Cancer genomics and biology 2015 - Meeting report

published_or_final_versio

Cysteamine Attenuates the Decreases in TrkB Protein Levels and the Anxiety/Depression-Like Behaviors in Mice Induced by Corticosterone Treatment

OBJECTIVE: Stress and glucocorticoid hormones, which are released into the circulation following stressful experiences, have been shown to contribute significantly to the manifestation of anxiety-like behaviors observed in many neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays an important role in stress-mediated changes in structural as well as functional neuroplasticity. Studies designed to elucidate the mechanisms whereby TrkB signaling is regulated in chronic stress might provide valuable information for the development of new therapeutic strategies for several stress-related psychiatric disorders. MATERIALS AND METHODS: We examined the potential of cysteamine, a neuroprotective compound to attenuate anxiety and depression like behaviors in a mouse model of anxiety/depression induced by chronic corticosterone exposure. RESULTS: Cysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus. Furthermore, cysteamine treatment reversed the anxiety and depression like behavioral abnormalities induced by chronic corticosterone treatment. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine. CONCLUSIONS: The animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders

92-Gene Molecular Profiling in Identification of Cancer Origin: A Retrospective Study in Chinese Population and Performance within Different Subgroups

BACKGROUND: After cancer diagnosis, therapy for the patient is largely dependent on the tumor origin, especially when a metastatic tumor is being treated. However, cases such as untypical metastasis, poorly differentiated tumors or even a limited number of tumor cells may lead to challenges in identifying the origin. Moreover, approximately 3% to 5% of total solid tumor patients will not have to have their tumor origin identified in their lifetime. The THEROS CancerTYPE ID® is designed for identifying the tumor origin with an objective, rapid and standardized procedure. METHODOLOGY AND PRINCIPAL FINDINGS: This is a blinded retrospective study to evaluate performance of the THEROS CancerTYPE ID® in a Chinese population. In total, 184 formalin-fixed paraffin-embedded (FFPE) samples of 23 tumor origins were collected from the tissue bank of Fudan University Shanghai Cancer Center (FDUSCC). A standard tumor cell enrichment process was used, and the prediction results were compared with reference diagnosis, which was confirmed by two experienced pathologists at FDUSCC. All of the 184 samples were successfully analyzed, and no tumor specimens were excluded because of sample quality issues. In total, 151 samples were correctly predicted. The agreement rate was 82.1%. A Pearson Chi-square test shows that there is no difference between this study and the previous evaluation test performed by bioTheranostics Inc. No statistically significant decrease was observed in either the metastasis group or tumors with high grades. CONCLUSIONS: A comparable result with previous work was obtained. Specifically, specimens with a high probability score (>0.85) have a high chance (agreement rate = 95%) of being correctly predicted. No performance difference was observed between primary and metastatic specimens, and no difference was observed among three tumor grades. The use of laser capture micro-dissection (LCM) makes the THEROS CancerTYPE ID® accessible to almost all of the cancer patients with different tumor statuses

Molecular gas kinematics within the central 250 pc of the Milky Way

Using spectral-line observations of HNCO, N2H+, and HNC, we investigate the kinematics of dense gas in the central ~250 pc of the Galaxy. We present SCOUSE (Semi-automated multi-COmponent Universal Spectral-line fitting Engine), a line fitting algorithm designed to analyse large volumes of spectral-line data efficiently and systematically. Unlike techniques which do not account for complex line profiles, SCOUSE accurately describes the {l, b, v_LSR} distribution of CMZ gas, which is asymmetric about Sgr A* in both position and velocity. Velocity dispersions range from 2.6 km/s28. The gas is distributed throughout several "streams", with projected lengths ~100-250 pc. We link the streams to individual clouds and sub-regions, including Sgr C, the 20 and 50 km/s clouds, the dust ridge, and Sgr B2. Shell-like emission features can be explained by the projection of independent molecular clouds in Sgr C and the newly identified conical profile of Sgr B2 in {l ,b, v_LSR} space. These features have previously invoked supernova-driven shells and cloud-cloud collisions as explanations. We instead caution against structure identification in velocity-integrated emission maps. Three geometries describing the 3-D structure of the CMZ are investigated: i) two spiral arms; ii) a closed elliptical orbit; iii) an open stream. While two spiral arms and an open stream qualitatively reproduce the gas distribution, the most recent parameterisation of the closed elliptical orbit does not. Finally, we discuss how proper motion measurements of masers can distinguish between these geometries, and suggest that this effort should be focused on the 20 km/s and 50 km/s clouds and Sgr C

Low metabolic activity of biofilm formed by Enterococcus faecalis isolated from healthy humans and wild mallards (Anas platyrhynchos)

It is widely known that Enterococcus faecalis virulence is related to its biofilm formation. Although Enterococci are common commensal organisms of the gastrointestinal tract, the difference between commensal and pathogen strains remain unclear. In this study, we compare the biochemical profile of the biofilms formed by two groups of medical and two groups of commensal strains. The medical strains were isolated as pathogens from infections of urinary tract and other infections (wounds, pus and bedsores), and the commensal strains were taken from faeces of healthy volunteers and faeces of wild mallards (Anas platyrhynchos) living in an urban environment. The properties of biofilms formed by medical and commensal strains differed significantly. Commensal strains showed lower metabolic activity and glucose uptake and higher biofilm biomass than the medical ones. Consistent with glucose uptake experiments, we found that the glucose dehydrogenase gene was more expressed in medical strains. These results indicate that higher metabolic activity and lower protein concentration of E. faecalis cells within biofilms are formed during infections.This work was supported by the Medical University of Gdansk research grant (GUMed W-65) and was financed partly by University of Gdansk research grant (BW 1440-5-0099-7). We are grateful to Katarzyna Zolkos for her help in catching mallards and Magdalena Remisiewicz for correcting the English. Catarina Seabra helped in preparing assays

A new and sensitive reaction rate method for spectrophotometric determination of trace amounts of thiourea in different water samples based on an induction period

BACKGROUNDAgrilus bigutattus (Fabricius) is a forest pest of increasing importance in the United Kingdom. The larvae damage weakened native oaks and are thought to contribute to premature tree death. Suspected links with acute oak decline (AOD) are not yet confirmed, but AOD-predisposed trees appear to become more susceptible to A. biguttatus attack. Thus, management may be necessary for control of this insect. To explore the possibility of monitoring beetle populations by baited traps, the host tree volatiles regulating A. biguttatus-oak interactions were studied. RESULTSBiologically active volatile organic compounds in dynamic headspace extracts of oak foliage and bark were identified initially by coupled gas chromatography-electroantennography (GC-EAG) and GC-mass spectrometry (GC-MS), and the structures were confirmed by GC coinjection with authentic compounds. Of two synthetic blends of these compounds comprising the active leaf volatiles, the simpler one containing three components evoked strongly positive behavioural responses in four-arm olfactometer tests with virgin females and males, although fresh leaf material was more efficient than the blend. The other blend, comprising a five-component mixture made up of bark volatiles, proved to be as behaviourally active for gravid females as bark tissue. CONCLUSIONSThese initial results on A. biguttatus chemical ecology reveal aspects of the role of attractive tree volatiles in the host-finding of beetles and underpin the development of semiochemically based surveillance strategies for this forest insect. (c) 2015 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry

Molecular gas kinematics within the central 250 pc of the Milky Way

Using spectral-line observations of HNCO, N2H+, and HNC, we investigate the kinematics of dense gas in the central ~250 pc of the Galaxy. We present SCOUSE (Semi-automated multi-COmponent Universal Spectral-line fitting Engine), a line fitting algorithm designed to analyse large volumes of spectral-line data efficiently and systematically. Unlike techniques which do not account for complex line profiles, SCOUSE accurately describes the {l, b, v_LSR} distribution of CMZ gas, which is asymmetric about Sgr A* in both position and velocity. Velocity dispersions range from 2.6 km/s28. The gas is distributed throughout several "streams", with projected lengths ~100-250 pc. We link the streams to individual clouds and sub-regions, including Sgr C, the 20 and 50 km/s clouds, the dust ridge, and Sgr B2. Shell-like emission features can be explained by the projection of independent molecular clouds in Sgr C and the newly identified conical profile of Sgr B2 in {l ,b, v_LSR} space. These features have previously invoked supernova-driven shells and cloud-cloud collisions as explanations. We instead caution against structure identification in velocity-integrated emission maps. Three geometries describing the 3-D structure of the CMZ are investigated: i) two spiral arms; ii) a closed elliptical orbit; iii) an open stream. While two spiral arms and an open stream qualitatively reproduce the gas distribution, the most recent parameterisation of the closed elliptical orbit does not. Finally, we discuss how proper motion measurements of masers can distinguish between these geometries, and suggest that this effort should be focused on the 20 km/s and 50 km/s clouds and Sgr C

Nicotinic acetylcholine receptor variants associated with susceptibility to chronic obstructive pulmonary disease: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>Only 10-15% of smokers develop chronic obstructive pulmonary disease (COPD) which indicates genetic susceptibility to the disease. Recent studies suggested an association between COPD and polymorphisms in <it>CHRNA </it>coding subunits of nicotinic acetylcholine receptor. Herein, we performed a meta-analysis to clarify the impact of <it>CHRNA </it>variants on COPD.</p> <p>Methods</p> <p>We searched Web of Knowledge and Medline from 1990 through June 2011 for COPD gene studies reporting variants on <it>CHRNA</it>. Pooled odds ratios (ORs) were calculated using the major allele or genotype as reference group.</p> <p>Results</p> <p>Among seven reported variants in <it>CHRNA</it>, rs1051730 was finally analyzed with sufficient studies. Totally 3460 COPD and 11437 controls from 7 individual studies were pooled-analyzed. A-allele of rs1051730 was associated with an increased risk of COPD regardless of smoking exposure (pooled OR = 1.26, 95% CI 1.18-1.34, p < 10^-5). At the genotypic level, the ORs gradually increased per A-allele (OR = 1.27 and 1.50 for GA and AA respectively, p < 10^-5). Besides, AA genotype exhibited an association with reduced FEV1% predicted (mean difference 3.51%, 95%CI 0.87-6.16%, p = 0.009) and increased risk of emphysema (OR 1.93, 95%CI 1.29-2.90, p = 0.001).</p> <p>Conclusions</p> <p>Our findings suggest that rs1051730 in <it>CHRNA </it>is a susceptibility variant for COPD, in terms of both airway obstruction and parenchyma destruction.</p