Intestinal insulin/IGF1 signalling through FoxO1 regulates epithelial integrity and susceptibility to colon cancer.

Obesity promotes the development of insulin resistance and increases the incidence of colitis-associated cancer (CAC), but whether a blunted insulin action specifically in intestinal epithelial cells (IECs) affects CAC is unknown. Here, we show that obesity impairs insulin sensitivity in IECs and that mice with IEC-specific inactivation of the insulin and IGF1 receptors exhibit enhanced CAC development as a consequence of impaired restoration of gut barrier function. Blunted insulin signalling retains the transcription factor FOXO1 in the nucleus to inhibit expression of Dsc3, thereby impairing desmosome formation and epithelial integrity. Both IEC-specific nuclear FoxO1ADA expression and IEC-specific Dsc3 inactivation recapitulate the impaired intestinal integrity and increased CAC burden. Spontaneous colonic tumour formation and compromised intestinal integrity are also observed upon IEC-specific coexpression of FoxO1ADA and a stable Myc variant, thus suggesting a molecular mechanism through which impaired insulin action and nuclear FOXO1 in IECs promotes CAC.

[Analysis of the protein pattern in physiologic and pathologic vitreous bodies by electrophoresis and immunologic identification]. / Analyse des Proteinmusters in physiologischen und pathologischen Glaskörpern durch Elektrophorese und immunologische Identifizierung.

The protein composition of normal and pathological human vitreous was analyzed using gradient SDS-PAGE and western blot. By electroblotting and immunodetection, the presence of ten proteins was proven in the normal vitreous. The major proteins included: albumin, transferrin, alpha-1-antitrypsin, and immunoglobulin G. For the detection of a distinct protein in the vitreous, western blot analysis seems to be an appropriate method. Using densitometric analysis of silver-stained gels, we compared the protein pattern of post-mortem vitreous, surgically obtained samples (from proliferative vitreous-retinopathy, proliferative diabetic retinopathy, and macular pucker patients), and serum. The protein composition of the pathological intraocular fluid was uniform, but different from that of normal vitreous and serum. These results suggest that a breakdown of the blood-retina barrier is the main reason for the increase of soluble proteins in the vitreous cavity under pathological conditions. The methods described allow detailed analysis of the vitreous protein pattern in intraocular proliferative disorders with a small sample volume (10 microliters).

Cuticle Ultrastructure of Criconemella curvata and Criconemella sphaerocephala (Nemata: Criconematidae).

Cuticle ultrastructure of Criconemella curvata and C. sphaerocephala females is presented; males were available only in the second species. Ultrathin sections revealed three major zones: cortical, median, and basal. The cortical zone in the females consists of an external and internal layer. In C. curvata the external layer is trilaminate and at each annule it is covered by a multilayered cap. In C. sphaerocephala the trilaminate layer is lacking and the external cortical layer includes an osmophilic coating. In both species the internal layer consists of alternate striated and unstriated sublayers. The median zone is fibrous with a central lacuna and the zone is interrupted between the annules. The basal zone of the cuticle is striated and narrower between each annule. The cuticle of the C. sphaerocephala male is typical of Tylenchida, except under both lateral fields; the striated layer becomes forked at the first incisure and the innermost two prongs of the fork overlap each other, resulting in a continuous striated band.