Detection of pathological response of axillary lymph node metastasis after neoadjuvant chemotherapy in breast cancer using multiphoton microscopy

Neoadjuvant treatment is often considered in breast cancer patients with axillary lymph node involvement, but most of patients do not have a pathologic complete response to therapy. The detection of residual nodal disease has a significant impact on adjuvant therapy recommendations which may improve survival. Here, we investigate whether multiphoton microscopy (MPM) could identify the pathological changes of axillary lymphatic metastasis after neoadjuvant chemotherapy in breast cancer. And furthermore, we find that there are obvious differences in seven collagen morphological features between normal node and residual axillary disease by combining with a semi-automatic image processing method, and also find that there are significant differences in four collagen features between the effective and no-response treatment groups. These research results indicate that MPM may help estimate axillary treatment response in the neoadjuvant setting and thereby tailor more appropriate and personalized adjuvant treatments for breast cancer patients.     

miR-155 inhibits the formation of hypertrophic scar fibroblasts by targeting HIF-1α via PI3K/AKT pathway

Hypertrophic scar (HS) is a serious skin fibrotic disease characterized by the excessive proliferation of fibroblasts and often considered as a kind of benign skin tumor. microRNA-155 (miR-155) is usually served as a promising marker in antitumor therapy. In view of the similarities of hypertrophic scar and tumor, it is predicted that miR-155 may be a novel therapeutic target in clinical trials. Here we found the expression levels of miR-155 was gradually down regulated and HIF-1α was upregulated in HS tissue and HS derived fibroblasts (HFs). And cell proliferation was inhibited when miR-155 was overexpressed or HIF-1α was silenced. Moreover, overexpression of miR-155 in HFs could reduce the expression of collagens in vitro and inhibit the collagen fibers arrangement in vivo, whereas miR-155 knockdown gave opposite results. Furthermore, we found that miR-155 directly targeted the HIF-1α, which could also independently inhibit the expression of collagens in vitro and obviously improved the appearance and architecture of the rabbit ear scar in vivo when it was silencing. Finally, we found that PI3K/AKT pathway was enrolled in these processes. Together, our results indicated that miR-155 was a critical regulator in the formation and development of hypertrophic scar and might be a potential molecular target for hypertrophic scar therapy.     

Geologic events coupled with Pleistocene climatic oscillations drove genetic variation of Omei treefrog (Rhacophorus omeimontis) in southern China

Collagens provide structural support and guidance cues within the extracellular matrix of metazoans. Mammalian collagens XIII, XXIII and XXV form a unique subgroup of type II transmembrane proteins, each comprising a short N-terminal cytosolic domain, a transmembrane domain and a largely collagenous ectodomain. We name these collagens as MACITs (Membrane-Associated Collagens with Interrupted Triple-helices), and here investigate their evolution and conserved properties. To date, these collagens have been studied only in mammals. Knowledge of the representation of MACITs in other extant metazoans is lacking. This question is of interest for understanding structural/functional relationships in the MACIT family and also for insight into the evolution of MACITs in relation to the secreted, fibrillar collagens that are present throughout the metazoa. MACITs are restricted to bilaterians and are represented in the Ecdysozoa, Hemichordata, Urochordata and Vertebrata (Gnathostomata). They were not identified in available early-diverging metazoans, Lophotrochozoa, Echinodermata, Cephalochordata or Vertebrata (Cyclostomata). Whereas invertebrates encode a single MACIT, collagens XIII/XXIII/XXV of jawed vertebrates are paralogues that originated from the two rounds of en-bloc genome duplication occurring early in vertebrate evolution. MACITs have conserved domain architecture in which a juxta-membrane furin-cleavage site and the C-terminal 34 residues are especially highly conserved, whereas the cytoplasmic domains are weakly conserved. To study protein expression and function in a metazoan with a single MACIT gene, we focused on Caenorhabditis elegans and its col-99 gene. A col-99 cDNA was cloned and expressed as protein in mammalian CHO cells, two antibodies against COL-99 protein were generated, and a col-99-bearing fosmid gene construct col-99::egfp::flag was used to generate transgenic C. elegans lines. The encoded COL-99 polypeptide is 85 kDa in size and forms a trimeric protein. COL-99 is plasma membrane-associated and undergoes furin-dependent ectodomain cleavage and shedding. COL-99 is detected in mouth, pharynx, body wall and the tail, mostly in motor neurons and muscle systems and is enriched at neuromuscular junctions. Through identification of MACITs in multiple metazoan phyla we developed a model for the evolution of MACITs. The experimental data demonstrate conservation of MACIT molecular and cellular properties and tissue localisations in the invertebrate, C. elegans.     

A New Hyperspectral Index for Estimating Copper Content in an Indicative Plant for the Exploration of Copper Deposit

Journal of Plant Growth Regulation - With the rapid development of hyperspectral technology, estimating metal content in plants by establishing the relationship between vegetation indices and metal...     

The glycoside hydrolase 28 member VdEPG1 is a virulence factor of Verticillium dahliae and interacts with the jasmonic acid pathway-related gene GhOPR9

Glycoside hydrolase (GH) family members act as virulence factors and regulate plant immune responses during pathogen infection. Here, we characterized the GH28 family member endopolygalacturonase VdEPG1 in Verticillium dahliae. VdEPG1 acts as a virulence factor during V. dahliae infection. The expression level of VdEPG1 was greatly increased in V. dahliae inoculated on cotton roots. VdEPG1 suppressed VdNLP1-mediated cell death by modulating pathogenesis-related genes in Nicotiana benthamiana. Knocking out VdEPG1 led to a significant decrease in the pathogenicity of V. dahliae in cotton. The deletion strains were more susceptible to osmotic stress and the ability of V. dahliae to utilize carbon sources was deficient. In addition, the deletion strains lost the ability to penetrate cellophane membrane, with mycelia showing a disordered arrangement on the membrane, and spore development was affected. A jasmonic acid (JA) pathway-related gene, GhOPR9, was identified as interacting with VdEPG1 in the yeast two-hybrid system. The interaction was further confirmed by bimolecular fluorescence complementation and luciferase complementation imaging assays in N. benthamiana leaves. GhOPR9 plays a positive role in the resistance of cotton to V. dahliae by regulating JA biosynthesis. These results indicate that VdEPG1 may be able to regulate host immune responses as a virulence factor through modulating the GhOPR9-mediated JA biosynthesis.     

Light Trapping Effect in Wing Scales of Butterfly Papilio peranthus and Its Simulations

Broadband light trapping effect and arrays of sub-wavelength textured structures based on the butterfly wing scales are applicable to solar cells and stealth technologies. In this paper, the fine optical structures in wing scales of butterfly Papilio peranthus, exhibiting efficient light trapping effect, were carefully examined. First, the reflectivity was measured by reflectance spectrum. Field Emission Scanning Electronic Microscope (FESEM) and Transmission Electron Microscope (TEM) were used to observe the coupling morphologies and structures of the scales. Then, the optimized 3D model of the coupling structure was created combining Scanning Electron Microscope (SEM) and TEM data. Afterwards, the mechanism of the light trapping effect of these structures was analyzed by simulation and theoretical calculations. A multilayer nano-structure of chitin and air was found. These structures are effective in increasing optical path, resulting in that most of the incident light can be trapped and adsorbed within the structure at last. Furthermore, the simulated optical results are consistent with the experimental and calculated ones. This result reliably confirms that these structures induce an efficient light trapping effect. This work can be used as a reference for in-depth study on the fabrication of highly efficient bionic optical devices, such as solar cells, photo detectors, high-contrast, antiglare, and so forth.     

Evaluation of the Association Between CD143 Gene Polymorphism and Psoriasis

Increased CD143 activity has been detected in various skin tissues, and this increase is partially caused by the intronic ID polymorphism. The genetic contribution of CD143 ID polymorphism to the progression of psoriasis, the commonest skin disease, has been extensively investigated, but reported with inconsistent results. The aim of this work was to gain new insights to shed light on the association between CD143 ID polymorphism and psoriasis risk. We systematically identified the studies examining the association of CD143 ID polymorphism with psoriasis risk. A meta-analysis combining data from all eligible studies was carried out. To evaluate the genetic association, we calculated odds ratio (OR) and its 95 % confidence intervals (CIs) for both genotypic models and allelic model. The final pooling dataset comprised ten studies. Meta-analysis of total samples did not suggest a notable association with psoriasis risk. However, subgroup analysis by ethnicity revealed a statistically significant association in East Asian samples (DD + ID vs. II: OR 0.86, 95 % CI 0.75–0.99, P_{heterogeneity} = 0.970; DD vs. ID: OR 0.85, 95 % CI 0.73–0.99, P_{heterogeneity} = 0.868; D vs. I: OR 0.86, 95 % CI 0.76–0.97, P_{heterogeneity} = 0.994). This meta-analysis demonstrated that the presence of CD143 ID polymorphism may modify the risk of psoriasis in individuals with East Asian ancestry.     

A Nuclear Export Signal Is Required for cGAS to Sense Cytosolic DNA

1. Download : Download high-res image (127KB)
2. Download : Download full-size image

     

Cyclopeptides design as blockers against HCV p7 channel in silico

ABSTRACT

The protein p7 in the hepatitis C virus (HCV) is a 63-residue transmembrane protein that oligomerizes to form an ion channel with cation selectivity. This protein is essential for the assembly and release of infectious viral particles. Structural analysis indicates that the bottleneck of the p7 hexamer channel is located on Asparagines at position 9 in the conical region with a pore radius of 3.9?Å, which is reduced to nearly 3.0?Å upon protonation. Amantadine and BIT225 binds in the hydrophobic pocket on the lipid-facing side of the p7 channel as allosteric inhibitors to stabilise the channel pore in a closed conformation. Here, we designed a series of cyclopeptides as inner channel blockers in the conical region based on chemical and physical characteristics of the channel bottleneck for the HCV p7 protein. As a result, cyclic-4-Asp is found to bind in the channel lumen between the gating residues Ile6 and Asn9 with a favourable binding affinity, perfectly fitting with the hydrophobic pocket in the conical region. Compared with amantadine and BIT225, we believe that the cylcopeptides have potential to be effective inhibitors against HCV p7 protein.