bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Origin of the Enhanced Acidity of Chalcocyclopentadienes (Cyclopentadiene Chalcogenols) in the Gas Phase
Authors: Hurtado Marcela , Lamsabhi Al M. , Mó Otilia , Yáñez Manuel , Guillemin Jean‐Claude
Published: February 2012

The intrinsic acidity of chalcocyclopentadienes (CpXH; X=O, S, Se, Te) is investigated by high‐level G3B3 and G2 ab initio as well as B3LYP DFT calculations, which show that, independent of the nature of the heteroatom, all chalcocyclopentadienes are stronger acids in the gas phase than cyclopentadiene. However the acidity does not increase regularly down the group, and the acidity enhancement for Te derivatives is five times larger than for O derivatives, but only twice that of S‐containing compounds. The most favorable deprotonation process corresponds to loss of the proton attached to the heteroatom, with the sole exception of the 5‐substituted 1,3‐cyclopentadienes, for which the O and S derivatives are predicted to behave as carbon acids. No matter the nature of the heteroatom, the 1‐substituted 1,3‐cyclopentadienes are the strongest acids. The intrinsic acidity of all isomers, namely, 1‐substituted, 2‐substituted, and 5‐substituted 1,3‐cyclopentadienes, increases with increasing aromaticity of the anion formed on deprotonation, and therefore the Te compound is the strongest acid for the three series. However, the intrinsic acidity of chalcocyclopentadienes is not dictated by aromaticity, so that, in general, the most stable deprotonated species do not coincide with the most aromatic ones.
Performance analysis of multi‐antenna relay communication systems with MRC
Authors: Guan Zhang‐Jun , Zhang Wei‐Jiong , Zhou Xi‐Lang
Published: February 2012

The performance of multi‐antenna relay communication systems is investigated in this letter. The source broadcasts the signal to all the relays and the destination. Decode‐and‐forward scheme is adopted at the relays, and the destination employs maximum ratio combining (MRC) technique to maximize the received signal‐to‐noise ratio. Closed‐form expressions of outage probability are derived in the MRC case and minimum routes MRC case. An adaptive grouping algorithm of relay antennas is also presented under the constraint of total antenna number. Simulation results show that the analytical curves agree with the simulated ones very well, and the performance of the proposed grouping algorithm is very close to the upper bound mentioned in other papers. Copyright © 2012 John Wiley & Sons, Ltd.
Programming and reprogramming neuronal subtypes in the central nervous system
Authors: Rouaux Caroline , Bhai Salman , Arlotta Paola
Published: February 2012

Recent discoveries in nuclear reprogramming have challenged the dogma that the identity of terminally differentiated cells cannot be changed. The identification of molecular mechanisms that reprogram differentiated cells to a new identity carries profound implications for regenerative medicine across organ systems. The central nervous system (CNS) has historically been considered to be largely immutable. However, recent studies indicate that even the adult CNS is imparted with the potential to change under the appropriate stimuli. Here, we review current knowledge regarding the capability of distinct cells within the CNS to reprogram their identity and consider the role of developmental signals in directing these cell fate decisions. Finally, we discuss the progress and current challenges of using developmental signals to precisely direct the generation of individual neuronal subtypes in the postnatal CNS and in the dish. © 2012 Wiley Periodicals, Inc. Develop Neurobiol 72: 1085–1098, 2012
Generation of Fbn1 conditional null mice implicates the extracellular microfibrils in osteoprogenitor recruitment
Authors: Cook Jason R. , Smaldone Silvia , Cozzolino Carmine , del Solar Maria , Lee‐Arteaga Sui , Nistala Harikiran , Ramirez Francesco
Published: February 2012

Loss‐of‐function experiments in mice have yielded invaluable mechanistic insights into the pathogenesis of Marfan syndrome (MFS) and implicitly, into the multiple roles fibrillin‐1 microfibrils play in the developing and adult organism. Unfortunately, neonatal death from aortic complications of mice lacking fibrillin‐1 (Fbn1−/− mice) has limited the scope of these studies. Here, we report the creation of a conditional mutant allele (Fbn1fneo) that contains loxP sites bordering exon1 of Fbn1 and an frt‐flanked neo expression cassette downstream of it. Fbn1fneo/+ mice were crossed with FLPeR mice and the resulting Fbn1Lox/+ progeny were crossed with Fbn1+/−;CMV‐Cre mice to generate Fbn1CMV−/− mice, which were found to phenocopy the vascular abnormalities of Fbn1−/− mice. Furthermore, mating Fbn1Lox/+ mice with Prx1‐Cre or Osx‐Cre mice revealed an unappreciated role of fibrillin‐1 microfibrils in restricting osteoprogenitor cell recruitment. Fbn1Lox/+ mice are, therefore, an informative genetic resource to further dissect MFS pathogenesis and the role of extracellular fibrillin‐1 assemblies in organ development and homeostasis. genesis 50:635–641, 2012. © 2012 Wiley Periodicals, Inc.
Statistical classification of vegetation and water depths in montane wetlands
Authors: Sharp Julia L. , Sojda Richard S. , Greenwood Mark , Rosenberry Donald O. , Warren Jeffrey M.
Published: February 2012

Relationships between water depths and density of submergent vegetation were studied in montane wetlands using statistical techniques based on clustering and an extension of regression trees. Sago pondweed (Stuckenia pectinata) was associated with lower average water depths than water milfoil (Myriophyllum sibiricum). We detected a nonlinear relationship when average water depths were used to predict percent cover in S. pectinata, with depths of 30–40 cm, producing the highest predicted average percent cover of S. pectinata; higher and lower depths resulted in lower percent cover predictions. For M. sibiricum, higher water depths were monotonically associated with higher average percent cover. To foster more S. pectinata and less M. sibiricum, managers might employ water control structures to reduce water depths below 1 m, using both temporary drawdowns and average depths of 30–40 cm. Other species responded less markedly to water depth variation. Should decreased water depths become more common, these results suggest an increase in S. pectinata and a decrease in M. sibiricum. Published in 2012. This article is a US Government work and is in the public domain in the USA.
N‐Doped Nb2O5 Sensitized by Carbon Nitride Polymer – Synthesis and High Photocatalytic Activity under Visible Light
Authors: Wang Xu , Chen Gang , Zhou Chao , Yu Yaoguang , Wang Gang
Published: February 2012

N‐doped Nb2O5 sensitized by carbon nitride polymer (CNNO) was synthesized as a yellowish powder by using urea as a carbon–nitrogen precursor. CNNO was tested as a catalyst for the visible‐light‐responsive photodegradation of dyes. HNbO3, one of the precursors of CNNO, was obtained from LiNbO3 by a H+–Li+ ion‐exchange reaction and then pyrolyzed at 400 °C to produce a Nb2O5 substrate. The photocatalytic activities of as‐prepared samples were evaluated by the degradation of Rhodamine B (RhB) under Xe lamp irradiation (λ > 400 nm), for which the photocatalysts showed relatively high activities. XRD, thermogravimetry and differential scanning calorimetry (TG–DSC), scanning electron microscopy (SEM), energy‐dispersive X‐ray spectroscopy (EDS), TEM, X‐ray photoelectron spectroscopy (XPS), UV/Vis diffuse reflectance spectroscopy (DRS), and Brunauer–Emmett–Teller (BET) measurements were utilized to explore the characteristics of the obtained samples. The results demonstrated that the surface of Nb2O5 was successfully coated, as a semitransparent layer of CN polymer surrouding the dark substrate was observed. UV/Vis DRS showed that the absorption edges of CNNO were shifted remarkably to the visible region relative to those of naked Nb2O5. These results revealed that the significantly enhanced photocatalytic activities of the CNNO samples originate from the CN polymer. The coating led to an efficient electron transfer between the CN polymer, which acted as a photosensitizer, and the N‐doped Nb2O5. The degradation mechanism that underlies the excellent photocatalytic activity of CNNO was discussed extensively.
Biscyclohexane‐Annulated Diethyl Dipyrrindicarboxylates: Observation of a Dipyrrin Form with Absent Visible Absorption
Authors: Tikhomirova Ksenia , Anisimov Alexander , Khoroshutin Andrey
Published: February 2012

A series of 2,3;7,8‐biscyclohexano‐fused diethyl 5‐aryldipyrrin‐1,9‐dicarboxylates have been synthesized [aryl = phenyl, 3,4‐dimethoxyphenyl and 2,3,5,6,8,9,11,12‐octahydro‐1,4,7,10,13‐benzopentaoxacyclopentadecine‐15‐yl (m‐benzo‐15‐crown‐5)]. The obtained compounds were shown to exist in two equilibrium forms in solution, with one exhibiting a visible absorption band (λabs 468–485 nm), and the other, “vis‐silent” form, having no absorption band in the visible region. The “vis‐silent” form has been isolated and characterized by NMR analysis, including two‐dimensional techniques. Quantum chemical calculations have also been performed, yielding two main conformations with proximate and distant arrangements of the nitrogen atoms. In the latter conformation the pyrrole–pyrrolene fragments were found to be nearly orthogonal, with no long chain of conjugation. Computational results confirm the spectroscopic findings. Two different forms were also characterized as their Mg2+ complex and investigated by UV/Vis and by NMR spectroscopic analyses and a clear difference was noted.
Pelletization of biochar from hydrothermally carbonized wood
Authors: Reza M. Toufiq , Lynam Joan G. , Vasquez Victor R. , Coronella Charles J.
Published: February 2012

Hydrothermal carbonization (HTC) is a pretreatment process for making a homogenized, carbon rich, and energy dense solid fuel, called biochar, from underutilized lignocellulosic biomass. Compared to raw biomass, HTC biochar is both more hydrophobic for better storage and more friable for better processing. In this pretreatment method, the biomass is treated with hot compressed water in the temperature range of 200–260°C. Hemicelluloses and water extractives react very quickly compared to cellulose. Lignin is relatively inert, resulting in a biochar with increased lignin content. Lignin acts as a binder for pelletization of pretreated lignocellulosic biomass. A hydraulic press with a controllable heated die was used for pelletization studies. The materials used to make pellets were raw loblolly pine and pine pretreated at different temperatures. The presence of solid bridges was observed in both raw pine pellets and HTC biochar pellets. Pellets made from HTC biochar exhibit favorable properties, including increased hydrophobicity, abrasion resistance, energy density, and mass density compared to pellets produced from raw pine or from dry torrefied pine. Pellets produced from biomass pretreated at 260°C have a volumetric fuel value 70% greater than pellets produced from untreated pine (38.8 MJ/m3 vs. 22.8 GJ/m3), a mass density of 1468 kg/m3, and a higher heating value of 26.4 MJ/kg. © 2012 American Institute of Chemical Engineers Environ Prog, 2012
Multi‐user coherent beamforming in packet‐based wireless systems
Authors: Oh Dong‐Chan , Lee Yong‐Hwan
Published: February 2012

In this paper, we propose a multi‐antenna technique that can simultaneously achieve spatial multiplexing and multi‐user diversity gain with the use of coherent beam weight of scheduled users. Multiple beams are utilised to maximise the spatial multiplexing gain while fully achieving the multi‐user diversity gain through each channel. Combined use of a beamforming and zero‐forcing encoding can suppress the inter‐stream interference at the transmitter. We also consider seamless adjustment of the number of beams for data transmission to maximise the sum‐rate capacity according to the operating condition. Simulation results show the effectiveness of the proposed scheme. Copyright © 2012 John Wiley & Sons, Ltd.
On the Compressibility of Gas Diffusion Layers in Proton Exchange Membrane Fuel Cells
Authors: Ismail M. S. , Hassanpour A. , Ingham D. B. , Ma L. , Pourkashanian M.
Published: February 2012

The mechanical behavior under compression for a number of gas diffusion layers (GDLs) and a sealing gasket used in proton exchange membrane fuel cells (PEMFCs) has been investigated. The results show that the stiffness of the carbon substrate increases with increasing polytetrafluoroethylene (PTFE) loading. Also, coating the carbon substrate with the microporous layer (MPL) significantly enhances the stiffness of the GDL. On the other hand, the stiffness of the GDL appears to slightly decrease with an increase in the PTFE loading present in the MPL. For a given practical compressive pressure, the mechanical behavior of the GDLs is hugely controlled by the less compressible sealing gaskets. Furthermore, it has been found that the compression curves for the tested materials must be corrected for machine compliance. Otherwise, the stiffness of the tested materials is significantly underestimated.
Investigation on Proton Conductivity of La2Ce2O7 in Wet Atmosphere: Dependence on Water Vapor Partial Pressure
Authors: Sun W. , Fang S. , Yan L. , Liu W.
Published: February 2012

The AC conductivity of fluorite‐structured La2Ce2O7 ceramic was measured under air and argon with different humidity between 250 and 550 °C. It was observed that the total conductivity in wet air and argon was higher than that under dry atmospheres. The effect of water vapor partial pressure ($ {P_{\rm {H_2{\rm O}}}} $) on the conductivity of La2Ce2O7 in air was investigated in detail. The total conductivity increased remarkably with the water vapor partial pressure, and this phenomenon became more notable at lower temperatures. The enhancement of the conductivity was attributed to the proton conduction behavior of La2Ce2O7 in wet atmospheres, and the proton conductivity reached 6.68 × 10–5 S cm–1 in wet air (3% H2O) at 550 °C. The relationship between the proton conductivity (σH) and $ {P_{\rm {H_2{\rm O}}}} $ in wet air could be fitted to $ \sigma_{\rm H} \propto {P_{\rm {H_2{\rm O}}}^{1/2}} $. The estimated proton transport number increased with increasing water vapor partial pressure and decreasing temperature, and varied between 0.05 and 0.89 in this study.
Aquaporin‐4 and epilepsy
Authors: Binder Devin K. , Nagelhus Erlend A. , Ottersen Ole Petter
Published: February 2012

Recent studies have implicated glial cells in modulation of synaptic transmission, so it is plausible that glial cells may have a functional role in the hyperexcitability characteristic of epilepsy. Indeed, alterations in distinct astrocyte membrane channels, receptors, and transporters have all been associated with the epileptic state. This review focuses on the potential roles of the glial water channel aquaporin‐4 (AQP4) in modulation of brain excitability and in epilepsy. We will review studies of mice lacking AQP4 (Aqp4−/− mice) or α‐syntrophin (an AQP4 anchoring protein) and discuss the available human studies demonstrating alterations of AQP4 in human epilepsy tissue specimens. We will conclude with new studies of AQP4 regulation and discuss the potential role of AQP4 in the development of epilepsy (epileptogenesis). While many questions remain unanswered, the available data indicate that AQP4 and its molecular partners may represent important new therapeutic targets. © 2012 Wiley Periodicals, Inc.
Seeking huntington disease biomarkers by multimodal, cross‐sectional basal ganglia imaging
Authors: Sánchez‐Castañeda Cristina , Cherubini Andrea , Elifani Francesca , Péran Patrice , Orobello Sara , Capelli Giovanni , Sabatini Umberto , Squitieri Ferdinando
Published: February 2012

Neurodegeneration of the striatum in Huntington disease (HD) is characterized by loss of medium‐spiny neurons, huntingtin nuclear inclusions, reactive gliosis, and iron accumulation. Neuroimaging allows in vivo detection of the macro‐ and micro‐structural changes that occur from presymptomatic stages of the disease (preHD). The aim of our study was to evaluate the reliability of multimodal imaging as an in vivo biomarker of vulnerability and development of the disease and to characterize macro‐ and micro‐structural changes in subcortical nuclei in HD. Macrostructure (T1‐weighted images), microstructure (diffusion tensor imaging), and iron content (R relaxometry) of subcortical nuclei and medial temporal lobe structures were evaluated by a 3 T scanner in 17 preHD carriers, 12 early‐stage patients and 29 matched controls. We observed a volume reduction and microstructural changes in the basal ganglia (caudate, putamen, and globus pallidus) and iron accumulation in the globus pallidus in both preHD and symptomatic subjects; all these features were significantly more pronounced in patients, in whom degeneration extended to the other subcortical nuclei (i.e., thalamus and accumbens). Mean diffusivity (MD) was the most powerful predictor in models explaining more than 50% of the variability in HD development in the caudate, putamen, and thalamus. These findings suggest that the measurement of MD may further enhance the well‐known predictive value of striatal volume to assess disease progression as it is highly sensitive to tissue microimpairment. Multimodal imaging may detect brain changes even in preHD stages. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
Abrupt behaviours of streamflow and sediment load variations of the Yangtze River basin, China
Authors: Zhang Qiang , Singh Vijay P. , Xu Chong‐Yu , Chen Xiaohong
Published: February 2012

Monthly sediment load and streamflow series spanning 1963–2004 from four hydrological stations situation in the main stem of the Yangtze River, China, are analysed using scanning t‐test and the simple two‐phase linear regression scheme. Results indicate significant changes in the sediment load and streamflow from the upper reach to the lower reach of the Yangtze River. Relatively consistent positive coherency relations can be detected between streamflow and sediment load in the upper reach and negative coherency in the middle and lower reaches. Interestingly, negative coherency is found mainly for larger time scales. Changes in sediment load are the result mainly of human influence; specifically, the construction of water reservoirs may be the major cause of negative coherency. Accentuating the human influence from the upper to the lower reach results in inconsistent correlations between sediment load and streamflow. Decreasing sediment load being observed in recent years has the potential to alter the topographical properties of the river channel and the consequent development and recession of the Yangtze Delta. Results of this study are of practical significance for river channel management and evaluation of the influence of human activities on the hydrological regimes of large rivers. Copyright © 2012 John Wiley & Sons, Ltd.
Immune response against Streptococcus gallolyticus in patients with adenomatous polyps in colon
Authors: Garza‐González Elvira , Ríos Merab , Bosques‐Padilla Francisco J. , Francois Fritz , Cho Ilseung , González Gloria M. , Pérez‐Pérez Guillermo I.
Published: February 2012

Our aim was to examine the humoral immune response against Streptococcus gallolyticus subspecies gallolyticus antigens in individuals subjected to a routine colonoscopy in which colon adenomatous polyps were present or not. Serum samples from 133 individuals with adenomatous polyps and serum samples from 53 individuals with a normal colonoscopy were included. Western blot was performed in all subjects using a whole cell antigen from S. gallolyticus ATCC 9809, and rabbit antisera against the whole cell bacteria was prepared as a control. By analyzing the immune profile of the rabbit‐immunized sera by Western‐blot, at least 22 proteins were identified as immunogenic in S. gallolyticus. When we evaluated sera from human subjects, two proteins of approximately 30 and 22 kDa were most prominent. Based on this 2‐protein band pattern, Western‐blot profiles from human subjects were compared. The detection of a protein band of 22 kDa was associated with the presence of adenomatous polyps in colon [odds ratios (OR) 7.98, 95% confidence intervals (CI): 3.54–17.93], p < 0.001. When the presence of the 30 kDa protein alone or both the 22 and 30 kDa proteins were analyzed, the OR increased to 22.37 (95% CI: 3.77–131.64), p < 0.001. The specificity was 84.9 for the presence of the 22 kDa protein, and 98.1 for the presence of the 30 kDa protein alone or both 22 and 30 kDa bands. Serum from individuals with adenomatous polyps recognized two proteins from S. gallolyticus. This result confirmed the possible association of S. gallolyticus with adenomatous polyps in the colon.
p38α MAPK mediates 17β‐estradiol inhibition of MMP‐2 and ‐9 expression and cell migration in human lovo colon cancer cells
Authors: Hsu Hsi‐Hsien , Liu Chung‐Jung , Shen Chia‐Yao , Chen Yi‐Jyun , Chen Li‐Mien , Kuo Wu‐Hsien , Lin Yueh‐Min , Chen Ray‐Jade , Tsai Chang‐Hai , Tsai Fuu‐Jen , Huang Chih‐Yang
Published: February 2012

Epidemiological studies demonstrate that the incidence and mortality rates of colorectal cancer in women are lower than in men. However, it is unknown if 17β‐estradiol (E2) treatment is sufficient to inhibit cell proliferation and cell migration in human colon cancer cells. Up‐regulation of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), and matrix metallopeptidases (MMPs) is reported to associate with the development of cancer cell mobility, metastasis, and subsequent malignant tumor. In the present study, we treated human LoVo colon cancer cells with E2 to explore whether E2 down‐regulates cell proliferation and migration, and to identify the precise molecular and cellular mechanisms behind the down‐regulatory responses. Here, we found that E2 treatment decreased cell proliferation and cell cycle‐regulating factors such as cyclin A, cyclin D1 and cyclin E. At the same time, E2 significantly inhibited cell migration and migration‐related factors such as uPA, tPA, MMP‐2, and MMP‐9. However, E2 treatment showed no effects on upregulating expression of plasminogen activator inhibitor‐1 (PAI‐1), tissue inhibitor of metalloproteinase‐1, ‐2, ‐3, and ‐4 (TIMP‐1, ‐2, ‐3, and ‐4). After administration of inhibitors including QNZ (NFκB inhibitor), LY294002 (Akt activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor) or SP600125 (JNK1/2 inhibitor), E2‐downregulated cell migration and expression of MMP‐2 and MMP‐9 in LoVo cells is markedly inhibited only by p38 MAPK inhibitors, SB203580. Application of specific target gene siRNA (ERα, ERβ, p38α, and p38β) to LoVo cells further confirmed that p38 MAPK mediates E2/ERs inhibition of MMP‐2 and ‐9 expression and cell motility in LoVo cells.

Collectively, these results suggest that E2 treatment down‐regulates cell proliferation by modulating the expression of cyclin A, cyclin D1 and cyclin E. E2 treatment simultaneously impaired cell migration by inhibiting the expression of uPA, tPA, MMP‐2, and MMP‐9 through E2/ERs − p38α MAPK signaling pathway in human LoVo colon cancer cells. J. Cell. Physiol. 227: 3648–3660, 2012. © 2012 Wiley Periodicals, Inc.
Trop‐2 inhibits prostate cancer cell adhesion to fibronectin through the β1 integrin‐RACK1 axis
Authors: Trerotola Marco , Li Jing , Alberti Saverio , Languino Lucia R.
Published: February 2012

Trop‐2 is a transmembrane glycoprotein upregulated in several human carcinomas, including prostate cancer (PrCa). Trop‐2 has been suggested to regulate cell–cell adhesion, given its high homology with the other member of the Trop family, Trop‐1/EpCAM, and its ability to bind the tight junction proteins claudin‐1 and claudin‐7. However, a role for Trop‐2 in cell adhesion to the extracellular matrix has never been postulated. Here, we show for the first time that Trop‐2 expression in PrCa cells correlates with their aggressiveness. Using either shRNA‐mediated silencing of Trop‐2 in cells that endogenously express it, or ectopic expression of Trop‐2 in cells that do not express it, we show that Trop‐2 inhibits PrCa cell adhesion to fibronectin (FN). In contrast, expression of another transmembrane receptor, αvβ5 integrin, does not affect cell adhesion to this ligand. We find that Trop‐2 does not modulate either protein or activation levels of the prominent FN receptors, β1 integrins, but acts through increasing β1 association with the adaptor molecule RACK1 and redistribution of RACK1 to the cell membrane. As a result of Trop‐2 expression, we also observe activation of Src and FAK, known to occur upon β1‐RACK1 interaction. These enhanced Src and FAK activities are not mediated by changes in either the activity of IGF‐IR, which is known to bind RACK1, or IGF‐IR's ability to associate with β1 integrins. In summary, our data demonstrate that the transmembrane receptor Trop‐2 is a regulator of PrCa cell adhesion to FN through activation of the β1 integrin‐RACK1‐FAK‐Src signaling axis. J. Cell. Physiol. 227: 3670–3677, 2012. © 2012 Wiley Periodicals, Inc.
Role of fibroblast growth factor 2 and wnt signaling in anabolic effects of parathyroid hormone on bone formation
Authors: Fei Yurong , Hurley Marja M.
Published: February 2012

Osteoporosis poses enormous health and economic burden worldwide. One of the very few anabolic agents for osteoporosis is parathyroid hormone (PTH). Although great progress has been made since the FDA approved PTH in 2002, the detailed mechanisms of the bone anabolic effects of intermittent PTH treatment is still not well understood. PTH bone anabolic effect is regulated by extracellular factors. Maximal bone anabolic effect of PTH requires fibroblast growth factor 2 (FGF2) signaling, which might be mediated by transcription factor activating transcription factor 4 (ATF4). Maximal bone anabolic effect of PTH also requires Wnt signaling. Particularly, Wnt antagonists such as sclerostin, dickkopf 1 (DKK1) and secreted frizzled related protein 1 (sFRP1) are promising targets to increase bone formation. Interestingly, FGF2 signaling modulates Wnt/β‐Catenin signaling pathway in bone. Therefore, multiple signaling pathways utilized by PTH are cross talking and working together to promote bone formation. Extensive studies on the mechanisms of action of PTH will help to identify new pathways that regulate bone formation, to improve available agents to stimulate bone formation, and to identify potential new anabolic agents for osteoporosis. J. Cell. Physiol. 227: 3539–3545, 2012. © 2012 Wiley Periodicals, Inc.
Nanog regulates molecules involved in stemness and cell cycle‐signaling pathway for maintenance of pluripotency of P19 embryonal carcinoma stem cells
Authors: Choi Seung‐Cheol , Choi Ji‐Hyun , Park Chi‐Yeon , Ahn Chul‐Min , Hong Soon‐Jun , Lim Do‐Sun
Published: February 2012

To identify potential downstream targets of Nanog, a key transcription factor in the maintenance of pluripotency of embryonic stem (ES) and embryonal carcinoma (EC) cells, global gene expression profiles in Nanog small interfering RNA (siRNA)‐transfected P19 EC stem cells were performed using cDNA, 60‐mer, and 30‐mer microarray platforms. The putative Nanog target genes identified by Nanog silencing were verified using reverse transcription‐polymerase chain reaction after Nanog overexpression. Downregulation of Nanog in P19 cells resulted in reduction of pluripotency markers, such as Fgf4, Klf2, Mtf2, Oct‐4, Rex1, Sox1, Yes, and Zfp143, whereas overexpression of Nanog in P19 cells reversely upregulated their expression. However, expressions of pluripotency markers Cripto, germ cell nuclear factor, Sox2, and Zfp57 as well as leukemia inhibitory factor (LIF)/Stat3 pathway molecules LIF, IL6st, and Stat3 were not affected after 48 h transfection with Nanog siRNA or construct. Nanog silencing also downregulated expression of molecules involved in the p53‐ and cell cycle‐signaling pathway (Atf3, Jdp2, Cul3, Hist1hic, and Bcl6), whereas expression of E2f1, Tob1, Lyn, and Smarcc1 was upregulated by Nanog silencing. Expressions of cyclins D1, D2, D3, and E1 as well as cyclin‐dependent kinase (Cdk) 1 and Cdk6 were downregulated by Nanog silencing in P19 cells, whereas Nanog overexpression reversely increased their expressions. Taken together, examination of global transcriptional changes after Nanog silencing followed by verification by Nanog overexpression has revealed new molecules involved in the maintenance of self‐renewal and in the regulation of the p53‐ and cell cycle‐pathway of P19 cells. J. Cell. Physiol. 227: 3678–3692, 2012. © 2012 Wiley Periodicals, Inc.
Facilitated diffusion of VEGF165 through descemet's membrane with sucrose octasulfate
Authors: Fannon Michael , Forsten‐Williams Kimberly , Zhao Bing , Bach Eva , Parekh Parag P. , Chu Chia Lin , Goerges‐Wildt Adrienne L , Buczek‐Thomas Jo Ann , Nugent Matthew A.
Published: February 2012

Vascular endothelial growth factor A (VEGF‐A) is a promoter of neovascularization and thus a popular therapeutic target for diseases involving excessive growth of blood vessels. In this study, we explored the potential of the disaccharide sucrose octasulfate (SOS) to alter VEGF165 diffusion through Descemet's membrane. Descemet's membranes were isolated from bovine eyes and used as a barrier between two chambers of a diffusion apparatus to measure VEGF transport. Diffusion studies revealed a dramatic increase in VEGF165 transport in the presence of SOS, with little diffusion of VEGF165 across the membrane over a 10‐h time course in the absence of SOS. Diffusion studies with VEGF121, a non‐heparin binding variant of VEGF, showed robust diffusion with or without SOS. To determine a possible mechanism, we measured the ability of SOS to inhibit VEGF interactions with extracellular matrix (ECM), using cell‐free and cell surface binding assays. Binding studies showed SOS had no effect on VEGF165 binding to either heparin‐coated plates or endothelial cell surfaces at less than mg/ml concentrations. In contrast, we show that SOS inhibited VEGF165 binding to fibronectin in a dose dependent manner and dramatically accelerated the rate of release of VEGF165 from fibronectin. SOS also inhibited the binding of VEGF165 to fibronectin‐rich ECM deposited by vascular smooth muscle cells. These results suggest that fibronectin‐rich extracellular matrices serve as barriers to VEGF165 diffusion by providing a network of binding sites that can trap and sequester the protein. Since the content of Descemet's membrane is typical of many basement membranes it is possible that they serve throughout the body as formidable barriers to VEGF165 diffusion and tightly regulate its bioavailability and distribution within tissues. J. Cell. Physiol. 227: 3693–3700, 2012. © 2012 Wiley Periodicals, Inc.
Recapitulation of mesenchymal condensation enhances in vitro chondrogenesis of human mesenchymal stem cells
Authors: Ghone Nalinkanth V. , Grayson Warren L.
Published: February 2012

Mesenchymal condensation is a critical transitional stage that precedes cartilage formation during embryonic development. We hypothesized that “priming” hMSCs to recapitulate mesenchymal condensation events prior to inducing differentiation would enhance their subsequent chondrogenic properties. Our prior studies have suggested that exposing hMSCs to hypoxia (2% O2) induces condensation‐like effects. We therefore assessed the effect of preconditioning for different time periods on the expression of condensation specific genes by growing hMSCs in expansion medium under different normoxic (20% O2) and hypoxic conditions for up to 2 weeks, and subsequently induced chondrogenesis of preconditioned hMSCs. The total cultivation time for each group was 4 weeks and the chondrogenic properties were assessed using gene expression, biochemical analysis, and histological staining. Our results demonstrated the benefits of preconditioning were both time‐ and oxygen‐dependent. Condensation specific genes, SOX‐9 and NCAM, were significantly up‐regulated in hypoxic conditions at the end of 1 week. COL X and MMP13 expression was also lower than the normoxic samples at this time point. However, this group did not exhibit more efficient chondrogenesis after 4 weeks. Instead, hMSCs preconditioned for 1 week and subsequently differentiated, both under 20% O2, resulted in the most efficient chondrogenesis. Interestingly, while hypoxia appears to positively enhance expression of chondrogenic genes, this did not produce an enhanced matrix accumulation. The results of this study emphasize the significance of considering the timing of specific cues in developing protocols for stem cell‐based therapies and underscore the complexity in regulating stem cell differentiation and tissue formation. J. Cell. Physiol. 227: 3701–3708, 2012. © 2012 Wiley Periodicals, Inc.
Non‐classical membrane trafficking processes galore
Authors: Chua Christelle En Lin , Lim Yi Shan , Lee Min Goo , Tang Bor Luen
Published: February 2012

Dogmatic views of how proteins and other cellular components may traffic within and between eukaryotic cells have been challenged in the past few years. Beyond the classical secretory/exocytic pathway and its established players, other pathways of cell surface membrane transport, generally termed “unconventional secretion,” are now better understood. More insights have also been gleaned on the roles of secreted or shedding microvesicles, either exosomal or ectosomal in origin, in unconventional secretion. Recent works have also revealed key molecular components, particularly the Golgi reassembly stacking protein (GRASP), and the importance of stress‐induced autophagy, in unconventional exocytic transport. This GRASP and autophagy‐dependent (GAD) mode appears to underlie the unconventional exocytosis of many soluble and membrane cargoes. Likewise, recent findings have revealed transport processes that contrast the classically known mitochondria import, namely vesicular transport from the mitochondria to peroxisomes and lysosomes. Mitochondria‐peroxisomal targeting of mitochondria‐derived vesicles appears to involve the retromer complex, which was classically associated with endosome‐Golgi membrane traffic. The routes of intracellular membrane transport and communications between eukaryotic organelles now appear far more complex that one would have imagined 10 years ago. J. Cell. Physiol. 227: 3722–3730, 2012. © 2012 Wiley Periodicals, Inc.
Role of FGFs/FGFRs in skeletal development and bone regeneration
Authors: Du Xiaolan , Xie Yangli , Xian Cory J. , Chen Lin
Published: February 2012

Fibroblast growth factor (FGF)/FGF (FGFR) signaling is an important pathway involved in skeletal development. Missense mutations in FGFs and FGFRs were found clinically to cause multiple congenital skeleton diseases including chondrodysplasia, craniosynostosis, syndromes with dysregulated phosphate metabolism. FGFs/FGFRs also have crucial roles in bone fracture repair and bone regeneration. Understanding the molecular mechanisms for the role of FGFs/FGFRs in the regulation of skeletal development, genetic skeletal diseases, and fracture healing will ultimately lead to better treatment of skeleton diseases caused by mutations of FGFs/FGFRs and fracture. This review summarizes the major findings on the role of FGF signaling in skeletal development, genetic skeletal diseases and bone healing, and discusses issues that remain to be resolved in applying FGF signaling‐related measures to promote bone healing. This review has also provided a perspective view on future work for exploring the roles and action mechanisms of FGF signaling in skeletal development, genetic skeletal diseases, and fracture healing. J. Cell. Physiol. 227: 3731–3743, 2012. © 2012 Wiley Periodicals, Inc.
Patient experiences of transitioning from hospital to home: An ethnographic quality improvement project
Authors: Cain Carol H. , Neuwirth Estee , Bellows Jim , Zuber Christi , Green Jennifer
Published: February 2012

BACKGROUND:

Little is known about patient perspectives of the transition from hospital to home.

OBJECTIVE:

To develop a richly detailed, patient‐centered view of patient and caregiver needs in the hospital‐to‐home transition.

DESIGN:

An ethnographic approach including participant observation and in‐depth, semi‐structured video recorded interviews.

SETTING:

Kaiser Permanente's Southern California, Colorado, and Hawaii regions.

PATIENTS:

Twenty‐four adult inpatients hospitalized for a range of acute and chronic conditions and characterized by variety in diagnoses, illness severity, planned or unplanned hospitalization, age, and ability to self manage.

RESULTS:

During the hospital‐to‐home transition, patients and caregivers expressed or demonstrated experiences in 6 domains: 1) translating knowledge into safe, health‐promoting actions at home; 2) inclusion of caregivers at every step of the transition process; 3) having readily available problem‐solving resources; 4) feeling connected to and trusting providers; 5) transitioning from illness‐defined experience to “normal” life; and 6) anticipating needs after discharge and making arrangements to meet them. The work of transitioning occurs for patients and caregivers in the hours and days after they return home and is fraught with challenges.

CONCLUSIONS:

Reducing readmissions will remain challenging without a broadened understanding of the types of support and coaching patients need after discharge. We are piloting strategies such as risk stratification and tailoring of care, a specialized phone number for recently discharged patients, standardized same‐day discharge summaries to primary care providers, medication reconciliation, follow‐up phone calls, and scheduling appointments before discharge. Journal of Hospital Medicine 2012; © 2012 Society of Hospital Medicine
Understanding organizational diversity management programs: A theoretical framework and directions for future research
Authors: Olsen Jesse E. , Martins Luis L.
Published: February 2012

With the changing demographic composition of the workforce, managing diversity in organizations is an important organizational function. Organizations have employed varying approaches to diversity management (DM), resulting in varying organizational outcomes. Meanwhile, researchers have called for more theoretical development within the DM area. We present a framework rooted in social and cross‐cultural psychological research, to foster theory development and empirical testing in the area of DM. We also derive several propositions to guide future research on DM and note some boundary conditions that suggest research opportunities of their own. Our framework contributes a theoretical conceptualization that enhances our understanding of organizations' DM efforts, integrates current typologies, and suggests new directions of inquiry for management scholars as well as guidelines for practitioners in the area. Copyright © 2012 John Wiley & Sons, Ltd.
Evaluation of Akt/mTOR activity in muscle atrophy after rotator cuff tears in a rat model
Authors: Liu Xuhui , Joshi Sunil K. , Samagh Sanjum P. , Dang Yu‐Xuan , Laron Dominique , Lovett David H. , Bodine Sue C. , Kim Hubert T. , Feeley Brian T.
Published: February 2012

Atrophy of the rotator cuff muscles is a factor that complicates the treatment of a massive rotator cuff tear (RCT). However, the molecular mechanisms that govern the development of muscle atrophy after RCTs have not been well defined. The Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role in maintaining muscle mass in response to mechanical loading. The role of this pathway in the development of muscle atrophy after a massive RCT remains unknown. The purpose of this study was to investigate the regulation of the Akt/mTOR pathway in the development of muscle atrophy after a RCT and suprascapular nerve (SSN) injury. We evaluated the activity of the Akt/mTOR signaling pathway and how this pathway interacts with two atrophy‐related genes, MuRF‐1 and MAFbx, in supraspinatus muscles of rats that underwent unilateral complete rotator cuff tendon transection or SSN transection. Akt/mTOR activity was significantly reduced after tendon rupture, but increased after nerve injury. MuRF‐1 and MAFbx were only up‐regulated following denervation. These results suggest that tendon transection leads to a decrease in protein synthesis with down‐regulation of the Akt/mTOR signaling pathway, whereas denervation leads to an increase in protein degradation via up‐regulation of expression of MuRF‐1 and MAFbx. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1440–1446, 2012
Tobacco alkaloids analyzed by Raman spectroscopy and DFT calculations
Authors: Baranska M. , Dobrowolski J. Cz. , Kaczor A. , Chruszcz‐Lipska K. , Gorz K. , Rygula A.
Published: February 2012

The tobacco alkaloids: nicotine, nornicotine, cotinine, anabasine, their protonated forms, and salts were analyzed by means of Raman spectroscopy supported by the density functional theory/B3LYP/aug‐cc‐pVDZ calculations. The analyses were performed based on Raman marker bands of neutral, monoprotonated, and diprotonated forms of tobacco alkaloids because in different surroundings various forms have been suggested to either dominate or to coexist. The form and distribution of nicotine directly in a plant and in phytopharmaceutical products were investigated by in situ Raman mapping. For the first time, the Raman optical activity spectrum of (−)‐nicotine in aqueous solution was measured and interpreted by means of the density functional theory calculations. The study provides a clear evidence that Raman spectroscopy techniques are powerful in efficient quality control and forensic and bioanalytical analyses of tobacco alkaloids. Copyright © 2012 John Wiley & Sons, Ltd.
Histopathology of de novo autoimmune hepatitis
Authors: Pongpaibul Ananya , Venick Robert S. , McDiarmid Sue V. , Lassman Charles R.
Published: February 2012

De novo autoimmune hepatitis (DAIH) is a well-recognized complication of pediatric liver transplantation (LT). The diagnosis is largely based on elevated liver function test results and the development of autoimmune antibodies. The histology of DAIH was first described in 1998. We present detailed histological data from the largest series to date of pretreatment and posttreatment biopsy samples from pediatric LT patients with DAIH. The histological evaluation included first an assessment of the predominant pattern of injury (hepatitis, rejection, or bile duct obstruction). Then, the necroinflammatory activity (interface, lobular, and perivenular), plasma cell density, rejection activity index, and fibrosis were scored. Seventy of 685 pediatric patients (10.2%) who underwent LT developed DAIH according to clinical and biopsy findings. Fifty-one pretreatment biopsy samples and 38 posttreatment biopsy samples were available for a retrospective review. The predominant pattern of injury (hepatitis, rejection, or bile duct obstruction) was determined, and biopsy samples were scored for the necroinflammatory activity (interface, lobular, and perivenular), plasma cell density, rejection activity index, and fibrosis. The most common pattern of injury was lobular hepatitis, which was frequently unaccompanied by interface necroinflammatory activity or prominent plasma cell infiltrates. Seven of the 51 cases had features strongly suggestive of acute rejection. Posttreatment biopsy samples showed a reduction in the degree of necroinflammatory activity and plasma cell infiltrates. In most patients, the degree of fibrosis was stable or had regressed. Because the histological features of DAIH are variable and nonspecific, a high index of suspicion and correlation with autoimmune antibodies are necessary to establish the diagnosis. In the majority of patients with DAIH, treatment appears to yield good clinical outcomes and histological improvements. Liver Transpl, 2012. © 2012 AASLD.
Crystallization of Poly(L‐/D‐Lactide) in the Presence of Electric Fields
Authors: Yuryev Yury , Wood‐Adams Paula M.
Published: February 2012

We report, for the first time, an enhancement in melt crystallization kinetics of poly(L‐/D‐lactide) (a type‐A1 polymer) in the presence of static electric fields as observed through measurement of the complex viscosity. Static electric fields of varying intensity (0–2.4 × 105 V m−1) are applied directly to the crystallizing polylactide melt at five different temperatures. The crystallization rate enhancement increases both with crystallization temperature and applied electric field intensity. An XRD analysis and optical microscopy studies allows us to attribute this to increased nucleation in the presence of an electric field. A technique allowing for the estimation of the rate of homogeneous nucleation induced by the electric field is developed.
Complexation of Tetraphenylthiophene‐Derived Ammonium Chloride to Poly(sodium vinylsulfonate) Polyelectrolytes: Aggregation‐Induced Emission Enhancement and Long‐Range Interaction
Authors: Chien Rong‐Hong , Lai Chung‐Tin , Hong Jin‐Long
Published: February 2012

Fluorescent tetraphenylthiophene (TP)‐derived ammonium cations TP‐NH3+ are synthesized and reacted with poly(sodium vinylsulfonate) (PSV) polyanions to obtain three PSV‐TP(x/y) (x/y = 4/1, 2/1 and 1/1) complexes with long‐range electrostatic interactions (LEI) and novel aggregation‐induced emission enhancement (AIEE) properties. Introduction of water into a dilute solution of PSV‐TP(x/y) in THF results in self‐aggregated particles with enhanced AIEE‐operative emission. PSV or NaCl electrolyte is applied to control the LEI forces stabilizing the aggregated particles, and the AIEE‐operative emissions can be thus manupulated. Due to the strong LEI forces, the solid PSV‐TP(4/1) has a high FL quantum yield of 0.91. The relationship between AIEE and LEI forces is evaluated.
The arterialized saphenous venous flow‐through flap with dual venous drainage
Authors: Rozen Warren M. , Ting Jeannette W. C. , Gilmour Robert F. , Leong James
Published: February 2012

Background:

Venous flow‐through flaps are well‐described options for small defects where donor site morbidity is undesirable or in areas where useful local veins are in close proximity to the defect, particularly in the extremities. However, higher rates of flap loss have limited their utility. The saphenous venous flap in particular has been widely sought as a useful flap, and while arterialization of this flap improved survival rates, congestion has remained a limiting feature. We describe report a modification in the design of saphenous venous flaps, whereby an arterialized flap is provided with a separate source of venous drainage, and demonstrate survival of substantially larger venous flaps than previously reported.

Methods:

In five consecutive patients, we describe three main modifications to the saphenous venous flap as previously described: (a) Using arterialized flaps only; (b) Reversing the flap to allow unimpeded flow during arterialization; and (c) Anastomosing additional vein(s) that are not connected to the central vein—especially at the periphery of the flap for true venous drainage.

Results:

There was a 0% complete flap loss rate (with only one case of superficial partial loss), and ultimately better survival than previous series of saphenous venous flaps described to date.

Conclusion:

The success of these techniques offers the potential to re‐establish flow to large segmental losses to axial arteries, offer safe and definitive flap coverage to traumatic wounds, improve the array of flap options in this setting, and minimize donor site morbidity. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.