Collagen is the most abundant protein in mammals and provides the Abdominal Aortic Aneurysm (AAA) wall with mechanical strength, stiffness and toughness. Specifically, the spatial orientation of collagen fibers in the wall has a major impact on its mechanical properties. Apart from valuable micro-histological information, this data can be integrated by histomechanical constitutive models thought to improve biomechanical simulations, i.e. to improve the biomechanical rupture risk assessment of AAAs. Tissue samples (n=24) from the AAA wall were harvested during elective AAA repair, fixated, embedded, sectioned and investigated under Polarized Light Microscopy. The birefringent properties of collagen were reinforced by picrosirius red staining and the three-dimensional collagen fiber orientations were identified with a universal rotary stage. Two constitutive models for collagen fibers were used to integrate the identified structural information in a macroscopic AAA wall model. The collagen fiber orientation in the AAA wall was considerably dispersed and could be captured by a Bingham distribution function (κ(1)= 11.6, κ(2)= 907). The dispersion was much larger in the tangential plane than in the cross-sectional plane and no significant difference amongst medial and adventitial layers could be identified. The layered directional organization of collagen in normal aortas was not evident in the AAA. The identified collagen organization combined with constitutive descriptions of collagen fibers that depend on its orientation, explain the anisotropic (orthotropic) mechanical properties of the AAA wall. The mechanical properties of collagen fibers largely depend on their undulation, which is an important structural parameter and requires further experimental investigation.

A novel label-free electrochemical aptasensor based on graphene-polyaniline (GR-PANI) nanocomposites film for dopamine (DA) determination was reported. The resulting GR-PANI layer exhibited good current response for DA determination. The good electron transfer activity might be attributed to the effect of GR and PANI. The highly conductive and biocompatible nanostructure of GR-PANI nanocomposites was characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). To quantify the amount of DA, the peaks of square-wave voltammetry (SWV) were monitored using the redox couple of an [Fe(CN)(6)](4-/3-) probe. The electrochemical aptasensor showed a linear response to DA in the range 0.007-90nmol/L and a limit of detection of 0.00198nmol/L (S/N=3). The electrochemical aptasensor was successfully tested on human serum samples.

The clinical features of psoriasis, characterized by sharply demarcated scaly erythematous plaques, are typically so distinctive that a diagnosis can easily be made on these grounds alone. However, there is great variability in treatment response between individual patients, and this may reflect heterogeneity of inflammatory networks driving the disease. In this study, whole-genome transcriptional profiling was used to characterize inflammatory and cytokine networks in 62 lesional skin samples obtained from patients with stable chronic plaque psoriasis. We were able to stratify lesions according to their inflammatory gene expression signatures, identifying those associated with strong (37% of patients), moderate (39%) and weak inflammatory infiltrates (24%). Additionally, we identified differences in cytokine signatures with heightened cytokine-response patterns in one sub-group of lesions (IL-13-strong; 50%) and attenuation of these patterns in a second sub-group (IL-13-weak; 50%). These sub-groups correlated with the composition of the inflammatory infiltrate, but were only weakly associated with increased risk allele frequency at some psoriasis susceptibility loci (e.g., REL, TRAF3IP2 and NOS2). Our findings highlight variable points in the inflammatory and cytokine networks known to drive chronic plaque psoriasis. Such heterogeneous aspects may shape clinical course and treatment responses, and can provide avenues for development of personalized treatments.

Bile acids are synthesized from cholesterol and are major risk factors for Barrett adenocarcinoma (BAC) of the esophagus. Caveolin-1 (Cav1), a scaffold protein of membrane caveolae, is transcriptionally regulated by cholesterol via sterol-responsive element-binding protein-1 (SREBP1). Cav1 protects squamous epithelia by controlling cell growth and stabilizing cell junctions and matrix adhesion. Cav1 is frequently down-regulated in human cancers; however, the molecular mechanisms that lead to this event are unknown. We show that the basal layer of the nonneoplastic human esophageal squamous epithelium expressed Cav1 mainly at intercellular junctions. In contrast, Cav1 was lost in 95% of tissue specimens from BAC patients (n = 100). A strong cytoplasmic expression of Cav1 correlated with poor survival in a small subgroup (n = 5) of BAC patients, and stable expression of an oncogenic Cav1 variant (Cav1-P132L) in the human BAC cell line OE19 promoted proliferation. Cav1 was also detectable in immortalized human squamous epithelial, Barrett esophagus (CPC), and squamous cell carcinoma cells (OE21), but was low in BAC cell lines (OE19, OE33). Mechanistically, bile acids down-regulated Cav1 expression by inhibition of the proteolytic cleavage of 125-kDa pre-SREBP1 from the endoplasmic reticulum/Golgi apparatus and nuclear translocation of active 68-kDa SREBP1. This block in SREBP1's posttranslational processing impaired transcriptional activation of SREBP1 response elements in the proximal human Cav1 promoter. Cav1 was also down-regulated in esophagi from C57BL/6 mice on a diet enriched with 1%(wt/wt) chenodeoxycholic acid. Mice deficient for Cav1 or the nuclear bile acid receptor farnesoid X receptor showed hyperplasia and hyperkeratosis of the basal cell layer of esophageal epithelia, respectively. These data indicate that bile acid-mediated down-regulation of Cav1 marks early changes in the squamous epithelium, which may contribute to onset of Barrett esophagus metaplasia and progression to BAC.

Recent experiments on vesicles formed from block copolymers with liquid-crystalline side chains reveal a rich variety of vesicle morphologies. The additional internal order ("structure") developed by these self-assembled block copolymer vesicles can lead to significantly deformed vesicles as a result of the delicate interplay between two-dimensional ordering and vesicle shape. The inevitable topological defects in structured vesicles of spherical topology also play an essential role in controlling the final vesicle morphology. Here we develop a minimal theoretical model for the morphology of the membrane structure with internal nematic/smectic order. Using both analytic and numerical approaches, we show that the possible low free energy morphologies include nano-size cylindrical micelles (nano-fibers), faceted tetrahedral vesicles, and ellipsoidal vesicles, as well as cylindrical vesicles. The tetrahedral vesicle is a particularly fascinating example of a faceted liquid-crystalline membrane. Faceted liquid vesicles may lead to the design of supramolecular structures with tetrahedral symmetry and new classes of nano-carriers.

BACKGROUND Skin aging is associated with intrinsic processes that compromise the structure of the extracellular matrix while promoting loss of functional and regenerative capacity. These processes are accompanied by a large-scale shift in gene expression, but underlying mechanisms are not understood and conservation of these mechanisms between humans and mice is uncertain. RESULTS We used genome-wide expression profiling to investigate the aging skin transcriptome. In humans, age-related shifts in gene expression were sex-specific. In females, aging increased expression of transcripts associated with T-cells, B-cells and dendritic cells, and decreased expression of genes in regions with elevated Zeb1, AP-2 and YY1 motif density. In males, however, these effects were contrasting or absent. When age-associated gene expression patterns in human skin were compared to those in tail skin from CB6F1 mice, overall human-mouse correspondence was weak. Moreover, inflammatory gene expression patterns were not induced with aging of mouse tail skin, and well-known aging biomarkers were in fact decreased (e.g., Clec7a, Lyz1 and Lyz2). These unexpected patterns and weak human-mouse correspondence may be due to decreased abundance of antigen presenting cells in mouse tail skin with age. CONCLUSIONS Aging is generally associated with a pro-inflammatory state, but we have identified an exception to this pattern with aging of CB6F1 mouse tail skin. Aging therefore does not uniformly heighten inflammatory status across all mouse tissues. Furthermore, we identified both intercellular and intracellular mechanisms of transcriptome aging, including those that are sex- and species-specific.

Pathway-based analysis has been recently used in joint tests of association between disease and a group of common genetic variants. Here we explore this idea for the joint effects analysis of rare genetic variants and their association with quantitative traits and disease. We accumulate multiple rare minor alleles in a genetic risk score for each individual in a given pathway; this score is then used to assess association with quantitative phenotypes and disease. We demonstrate that this approach may be better than studying single rare variants or a gene risk score for identifying individuals with significantly greater risk.

INTRODUCTION : Combination of multiple biomarkers representing distinct aspects of tumor biology will have a better prognostic value. This study was to identify prognostic subgroups of colon adenocarcinoma by combined analysis of synuclein-gamma (SNCG), a human homologue of piwi (Hiwi), phosphatase of regenerating liver-3 (PRL-3), arrest-defective protein 1, homolog A (ARD1) and clinicopathologic features in 225 colon adenocarcinoma specimens. METHODS : Immunohistochemistry for 4 tumor markers was performed in whole tissue sections from 225 colon adenocarcinoma patients with complete clinicopathologic data and up to 10-year follow-up. The immunohistochemical expression patterns were examined individually and in multimarker combinations. Univariate and multivariate analyses were performed to identify independent predictive markers of poor outcome. RESULTS : With the tumor marker positive rate [32.0%(62/225) for SNCG; 76.9%(173/225) for combined SNCG/Hiwi/PRL-3/ARD1] and the detecting accuracy [61.9%(252/407) for SNCG; 82.6%(336/407) for combined SNCG/Hiwi/PRL-3/ARD1] increasing, incremental value of combined SNCG/Hiwi/PRL-3/ARD1 (P < 0.001; hazard ratios (HR), 3.2) to poor outcome was found. Stratified by lymph node, Hiwi alone (P = 0.004; HR, 3.2) led to poor outcome in patients without lymph node metastasis (LN-), and SNCG (P < 0.001; HR, 2.5) had independently poor prognostic value for patients with lymph node metastasis (LN+). CONCLUSIONS : Multimarker phenotypes improved tumor positive rate, detecting accuracy and prognostic value. In addition, a subgroup of more aggressive tumors can be identified by evaluating Hiwi level in LN- cancer, and SNCG level in LN+ cancer.

Highly ordered mesoporous Cr(2)O(3) materials with high specific surface area and narrow pore size distribution were successfully prepared by a vacuum assisted impregnation method. Both 2-dimensional hexagonal and 3-dimensional cubic Cr(2)O(3) mesoporous replicas from SBA-15 and KIT-6 templates exhibit enhanced performance for gas sensors and lithium ion batteries, compared to the bulk Cr(2)O(3) counterpart.

An imprinted electrochemical sensor based on polypyrrole-sulfonated graphene (PPy-SG)/hyaluronic acid-multiwalled carbon nanotubes (HA-MWCNTs) for sensitive detection of tryptamine was presented. Molecularly imprinted polymers (MIPs) were synthesized by electropolymerization using tryptamine as the template, and para-aminobenzoic acid (pABA) as the monomer. The surface feature of the modified electrode was characterized by cyclic voltammetry (CV). The proposed sensor was tested by chronoamperometry. Several important parameters controlling the performance of the molecularly imprinted sensor were investigated and optimized. The results showed that the PPy-SG composites films showed improved conductivity and electrochemical performances. HA-MWCNTs bionanocomposites could enhance the current response evidently. The good selectivity of the sensor allowed three discriminations of tryptamine from interferents, which include tyramine, dopamine and tryptophan. Under the optimal conditions, a linear ranging from 9.0×10(-8) mol L(-1) to 7.0×10(-5) mol L(-1) for the detection of tryptamine was observed with the detection limit of 7.4×10(-8) mol L(-1)(S/N=3). This imprinted electrochemical sensor was successfully employed to detect tryptamine in real samples.