bluuebunny/crossref_metadata_2025 huggingface dataset:
The fungal microbiome in chronic rhinosinusitis: richness, diversity, postoperative changes and patient outcomes
Authors: Cleland Edward John , Bassioni Ahmed , Boase Samuel , Dowd Scot , Vreugde Sarah , Wormald Peter‐John
Published: February 2014

Background

Our understanding of fungi in chronic rhinosinusitis (CRS) has been limited by previously employed detection techniques. This study examines the fungal component of the microbiome in CRS patients and controls using a highly sensitive culture‐independent molecular technique. The aims of this study include the characterization of fungal richness, prevalence, abundance, temporal changes, and their relationship with patient outcomes.

Methods

Swabs were collected from the sinuses of 23 CRS patients and 11 controls. Collection occurred intraoperatively, and at 6 and 12 weeks postoperatively. DNA was extracted from the swabs and fungal outcomes were determined through 18S ribosomal DNA (rDNA) fungal tag‐encoded FLX amplicon pyrosequencing.

Results

Fungi were ubiquitous to all patients. A total of 207 fungal genera were detected, with a mean sample richness of 8.18 and 12.14 in the control and CRS groups, respectively. Malassezia was detected in all patients at surgery and was also the most abundant. Postoperatively, fungal richness decreased (p < 0.05) and was associated with declines in the prevalence of Fusarium and Neocosmospora (p < 0.05). Neocosmospora was also less abundant postoperatively (p < 0.05). No correlations were found with quality of life.

Conclusion

This is the first study to use a highly sensitive pyrosequencing technique to reveal the true diversity of fungi in the sinuses of CRS patients and postoperative changes in richness. The presence of Malassezia, a genus not previously described in the sinuses, is of great interest, and its potential as a disease modifier should see further investigation given its association with atopic disease.
Zinc‐Catalyzed Depolymerization of End‐of‐Life Polysiloxanes
Authors: Enthaler Stephan
Published: February 2014

Polymers occupy an important role in our current society. Besides their great success, an issue is the accumulation of huge amounts of end‐of‐life polymers. Currently, the waste management is based primarily on landfills, thermal recycling, and downcycling. Notably, only a small portion of end‐of‐life materials is recycled by depolymerization, which refers to the creation of synthetic precursors that can be polymerized to new polymers to close the cycle. Widely used polymers in modern times are silicones (polysiloxanes), the intrinsic properties of which make their depolymerization demanding; only a few high‐temperature or less environmentally friendly processes have been reported. In this regard, we have established an efficient low‐temperature protocol for the depolymerization of silicones with benzoyl fluoride in the presence of cheap zinc salts as precatalysts to yield defined products. Notably, the products can be useful synthetic precursors for the preparation of new polymers, so that an overall recycling process is feasible.
Enantioselective Palladium‐Catalyzed Insertion of α‐Aryl‐α‐diazoacetates into the OH Bonds of Phenols
Authors: Xie Xiu‐Lan , Zhu Shou‐Fei , Guo Jun‐Xia , Cai Yan , Zhou Qi‐Lin
Published: February 2014

A palladium‐catalyzed asymmetric OH insertion reaction was developed. Palladium complexes with chiral spiro bisoxazoline ligands promoted the insertion of α‐aryl‐α‐diazoacetates into the OH bond of phenols with high yield and excellent enantioselectivity under mild reaction conditions. This palladium‐catalyzed asymmetric OH insertion reaction provided an efficient and highly enantioselective method for the preparation of synthetically useful optically active α‐aryl‐α‐aryloxyacetates.
Molecular Engineering of Push–Pull Porphyrin Dyes for Highly Efficient Dye‐Sensitized Solar Cells: The Role of Benzene Spacers
Authors: Yella Aswani , Mai Chi‐Lun , Zakeeruddin Shaik M. , Chang Shu‐Nung , Hsieh Chi‐Hung , Yeh Chen‐Yu , Grätzel Michael
Published: February 2014

Porphyrins have drawn much attention as sensitizers owing to the large absorption coefficients of their Soret and Q bands in the visible region. In a donor and acceptor zinc porphyrin we applied a new strategy of introducing 2,1,3‐benzothiadiazole (BTD) as a π‐conjugated linker between the anchoring group and the porphyrin chromophore to broaden the absorption spectra to fill the valley between the Soret and Q bands. With this novel approach, we observed 12.75 % power‐conversion efficiency under simulated one‐sun illumination (AM1.5G, 100 mW cm−2). In this study, we showed the importance of introducing the phenyl group as a spacer between the BTD and the zinc porphyrin in achieving high power‐conversion efficiencies. Time‐resolved fluorescence, transient‐photocurrent‐decay, and transient‐photovoltage‐decay measurements were employed to determine the electron‐injection dynamics and the lifetime of the photogenerated charge carriers.
Folding of Synthetic Homogeneous Glycoproteins in the Presence of a Glycoprotein Folding Sensor Enzyme
Authors: Dedola Simone , Izumi Masayuki , Makimura Yutaka , Seko Akira , Kanamori Akiko , Sakono Masafumi , Ito Yukishige , Kajihara Yasuhiro
Published: February 2014

UDP‐glucose:glycoprotein glucosyltransferase (UGGT) plays a key role in recognizing folded and misfolded glycoproteins in the glycoprotein quality control system of the endoplasmic reticulum. UGGT detects misfolded glycoproteins and re‐glucosylates them as a tag for misfolded glycoproteins. A flexible model to reproduce in vitro folding of a glycoprotein in the presence of UGGT in a mixture containing correctly folded, folding intermediates, and misfolded glycoproteins is described. The data demonstrates that UGGT can re‐glucosylate all intermediates in the in vitro folding experiments, thus indicating that UGGT inspects not only final folded products, but also the glycoprotein folding intermediates.
Crystal Engineering of Dual Channel p/n Organic Semiconductors by Complementary Hydrogen Bonding
Authors: Black Hayden T. , Perepichka Dmitrii F.
Published: February 2014

The supramolecular arrangement of organic semiconductors in the solid state is as critical for their device properties as the molecular structure, but is much more difficult to control. To enable supramolecular design of semiconducting materials, we introduced dipyrrolopyridine as a new donor semiconductor capable of complementary hydogen bonding with naphthalenediimide acceptors. Through a combination of solution, crystallographic, and device studies, we show that the self‐assembly driven by H bonding a) modulates the charge‐transfer interactions between the donor and acceptor, b) allows for precise control over the solid‐state packing, and c) leads to a combination of the charge‐transport properties of the individual components. The predictive power of this approach was demonstrated in the synthesis of three new coassembled materials which show both hole and electron transport in single‐crystal field‐effect transistors. These studies provide a foundation for advanced solid‐state engineering in organic electronics, capitalizing on the complementary H bonding.
Preparation and characterization of polyamide 66/poly(hydroxyl ether of bisphenol A) blends without compatibilizer
Authors: An Jingjing , Cao Xinyu , Ma Yongmei , Ke Yucai , Yang Huahao , Wang Haiqiao , Wang Fosong
Published: February 2014

The polyamide 66 (PA66)/poly(hydroxyl ether of bisphenol A) (PHE) blend was successfully prepared by twin‐screw extrusion without the addition of any compatibilizer. The PA66/PHE blends had a microphase‐separated structure that varied from a sea‐island structure to a cocontinuous structure, and the mechanical properties were higher than the anticipated values on the basis of the rule of mixtures, which showed a synergistic effect. Fourier transform infrared spectroscopy and dynamic mechanical analysis illustrated that there was hydrogen‐bonding interaction between the amide groups of the PA66 and the pendant hydroxyl groups of the PHE. This led to the some degree of compatibility and the improvement in the mechanical properties of the blends. The polarized optical microscopy observation showed that the PA66 spherulites of the blend became smaller and more imperfect compared to those of the pure PA66, and differential scanning calorimetry measurement also showed a decrease in the melting temperatures of PA66 of the blend. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40437.
Introducing primary and tertiary amino groups into a neutral polymer: A simple way to fabricating highly efficient nonviral vectors for gene delivery
Authors: Hu Xiufeng , Wang Hongbo , Yang Jianhai , Liu Wenguang , Wang Wei
Published: February 2014

In this work, a brushed polycationic polymer with primary and tertiary amino groups was designed and synthesized for gene delivery. The backbone polymer was poly(N‐hydroxyethylacrylamide) (PHEAA) by the atom transfer radical polymerization (ATRP), and then 3,3′‐diaminodipropylamine (DPA) was grafted onto the PHEAA by the reaction between hydroxyl and the secondary amine. A brushed PHEAA‐DPA cationic polymer was achieved with primary and tertiary amino groups and the ratio was 2 : 1. The PHEAA100‐DPA and PHEAA200‐DPA could effectively condense plasmid DNA (pDNA) at the weight ratio of vector/DNA of 0.6 and 0.4, respectively. The cytotoxicity of PHEAA‐DPA/pDNA to COS‐7 cells and HepG‐2 cells within the weight ratio of vector/DNA of 16 : 1 was lower than that of PEI25k, and cell viability decreased with the increment of the weight ratio. Although the cytotoxicity of PHEAA100‐DPA/pDNA was lower than PHEAA200‐DPA/pDNA, the latter possessed higher transfection efficiency at the same weight ratio both in COS‐7 cells and HepG‐2 cells, compared with PEI25k, the transfection efficiency of PHEAA200‐DPA/pDNA was better in COS‐7 cells and HepG‐2 cells with the weight ratio of 12 : 1 and 10 : 1, respectively. These results showed that the PHEAA‐DPA with less cytotoxicity and higher gene transfection efficiency has a broad perspective in gene therapy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40468.
Thermal degradation behavior and gas phase flame‐retardant mechanism of polylactide/PCPP blends
Authors: Lin Haijuan , Han Lijing , Dong Lisong
Published: February 2014

The thermal degradation behavior of the blend based on polylactide (PLA) and poly(1,2‐propanediol 2‐carboxyethyl phenyl phosphinate) (PCPP) was investigated by the thermogravimetric analysis (TGA). Thermal degradation activation energies (Ea) of neat PLA and PLA/15% PCPP blend were calculated via the Flynn–Wall–Ozawa method. The Ea of the blends increased with the addition of PCPP increasing when the conversion was higher than 10%. In addition, the appropriate conversion models for the thermal degradation process of PLA and PLA/15% PCPP were studied via the Criado method. At the same time, the main gaseous decomposition products of PLA and its blend were identified by TGA/infrared spectrometry (TGA–FTIR) analysis. And it revealed that the PCPP improved the flame‐retardant property of PLA via altering the release of the flammable gas and nonflammable gas. Moreover, the PCPP improved the flame‐retardant property of PLA by inhibiting exothermic oxidation reactions in the combustion, which was further proved by pyrolysis–gas chromatography–mass spectrometry analysis. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40480.
Military Service as Child Sacrifice: Oedipal and Odyssean Perspectives
Authors: Peterson Charles Andrew
Published: February 2014

Rudyard Kipling was determined to send his sickly, extremely near‐sighted, son, Jack into the meat grinder that was World War I. His son was killed shortly after reaching the front. Kipling's readiness to sacrifice his son will be compared with Abraham's willingness to sacrifice his son, Isaac; both parents were willing to sacrifice their sons for a higher cause. How parents, especially combat veterans who may have been traumatized themselves, view military service will certainly influence how their sons resist or be prepared for military service. Is trauma passed from one generation to the next? Are parents willing to sacrifice their children? Oedipal families will view the prospect of child sacrifice differently than will Odyssean families. These antipodal perspectives will be contrasted as we follow how World War II combat vets prepared Vietnam era sons for service and combat. Composite voices are used to illustrate different vantage points. Tentative suggestions are offered for parents, their children and recruiters. Copyright © 2014 John Wiley & Sons, Ltd.
The short appendix vermiformis as a risk factor for colorectal cancer
Authors: Cakmak Yusuf Ozgur , Ergelen Rabia , Ekinci Gazanfer , Kaspar Elif Cigdem
Published: February 2014

The human appendix vermiformis is regarded as an evolutionarily vestigial organ, although it has presumptive immune system functions and appears to support beneficial bacterial gut flora, both of which could influence cancer progression. A review of the comparative anatomy of the mammalian appendix reveals a significantly longer appendix in herbivores than in carnivorous animals. The lengthier appendix vermiformis in herbivores has been associated with the presence of cellulose‐digesting bacteria that colonize the structure. In light of recent studies that have reported the digestion of small amounts of cellulose in humans and the preventive effects of a vegetarian diet on colon cancer, we conducted a retrospective study of abdominal CT scans of 60 colon cancer patients and 60 healthy people to investigate a possible relationship between colon cancer and appendix vermiformis length. The mean length of the appendix in cancer patients [65.178 mm ± 13.46 (SD)] was shorter than that in the healthy control group [101.99 mm ± 16.58 (SD)] and the difference was statistically significant (P < 0.001). Statistical analysis demonstrated that the ages of the cancer patient group and the control group did not differ significantly (P = 0.534). The results of the present study indicate that the appendix is not merely a vestigial structure or regressed lymphoid tissue, but rather an organ that could be critical in the development of colon cancer, whether as a result of congenital or acquired appendicular factors. Clin. Anat. 27:498–502, 2014. © 2014 Wiley Periodicals, Inc.
Rat cortex and hippocampus‐derived soluble factors for the induction of adipose‐derived mesenchymal stem cells into neuron‐like cells
Authors: Han Chao , Song Lin , Liu Yang , Zou Wei , Jiang Chen , Liu Jing
Published: February 2014

To simulate brain microenvironment, adipose‐derived mesenchymal stem cells (AMSC) were induced to differentiate to neuronal‐like cells in rat cortex and hippocampus medium (Cox + Hip). First, isolated AMSC were characterized by flow cytometer and the capacity of adipogenesis and osteogenesis. After induction in rat cortex and hippocampus conditioned medium, the cell morphological change was examined and neural marker proteins (β‐Ш‐Tubulin, NSE, Nissl body) expression was detected by immunofluorescence staining. A variety of synaptic marker proteins, including GAP43, SHANK2, SHANK3 and Bassoon body, were detected. ELISA was used to measure brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) secretion at different time‐points. AMSCs positively expressed CD13, CD44 and CD90 and could differentiate into osteoblasts or adipocytes. After induction in Cox + Hip medium for 14 days, cells had a typical neuronal perikaryal appearance, which was suggestive of neuronal differentiation. After 14 days of Cox + Hip treatment, the percentage of cells expressing β‐Ⅲ‐Tubulin, NSE and Nissl was 53.9 ± 0.8%, 51.3 ± 1.7% and 16.4 ± 2.1%, respectively. Expression of GAP43, SHANK2, SHANK3 and Bassoon body was detected, indicating synapse formation after treatment in Cox + Hip medium. Differentiated AMSCs secreted neurotrophic factors NGF and BDNF. Thus rat cortex and hippocampus‐derived soluble factors can induce AMSCs to a neuronal‐like phenotype, suggesting that AMSCs have a dual role in supplementing newborn neurons and secreting neurotrophic factors, and therefore could be help as a potential treatment for nervous system diseases.
High Catalytic Performance of MoO3‐Bi2SiO5/SiO2 for the Gas‐Phase Epoxidation of Propylene by Molecular Oxygen
Authors: Pang Yijun , Chen Xiaohui , Xu Chengzhi , Lei Yangjun , Wei Kemei
Published: February 2014

MoO3‐Bi2SiO5/SiO2 catalysts with a Mo/Bi molar ratio of 5, prepared by a two‐step hydrothermal and simple impregnation method, were investigated for the epoxidation of propylene by O2 and characterized by XRD, N2 absorption–desorption isotherms, thermogravimetric analysis (TGA), temperature‐programmed reduction, NH3 temperature‐programmed desorption (TPD), and IR, Raman, and X‐ray photoelectron spectroscopy (XPS). On MoO3‐Bi2SiO5/SiO2 with Mo/Bi=5 calcined at 723 K, a propylene conversion of 21.99 % and a propylene oxide selectivity of 55.14 % were obtained at 0.15 MPa, 673 K, and flow rates of C3H6/O2/N2=1/4/20 cm3 min−1. XRD, IR spectroscopy, and XPS results show that Bi2SiO5 and MoO3 are crystalline nanoparticles. NH3‐TPD results indicate that the surface acid sites are necessary for the high catalytic activity. The results of TGA and N2 absorption–desorption isotherms reveal that a reasonable calcination temperature is 723 K. The reaction mechanism of propylene epoxidation on MoO3‐Bi2SiO5/SiO2 catalysis is hypothesized to involve an allylic radical generated at the molybdenum oxide species and the activation of O2 at the bismuth oxide cations.
Efficient Biocatalytic Degradation of Pollutants by Enzyme‐Releasing Self‐Propelled Motors
Authors: Orozco Jahir , Vilela Diana , Valdés‐Ramírez Gabriela , Fedorak Yuri , Escarpa Alberto , Vazquez‐Duhalt Rafael , Wang Joseph
Published: February 2014

The first example of a self‐propelled tubular motor that releases an enzyme for the efficient biocatalytic degradation of chemical pollutants is demonstrated. How the motors are self‐propelled by the Marangoni effect, involving simultaneous release of SDS surfactant and the enzyme remediation agent (laccase) in the polluted sample, is illustrated. The movement induces fluid convection and leads to the rapid dispersion of laccase into the contaminated solution and to a dramatically accelerated biocatalytic decontamination process. The greatly improved degradation efficiency, compared to quiescent solutions containing excess levels of the free enzyme, is illustrated for the efficient biocatalytic degradation of phenolic and azo‐type pollutants. The high efficiency of the motor‐based decontamination approach makes it extremely attractive for a wide‐range of remediation processes in the environmental, defense and public health fields.
Atmospheric Nitrogen and Phosphorus Deposition at Three Sites in Nanjing, China, and Possible Links to Nitrogen Deposition Sources
Authors: Sun Liying , Liu Yinglie , Wang Jinyang , Khalil Mohammad Aslam K. , Zou Jianwen , Xiong Zhengqin
Published: February 2014

Atmospheric deposition is a global and increasing threat to ecosystem function. Here, we analyzed bulk and wet deposition of inorganic N, total phosphorus (TP) and δ15N of NH4–N and NO3–N at three sites in Nanjing from March 2010 to February 2012. Results showed that bulk deposition fluxes of inorganic N and TP averaged 54.82 kg N ha–1 year–1 and 1.82 kg P ha–1 year–1, respectively. The N/P bulk deposition ratio reached 30/1, leading ecosystems toward P‐limitation. Wet deposition fluxes of inorganic N and TP were 25.65 kg N ha–1 year–1 and 1.29 kg P ha–1 year–1, respectively, suggesting the potential contribution of inorganic N from dry deposition. Based on the δ15N values of NH4–N and NO3–N and model results, we found that chemical fertilizers and animal manures contributed to the reduced N deposition and fossil fuel and soil emissions contributed to the oxidized N deposition, depending upon the time and site. Agriculture sector contributed almost twice as industry while animal manures contributed significantly within agriculture.
Mutational analysis and clinical correlation of metastatic colorectal cancer
Authors: Russo Andrea L. , Borger Darrell R. , Szymonifka Jackie , Ryan David P. , Wo Jennifer Y. , Blaszkowsky Lawrence S. , Kwak Eunice L. , Allen Jill N. , Wadlow Raymond C. , Zhu Andrew X. , Murphy Janet E. , Faris Jason E. , Dias‐Santagata Dora , Haigis Kevin M. , Ellisen Leif W. , Iafrate Anthony J. , Hong Theodore S.
Published: February 2014

BACKGROUND

Early identification of mutations may guide patients with metastatic colorectal cancer toward targeted therapies that may be life prolonging. The authors assessed tumor genotype correlations with clinical characteristics to determine whether mutational profiling can account for clinical similarities, differences, and outcomes.

METHODS

Under Institutional Review Board approval, 222 patients with metastatic colon adenocarcinoma (n = 158) and rectal adenocarcinoma (n = 64) who underwent clinical tumor genotyping were reviewed. Multiplexed tumor genotyping screened for >150 mutations across 15 commonly mutated cancer genes. The chi‐square test was used to assess genotype frequency by tumor site and additional clinical characteristics. Cox multivariate analysis was used to assess the impact of genotype on overall survival.

RESULTS

Broad‐based tumor genotyping revealed clinical and anatomic differences that could be linked to gene mutations. NRAS mutations were associated with rectal cancer versus colon cancer (12.5% vs 0.6%; P < .001) and with age ≥56 years (7% vs 0.9%; P = .02). Conversely, v‐raf murine sarcoma viral oncogene homolog B (BRAF) mutations were associated with colon cancer (13% vs 3%; P = .024) and older age (15.8% vs 4.6%; P = .006). TP53 mutations were associated with rectal cancer (30% vs 18%; P = .048), younger age (14% vs 28.7%; P = .007), and men (26.4% vs 14%; P = .03). Lung metastases were associated with PIK3CA mutations (23% vs 8.7%; P = .004). Only mutations in BRAF were independently associated with decreased overall survival (hazard ratio, 2.4; 95% confidence interval, 1.09‐5.27; P = .029).

CONCLUSIONS

The current study suggests that underlying molecular profiles can differ between colon and rectal cancers. Further investigation is warranted to assess whether the differences identified are important in determining the optimal treatment course for these patients. Cancer 2014;120:1482–1490. © 2014 American Cancer Society.
Height, body mass index (BMI), BMI change, and the risk of estrogen receptor‐positive, HER2‐positive, and triple‐negative breast cancer among women ages 20 to 44 years
Authors: Kawai Masaaki , Malone Kathleen E. , Tang Mei‐Tzu C. , Li Christopher I.
Published: February 2014

BACKGROUND

The evidence regarding correlations between various anthropometric characteristics and breast cancer risk among young women is mixed, and few studies have assessed these associations by subtype.

METHODS

This was a population‐based, case‐control study of 779 women with estrogen receptor (ER)‐positive breast cancer; 182 women with ER‐negative/human epidermal growth factor‐2 (HER2)‐negative/progesterone receptor‐negative (triple‐negative [TN]) breast cancer; and 60 women with ER‐negative/HER2‐overexpressing, invasive breast cancer ages 20 to 44 years who were diagnosed from 2004 to 2010 in the Seattle‐Puget Sound metropolitan area; as well as 939 cancer‐free controls. Associations between height and body mass index (BMI) at different time points in relation to breast cancer risk were assessed using polytomous logistic regression.

RESULTS

Height, BMI at age 18 years, and BMI at the reference date were not related to the risks of ER‐positive, TN, or HER2‐overexpressing breast cancer. Changes in BMI from age 18 years to the reference date were not related to the risk of either ER‐positive or HER2‐overexpressing breast cancer. However, compared with women who had a BMI change from 0 to 4.9 kg/m2 from age 18 years to the reference date, those who experienced a BMI increase ≥10 kg/m2 during the same interval had a 2.0‐fold (95% confidence interval, 1.2‐fold to 3.3‐fold increase) increased risk of TN breast cancer. For women with ER‐positive disease, there was some evidence that parity modified the effect of BMI change (Pinteraction = .002), because a BMI increase of ≥10 kg/m2 was associated with a reduced risk of ER‐positive disease only among nulliparous women (odds ratio, 0.3; 95% confidence interval, 0.2‐0.6).

CONCLUSIONS

The correlations appear to differ substantially between BMI change and the risks of TN breast cancer and ER‐positive breast cancer. Cancer 2014;120:1548–1556. © 2014 American Cancer Society.
Cortical hypoplasia and ventriculomegaly of p73‐deficient mice: Developmental and adult analysis
Authors: Medina‐Bolívar Carolina , González‐Arnay Emilio , Talos Flaminia , González‐Gómez Miriam , Moll Ute M. , Meyer Gundela
Published: February 2014

Trp73, a member of the p53 gene family, plays a crucial role in neural development. We describe two main phenotypic variants of p73 deficiency in the brain, a severe one characterized by massive apoptosis in the cortex leading to early postnatal death and a milder, non‐/low‐apoptosis one in which 50% of pups may reach adulthood using an intensive‐care breeding protocol. Both variants display the core triad of p73 deficiency: cortical hypoplasia, hippocampal malformations, and ventriculomegaly. We studied the development of the neocortex in p73 KO mice from early embryonic life into advanced age (25 months). Already at E14.5, the incipient cortical plate of the p73 KO brains showed a reduced width. Examination of adult neocortex revealed a generalized, nonprogressive reduction by 10–20%. Area‐specific architectonic landmarks and lamination were preserved in all cortical areas. The surviving adult animals had moderate ventricular distension, whereas pups of the early lethal phenotypic variant showed severe ventriculomegaly. Ependymal cells of wild‐type ventricles strongly express p73 and are particularly vulnerable to p73 deficiency. Ependymal denudation by apoptosis and reduction of ependymal cilia were already evident in young mice, with complete absence of cilia in older animals. Loss of p73 function in the ependyma may thus be one determining factor for chronic hydrocephalus, which leads to atrophy of subcortical structures (striatum, septum, amygdala). p73 Is thus involved in a variety of CNS activities ranging from embryonic regulation of brain size to the control of cerebrospinal fluid homeostasis in the adult brain via maintenance of the ependyma. J. Comp. Neurol. 522:2663–2679, 2014. © 2014 Wiley Periodicals, Inc.
X‐ray Absorption Near‐Edge Structure and Nuclear Magnetic Resonance Study of the Lithium–Sulfur Battery and its Components
Authors: Patel Manu U. M. , Arčon Iztok , Aquilanti Giuliana , Stievano Lorenzo , Mali Gregor , Dominko Robert
Published: February 2014

Understanding the mechanism(s) of polysulfide formation and knowledge about the interactions of sulfur and polysulfides with a host matrix and electrolyte are essential for the development of long‐cycle‐life lithium–sulfur (Li–S) batteries. To achieve this goal, new analytical tools need to be developed. Herein, sulfur K‐edge X‐ray absorption near‐edge structure (XANES) and 6,7Li magic‐angle spinning (MAS) NMR studies on a Li–S battery and its sulfur components are reported. The characterization of different stoichiometric mixtures of sulfur and lithium compounds (polysulfides), synthesized through a chemical route with all‐sulfur‐based components in the Li–S battery (sulfur and electrolyte), enables the understanding of changes in the batteries measured in postmortem mode and in operando mode. A detailed XANES analysis is performed on different battery components (cathode composite and separator). The relative amounts of each sulfur compound in the cathode and separator are determined precisely, according to the linear combination fit of the XANES spectra, by using reference compounds. Complementary information about the lithium species within the cathode are obtained by using 7Li MAS NMR spectroscopy. The setup for the in operando XANES measurements can be viewed as a valuable analytical tool that can aid the understanding of the sulfur environment in Li–S batteries.
Hierarchically Porous Carbon with Manganese Oxides as Highly Efficient Electrode for Asymmetric Supercapacitors
Authors: Chou Tsu‐chin , Doong Ruey‐an , Hu Chi‐chang , Zhang Bingsen , Su Dang Sheng
Published: February 2014

A promising energy storage material, MnO2/hierarchically porous carbon (HPC) nanocomposites, with exceptional electrochemical performance and ultrahigh energy density was developed for asymmetric supercapacitor applications. The microstructures of MnO2/HPC nanocomposites were characterized by transmission electron microscopy, scanning transmission electron microscopy, and electron dispersive X‐ray elemental mapping analysis. The 3–5 nm MnO2 nanocrystals at mass loadings of 7.3–10.8 wt % are homogeneously distributed onto the HPCs, and the utilization efficiency of MnO2 on specific capacitance can be enhanced to 94–96 %. By combining the ultrahigh utilization efficiency of MnO2 and the conductive and ion‐transport advantages of HPCs, MnO2/HPC electrodes can achieve higher specific capacitance values (196 F g−1) than those of pure carbon electrodes (60.8 F g−1), and maintain their superior rate capability in neutral electrolyte solutions. The asymmetric supercapacitor consisting of a MnO2/HPC cathode and a HPC anode shows an excellent performance with energy and power densities of 15.3 Wh kg−1 and 19.8 kW kg−1, respectively, at a cell voltage of 2 V. Results obtained herein demonstrate the excellence of MnO2/HPC nanocomposites as energy storage material and open an avenue to fabricate the next generation supercapacitors with both high power and energy densities.
CCR7‐mediated migration in the thymus controls γδ T‐cell development
Authors: Reinhardt Annika , Ravens Sarina , Fleige Henrike , Haas Jan D. , Oberdörfer Linda , Łyszkiewicz Marcin , Förster Reinhold , Prinz Immo
Published: February 2014

αβ T‐cell development and selection proceed while thymocytes successively migrate through distinct regions of the thymus. For γδ T cells, the interplay of intrathymic migration and cell differentiation is less well understood. Here, we crossed C‐C chemokine receptor (CCR)7‐deficient (Ccr7−/−) and CCR9‐deficient mice (Ccr9−/−) to mice with a TcrdH2BeGFP reporter background to investigate the impact of thymic localization on γδ T‐cell development. γδ T‐cell frequencies and numbers were decreased in CCR7‐deficient and increased in CCR9‐deficient mice. Transfer of CCR7‐ or CCR9‐deficient BM into irradiated C57BL/6 WT recipients reproduced these phenotypes, pointing toward cell‐intrinsic migration defects. Monitoring recent thymic emigrants by intrathymic labeling allowed us to identify decreased thymic γδ T‐cell output in CCR7‐deficient mice. In vitro, CCR7‐deficient precursors showed normal γδ T‐cell development. Immunohistology revealed that CCR7 and CCR9 expression was important for γδ T‐cell localization within thymic medulla or cortex, respectively. However, γδ T‐cell motility was unaltered in CCR7‐ or CCR9‐deficient thymi. Together, our results suggest that proper intrathymic localization is important for normal γδ T‐cell development.
Iodo(trisyl)sulfane: Reactivity of a Stable Alkanesulfenyl Iodide towards Antithyroid Drugs
Authors: Wismach Cathleen , Jones Peter G. , du Mont Wolf‐Walther , Mugesh Govindasamy , Papke Ulrich , Linden H. Bernhard , Arca Massimiliano , Lippolis Vito
Published: February 2014

Iodination of tris(trimethylsilyl)methanethiol (trisylthiol, TsiSH) in tetrahydrofuran provides the new thermally stable alkanesulfenyl iodide [iodo(trisyl)sulfane, TsiSI] as a violet solid. Iodo(trisyl)sulfane exhibits iodine–iodine contacts between pairs of TsiSI molecules in the solid state. Properties of TsiSI were studied by vibrational spectroscopy and with the help of density functional calculations. TsiSI reacts in the presence of triethylamine with the antithyroid drugs 6‐n‐propyl‐ and 6‐methylthiouracil (PTU, MTU) and with N‐methylmethimazole (MMI) to form unsymmetric disulfides that were investigated by means of X‐ray crystallography. In the solid state, the PTU and MTU derivatives exist as hydrogen‐bonded centrosymmetric dimers, whereas the MMI‐derived disulfide is an unsymmetric monomer.
Design and Synthesis of Pironetin Analogue/Combretastatin A‐4 Hybrids and Evaluation of Their Cytotoxic Activity
Authors: Torijano‐Gutiérrez Sandra , Vilanova Concepción , Díaz‐Oltra Santiago , Murga Juan , Falomir Eva , Carda Miguel , Marco J. Alberto
Published: February 2014

We describe the preparation of a series of hybrid molecules containing a combretastatin A‐4 moiety and a pironetin analogue fragment linked by an ester spacer of variable length. The cytotoxic activities of these compounds have been measured and the relationship between the structure and cytotoxicity is discussed. Some of the tested compounds showed cytotoxicity values of the same order of magnitude as those of the parental molecules, combretastatin A‐4 and pironetin, and were less toxic than the latter for normal cells.
Modification of radiation‐induced DNA double strand break repair pathways by chemicals extracted from Podophyllum hexandrum: An in vitro study in human blood leukocytes
Authors: Srivastava Nitya N. , Shukla Sandeep K. , Yashavarddhan M.H. , Devi Memita , Tripathi Rajendra P. , Gupta Manju L.
Published: February 2014

Radiation exposure is a serious threat to biomolecules, particularly DNA, proteins and lipids. Various exogenous substances have been reported to protect these biomolecules. In this study we explored the effect of pre‐treatment with G‐002M, a mixture of three active derivatives isolated from the rhizomes of Podophyllum hexandrum, on DNA damage response in irradiated human blood leukocytes. Blood was collected from healthy male volunteers, preincubated with G‐002M and then irradiated with various doses of radiation. Samples were analyzed using flow cytometry to quantify DNA double strand break (DSB) biomarkers including γ‐H2AX, P53BP1 and levels of ligase IV. Blood samples were irradiated in vitro and processed to determine time and dose‐dependent kinetics. Semiquantitative RT‐PCR was performed at various time points to measure gene expression of DNA‐PKcs, Ku80, ATM, and 53BP1; each of these genes is involved in DNA repair signaling. Pre‐treatment of blood with G‐002M resulted in reduction of γ‐H2AX and P53BP1 biomarkers levels and elevated ligase IV levels relative to non‐G‐002M‐treated irradiated cells. These results confirm suppression in radiation‐induced DNA DSBs. Samples pre‐treated with G‐002M and then irradiated also showed significant up‐regulation of DNA‐PKcs and Ku80 and downregulation of ATM and 53BP1 gene expressions, suggesting that G‐002M plays a protective role against DNA damage. The protective effect of G‐002M may be due to its ability to scavange radiation‐induced free radicals or assist in DNA repair. Further studies are needed to decipher the role of G‐002M on signaling molecules involved in radiation‐induced DNA damage repair pathways. Environ. Mol. Mutagen. 55:436–448, 2014. © 2014 Wiley Periodicals, Inc.
A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis
Authors: Zadra Giorgia , Photopoulos Cornelia , Tyekucheva Svitlana , Heidari Pedram , Weng Qing Ping , Fedele Giuseppe , Liu Hong , Scaglia Natalia , Priolo Carmen , Sicinska Ewa , Mahmood Umar , Signoretti Sabina , Birnberg Neal , Loda Massimo
Published: February 2014

5′AMP‐activated kinase (AMPK) constitutes a hub for cellular metabolic and growth control, thus representing an ideal therapeutic target for prostate cancers (PCas) characterized by increased lipogenesis and activation of mTORC1 pathway. However, whether AMPK activation itself is sufficient to block cancer cell growth remains to be determined. A small molecule screening was performed and identified MT 63–78, a specific and potent direct AMPK activator. Here, we show that direct activation of AMPK inhibits PCa cell growth in androgen sensitive and castration resistant PCa (CRPC) models, induces mitotic arrest, and apoptosis. In vivo, AMPK activation is sufficient to reduce PCa growth, whereas the allelic loss of its catalytic subunits fosters PCa development. Importantly, despite mTORC1 blockade, the suppression of de novo lipogenesis is the underpinning mechanism responsible for AMPK‐mediated PCa growth inhibition, suggesting AMPK as a therapeutic target especially for lipogenesis‐driven PCas. Finally, we demonstrate that MT 63–78 enhances the growth inhibitory effect of AR signaling inhibitors MDV3100 and abiraterone. This study thus provides a rationale for their combined use in CRPC treatment.
On the tweet arrival process at Twitter: analysis and applications
Authors: González Roberto , Muñoz Alfonso , Hernández José Alberto , Cuevas Rubén
Published: February 2014

This work provides a novel measurement‐based analysis of the tweet arrival traffic process at Twitter. The analysis considers more than one million total tweets collected at 48 different times of the day (o'clock and half‐past every hour). We observe a 3.5‐tweet/ms average rate with a valley of 2.5 tweets/ms at 10 AM (GMT+1) and a peak at 3 PM (GMT+1) of about 5 tweets/ms. We further model the traffic pattern as a Gaussian process, and we validate such an assumption with multiple normality tests. Finally, we overview a number of applications where such a model may show its utility, namely infrastructure dimensioning and upgrading, the detection of outlier events, energy efficiency and so on. Copyright © 2014 John Wiley & Sons, Ltd.
BCL2 mutation spectrum in B‐cell non‐Hodgkin lymphomas and patterns associated with evolution of follicular lymphoma
Authors: Burkhard Regula , Bhagat Govind , Cogliatti Sergio B. , Rossi Davide , Gaidano Gianluca , Pasqualucci Laura , Novak Urban
Published: February 2014

BCL2 is a target of somatic hypermutation in t(14;18) positive and also in a small fraction of t(14;18) negative diffuse large B‐cell lymphoma (DLBCL), suggesting an aberrant role of somatic hypermutation (ASHM). To elucidate the prevalence of BCL2 mutations in lymphomas other than DLBCL, we Sanger‐sequenced the hypermutable region of the BCL2 gene in a panel of 69 mature B‐cell lymphomas, including Richter's syndrome DLBCL, marginal‐zone lymphomas, post‐transplant lymphoproliferative disorders, HIV‐associated and common‐variable immunodeficiency‐associated DLBCL, all known to harbour ASHM‐dependent mutations in other genes, as well as 16 t(14,18) negative and 21 t(14;18) positive follicular lymphomas (FLs). We also investigated the pattern of BCL2 mutations in longitudinal samples from 10 FL patients relapsing to FL or transforming to DLBCL (tFL). By direct sequencing, we found clonally represented BCL2 mutations in 2/16 (13%) of t(14;18) negative FLs, 2/16 (13%) HIV‐DLBCLs, 1/9 (11%) of Richter's syndrome DLBCL, 1/17 (6%) of post‐transplant lymphoproliferative disorders and 1/2 (50%) common‐variable immunodeficiency‐associated DLBCL. The proportion of mutated cases was significantly lower than in FLs carrying the t(14;18) translocation (15/21, 71%). However, the absence of t(14;18) by FISH or PCR and the molecular features of the mutations strongly suggest that BCL2 represents an additional target of ASHM in these entities. Analysis of the BCL2 mutation pattern in clonally related FL/FL and FL/tFL samples revealed two distinct scenarios of genomic evolution: (i) direct evolution from the antecedent FL clone, with few novel clonal mutations acquired by the tFL major clone, and (ii) evolution from a common mutated long‐lived progenitor cell, which subsequently acquired distinct mutations in the FL and in the relapsed or transformed counterpart. Copyright © 2014 John Wiley & Sons, Ltd.
Targeting high‐grade B cell lymphoma with CD19‐specific T cells
Authors: Lehmann Frank M. , Maurberger Anna , Feicht Samantha , Helm Florian , Ladinig Camilla , Kieback Elisa , Uckert Wolfgang , Kammertöns Thomas , Kremmer Elisabeth , Mautner Josef , Gerbitz Armin , Bornkamm Georg W.
Published: February 2014

Adoptive T cell therapy is an important additional treatment option for malignant diseases resistant to chemotherapy. Using a murine high‐grade B cell lymphoma model, we have addressed the question whether the B cell differentiation antigen CD19 can act as rejection antigen. CD19−/− mice inoculated with CD19+ B cell lymphoma cells showed higher survival rates than WT mice and were protected against additional tumor challenge. T cell depletion prior to tumor transfer completely abolished the protective response. By heterotypic vaccination of CD19−/− mice against murine CD19, survival after tumor challenge was significantly increased. To define protective epitopes within the CD19 molecule, T cells collected from mice that had survived the tumor transfer were analyzed for IFNγ secretion in response to CD19‐derived peptides. The majority of mice exhibited a CD4+ T cell response to CD19 peptide 27, which was the most dominant epitope after CD19 vaccination. A peptide 27‐specific CD4+ T cell line protected CD19−/− mice against challenge with CD19+ lymphoma and also cured a significant proportion of WT mice from recurrent disease in a model of minimal residual disease after chemotherapy. In conclusion, our data highlight CD19‐specific CD4+ T cells for adoptive T cell therapy of B cell lymphomas.
MicroRNA control of epithelial‐mesenchymal transition in cancer stem cells
Authors: Hao Jin , Zhang Yueling , Deng Mengzhao , Ye Rui , Zhao Sen , Wang Yating , Li Juan , Zhao Zhihe
Published: February 2014

Cancer stem cells (CSCs) represent a small subset of cancer cell populations that possess characteristics associated with normal stem cells. They have the ability to self‐renew, and are able to generate diverse tumor cells and account for metastases. Therefore, CSCs are widely accepted as potential mediators of therapeutic resistance and novel targets for anti‐cancer treatments. Recent progress has highlighted the significance of epithelial–mesenchymal transition (EMT) process in CSC formation, as well as the crucial role of microRNAs in controlling EMT and cancer metastasis. MicroRNAs are also reported to take part in the control of CSC functions and the regulation of cancer progression by affecting EMT process. Thus, it is highly crucial to develop deeper understanding of the mechanisms that how microRNAs control EMT processes and regulate CSC functions for better therapeutics of cancer disease. Herein we make this review to summarize the current understanding of the regulatory mechanisms of EMT in CSC initiation, with a special focus on the role of microRNAs in EMT control, and discuss the implications of targeting CSCs for cancer therapeutics.
CD24 knockout prevents colorectal cancer in chemically induced colon carcinogenesis and in APCMin/CD24 double knockout transgenic mice
Authors: Naumov Inna , Zilberberg Alona , Shapira Shiran , Avivi Doran , Kazanov Dina , Rosin‐Arbesfeld Rina , Arber Nadir , Kraus Sarah
Published: February 2014

Increased expression of CD24 is seen in a large variety of solid tumors, including up to 90% of gastrointestinal (GI) tumors. Stable derivatives of SW480 colorectal cancer (CRC) cells that overexpress CD24 proliferate faster, and increase cell motility, saturation density, plating efficiency, and growth in soft agar. They also produce larger tumors in nude mice as compared to the parental SW480 cells. Most significantly, even depletion of one copy of the CD24 allele in the APCMin/+ mice of a transgenic mouse model led to a dramatic reduction in tumor burden in all sections of the small intestine. Homozygous deletion of both CD24 alleles resulted in complete abolishment of tumor formation. Moreover, CD24 knockout mice exhibited resistance to chemically induced inflammation‐associated CRC. Finally, a new signal transduction pathway is suggested: namely, CD24 expression downstream to COX2 and PGE2 synthesis, which is directly regulated by β‐catenin. CD24 is shown in vitro and in vivo as being an important oncogene in the gut, and one that plays a critical role in the initiation and progression of carcinogenesis.
High hydrostatic pressure induces immunogenic cell death in human tumor cells
Authors: Fucikova Jitka , Moserova Irena , Truxova Iva , Hermanova Ivana , Vancurova Irena , Partlova Simona , Fialova Anna , Sojka Ludek , Cartron Pierre‐Francois , Houska Milan , Rob Lukas , Bartunkova Jirina , Spisek Radek
Published: February 2014

Recent studies have identified molecular events characteristic of immunogenic cell death (ICD), including surface exposure of calreticulin (CRT), the heat shock proteins HSP70 and HSP90, the release of high‐mobility group box protein 1 (HMGB1) and the release of ATP from dying cells. We investigated the potential of high hydrostatic pressure (HHP) to induce ICD in human tumor cells. HHP induced the rapid expression of HSP70, HSP90 and CRT on the cell surface. HHP also induced the release of HMGB1 and ATP. The interaction of dendritic cells (DCs) with HHP‐treated tumor cells led to a more rapid rate of DC phagocytosis, upregulation of CD83, CD86 and HLA‐DR and the release of interleukin IL‐6, IL‐12p70 and TNF‐α. DCs pulsed with tumor cells killed by HHP induced high numbers of tumor‐specific T cells. DCs pulsed with HHP‐treated tumor cells also induced the lowest number of regulatory T cells. In addition, we found that the key features of the endoplasmic reticulum stress‐mediated apoptotic pathway, such as reactive oxygen species production, phosphorylation of the translation initiation factor eIF2α and activation of caspase‐8, were activated by HHP treatment. Therefore, HHP acts as a reliable and potent inducer of ICD in human tumor cells.
SHALL WE DANCE? MUSIC AS A PORT OF ENTRANCE TO MATERNAL–INFANT INTERSUBJECTIVITY IN A CONTEXT OF POSTNATAL DEPRESSION
Authors: Van Puyvelde Martine , Rodrigues Helena , Loots Gerrit , De Coster Lotta , Du Ville Kevin , Matthijs Liesbeth , Simcock David , Pattyn Nathalie
Published: February 2014

The present study introduces the concept of a mother–infant group therapy that makes use of music, singing, and moving to establish maternal–infant intersubjectivity. It was conducted in a residential mother–baby unit for mothers with postnatal depression and their infants over a 5‐week period. Maternal–infant intersubjectivity of four dyads in relation to the group dynamics were microanalyzed for Sessions 1 and 5. We made within‐session (i.e., beginning–middle–end) and between‐session (Session 1 vs. Session 5) comparisons for the number of intersubjectivity moments (ISMs), total time of intersubjectivity (IST), and the mean duration of ISMs on a dyadic (i.e., own mother/infant involved) and a nondyadic level (i.e., own mother/infant not involved). In addition, three ISM levels (degree of group contribution) were distinguished. The results indicated a significant increase of ISMs/IST from Session 1 to Session 5. Within‐session analyses showed that ISMs/IST significantly decreased through Session 1 and remained stable throughout Session 5. Intersubjectivity occurred mainly on ISM Level 1 during Session 1 and on ISM Level 3 during Session 5, suggesting increased dyadic autonomy and self‐efficacy. The results are discussed in relation to the musical characteristics of mother–infant dyads, music improvisation techniques, group processes, and intersubjective development.