Positional differences in the wound transcriptome of skin and oral mucosa

<p>Abstract</p> <p>Background</p> <p>When compared to skin, oral mucosal wounds heal rapidly and with reduced scar formation. Recent studies suggest that intrinsic differences in inflammation, growth factor production, levels of stem cells, and cellular proliferation capacity may underlie the exceptional healing that occurs in oral mucosa. The current study was designed to compare the transcriptomes of oral mucosal and skin wounds in order to identify critical differences in the healing response at these two sites using an unbiased approach.</p> <p>Results</p> <p>Using microarray analysis, we explored the differences in gene expression in skin and oral mucosal wound healing in a murine model of paired equivalent sized wounds. Samples were examined from days 0 to 10 and spanned all stages of the wound healing process. Using unwounded matched tissue as a control, filtering identified 1,479 probe sets in skin wounds yet only 502 probe sets in mucosal wounds that were significantly differentially expressed over time. Clusters of genes that showed similar patterns of expression were also identified in each wound type. Analysis of functionally related gene expression demonstrated dramatically different reactions to injury between skin and mucosal wounds. To explore whether site-specific differences might be derived from intrinsic differences in cellular responses at each site, we compared the response of isolated epithelial cells from skin and oral mucosa to a defined in vitro stimulus. When cytokine levels were measured, epithelial cells from skin produced significantly higher amounts of proinflammatory cytokines than cells from oral mucosa.</p> <p>Conclusions</p> <p>The results provide the first detailed molecular profile of the site-specific differences in the genetic response to injury in mucosa and skin, and suggest the divergent reactions to injury may derive from intrinsic differences in the cellular responses at each site.</p

Bridge Lessons Learned from the Wenchuan China, Earthquake

A strong earthquake of M7.9 occurred in Wenchuan County in Sichuan Province, China, on May 12, 2008. This paper presents the field observations on various types of bridge damages, including unseating of girders, longitudinal and transverse offset of decks, pounding at expansion joints, shear key failure, bearing displacement, column shear, and flexible cracks. Plausible causes of damages and collapses are discussed and the lessons learned from this event are briefly summarized. Some of the postearthquake temporary constructions are also reported

N-Terminal Pro–B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study

Background Contemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. Objectives This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. Methods Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (−) likelihood ratios (LRs) for acute HF. Results Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR− was 0.09 (95% CI: 0.05 to 0.13). Conclusions In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF

The trough-system algorithm and its application to spatial modeling of Greenland subglacial topography

This is the published version. Copyright 2014 Herzfeld et al.Dynamic ice-sheet models are used to assess the contribution of mass loss from the Greenland ice sheet to sea-level rise. Mass transfer from ice sheet to ocean is in a large part through outlet glaciers. Bed topography plays an important role in ice dynamics, since the acceleration from the slow-moving inland ice to an ice stream is in many cases caused by the existence of a subglacial trough or trough system. Problems are that most subglacial troughs are features of a scale not resolved in most ice-sheet models and that radar measurements of subglacial topography do not always reach the bottoms of narrow troughs. The trough-system algorithm introduced here employs mathematical morphology and algebraic topology to correctly represent subscale features in a topographic generalization, so the effects of troughs on ice flow are retained in ice-dynamic models. The algorithm is applied to derive a spatial elevation model of Greenland subglacial topography, integrating recently collected radar measurements (CReSIS data) of the Jakobshavn Isbræ, Helheim, Kangerdlussuaq and Petermann glacier regions. The resultant JakHelKanPet digital elevation model has been applied in dynamic ice-sheet modeling and sea-level-rise assessment

Suppression of non-small cell lung tumor development by the let-7 microRNA family

Many microRNAs (miRNAs) target mRNAs involved in processes aberrant in tumorigenesis, such as proliferation, survival, and differentiation. In particular, the let-7 miRNA family has been proposed to function in tumor suppression, because reduced expression of let-7 family members is common in non-small cell lung cancer (NSCLC). Here, we show that let-7 functionally inhibits non-small cell tumor development. Ectopic expression of let-7g in K-RasG12D-expressing murine lung cancer cells induced both cell cycle arrest and cell death. In tumor xenografts, we observed significant growth reduction of both murine and human non-small cell lung tumors when overexpression of let-7g was induced from lentiviral vectors. In let-7g expressing tumors, reductions in Ras family and HMGA2 protein levels were detected. Importantly, let-7g-mediated tumor suppression was more potent in lung cancer cell lines harboring oncogenic K-Ras mutations than in lines with other mutations. Ectopic expression of K-RasG12D largely rescued let-7g mediated tumor suppression, whereas ectopic expression of HMGA2 was less effective. Finally, in an autochthonous model of NSCLC in the mouse, let-7g expression substantially reduced lung tumor burden.</p

Suppression of non-small cell lung tumor development by the let-7 microRNA family

Many microRNAs (miRNAs) target mRNAs involved in processes aberrant in tumorigenesis, such as proliferation, survival, and differentiation. In particular, the let-7 miRNA family has been proposed to function in tumor suppression, because reduced expression of let-7 family members is common in non-small cell lung cancer (NSCLC). Here, we show that let-7 functionally inhibits non-small cell tumor development. Ectopic expression of let-7g in K-RasG12D-expressing murine lung cancer cells induced both cell cycle arrest and cell death. In tumor xenografts, we observed significant growth reduction of both murine and human non-small cell lung tumors when overexpression of let-7g was induced from lentiviral vectors. In let-7g expressing tumors, reductions in Ras family and HMGA2 protein levels were detected. Importantly, let-7g-mediated tumor suppression was more potent in lung cancer cell lines harboring oncogenic K-Ras mutations than in lines with other mutations. Ectopic expression of K-RasG12D largely rescued let-7g mediated tumor suppression, whereas ectopic expression of HMGA2 was less effective. Finally, in an autochthonous model of NSCLC in the mouse, let-7g expression substantially reduced lung tumor burden.</p

Activation of intestinal spinal afferent endings by changes in intra‐mesenteric arterial pressure

Author manuscript made available following 12 month embargo from date of publication (25 June 2015) in accordance with publisher copyright policy.KEY POINTS: A major class of mechano-nociceptors to the intestine have mechanotransduction sites on extramural and intramural arteries and arterioles ('vascular afferents'). These sensory neurons can be activated by compression or axial stretch of vessels. Using isolated preparations we showed that increasing intra-arterial pressure, within the physiological range, activated mechano-nociceptors on vessels in intact mesenteric arcades, but not in isolated arteries. This suggests that distortion of the branching vascular tree is the mechanical adequate stimulus for these sensory neurons, rather than simple distension. The same rises in pressure also activated intestinal peristalsis in a partially capsaicin-sensitive manner indicating that pressure-sensitive vascular afferents influence enteric circuits. The results identify the mechanical adequate stimulus for a major class of mechano-nociceptors with endings on blood vessels supplying the gut wall; these afferents have similar endings to ones supplying other viscera, striated muscle and dural vessels. ABSTRACT: Spinal sensory neurons innervate many large blood vessels throughout the body. Their activation causes the hallmarks of neurogenic inflammation: vasodilatation through the release of the neuropeptide calcitonin gene-related peptide and plasma extravasation via tachykinins. The same vasodilator afferent neurons show mechanical sensitivity, responding to crushing, compression or axial stretch of blood vessels - responses which activate pain pathways and which can be modified by cell damage and inflammation. In the present study, we tested whether spinal afferent axons ending on branching mesenteric arteries ('vascular afferents') are sensitive to increased intravascular pressure. From a holding pressure of 5 mmHg, distension to 20, 40, 60 or 80 mmHg caused graded, slowly adapting increases in firing of vascular afferents. Many of the same afferent units showed responses to axial stretch, which summed with responses evoked by raised pressure. Many vascular afferents were also sensitive to raised temperature, capsaicin and/or local compression with von Frey hairs. However, responses to raised pressure in single, isolated vessels were negligible, suggesting that the adequate stimulus is distortion of the arterial arcade rather than distension per se. Increasing arterial pressure often triggered peristaltic contractions in the neighbouring segment of intestine, an effect that was mimicked by acute exposure to capsaicin (1 μm) and which was reduced after desensitisation to capsaicin. These results indicate that sensory fibres with perivascular endings are sensitive to pressure-induced distortion of branched arteries, in addition to compression and axial stretch, and that they contribute functional inputs to enteric motor circuits

Style Separation and Synthesis via Generative Adversarial Networks

Style synthesis attracts great interests recently, while few works focus on its dual problem "style separation". In this paper, we propose the Style Separation and Synthesis Generative Adversarial Network (S3-GAN) to simultaneously implement style separation and style synthesis on object photographs of specific categories. Based on the assumption that the object photographs lie on a manifold, and the contents and styles are independent, we employ S3-GAN to build mappings between the manifold and a latent vector space for separating and synthesizing the contents and styles. The S3-GAN consists of an encoder network, a generator network, and an adversarial network. The encoder network performs style separation by mapping an object photograph to a latent vector. Two halves of the latent vector represent the content and style, respectively. The generator network performs style synthesis by taking a concatenated vector as input. The concatenated vector contains the style half vector of the style target image and the content half vector of the content target image. Once obtaining the images from the generator network, an adversarial network is imposed to generate more photo-realistic images. Experiments on CelebA and UT Zappos 50K datasets demonstrate that the S3-GAN has the capacity of style separation and synthesis simultaneously, and could capture various styles in a single model