Optimized Automated Analysis of Live Neuronal Mitochondria Homeostasis Modulation by Isoform-Specific Retinoic Acid Receptors.

The complex mitochondrial network makes it very challenging to segment, follow, and analyze live cells. MATLAB tools allow the analysis of mitochondria in timelapse files, considerably simplifying and speeding up the process of image processing. Nonetheless, existing tools produce a large output volume, requiring individual manual attention, and basic experimental setups have an output of thousands of files, each requiring extensive and time-consuming handling.

Novel therapeutic strategies targeting mitochondria as a gateway in neurodegeneration.

In recent years, multiple disciplines have focused on mitochondrial biology and contributed to understanding its relevance towards adult-onset neurodegenerative disorders. These are complex dynamic organelles that have a variety of functions in ensuring cellular health and homeostasis. The plethora of mitochondrial functionalities confers them an intrinsic susceptibility to internal and external stressors (such as mutation accumulation or environmental toxins), particularly so in long-lived postmitotic cells such as neurons.

Revisiting APP secretases: an overview on the holistic effects of retinoic acid receptor stimulation in APP processing.

Alzheimer's disease (AD) is the leading cause of dementia worldwide and is characterized by the accumulation of the β-amyloid peptide (Aβ) in the brain, along with profound alterations in phosphorylation-related events and regulatory pathways. The production of the neurotoxic Aβ peptide via amyloid precursor protein (APP) proteolysis is a crucial step in AD development. APP is highly expressed in the brain and is complexly metabolized by a series of sequential secretases, commonly denoted the α-, β-, and γ-cleavages.

BRCA gene mutations do not shape the extent and organization of tumor infiltrating lymphocytes in triple negative breast cancer.

This study investigated the prevalence of TIL subpopulations, TLS, PD-1 and PD-L1 in tumors from TNBC patients harboring wild-type or mutated BRCA1 or BRCA2 germline genes. This TNBC cohort included 85% TIL-positive (≥10%) tumors with 21% classified as TIL (≥50%). Interestingly, the BRCA group had a significantly higher incidence of TIL tumors compared to the BRCA group (P = 0.

Celiac Male's Gluten-Free Diet Profile: Comparison to that of the Control Population and Celiac Women.

The aim of the present work was to analyze the body composition and dietary profile of Spanish celiac men and to compare them to control men and celiac women from our previous studies. Forty-two celiac men (31.5 ± 11.

Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging.

Chromosome translocations are especially frequent in human lymphomas and leukemias but are insufficient to drive carcinogenesis. Indeed, several of the so-called tumor specific translocations have been detected in peripheral blood of healthy individuals, finding a higher frequency of some of them with aging. The inappropriate repair of DNA double strand breaks by the nonhomologous end joining (NHEJ) pathway is one of the reasons for a translocation to occur.

Expression analysis in intestinal mucosa reveals complex relations among genes under the association peaks in celiac disease.

Celiac disease is a chronic immune-mediated disorder with an important genetic component. To date, there are 57 independent association signals from 39 non-HLA loci, and a total of 66 candidate genes have been proposed. We aimed to scrutinize the functional implication of 45 of those genes by analyzing their expression in the disease tissue of celiac patients (at diagnosis/treatment) compared with non-celiac controls.

A trichobezoar in a child with undiagnosed celiac disease: a case report.

Celiac disease is a chronic, immune-mediated enteropathy caused by a permanent sensitivity to ingested gluten cereals that develops in genetically susceptible individuals. The classic presentation of celiac disease includes symptoms of malabsorption but has long been associated with cognitive, emotional, and behavioral disorders. We describe an 8-year-old patient with non-scarring alopecia and diagnosed with trichotillomania.

Alteration of tight junction gene expression in celiac disease.

Objective: The aim of the present study was to characterize the deregulation of epithelial tight junction genes and investigate its reversibility on removal of dietary gluten in small intestinal mucosa in celiac disease (CD).

Methods: The expression levels of 23 genes related to tight junctions were studied in biopsies from 16 patients with active CD and compared with biopsies from the same patients taken after 2 years on gluten-free diet (GFD) and with 16 non-CD controls.

Results: Nine genes showed altered expression levels in patients with active disease (CLDN2, PARD6A, ZAK, SYMPK, MYH14, and ACTB were upregulated, whereas MAGI1, TJP1, and PPP2R3A were downregulated).

Coregulation and modulation of NFκB-related genes in celiac disease: uncovered aspects of gut mucosal inflammation.

It is known that the NFκB route is constitutively upregulated in celiac disease (CD), an immune-mediated disorder of the gut caused by intolerance to ingested gluten. Our aim was to scrutinize the expression patterns of several of the most biologically relevant components of the NFκB route in intestinal biopsies from active and treated patients and after in vitro gliadin challenge, and to assess normalization of the expression using an inhibitor of the MALT1 paracaspase. The expression of 93 NFκB genes was measured by RT-PCR in a set of uncultured active and treated CD and control biopsies, and in cultured biopsy series challenged with gliadin, the NFκB modulator, both compounds and none.

Accuracy in copy number calling by qPCR and PRT: a matter of DNA.

The possible implication of copy number variation (CNV) in the genetic susceptibility to human disease needs to be assessed using robust methods that can be applied at a population scale. In this report, we analyze the performance of the two major techniques, quantitative PCR (qPCR) and paralog ratio test (PRT), and investigate the influence of input DNA amount and template integrity on the reliability of both methods. Analysis of three genes (PRELID1, SYNPO and DEFB4) in a large sample set showed that both methods are prone to false copy number assignments if sufficient attention is not paid to DNA concentration and quality.

Angiogenesis-related gene expression analysis in celiac disease.

Celiac disease (CD) involves disturbance of the small-bowel mucosal vascular network, and transglutaminase autoantibodies (TGA) have been related to angiogenesis disturbance, a complex phenomenon probably also influenced by common genetic variants in angiogenesis-related genes. A set of genes with "angiogenesis" GO term identified in a previous expression microarray experiment (SCG2, STAB1, TGFA, ANG, ERBB2, GNA13, PML, CASP8, ECGF1, JAG1, HIF1A, TNFSF13 and TGM2) was selected for genetic and functional studies. SNPs that showed a trend for association with CD in the first GWAS were genotyped in 555 patients and 541 controls.

[Nutritional profile of foods offered and dietary intake in school canteens in Biscay].

Introduction: Nowadays the school canteen occupies a central place in the supply and in the nutritional education of the children in school age.

Objectives: To assess the nutritional adequacy of the school menus and the food intake of the children.

Methods: 1,500 trays were selected in six school dining rooms of Biscay.

Upregulation of KIR3DL1 gene expression in intestinal mucosa in active celiac disease.

Killer cell immunoglobulin-like receptors (KIRs) modulate natural killer (NK) and T-cell function by human leukocyte antigen class I interaction and have been implicated in celiac disease (CD). Qualitative expression of 16 KIR genes was determined in biopsies from 22 CD patients at diagnosis and after >2 years on a gluten-free diet (GFD). Quantitative expression analysis of KIR2DL4, KIR3DL1, KIR3DL3, and KLRC2 (a marker of an NK-reprogrammed T-cell subpopulation augmented in CD) was performed in 35 additional CD biopsy pairs and 14 non-CD control biopsies.

Analysis of beta-defensin and Toll-like receptor gene copy number variation in celiac disease.

Celiac disease (CD) is an immune-mediated disorder of the gut in which innate and adaptive responses are involved. Toll-like receptor (TLR) 2 and TLR4 participate in host defense through antigen recognition, and show altered expression in CD gut mucosa. beta-defensins are inducible antimicrobial peptides, and DEFB gene copy number polymorphisms have been associated with autoimmune and inflammatory disorders.

Cow's-milk-free diet as a therapeutic option in childhood chronic constipation.

Objectives: It has been reported that a number of children with constipation respond to a diet free of cow's-milk (CM) proteins, although evidence is lacking to support an immunoglobulin E-mediated mechanism.

Patients And Methods: We performed an open-label crossover study comparing CM and rice milk in 69 children who fulfilled Rome III criteria for chronic constipation. Clinical, physical, and immunologic parameters of patients who responded (R) and who did not respond (NR) to a CM-free diet were compared.

Long-term and acute effects of gliadin on small intestine of patients on potentially pathogenic networks in celiac disease.

Celiac disease (CD) is a complex, immune-mediated intolerance to gliadin that develops in genetically susceptible individuals. Although the main driving force of the disease is an aberrant autoimmune response, several other pathogenic mechanisms, many still unidentified, are also involved. In order to describe at a network level the alterations provoked by a gliadin insult on the intestinal mucosa of patients, we compared the expression profiles of biopsies from 9 active and 9 treated patients (long-term effects of gliadin), and of 10 biopsies from gluten-free diet treated patients that were incubated in vitro with or without gliadin (acute effects) and integrated significantly altered transcripts into potentially pathogenic biological processes.

A regulatory single nucleotide polymorphism in the ubiquitin D gene associated with celiac disease.

An aberrant immune response triggered by dietary gluten is the main driving force underlying celiac disease (CD), but other biologic pathways that are dysregulated also participate in disease development. Genetic variation within these pathways might influence expression, contributing to susceptibility to CD. We have investigated the implication of ubiquitin D (UBD), a member of the ubiquitin-proteasome system that is strongly upregulated in the intestinal mucosa of active CD.

Chromosome instability in lymphocytes of children with coeliac disease.

Undiagnosed individuals with celiac disease (CD) or those who do not comply with gluten-free diet (GFD) are at a higher risk of developing malignancies. A possible origin of chromosomal alteration in autoimmune reaction could be mistakes in the rearrangement of V(D)J of the IgH gene. Our aim was to verify whether higher genomic instability was found in coeliac individuals and whether GFD reduced it.

Combined functional and positional gene information for the identification of susceptibility variants in celiac disease.

Background & Aims: Celiac disease is a complex, immune-mediated disorder of the intestinal mucosa with a strong genetic component. HLA-DQ2 is the major determinant of risk, but other minor genes, still to be identified, also are involved.

Methods: We designed a strategy that combines gene expression profiling of intestinal biopsy specimens, linkage region information, and different bioinformatics tools for the selection of potentially regulatory single-nucleotide polymorphisms (SNPs) involved in the disease.

The functional R620W variant of the PTPN22 gene is associated with celiac disease.

The functional (R620W) variant of human PTPN22 (protein tyrosine phosphatase non-receptor 22) gene has been implicated in the risk to several autoimmune disorders, including type 1 diabetes, Graves' disease, rheumatoid arthritis and systemic lupus erythematosus. In an association study of this single nucleotide polymorphism with celiac disease (CD), comparison of 262 young diagnosis patients and 214 adult controls from Spain showed a higher frequency of the minor allele in the CD group (9.7% vs 5.

Toll-like receptor 4 (TLR4) gene polymorphisms in celiac disease.

Toll-like receptors (TLRs) participate in the first line of immune defense through antigen pattern recognition, and ligands include exogenous and host-derived molecules. Coding variants in TLR4 have been associated with autoimmune diseases like ulcerative colitis, Crohn's disease, and rheumatoid arthritis. Our aim was to determine whether these polymorphisms are associated with celiac disease (CD).

Two-year follow-up of anti-transglutaminase autoantibodies among celiac children on gluten-free diet: comparison of IgG and IgA.

Objectives: To investigate the evolution of IgA and IgG autoantibodies against tissue transglutaminase (tTGase) in celiac patients on gluten-free diet (GFD).

Methods: IgA and IgG anti-tTGAse autoantibodies was evaluated in 93 patients (58 girls and 35 boys; mean age 3.56 +/- 3.

Association of KIR2DL5B gene with celiac disease supports the susceptibility locus on 19q13.4.

Genome-wide scans have detected linkage to celiac disease (CD) in several genomic locations, including 19q13.4. Killer immunoglobulin-like receptor (KIR) genes map to the region and encode receptors of natural killer (NK) cells and certain T cells that modulate cytolitic activity through interactions with HLA class I ligands, participating in the innate immune response.