Receptor-mediated activation of heterotrimeric guanine nucleotide-binding proteins (G proteins) results in the dissociation of alpha from beta gamma subunits, thereby allowing both to regulate effectors. Little is known about the regions of effectors required for recognition of G beta gamma. A peptide encoding residues 956 to 982 of adenylyl cyclase 2 specifically blocked G beta gamma stimulation of adenylyl cyclase 2, phospholipase C-beta 3, potassium channels, and beta-adrenergic receptor kinase as well as inhibition of calmodulin-stimulated adenylyl cyclases, but had no effect on interactions between G beta gamma and G alpha o. Substitutions in this peptide identified a functionally important motif, Gln-X-X-Glu-Arg, that is also conserved in regions of potassium channels and beta-adrenergic receptor kinases that participate in G beta gamma interactions. Thus, the region defined by residues 956 to 982 of adenylyl cyclase 2 may contain determinants important for receiving signals from G beta gamma.

These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

Red blood cell distribution width (RDW), a parameter that used to differentiate the type of anemia for several decades, recent studies suggest it was a prognostic factor in various types of cancer patients. However, the prognostic value of RDW in cancer patients remains controversial. Here, we performed a meta-analysis and systematic review to evaluate the prognostic value of RDW in cancer patients. Relevant studies were picked out from the databases of Web of Science, Embase, Pubmed and Cochrane Library. A total of 16 papers with 4267 patients were included in this meta-analysis, and the combined results indicated that elevated RDW was associated with poor over survival (OS) (HR = 1.47, 95%CI:1.29-1.66), poor cancer-specific survival (CSS) (HR = 1.46, 95%CI:1.08-1.85), poor disease-free survival (DFS) (HR = 1.91, 95%CI:1.27-2.56), poor event-free survival (EFS) (HR = 2.98, 95%CI:0.57-5.39) and poor progress-free survival (PFS) (HR = 3.21, 95%CI:0.33-6.75) after treatment. Furthermore, the similar results were observed in subgroup analysis stratified by cancer type, cutoff value of RDW, sample size and ethnicity. In conclusion, this meta-analysis demonstrated that RDW may be a potential prognostic marker in patients with cancer, and high RDW may also be associated with poor outcomes.

A BSTR ACTReceptors activate adenylyl cyclases through the G␣ s subunit. Previous studies from our laboratory have shown in certain cell types that express adenylyl cyclase 6 (AC6), heterologous desensitization included reduction of the capability of adenylyl cyclases to be stimulated by G␣ This region contains a conserved motif present in most adenylyl cyclases; however, the PKA phosphorylation site is unique to members of the AC6 family. These observations suggest a mechanism of how isoform selective regulatory diversity can be obtained within conserved regions involved in signal communication.Transmembrane signaling through the receptor-G s -adenylyl cyclase complex has long been studied as a model for signal transduction through heterotrimeric G proteins. Receptor activation of G s results in the dissociation of G␣ s from G␤␥, and the activated G␣ s stimulates adenylyl cyclase (1). Nine G␣ s -regulated adenylyl cyclases have currently been cloned, and the different isoforms of adenylyl cyclases are differentially regulated (2-4). One aspect of this differential regulation is their susceptibility to participate in heterologous desensitization. Previous studies from our laboratory have shown that in addition to receptor desensitization (5), the glucagonsensitive adenylyl cyclase can undergo desensitization at the level of G s (6) and adenylyl cyclase (7). Desensitization at the level of adenylyl cyclase is a cAMP-dependent process and was observed in hepatocytes and S49 lymphoma cells where a decrease in G␣ s -mediated adenylyl cyclase activities was seen. Cloning of adenylyl cyclase cDNAs from hepatocytes and S49 lymphoma cells indicated that adenylyl cyclase 6 (AC6) was present in both cells (7). We reasoned that the common sensitivity in hepatocytes and S49 cells of adenylyl cyclase activity to protein kinase A (PKA) could be caused by AC6. Hence we studied the effects of PKA on G␣ s regulation of AC6. MATERIALS AND METHODS Materials. [␣-32 P]ATP was from New England Nuclear. Purified catalytic subunit of PKA was purchased from Promega. Tissue culture reagents and fetal calf serum were from GIBCO. WIPTIDE and reagents for peptide synthesis were from Bachem. Anti-FLAG M2 column was from Kodak. All other reagents used were the highest grade available.Expression of Adenylyl Cyclases. AC1, AC2, and AC6 were tagged with the FLAG epitope at the N terminus. The FLAG tagged AC1 (8) and AC6 were constructed by using a strategy similar to that used for AC2 (9). The epitope-tagged adenylyl cyclases were expressed in Hi-5 cells by infection with recombinant baculovirus containing the required adenylyl cyclase insert. Hi-5 cells were infected with a multiplicity of 5-10, and membranes were prepared from infected cells 48 hrs after infection as described (9).PKA Treatment. Hi-5 cell membranes containing the recombinant adenylyl cyclase were treated for 15 min in a solution of 25 mM Tris⅐HCl, 10 mM MgCl 2 , 0.8 mM ATP, and protease inhibitor mixture (10) with and without 50-75 nM PKA catalytic subunit. After treatment the...

PURPOSE.Although eye dominance assessment is used to assist clinical decision-making, current understanding is limited by inconsistencies across the range of available tests. A new psychophysical test of sensory eye dominance has been developed that objectively measures the relative contribution of each eye to a fused suprathreshold binocular percept. METHODS. Six standard tests and the newly developed test were used to measure motor and sensory dominance in a group of 44 binocularly normal individuals (mean age, 29.5 Ϯ 9.10 years). The new test required observers to perform a motion coherence task under dichoptic viewing conditions, wherein a population of moving, luminance-defined signal (coherently moving) and noise (randomly moving) dots were presented separately to each eye. The observers judged the motion direction of the signal dots. Motion coherence thresholds were measured by varying the ratio of signal-to-noise dots, in a staircase procedure. RESULTS. The new dichoptic motion coherence threshold test revealed a clear bimodal distribution of sensory eye dominance strength, wherein the majority of the participants (61%) showed weak dominance, but a significant minority (39%) showed strong dominance. Subsequent analysis revealed that the strong-dominance group showed greater consistency across the range of traditional eye dominance tests used. CONCLUSIONS. This new quantitative dichoptic motion coherence threshold technique suggests that there are two separate sensory eye dominance strength distributions among observers with normal binocular vision: weak and strong eye dominance. This finding may provide a basis for clinical decision-making by indicating whether eye dominance is likely to be an important consideration in a particular patient. (Invest Ophthalmol Vis Sci. 2010;51:6875-6881)

Detecting and locating surface defects in textured materials is a crucial but challenging problem due to factors such as texture variations and lack of adequate defective samples prior to testing. In this paper we present a novel unsupervised method for automatically detecting defects in fabrics based on a deep convolutional generative adversarial network (DCGAN). The proposed method extends the standard DCGAN, which consists of a discriminator and a generator, by introducing a new encoder component. With the assistance of this encoder, our model can reconstruct a given query image such that no defects but only normal textures will be preserved in the reconstruction. Therefore, when subtracting the reconstruction from the original image, a residual map can be created to highlight potential defective regions. Besides, our model generates a likelihood map for the image under inspection where each pixel value indicates the probability of occurrence of defects at that location. The residual map and the likelihood map are then synthesized together to form an enhanced fusion map. Typically, the fusion map exhibits uniform gray levels over defect-free regions but distinct deviations over defective areas, which can be further thresholded to produce a binarized segmentation result. Our model can be unsupervisedly trained by feeding with a set of small-sized image patches picked from a few defect-free examples. The training is divided into several successively performed stages, each under an individual training strategy. The performance of the proposed method has been extensively evaluated by a variety of real fabric samples. The experimental results in comparison with other methods demonstrate its effectiveness in fabric defect detection.

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BackgroundCardiovascular disease (CVD) is the leading cause of global disease burden. Although stroke was thought to be more prevalent than coronary heart disease (CHD) in Chinese, the epidemic pattern might have been changed in some rural areas nowadays. This study was to estimate up-to-date prevalence of CVD and its risk factors in rural communities of Fangshan District, Beijing, China.MethodsA cross-sectional population survey was carried out by stratified cluster sampling. A total of 58,308 rural residents aged over 40 years were surveyed by face-to-face interview and physical examination during 2008 and 2010. The standardized prevalence was calculated according to adult sample data of China's 5th Population Census in 2000, and the adjusted prevalence odds ratio (POR) was calculated for the association of CHD/stroke with its cardiovascular risk factors in multivariate logistic regression models.ResultsAge- and sex-standardized prevalence was 5.6% for CHD (5.2% in males and 5.9% in females), higher than the counterpart of 3.7% (4.7% in males and 2.6% in females) for stroke. Compared with previous studies, higher prevalence of 7.7%, 47.2%, 53.3% in males and 8.2%, 44.8%, 60.7% in females for diabetes, hypertension and overweight/obesity were presented accordingly. Moreover, adjusted POR (95% confidence interval) of diabetes, obesity, stage 1 and stage 2 hypertension for CHD as 2.51 (2.29 to 2.75), 1.53 (1.38 to 1.70), 1.13 (1.02 to 1.26) and 1.35 (1.20 to 1.52), and for stroke as 2.24 (1.98 to 2.52), 1.25 (1.09 to 1.44), 1.44 (1.25 to 1.66) and 1.70 (1.46 to 1.98) were shown respectively in the multivariate logistic regression models.ConclusionsHigh prevalence of CVD and probably changed epidemic pattern in rural communities of Beijing, together with the prevalent cardiovascular risk factors and population aging, might cause public health challenges in rural Chinese population.