Type I interferon signaling pathway enhances immune-checkpoint inhibition in KRAS mutant lung tumors.

Lung cancer is the leading cause of cancer mortality worldwide. KRAS oncogenes are responsible for at least a quarter of lung adenocarcinomas, the main subtype of lung cancer. After four decades of intense research, selective inhibitors of KRAS oncoproteins are finally reaching the clinic.

Apolipoprotein E-ε2 and Resistance to Atherosclerosis in Midlife: The PESA Observational Study.

Background: APOE is a known genetic contributor to cardiovascular disease, but the differential role alleles play in subclinical atherosclerosis remains unclear.

Methods: The PESA (Progression of Early Subclinical Atherosclerosis) is an observational cohort study that recruited 4184 middle-aged asymptomatic individuals to be screened for cardiovascular risk and multiterritorial subclinical atherosclerosis. Participants were -genotyped, and omics data were additionally evaluated.

Subclinical atherosclerosis and accelerated epigenetic age mediated by inflammation: a multi-omics study.

Aims: Epigenetic age is emerging as a personalized and accurate predictor of biological age. The aim of this article is to assess the association of subclinical atherosclerosis with accelerated epigenetic age and to investigate the underlying mechanisms mediating this association.

Methods And Results: Whole blood methylomics, transcriptomics, and plasma proteomics were obtained for 391 participants of the Progression of Early Subclinical Atherosclerosis study.

A Human Hereditary Cardiomyopathy Shares a Genetic Substrate With Bicuspid Aortic Valve.

Background: The complex genetics underlying human cardiac disease is evidenced by its heterogenous manifestation, multigenic basis, and sporadic occurrence. These features have hampered disease modeling and mechanistic understanding. Here, we show that 2 structural cardiac diseases, left ventricular noncompaction (LVNC) and bicuspid aortic valve, can be caused by a set of inherited heterozygous gene mutations affecting the NOTCH ligand regulator MIB1 (MINDBOMB1) and cosegregating genes.

expansion of a CD9 decidual-like NK cell subset following autologous hematopoietic stem cell transplantation.

Autologous hematopoietic stem cell transplantation (autoHSCT) is a treatment option for hematological disorders and pediatric solid tumors. After an autoHSCT, natural killer (NK) cells are the first lymphocyte subset returning to normal levels. To uncover global changes during NK cell reconstitution after autoHSCT, we performed RNA-sequencing on NK cells before and after autoHSCT.

Long-Term Dabigatran Treatment Delays Alzheimer's Disease Pathogenesis in the TgCRND8 Mouse Model.

Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with important vascular and hemostatic alterations that should be taken into account during diagnosis and treatment.

Objectives: This study evaluates whether anticoagulation with dabigatran, a clinically approved oral direct thrombin inhibitor with a low risk of intracerebral hemorrhage, ameliorates AD pathogenesis in a transgenic mouse model of AD.

Methods: TgCRND8 AD mice and their wild-type littermates were treated for 1 year with dabigatran etexilate or placebo.

Genomic characterization of the first oral avian papillomavirus in a colony of breeding canaries (Serinus canaria).

Papillomaviruses are non-enveloped, DNA viruses that infect skin and mucosa of a wide variety of vertebrates, causing neoplasias or simply persisting asymptomatically. Avian papillomaviruses, with six fully sequenced genomes, are the second most studied group after mammalian papillomaviruses. In this study, we describe the first oral avian papillomavirus, detected in the tongue of a dead Yorkshire canary (Serinus canaria) and in oral swabs of the same bird and other two live canaries from an aviary in Madrid, Spain.

A novel phosphatidylinositol 3-kinase (PI3K) inhibitor directs a potent FOXO-dependent, p53-independent cell cycle arrest phenotype characterized by the differential induction of a subset of FOXO-regulated genes.

Introduction: The activation of the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway is one the most frequent genetic events in breast cancer, consequently the development of PI3K inhibitors has attracted much attention. Here we evaluate the effect of PI3K inhibition on global gene expression in breast cancer cells.

Methods: We used a range of methodologies that include in silico compound analysis, in vitro kinase assays, cell invasion assays, proliferation assays, genome-wide transcription studies (Agilent Technologies full genome arrays), gene set enrichment analysis, quantitative real-time PCR, immunoblotting in addition to chromatin immunoprecipitation.

AG-NGS: a powerful and user-friendly computing application for the semi-automated preparation of next-generation sequencing libraries using open liquid handling platforms.

Next-generation sequencing (NGS) is becoming one of the most widely used technologies in the field of genomics. Library preparation is one of the most critical, hands-on, and time-consuming steps in the NGS workflow. Each library must be prepared in an independent well, increasing the number of hours required for a sequencing run and the risk of human-introduced error.

Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass.

Background: The progression towards type 2 diabetes depends on the allostatic response of pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse failed to expand its beta cell mass.

Characterization of host genetic expression patterns in HIV-infected individuals with divergent disease progression.

The course of HIV-1 infection shows a variety of clinical phenotypes with an important involvement of host factors. We compare host gene expression patterns in CD3+ T cells from two of these phenotypes: long-term non-progressor patients (LTNP) and matched control patients with standard HIV disease progression. Array analysis revealed over-expression of 322 genes in progressors and 136 in LTNP.

Automatic genomics: a user-friendly program for the automatic designing and plate loading of medium-throughput qPCR experiments.

Quantitative PCR (qPCR) remains the method of choice for gene and microRNA (miRNA) expression studies. Many laboratories wish to automate some or all of the steps of medium-throughput qPCR experiments through the use of various types of liquid handling robots. However, it is not uncommon to find cases in which scripts provided by the robot supplier are too rigid for user-specific applications, do not include all the desired options, or are too complicated to be modified by a nonprofessional programmer.

Large-scale gene expression in bone marrow mesenchymal stem cells: a putative role for COL10A1 in osteoarthritis.

Objectives: To elucidate disease-specific molecular changes occurring in osteoarthritis (OA) by analysing the differential gene expression profiles of bone marrow mesenchymal stem cells (BM-MSCs) from patients with OA compared with those without OA.

Methods: Expression profiles of BM-MSCs from eight paired patients with OA and patients with hip fracture without signs of OA were compared by DNA microarray expression analysis and significant differences were evaluated by computational Gene Set Enrichment Analysis. To validate the involvement of COL10A1 as part of the most downregulated gene set in OA, three tagging single nucleotide polymorphisms were genotyped in 191 patients with OA and 283 controls.

Processing of Agilent microRNA array data.

Background: The Agilent microRNA microarray platform interrogates each microRNA with several copies of distinct oligonucleotide probes and integrates the results into a total gene signal (TGS), using a proprietary algorithm that makes use of the background subtracted signal. The TGS can be normalized between arrays, and the Agilent recommendation is either not to normalize or to normalize to the 75th percentile signal intensity. The robust multiarray average algorithm (RMA) is an alternative method, originally developed to obtain a summary measure of mRNA Affymetrix gene expression arrays by using a linear model that takes into account the probe affinity effect.

Regulation of the microRNA processor DGCR8 by the tumor suppressor ING1.

The ING family of tumor suppressor proteins controls several cellular functions relevant to antitumor protection, such as cell cycle control, apoptosis, senescence, or migration. ING proteins are functionally linked to the p53 pathway, and they participate in transcriptional control via the recognition of histone marks and recruitment of protein complexes with chromatin-modifying activity to specific promoters. Here, we have investigated the global effect of ING1 in gene regulation through genome-wide analysis of expression profiles in primary embryonic fibroblasts deficient for the Ing1 locus.

Hemizygous subtelomeres of an African trypanosome chromosome may account for over 75% of chromosome length.

African trypanosomes are parasitic protozoa that infect a wide range of mammals, including humans. These parasites remain extracellular in the mammalian bloodstream, where antigenic variation allows them to survive the immune response. The Trypanosoma brucei nuclear genome sequence has been published recently.

Isolation and characterization of a cDNA encoding a putative high mobility group (HMG)--box protein from stored mRNA in resting cysts of the ciliate Oxytricha (Sterkiella) nova: ciliate macronuclear gene encoding a putative HMG-box protein.

We have isolated an cDNA after applying a DDRT-PCR analysis on mRNA from mature resting cysts of the ciliate Oxytricha (Sterkiella) nova. From this cDNA fragment the complete macronuclear minichromosome was obtained by using the Mac-End-PCR method. After cloning and sequencing, this cDNA shown certain similarity to HMG-like proteins.

A simple and rapid PCR-based method to isolate complete small macronuclear minichromosomes from hypotrich ciliates: 5S rDNA and S26 ribosomal protein gene of Oxytricha (Sterkiella) nova.

Hypotrich ciliates present a macronuclear genome consisting of gene-sized instead of chromosome-sized DNA molecules. Exploiting this unique eukaryotic genome feature, we introduce, for the first time in ciliates, a rapid and easy PCR method using telomeric primers to isolate small complete macronuclear DNA molecules or minichromosomes. Two presumably abundant macronuclear DNA molecules, containing ribosomal genes, were amplified from the Oxytricha (Sterkiella) nova complete genome after using this method, and then were cloned and sequenced.