Deregulation of Neuro-Developmental Genes and Primary Cilium Cytoskeleton Anomalies in iPSC Retinal Sheets from Human Syndromic Ciliopathies.

Ciliopathies are heterogeneous genetic diseases affecting primary cilium structure and function. Meckel-Gruber (MKS) and Bardet-Biedl (BBS) syndromes are severe ciliopathies characterized by skeletal and neurodevelopment anomalies, including polydactyly, cognitive impairment, and retinal degeneration. We describe the generation and molecular characterization of human induced pluripotent stem cell (iPSC)-derived retinal sheets (RSs) from controls, and MKS (TMEM67) and BBS (BBS10) cases.

Three dimensional analysis of brace biomechanical efficacy for patients with AIS.

Purpose: Corrective three dimensional (3D) effect of different braces is debatable. We evaluated differences in in-brace radiographic correction comparing a custom thoracic-lumbo-sacral-orthosis (TLSO) (T) brace to a Chêneau type TLSO (C) brace using 3D EOS reconstruction technology. Our primary research question was the 3D effect of brace on the spine and in particularly the apical vertebra rotation (AVR).

Uropathogenic Escherichia coli infection: potential importance of epigenetics.

Patients suffering from recurrent urinary tract infections (UTIs) may be maintained on antibiotic prophylaxis, or even treated by surgery. However, there are no biological data on which to base such treatment selection for the individual patient. This highlights the need for a biological marker that might predict UTI recurrence risk.

Modifier gene studies to identify new therapeutic targets in cystic fibrosis.

Since the discovery of the CFTR gene mutations which cause cystic fibrosis (CF) in 1989 the average life expectancy of CF patients has almost doubled and now exceeds 37 years. The advances in molecular diagnostics and medical treatments expanded beyond the CF patient population as some of the newest treatments are also being tested for treatment of complex diseases such as COPD and other inherited disorders. Rapid development of CF therapeutics is important for the cystic fibrosis community and is an excellent example for other nonprofit organizations, disease foundations and pharmaceutical companies alike.

Cell surface dynamics of CFTR: the ins and outs.

Ganeshan et al. (Biochem Biophys. Acta 1173 (2007) 192-200) recent study documents the effect of N-WASP inhibition and actin cytoskeleton disruption on the constitutive internalization and recycling of the cystic fibrosis transmembrane conductance regulator (CFTR) channel.

Intracellular routing of plasmid DNA during non-viral gene transfer.

Gene transfer using non-viral vectors is a promising approach for the safe delivery of therapeutic DNA in genetic and acquired human diseases. Whereas the lack of specific immune response favors the use of plasmid-cationic polymer complexes, the limited efficacy and short duration of transgene expression impose major hurdles in the application of non-viral gene delivery techniques. Here, we review the major cellular, metabolic and physico-chemical impediments that non-viral vectors encounter before plasmid DNA enters the nucleus.

Intracellular barriers to non-viral gene transfer.

Non-viral vector mediated gene transfer, compared to viral vector mediated one, is a promising tool for the safe delivery of therapeutic DNA in genetic and acquired human diseases. Although the lack of specific immune response favor the clinical application of non-viral vectors, comprising of an expression cassette complexed to cationic liposome or cationic polymer, the limited efficacy and short duration of transgene expression impose major hurdles in the widespread application of non-viral gene therapy. The trafficking of transgene, complexed with chemical vectors, has been the subject of intensive investigations to improve our understanding of cellular and extracellular barriers impeding gene delivery.