Innervation of a prefabricated flap: a new experimental model.

Introduction. Flap innervation by neoaxonogenesis is a promising field of investigation. The authors evaluated the possibility of innervating an acellular collagen scaffold as component of a potential prefabricated flap. Materials and Methods. Collagen matrix sheets were implanted around the femoral bundle of a murine model to produce two flaps on proximal and distal nerve stumps based on a flow-through model. After thirty days, nerve regeneration and integration into the collagen matrix were evaluated. The specimens were microscopically analyzed to study Schwann cell colonization and axonal integration with the matrix. Axonal count and density were assessed and statistically evaluated. Results. Qualitative structural and ultrastructural evaluation indicated integration, with axonal fibers merged within the collagen matrix, along with a newly formed vascular network on the proximal flap. Wallerian degeneration occurred inside the distal chamber. Axonal count and density did not show statistically significant differences between the nerve inside the proximal flap and the control side. Conclusions. Innervation of an acellular matrix can be obtained by direct nerve stump implantation. The flow-through system was relatively easy to build and reliable to provide adequate blood supply. The collagen scaffold may be a promising support or further studies of preinnervated microsurgical flaps

On the Temperature Dependence of the Shear Viscosity and Holography

We examine the structure of the shear viscosity to entropy density ratio eta/s in holographic theories of gravity coupled to a scalar field, in the presence of higher derivative corrections. Thanks to a non-trivial scalar field profile, eta/s in this setup generically runs as a function of temperature. In particular, its temperature behavior is dictated by the shape of the scalar potential and of the scalar couplings to the higher derivative terms. We consider a number of dilatonic setups, but focus mostly on phenomenological models that are QCD-like. We determine the geometric conditions needed to identify local and global minima for eta/s as a function of temperature, which translate to restrictions on the signs and ranges of the higher derivative couplings. Finally, such restrictions lead to an holographic argument for the existence of a global minimum for eta/s in these models, at or above the deconfinement transition.Comment: references adde

Acetylated histone variant H2A.Z is involved in the activation of neo-enhancers in prostate cancer.

Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodeled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Altogether these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer

Migraine aura: retracting particle-like waves in weakly susceptible cortex

Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]<1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]>>1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale

Helical Chirality: a Link between Local Interactions and Global Topology in DNA

DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

Induction of lung lesions in Wistar rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate

<p>Abstract</p> <p>Background</p> <p>The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by suitable laboratory animal models, such as animals treated with the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the current study, we established a novel lung cancer model in Wistar rats treated with NNK. Using this model, we assessed the effects of two chemopreventive agents, aspirin and phenethyl isothiocyanate (PEITC), on tumor progression.</p> <p>Methods</p> <p>First, rats were treated with a single-dose of NNK by intratracheal instillation; control rats received iodized oil. The animals were then sacrificed on the indicated day after drug administration and examined for tumors in the target organs. PCNA, p63 and COX-2 expression were analyzed in the preneoplastic lung lesions. Second, rats were treated with a single-dose of NNK (25 mg/kg body weight) in the absence or presence of aspirin and/or PEITC in the daily diet. The control group received only the vehicle in the regular diet. The animals were sacrificed on day 91 after bronchial instillation of NNK. Lungs were collected and processed for histopathological and immunohistochemical assays.</p> <p>Results</p> <p>NNK induced preneoplastic lesions in lungs, including 33.3% alveolar hyperplasia and 55.6% alveolar atypical dysplasia. COX-2 expression increased similarly in alveolar hyperplasia and alveolar atypical dysplasia, while PCNA expression increased more significantly in the latter than the former. No p63 expression was detected in the preneoplastic lesions. In the second study, the incidences of alveolar atypical dysplasia were reduced to 10%, 10% and 0%, respectively, in the aspirin, PEITC and aspirin and PEITC groups, compared with 62.5% in the carcinogen-treated control group. COX-2 expression decreased after dietary aspirin or aspirin and PEITC treatment. PCNA expression was significantly reduced in the aspirin and PEITC group.</p> <p>Conclusion</p> <p>(1) A single dose of 25 mg/kg body weight NNK by intratracheal instillation is sufficient to induce preneoplastic lesions in Wistar rat lungs. (2) COX-2 takes part in NNK-induced tumorigenesis but is not involved in proliferation. (3) Aspirin and PEITC have protective effects in the early stages of tumor progression initiated by NNK.</p

Response of lymphocyte subsets and cytokines to Shenyang prescription in Sprague-Dawley rats with tongue squamous cell carcinomas induced by 4NQO

BACKGROUND: The study was designed to investigate immunocompetence in relation to cancer progression in rat and to assess the effect of the traditional Chinese anti-cancer medicine, "Shenyang" prescription, on immunity. METHODS: 4-Nitroquinoline-1-oxide (4NQO) was administered to 80 Sprague-Dawley (SD) rats via the drinking water for up to 36 weeks. Tongue squamous cell carcinoma (SCC) was confirmed by pathological examination in 61 rats. "Shenyang" prescription was administered to subgroups of these rats, and blood samples were taken before and after treatment. Lymphocyte subsets were determined by flow cytometry. Serum Th1 and Th2-type cytokines were assessed by an enzyme-linked immunosorbent assay. RESULTS: As the cancer progressed at the tongue root, the percentage of CD3+CD4+ T lymphocytes and NK cells and the levels of IFN-γ and IL-2 decreased gradually, while the percentage of CD3+CD8+ T lymphocytes and the levels of IL-4 and IL-10 increased. The CD4+/CD8+ ratios were lower in the cancer groups than in the control group. However, after administering "Shenyang" prescription, the levels of CD3+CD4+ T lymphocytes, NK cells, IFN-γ and IL-2 increased, while the CD3+CD8+ T lymphocyte counts and the levels of IL-4 and IL-10 decreased. CONCLUSION: 4NQO-induced lesions were good models for exploring oral cavity carcinogenesis. The rats with 4NQO-induced SCC demonstrated abnormalities in lymphocyte subsets and a shift from Th1-type to Th2-type, which were good models for assessing the effect of anticancer agent on immunity. Oral cancer progression was associated with an aggressive disturbance of immune function. "Shenyang" prescription has the ability to improve the disturbance of immune function

Immunoassays Based on Penicillium marneffei Mp1p Derived from Pichia pastoris Expression System for Diagnosis of Penicilliosis

BACKGROUND: Penicillium marneffei is a dimorphic fungus endemic in Southeast Asia. It can cause fatal penicilliosis in humans, particularly in HIV-infected people. Diagnosis of this infection is difficult because its clinical manifestations are not distinctive. Specialized laboratory tests are necessary to establish a definitive diagnosis for successful management. We have demonstrated previously that a cell wall mannoprotein Mp1p, abundant in P. marneffei, is a potential biomarker for diagnosis of P. marneffei infections. In the present study, we describe immunoassays based on Mp1p derived from the yeast Pichia pastoris expression system. METHODOLOGY/PRINCIPAL FINDINGS: We generated monoclonal antibodies (MAbs) and rabbit polyclonal antibodies (PAbs) against Mp1p expressed in P. pastoris. Subsequently, we developed two Mp1p antigen capture ELISAs which employed MAbs for both the capture and detecting antibodies (MAb-MAb pair) or PAbs and MAbs as the capture and detecting antibodies (PAbs-MAb pair) respectively. The two Mp1p antigen ELISAs detected Mp1p specifically in cultures of P. marneffei yeast phase at 37-40 degrees C and had no cross-reaction with other tested pathogenic fungi. The sensitivities and specificities of the two antigen assays were found to be 55% (11/20) and 99.6% (538/540) for MAb-MAb Mp1p ELISA, and 75% (15/20) and 99.4% (537/540) for PAbs-MAb Mp1p ELISA performed using 20 sera with culture-confirmed penicilliosis, and 540 control sera from 15 other mycosis patients and 525 healthy donors. Meanwhile, we also developed an anti-Mp1p IgG antibody ELISA with an evaluated sensitivity of 30% (6/20) and a specificity of 98.5% (532/540) using the same sera. Furthermore, combining the results of Mp1p antigen and antibody detection improved the sensitivity of diagnosis to 100% (20/20). CONCLUSIONS/SIGNIFICANCE: Simultaneous detection of antigen and antibody using the immunoassays based on Mp1p derived from P. pastoris greatly improves detection sensitivity. The procedures should be useful for the routine diagnosis of penicilliosis.published_or_final_versio

Detection and Phylogenetic Analysis of Wolbachia in the Asiatic Rice Leafroller, Cnaphalocrocis medinalis, in Chinese Populations

Wolbachia are a group of intracellular inherited endosymbiontic bacteria infecting a wide range of insects. In this study the infection status of Wolbachia (Rickettsiales: Rickettsiaceae) was measured in the Asiatic rice leafroller, Cnaphalocrocis medinalis (Guenée) (Lepidoptera: Pyralidae), from twenty locations in China by sequencing wsp, ftsZ and 16S rDNA genes. The results showed high infection rates of Wolbachia in C. medinalis populations. Wolbachia was detected in all geographically separate populations; the average infection rate was ∼ 62.5%, and the highest rates were 90% in Wenzhou and Yangzhou populations. The Wolbachia detected in different C. medinalis populations were 100% identical to each other when wsp, ftsZ, and 16S rDNA sequences were compared, with all sequences belonging to the Wolbachia B supergroup. Based on wsp, ftsZ and 16S rDNA sequences of Wolbachia, three phylogenetic trees of similar pattern emerged. This analysis indicated the possibility of inter-species and intra-species horizontal transmission of Wolbachia in different arthropods in related geographical regions. The migration route of C. medinalis in mainland China was also discussed since large differentiation had been found between the wsp sequences of Chinese and Thai populations

Novel molecular approach to define pest species status and tritrophic interactions from historical Bemisia specimens

Museum specimens represent valuable genomic resources for understanding host-endosymbiont/parasitoid evolutionary relationships, resolving species complexes and nomenclatural problems. However, museum collections suffer DNA degradation, making them challenging for molecular-based studies. Here, the mitogenomes of a single 1912 Sri Lankan Bemisia emiliae cotype puparium, and of a 1942 Japanese Bemisia puparium are characterised using a Next-Generation Sequencing approach. Whiteflies are small sap-sucking insects including B. tabaci pest species complex. Bemisia emiliae’s draft mitogenome showed a high degree of homology with published B. tabaci mitogenomes, and exhibited 98–100% partial mitochondrial DNA Cytochrome Oxidase I (mtCOI) gene identity with the B. tabaci species known as Asia II-7. The partial mtCOI gene of the Japanese specimen shared 99% sequence identity with the Bemisia ‘JpL’ genetic group. Metagenomic analysis identified bacterial sequences in both Bemisia specimens, while hymenopteran sequences were also identified in the Japanese Bemisia puparium, including complete mtCOI and rRNA genes, and various partial mtDNA genes. At 88–90% mtCOI sequence identity to Aphelinidae wasps, we concluded that the 1942 Bemisia nymph was parasitized by an Eretmocerus parasitoid wasp. Our approach enables the characterisation of genomes and associated metagenomic communities of museum specimens using 1.5 ng gDNA, and to infer historical tritrophic relationships in Bemisia whiteflies.© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. The attached file is the published pdf