Prevalence of Inflammatory Pathways Over Immuno-Tolerance in Peripheral Blood Mononuclear Cells of Recent-Onset Type 1 Diabetes.

Background: Changes in innate and adaptive immunity occurring in/around pancreatic islets had been observed in peripheral blood mononuclear cells (PBMC) of Caucasian T1D patients by some, but not all researchers. The aim of our study was to investigate whether gene expression patterns of PBMC of the highly admixed Brazilian population could add knowledge about T1D pathogenic mechanisms.

Methods: We assessed global gene expression in PBMC from two groups matched for age, sex and BMI: 20 patients with recent-onset T1D (≤ 6 months from diagnosis, in a time when the autoimmune process is still highly active), testing positive for one or more islet autoantibodies and 20 islet autoantibody-negative healthy controls.

ReMap 2022: a database of Human, Mouse, Drosophila and Arabidopsis regulatory regions from an integrative analysis of DNA-binding sequencing experiments.

ReMap (https://remap.univ-amu.fr) aims to provide manually curated, high-quality catalogs of regulatory regions resulting from a large-scale integrative analysis of DNA-binding experiments in Human, Mouse, Fly and Arabidopsis thaliana for hundreds of transcription factors and regulators.

Understanding Human Cerebral Malaria through a Blood Transcriptomic Signature: Evidences for Erythrocyte Alteration, Immune/Inflammatory Dysregulation, and Brain Dysfunction.

Background: Cerebral malaria (CM), a reversible encephalopathy affecting young children, is a medical emergency requiring rapid clinical assessment and treatment. However, understanding of the genes/proteins and the biological pathways involved in the disease outcome is still limited.

Methods: We have performed a whole transcriptomic analysis of blood samples from Malian children with CM or uncomplicated malaria (UM).

ERBB2b mRNA isoform encodes a nuclear variant of the ERBB2 oncogene in breast cancer.

The presence of nuclear ERBB2 receptor-type tyrosine kinase is one of the causes of the resistance to membrane ERBB2-targeted therapy in breast cancers. It has been previously reported that this nuclear location arises through at least two different mechanisms: proteolytic shedding of the extracellular domain of the full-length receptor and translation of the messenger RNA (mRNA)-encoding ERBB2 from internal initiation codons. Here, we report a new mechanism and function where a significant portion of nuclear ERBB2 results from the translation of the variant ERBB2 mRNA under the transcriptional control of a distal promoter that is actively used in breast cancer cells.

The nature of the electron acceptor (MnIV/NO3) triggers the differential expression of genes associated with stress and ammonium limitation responses in Shewanella algae C6G3.

Shewanella algae C6G3 can dissimilatively reduce nitrate into ammonium and manganese oxide (MnIV) into MnII. It has the unusual ability to anaerobically produce nitrite from ammonium in the presence of MnIV. To gain insight into their metabolic capabilities, global mRNA expression patterns were investigated by RNA-seq and qRT-PCR in cells growing with lactate and ammonium as carbon and nitrogen sources, and with either MnIV or nitrate as electron acceptors.

Novel Intergenically Spliced Chimera, , Is Associated with Aggressive T-ALL Biology and Outcome.

Leukemias are frequently characterized by the expression of oncogenic fusion chimeras that normally arise due to chromosomal rearrangements. Intergenically spliced chimeric RNAs (ISC) are transcribed in the absence of structural genomic changes, and aberrant ISC expression is now recognized as a potential driver of cancer. To better understand these potential oncogenic drivers, high-throughput RNA sequencing was performed on T-acute lymphoblastic leukemia (T-ALL) patient specimens ( = 24), and candidate T-ALL-related ISCs were identified ( = 55; a median of 4/patient).

Translational Identification of Transcriptional Signatures of Major Depression and Antidepressant Response.

Major depressive disorder (MDD) is a highly prevalent mental illness whose therapy management remains uncertain, with more than 20% of patients who do not achieve response to antidepressants. Therefore, identification of reliable biomarkers to predict response to treatment will greatly improve MDD patient medical care. Due to the inaccessibility and lack of brain tissues from living MDD patients to study depression, researches using animal models have been useful in improving sensitivity and specificity of identifying biomarkers.

CD8 T Cells from Human Neonates Are Biased toward an Innate Immune Response.

To better understand why human neonates show a poor response to intracellular pathogens, we compared gene expression and histone modification profiles of neonatal naive CD8 T cells with that of their adult counterparts. We found that neonatal lymphocytes have a distinct epigenomic landscape associated with a lower expression of genes involved in T cell receptor (TCR) signaling and cytotoxicity and a higher expression of genes involved in the cell cycle and innate immunity. Functional studies corroborated that neonatal CD8 T cells are less cytotoxic, transcribe antimicrobial peptides, and produce reactive oxygen species.

Natural killer cells in acute myeloid leukemia patients: from phenotype to transcriptomic analysis.

Chemotherapies allow complete remission in more than 50 % of patients with acute myeloid leukemia (AML), however, with frequent relapse. This suggests that residual leukemic cells may escape to chemotherapy and immune system. Natural killer (NK) cells from AML patients (AML-NK) have a weaker natural cytotoxicity-activating receptors (NCRs) expression than NK cells from healthy donors (HD-NK).

Predisposition to treatment response in major depressive episode: A peripheral blood gene coexpression network analysis.

Antidepressant efficacy is insufficient, unpredictable and poorly understood in major depressive episode (MDE). Gene expression studies allow for the identification of significantly dysregulated genes but can limit the exploration of biological pathways. In the present study, we proposed a gene coexpression analysis to investigate biological pathways associated with treatment response predisposition and their regulation by microRNAs (miRNAs) in peripheral blood samples of MDE and healthy control subjects.

Deciphering the adaptation strategies of Desulfovibrio piezophilus to hydrostatic pressure through metabolic and transcriptional analyses.

Desulfovibrio piezophilus strain C1TLV30(T) is a mesophilic piezophilic sulfate-reducer isolated from Wood Falls at 1700 m depth in the Mediterranean Sea. In this study, we analysed the effect of the hydrostatic pressure on this deep-sea living bacterium at the physiologic and transcriptomic levels. Our results showed that lactate oxidation and energy metabolism were affected by the hydrostatic pressure.

A Positive Feed-forward Loop Associating EGR1 and PDGFA Promotes Proliferation and Self-renewal in Glioblastoma Stem Cells.

Glioblastomas are the most common primary brain tumors, highly vascularized, infiltrating, and resistant to current therapies. This cancer leads to a fatal outcome in less than 18 months. The aggressive behavior of glioblastomas, including resistance to current treatments and tumor recurrence, has been attributed to glioma stemlike/progenitor cells.

CX3CR1 is dysregulated in blood and brain from schizophrenia patients.

The molecular mechanisms underlying schizophrenia remain largely unknown. Although schizophrenia is a mental disorder, there is increasing evidence to indicate that inflammatory processes driven by diverse environmental factors play a significant role in its development. With gene expression studies having been conducted across a variety of sample types, e.

Sperm mRNAs and microRNAs as candidate markers for the impact of toxicants on human spermatogenesis: an application to tobacco smoking.

Spermatozoa contain a complex population of RNAs including messenger RNAs (mRNAs) and small RNAs such as microRNAs (miRNA). It has been reported that these RNAs can be used to understand the mechanisms by which toxicological exposure affects spermatogenesis. The aim of our study was to compare mRNA and miRNA profiles in spermatozoa from eight smokers and eight non-smokers, and search for potential relationships between mRNA and miRNA variation.

Transcription-dependent generation of a specialized chromatin structure at the TCRβ locus.

V(D)J recombination assembles Ag receptor genes during lymphocyte development. Enhancers at AR loci are known to control V(D)J recombination at associated alleles, in part by increasing chromatin accessibility of the locus, to allow the recombination machinery to gain access to its chromosomal substrates. However, whether there is a specific mechanism to induce chromatin accessibility at AR loci is still unclear.

Transcriptomics reveal several gene expression patterns in the piezophile Desulfovibrio hydrothermalis in response to hydrostatic pressure.

RNA-seq was used to study the response of Desulfovibrio hydrothermalis, isolated from a deep-sea hydrothermal chimney on the East-Pacific Rise at a depth of 2,600 m, to various hydrostatic pressure growth conditions. The transcriptomic datasets obtained after growth at 26, 10 and 0.1 MPa identified only 65 differentially expressed genes that were distributed among four main categories: aromatic amino acid and glutamate metabolisms, energy metabolism, signal transduction, and unknown function.

Divergent transcription is associated with promoters of transcriptional regulators.

Background: Divergent transcription is a wide-spread phenomenon in mammals. For instance, short bidirectional transcripts are a hallmark of active promoters, while longer transcripts can be detected antisense from active genes in conditions where the RNA degradation machinery is inhibited. Moreover, many described long non-coding RNAs (lncRNAs) are transcribed antisense from coding gene promoters.

Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B.

The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle, yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified, we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures.

Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode.

To date, it remains impossible to guarantee that short-term treatment given to a patient suffering from a major depressive episode (MDE) will improve long-term efficacy. Objective biological measurements and biomarkers that could help in predicting the clinical evolution of MDE are still warranted. To better understand the reason nearly half of MDE patients respond poorly to current antidepressive treatments, we examined the gene expression profile of peripheral blood samples collected from 16 severe MDE patients and 13 matched controls.

TranscriptomeBrowser 3.0: introducing a new compendium of molecular interactions and a new visualization tool for the study of gene regulatory networks.

Background: Deciphering gene regulatory networks by in silico approaches is a crucial step in the study of the molecular perturbations that occur in diseases. The development of regulatory maps is a tedious process requiring the comprehensive integration of various evidences scattered over biological databases. Thus, the research community would greatly benefit from having a unified database storing known and predicted molecular interactions.

Genome-wide analysis of familial dysautonomia and kinetin target genes with patient olfactory ecto-mesenchymal stem cells.

Familial dysautonomia (FD) is a rare inherited neurodegenerative disorder. The most common mutation is a c.2204+6T>C transition in the 5' splice site (5'ss) of IKBKAP intron 20, which causes a tissue-specific skipping of exon 20, resulting in lower synthesis of IKAP/hELP1 protein.

Olfactory stem cells, a new cellular model for studying molecular mechanisms underlying familial dysautonomia.

Background: Familial dysautonomia (FD) is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system.

Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.

Background: Deciphering host responses contributing to dengue shock syndrome (DSS), the life-threatening form of acute viral dengue infections, is required to improve both the differential prognosis and the treatments provided to DSS patients, a challenge for clinicians.

Methodology/principal Findings: Based on a prospective study, we analyzed the genome-wide expression profiles of whole blood cells from 48 matched Cambodian children: 19 progressed to DSS while 16 and 13 presented respectively classical dengue fever (DF) or dengue hemorrhagic fever grades I/II (DHF). Using multi-way analysis of variance (ANOVA) and adjustment of p-values to control the False Discovery Rate (FDR<10%), we identified a signature of 2959 genes differentiating DSS patients from both DF and DHF, and showed a strong association of this DSS-gene signature with the dengue disease phenotype.