Neurotransmitter identity and electrophysiological phenotype are genetically coupled in midbrain dopaminergic neurons.

Most neuronal types have a well-identified electrical phenotype. It is now admitted that a same phenotype can be produced using multiple biophysical solutions defined by ion channel expression levels. This argues that systems-level approaches are necessary to understand electrical phenotype genesis and stability.

LGI1 tunes intrinsic excitability by regulating the density of axonal Kv1 channels.

Autosomal dominant epilepsy with auditory features results from mutations in leucine-rich glioma-inactivated 1 (LGI1), a soluble glycoprotein secreted by neurons. Animal models of LGI1 depletion display spontaneous seizures, however, the function of LGI1 and the mechanisms by which deficiency leads to epilepsy are unknown. We investigated the effects of pure recombinant LGI1 and genetic depletion on intrinsic excitability, in the absence of synaptic input, in hippocampal CA3 neurons, a classical focus for epileptogenesis.

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.

Analysis of T-cell receptor-γ gene rearrangements using heteroduplex analysis by high-resolution microcapillary electrophoresis.

Determination of T-cell clonality has an important additional value for diagnosis of T-cell lymphomas. Various molecular methods have been developed, including polymerase chain reaction (PCR) of T-cell receptor γ (TCRγ). The detection of PCR products usually relies commonly on either GeneScan (GS) analysis or heteroduplex (HD) analysis by polyacrylamide gel electrophoresis (PAGE).

Development of plasmid calibrators for absolute quantification of miRNAs by using real-time qPCR.

MicroRNAs (miRNAs) are small noncoding RNAs of approximately 18 to 25 nucleotides in length that negatively regulate gene expression via either the degradation or translational inhibition of their target mRNAs. Because miRNAs are essential for the regulation of critical physiological processes as well as a variety of pathological events, they have emerged as a novel class of molecular diagnostic biomarkers and therapeutic agents or targets. Accordingly, the need for novel methods for the quantification of miRNA has increased due to interest in their clinical implications.

Cloned IGH VDJ targets as tools for personalized minimal residual disease monitoring in mature lymphoid malignancies; a feasibility study in mantle cell lymphoma by the Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang.

Molecular minimal residual disease (MRD) analysis is fast emerging as an essential clinical decision-making tool for the treatment and follow-up of mature B cell malignancies. Current EuroMRD consensus IGH real-time quantitative polymerase chain reaction RQ-PCR assays rely on flow cytometric assessment of diagnostic tumour burdens to construct 'normalized', patient-specific, diagnostic DNA-based MRD quantification standards. Here, we propose a new 'hybrid' assay that relies on plasmid-based quantification of patient-specific IGH VDJ targets by consensus IGH real time (RQ)-PCR, combined with EuroMRD guidelines, for MRD monitoring in lymphoid malignancies.

Posttranscriptional deregulation of MYC via PTEN constitutes a major alternative pathway of MYC activation in T-cell acute lymphoblastic leukemia.

Cumulative evidence indicates that MYC, one of the major downstream effectors of NOTCH1, is a critical component of T-cell acute lymphoblastic leukemia (T-ALL) oncogenesis and a potential candidate for targeted therapy. However, MYC is a complex oncogene, involving both fine protein dosage and cell-context dependency, and detailed understanding of MYC-mediated oncogenesis in T-ALL is still lacking. To better understand how MYC is interspersed in the complex T-ALL oncogenic networks, we performed a thorough molecular and biochemical analysis of MYC activation in a comprehensive collection of primary adult and pediatric patient samples.

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.

Hypoxia inducible factor 1alpha gene (HIF-1alpha) splice variants: potential prognostic biomarkers in breast cancer.

Background: Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. The HIF-1 protein is composed of two HIF-1alpha and HIF-1beta/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. The prognostic relevance of HIF-1alpha protein overexpression has been shown in breast cancer.

Clinical variations modulate patterns of gene expression and define blood biomarkers in major depression.

The aim of the study is to compare the expression level of candidate genes between patients suffering from a severe major depressive episode (MDE) and controls, and also among patients during MDE evolution. After a comprehensive review of the biological data related to mood disorders, we initiated a hypothesis-driven exploration of candidate mRNAs. Using RT-qPCR, we analyzed peripheral blood mononuclear cells (PBMCs) mRNA obtained from a homogeneous population of 11 patients who suffered from severe melancholic MDE.

Development of a biochip-based assay integrated in a global strategy for identification of fusion transcripts in acute myeloid leukemia: a work flow for acute myeloid leukemia diagnosis.

Three major types of rearrangements are involved in acute myeloid leukemias (AML): t(8;21)(q22;q22), inv(16)(p13q22), and 11q23/MLL abnormalities. Their precise identification becomes essential for diagnosis, prognosis, and therapeutic choices. Resulting fusion transcripts (FT) are also powerful markers for monitoring the efficacy of treatment, the minimal residual disease (MRD) and could become therapeutic targets.