bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular transcriptomics—Dissection of the mRNA composition in the axonal compartment of sensory neurons
Authors: Minis Adi , Dahary Dvir , Manor Ohad , Leshkowitz Dena , Pilpel Yitzhak , Yaron Avraham
Published: October 2013

RNA localization is a regulatory mechanism that is conserved from bacteria to mammals. Yet, little is known about the mechanism and the logic that govern the distribution of RNA transcripts within the cell. Here, we present a novel organ culture system, which enables the isolation of RNA specifically from NGF dependent re‐growing peripheral axons of mouse embryo, sensory neurons. In combination with massive parallel sequencing technology, we determine the subcellular localization of most transcripts in the transcriptome. We found that the axon is enriched in mRNAs that encode secreted proteins, transcription factors, and the translation machinery. In contrast, the axon was largely depleted from mRNAs encoding transmembrane proteins, a particularly interesting finding, since many of these gene products are specifically expressed in the tip of the axon at the protein level. Comparison of the mitochondrial mRNAs encoded in the nucleus with those encoded in the mitochondria, uncovered completely different localization pattern, with the latter much enriched in the axon fraction. This discovery is intriguing since the protein products encoded by the nuclear and mitochondrial genome form large co‐complexes. Finally, focusing on alternative splice variants that are specific to axonal fractions, we find short sequence motifs that are enriched in the axonal transcriptome. Together our findings shed light on the extensive role of RNA localization and its characteristics. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 365–381, 2014
Multilocus analyses indicate a mosaic distribution of hybrid populations in ground squirrels (genusIctidomys)
Authors: Thompson Cody W. , Anwarali Khan Faisal Ali , Stangl Frederick B. , Baker Robert J. , Bradley Robert D.
Published: October 2013

DNAsequence data from mitochondrial cytochrome‐b(Cytb) and Y‐linked structural maintenance of chromosomes (SmcY) genes were combined with 478 nuclear loci obtained from amplified fragment length polymorphisms (AFLP) to assess the extent of hybridization and genetic spatial structure of populations in two hybridizing species of ground squirrel (Ictidomys parvidensandIctidomys tridecemlineatus). Based onAFLPanalyses of 134 individuals from 28 populations, 10 populations were identified that possessed hybrid individuals. Overall estimates ofFSTvalues revealed strong support for population structure in theCytb data set; however, analyses of theSmcYgene and theAFLPdata indicated ongoing gene flow between species. PairwiseFSTcomparisons of populations were not significant for theSmcYgene; although they were significant for theCytb gene, indicating that these populations were structured and that gene flow was minimal. Therefore, gene flow betweenI. parvidensandI. tridecemlineatusappeared to be restricted to populations that exhibited hybridization. In addition, the fragmented nature of the geographic landscape suggested limited gene flow between populations. As a result, the distributional pattern of interspersed parental and hybrid populations were compatible with a mosaic hybrid zone model. Because ground squirrels display female philopatry and male‐biased dispersal, the ecology of these species is compatible with this hypothesis.
Metacommunity structuring in stream networks: roles of dispersal mode, distance type, and regional environmental context
Authors: Grönroos Mira , Heino Jani , Siqueira Tadeu , Landeiro Victor L. , Kotanen Juho , Bini Luis M.
Published: October 2013

Within a metacommunity, both environmental and spatial processes regulate variation in local community structure. The strength of these processes may vary depending on species traits (e.g., dispersal mode) or the characteristics of the regions studied (e.g., spatial extent, environmental heterogeneity). We studied the metacommunity structuring of three groups of stream macroinvertebrates differing in their overland dispersal mode (passive dispersers with aquatic adults; passive dispersers with terrestrial adults; active dispersers with terrestrial adults). We predicted that environmental structuring should be more important for active dispersers, because of their better ability to track environmental variability, and that spatial structuring should be more important for species with aquatic adults, because of stronger dispersal limitation. We sampled a total of 70 stream riffle sites in three drainage basins. Environmental heterogeneity was unrelated to spatial extent among our study regions, allowing us to examine the effects of these two factors on metacommunity structuring. We used partial redundancy analysis and Moran's eigenvector maps based on overland and watercourse distances to study the relative importance of environmental control and spatial structuring. We found that, compared with environmental control, spatial structuring was generally negligible, and it did not vary according to our predictions. In general, active dispersers with terrestrial adults showed stronger environmental control than the two passively dispersing groups, suggesting that the species dispersing actively are better able to track environmental variability. There were no clear differences in the results based on watercourse and overland distances. The variability in metacommunity structuring among basins was not related to the differences in the environmental heterogeneity and spatial extent. Our study emphasized that (1) environmental control is prevailing in stream metacommunities, (2) dispersal mode may have an important effect on metacommunity structuring, and (3) some factors other than spatial extent or environmental heterogeneity contributed to the differences among the basins.
Synthesis and Characterisation of Hydrated Calcium Pyrophosphate Phases of Biological Interest
Authors: Gras Pierre , Rey Christian , Marsan Olivier , Sarda Stéphanie , Combes Christèle
Published: October 2013

The details of a synthesis method for biologically relevant hydrated calcium pyrophosphates (CPPs, Ca2P2O7·nH2O) has been elucidated. Control of the pH (from 3.6 to 5.8) and the temperature (from 25 to 90 °C) during the synthesis enabled the preparation of four pure CPP phases within one hour without intermediates: monoclinic and triclinic calcium pyrophosphate dihydrate (CPPD, Ca2P2O7·2H2O), which are the two CPP phases detected in vivo in joints of arthritic patients, monoclinic tetrahydrate β (CPPT, Ca2P2O7·4H2O) and an amorphous phase (a‐CPP, Ca2P2O7·nH2O). Four domains corresponding to the four different phases of hydrated calcium pyrophosphate were identified; a‐CPP was synthesised over a very wide pH and temperature range (up to 90 °C) within the domain of synthesis conditions explored, including physiological conditions (pH 7.4 and 37 °C). The as‐synthesised hydrated CPP phases were characterised by complementary techniques (powder X‐ray diffraction, FTIR and Raman spectroscopy, scanning electron microscopy and thermogravimetry) and chemical analyses. Rietveld refinement analyses of the as‐synthesised crystalline phases were performed, and there were significant differences between the m‐CPPD X‐ray diffraction pattern observed and previously published cell parameters. Vibrational spectroscopy allowed the crystalline and amorphous phases synthesised to be clearly distinguished and identified owing to the high flexibility of the pyrophosphate anion. Chemical analyses showed that the synthesis conditions used in this study did not allow significant hydrolysis of the pyrophosphate ions into phosphate ions, and the number of water molecules associated with each synthesised CPP phase was determined by thermogravimetric analysis. Different mechanisms of dehydration were also identified. The study of the formation of synthetic and well‐characterised hydrated calcium pyrophosphate phases and their availability in large amounts in vitro could allow progress to be made on the biological role of these phases and their possible transformations. This could also aid their detection in patients suffering from disease caused by calcium salt crystals and could clarify the mechanism by which CPP crystals form and evolve in vivo.
η2‐Coordination of a Phosphaalkyne to an Amino Olefin Nickel Complex and Regioselective Catalyzed Cyclooligomerization to Dewar 1,3,5‐Triphosphabenzene
Authors: Trincado Mónica , Rosenthal Amos J. , Vogt Matthias , Grützmacher Hansjörg
Published: October 2013

We report herein an efficient synthesis of a Dewar‐triphosphabenzene derived from [2+2+2] cycloaddition of three phosphaalkyne molecules promoted by an amino olefin Ni0complex as the catalyst. Amino diolefin NiIcomplex1serves as a precursor complex that reacts with triphenylmethylphosphaethyne under reducing conditions at low temperature to give Ni0complex3with a coordinated phosphaalkyne in a η2‐mode. The structure of3was determined by X‐ray diffraction methods and suggests a bonding situation for the phosphaalkyne that is between a side‐on coordinated C≡P molecule and a metallaphosphacyclopropene structure. The reaction of3with a 10‐fold excess of phosphaethylene under reducing conditions at room temperature resulted in the formation of 2,4,6‐tris(triphenylmethyl)‐Dewar‐1,3,5‐triphosphabenzene (4) in good yield.
Palladium‐Catalyzed Cross‐Coupling of 2‐Chloroquinoxaline N‐Oxides with Arylboronic Acids
Authors: Maichrowski Jan , Hübner Eike G. , Kaufmann Dieter E.
Published: October 2013

A selection of 2‐chloro‐substituted O‐alkylquinoxaline N‐oxides, easily accessible by the one‐step annulation reaction of 4‐fluoroaniline with 1,1,2‐trichloro‐2‐nitroethylene and subsequent O‐alkylation, was arylated at the chloronitrone unit in yields up to 96 %. This first efficient Pd‐catalyzed Suzuki–Miyaura reaction of chloroquinoxaline N‐oxides with arylboronic acids led to new 2‐arylquinoxaline N‐oxides. The scope and limitations of this arylation reaction were investigated, and the role of some sterically demanding boronic acids in the cross‐coupling reaction was evaluated by means of DFT calculations. Additionally, the Pd‐catalyzed C‐arylation of the amide unit of selected quinoxalinone derivatives was accomplished.
Salt‐Solubilization and Ion‐Pair Recognition by a Quinoline‐Substituted Crown Ether
Authors: Sun Zhan‐Hu , Pan Fang‐Fang , Triyanti  , Albrecht Markus , Raabe Gerhard
Published: October 2013

A novel quinoline‐substituted crown ether has been synthesized as a receptor for ion pairs and its binding behavior was investigated in various solvents. The binding of ion pairs in [D6]DMSO and in mixed [D6]DMSO/CD3CN/CDCl3 solvents was studied and the results revealed positive cooperativity effects. As a novel solubilizing agent, the crown ether can extract halide salts into organic media, especially chloride salts. ESI MS provided evidence for the formation of salt‐receptor complexes. A recycling experiment showed that the receptor can solubilize salts and can be recovered. This process can be performed as a cycle. This study validates the idea that a straightforward combination of a common anion receptor and a well‐studied cation complexation moiety enables the formation of ion‐pair receptors and solubilizers of salts in organic solvents.
Regioselective Oxidative Dehydrogenation under Nonenzymatic Conditions: A Synthetic Route to Gossypol
Authors: Li Ling , Liu Yuxiu , Wang Qingmin
Published: October 2013

A practical and scalable route was developed for the total synthesis of gossypol to allow for the construction of dozens of gossypol derivatives. tBuO2Ac was found to be a highly efficient oxidant for the polymerization of hemigossypol through a biosynthetic process under nonenzymatic conditions to give gossypol. Hemigossypol was synthesized on a gram scale by starting from commercially available carvacrol and dimethyl succinate and using a Stobbe condensation, an electrophilic cyclization, and the Michael addition of ortho‐quinone methide as key steps.
Rhodium‐Catalyzed Intramolecular Difluoromethylenative Dearomatization of Phenols
Authors: Li Yajun , Zhang Lisi , Zhang Li , Wu Yongming , Gong Yuefa
Published: October 2013

Rhodium‐catalyzed intramolecular difluoromethylenative dearomatization of phenols to yield azaspirocyclohexadienones containing all‐carbon quaternary centers in good to excellent yields was developed. A variety of functional groups proved compatible with the transformation. This method could also be used for difluoromethylenative dearomatization of indoles. Preliminary mechanism studies suggest that a pure radical mechanism is not involved in this reaction.
The Anti‐Bredt Red Flag! Reassignment of Neoveratrenone
Authors: Savchenko Andrei I. , Williams Craig M.
Published: October 2013

The bicyclo[3.3.1]non‐1‐en‐3‐one motif, which has yet to be observed in natural products, was recently reported within the skeleton of neoveratrenone. On the basis of Bredt's rule, a plausible reassignment matching closely the C‐nor‐D‐homo steroidal ring system has been proposed herein.
Highly Ordered TiO2 Nanotubes for Electrochemical Sensing of Hair Dye Basic Brown 17
Authors: de Oliveira R. A. G. , Zanoni M. V. B.
Published: October 2013

Self‐organized Ti/TiO2 nanotubular array electrodes were prepared by electrochemical anodization and used to monitor the reduction of the hair dye basic brown 17 (BB17) at a potential of −0.60 V vs. Ag/AgCl. Analytical curves were obtained from 1.0×10−6 to 8.0×10−5 mol L−1 with a detection limit of 1.3×10−7 mol L−1 by using the best experimental conditions, linear scan voltammetry at pH 6, scan rate=60 mV s−1, and accumulation time=5 min. The detection system performance was not interfered by other hair dyes and successfully used to determine the dye in tap water samples.
Aptamer‐based thrombin assay on microfluidic platform
Authors: Chen Fang‐yuan , Wang Zheng , Li Peng , Lian Hong‐Zhen , Chen Hong‐Yuan
Published: October 2013

A facile and sensitive aptamer‐based protocol has been developed for protein assay on microfluidic platform with fluorescence detection using an off‐chip microarray scanner. Aptamer‐functionalized magnetic beads were used to capture thrombin that binds to a second aptamer fluorescently labeled by Cy3. Experimental conditions, such as incubation time and temperature, washing time, interfering proteins, and aptamer, etc., were optimized for the microchip method. This work demonstrated there was a good relationship between fluorescence intensity and thrombin concentration in the range of 65–1000 ng/mL with the RSD less than 8%. Notably, an analysis only needs 1 μL volume of sample injection and this system can capture extremely tiny amount thrombin (0.4 fmol). This method has been successfully applied to assay of thrombin in human serum with the recovery of 79.74–95.94%.
Activin receptor‐like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes
Authors: Yoon Jeong‐Hwan , Jung Su Myung , Park Seok Hee , Kato Mitsuyasu , Yamashita Tadashi , Lee In‐Kyu , Sudo Katsuko , Nakae Susumu , Han Jin Soo , Kim Ok‐Hee , Oh Byung‐Chul , Sumida Takayuki , Kuroda Masahiko , Ju Ji‐Hyeon , Jung Kyeong Cheon , Park Seong Hoe , Kim Dae‐Kee , Mamura Mizuko
Published: October 2013

Varieties of transforming growth factor‐β (TGF‐β) antagonists have been developed to intervene with excessive TGF‐β signalling activity in cancer. Activin receptor‐like kinase5 (ALK5) inhibitors antagonize TGF‐β signalling by blocking TGF‐β receptor‐activated Smad (R‐Smad) phosphorylation. Here we report the novel mechanisms how ALK5 inhibitors exert a therapeutic effect on a mouse B16 melanoma model. Oral treatment with a novel ALK5 inhibitor, EW‐7197 (2.5 mg/kg daily) or a representative ALK5 inhibitor, LY‐2157299 (75 mg/kg bid) suppressed the progression of melanoma with enhanced cytotoxic T‐lymphocyte (CTL) responses. Notably, ALK5 inhibitors not only blocked R‐Smad phosphorylation, but also induced ubiquitin‐mediated degradation of the common Smad, Smad4 mainly in CD8+ T cells in melanoma‐bearing mice. Accordingly, T‐cell‐specific deletion of Smad4 was sufficient to suppress the progression of melanoma. We further identified eomesodermin (Eomes), the T‐box transcription factor regulating CTL functions, as a specific target repressed by TGF‐β via Smad4 and Smad3 in CD8+ T cells. Thus, ALK5 inhibition enhances anti‐melanoma CTL responses through ubiquitin‐mediated degradation of Smad4 in addition to the direct inhibitory effect on R‐Smad phosphorylation.
Combining ungrouped and grouped wildfire data to estimate fire risk
Authors: Hernandez‐Magallanes I.
Published: October 2013

Frequently, models are required to combine information obtained from different data sources and on different scales. In this work, we are interested in estimating the risk of wildfire ignition in the USA for a particular time and location by merging two levels of data, namely, individual points and aggregate count of points into areas. The data for federal lands consist of the point location and time of each fire. Nonfederal fires are aggregated by county for a particular year. The probability model is based on the wildfire point process. Assuming a smooth intensity function, a locally weighted likelihood fit is used, which incorporates the group effect. A logit model is used under the assumption of the existence of a latent process, and fuel conditions are included as a covariate. The model assessment is based on a residual analysis, while the False Discovery Rate detects spatial patterns. A benefit of the proposed model is that there is no need of arbitrary aggregation of individual fires into counts. A map of predicted probability of ignition for the Midwest US in 1990 is included. The predicted ignition probabilities and the estimated total number of expected fires are required for the allocation of resources. Copyright © 2013 John Wiley & Sons, Ltd.
Kinematic response of single piles to vertically incident P‐waves
Authors: Liu Qijian , Deng Fangjun , He Yibin
Published: October 2013

Dynamic response of single piles to seismic waves is fundamentally different from the free‐field motion because of the interaction between the pile and the surrounding soil. Considering soil–pile interaction, this paper presents a new displacement model for the steady‐state kinematic response of single piles to vertically incident P‐waves on the basis of a continuum model. The governing equations and boundary conditions of the two undetermined functions in the model are obtained to be coupled by using Hamilton's principle. Then, the two unknown functions are decoupled and solved by an iterative algorithm numerically. A parametric study is performed to investigate the effects of the properties of the soil–pile system on the kinematic response of single piles. It is shown that the effects of the pile–soil modulus ratio, the slenderness ratio of the pile, and the frequency of the incident excitations are very significant. By contrast, the influence of soil damping on the kinematics of the system is slight and can be neglected. Copyright © 2013 John Wiley & Sons, Ltd.
Application of a tenax model to assess bioavailability of polychlorinated biphenyls in field sediments
Authors: Mackenbach Elizabeth M. , Harwood Amanda D. , Mills Marc A. , Landrum Peter F. , Lydy Michael J.
Published: October 2013

Recent literature has shown that bioavailability-based techniques, such as Tenax extraction, can estimate sediment exposure to benthos. In a previous study by the authors, Tenax extraction was used to create and validate a literature-based Tenax model to predict oligochaete bioaccumulation of polychlorinated biphenyls (PCBs) from sediment; however, its ability to assess sediment remediation was unknown. The present study further tested the Tenax model by examining the impacts of remediation on surface sediment concentrations, Tenax extractable concentrations, and tissue concentrations of laboratory-exposed Lumbriculus variegatus. Tenax extractable concentration was an effective exposure metric to evaluate changes in Lumbriculus exposure preremediation and postremediation, with 75% of the postremediation data corresponding to the Tenax model. At nondredged sites, bioaccumulation was better predicted by the Tenax model, with 86% of the data falling within the 95% confidence intervals, than at dredged sites, for which only 64% of the data fit the Tenax model. In both pre- and postdredge conditions, when the model failed, it was conservative, predicting higher PCB concentrations than observed in the oligochaetes, particularly for the postdredge data. The present study advances understanding of the applicability of the Tenax model for use when examining systems that may have undergone significant disturbances. The Tenax model provides a unique tool for quickly quantifying potential exposure to benthic organisms. Environ Toxicol Chem 2014;33:286–292. © 2013 SETAC
Interactions between mercury and phytoplankton: Speciation, bioavailability, and internal handling
Authors: Le Faucheur Séverine , Campbell Peter G.C. , Fortin Claude , Slaveykova Vera I.
Published: October 2013

The present review describes and discusses key interactions between mercury (Hg) and phytoplankton to highlight the role of phytoplankton in the biogeochemical cycle of Hg and to understand direct or indirect Hg effects on phytoplankton. Phytoplankton are exposed to various Hg species in surface waters. Through Hg uptake, phytoplankton affect the concentration, speciation, and fate of Hg in aquatic systems. The mechanisms by which phytoplankton take up Hg are still not well known, but several studies have suggested that both facilitated transport and passive diffusion could be involved. Once internalized, Hg will impact several physiological processes, including photosynthesis. To counteract these negative effects, phytoplankton have developed several detoxification strategies, such as the reduction of Hg to elemental Hg or its sequestration by intracellular ligands. Based on the toxicological studies performed so far in the laboratory, Hg is unlikely to be toxic to phytoplankton when they are exposed to environmentally relevant Hg concentrations. However, this statement should be taken with caution because questions remain as to which Hg species control Hg bioavailability and about Hg uptake mechanisms. Finally, phytoplankton are primary producers, and accumulated Hg will be transferred to higher consumers. Phytoplankton are a key component in aquatic systems, and their interactions with Hg need to be further studied to fully comprehend the biogeochemical cycle of Hg and the impact of this ubiquitous metal on ecosystems. Environ Toxicol Chem 2014;33:1211–1224. © 2013 SETAC
Oxidative stress responses of gulf killifish exposed to hydrocarbons from the Deepwater Horizon oil spill: Potential implications for aquatic food resources
Authors: Crowe Kristi M. , Newton Joseph C. , Kaltenboeck Bernhard , Johnson Calvin
Published: October 2013

Ecosystem effects of polycyclic aromatic hydrocarbons (PAHs) remain under investigation following the Gulf of Mexico Deepwater Horizon oil spill. Fundulus grandis, an established indicator of aquatic ecosystem health, was investigated because this species shares genes and biochemical pathways with higher trophic–level fish and plays an important role in the gulf food chain. Oxidative stress responses including hepatic cytochrome P4501A (CYP1A) and serum antioxidant capacity were evaluated in fish exposed to PAHs. Fish were exposed to water-accommodated fractions (WAFs) of crude oil (7.0  ± 0.10 mg/L C6-C28) after which solutions were diluted below the level of detection over 8 h using 15 ppt aerated artificial seawater. Before euthanasia, fish remained in aquaria for 12 h, 24 h, or 48 h. Three replicate experiments were conducted at each time point using unexposed fish as experimental controls. Significant differences (p < 0.05) in CYP1A induction were observed in exposed versus control fish at 24 h. Expression of CYP1A increased by 25%, 66%, and 23% in exposed fish at 12 h, 24 h, and 48 h, respectively. Significant increases were observed in antioxidant capacity of nonenzymatic antioxidants in exposed versus control fish at each time point. Given the activity of CYP1A, radicals formed during PAH detoxification likely resulted in increased oxidant load requiring elevated antioxidant defenses. Research is needed to determine the duration of oxidative stress responses considering the potential for lipid oxidation in exposed fish or species feeding on exposed fish. Environ Toxicol Chem 2014;33:370–374. © 2013 SETAC
A molecular method for assessing the effects of potential contaminants on the rate of zebrafish (Danio rerio) development
Authors: Beasley Amy , Graham Chris , Otter Ryan , Elrod-Erickson Matthew
Published: October 2013

Monitoring expression of the developmentally regulated genes shh, sox2, and tnnt1 by reverse transcriptase polymerase chain reaction (RT-PCR) allows determination of the rate of embryogenesis in zebrafish (Danio rerio) embryos without direct visual observation. The utility of combining this approach and morphological methods during toxicity studies was demonstrated with embryos developing at either 28.5 °C or 24.5 °C and with embryos exposed to sublethal doses of silver nanoparticles. Environ Toxicol Chem 2014;33:238–242. © 2013 SETAC
P16INK4A immunostaining is a strong indicator for high‐risk‐HPV‐associated oropharyngeal carcinomas and dysplasias, but is unreliable to predict low‐risk‐HPV‐infection in head and neck papillomas and laryngeal dysplasias
Authors: Mooren Jeroen J. , Gültekin Sibel E. , Straetmans Jos M.J.A.A. , Haesevoets Annick , Peutz‐Kootstra Carine J. , Huebbers Christian U. , Dienes Hans P. , Wieland Ulrike , Ramaekers Frans C.S. , Kremer Bernd , Speel Ernst‐Jan M. , Klussmann Jens P.
Published: October 2013

Human papillomavirus (HPV) is a risk factor for the development of benign and malignant mucosal head and neck lesions. P16INK4A is often used as a surrogate marker for HPV‐infection, although there is still controversy with respect its reliability. Our aim was to determine if p16INK4A overexpression can accurately predict both high‐risk and low‐risk‐HPV‐presence in (pre)malignant and benign head and neck lesions. P16INK4A immunohistochemistry was performed on paraffin‐embedded tissue sections of 162 oropharyngeal squamous cell carcinomas (OPSCC), 14 tonsillar and 23 laryngeal dysplasias, and 20 tonsillar and 27 laryngeal papillomas. PCR, enzyme‐immunoassay and FISH analysis were used to assess HPV‐presence and type. Of the 162 OPSCC and 14 tonsillar dysplasias, 51 (31%) and 10 (71%) were HPV16‐positive, respectively. All tonsillar papillomas were HPV‐negative and four laryngeal dysplasias and 26 laryngeal papillomas were positive for HPV6 or −11. P16INK4A immunohistochemistry revealed a strong nuclear and cytoplasmic staining in 50 out of 51 HPV16‐positive and 5 out of 111 HPV‐negative OPSCC (p < 0.0001) and in all HPV16‐positive tonsillar dysplasias, whereas highly variable staining patterns were detected in the papillomas and laryngeal dysplasias, irrespective of the HPV‐status. In addition, the latter lesions generally showed a higher nuclear than cytoplasmic p16INK4A immunostaining intensity. In conclusion, our data show that strong nuclear and cytoplasmic p16INK4A overexpression is a reliable surrogate indicator for HPV16 in OPSCC and (adjacent) dysplasias. For HPV6 or −11‐positive and HPV‐negative benign and premalignant lesions of the tonsil and larynx, however, p16INK4A immunostaining is highly variable and cannot be recommended to predict HPV‐presence.
A positive feedback loop between STAT3 and cyclooxygenase‐2 gene may contribute to Helicobacter pylori‐associated human gastric tumorigenesis
Authors: Xiong Hua , Du Wan , Sun Tian‐Tian , Lin Yan‐Wei , Wang Ji‐Lin , Hong Jie , Fang Jing‐Yuan
Published: October 2013

Persistent infection with Helicobacter pylori (H. pylori) contributes to gastric diseases including chronic gastritis and gastric cancer. However, the pathogenesis of this carcinogenic bacterium has not been completely elucidated. Here, we report that H. pylori rapidly triggers STAT3 signaling and induces STAT3‐dependent COX‐2 expression both in vitro and in vivo. STAT3 upregulats COX‐2 by binding to and increasing the activity of COX‐2 promoter. COX‐2 in turn regulates IL‐6/STAT3 signaling under basal conditions and during H. pylori infection. These findings suggest that a positive feedback loop between STAT3 and COX‐2 exists in the basal condition and H. pylori infectious condition. Immunohistochemical staining revealed that H. pylori‐positive gastritis tissues exhibited markedly higher levels of pSTAT3Tyr705 than H. pylori‐negative ones. High pSTAT3Tyr705 levels are correlated with intestinal metaplasia and dysplasia, suggesting pSTAT3Tyr705 may be useful in the early detection of gastric tumorigenesis. Additionally, a strong positive correlation between STAT3/pSTAT3Tyr705 levels and COX‐2 expression was identified in gastritis and gastric cancer tissues. Together, these findings provide new evidence for a positive feedback loop between STAT3 signaling and COX‐2 in H. pylori pathogenesis and may lead to new approaches for early detection and effective therapy of gastric cancer.
The FOXE1 locus is a major genetic determinant for familial nonmedullary thyroid carcinoma
Authors: Bonora Elena , Rizzato Cosmeri , Diquigiovanni Chiara , Oudot‐Mellakh Tiphaine , Campa Daniele , Vargiolu Manuela , Guedj Mickaël ,   The NMTC Consortium, McKay James D. , Romeo Giovanni , Canzian Federico , Lesueur Fabienne
Published: October 2013

Thyroid cancer is the most common endocrine malignancy and nonmedullary thyroid carcinoma (NMTC) represents 90% of all cases. NMTC risk in first‐degree relatives of affected cases is elevated fivefold to ninefold. Familial NMTC (FNMTC) accounts for about 3–7% of all thyroid tumors and is a more aggressive clinical entity than its sporadic counterparts. Linkage analysis on high‐risk families performed a decade ago mapped several susceptibility loci, but did not lead to the identification of high‐penetrance causal germline mutations. More recently, a genome‐wide association study (GWAS) identified common single nucleotide polymorphisms (SNPs) affecting the risk of sporadic NMTC. We sought to verify if the newly identified genetic risk factors for NMTC are relevant for FNMTC as well. We genotyped 23 SNPs at 11 candidate loci in 672 subjects belonging to 133 pedigrees with at least two NMTC cases. Statistical analysis was performed using family‐based association tests, modified quasi‐likelihood score and logistic‐normal models. SNPs at 9q22.33 near FOXE1 showed convincing evidence of association with NMTC risk in these high‐risk families. The other tested loci resulted negative. These findings confirm the importance of the SNPs identified by recent GWAS on sporadic NMTC on FNMTC as well. However, the proposed FOXE1 causal variants do not show the strongest association signal. Moreover, mutation screening of the FOXE1 coding sequence in the FNMTC cases did not identify rarer causal variants, suggesting that other yet unidentified variants at this locus are involved in FNMTC etiology.
SOCIAL WITHDRAWAL BEHAVIOR IN INFANCY: A HISTORY OF THE CONCEPT AND A REVIEW OF PUBLISHED STUDIES USING THE ALARM DISTRESS BABY SCALE
Authors: Guedeney Antoine , Matthey Stephen , Puura Kaija
Published: October 2013

This article reviews the studies using or validating the Alarm Distress Baby Scale (ADBB; A. Guedeney & J. Fermanian, ) within different countries, different populations, and different settings. After a brief summary of the theoretical backgrounds of infant social behavior, the results of the main controlled and methodologically comparable studies are summarized and discussed. Second, the results of some observational studies as well as different models of factor analysis are presented. The modified, five‐item ADBB (m‐ADBB) Scale is described. Finally, perspectives for future research and training are presented.
Spiritual Disclosure and Ego Resiliency: Validating Spiritual Competencies
Authors: Brelsford Gina M. , Ciarrocchi Joseph
Published: October 2013

Counselor spiritual and religious competency depends primarily on the ability to facilitate client spiritual disclosure. Little is known, however, about the empirical qualities of spiritual disclosure. In a sample of 318 adults (mean age = 44 years), spiritual disclosure independently predicted ego resiliency, a critical quality for stress‐related growth. Spiritual disclosure predicted ego resiliency over the partial mediators of the 5 factors of personality, general global disclosure, and congregational support. Implications for professional counseling ethics are discussed.
Exploring Taiwanese Female Pastors' Intimate Relationships: Using the Story of the Levite's Concubine
Authors: Lin Yu‐Fen , Li Chi‐Sing , Irby Beverly , Brown Genevieve
Published: October 2013

The authors investigated intimate relationships and violence toward women, using group discussions and focus group techniques from a feminist group counseling perspective, with Taiwanese Presbyterian female pastors. The story of the Levite's concubine and the feminist commentary were provided to a group of Taiwanese female pastors to read at the beginning of the focus group session. The women's perspectives of their intimate relationship experiences in light of the biblical story were explored. The 6 themes related to participants' intimate relationships were generated and are discussed.
Assessment of the genotoxic and carcinogenic potentials of 3‐aminothiophene derivatives using in vitro and in silico methodologies
Authors: Lepailleur Alban , Bureau Ronan , Halm‐Lemeille Marie‐Pierre , Bouquet Michel , Pecquet Régis , Paris‐Soubayrol Christine , Goff Jérémie Le. , André Véronique , Lecluse Yannick , Lebailly Pierre , Maire Marie‐Aline , Vasseur Paule
Published: October 2013

Thiophene derivatives, a class of compounds widely used in products such as pharmaceuticals, agrochemicals or dyestuffs, represent chemicals of concern. Indeed, the thiophene ring is often considered as a structural moiety that may be involved in toxic effects in humans. We primarily focus on the genotoxic/mutagenic and carcinogenic potentials of the methyl 3‐amino‐4‐methylthiophene‐2‐carboxylate (1), a precursor of the articaine local anesthetic (4) which falls within the scope of the European REACH (Registration, Evaluation, Authorisation and restriction of CHemicals) legislation. To discern some structure–toxicity relationships, we also studied two related compounds, namely the 3‐amino 4‐methylthiophene (2) and the 2‐acetyl 4‐chlorothiophene (3). Techniques employed to assess mutagenic and DNA‐damaging effects involved the Salmonella mutagenicity assay (or Ames test) and the single‐cell gel electrophoresis assay (or Comet assay). In the range of tested doses, none of these derivatives led to a positive response in the Ames tests and DNA damage was only observed in the Comet assay after high concentration exposure of 2. The study of their carcinogenic potential using the in vitro SHE (Syrian Hamster Embryo) cell transformation assay (CTA) highlighted the activity of compound 2. A combination of experimental data with in silico predictions of the reactivity of thiophene derivatives towards cytochrome P450 (CYP450), enabled us to hypothesize possible pathways leading to these toxicological profiles. Copyright © 2013 John Wiley & Sons, Ltd.
Interdependence of Muscle Atrophy and Bone Loss Induced by Mechanical Unloading
Authors: Lloyd Shane A , Lang Charles H , Zhang Yue , Paul Emmanuel M , Laufenberg Lacee J , Lewis Gregory S , Donahue Henry J
Published: October 2013

Mechanical unloading induces muscle atrophy and bone loss; however, the time course and interdependence of these effects is not well defined. We subjected 4-month-old C57BL/6J mice to hindlimb suspension (HLS) for 3 weeks, euthanizing 12 to 16 mice on day (D) 0, 7, 14, and 21. Lean mass was 7% to 9% lower for HLS versus control from D7–21. Absolute mass of the gastrocnemius (gastroc) decreased 8% by D7, and was maximally decreased 16% by D14 of HLS. mRNA levels of Atrogin-1 in the gastroc and quadriceps (quad) were increased 99% and 122%, respectively, at D7 of HLS. Similar increases in MuRF1 mRNA levels occurred at D7. Both atrogenes returned to baseline by D14. Protein synthesis in gastroc and quad was reduced 30% from D7–14 of HLS, returning to baseline by D21. HLS decreased phosphorylation of SK61, a substrate of mammalian target of rapamycin (mTOR), on D7–21, whereas 4E-BP1 was not lower until D21. Cortical thickness of the femur and tibia did not decrease until D14 of HLS. Cortical bone of controls did not change over time. HLS mice had lower distal femur bone volume fraction (−22%) by D14; however, the effects of HLS were eliminated by D21 because of the decline of trabecular bone mass of controls. Femur strength was decreased approximately 13% by D14 of HLS, with no change in tibia mechanical properties at any time point. This investigation reveals that muscle atrophy precedes bone loss during unloading and may contribute to subsequent skeletal deficits. Countermeasures that preserve muscle may reduce bone loss induced by mechanical unloading or prolonged disuse. Trabecular bone loss with age, similar to that which occurs in mature astronauts, is superimposed on unloading. Preservation of muscle mass, cortical structure, and bone strength during the experiment suggests muscle may have a greater effect on cortical than trabecular bone. © 2014 American Society for Bone and Mineral Research.
Connective Tissue Growth Factor (CTGF/CCN2) Negatively Regulates BMP‐2 Induced Osteoblast Differentiation and Signaling
Authors: Mundy Christina , Gannon Maureen , Popoff Steven N.
Published: October 2013

Connective tissue growth factor (CTGF/CCN2) and bone morphogenetic protein (BMP)‐2 are both produced and secreted by osteoblasts. Both proteins have been shown to have independent effects in regulating osteoblast proliferation, maturation and mineralization. However, how these two proteins interact during osteoblast differentiation remains unknown. In this study, we utilized two cell culture model systems, osteoblasts derived from CTGF knockout (KO) mice and osteoblasts infected with an adenovirus which over‐expresses CTGF (Ad‐CTGF), to investigate the effects of CTGF and BMP‐2 on osteoblast development and function in vitro. Contrary to a previously published report, osteoblast maturation and mineralization were similar in osteogenic cultures derived from KO and WT calvaria in the absence of BMP‐2 stimulation. Interestingly, in KO and WT osteoblast cultures stimulated with BMP‐2, the KO osteoblasts exhibited enhanced osteoblast differentiation. This increase in osteoblast differentiation was accompanied by increased protein levels of phosphorylated Smad 1/5/8 and mRNA expression levels of bone morphogenetic protein receptor Ib. We also examined osteoblast differentiation in cultures that were infected with an adenoviral‐CTGF vector (Ad‐CTGF) and in controls. Continuous over‐expression of CTGF resulted in decreased osteoblast maturation and mineralization in both unstimulated and BMP‐2 stimulated cultures. Impaired osteoblast differentiation in cultures over‐expressing CTGF was accompanied by decreased protein levels of phosphorylated Smad 1/5/8. Collectively, the data from these studies demonstrate that CTGF acts to negatively regulate BMP‐2 induced signaling and osteoblast differentiation, and warrant additional studies to determine the precise mechanism(s) responsible for this effect. J. Cell. Physiol. 229: 672–681, 2014. © 2013 Wiley Periodicals, Inc.
First Clinical Experience With TRV130: Pharmacokinetics and Pharmacodynamics in Healthy Volunteers
Authors: Soergel David G. , Ann Subach Ruth , Sadler Brian , Connell John , Marion Alan S. , Cowan Conrad L. , Violin Jonathan D. , Lark Michael W.
Published: October 2013

TRV130 is a G protein‐biased ligand at the µ‐opioid receptor. In preclinical studies it was potently analgesic while causing less respiratory depression and gastrointestinal dysfunction than morphine, suggesting unique benefits in acute pain management. A first‐in‐human study was conducted with ascending doses of TRV130 to explore its tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers. TRV130 was well‐tolerated over the dose range 0.15 to 7 mg administered intravenously over 1 hour. TRV130 geometric mean exposure and Cmax were dose‐linear, with AUC0–inf of 2.52 to 205.97 ng h/mL and Cmax of 1.04 to 102.36 ng/mL across the dose range tested, with half‐life of 1.6–2.7 hours. A 1.5 mg dose of TRV130 was also well‐tolerated when administered as 30, 15, 5, and 1 minute infusions. TRV130 pharmacokinetics were modestly affected by CYP2D6 phenotype: clearance was reduced by 53% in CYP2D6 poor metabolizers.TRV130 caused dose‐ and exposure‐related pupil constriction, confirming central compartment µ‐opioid receptor engagement. Marked pupil constriction was noted at 2.2, 4, and 7 mg doses. Nausea and vomiting observed at the 7 mg dose limited further dose escalation. These findings suggest that TRV130 may have a broad margin between doses causing µ‐opioid receptor‐mediated pharmacology and doses causing µ‐opioid receptor‐mediated intolerance.
Desulfurization activity of metal oxides blended into walnut shell based activated carbons
Authors: Guo Jia‐Xiu , Fan Lu , Peng Jian‐Fei , Chen Jie , Yin Hua‐Qiang , Jiang Wen‐Ju
Published: October 2013

BACKGROUND

Walnut shell, a nutshell waste, was used to prepare activated carbons (AC) for desulfurization. Titanium ore (TO), TiO2 or Fe2O3 was blended into the resulting carbonized powders, which were extruded into cylinders and activated under CO2 atmosphere. The desulfurization activity of samples was evaluated in a fixed bed under a simulated gaseous mixture from coal combustion.

RESULTS

Walnut shell can be used to prepare activated carbons (AC) for desulfurization, giving an AC surface area of 401.2 m2 g−1. When TO, TiO2 or Fe2O3 were added into the AC, the surface area of ACTO2, ACT2 and ACF2 increased to 937.1, 661.8 and 791.0 m2 g−1. Ti and Fe in TO are changed into anatase TiO2 and Fe2O3 in ACTOx, and TiO2 and Fe2O3 exist in ACTx and ACFx, respectively. The optimum additive dosage of ACTOx, ACTx and ACFx is 2%. The breakthrough sulfur capacity of ACT2 is higher than that of ACTO2 and ACF2, but other ACTOx is better than ACTx and ACFx, indicating that TiO2 and Fe2O3 have synergistic effects in ACTOx.

CONCLUSION

Pore structure and metal oxides are the main factors which influence the desulfurization performance of catalysts. © 2013 Society of Chemical Industry
Ti/TiO2 nanotubes enhance Mycobacterium fortuitum, Mycobacterium chelonae and Mycobacterium abscessus inactivation in water
Authors: Brugnera Michelle Fernanda , Miyata Marcelo , Zocolo Guilherme Julião , Leite Clarice Queico Fujimura , Zanoni Maria Valnice Boldrin
Published: October 2013

BACKGROUND

Rapid‐growing mycobacteria are difficult to eradicate using common disinfection practices, when compared with coliforms. They are resistant to chlorination, which is commonly used in swimming pool and drinking water treatment. They also resist treatment with glutaraldehyde (GA), benzalkonium chloride, organomercury compounds, chlorohexidine, and even autoclavation. So, the present work describes the development of a new treatment method for Mycobacterium disinfection based on phoelectrocatalytical oxidation at Ti/TiO2 nanotubes electrodes, which could be a promising alternative for its inactivation in a short treatment time.

RESULTS

Nanotubular TiO2 was grown on Ti surface using electrochemical anodization in fluoride medium and applied to photoelectrocatalytic inactivation of 103 CFU mL‐1 Mycobaterium fortuitum, M. chelonae, and M. abscessus, which was achieved after 3 min treatment. The metabolites released during cellular lysis were also degraded with 240 min of photoelectrocatalytical treatment, as monitored by mass spectroscopy measurements. Mineralization was greater than 70% under optimum conditions. The photoelectrocatalytic method gave better results than the photolytic and photocatalytic techniques. The method provided the most efficient mycobacterial inactivation and TOC removal rate, thus being the best to disinfect mycobacterium‐infected water.

CONCLUSION

Photoelectrodes based on Ti/TiO2 nanotubes prepared by electrochemical anodization are a powerful alternative to disinfect mycobacterium‐ contaminated water. © 2013 Society of Chemical Industry
Endoscopic papillary large‐balloon dilation versus endoscopic papillary regular‐balloon dilation for removal of large bile‐duct stones
Authors: Fujisawa Toshio , Kagawa Koichi , Hisatomi Kantaro , Kubota Kensuke , Nakajima Atsushi , Matsuhashi Nobuyuki
Published: October 2013

Background

Endoscopic papillary large‐balloon dilation (EPLBD) became popular for the treatment of large common bile‐duct stones (CBDS), and its feasibility has been reported in comparison to endoscopic sphincterotomy. However, the comparison between EPLBD and endoscopic papillary regular‐balloon dilation (EPBD) has not been reported. In the present study, the efficacy and complications of EPLBD were compared with those of EPBD.

Methods

We retrospectively assessed 334 consecutive patients with CBDS of any size that were treated by either EPLBD or EPBD between January 2008 and December 2012.

Results

In cases with large CBDS (>10 mm), EPLBD and EPBD had similar results in terms of the success rate of stone removal in the first (65% vs. 84%) and total attempts (100% vs. 95%), use of mechanical lithotripter (64% vs. 80%), and procedure time (48.0 ± 17.8 min vs. 44.1 ± 17.1 min). The necessity for crushing stones with a mechanical lithotripter was significantly decreased in EPLBD compared to EPBD (25% vs. 80%). In all cases with CBDS, there was no significant difference in complication rates between EPLBD and EPBD (3.3% vs. 4.7%).

Conclusions

Compared to EPBD, EPLBD appears safe and effective for removing large CBDS and decreases the necessity of lithotripsy.
MAINSTREAMING GENDER OR RECONSTITUTING THE MAINSTREAM? GENDER KNOWLEDGE IN DEVELOPMENT
Authors: Mukhopadhyay Maitrayee
Published: October 2013

Critical reviewers of gender mainstreaming as a practice agree that its transformatory potential has remained unfulfilled. This paper, based on radical readings of three conferences organised to review gender mainstreaming argues that gender has been institutionalised in development organisations although not as gender and development theorists and practitioners would have liked. This paper uses the critical readings to excavate the technologies of power of development governmentalities that structure the institutionalisation process and frame feminist practice. It shows how radical feminist projects of transformation become complicit with the imperatives of development categories and projects. Copyright © 2013 John Wiley & Sons, Ltd.
THE MICROPOLITICS OF EVAPORATION: GENDER MAINSTREAMING INSTRUMENTS IN PRACTICE
Authors: van Eerdewijk Anouka
Published: October 2013

Dutch development agencies have actively taken up gender mainstreaming strategies since the mid‐1990s. This article considers two gender mainstreaming instruments, gender targets and gender assessments, and investigates their transformative effect. A five shifts approach is applied to both the instruments' design on paper and the implementation in practice. The analysis reveals two disconnections, which undermine their transformative potential: between organisational and operational level of policies and between the administrative and conceptual aspects. The emptying and narrowing down of the concept of gender is made possible because the desired transformation of policy is made an individual affair rather than institutional affair. Copyright © 2013 John Wiley & Sons, Ltd.