Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly.

Human Mental Retardation (MR) is a common and highly heterogeneous pediatric disorder affecting around 3% of the general population; at least 215 X-linked MR (XLMR) conditions have been described, and mutations have been identified in 83 different genes, encoding proteins with a variety of function, such as chromatin remodeling, synaptic function, and intracellular trafficking. The small GTPases of the RAB family, which play an essential role in intracellular vesicular trafficking, have been shown to be involved in MR. We report here the identification of mutations in the small GTPase RAB39B gene in two male patients.

Role of biophysical parameters on ex vivo and in vivo gene transfer to the airway epithelium by polyethylenimine/albumin complexes.

Efficient gene transfer to the airways by nonviral vectors is a function of different parameters, among which the size and the charge of the transfecting particles. The aim of this study was to determine the transfection efficiency of polyethylenimine (PEI)/albumin polyplexes in ex vivo and in vivo models of respiratory epithelium and to correlate it with biophysical characteristics of the particles. Complexes were obtained by adding different amounts of human serum albumin (HSA) to PEI polyplexes preformed in saline.

Dysregulated interleukin-8 secretion and NF-kappaB activity in human cystic fibrosis nasal epithelial cells.

Background: It is not clear whether cystic fibrosis (CF) airway inflammation is a consequence of bacterial infection or is intrinsically dysregulated. The aim of this study was to investigate IL-8 secretion and NF-kappaB activity in primary respiratory epithelial cells cultured from nasal polyps obtained from CF and non-CF subjects.

Methods: NF-kappaB activity was studied by electrophoretic mobility-shift and quantitative colorimetric assays in nuclear extracts.

Na+/H+ exchanger regulatory factor isoform 1 overexpression modulates cystic fibrosis transmembrane conductance regulator (CFTR) expression and activity in human airway 16HBE14o- cells and rescues DeltaF508 CFTR functional expression in cystic fibrosis cells.

There is evidence that cystic fibrosis transmembrane conductance regulator (CFTR) interacting proteins play critical roles in the proper expression and function of CFTR. The Na(+)/H(+) exchanger regulatory factor isoform 1 (NHERF1) was the first identified CFTR-binding protein. Here we further clarify the role of NHERF1 in the regulation of CFTR activity in two human bronchial epithelial cell lines: the normal, 16HBE14o-, and the homozygous DeltaF508 CFTR, CFBE41o-.

Serum albumin enhances polyethylenimine-mediated gene delivery to human respiratory epithelial cells.

Background: The interaction of polyethylenimine (PEI) polyplexes with proteins in cystic fibrosis (CF) airway secretions poses a significant hurdle to this nonviral delivery system. The aim of this study was to evaluate whether albumin may increase the efficiency of PEI complexes in mediating gene transfer into respiratory epithelial cells in the presence of CF mucus.

Methods: PEI (25 kDa) was complexed to DNA in the presence of human serum albumin (HSA) and used to transfect confluent A549 and 9HTEo- cells.

Expression pattern of the JAB1/CSN5 gene during murine embryogenesis: colocalization with NEDD8.

The COP9 signalosome (CSN) is a conserved multiprotein complex, with an important developmental role in several organisms, ranging from plants to mammalians. The influence of the CSN on several signaling and developmental processes has been ascribed to its ability to regulate degradation of a number of signaling proteins by the ubiquitin-proteasome system. The CSN controls the function of the SCF ubiquitin-ligase complex through an enzymatic activity that removes the small ubiquitin-like molecule NEDD8 from the cullin component of the SCF and that requires subunit 5 of the CSN (JAB1/CSN5).

Inhibition of nonviral cationic liposome-mediated gene transfer into primary human respiratory cells by interferon-gamma.

The effect of interferon (IFN) gamma on cationic liposome-mediated gene transfer into primary respiratory epithelial cells was investigated. Treatment of primary respiratory epithelial cells with IFN-gamma resulted in a dose-dependent increase in the intermediate filament cytokeratin 13 and a decrease in cellular proliferation, indicating that respiratory cells underwent squamous differentiation. IFN-gamma pretreatment resulted in a dramatic inhibition of transfection efficiency mediated by a cationic liposome (DOTAP).