An Estimate of the Incidence and Prevalence of Stroke in Africa:A Systematic Review and Meta-Analysis

Background: Stroke is increasingly becoming a challenging public health issue in Africa, and the non-availability of data has limited research output and consequently the response to this burden. This study aimed to estimate the incidence and prevalence of stroke in Africa in 2009 towards improved policy response and management of the disease in the region. Methods: A systematic search of Medline, EMBASE and Global Health for original population-based or hospital-based studies on stroke was conducted. A random effect meta-analysis was conducted on crude stroke incidence and prevalence rates, and a meta-regression-like epidemiological model was applied on all data points. The fitted curve generated from the model was used to estimate incident cases of stroke and number of stroke survivors in Africa at midpoints of the United Nation population 5-year age groups for the year 2009. Results: The literature search yielded a total of 1227 studies. 19 studies from 10 African countries were selected. 483 thousand new stroke cases among people aged 15 years or more were estimated in Africa in 2009, equivalent to 81.2 (13.2– 94.9)/100,000 person years. A total of 1.89 million stroke survivors among people aged 15 years or more were estimated in Africa in 2009, with a prevalence of 317.3 (314.0–748.2)/100000 population. Comparable figures for the year 2013 based on the same rates would amount to 535 thousand (87.0–625.3) new stroke cases and 2.09 million (2.06–4.93) stroke survivors, suggesting an increase of 10.8% and 9.6% of incident stroke cases and stroke survivors respectively, attributable to population growth and ageing between 2009 and 2013. Conclusion: The findings of this review suggest the burden of stroke in Africa is high and still increasing. There is need for more research on stroke and other vascular risk factors towards instituting appropriate policy, and effective preventive and management measures

Sensitive photoreceiver based on carbon nanotube/tobacco cell composite material

Analysis of complete capsid sequences of the emerging norovirus GII.17 Kawasaki 308 from 13 countries demonstrated that they originated from a single haplotype since the initial emergence in China in late 2014. Global spread of a sublineage SL2 was identified. A new sublineage SL3 emerged in China in 2016