Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred CFTR-knockout mice

This article is available open access through the publisher’s website at the link below. Copyright © 2008 The American Society of Gene Therapy.Due to its early onset and severe prognosis, cystic fibrosis (CF) has been suggested as a candidate disease for in utero gene therapy. In 1997, a study was published claiming that to how transient prenatal expression of CF transmembrane conductance regulator (CFTR) from an in utero –injected adenovirus vector could achieve permanent reversal of the CF intestinal pathology in adult CF knockout mice, despite the loss of CFTR transgene expression by birth. This would imply that the underlying cause of CF is a prenatal defect for which lifelong cure can be achieved by transient prenatal expression of CFTR. Despite criticism at the time of publication, no independent verification of this contentious finding has been published so far. This is vital for the development of future therapeutic strategies as it may determine whether CF gene therapy should be performed prenatally or postnatally. We therefore reinvestigated this finding with an identical adenoviral vector and a knockout CF mouse line (CftrtmlCam) with a completely inbred genetic background to eliminate any effects due to genetic variation. After delivery of the CFTR-expressing adenovirus to the fetal mouse, both vector DNA and transgenic CFTR expression were detected in treated animals postpartum but statistically no significant difference in survival was observed between the Cftr–/– mice treated with the CFTR-adenovirus and those treated with the control vector.Sport Aiding Medical Research for Kids, the Cystic Fibrosis Trust, and the Katharine Dormandy Trust

Multi-Omics of Tomato Glandular Trichomes Reveals Distinct Features of Central Carbon Metabolism Supporting High Productivity of Specialized Metabolites

Glandular trichomes are metabolic cell factories with the capacity to produce large quantities of secondary metabolites. Little is known about the connection between central carbon metabolism and metabolic productivity for secondary metabolites in glandular trichomes. To address this gap in our knowledge, we performed comparative metabolomics, transcriptomics, proteomics, and (13)C-labeling of type VI glandular trichomes and leaves from a cultivated (Solanum lycopersicum LA4024) and a wild (Solanum habrochaites LA1777) tomato accession. Specific features of glandular trichomes that drive the formation of secondary metabolites could be identified. Tomato type VI trichomes are photosynthetic but acquire their carbon essentially from leaf sucrose. The energy and reducing power from photosynthesis are used to support the biosynthesis of secondary metabolites, while the comparatively reduced Calvin-Benson-Bassham cycle activity may be involved in recycling metabolic CO2 Glandular trichomes cope with oxidative stress by producing high levels of polyunsaturated fatty acids, oxylipins, and glutathione. Finally, distinct mechanisms are present in glandular trichomes to increase the supply of precursors for the isoprenoid pathways. Particularly, the citrate-malate shuttle supplies cytosolic acetyl-CoA and plastidic glycolysis and malic enzyme support the formation of plastidic pyruvate. A model is proposed on how glandular trichomes achieve high metabolic productivity

Validating the German Short Basic Psychological Need Satisfaction and Frustration Scale in Individuals with Depression

Satisfaction and frustration of the needs for autonomy, competence, and relatedness, as assessed with the 24-item Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS), have been found to be crucial indicators of individuals’ psychological health. To increase the usability of this scale within a clinical and health services research context, we aimed to validate a German short version (12 items) of this scale in individuals with depression including the examination of the relations from need frustration and need satisfaction to ill-being and quality of life (QOL). This cross-sectional study involved 344 adults diagnosed with depression (Mage (SD) = 47.5 years (11.1); 71.8% females). Confirmatory factor analyses indicated that the short version of the BPNSFS was not only reliable, but also fitted a six-factor structure (i.e., satisfaction/frustration X type of need). Subsequent structural equation modeling showed that need frustration related positively to indicators of ill-being and negatively to QOL. Surprisingly, need satisfaction did not predict differences in ill-being or QOL. The short form of the BPNSFS represents a practical instrument to measure need satisfaction and frustration in people with depression. Further, the results support recent evidence on the importance of especially need frustration in the prediction of psychopathology

Validating the German Short Basic Psychological Need Satisfaction and Frustration Scale in Individuals with Depression

Satisfaction and frustration of the needs for autonomy, competence, and relatedness, as assessed with the 24-item Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS), have been found to be crucial indicators of individuals’ psychological health. To increase the usability of this scale within a clinical and health services research context, we aimed to validate a German short version (12 items) of this scale in individuals with depression including the examination of the relations from need frustration and need satisfaction to ill-being and quality of life (QOL). This cross-sectional study involved 344 adults diagnosed with depression (Mage (SD) = 47.5 years (11.1); 71.8% females). Confirmatory factor analyses indicated that the short version of the BPNSFS was not only reliable, but also fitted a six-factor structure (i.e., satisfaction/frustration X type of need). Subsequent structural equation modeling showed that need frustration related positively to indicators of ill-being and negatively to QOL. Surprisingly, need satisfaction did not predict differences in ill-being or QOL. The short form of the BPNSFS represents a practical instrument to measure need satisfaction and frustration in people with depression. Further, the results support recent evidence on the importance of especially need frustration in the prediction of psychopathology