A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus

Cell-cell contacts play a vital role in intracellular signaling, although the molecular mechanisms of these signaling pathways are not fully understood. E-cadherin, an important mediator of cell-cell adhesions, has been shown to be cleaved by γ-secretase. This cleavage releases a fragment of E-cadherin, E-cadherin C-terminal fragment 2 (E-cad/CTF2), into the cytosol. Here, we study the fate and function of this fragment. First, we show that coexpression of the cadherin-binding protein, p120 catenin (p120), enhances the nuclear translocation of E-cad/CTF2. By knocking down p120 with short interfering RNA, we also demonstrate that p120 is necessary for the nuclear localization of E-cad/CTF2. Furthermore, p120 enhances and is required for the specific binding of E-cad/CTF2 to DNA. Finally, we show that E-cad/CTF2 can regulate the p120-Kaiso-mediated signaling pathway in the nucleus. These data indicate a novel role for cleaved E-cadherin in the nucleus

Studying Cat (Felis catus) Diabetes: Beware of the Acromegalic Imposter

Naturally occurring diabetes mellitus (DM) is common in domestic cats (Felis catus). It has been proposed as a model for human Type 2 DM given many shared features. Small case studies demonstrate feline DM also occurs as a result of insulin resistance due to a somatotrophinoma. The current study estimates the prevalence of hypersomatotropism or acromegaly in the largest cohort of diabetic cats to date, evaluates clinical presentation and ease of recognition. Diabetic cats were screened for hypersomatotropism using serum total insulin-like growth factor-1 (IGF-1; radioimmunoassay), followed by further evaluation of a subset of cases with suggestive IGF-1 (>1000 ng/ml) through pituitary imaging and/ or histopathology. Clinicians indicated pre-test suspicion for hypersomatotropism. In total 1221 diabetic cats were screened; 319 (26.1%) demonstrated a serum IGF-1>1000 ng/ml (95% confidence interval: 23.6-28.6%). Of these cats a subset of 63 (20%) underwent pituitary imaging and 56/63 (89%) had a pituitary tumour on computed tomography; an additional three on magnetic resonance imaging and one on necropsy. These data suggest a positive predictive value of serum IGF-1 for hypersomatotropism of 95% (95% confidence interval: 90-100%), thus suggesting the overall hypersomatotropism prevalence among UK diabetic cats to be 24.8% (95% confidence interval: 21.2-28.6%). Only 24% of clinicians indicated a strong pre-test suspicion; most hypersomatotropism cats did not display typical phenotypical acromegaly signs. The current data suggest hypersomatotropism screening should be considered when studying diabetic cats and opportunities exist for comparative acromegaly research, especially in light of the many detected communalities with the human disease

Quorum Sensing in \u3ci\u3eCandida albicans\u3c/i\u3e: Probing Farnesol’s Mode of Action with 40 Natural and Synthetic Farnesol Analogs

The dimorphic fungus Candida albicans produces extracellular farnesol (3,7, 11-trimethyl-2,6,10-dodecatriene- 1-ol) which acts as a quorum-sensing molecule (QSM) to suppress filamentation. Of four possible geometric isomers of farnesol, only the E,E isomer possesses QSM activity. We tested 40 natural and synthetic analogs of farnesol for their activity in an N-acetylglucosamine-induced differentiation assay for germ tube formation (GTF). Modified structural features include the head group, chain length, presence or absence of the three double bonds, substitution of a backbone carbon by S, O, N, and Se heteroatoms, presence or absence of a 3-methyl branch, and the bulkiness of the hydrophobic tail. Of the 40 compounds, 22 showed QSM activity by their ability to reduce GTF by 50%. However, even the most active of the analogs tested had only 7.3% of the activity of E,E-farnesol. Structure-activity relationships were examined in terms of the likely presence in C. albicans of a farnesol binding receptor protein. Includes supplemental material

Patterned Irradiation of YBa_2Cu_3O_(7-x) Thin Films

We present a new experiment on YBa_2Cu_3O_{7-x} (YBCO) thin films using spatially resolved heavy ion irradiation. Structures consisting of a periodic array of strong and weak pinning channels were created with the help of metal masks. The channels formed an angle of +/-45 Deg with respect to the symmetry axis of the photolithographically patterned structures. Investigations of the anisotropic transport properties of these structures were performed. We found striking resemblance to guided vortex motion as it was observed in YBCO single crystals containing an array of unidirected twin boundaries. The use of two additional test bridges allowed to determine in parallel the resistivities of the irradiated and unirradiated parts as well as the respective current-voltage characteristics. These measurements provided the input parameters for a numerical simulation of the potential distribution of the Hall patterning. In contrast to the unidirected twin boundaries in our experiment both strong and weak pinning regions are spatially extended. The interfaces between unirradiated and irradiated regions therefore form a Bose-glass contact. The experimentally observed magnetic field dependence of the transverse voltage vanishes faster than expected from the numerical simulation and we interpret this as a hydrodynamical interaction between a Bose-glass phase and a vortex liquid.Comment: 7 pages, 8 Eps figures included. Submitted to PR

Evaluation of semiautomated internal carotid artery stenosis quantification from 3-dimensional contrast-enhanced magnetic resonance angiograms

Rationale and Objectives: The performance of a semiautomatic technique for internal carotid artery (ICA) stenosis quantification of the internal carotid artery in contrast-enhanced magnetic resonance angiography was evaluated. Materials and Methods: The degree of stenosis of 52 ICAs was quantified by measuring the cross-sectional area along the center lumen line. This was performed both by 3 independent observers and the semiautomated method. The degree of stenosis was defined as the amount of cross-sectional lumen reduction. Results: Agreement between the method and observers was good (weighted-kappa, kappa(w) = 0.89). Reproducibility of measurements of the semiautomated technique was better (kappa(w) = 0.97) than that of the observers (kappa(w) = 0.76), and the evaluated technique was considerably less time-consuming. Conclusions: Because the user interaction is limited, this technique can be used to replace an expert observer in 3-dimensional stenosis quantification of the ICA at CE-MRA in clinical practice