Novartis

About: Novartis is a company organization based out in Basel, Switzerland. It is known for research contribution in the topics: Alkyl & Population. The organization has 41930 authors who have published 50566 publications receiving 1978996 citations. The organization is also known as: Novartis International AG.

Bicyclic nucleosides, oligonucleotides, process for their preparation and intermediates

Abstract: Compounds of the formula I in the form of the racemates or enantiomers thereof, ##STR1## in which R 1 and R 2 independently of one another are hydrogen or a protective group, and B is a purine or pyrimidine radical or an analogue thereof, can be used as antiviral active ingredients or for the preparation of biologically active oligonucleotides.

Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates.

Abstract: Cell-based diabetes therapy requires an abundant cell source. Here, we report reversal of diabetes for more than 100 d in cynomolgus macaques after intraportal transplantation of cultured islets from genetically unmodified pigs without Gal-specific antibody manipulation. Immunotherapy with CD25-specific and CD154-specific monoclonal antibodies, FTY720 (or tacrolimus), everolimus and leflunomide suppressed indirect activation of T cells, elicitation of non-Gal pig-specific IgG antibody, intragraft expression of proinflammatory cytokines and invasion of infiltrating mononuclear cells into islets.

Outcome Prediction for Estrogen Receptor–Positive Breast Cancer Based on Postneoadjuvant Endocrine Therapy Tumor Characteristics

Abstract: An accurate test to predict the effectiveness of adjuvant endocrine therapy for hormone receptor – positive breast cancer on an individual basis would be an important advance ( 1 ). Current approaches focus on biomarker analysis of the diagnostic specimen. An alternative is to treat patients with an endocrine agent for several months before surgery to identify tumors that are responsive to treatment, with the assumption that responsiveness indicates a lower risk of relapse. However, compared with neoadjuvant chemotherapy studies ( 2 ), fewer neoadjuvant endocrine therapy trials have been conducted; thus, fewer data are available to link postneoadjuvant therapy tumor characteristics and survival. The P024 neoadjuvant endocrine therapy trial, which compared 4 months of letrozole and tamoxifen before surgery ( 3 , 4 ), now has suffi cient follow-up (median >60 months) to address the relationships between postneoadjuvant endocrine therapy tumor characteristics and risk of early relapse. In this study, we used data from P024 to examine pathological stage posttreatment, histological grade posttreatment, response to treatment, and the biomarker status of the surgical specimen to develop a prognostic

Evaluation of quantitative miRNA expression platforms in the microRNA quality control (miRQC) study

Abstract: MicroRNAs are important negative regulators of protein-coding gene expression and have been studied intensively over the past years. Several measurement platforms have been developed to determine relative miRNA abundance in biological samples using different technologies such as small RNA sequencing, reverse transcription-quantitative PCR (RT-qPCR) and (microarray) hybridization. In this study, we systematically compared 12 commercially available platforms for analysis of microRNA expression. We measured an identical set of 20 standardized positive and negative control samples, including human universal reference RNA, human brain RNA and titrations thereof, human serum samples and synthetic spikes from microRNA family members with varying homology. We developed robust quality metrics to objectively assess platform performance in terms of reproducibility, sensitivity, accuracy, specificity and concordance of differential expression. The results indicate that each method has its strengths and weaknesses, which help to guide informed selection of a quantitative microRNA gene expression platform for particular study goals.

Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse

Abstract: DNA methylation is an important epigenetic modification regulating various biological phenomena, including genomic imprinting and transposon silencing. It is known that methylation of the differentially methylated regions (DMRs) associated with paternally imprinted genes and of some repetitive elements occurs during male germ cell development in the mouse. We have performed a detailed methylation analysis of the paternally methylated DMRs (H19, Dlk1/Gtl2 and Rasgrf1), interspersed repeats [SineB1, intracisternal A particle (IAP) and Line1] and satellite repeats (major and minor) to determine the timing of this de novo methylation in male germ cells. Furthermore, we have examined the roles of the de novo methyltransferases (Dnmt3a and Dnmt3b) and related protein (Dnmt3L) in this process. We found that methylation of all DMRs and repeats occurred progressively in fetal prospermatogonia and was completed by the newborn stage. Analysis of newborn prospermatogonia from germline-specific Dnmt3a and Dnmt3b knockout mice revealed that Dnmt3a mainly methylates the H19 and Dlk1/Gtl2 DMRs and a short interspersed repeat SineB1. Both Dnmt3a and Dnmt3b were involved in the methylation of Rasgrf1 DMR and long interspersed repeats IAP and Line1. Only Dnmt3b was required for the methylation of the satellite repeats. These results indicate both common and differential target specificities of Dnmt3a and Dnmt3b in vivo. Finally, all these sequences showed moderate to severe hypomethylation in Dnmt3L-deficient prospermatogonia, indicating the critical function and broad specificity of this factor in de novo methylation.