Molecular, Immunological, and Clinical Features of 16 Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease.

Purpose: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency, triggered by non-tuberculous mycobacteria or Bacillus Calmette-Guérin (BCG) vaccines and characterized by severe diseases. All known genetic etiologies are inborn errors of IFN-γ-mediated immunity. Here, we report the molecular, cellular, and clinical features of patients from 15 Iranian families with disseminated disease without vaccination (2 patients) or following live BCG vaccination (14 patients).

Changes in motor function and brain cortex mitochondrial active oxygen species production in aged mice.

Neuronal ageing is a complex physiological process, associated to metabolic and motor changes. In this study, 3 and 17 months old male Swiss mice were used. Aged mice exhibited a significant reduction in motor performance and walking footprint pattern.

Trypanosoma cruzi 13C-labeled O-Glycan standards for mass spectrometry.

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease, a debilitating condition that affects over 10 million humans in the American continents. In addition to its traditional mode of human entry via the "kissing bug" in endemic areas, the infection can also be spread in non-endemic countries through blood transfusion, organ transplantation, eating food contaminated with the parasites, and from mother to fetus. Previous NMR-based studies established that the parasite expresses a variety of strain-specific and developmentally-regulated O-glycans that may contribute to virulence.

Potential Applications of Silk Fibroin as Vascular Implants: A Review.

Cardiovascular disease is a worldwide main cause of morbidity and mortality. Treatment alternatives include the use of cardiovascular implants that have generated a constant search for materials, and transformation processes that provide structures similar to those that need to be replaced. Among the biomaterials available for vascular implants, silk fibroin (SF) is of great interest because it is a natural, biodegradable, biocompatible protein.

IFN-γ and CD25 drive distinct pathologic features during hemophagocytic lymphohistiocytosis.

Background: Inflammatory activation of CD8 T cells can, when left unchecked, drive severe immunopathology. Hyperstimulation of CD8 T cells through a broad set of triggering signals can precipitate hemophagocytic lymphohistiocytosis (HLH), a life-threatening systemic inflammatory disorder.

Objective: The mechanism linking CD8 T-cell hyperactivation to pathology is controversial, with excessive production of IFN-γ and, more recently, excessive consumption of IL-2, which are proposed as competing hypotheses.

Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common missense variant.

Inherited IL-12Rβ1 and TYK2 deficiencies impair both IL-12- and IL-23-dependent IFN-γ immunity and are rare monogenic causes of tuberculosis, each found in less than 1/600,000 individuals. We show that homozygosity for the common P1104A allele, which is found in about 1/600 Europeans and between 1/1000 and 1/10,000 individuals in regions other than East Asia, is more frequent in a cohort of patients with tuberculosis from endemic areas than in ethnicity-adjusted controls ( = 8.37 × 10; odds ratio, 89.

VarQ: A Tool for the Structural and Functional Analysis of Human Protein Variants.

Understanding the functional effect of Single Amino acid Substitutions (SAS), derived from the occurrence of single nucleotide variants (SNVs), and their relation to disease development is a major issue in clinical genomics. Despite the existence of several bioinformatic algorithms and servers that predict if a SAS is pathogenic or not, they give little or no information at all on the reasons for pathogenicity prediction and on the actual predicted effect of the SAS on the protein function. Moreover, few actual methods take into account structural information when available for automated analysis.

How much for a broken heart? Costs of cardiovascular disease in Colombia using a person-based approach.

The shift of the Noncommunicable Diseases (NCDs) epidemic, including cardiovascular disease, from developed to Low and Middle Income Countries (LMIC), creates new challenges in contexts where there is poor information on healthcare costs. Clearly this information is essential for planning, and its relevance is even more valuable as a driver for prevention and control of NCDs. This paper begins to address that handicap by estimating the healthcare cost of Cardiovascular Disease (Coronary Heart Disease and Stroke) in Colombia, using a person-based approach.

Rescue of recurrent deep intronic mutation underlying cell type-dependent quantitative NEMO deficiency.

X-linked dominant incontinentia pigmenti (IP) and X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) are caused by loss-of-function and hypomorphic IKBKG (also known as NEMO) mutations, respectively. We describe a European mother with mild IP and a Japanese mother without IP, whose 3 boys with EDA-ID died from ID. We identify the same private variant in an intron of IKBKG, IVS4+866 C>T, which was inherited from and occurred de novo in the European mother and Japanese mother, respectively.

Dysregulated gene expression predicts tumor aggressiveness in African-American prostate cancer patients.

Molecular mechanisms underlying the health disparity of prostate cancer (PCa) have not been fully determined. In this study, we applied bioinformatic approach to identify and validate dysregulated genes associated with tumor aggressiveness in African American (AA) compared to Caucasian American (CA) men with PCa. We retrieved and analyzed microarray data from 619 PCa patients, 412 AA and 207 CA, and we validated these genes in tumor tissues and cell lines by Real-Time PCR, Western blot, immunocytochemistry (ICC) and immunohistochemistry (IHC) analyses.

Alcohol hangover effects on brain cortex non-synaptic mitochondria and synaptosomes bioenergetics.

Alcohol hangover (AH) has been associated with oxidative stress and mitochondrial dysfunction. We herein postulate that AH-induced mitochondrial alterations can be due to a different pattern of response in synaptosomes and non-synaptic (NS) mitochondria. Mice received intraperitoneal (i.

Copy number variations and founder effect underlying complete IL-10Rβ deficiency in Portuguese kindreds.

Mutations in interleukin-10 receptor (IL-10R) genes are one cause of very early-onset inflammatory bowel disease with perianal lesions, which can be cured by hematopoietic stem cell transplantation. Using a functional test, which assesses responsiveness of peripheral monocytes to IL-10, we identified three unrelated Portuguese patients carrying two novel IL-10RB mutations. In the three patients, sequencing of genomic DNA identified the same large deletion of exon 3 which precluded protein expression.

Spatial congruence between multiple stressors in the Mediterranean Sea may reduce its resilience to climate impacts.

Climate impacts on marine ecosystems may be exacerbated by other, more local stressors interacting synergistically, such as pollution and overexploitation of marine resources. The reduction of these human stressors has been proposed as an achievable way of retaining ecosystems within a "safe operating space" (SOS), where they remain resilient to ongoing climate change. However, the operability of an SOS requires a thorough understanding of the spatial distribution of these climate and human impacts.

Morphological differences in lower facial third soft tissues in children with and without gingival smile: A cross-sectional comparative study.

Aim: The aim of the present study was to establish the relationship between lower facial third and smile type in silent mixed-dentition patients.

Methods: This cross-sectional study, approved by the ethics committee, was conducted in a population of 2760 children, from which a convenient sample of 198 was included: 75 with gingival smile (GS) and 123 without GS (1:1.64).

Mendelian susceptibility to mycobacterial disease: 2014-2018 update.

Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of IFN-γ immunity. Since 1996, disease-causing mutations have been found in 11 genes, which, through allelic heterogeneity, underlie 21 different genetic disorders. We briefly review here progress in the study of molecular, cellular and clinical aspects of MSMD since the last comprehensive review published in 2014.

Early-Onset Invasive Infection Due to Corynespora cassiicola Associated with Compound Heterozygous CARD9 Mutations in a Colombian Patient.

Purpose: CARD9 deficiency is an inborn error of immunity that predisposes otherwise healthy humans to mucocutaneous and invasive fungal infections, mostly caused by Candida, but also by dermatophytes, Aspergillus, and other fungi. Phaeohyphomycosis are an emerging group of fungal infections caused by dematiaceous fungi (phaeohyphomycetes) and are being increasingly identified in patients with CARD9 deficiency. The Corynespora genus belongs to phaeohyphomycetes and only one adult patient with CARD9 deficiency has been reported to suffer from invasive disease caused by C.

Impaired IL-12- and IL-23-Mediated Immunity Due to IL-12Rβ1 Deficiency in Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease.

Purpose: Inborn errors of IFN-γ-mediated immunity underlie Mendelian Susceptibility to Mycobacterial Disease (MSMD), which is characterized by an increased susceptibility to severe and recurrent infections caused by weakly virulent mycobacteria, such as Bacillus Calmette-Guérin (BCG) vaccines and environmental, nontuberculous mycobacteria (NTM).

Methods: In this study, we investigated four patients from four unrelated consanguineous families from Isfahan, Iran, with disseminated BCG disease. We evaluated the patients' whole blood cell response to IL-12 and IFN-γ, IL-12Rβ1 expression on T cell blasts, and sequenced candidate genes.

T-cell defects in patients with germline mutations account for combined immunodeficiency.

ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline biallelic mutations in have been recently described in 6 patients with clinical features of combined immunodeficiency (CID), whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B deficiency may also lead to cytoskeleton and functional defects in T cells.

Generalized Jacobi-Weierstrass operators and Jacobi expansions.

We present a realization for some -functionals associated with Jacobi expansions in terms of generalized Jacobi-Weierstrass operators. Fractional powers of the operators as well as results concerning simultaneous approximation and Nikolskii-Stechkin type inequalities are also considered.

Disruption of an antimycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency.

Human inborn errors of IFN-γ immunity underlie mycobacterial diseases. We describe patients with Mycobacterium bovis (BCG) disease who are homozygous for loss-of-function mutations of SPPL2A. This gene encodes a transmembrane protease that degrades the N-terminal fragment (NTF) of CD74 (HLA invariant chain) in antigen-presenting cells.