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Find video protocols related to scientific articles indexed in Pubmed.
Effects of gabexate mesilate on coagulopathy and organ dysfunction in rats with endotoxemia: a potential use of thrombelastography in endotoxin-induced sepsis.
Blood Coagul. Fibrinolysis
PUBLISHED: 11-15-2014
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Sepsis and its associated multiple organ failure are related to high mortality in critical patients. Several studies have reported that gabexate mesilate, a synthetic inhibitor of trypsin-like serine protease, protects tissues/organs against injury in the models of endotoxemia. The aim of this study was to examine whether gabexate mesilate could attenuate coagulopathy and organ dysfunction in lipopolysaccharide (LPS)-induced sepsis model by using thrombelastography (TEG). LPS (7.5?mg/kg/h, intravenouly for 4?h) was administered to male adult Wistar rats. Some of the LPS rats received a continuous infusion of gabexate mesilate (10?mg/kg/h, intravenously for 8.5?h) for 30?min before the LPS administration. Variable parameters of hemodynamics, biochemistry, hemostasis and inflammatory response were measured for 6?h after the LPS infusion. TEG variables (R-time, K-time, ?-angle, and maximal amplitude) were also measured. The pretreatment of LPS rats with gabexate mesilate significantly attenuated the lung, liver and kidney dysfunction, consumptive coagulopathy, the increases in serum tumor necrosis factor-?, interleukin-6, plasma thrombin-antithrombin complex and plasminogen activator inhibitor-1, and neutrophils infiltration score in lung, liver and kidney, compared with the LPS alone group. In addition, TEG parameters correlated with tissue and liver injury in the late phase of endotoxemia. In particular, a strong negative correlation between maximal amplitude at 4?h and Ln (lactate dehydrogenase) at 6?h after LPS infusion was noted (r?=?-0.752, P?
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Establishment of a New Ovarian Cancer Cell Line CA5171.
Reprod Sci
PUBLISHED: 11-15-2014
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A new cell line, CA5171, derived from a chemotherapy-naive, high-grade undifferentiated ovarian carcinoma was established and characterized. The CA5171 cells presented with cobblestone morphology and a doubling time of 24 hours. Gene mutation analysis showed that the cells belonged to the type II ovarian cancer pathway with mutations of PIK3CA, PTEN, and TP53. Single-nucleotide polymorphism array analysis showed no homozygous gene deletion; however, several loci of gene copy number gains were noted in chromosome 1, 2, 5, 9, 10, 12, 15, 16, 20, and X. The in vitro and in vivo experiments showed that the cells were sensitive to paclitaxel and doxorubicin, but resistant to cisplatin. The cells also presented epithelial-mesenchymal transition properties that may have been related to their invasion and migration potential. The CA5171 cells show the potential as a new cell line for studies on epithelial ovarian carcinoma.
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Dihydroxanthenones from the fermentation product of an endophytic fungus Gliomastix murorum.
J Asian Nat Prod Res
PUBLISHED: 11-14-2014
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Three new dihydroxanthones, muroxanthenones A-C (1-3), together with three known dihydroxanthones (4-6) were isolated from the fermentation products of an endophytic fungus Gliomastix murorum. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compound 3 showed high cytotoxicities against NB4 and PC3 cell with IC50 values of 2.2 and 2.8 ?M. The other compounds also showed moderate cytotoxicities for some tested cell lines with IC50 values between 4.1 and 9.5 ?M.
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Development, Regeneration, and Evolution of Feathers.
Annu Rev Anim Biosci
PUBLISHED: 11-12-2014
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The feather is a complex ectodermal organ with hierarchical branching patterns. It provides functions in endothermy, communication, and flight. Studies of feather growth, cycling, and health are of fundamental importance to avian biology and poultry science. In addition, feathers are an excellent model for morphogenesis studies because of their accessibility, and their distinct patterns can be used to assay the roles of specific molecular pathways. Here we review the progress in aspects of development, regeneration, and evolution during the past three decades. We cover the development of feather buds in chicken embryos, regenerative cycling of feather follicle stem cells, formation of barb branching patterns, emergence of intrafeather pigmentation patterns, interplay of hormones and feather growth, and the genetic identification of several feather variants. The discovery of feathered dinosaurs redefines the relationship between feathers and birds. Inspiration from biomaterials and flight research further fuels biomimetic potential of feathers as a multidisciplinary research focal point. Expected final online publication date for the Annual Review of Animal Biosciences Volume 3 is February 15, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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Chemical Bonding in a Linear Chromium Metal String Complex.
Inorg Chem
PUBLISHED: 11-11-2014
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A combined experimental and theoretical electron density study of the shortest trichromium metal wire, Cr3(dpa)4Cl2·(C2H5OC2H5)x(CH2Cl2)1-x (1, dpa = bis(2-pyridyl)amido), is reported. High resolution X-ray diffraction data has been collected both at 100 K using a conventional X-ray source (DS1) and at 15 K using a synchrotron X-ray source (DS2). The linear chromium string is terminated by Cl(-) ions at both ends, and each Cr atom is also coordinated by four N atoms from bridging dpa ligands. The two Cr-Cr bond distances are unequal at 100 K (with d(Cr1-Cr2) being 0.029 Å shorter than d(Cr2-Cr3)) but at 15 K they are almost equal (0.002 Å difference). Analysis of the slightly elongated thermal ellipsoids of the Cr2 atom suggests that it is not due to disorder, but the presence of a shallow potential energy surface. Laplacian maps clearly show local valence shell charge concentration (VSCC) in the electron density along the bisector of the equatorial Cr-N bonds. Integration over the atomic basins indicates that Cr2 has smaller atomic charge and volume than Cr1 and Cr3. The topological characterization of the Cr-Cr bonds indicates partly covalent characters with electron density at the bond critical point of ?0.3 e Å(-3) and negative total energy density. The delocalization index of Cr-Cr is 0.8 for Cr1-Cr2 and 0.08 for Cr1-Cr3. Second-order perturbation analysis shows high stabilization energy of the Cr-Cr bonds (E(2) ? 190 kcal mol(-1)). Delocalization indices and source function and natural bond orbital analyses are all indicative of localized Cr-Cr bonding interactions.
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Perivascular Derived Stem Cells with Neural Crest Characteristics are Involved in Tendon Repair.
Stem Cells Dev.
PUBLISHED: 11-11-2014
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Tendons and ligaments exhibit limited regenerative capacity following injury, with damaged tissue being replaced by a fibrotic scar. The physiological role of scar tissue is complex and has been studied extensively. In this study we demonstrate that rat tendons contain a unique subpopulation of cells exhibiting stem cell characteristics, including clonogenicity, multipotency, and self-renewal capacity. Additionally, these putative stem cells expressed markers consistent with neural crest stem cells. Using immunofluorescent labeling, we identified P75+ (p75 neurotrophin receptor) cells in the perivascular regions of native rat tendon. Importantly, P75+ cells were frequently localized near vascular cells expressing ?-smooth muscle actin (SMA+) and increased in number within the peritenon after injury. Ultrastructural analysis showed that perivascular cells detached from vessels in response to injury, migrated into the interstitial space and deposited extracellular matrix (ECM). Characterization of P75+ cells isolated from the scar tissue indicated that this population also expressed the neural crest stem cell markers vimentin, Sox 10, and Snail. In conclusion, our results suggest that neural crest-like stem cells of perivascular origin reside within the rat peritenon and give rise to scar-forming stromal cells following tendon injury.
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Bifunctional ectodermal stem cells around the nail display dual fate homeostasis and adaptive wounding response toward nail regeneration.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-02-2014
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Regulation of adult stem cells (SCs) is fundamental for organ maintenance and tissue regeneration. On the body surface, different ectodermal organs exhibit distinctive modes of regeneration and the dynamics of their SC homeostasis remain to be unraveled. A slow cycling characteristic has been used to identify SCs in hair follicles and sweat glands; however, whether a quiescent population exists in continuously growing nails remains unknown. Using an in vivo label retaining cells (LRCs) system, we detected an unreported population of quiescent cells within the basal layer of the nail proximal fold, organized in a ring-like configuration around the nail root. These nail LRCs express the hair stem cell marker, keratin 15 (K15), and lineage tracing show that these K15-derived cells can contribute to both the nail structure and peri-nail epidermis, and more toward the latter. Thus, this stem cell population is bifunctional. Upon nail plucking injury, the homeostasis is tilted with these SCs dominantly delivering progeny to the nail matrix and differentiated nail plate, demonstrating their plasticity to adapt to wounding stimuli. Moreover, in vivo engraftment experiments established that transplanted nail LRCs can actively participate in functional nail regeneration. Transcriptional profiling of isolated nail LRCs revealed bone morphogenetic protein signaling favors nail differentiation over epidermal fate. Taken together, we have found a previously unidentified ring-configured population of bifunctional SCs, located at the interface between the nail appendage organ and adjacent epidermis, which physiologically display coordinated homeostatic dynamics but are capable of rediverting stem cell flow in response to injury.
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The Miaoyao Fanggan Sachets regulate humoral immunity and cellular immunity in mice.
J Complement Integr Med
PUBLISHED: 09-17-2014
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Abstract Background: Although some studies in the southeast part of Guizhou Province have suggested that Miaoyao Fanggan Sachets (MFS) prevent influenza, little is known about its influence on immune systems. Influenza virus mainly infects immune-compromised individuals. The effects of MFS have mainly been recognized in clinical practice. However, there have been relatively few studies on its biological mechanism. Here we investigated whether MFS was able to affect the mucosal immunization and the activation of alveolar macrophages (AM), CD4+and CD8+ T-cells in vivo. Methods: Eighty Kunming male mice were treated with MFS continuously or intermittently with Yu-Ping-Feng powder (YPF-P) (positive control group) or with normal saline (NS) (control group) for 4 weeks, respectively. Mice treated with MFS were further divided into the continuous inhalation group (12 h daily/4 weeks) and the discontinuous inhalation group (1 h, three times a day for 4 weeks). Mice in both groups were placed under 0.5 m3 masks which had four ventilation holes (10×15 cm) containing 40 g MFS. Positive control mice were orally treated with YPF-P 0.2 mg/10 g/day once a day for 4 weeks. Control mice were orally treated with equal volumes of NS once a day for 4 weeks. MFS was replaced every 6 days. Administration of YPF-P was used as a positive control since it has been used as an established Traditional Chinese Medicine (TCM) treatment before. After 4 weeks, mice in all experimental groups were sacrificed. IgA and IgG1 in lung and blood serum were detected by Western blot and enzyme-linked immuno sorbent assay (ELISA). The expression of alveolar macrophages (AM) in mice was analyzed by immunochemistry test based on CD68+staining. Blood samples were collected in which CD4+and CD8+T-cells were analyzed by flow cytometry. Results: Mice continuously and intermittently inhaling MFS showed a moderate increase in IgA and IgG1 protein levels compared with mice in the control groups. There was also a slightly significant increase in the number of AM in the continuous inhalation group compared with mice in the control groups (p<0.05). Furthermore, compared with controls, there was also a slightly significant increase in the number and percentage of CD4+and CD8+T-cells in both the continuous inhalation group and the discontinuous inhalation group (p<0.05). Conclusions: MFS was able to up-regulate the protein levels of sIgA and IgG1. Meanwhile, MFS could activate AM, CD4+and CD8+T-cells in mice. Our data have, for the first time, demonstrated that the protection against influenza by MFS is partly through activation of the innate and adaptive cell-mediated immune responses, indicating MFS as a potential new immune-modulatory agent for respiratory tract infectious disease.
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A Flexible Sulfur-Graphene-Polypropylene Separator Integrated Electrode for Advanced Li-S Batteries.
Adv. Mater. Weinheim
PUBLISHED: 09-11-2014
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A flexible Li-S battery based on an integrated structure of sulfur and graphene on a separator is developed. The internal graphene current collector offers a continuous conductive pathway, a modified interface with sulfur, and a good barrier to and an effective reservoir for dissolved polysulfides, consequently improving the capacity and cyclic life of the Li-S battery.
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Cohort Profile: The Social Environment and Biomarkers of Aging Study (SEBAS) in Taiwan.
Int J Epidemiol
PUBLISHED: 09-11-2014
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The Social Environment and Biomarkers of Aging Study (SEBAS) is a nationally representative longitudinal survey of Taiwanese middle-aged and older adults. It adds the collection of biomarkers and performance assessments to the Taiwan Longitudinal Study of Aging (TLSA), a nationally representative study of adults aged 60 and over, including the institutionalized population. The TLSA began in 1989, with follow-ups approximately every 3 years; younger refresher cohorts were added in 1996 and 2003. The first wave of SEBAS, based on a sub-sample of respondents from the 1999 TLSA, was conducted in 2000. A total of 1023 respondents completed both a face-to-face home interview and, several weeks later, a hospital-based physical examination. In addition to a 12-h (7?pm-7?am) urine specimen collected the night before and a fasting blood specimen collected during the examination, trained staff measured blood pressure, height, weight and waist and hip circumferences. A second wave of SEBAS was conducted in 2006 using a similar protocol to SEBAS 2000, but with the addition of performance assessments conducted by the interviewers at the end of the home interview. Both waves of SEBAS also included measures of health status (physical, emotional, cognitive), health behaviours, social relationships and exposure to stressors. The SEBAS data, which are publicly available at [http://www.icpsr.umich.edu/icpsrweb/NACDA/studies/3792/version/5], allow researchers to explore the relationships among life challenges, the social environment and health and to examine the antecedents, correlates and consequences of change in biological measures and health.
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Growth of metal-catalyst-free nitrogen-doped metallic single-wall carbon nanotubes.
Nanoscale
PUBLISHED: 09-05-2014
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Nitrogen-doped (N-doped) single-wall carbon nanotubes (SWCNTs) were synthesized by chemical vapor deposition using SiOx nanoparticles as a catalyst and ethylenediamine as the source of both carbon and nitrogen. The N-doped SWCNTs have a mean diameter of 1.1 nm and a narrow diameter range, with 92% of them having diameters from 0.7 to 1.4 nm. Multi-wavelength laser Raman spectra and temperature-dependent electrical resistance indicate that the SWCNT sample is enriched with metallic nanotubes. These N-doped SWCNTs showed excellent electrocatalytic activity for the oxygen reduction reaction and highly selective and sensitive sensing ability for dopamine detection.
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Increasing the Visible Light Absorption of Graphitic Carbon Nitride (Melon) Photocatalysts by Homogeneous Self-Modification with Nitrogen Vacancies.
Adv. Mater. Weinheim
PUBLISHED: 09-03-2014
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A novel reduced melon photocatalyst with a bandgap of 2.03 eV developed here has a widened visible light absorption range and suppressed radiative recombination of photo-excited charge carriers due to the homogeneous self-modification with nitrogen vacancies. As a consequence, the reduced melon shows a much superior photocatalytic activity compared to the pristine melon in generating •OH radicals and degrading the organic pollutant Rhodamine B.
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Investigation of Dermis-derived Hydrogels for Wound Healing Applications.
Biomed J
PUBLISHED: 09-02-2014
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Background: Wound healing and skin tissue engineering are mediated, in part, by interactions between cells and the extracellular matrix (ECM). A subset of the ECM, basement membranes (BM), plays a vital role in regulating proper skin healing and function. Methods: ECM-rich, tissue-specific hydrogels were extracted and assembled from dermis samples. These hydrogels contain BM proteins vital to skin regeneration, including laminin ?3, collagen IV, and collagen VII. The extracts could be assembled to form hydrogels by either temperature or pH mechanism, with the mechanical properties and structure varying with the mechanism of assembly. A wound healing model was developed to investigate the ability of these hydrogels to enhance healing with a single application in vivo. Results: The pH, but not temperature gels were easily applied to the wounds. There were no signs of increased inflammation due to the application of the hydrogels. The width of granulation tissue at the first week was reduced (p = 0.064) relative to controls with the application of hydrogel. There were no changes in wound closure rates or vessel density. Conclusions: Dermis-derived hydrogels contain BM proteins important for skin regeneration. They can be easily applied, but their poor mechanical strength and rapid degradation may hinder their biological effects.
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SnapShot: Branching Morphogenesis.
Cell
PUBLISHED: 08-30-2014
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Ectodermal appendages such as feathers, hair, mammary glands, salivary glands, and sweat glands form branches, allowing much-increased surface for functional differentiation and secretion. Here, the principles of branching morphogenesis are exemplified by the mammary gland and feathers.
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Evaluating 3D-Printed Biomaterials as Scaffolds for Vascularized Bone Tissue Engineering.
Adv. Mater. Weinheim
PUBLISHED: 08-27-2014
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There is an unmet need for a consistent set of tools for the evaluation of 3D-printed constructs. A toolbox developed to design, characterize, and evaluate 3D-printed poly(propylene fumarate) scaffolds is proposed for vascularized engineered tissues. This toolbox combines modular design and non-destructive fabricated design evaluation, evaluates biocompatibility and mechanical properties, and models angiogenesis.
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Genomic organization, transcriptomic analysis, and functional characterization of avian ?- and ?-keratins in diverse feather forms.
Genome Biol Evol
PUBLISHED: 08-24-2014
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Feathers are hallmark avian integument appendages, although they were also present on theropods. They are composed of flexible corneous materials made of ?- and ?-keratins, but their genomic organization and their functional roles in feathers have not been well studied. First, we made an exhaustive search of ?- and ?-keratin genes in the new chicken genome assembly (Galgal4). Then, using transcriptomic analysis, we studied ?- and ?-keratin gene expression patterns in five types of feather epidermis. The expression patterns of ?-keratin genes were different in different feather types, whereas those of ?-keratin genes were less variable. In addition, we obtained extensive ?- and ?-keratin mRNA in situ hybridization data, showing that ?-keratins and ?-keratins are preferentially expressed in different parts of the feather components. Together, our data suggest that feather morphological and structural diversity can largely be attributed to differential combinations of ?- and ?-keratin genes in different intrafeather regions and/or feather types from different body parts. The expression profiles provide new insights into the evolutionary origin and diversification of feathers. Finally, functional analysis using mutant chicken keratin forms based on those found in the human ?-keratin mutation database led to abnormal phenotypes. This demonstrates that the chicken can be a convenient model for studying the molecular biology of human keratin-based diseases.
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From Theory to Evidence: Long-Term Evaluation of the Mechanism of Action and Flap Integration of Distal Vascularized Lymph Node Transfers.
J Reconstr Microsurg
PUBLISHED: 08-19-2014
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Background?Nonanatomic (distal) placement of vascularized lymph node (VLN) transfers have shown efficacy in the treatment of extremity lymphedema, but the mechanism by which these flaps provide relief of lymphedema remains unclear. Intrinsic lymphovenous connections have been previously shown to exist in the transferred flap. But, the long-term interaction of the VLN flap and surrounding lymphedematous extremity has not been previously investigated. Patients and Methods?A retrospective review of a prospective maintained database of patients who underwent VLN transfer was evaluated. Patients who underwent distal VLN transfer and had more than 1-year follow-up were identified. Lymphodynamic evaluation was performed using 0.3 to 0.6 mL indocyanine green (ICG) injection at 5 cm proximal to the flap edge on identified patients. Migration direction of dye and latency period was evaluated. Results?In total, 20 patients were identified who met inclusion criteria. Average long-term follow-up was 27.3 months. The average circumference reduction of the affected extremity was 40.5%. ICG appearance within the VLN flap was found in all patients occurring on average in 178.3 seconds. In all cases, flow occurred in the distal direction (toward the flap) with proximal placement of dye. Latency period was found to inversely correlate with circumference reduction (p?
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Switching the selectivity of the photoreduction reaction of carbon dioxide by controlling the band structure of a g-C3N4 photocatalyst.
Chem. Commun. (Camb.)
PUBLISHED: 08-05-2014
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The selectivity of the CO2 photoreduction reaction in the presence of water vapour can be modulated by the band structure of a g-C3N4 photocatalyst. The major products obtained using bulk g-C3N4 with a bandgap of 2.77 eV and g-C3N4 nanosheets with a bandgap of 2.97 eV are acetaldehyde (CH3CHO) and methane (CH4), respectively.
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Selective deposition of redox co-catalyst(s) to improve the photocatalytic activity of single-domain ferroelectric PbTiO? nanoplates.
Chem. Commun. (Camb.)
PUBLISHED: 07-30-2014
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With the assistance of a ferroelectric field in PbTiO3 nanoplates, noble metals and metal oxides can be selectively deposited on the positively and negatively charged {001} facets of the nanoplates. Compared to PbTiO3 with randomly deposited reducing co-catalyst Pt particles, photocatalytic H2 evolution on PbTiO3 with Pt particles selectively deposited on the positively charged {001} facet is an order of magnitude better.
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Ultrastructural characteristics of 5BrdU labeling retention cells including stem cells of regenerating feathers in chicken.
J. Morphol.
PUBLISHED: 07-24-2014
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Feathers regenerate from stem cells localized in a region of the follicle indicated as the bulge of the collar. Stem cells are slow cycling cells and some of these cells can be identified after labeling experiments using 5-bromo-deoxyuridine to detect label retaining cells (5BrdU LRCs). The present electron microscopic analysis of 5BrdU LRCs has described the ultrastructural characteristics of small cells present in the bulge region of the follicle in regenerating feathers of chickens that include stem cells. Labeled feather stem cells are smaller than 10 lm in average diameter, possess large nuclei with high nuclear/cytoplasmic ratio, and contain evenly distributed ribosomes, sparse bundles of intermediate filaments, scarce or no endoplasmic reticulum, and few mitochondria. The nuclei are mainly euchromatic with a variable amount of heterochromatin clumps and the nucleoli show developed granular and fibrillar components. These features indicate that feather stem cells are transcriptionally active cells for ribosomal and proteins synthesis. The cell surface of feather stem cells often shows small and irregular folds resembling microvilli in contact with the surrounding cells. The latter characteristics may be related to the exchange of molecules and/or with the migration of stem cells among other epithelial cells of the collar epithelium.
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High-Volume Hydrodissection: Assessment of Deep Inferior Epigastric Perforator Flap Perfusion Using Laser Doppler.
Ann Plast Surg
PUBLISHED: 07-09-2014
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High-volume hydrodissection of intramuscular perforators of deep inferior epigastric perforator (DIEP) flaps in Sprague-Dawley rats has previously demonstrated a significant reduction in dissection time while simultaneously increasing the safety of dissection. However, increasing volumes of fluid injected into the closed rectus compartment may have adverse consequences on perfusion to the overlying flap. A prospective experimental animal study was performed to define a safe upper limit of volume injection for high-volume hydrodissection. Eight Sprague-Dawley rats underwent bilateral "DIEP" flap dissections with varying volumes of fluid (1, 3, 6, and 9 mL) injected into the study side. The primary outcome measurement was overlying tissue perfusion, measured using laser Doppler imaging, at 6 separate time points during the flap harvest. Although no significant difference in perfusion was noted between study and control sides despite increasing volumes of injection, a trend toward significant altered perfusion was noted immediately after injection in the 9-mL study group. Six milliliters is defined as the safe upper limit volume of injection into the closed rectus compartment without significantly altering overlying flap perfusion in our Sprague-Dawley rats. Using volumetric analysis, these data translate to 425 mL as the safe upper limit for high-volume hydrodissection for a single average sized human rectus sheath during DIEP flap harvesting. The mechanical and potentially pharmacologic implications of these data in humans remain to be seen.
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A strategic approach for DIEP flap breast reconstruction in patients with a vertical midline abdominal scar.
Ann Plast Surg
PUBLISHED: 07-09-2014
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Deep inferior epigastric perforator (DIEP) flaps have become broadly accepted for autologous breast reconstruction. Our aim was to analyze outcomes and describe technical strategies to improve survival when harvesting the entire DIEP flap with a midline scar.
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Preparation of metallic single-wall carbon nanotubes by selective etching.
ACS Nano
PUBLISHED: 06-25-2014
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We report the bulk synthesis of a sample with a high concentration of metallic single-wall carbon nanotubes (m-SWCNTs) using a modified floating catalyst chemical vapor deposition method with methane as the carbon precursor. By tuning experimental parameters, such as species and flux of carrier gases, catalyst concentration, growth temperature, etc., small-diameter semiconducting SWCNTs (s-SWCNTs) and large-diameter m-SWCNTs were obtained. Using identical growth conditions, at a temperature of 1000 °C, it was found that the addition of hydrogen as an etchant gas resulted in the preferential removal of the smaller diameter s-SWCNTs. As a result, a sample enriched with large-diameter metallic SWCNTs was obtained. The self-assembled fishnet-like m-SWCNT network showed excellent optical transparency and electrical conductivity.
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One-pot synthesis of metal-carbon nanotubes network hybrids as highly efficient catalysts for oxygen evolution reaction of water splitting.
ACS Appl Mater Interfaces
PUBLISHED: 06-23-2014
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Oxygen evaluation reaction (OER) is the most important reaction in hydrogen production from water splitting. Here we developed metal-carbon nanotubes (M-CNTs) hybrids with high metal oxide catalyst loading synthesized by arc-discharge and chemical vapor deposition (CVD) methods as electrocatalysts for OER in alkaline solutions. The M-CNTs hybrids produced by arc-discharge (M-CNTs-Arc) and CVD (M-CNTs-CVD) exhibit a core-shell-like structure, in which metal nanoparticles (NPs) encapsulated by graphite shells are connected by carbon nanotubes (CNTs), forming M-CNTs network hybrids. M-CNTs-Arc has NiCo0.16Fe0.34 metal core and shows very high activity and superior stability for OER, achieving 100 A g(-1) at an overpotential (?) of 0.29 V and 500 A g(-1) at ? = 0.37 V in 1 M KOH solution. This is probably the highest activity reported for OER in alkaline solutions. The reaction follows the first-order kinetics with respect to OH(-) concentration and Tafel slope of 34 mV dec(-1). The results demonstrate a highly efficient, scalable, and low-cost one-step synthesis method for developing highly active and stable catalysts for electrochemical water splitting in alkaline solutions.
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Vascularized lymph node flap transfer and lymphovenous anastomosis for klippel-trenaunay syndrome with congenital lymphedema.
Plast Reconstr Surg Glob Open
PUBLISHED: 06-01-2014
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A female patient with Klippel-Trenaunay syndrome, including hypertrophic bone and soft tissue in the forelimbs, bilateral lower limbs lymphedema, port-wine stains, and superficial veins of Servelle, was presented. The diagnosis of lymphedema was confirmed by lymphoscintigraphy and indocyanine green lymphography. The novel treatments consisted of vascularized lymph node transplantation to the left lymphedematous extremity and lymphovenous anastomosis to the right lymphedematous extremity. Significant improvements in subjective and objective clinical outcome were observed early in the postoperative period with continued improvements during the follow-up period.
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Defining dermal adipose tissue.
Exp. Dermatol.
PUBLISHED: 05-15-2014
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Here, we explore the evolution and development of skin-associated adipose tissue with the goal of establishing nomenclature for this tissue. Underlying the reticular dermis, a thick layer of adipocytes exists that encases mature hair follicles in rodents and humans. The association of lipid-filled cells with the skin is found in many invertebrate and vertebrate species. Historically, this layer of adipocytes has been termed subcutaneous adipose, hypodermis and subcutis. Recent data have revealed a common precursor for dermal fibroblasts and intradermal adipocytes during development. Furthermore, the development of adipocytes in the skin is independent from that of subcutaneous adipose tissue development. Finally, the role of adipocytes has been shown to be relevant for epidermal homoeostasis during hair follicle regeneration and wound healing. Thus, we propose a refined nomenclature for the cells and adipose tissue underlying the reticular dermis as intradermal adipocytes and dermal white adipose tissue, respectively.
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Modulating hair follicle size with Wnt10b/DKK1 during hair regeneration.
Exp. Dermatol.
PUBLISHED: 04-15-2014
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Hair follicles have characteristic sizes corresponding to their cycle-specific stage. However, how the anagen hair follicle specifies its size remains elusive. Here, we showed that in response to prolonged ectopic Wnt10b-mediated ?-catenin activation, regenerating anagen hair follicles grew larger in size. In particular, the hair bulb, dermal papilla and hair shaft became enlarged, while the formation of different hair types (Guard, Awl, Auchene and Zigzag) was unaffected. Interestingly, we found that the effect of exogenous WNT10b was mainly on Zigzag and less on the other kinds of hairs. We observed dramatically enhanced proliferation within the matrix, DP and hair shaft of the enlarged AdWnt10b-treated hair follicles compared with those of normal hair follicles at P98. Furthermore, expression of CD34, a specific hair stem cell marker, was increased in its number to the bulge region after AdWnt10b treatment. Ectopic expression of CD34 throughout the ORS region was also observed. Many CD34-positive hair stem cells were actively proliferating in AdWnt10b-induced hair follicles. Importantly, subsequent co-treatment with the Wnt inhibitor, DKK1, reduced hair follicle enlargement and decreased proliferation and ectopic localization of hair stem cells. Moreover, injection of DKK1 during early anagen significantly reduced the width of prospective hairs. Together, these findings strongly suggest that Wnt10b/DKK1 can modulate hair follicle size during hair regeneration.
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Regeneration of reptilian scales after wounding: neogenesis, regional difference, and molecular modules.
Regeneration
PUBLISHED: 03-26-2014
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Lizard skin can produce scales during embryonic development, tail regeneration, and wound healing; however, underlying molecular signaling and extracellular matrix protein expression remains unknown. We mapped cell proliferation, signaling and extracellular matrix proteins in regenerating and developing lizard scales in different body regions with different wound severity. Following lizard tail autotomy (self-amputation), de novo scales regenerate from regenerating tail blastema. Despite topological differences between embryonic and adult scale formation, asymmetric cell proliferation produces the newly formed outer scale surface. Regionally different responses to wounding were observed; open wounds induced better scale regeneration from tail skin than trunk skin. Molecular studies suggest NCAM enriched dermal regions exhibit higher cell proliferation associated with scale growth. ?-catenin may be involved in epidermal scale differentiation. Dynamic tenascin-C expression suggests its involvement in regeneration. We conclude that different skin regions exhibit different competence for de novo scale formation. While cellular and morphogenetic paths differ during development and regeneration of lizard scale formation, they share general proliferation patterns, epithelial-mesenchymal interactions and similar molecular modules composed of adhesion and extracellular matrix molecules.
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Direct observation of atomic dynamics and silicon doping at a topological defect in graphene.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-16-2014
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Chemical decoration of defects is an effective way to functionalize graphene and to study mechanisms of their interaction with environment. We monitored dynamic atomic processes during the formation of a rotary Si trimer in monolayer graphene using an aberration-corrected scanning-transmission electron microscope. An incoming Si atom competed with and replaced a metastable C dimer next to a pair of Si substitutional atoms at a topological defect in graphene, producing a Si trimer. Other atomic events including removal of single C atoms, incorporation and relocation of a C dimer, reversible C-C bond rotation, and vibration of Si atoms occurred before the final formation of the Si trimer. Theoretical calculations indicate that it requires 2.0?eV to rotate the Si trimer. Our real-time results provide insight with atomic precision for reaction dynamics during chemical doping at defects in graphene, which have implications for defect nanoengineering of graphene.
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Developing a Lower Limb Lymphedema Animal Model with Combined Lymphadenectomy and Low-dose Radiation.
Plast Reconstr Surg Glob Open
PUBLISHED: 03-01-2014
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This study was aimed to establish a consistent lower limb lymphedema animal model for further investigation of the mechanism and treatment of lymphedema.
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Monitoring patient-centered outcomes through the progression of breast reconstruction: a multicentered prospective longitudinal evaluation.
Breast Cancer Res. Treat.
PUBLISHED: 02-19-2014
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Studies have shown that having breast reconstruction has a positive influence on patient satisfaction and health-related quality of life (HRQoL) at the conclusion of treatment. However, no study has critically evaluated changes to these patient-reported outcomes during the process of undergoing breast reconstruction. This study was to prospectively evaluate changes to patient-centered metrics through the progression of breast reconstruction. An IRB-approved prospective, multi-institutional study was performed for all patients undergoing breast reconstruction between 2009 and 2011. The Breast-Q reconstruction questionnaire was used for evaluation of HRQoL and was administered at five intervals in the perioperative period. Longitudinal evaluation was performed to assess changes to HRQoL metrics during this perioperative interval. One hundred and ten patients were enrolled, and 100 patients (91.9 %) completed appropriate follow-up. Preoperative HRQoL scores were higher in patients electing to forgo reconstruction (P < 0.004), while postoperative HRQoL scores consistently deteriorated at multiple time points following mastectomy as compared to reconstructed patients. On subgroup analysis, results indicated lower initial HRQoL scores in delayed reconstruction (P < 0.05) as compared to immediate reconstruction. These scores did, however, merge at approximately 9 months postoperatively. Changes to HRQoL outcomes occur through progression of breast reconstruction. Within the first year of surgery, early decreases are mirrored by significant increases at later time points above baseline levels when evaluating most forms of reconstruction. Choosing against reconstruction will likely result in continued deterioration of HRQoL for patients undergoing cancer surgery, but steady improvements can be expected if delayed reconstruction is chosen.
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Regenerative hair waves in aging mice and extra-follicular modulators follistatin, dkk1, and sfrp4.
J. Invest. Dermatol.
PUBLISHED: 02-12-2014
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Hair cycling is modulated by factors both intrinsic and extrinsic to hair follicles. Cycling defects lead to conditions such as aging-associated alopecia. Recently, we demonstrated that mouse skin exhibits regenerative hair waves, reflecting a coordinated regenerative behavior in follicle populations. Here, we use this model to explore the regenerative behavior of aging mouse skin. Old mice (>18 months) tracked over several months show that with progressing age, hair waves slow down, wave propagation becomes restricted, and hair cycle domains fragment into smaller domains. Transplanting aged donor mouse skin to a young host can restore donor cycling within a 3?mm range of the interface, suggesting that changes are due to extracellular factors. Therefore, hair stem cells in aged skin can be reactivated. Molecular studies show that extra-follicular modulators Bmp2, Dkk1, and Sfrp4 increase in early anagen. Further, we identify follistatin as an extra-follicular modulator, which is highly expressed in late telogen and early anagen. Indeed, follistatin induces hair wave propagation and its level decreases in aging mice. We present an excitable medium model to simulate the cycling behavior in aging mice and illustrate how the interorgan macroenvironment can regulate the aging process by integrating both "activator" and "inhibitor" signals.
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The mechanism of vascularized lymph node transfer for lymphedema: natural lymphaticovenous drainage.
Plast. Reconstr. Surg.
PUBLISHED: 01-29-2014
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Vascularized lymph node flap transfer for the treatment of upper and lower limb lymphedema has had promising results. This study was performed to investigate the mechanism of lymph drainage of a vascularized lymph node flap both experimentally and clinically.
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Dkk2/Frzb in the dermal papillae regulates feather regeneration.
Dev. Biol.
PUBLISHED: 01-13-2014
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Avian feathers have robust growth and regeneration capability. To evaluate the contribution of signaling molecules and pathways in these processes, we profiled gene expression in the feather follicle using an absolute quantification approach. We identified hundreds of genes that mark specific components of the feather follicle: the dermal papillae (DP) which controls feather regeneration and axis formation, the pulp mesenchyme (Pp) which is derived from DP cells and nourishes the feather follicle, and the ramogenic zone epithelium (Erz) where a feather starts to branch. The feather DP is enriched in BMP/TGF-? signaling molecules and inhibitors for Wnt signaling including Dkk2/Frzb. Wnt ligands are mainly expressed in the feather epithelium and pulp. We find that while Wnt signaling is required for the maintenance of DP marker gene expression and feather regeneration, excessive Wnt signaling delays regeneration and reduces pulp formation. Manipulating Dkk2/Frzb expression by lentiviral-mediated overexpression, shRNA-knockdown, or by antibody neutralization resulted in dual feather axes formation. Our results suggest that the Wnt signaling in the proximal feather follicle is fine-tuned to accommodate feather regeneration and axis formation.
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Macroenvironmental regulation of hair cycling and collective regenerative behavior.
Cold Spring Harb Perspect Med
PUBLISHED: 01-04-2014
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The hair follicle (HF) regeneration paradigm provides a unique opportunity for studying the collective behavior of stem cells in living animals. Activation of HF stem cells depends on the core inhibitory BMP and activating WNT signals operating within the HF microenvironment. Additionally, HFs receive multilayered signaling inputs from the extrafollicular macroenvironment, which includes dermis, adipocytes, neighboring HFs, hormones, and external stimuli. These activators/inhibitors are integrated across multiple stem-cell niches to produce dynamic hair growth patterns. Because of their pigmentation, these patterns can be easily studied on live shaved animals. Comparing to autonomous regeneration of one HF, populations of HFs display coupled decision making, allowing for more robust and adaptable regenerative behavior to occur collectively. The generic cellular automata model used to simulate coordinated HF cycling here can be extended to study population-level behavior of other complex biological systems made of cycling elements.
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Adjuvant potential of selegiline in attenuating organ dysfunction in septic rats with peritonitis.
PLoS ONE
PUBLISHED: 01-01-2014
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Selegiline, an anti-Parkinson drug, has antioxidant and anti-apoptotic effects. To explore the effect of selegiline on sepsis, we used a clinically relevant animal model of polymicrobial sepsis. Cecal ligation and puncture (CLP) or sham operation was performed in male rats under anesthesia. Three hours after surgery, animals were randomized to receive intravenously selegiline (3 mg/kg) or an equivalent volume of saline. The administration of CLP rats with selegiline (i) increased arterial blood pressure and vascular responsiveness to norepinephrine, (ii) reduced plasma liver and kidney dysfunction, (iii) attenuated metabolic acidosis, (iv) decreased neutrophil infiltration in liver and lung, and (v) improved survival rate (from 44% to 65%), compared to those in the CLP alone rats. The CLP-induced increases of plasma interleukin-6, organ superoxide levels, and liver inducible nitric oxide synthase and caspase-3 expressions were ameliorated by selegiline treatment. In addition, the histological changes in liver and lung were significantly attenuated in the selegiline -treated CLP group compared to those in the CLP group. The improvement of organ dysfunction and survival through reducing inflammation, oxidative stress and apoptosis in peritonitis-induced sepsis by selegiline has potential as an adjuvant agent for critical ill.
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Perivascular adipose tissue inhibits endothelial function of rat aortas via caveolin-1.
PLoS ONE
PUBLISHED: 01-01-2014
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Perivascular adipose tissue (PVAT)-derived factors have been proposed to play an important role in the pathogenesis of atherosclerosis. Caveolin-1 (Cav-1), occupying the calcium/calmodulin binding site of endothelial NO synthase (eNOS) and then inhibiting nitric oxide (NO) production, is also involved in the development of atherosclerosis. Thus, we investigated whether PVAT regulated vascular tone via Cav-1 and/or endothelial NO pathways. Isometric tension studies were carried out in isolated thoracic aortas from Wistar rats in the presence and absence of PVAT. Concentration-response curves of phenylephrine, acetylcholine, and sodium nitroprusside were illustrated to examine the vascular reactivity and endothelial function. The protein expressions of eNOS and Cav-1 were also examined in aortic homogenates. Our results demonstrated that PVAT significantly enhanced vasoconstriction and inhibited vasodilatation via endothelium-dependent mechanism. The aortic NO production was diminished after PVAT treatment, whereas protein expression and activity of eNOS were not significantly affected. In addition, Cav-1 protein expression was significantly increased in aortas with PVAT transfer. Furthermore, a caveolae depleter methyl-?-cyclodextrin abolished the effect of PVAT on the enhancement of vasoconstriction, and reversed the impairment of aortic NO production. In conclusion, unknown factor(s) released from PVAT may inhibit endothelial NO production and induce vasocontraction via an increase of Cav-1 protein expression.
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Phosphoproteomics and bioinformatics analyses of spinal cord proteins in rats with morphine tolerance.
PLoS ONE
PUBLISHED: 01-01-2014
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Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance.
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Structural Changes in Iron Oxide and Gold Catalysts during Nucleation of Carbon Nanotubes Studied by In Situ Transmission Electron Microscopy.
ACS Nano
PUBLISHED: 12-24-2013
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We report a simple, versatile in situ transmission electron microscopy (TEM) approach for investigating the nucleation and growth mechanism of carbon nanotubes (CNTs), by which the composition, phase transition, and physical state of various catalysts can be clearly resolved. In our approach, catalyst nanoparticles (NPs) are placed in a multiwall CNT "tubular furnace" with two open ends, and a high temperature is obtained by Joule heating in the specimen chamber of a TEM. The carbon is supplied by electron irradiation-induced injection of carbon atoms. Comparative studies on the catalytic behavior of traditional iron oxide and recently discovered gold catalysts were performed. It was found that the growth of CNTs from iron oxide involves the reduction of Fe2O3 to Fe3C, nucleation and growth of CNTs from partially liquefied Fe3C, and finally the formation of elemental Fe when the growth stops. In contrast, while changes in shape, size, and orientation were also observed for the fluctuating Au NPs, no chemical reactions or phase transitions occurred during the nucleation of CNTs. These two distinct nucleation and growth processes and mechanisms would be valuable for the structure-controlled growth of CNTs by catalyst design and engineering.
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Edge-controlled growth and kinetics of single-crystal graphene domains by chemical vapor deposition.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-02-2013
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The controlled growth of large-area, high-quality, single-crystal graphene is highly desired for applications in electronics and optoelectronics; however, the production of this material remains challenging because the atomistic mechanism that governs graphene growth is not well understood. The edges of graphene, which are the sites at which carbon accumulates in the two-dimensional honeycomb lattice, influence many properties, including the electronic properties and chemical reactivity of graphene, and they are expected to significantly influence its growth. We demonstrate the growth of single-crystal graphene domains with controlled edges that range from zigzag to armchair orientations via growth-etching-regrowth in a chemical vapor deposition process. We have observed that both the growth and the etching rates of a single-crystal graphene domain increase linearly with the slanted angle of its edges from 0° to ?19° and that the rates for an armchair edge are faster than those for a zigzag edge. Such edge-structure-dependent growth/etching kinetics of graphene can be well explained at the atomic level based on the concentrations of the kinks on various edges and allow the evolution and control of the edge and morphology in single-crystal graphene following the classical kinetic Wulff construction theory. Using these findings, we propose several strategies for the fabrication of wafer-sized, high-quality, single-crystal graphene.
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Sarcomatoid carcinoma in head and neck: a review of 30 years of experience-clinical outcomes and reconstructive results.
Ann Plast Surg
PUBLISHED: 11-29-2013
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Sarcomatoid carcinoma (SaCa) is a rare variant of squamous cell carcinoma (SCC) with sarcomatoid features. This study investigated the clinical presentation and outcomes of head and neck SaCa. In addition, reconstructive outcome for a subset of patients was also evaluated.
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Synthesis of mesoporous single crystal rutile TiO2 with improved photocatalytic and photoelectrochemical activities.
Chem. Commun. (Camb.)
PUBLISHED: 11-08-2013
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Mesoporous single crystal rutile TiO2 with clear facets was prepared by a seeded template method. As a result of unique microstructure, the resulting TiO2 exhibits remarkably improved photocatalytic and photoelectrochemical activities in hydrogen or oxygen evolution.
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An ectopic approach for engineering a vascularized tracheal substitute.
Biomaterials
PUBLISHED: 09-26-2013
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Tissue engineering can provide alternatives to current methods for tracheal reconstruction. Here we describe an approach for ectopic engineering of vascularized trachea based on the implantation of co-cultured scaffolds surrounded by a muscle flap. Poly(L-lactic-co-glycolic acid) (PLGA) or poly(?-caprolactone) (PCL) scaffolds were seeded with chondrocytes, bone marrow stem cells and co-cultured both cells respectively (8 groups), wrapped in a pedicled muscle flap, placed as an ectopic culture on the abdominal wall of rabbits (n = 24), and harvested after two and four weeks. Analysis of the biochemical and mechanical properties demonstrated that the PCL scaffold with co-culture cells seeding displayed the optimal chondrogenesis with adequate rigidity to maintain the cylindrical shape and luminal patency. Histological analysis confirmed that cartilage formed in the co-culture groups contained a more homogeneous and higher extracellular matrix content. The luminal surfaces appeared to support adequate epithelialization due to the formation of vascularized capsular tissue. A prefabricated neo-trachea was transferred to the defect as a tracheal replacement and yielded satisfactory results. These encouraging results indicate that our co-culture approach may enable the development of a clinically applicable neo-trachea.
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The use of magnetic resonance angiography in vascularized groin lymph node transfer: an anatomic study.
J Reconstr Microsurg
PUBLISHED: 09-09-2013
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Vascularized groin lymph node transfer (VGLNT) has been successfully used to treat lymphedema. However, lack of familiarity with the inguinal node anatomy and concerns regarding donor site morbidity have limited its widespread use. The purpose of this study was to use magnetic resonance angiography (MRA) to clarify the inguinal anatomy and provide a reliable method for identifying the location of the superficial transverse inguinal lymph nodes. In this study MRA was used to evaluate the superficial inguinal lymph nodes in 117 patients. Coordinates of lymph nodes were plotted relative to an axis from the anterior superior iliac spine (ASIS) to the pubic tubercle (PT). The nodes were also plotted relative to the superficial circumflex iliac vein (SCIV) and superficial inferior epigastric vein (SIEV). A total of 1,938 lymph nodes were identified. These lymph nodes were concentrated on one-third the distance from the PT toward the ASIS and 3 cm perpendicularly below this line. About 67% of the superficial inguinal nodes were located within the bifurcation of the SIEV and SCIV. The results from this study provide useful guidelines for locating lymph nodes targeted for VGLNT.
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Nuclear topology, epigenetics, and keratinocyte differentiation.
J. Invest. Dermatol.
PUBLISHED: 08-17-2013
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Recent progress in epigenetics reveals dynamic chromatin interactions in the nucleus during development, regeneration, reprogramming, and in disease. Higher-order chromatin organization is manifested as changes in the topological distribution of eu-/heterochromatin and in nuclear morphology. We are now able to gain new knowledge about these changes at the genomic level.
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High-risk human papillomavirus, other than type 16/18, in predominantly older Taiwanese women with high-grade cervical preinvasive lesions.
Taiwan J Obstet Gynecol
PUBLISHED: 08-07-2013
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To investigate the various genotypes of human papillomavirus (HPV) in Taiwanese women patients with abnormal cervical cytology and analyze the associations between HPV types, cervical preinvasive lesions, and the medical characteristics of these patients.
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Facile synthesis of heterotrimetallic metal-string complex [NiCoRh(dpa)4Cl2] through direct metal replacement.
Chem. Commun. (Camb.)
PUBLISHED: 07-30-2013
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This communication provides a practical strategy for the synthesis of heterotrimetallic extended metal atom chains with supported dpa(-) ligands. The transformation of the CoCoRh to a NiCoRh trinuclear complex can be achieved by direct metallic replacement. Furthermore, the first (CoRh)(4+) metal-metal bond is described here.
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Subcutaneous tissue expansion and subsequent subpectoral implantation for breast reconstruction in Asian patients: safety and outcome.
Ann Plast Surg
PUBLISHED: 06-19-2013
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Asian women are generally thin with smaller breasts. The objective was to investigate the outcomes for patients who underwent 2-stage breast reconstruction using subcutaneous expansion followed by subpectoral implantation. Between 2003 and 2008, 22 patients underwent subcutaneous expansion and subsequent submuscular implantation for 23 breast reconstructions. Mean age was 44.6 ± 7.0 years. The outcome was assessed with a pain visual analog scale, a questionnaire, and the cosmesis. Mean expansion volume was 350.3 ± 80.8 mL. Mean implant size was 306.7 ± 84.6 mL. The complication rate was 8.6%, 13.0% in first and second stages. Mean pain scale was 2 ± 1.4. At a mean follow-up of 42.5 ± 18 months, patients satisfaction was 3.2 ± 0.9. Overall shape of the reconstructed breast was rated as 2.8 ± 0.5. Subcutaneous expansion with subsequent subpectoral implantation is feasible and reliable in low body mass index, nonsmoking, nonradiated patients with small and projective breasts.
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Vascularized groin lymph node flap transfer for postmastectomy upper limb lymphedema: flap anatomy, recipient sites, and outcomes.
Plast. Reconstr. Surg.
PUBLISHED: 05-30-2013
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Vascularized groin lymph node flap transfer is an emerging approach to the treatment of postmastectomy upper limb lymphedema. The authors describe the pertinent flap anatomy, surgical technique including different recipient sites, and outcome of this technique.
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Local circadian clock gates cell cycle progression of transient amplifying cells during regenerative hair cycling.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-20-2013
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Regenerative cycling of hair follicles offers an unique opportunity to explore the role of circadian clock in physiological tissue regeneration. We focused on the role of circadian clock in actively proliferating transient amplifying cells, as opposed to quiescent stem cells. We identified two key sites of peripheral circadian clock activity specific to regenerating anagen hair follicles, namely epithelial matrix and mesenchymal dermal papilla. We showed that peripheral circadian clock in epithelial matrix cells generates prominent daily mitotic rhythm. As a consequence of this mitotic rhythmicity, hairs grow faster in the morning than in the evening. Because cells are the most susceptible to DNA damage during mitosis, this cycle leads to a remarkable time-of-day-dependent sensitivity of growing hair follicles to genotoxic stress. Same doses of ?-radiation caused dramatic hair loss in wild-type mice when administered in the morning, during mitotic peak, compared with the evening, when hair loss is minimal. This diurnal radioprotective effect becomes lost in circadian mutants, consistent with asynchronous mitoses in their hair follicles. Clock coordinates cell cycle progression with genotoxic stress responses by synchronizing Cdc2/Cyclin B-mediated G2/M checkpoint. Our results uncover diurnal mitotic gating as the essential protective mechanism in highly proliferative hair follicles and offer strategies for minimizing or maximizing cytotoxicity of radiation therapies.
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Many paths to alopecia via compromised regeneration of hair follicle stem cells.
J. Invest. Dermatol.
PUBLISHED: 05-16-2013
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Alopecia can be caused by defective formation, defective regeneration, or increased destruction of hair follicles. Much work has elucidated the roles of diffusible morphogens in modulating hair follicle stem cell activities. Recent studies have revealed novel molecular events within the nucleus, which are required for the activation and progression of hair stem cells. These studies will provide new clues and targets for designing therapeutic strategies for hair loss.
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Specialized stem cell niche enables repetitive renewal of alligator teeth.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-13-2013
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Reptiles and fish have robust regenerative powers for tooth renewal. However, extant mammals can either renew their teeth one time (diphyodont dentition) or not at all (monophyodont dentition). Humans replace their milk teeth with permanent teeth and then lose their ability for tooth renewal. Here, we study tooth renewal in a crocodilian model, the American alligator, which has well-organized teeth similar to mammals but can still undergo life-long renewal. Each alligator tooth is a complex family unit composed of the functional tooth, successional tooth, and dental lamina. Using multiple mitotic labeling, we map putative stem cells to the distal enlarged bulge of the dental lamina that contains quiescent odontogenic progenitors that can be activated during physiological exfoliation or artificial extraction. Tooth cycle initiation correlates with ?-catenin activation and soluble frizzled-related protein 1 disappearance in the bulge. The dermal niche adjacent to the dermal lamina dynamically expresses neural cell adhesion molecule, tenascin-C, and other molecules. Furthermore, in development, asymmetric ?-catenin localization leads to the formation of a heterochronous and complex tooth family unit configuration. Understanding how these signaling molecules interact in tooth development in this model may help us to learn how to stimulate growth of adult teeth in mammals.
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The benefits of estrogen or selective estrogen receptor modulator on kidney and its related disease-chronic kidney disease-mineral and bone disorder: osteoporosis.
J Chin Med Assoc
PUBLISHED: 05-09-2013
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An umbrella concept addressing the relationship between chronic kidney disease (CKD) and mineral and bone disorders has been developed in recent years. Given the high prevalence of osteoporosis-related fractures in postmenopausal women with CKD, especially those undergoing chronic hemodialysis, the strategy used in the prevention and management of CKD and its associated osteoporosis in these postmenopausal women has become a topic of substantial debate. This controversy has ongoing relevance because osteoporosis results in a significant economic burden secondary to increased morbidity and mortality. The perfect goal of treatment and prevention includes both bone protection and renal protection, or at least protection of one disease without compromising the other disease. Both CKD and osteoporosis are frequently observed in the same patients, and often have parallel progression in postmenopausal women. Estrogen, the main female hormone during reproductive age, has been reported to have a protective effect on kidney fibrosis in several animal models, and is also considered one of the most effective drugs in the management of postmenopausal women with osteoporosis and prevention of osteoporosis. However, due to the many adverse events associated with the use of estrogen with and without progestin, some of which have contributed to significant morbidity and mortality, drug modification, which has had fewer reported incidences of adverse events without compromising the protective effect on both the kidney and bone, may have an easier road to acceptance. Therapeutic alternatives, such as the selective estrogen receptor modulators (SERMs), have shown the benefits of estrogen on bone, serum lipid levels, and renal protection, without any adverse effects on the breast and endometrium. The Multiple Outcomes of Raloxifene Evaluation trial (MORE) and its extension-Continuing Outcomes Relevant to Evista (CORE), a double-blind, randomized clinical trial encompassing postmenopausal women with osteoporosis, showed promising results in both bone and renal studies. Raloxifene increased bone mineral density (BMD) in the spine and femoral neck and reduced the risk of vertebral fracture. In addition, raloxifene slowed the increase in the rate of serum creatinine and also significantly slowed the decrease in the estimated glomerular filtration rate; of most importance, raloxifene use was associated with significantly fewer kidney-related adverse events. Hemodialyzed women on raloxifene treatment demonstrated increased trabecular BMD, a decrease in bone resorption markers, and a decrease in the low-density lipoprotein-cholesterol value. Thus, raloxifene and, most likely, other SERMs could be better in place of estrogen in the management of postmenopausal women with CKD and its associated osteoporosis, although much evidence should be provided in the advanced-stage CKD, especially in the Stage 5 CKD patients on dialysis.
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Interferon-gamma in ascites could be a predictive biomarker of outcome in ovarian carcinoma.
Gynecol. Oncol.
PUBLISHED: 04-23-2013
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The ovarian cancer-associated ascites is an ideal material for evaluating the interaction between the host immune system and cancer cells in the tumor micro-environment. The aim of this study was to investigate whether the selected target cytokine expression levels in ascites could serve as an immune biomarker for predicting outcomes in ovarian cancer.
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Shaping organs by a wingless-int/Notch/nonmuscle myosin module which orients feather bud elongation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-01-2013
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How organs are shaped to specific forms is a fundamental issue in developmental biology. To address this question, we used the repetitive, periodic pattern of feather morphogenesis on chicken skin as a model. Avian feathers within a single tract extend from dome-shaped primordia to thin conical structures with a common axis of orientation. From a systems biology perspective, the process is precise and robust. Using tissue transplantation assays, we demonstrate that a "zone of polarizing activity," localized in the posterior feather bud, is necessary and sufficient to mediate the directional elongation. This region contains a spatially well-defined nuclear ?-catenin zone, which is induced by wingless-int (Wnt)7a protein diffusing in from posterior bud epithelium. Misexpressing nuclear ?-catenin randomizes feather polarity. This dermal nuclear ?-catenin zone, surrounded by Notch1 positive dermal cells, induces Jagged1. Inhibition of Notch signaling disrupts the spatial configuration of the nuclear ?-catenin zone and leads to randomized feather polarity. Mathematical modeling predicts that lateral inhibition, mediated by Notch signaling, functions to reduce Wnt7a gradient variations and fluctuations to form the sharp boundary observed for the dermal ?-catenin zone. This zone is also enriched for nonmuscle myosin IIB. Suppressing nonmuscle myosin IIB disrupts directional cell rearrangements and abolishes feather bud elongation. These data suggest that a unique molecular module involving chemical-mechanical coupling converts a pliable chemical gradient to a precise domain, ready for subsequent mechanical action, thus defining the position, boundary, and duration of localized morphogenetic activity that molds the shape of growing organs.
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Module-based complexity formation: periodic patterning in feathers and hairs.
Wiley Interdiscip Rev Dev Biol
PUBLISHED: 03-30-2013
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Patterns describe order which emerges from homogeneity. Complex patterns on the integument are striking because of their visibility throughout an organism’s lifespan. Periodic patterning is an effective design because the ensemble of hair or feather follicles (modules) allows the generation of complexity, including regional variations and cyclic regeneration, giving the skin appendages a new lease on life. Spatial patterns include the arrangements of feathers and hairs in specific number, size, and spacing.We explorehowa field of equivalent progenitor cells can generate periodically arranged modules based on genetic information, physical–chemical rules and developmental timing. Reconstitution experiments suggest a competitive equilibrium regulated by activators/inhibitors involving Turing reaction-diffusion. Temporal patterns result from oscillating stem cell activities within each module (microenvironment regulation), reflected as growth (anagen) and resting (telogen) phases during the cycling of feather and hair follicles. Stimulating modules with activators initiates the spread of regenerative hair waves, while global inhibitors outside each module (macroenvironment) prevent this. Different wave patterns can be simulated by cellular automata principles. Hormonal status and seasonal changes can modulate appendage phenotypes, leading to ‘organ metamorphosis’, with multiple ectodermal organ phenotypes generated from the same precursors. We discuss potential novel evolutionary steps using this module-based complexity in several amniote integument organs, exemplified by the spectacular peacock feather pattern. We thus explore the application of the acquired knowledge of patterning in tissue engineering. New hair follicles can be generated after wounding. Hairs and feathers can be reconstituted through self-organization of dissociated progenitor cells.
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Sox2 marks epithelial competence to generate teeth in mammals and reptiles.
Development
PUBLISHED: 03-05-2013
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Tooth renewal is initiated from epithelium associated with existing teeth. The development of new teeth requires dental epithelial cells that have competence for tooth formation, but specific marker genes for these cells have not been identified. Here, we analyzed expression patterns of the transcription factor Sox2 in two different modes of successional tooth formation: tooth replacement and serial addition of primary teeth. We observed specific Sox2 expression in the dental lamina that gives rise to successional teeth in mammals with one round of tooth replacement as well as in reptiles with continuous tooth replacement. Sox2 was also expressed in the dental lamina during serial addition of mammalian molars, and genetic lineage tracing indicated that Sox2(+) cells of the first molar give rise to the epithelial cell lineages of the second and third molars. Moreover, conditional deletion of Sox2 resulted in hyperplastic epithelium in the forming posterior molars. Our results indicate that the Sox2(+) dental epithelium has competence for successional tooth formation and that Sox2 regulates the progenitor state of dental epithelial cells. The findings imply that the function of Sox2 has been conserved during evolution and that tooth replacement and serial addition of primary teeth represent variations of the same developmental process. The expression patterns of Sox2 support the hypothesis that dormant capacity for continuous tooth renewal exists in mammals.
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Pretreatment interleukin-6 serum levels are associated with patient survival for oral cavity squamous cell carcinoma.
Otolaryngol Head Neck Surg
PUBLISHED: 02-20-2013
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This study aims to determine the role of serum interleukin-6 concentration for oral cavity squamous cell carcinomas.
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FGF-1 delivery from multilayer alginate microbeads stimulates a rapid and persistent increase in vascular density.
Microvasc. Res.
PUBLISHED: 02-16-2013
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In recent years, great advances have been made in the use of islet transplantation as a treatment for type I diabetes. Indeed, it is possible that stimulation of local neovascularization upon transplantation could improve functional graft outcomes. In the present study, we investigate the use of multilayered alginate microbeads to provide a sustained delivery of FGF-1, and whether this results in increased neovascularization in vivo. Multilayered alginate microbeads, loaded with either 150ng or 600ng of FGF-1 in the outer layer, were surgically implanted into rats using an omentum pouch model and compared to empty microbead implants. Rats were sacrificed at 4days, 1week, and 6weeks. Staining for CD31 showed that both conditions of FGF-1 loaded microbeads resulted in a significantly higher vessel density at all time points studied. Moreover, at 6weeks, alginate microbeads containing 600ng FGF-1 provided a greater vascular density compared to both the control group and the microbeads loaded with 150ng FGF-1. Omenta analyzed via staining for smooth muscle alpha actin showed no variation in mural cell density at either 4days or 1week. At 6weeks, however, omenta exposed to microbeads loaded with 600ng FGF-1 showed an increase in mural cell staining compared to controls. These results suggest that the sustained delivery of FGF-1 from multilayered alginate microbeads results in a rapid and persistent vascular response. An increase in the local blood supply could reduce the number of islets required for transplantation in order to achieve clinical efficacy.
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Possible biomarkers of early mortality in peritonitis-induced sepsis rats.
J. Surg. Res.
PUBLISHED: 01-10-2013
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Sepsis induced by cecal ligation and puncture (CLP) is accompanied by circulatory failure, multiple organ dysfunction syndrome, metabolic acidosis, and electrolyte imbalance in rats. However, it remains uncertain which parameters can be used to predict the mortality of septic rats. Thus, the aim of this study was to examine which possible biomarkers were associated with mortality in the CLP-induced sepsis model.
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Tuning Wnt signals for more or fewer hairs.
J. Invest. Dermatol.
PUBLISHED: 01-10-2013
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Activation of ?-catenin was shown to be of central importance for hair development and cycling. Recent progress brought more understanding to how Wnt signaling is regulated during hair follicle generation and regeneration, telogen-anagen reentry, and extra-follicular macro-environmental modulation. This new understanding presents multiple possibilities to fine tune Wnt signaling for desired hair growth.
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Feather regeneration as a model for organogenesis.
Dev. Growth Differ.
PUBLISHED: 01-09-2013
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In the process of organogenesis, different cell types form organized tissues and tissues are integrated into an organ. Most organs form in the developmental stage, but new organs can also form in physiological states or following injuries during adulthood. Feathers are a good model to study post-natal organogenesis because they regenerate episodically under physiological conditions and in response to injuries such as plucking. Epidermal stem cells in the collar can respond to activation signals. Dermal papilla located at the follicle base controls the regenerative process. Adhesion molecules (e.g., neural cell adhesion molecule (NCAM), tenascin), morphogens (e.g., Wnt3a, sprouty, fibroblast growth factor [FGF]10), and differentiation markers (e.g., keratins) are expressed dynamically in initiation, growth and resting phases of the feather cycle. Epidermal cells are shaped into different feather morphologies based on the molecular micro-environment at the moment of morphogenesis. Chicken feather variants provide a rich resource for us to identify genetic determinants involved in feather regeneration and morphogenesis. An example of using genome-wide single nucleotide polymorphism (SNP) analysis to identify alpha keratin 75 as the mutation in frizzled chickens is demonstrated. Due to its accessibility to experimental manipulation and observation, results of regeneration can be analyzed in a comprehensive way. The layout of time dimension along the distal (formed earlier) to proximal (formed later) feather axis makes the morphological analyses easier. Therefore feather regeneration can be a unique model for understanding organogenesis: from activation of stem cells under various physiological conditions to serving as the Rosetta stone for deciphering the language of morphogenesis.
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RhoA/Rho-kinase and nitric oxide in vascular reactivity in rats with endotoxaemia.
PLoS ONE
PUBLISHED: 01-08-2013
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RhoA/Rho-kinase (RhoA/ROK) pathway promotes vasoconstriction by calcium sensitivity mechanism. LPS causes nitric oxide (NO) overproduction to induce vascular hyporeactivity. Thus, we tried to examine the role of RhoA/ROK and NO in the regulation of vascular reactivity in different time-point of endotoxaemia. Male Wistar rats were intravenously infused for 10 min with saline or E. coli endotoxin (lipopolysaccharide, LPS, 10 mg/kg) and divided to five groups (n?=?8 in each group): (i) Control, sacrificed at 6 h after saline infusion; (ii) LPS1h, sacrificed at 1 h after LPS infusion; (iii) LPS2h, sacrificed at 2 h after LPS infusion; (iv) LPS4h, sacrificed at 4 h after LPS infusion; and (v) LPS6h, sacrificed at 6 h after LPS infusion. LPS1h and LPS2h were regarded as early endotoxaemia, whereas LPS4h and LPS6h were regarded as late endotoxaemia. Indeed, our results showed that LPS reproduced a biphasic hypotension and sustained vascular hyporeactivity to noradrenaline (NA) in vivo. Interestingly, this hyporeactivity did not occur in ex vivo during early endotoxaemia. This could be due to increases of aortic RhoA activity (n?=?5, P<0.05) and myosin phosphatase targeting subunit 1 phosphorylation (n?=?3, P<0.05). In addition, pressor response to NA and vascular reactivity in early endotoxaemia were inhibited by ROK inhibitor, Y27632. Furthermore, plasma bradykinin was increased at 10 min (24.6±13.7 ng/mL, n?=?5, P<0.05) and aortic endothelial NO synthase expression was increased at 1 h (+200%. n?=?3, P<0.05) after LPS. In late endotoxaemia, the vascular hyporeactivity was associated with aortic inducible NO synthase expression (n?=?3, P<0.05) and an increased serum NO level (n?=?8, P<0.05). Thus, an increased RhoA activity could compensate vascular hyporeactivity in early endotoxaemia, and the large NO production inhibiting RhoA activity would lead to vascular hyporeactivity eventually.
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Therapeutic strategy for hair regeneration: hair cycle activation, niche environment modulation, wound-induced follicle neogenesis, and stem cell engineering.
Expert Opin Biol Ther
PUBLISHED: 01-05-2013
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There are major new advancements in the fields of stem cell biology, developmental biology, regenerative hair cycling, and tissue engineering. The time is ripe to integrate, translate, and apply these findings to tissue engineering and regenerative medicine. Readers will learn about new progress in cellular and molecular aspects of hair follicle development, regeneration, and potential therapeutic opportunities these advances may offer.
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Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-04-2013
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Hair follicles facilitate the study of stem cell behavior because stem cells in progressive activation stages, ordered within the follicle architecture, are capable of cyclic regeneration. To study the gene network governing the homeostasis of hair bulge stem cells, we developed a Keratin 15-driven genetic model to directly perturb molecular signaling in the stem cells. We visualize the behavior of these modified stem cells, evaluating their hair-regenerating ability and profile their molecular expression. Bone morphogenetic protein (BMP)-inactivated stem cells exhibit molecular profiles resembling those of hair germs, yet still possess multipotentiality in vivo. These cells also exhibit up-regulation of Wnt7a, Wnt7b, and Wnt16 ligands and Frizzled (Fzd) 10 receptor. We demonstrate direct transcriptional modulation of the Wnt7a promoter. These results highlight a previously unknown intra-stem cell antagonistic competition, between BMP and Wnt signaling, to balance stem cell activity. Reduced BMP signaling and increased Wnt signaling tilts each stem cell toward a hair germ fate and, vice versa, based on a continuous scale dependent on the ratio of BMP/Wnt activity. This work reveals one more hierarchical layer regulating stem cell homeostasis beneath the stem cell-dermal papilla-based epithelial-mesenchymal interaction layer and the hair follicle-intradermal adipocyte-based tissue interaction layer. Although hierarchical layers are all based on BMP/Wnt signaling, the multilayered control ensures that all information is taken into consideration and allows hair stem cells to sum up the total activators/inhibitors involved in making the decision of activation.
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Influence of crosslinking on the stiffness and degradation of dermis-derived hydrogels.
J Biomed Mater Res A
PUBLISHED: 01-02-2013
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Natural hydrogels have been investigated for three-dimensional tissue reconstruction and regeneration given their ability to emulate the structural complexity of multi-component extracellular matrices (ECM). Hydrogels rich in ECM can be extracted and assembled from soft tissues, retain a composition specific to the tissue source, and stimulate vascularized tissue formation. However, poor mechanical properties and rapid degradation hinder their performance in regenerative applications. This study investigates the effect of glutaraldehyde (GA) crosslinking on the mechanical properties, biological activity, and degradation of dermis-isolated ECM-rich hydrogels. Compression tests indicated that hydrogel elastic moduli and yield stress values increased significantly with GA exposure time. Lyophilization was shown to decrease yield stress values with respect to non-lyophilized gels. Crosslinked ECM, unlike non-crosslinked gels, was resistant to pepsin degradation in vitro. In a rodent subcutaneous implant model, crosslinking for 0.5 hours or longer drastically slowed degradation relative to controls. Inflammation was low and mature vascularized granulation tissue was observed in all gels, with an increase in vessel density at 1 week in crosslinked gels relative to controls. These results support the potential use of dermis-derived hydrogels as materials for tissue engineering applications and suggest that crosslinking can enhance mechanical properties and prolong hydrogel lifetime while promoting vascularized tissue formation.
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Postoperative alcohol withdrawal syndrome and neuropsychological disorder in patients after head and neck cancer ablation followed by microsurgical free tissue transfer.
J Reconstr Microsurg
PUBLISHED: 01-02-2013
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The use of microsurgical free flap reconstruction has resulted in improved patient outcomes and survival after head and neck cancer resection. Although postoperative care in an intensive care unit (ICU) for airway management and flap surveillance can increase the success rate, any accompanying neuropsychological problems can potentially affect the outcome.
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Fusion protein vaccines targeting two tumor antigens generate synergistic anti-tumor effects.
PLoS ONE
PUBLISHED: 01-01-2013
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Human papillomavirus (HPV) has been consistently implicated in causing several kinds of malignancies, and two HPV oncogenes, E6 and E7, represent two potential target antigens for cancer vaccines. We developed two fusion protein vaccines, PE(?III)/E6 and PE(?III)/E7 by targeting these two tumor antigens to test whether a combination of two fusion proteins can generate more potent anti-tumor effects than a single fusion protein.
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Epigenetic silencing of BLU through interfering apoptosis results in chemoresistance and poor prognosis of ovarian serous carcinoma patients.
Endocr. Relat. Cancer
PUBLISHED: 01-01-2013
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Epithelial ovarian carcinoma is usually present at the advanced stage, during which the patients generally have poor prognosis. Our study aimed to evaluate the correlation of gene methylation and the clinical outcome of patients with advanced-stage, high-grade ovarian serous carcinoma. The methylation status of eight candidate genes was first evaluated by methylation-specific PCR and capillary electrophoresis to select three potential genes including DAPK, CDH1, and BLU (ZMYND10) from the exercise group of 40 patients. The methylation status of these three genes was further investigated in the validation group consisting of 136 patients. Patients with methylated BLU had significantly shorter progression-free survival (PFS; hazard ratio (HR) 1.48, 95% CI 1.01-2.56, P=0.013) and overall survival (OS; HR 1.83, 95% CI 1.07-3.11, P=0.027) in the multivariate analysis. Methylation of BLU was also an independent risk factor for 58 patients undergoing optimal debulking surgery for PFS (HR 2.37, 95% CI 1.03-5.42, P=0.043) and OS (HR 3.96, 95% CI 1.45-10.81, P=0.007) in the multivariate analysis. A possible mechanism of BLU in chemoresistance was investigated in ovarian cancer cell lines by in vitro apoptotic assays. In vitro studies have shown that BLU could upregulate the expression of BAX and enhance the effect of paclitaxel-induced apoptosis in ovarian cancer cells. Our study suggested that methylation of BLU could be a potential prognostic biomarker for advanced ovarian serous carcinoma.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.