Proteomic data on the nuclear interactome of human MCM9.

We present data relating to the interactome of MCM9 from the nuclei of human cells. MCM9 belongs to the AAA+ superfamily, and contains an MCM domain and motifs that may confer DNA helicase activity. MCM9 has been shown to bind MCM8, and has been implicated in DNA replication and homologous recombination.

MCM9 Is Required for Mammalian DNA Mismatch Repair.

DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects DNA polymerase errors during replication to maintain genomic integrity. In E. coli, the DNA helicase UvrD is implicated in MMR, yet an analogous helicase activity has not been identified in eukaryotes.

Increased FAT/CD36 cycling and lipid accumulation in myotubes derived from obese type 2 diabetic patients.

Background: Permanent fatty acid translocase (FAT/)CD36 relocation has previously been shown to be related to abnormal lipid accumulation in the skeletal muscle of type 2 diabetic patients, however mechanisms responsible for the regulation of FAT/CD36 expression and localization are not well characterized in human skeletal muscle.

Methodology/principal Findings: Primary muscle cells derived from obese type 2 diabetic patients (OBT2D) and from healthy subjects (Control) were used to examine the regulation of FAT/CD36. We showed that compared to Control myotubes, FAT/CD36 was continuously cycling between intracellular compartments and the cell surface in OBT2D myotubes, independently of lipid raft association, leading to increased cell surface FAT/CD36 localization and lipid accumulation.

Abnormal metabolism flexibility in response to high palmitate concentrations in myotubes derived from obese type 2 diabetic patients.

Insulin resistance in type 2 diabetes (T2D) is associated with intramuscular lipid (IMCL) accumulation. To determine whether impaired lipid oxidation is involved in IMCL accumulation, we measured expression of genes involved in mitochondrial oxidative metabolism or biogenesis, mitochondrial content and palmitate beta-oxidation before and after palmitate overload (600μM for 16h), in myotubes derived from healthy subjects and obese T2D patients. Mitochondrial gene expression, content and network were not different between groups.

Lipid content and response to insulin are not invariably linked in human muscle cells.

In type 2 diabetes, a strong correlation between intramyocellular lipid accumulation and insulin resistance exists but whether intramyocellular accumulation is a cause or a consequence of insulin resistance is not clear. Lipid accumulation and response to insulin were evaluated in primary human myotubes derived from non-diabetic subjects and type 2 diabetic patients. Myotubes derived from type 2 diabetic patients had a defective response to insulin without showing a significant increase in lipid accumulation compared to myotubes derived from non-diabetic subjects.

[Physical exercise and insulin resistance: from muscle metabolic physiopathology to therapeutics].

Insulin resistance which characterises obesity and type 2 diabetes depends on genetic and environmental factors. Sedentarity plays a key role in the development of insulin resistance and skeletal muscle of obese or type 2 diabetes patients shows several abnormalities of carbohydrate and fat metabolism. Exercice training by its beneficial effects on skeletal muscle and particularly on mitochondrial function is efficient to prevent and to treat obesity and type 2 diabetes.

Inhibition of Notch signaling induces myotube hypertrophy by recruiting a subpopulation of reserve cells.

During muscle differentiation, a population of quiescent undifferentiated myoblasts (reserve cells) emerges among mature muscle cells. However, the molecular mechanisms underlying such cell segregation and the characterization of this subpopulation of myoblasts remain to be determined. Notch is known to control the behavior and fate of murine muscle stem cells.

Intracellular retention of caveolin 1 in presenilin-deficient cells.

Mutations in genes encoding presenilins (PS1 and PS2) are responsible for the majority of early onset familial Alzheimer's disease. PS, a critical component of gamma-secretase, is responsible for the intramembranous cleavage of amyloid precursor protein and Notch. Other physiological functions have been assigned to PS without any clear identification of the mechanisms underlying these multiple biological roles.

Transient induction of cyclin A in loaded chicken skeletal muscle.

Cell proliferation is believed to contribute to the increased synthesis rate during load-induced growth of avian anterior latissimus dorsi (ALD) skeletal muscle, but the relative contribution of different cell types to this proliferative response and the time course of cell activation are not well documented. The present investigation measured the abundance and localization of cyclin A protein, which is uniquely present in proliferating cells and required for the entry of vertebrate cells into the DNA synthesis phase during the time course of chicken ALD loading. Total protein content in 1.

Identification and characterization of presenilin-independent Notch signaling.

Presenilin (PS) proteins control the proteolytic cleavage that precedes nuclear access of the Notch intracellular domain. Here we observe that a partial activation of the HES1 promoter can be detected in PS1/PS2 (PS1/2) double null cells using Notch1 Delta E constructs or following Delta 1 stimulation, despite an apparent abolition of the production and nuclear accumulation of the Notch intracellular domain. PS1/2-independent Notch activation is sensitive to Numblike, a physiological inhibitor of Notch.