Feedback cooling of a single trapped ion

Based on a real-time measurement of the motion of a single ion in a Paul trap, we demonstrate its electro-mechanical cooling below the Doppler limit by homodyne feedback control (cold damping). The feedback cooling results are well described by a model based on a quantum mechanical Master Equation.Comment: 4 pages, 3 figure

Double-strand break repair and colorectal cancer: gene variants within 3' UTRs and microRNAs binding as modulators of cancer risk and clinical outcome

Genetic variations in 3' untranslated regions of target genes may affect microRNA binding, resulting in differential protein expression. microRNAs regulate DNA repair, and single-nucleotide polymorphisms in miRNA binding sites (miRSNPs) may account for interindividual differences in the DNA repair capacity. Our hypothesis is that miRSNPs in relevant DNA repair genes may ultimately affect cancer susceptibility and impact prognosis.In the present study, we analysed the association of polymorphisms in predicted microRNA target sites of double-strand breaks (DSBs) repair genes with colorectal cancer (CRC) risk and clinical outcome. Twenty-one miRSNPs in non-homologous end-joining and homologous recombination pathways were assessed in 1111 cases and 1469 controls. The variant CC genotype of rs2155209 in MRE11A was strongly associated with decreased cancer risk when compared with the other genotypes (OR 0.54, 95% CI 0.38-0.76, p = 0.0004). A reduced expression of the reporter gene was observed for the C allele of this polymorphism by in vitro assay, suggesting a more efficient interaction with potentially binding miRNAs. In colon cancer patients, the rs2155209 CC genotype was associated with shorter survival while the TT genotype of RAD52 rs11226 with longer survival when both compared with their respective more frequent genotypes (HR 1.63, 95% CI 1.06-2.51, p = 0.03 HR 0.60, 95% CI 0.41-0.89, p = 0.01, respectively). miRSNPs in DSB repair genes involved in the maintenance of genomic stability may have a role on CRC susceptibility and clinical outcome

Fusobacterium nucleatum tumor DNA levels are associated with survival in colorectal cancer patients

Made available in DSpace on 2019-10-06T17:16:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01There is increasing evidence indicating a role for Fusobacterium nucleatum (F. nucleatum) in colorectal cancer (CRC) development and prognosis. This study evaluated F. nucleatum as a prognostic biomarker, by assessing its association with post-diagnosis survival from CRC. From September 2008 to April 2012 CRC patients (n = 190) were recruited from three hospitals within the Czech Republic. F. nucleatum DNA copies were measured in adjacent non-malignant and colorectal tumor tissues using quantitative real-time PCR. Cox Proportional Hazards (HR) models were applied to evaluate the association between F. nucleatum DNA and overall survival, adjusting for key confounders. Risk prediction modeling was conducted to evaluate the ability to predict survival based on F. nucleatum status. High, compared with low, levels of F. nucleatum in colorectal tumor tissues were associated with poorer overall survival (adjusted HR 1.68, 95% CI 1.02–2.77), which was slightly attenuated after additional adjustment for microsatellite instability status. However, inclusion of F. nucleatum in risk prediction models did not improve the ability to identify patients who died beyond known prognostic factors such as disease pathology staging. Although the increased presence of F. nucleatum was associated with poorer prognosis in CRC patients, this may have limited clinical relevance as a prognostic biomarker.Centre for Public Health Queen’s University BelfastDepartment of Biology São Paulo State University UNESPInstitute of Biology and Medical Genetics First Faculty of Medicine Charles UniversityDepartment of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of SciencesDepartment of Surgery General University Hospital in PragueDepartment of Surgery First Faculty of Medicine Charles University and Thomayer HospitalBiomedical Centre Faculty of Medicine in Pilsen Charles UniversityDepartment of Oncology First Faculty of Medicine Charles University and Thomayer HospitalCancer Biology and Therapeutics Group School of Biomolecular and Biomedical Science UCD Conway Institute University College DublinDepartment of Biology São Paulo State University UNES

Early over expression of messenger RNA for multiple genes, including insulin, in the Pancreatic Lymph Nodes of NOD mice is associated with Islet Autoimmunity

<p>Abstract</p> <p>Background</p> <p>Autoimmune diabetes (T1D) onset is preceded by a long inflammatory process directed against the insulin-secreting β cells of the pancreas. Deciphering the early autoimmune mechanisms represents a challenge due to the absence of clinical signs at early disease stages. The aim of this study was to identify genes implicated in the early steps of the autoimmune process, prior to inflammation, in T1D. We have previously established that insulin autoantibodies (E-IAA) predict early diabetes onset delineating an early phenotypic check point (window 1) in disease pathogenesis. We used this sub-phenotype and applied differential gene expression analysis in the pancreatic lymph nodes (PLN) of 5 weeks old Non Obese Diabetic (NOD) mice differing solely upon the presence or absence of E-IAA. Analysis of gene expression profiles has the potential to provide a global understanding of the disease and to generate novel hypothesis concerning the initiation of the autoimmune process.</p> <p>Methods</p> <p>Animals have been screened weekly for the presence of E-IAA between 3 and 5 weeks of age. E-IAA positive or negative NOD mice at least twice were selected and RNAs isolated from the PLN were used for microarray analysis. Comparison of transcriptional profiles between positive and negative animals and functional annotations of the resulting differentially expressed genes, using software together with manual literature data mining, have been performed.</p> <p>Results</p> <p>The expression of 165 genes was modulated between E-IAA positive and negative PLN. In particular, genes coding for insulin and for proteins known to be implicated in tissue remodelling and Th1 immunity have been found to be highly differentially expressed. Forty one genes showed over 5 fold differences between the two sets of samples and 30 code for extracellular proteins. This class of proteins represents potential diagnostic markers and drug targets for T1D.</p> <p>Conclusion</p> <p>Our data strongly suggest that the immune related mechanisms taking place at this early age in the PLN, correlate with homeostatic changes influencing tissue integrity of the adjacent pancreatic tissue. Functional analysis of the identified genes suggested that similar mechanisms might be operating during pre-inflammatory processes deployed in tissues i) hosting parasitic microorganisms and ii) experiencing unrestricted invasion by tumour cells.</p

Improvement of Anaemia in Patients with Primary Myelofibrosis by Low-Dose Thalidomide and Prednisone

Background: A combination of low-dose thalidomide and corticosteroids is a treatment option for anaemic patients with primary myelofibrosis (PMF) who are not eligible for allogeneic hematopoietic stem cell transplantation. Methods: We describe the outcomes of 13 patients with PMF treated with thalidomide 50 mg daily in combination with prednisone 0.5 mg/kg daily. Treatment responses were seen in 10/13 (77%) patients with a median onset of therapeutic effect at 4 weeks (range 3–7 weeks) after treatment initiation. Improvements of anaemia and thrombocytopenia and reduction in splenomegaly were observed in 70%, 38%, and 30% of patients, respectively. Four of six initially transfusion-dependent patients became transfusion independent following the therapy. The median duration of treatment response was 18 months (range 3–35 months). The treatment was well tolerated, with only one patient discontinuing therapy due to toxicity. Responders included both patients with and without JAK2 V617F, and included patients with both newly diagnosed and longstanding PMF. Conclusions: Our retrospective analysis confirmed that the therapy with low-doses thalidomide with prednisone in patients with PMF achieves significant response rate in anaemia with low treatment toxicity

Methylation-Based Therapies for Colorectal Cancer

Colorectal carcinogenesis (CRC) is caused by the gradual long-term accumulation of both genetic and epigenetic changes. Recently, epigenetic alterations have been included in the classification of the CRC molecular subtype, and this points out their prognostic impact. As epigenetic modifications are reversible, they may represent relevant therapeutic targets. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), regulates gene expression. For many years, the deregulation of DNA methylation has been considered to play a substantial part in CRC etiology and evolution. Despite considerable advances in CRC treatment, patient therapy response persists as limited, and their profit from systemic therapies are often hampered by the introduction of chemoresistance. In addition, inter-individual changes in therapy response in CRC patients can arise from their specific (epi)genetic compositions. In this review article, we summarize the options of CRC treatment based on DNA methylation status for their predictive value. This review also includes the therapy outcomes based on the patient&rsquo;s methylation status in CRC patients. In addition, the current challenge of research is to develop therapeutic inhibitors of DNMT. Based on the essential role of DNA methylation in CRC development, the application of DNMT inhibitors was recently proposed for the treatment of CRC patients, especially in patients with DNA hypermethylation