bluuebunny/crossref_metadata_2025 huggingface dataset:
TRAIL is Involved in the Tumoricidal Activity of Mouse Natural Killer Cells Stimulated by Newcastle Disease Virus in Vitro
Authors: Song De‐Zhi , Liang Ying , Xiao Qing , Yin Jun , Gong Jin‐Ling , Lai Zhen‐Ping , Zhang Zeng‐Feng , Gao Ling‐Xi , Fan Xiao‐Hui
Published: August 2013

Newcastle disease virus (NDV) is a potential antitumor agent, and its antitumor effect has been evaluated in preclinical tests. However, the mechanisms of NDV‐based antitumor therapy are still not completely clear. In the present study we found that NDV‐stimulation enhanced the killing ability of mouse spleen natural killer (NK) cells towards mouse hepatoma cell lines, and tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) plays an important role in this tumoricidal activity. NDV stimulation induced up‐regulation of TRAIL both at the mRNA and protein levels in NK cells. Blocking TRAIL by antibody (Ab) almost completely eliminated the killing effect of NK cells on hepatoma cell lines. Furthermore, neutralizing interferon (IFN)‐γ by Ab could inhibit TRAIL expression and tumoricidal activity of NDV‐stimulated NK cells. These results indicated a substantial role of TRAIL as an effector molecule in NDV‐induced NK cells mediated tumoricidal activity. The NDV stimulation triggered TRAIL expression in mouse spleen NK cells could be mediated by IFN‐γ induction. Anat Rec, 296:1552–1560, 2013. © 2013 Wiley Periodicals, Inc.
Incorporation of Nucleoside Probes Opposite O6‐Methylguanine by Sulfolobus solfataricus DNA Polymerase Dpo4: Importance of Hydrogen Bonding
Authors: Stornetta Alessia , Angelov Todor , Guengerich F. Peter , Sturla Shana J.
Published: August 2013

O6‐Methylguanine (O6‐MeG) is a mutagenic DNA lesion, arising from the action of methylating agents on guanine (G) in DNA. Dpo4, an archaeal low‐fidelity Y‐family DNA polymerase involved in translesion DNA synthesis (TLS), is a model for studying how human Y‐family polymerases bypass DNA adducts. Previous work showed that Dpo4‐mediated dTTP incorporation is favored opposite O6‐MeG rather than opposite G. However, factors influencing the preference of Dpo4 to incorporate dTTP opposite O6‐MeG are not fully defined. In this study, we investigated the influence of structural features of incoming dNTPs on their enzymatic incorporation opposite O6‐MeG in a DNA template. To this end, we utilized a new fluorescence‐based primer extension assay to evaluate the incorporation efficiency of a panel of synthetic dNTPs opposite G or O6‐MeG by Dpo4. In single‐dNTP primer extension studies, the synthetic dNTPs were preferentially incorporated opposite G, relative to O6‐MeG. Moreover, pyrimidine‐based dNTPs were generally better incorporated than purine‐based syn‐conformation dNTPs. The results suggest that hydrophobicity of the incoming dNTP appears to have little influence on the process of nucleotide selection by Dpo4, with hydrogen bonding capacity being a major influence. Additionally, modifications at the C2‐position of dCTP increase the selectivity for incorporation opposite O6‐MeG without a significant loss of efficiency.
Mental retardation‐related protease, motopsin (prss12), binds to the BRICHOS domain of the integral membrane protein 2a
Authors: Mitsui Shinichi , Osako Yoji , Yuri Kazunari
Published: August 2013

Motopsin (prss12), a mosaic serine protease secreted by neuronal cells, is believed to be important for cognitive function, as the loss of its function causes severe nonsyndromic mental retardation. To understand the molecular role of motopsin, we identified the integral membrane protein 2a (Itm2a) as a motopsin‐interacting protein using a yeast two‐hybrid system. A pull‐down assay showed that the BRICHOS domain of Itm2a was essential for this interaction. Motopsin and Itm2a co‐localized in COS cells and in cultured neurons when transiently expressed in these cells. Both proteins were co‐immunoprecipitated from lysates of these transfected COS cells. Itm2a was strongly detected in a brain lysate prepared between postnatal day 0 and 10, during which period motopsin protein was also enriched in the brain. Immunohistochemistry detected Itm2a as patchy spots along endothelial cells of brain capillaries (which also expressed myosin II regulatory light chain [RLC]), and on glial fibrillary acidic protein (GFAP)‐positive processes in the developing cerebral cortex. The data raise the possibility that secreted motopsin interacts with endothelial cells in the developing brain.
Analysis of epothilone B‐induced cell death in normal ovarian cells
Authors: Rogalska Aneta , Gajek Arkadiusz , Marczak Agnieszka
Published: August 2013

We have investigated the mode of cell death induced by a new microtubule‐stabilizing agent, epothilone B (EpoB, patupilone), and a clinically used medicine, paclitaxel (PTX), in normal ovarian cells. Using fluorescence microscopy, polyacrylamide gel electrophoresis preceding Western blot analysis, as well as spectrofluorimetric and colorimetric detection, we demonstrate that, compared to EpoB, PTX induced high time‐dependent morphological and biochemical changes typical of apoptosis. Induction of apoptosis followed an early increase in p53 levels. Apoptosis reached its maximum at 24–48 h. At the same time, there was a significant increase in caspase‐9 and ‐3 activity and PARP fragmentation, which suggests that an intrinsic path was involved. Apoptosis in MM14 cells was increased more by PTX than EpoB, and also induced more necrosis responsible for inflammation (1.4‐fold) than EpoB.
Human foreskin fibroblast‐like stromal cells can differentiate into functional hepatocytic cells
Authors: Huang Hsing‐I , Chen Shao‐Kuan , Wang Robert Y.‐L. , Shen Chia‐Rui , Cheng Yu‐Che
Published: August 2013

Foreskin fibroblast‐like stromal cells (FDSCs) are progenitors isolated from human tissue that can differentiate into diverse cell types. Many types of stem cells can differentiate into hepatocyte‐like cells, which could be used for drug testing or in liver regeneration therapy, but whether FDSCs can be converted into functional hepatocytes is unknown. FDSCs show divergent properties when cultured in distinct media, forming spheres in Dulbecco's modified Eagle's medium (DMEM) containing F12, epidermal growth factor (EGF), and basic fibroblast growth factor (b‐FGF), but have fibroblast‐like morphology when cultured in DMEM‐based growth medium. Both cell populations express the typical mesenchymal stem cell markers CD90, CD105, and CD73, but the p75 neurotrophin receptor (p75NTR) was detected only in FDSC spheres. Both types of FDSCs can differentiate into hepatocyte‐like cells, which express typical liver markers, including albumin and hepatocyte paraffin 1 (Hep Par1), along with liver‐specific biological activities. When plasmids containing the human hepatitis B virus (HBV) genome were transfected transiently into FDSCs, differentiated hepatocyte‐like cells secrete large amounts of HBe and HBs antigens. FDSCs could be used for clinical hepatic therapy and/or serve as a model of HBV.
Evaluating cis‐2,6‐Dimethylpiperidide (cis‐DMP) as a Base Component in Lithium‐Mediated Zincation Chemistry
Authors: Armstrong David R. , Garden Jennifer A. , Kennedy Alan R. , Leenhouts Sarah M. , Mulvey Robert E. , O'Keefe Philip , O'Hara Charles T. , Steven Alan
Published: August 2013

Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6‐tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non‐TMP based mixed‐metal bases and, as cis‐2,6‐dimethylpiperidide (cis‐DMP) was chosen as the alternative amide, developing cis‐DMP zincate chemistry which has received meagre attention compared to that of its methyl‐rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis‐DMP)Et2] (TMEDA=N,N,N′,N′‐tetramethylethylenediamine) has been synthesised by co‐complexation of Li(cis‐DMP), Et2Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X‐ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N‐diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis‐DMP)Et2] has been probed and contrasted with that of the known but previously uninvestigated di‐tert‐butylzincate, [(TMEDA)LiZn(cis‐DMP)tBu2]. The former was found to be the superior base (for example, producing the ortho‐deuteriated product in respective yields of 78 % and 48 % following D2O quenching of zincated benzamide intermediates). An 88 % yield of 2‐iodo‐N,N‐diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3‐hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et2Zn and TMEDA system. Under certain conditions, the cis‐DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di‐tert‐butylzincate and crystallographically characterised, namely the pre‐metallation complex [{(iPr)2N(Ph)CO}LiZn(cis‐DMP)tBu2] and the post‐metallation complex [(TMEDA)Li(cis‐DMP){2‐[1‐C(=O)N(iPr)2]C6H4}Zn(tBu)], shed valuable light on the structures and mechanisms involved in these alkali‐metal‐mediated zincation reactions. Aspects of these reactions are also modelled by DFT calculations.
A Hybrid Ring‐Opening Metathesis Polymerization Catalyst Based on an Engineered Variant of the β‐Barrel Protein FhuA
Authors: Philippart Freddi , Arlt Marcus , Gotzen Steve , Tenne Stefanie‐Joana , Bocola Marco , Chen Hsui‐Hui , Zhu Leilei , Schwaneberg Ulrich , Okuda Jun
Published: August 2013

A β‐barrel protein hybrid catalyst was prepared by covalently anchoring a Grubbs–Hoveyda type olefin metathesis catalyst at a single accessible cysteine amino acid in the barrel interior of a variant of β‐barrel transmembrane protein ferric hydroxamate uptake protein component A (FhuA). Activity of this hybrid catalyst type was demonstrated by ring‐opening metathesis polymerization of a 7‐oxanorbornene derivative in aqueous solution.
Activation of Methane by Os+: Guided‐Ion‐Beam and Theoretical Studies
Authors: Armentrout P. B. , Parke Laura , Hinton Christopher , Citir Murat
Published: August 2013

Activation of methane by the third‐row transition‐metal cation Os+ is studied experimentally by examining the kinetic energy dependence of reactions of Os+ with CH4 and CD4 using guided‐ion‐beam tandem mass spectrometry. A flow tube ion source produces Os+ in its electronic ground state and primarily in the ground spin–orbit level. Dehydrogenation to form [Os,C,2 H]++H2 is exothermic, efficient, and the only process observed at low energies for reaction of Os+ with methane, whereas OsH+ dominates the product spectrum at higher energies. The kinetic energy dependences of the cross sections for several endothermic reactions are analyzed to give 0 K bond dissociation energies (in eV) of D0(Os+C)=6.20±0.21, D0(Os+CH)=6.77±0.15, and D0(Os+CH3)=3.00±0.17. Because it is formed exothermically, D0(Os+CH2) must be greater than 4.71 eV, and a speculative interpretation suggests the exothermicity exceeds 0.6 eV. Quantum chemical calculations at the B3LYP/def2‐TZVPP level show reasonable agreement with the experimental bond energies and with previous theoretical values available. Theory also provides the electronic structures of the product species as well as intermediates and transition states along the reactive potential energy surfaces. Notably, the structure of the dehydrogenation product is predicted to be HOsCH+, rather than OsCH2+, in contrast to previous work.
Decomposing textures of hexagonal magnesium alloys with fiber component
Authors: Qian C. , Tang J. G. , Zhang X. M. , Tang C. P. , Deng Y. L.
Published: August 2013

The orientation distribution function (ODF) calculated from measured pole figures with series expansion method is decomposed into texture components of Gauss type distribution and the volume fraction of texture components can be calculated with the model distribution function. Firstly, as fiber texture components are often found in magnesium alloy, the series expansion coefficients for Gauss type fiber components are derived. Secondly, as the textures of magnesium is very complicated, the group decomposing method, i.e., a major component accompanied by several minor components with trivial misorientation from the major one, is proposed to ensure better fitting or decomposing results. Finally, the group decomposing method is used to calculate the texture volume fraction of two typical experimental ODFs.
Well‐defined Sb2S3 nanostructures: citric acid‐assisted synthesis, electrochemical hydrogen storage properties
Authors: Yan Chunshuang , Chen Gang , Jin Rencheng , Zou Xian , Xu Haiming , Lv Chade
Published: August 2013

Well‐defined (three‐dimensional) 3‐D dandelion‐like Sb2S3 nanostructures consisted of numerous nanorods have been achieved via a facile citric acid‐assisted solvothermal process. The as‐prepared products were characterized by X‐ray diffraction (XRD), field‐emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and high‐resolution TEM (HRTEM), respectively. The influence factors of the formation of the hierarchical Sb2S3 nanostructures are discussed in details based on FESEM characterizations. By simply controlling the quantity of citric acid, the nucleation and growth process can be readily tuned, which brings the different morphologies and nanostructures of the final products. On the basis of a series of contrastive experiments, the aggregation‐based process and anisotropic growth mechanism are reasonably proposed to understand the formation mechanism of Sb2S3 hierarchical architectures with distinctive morphologies including nanorods, and dandelion‐like nanostructures. Charge‐discharge curves of the obtained Sb2S3 nanostructures were measured to investigate their electrochemical hydrogen storage behaviors. It revealed that the morphology played a key role on the hydrogen storage capacity of Sb2S3 nanostructure. The dandelion‐like Sb2S3 nanostructures exhibited higher hydrogen storage capacity (108 mAh g−1) than that of Sb2S3 nanorods (95 mAh g−1) at room temperature.
Neural stem cell apoptosis after low‐methylmercury exposures in postnatal hippocampus produce persistent cell loss and adolescent memory deficits
Authors: Sokolowski Katie , Obiorah Maryann , Robinson Kelsey , McCandlish Elizabeth , Buckley Brian , DiCicco‐Bloom Emanuel
Published: August 2013

The developing brain is particularly sensitive to exposures to environmental contaminants. In contrast to the adult, the developing brain contains large numbers of dividing neuronal precursors, suggesting that they may be vulnerable targets. The postnatal day 7 (P7) rat hippocampus has populations of both mature neurons in the CA1–3 region as well as neural stem cells (NSC) in the dentate gyrus (DG) hilus, which actively produce new neurons that migrate to the granule cell layer (GCL). Using this well‐characterized NSC population, we examined the impact of low levels of methylmercury (MeHg) on proliferation, neurogenesis, and subsequent adolescent learning and memory behavior. Assessing a range of exposures, we found that a single subcutaneous injection of 0.6 µg/g MeHg in P7 rats induced caspase activation in proliferating NSC of the hilus and GCL. This acute NSC death had lasting impact on the DG at P21, reducing cell numbers in the hilus by 22% and the GCL by 27%, as well as reductions in neural precursor proliferation by 25%. In contrast, non‐proliferative CA1–3 pyramidal neuron cell number was unchanged. Furthermore, animals exposed to P7 MeHg exhibited an adolescent spatial memory deficit as assessed by Morris water maze. These results suggest that environmentally relevant levels of MeHg exposure may decrease NSC populations and, despite ongoing neurogenesis, the brain may not restore the hippocampal cell deficits, which may contribute to hippocampal‐dependent memory deficits during adolescence. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 936–949, 2013
Impact of Different Surfactants and their Mixtures on Methane‐Hydrate Formation
Authors: Fazlali Alireza , Kazemi Seyedeh‐Atieh , Keshavarz‐Moraveji Mostafa , Mohammadi Amir H.
Published: August 2013

Gas hydrates can be used as a potential means for natural gas storage. Design of a gas‐hydrate‐based unit requires accurate knowledge of hydrate‐formation kinetics especially in the presence of promoters. In this study, the effects of sodium dodecyl sulfate (SDS), hexa decyl trimethyl ammonium bromide (HTABr), polyoxy ethylene(20) cetyl ether (Brij‐58) and mixtures of SDS with HTABr and Brij‐58 have been investigated to determine their influence on the methane‐hydrate‐formation kinetics and thermodynamics. The study on the kinetics of hydrate formation is focused on the induction time and hydrate‐formation rate. It is found that induction time of hydrate formation in the presence of a promoter is reduced considerably for each test compared with a pure water test. The minimum value of the induction time is found for a mixture of SDS (500 ppm) with HTABr (700 ppm). All of the surfactants and their mixtures can be designated as hydrate‐formation promoters in the concentration ranges studied in the present work and can increase the hydrate‐formation rate. SDS at a concentration of 500 ppm is determined to be the best hydrate‐formation promoter among the surfactants tested. The percent conversion of methane to hydrate is increased in the presence of these surfactants at the end of hydrate formation. The maximum value of the conversion is observed for the 500 ppm concentration of SDS. The results demonstrate that these surfactants and their corresponding mixtures have no significant effect on the thermodynamics of methane hydrate formation.
Review of Maximum‐Power‐Point Tracking Techniques for Solar‐Photovoltaic Systems
Authors: Rawat Rahul , Chandel S. S.
Published: August 2013

Solar‐photovoltaic systems are being widely used and promoted worldwide for pollution‐free power generation. The power extraction from solar photovoltaic (PV) systems can be maximized by using maximum‐power‐point tracking (MPPT) techniques between the photovoltaic array and the load. The MPPT technique searches the maximum‐power‐point and command system to enable operation at that point and enrich the overall efficiency of PV system. Substantial research has been performed on MPPT techniques to improve the efficiency, simplicity, response time, and steady‐state error. In this paper, a study of 21 different maximum power point tracking techniques used in photovoltaic systems has been performed to provide the latest update on conventional and advanced techniques and highlight the main features and limitations. The modified variable step incremental conductance technique is found to be the best among all in terms of steady‐state error, response time, convergence time, and efficiency. Possible areas of further research are also identified.
Lithospheric fabric variations in central North America: Influence of rifting and Archean tectonic styles
Authors: Frederiksen A. W. , Deniset I. , Ola O. , Toni D.
Published: August 2013

Upper mantle fabric, as detected by shear wave splitting measurements, records lithospheric strain history that may be related to past tectonic events. We present SKS (core‐refracted shear wave) splitting measurements taken around the western Great Lakes, North America: the Archean Superior Province (SP) and surroundings. We analyze 40 sites in the USA and 5 in Canada and outline a region of strong anisotropy corresponding to a high‐velocity zone in tomographic models, which we dub the Western Superior Mantle Anomaly (WSMA) and interpret to represent a preserved fabric from accretion of the SP. To the southwest of the WSMA, we locate a region of rotated fast direction corresponding to a linear low‐velocity feature observed by tomography and which may represent a failed branch of the Mid‐Continent Rift. Further south, within the Minnesota River Valley Terrane, the split times drop to near zero, suggesting isotropic lithosphere resulting from vertical (diapiric) rather than horizontal tectonic processes.
Steady late quaternary slip rate on the Cinarcik section of the North Anatolian fault near Istanbul, Turkey
Authors: Kurt Hulya , Sorlien C. C. , Seeber L. , Steckler M. S. , Shillington D. J. , Cifci G. , Cormier M.‐H. , Dessa J.‐X. , Atgin O. , Dondurur D. , Demirbag E. , Okay S. , Imren C. , Gurcay S. , Carton H.
Published: August 2013

The distribution of plate motion between multiple fault strands and how this distribution may evolve remain poorly understood, despite the key implications for seismic hazards. The North Anatolian Fault in northwest Turkey is a prime example of a multistranded continental transform. Here we present the first constraints on late Quaternary slip rates on its northern branch across the Cinarcik Basin in the eastern Marmara Sea. We use both deep penetration and high‐resolution multichannel seismic reflection data with a stratigraphic age model to show that a depocenter has persisted near the fault bend responsible for that transform basin. Successively older depocenters have been transported westward by fault motion relative to Eurasia, indicating a uniform right‐lateral slip rate of 18.5 mm/yr over the last 500,000 years, compared to overall GPS rates (23–24 mm/yr). Thus, the northern branch has slipped at a nearly constant rate and has accounted for most of the relative plate motion between Eurasia and Anatolia since ~0.5 Ma.
Human CD14+CTLA-4+ Regulatory Dendritic Cells Suppress T-Cell Response by Cytotoxic T-Lymphocyte Antigen-4-Dependent IL-10 and Indoleamine-2,3-Dioxygenase Production in Hepatocellular Carcinoma
Authors: Han Yanmei , Chen Zhubo , Yang Yuan , Jiang Zhengping , Gu Yan , Liu Yangfang , Lin Chuan , Pan Zeya , Yu Yizhi , Jiang Minghong , Zhou Weiping , Cao Xuetao
Published: August 2013

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. HCC-induced immunosuppression often leads to ineffectiveness of immuno-promoting therapies. Currently, suppressing the suppressors has become the potential strategy for cancer immunotherapy. So, figuring out the immunosuppressive mechanisms induced and employed by HCC will be helpful to the design and application of HCC immunotherapy. Here, we identified one new subset of human CD14+CTLA-4+ regulatory dendritic cells (CD14+DCs) in HCC patients, representing ˜13% of peripheral blood mononuclear cells. CD14+DCs significantly suppress T-cell response

in vitro

through interleukin (IL)-10 and indoleamine-2,3-dioxygenase (IDO). Unexpectedly, CD14+DCs expressed high levels of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1, and CTLA-4 was found to be essential to IL-10 and IDO production. So, we identified a novel human tumor-induced regulatory DC subset, which suppresses antitumor immune response through CTLA-4-dependent IL-10 and IDO production, thus indicating the important role of nonregulatory T-cell-derived CTLA-4 in tumor-immune escape or immunosuppression.

Conclusions

: These data outline one mechanism for HCC to induce systemic immunosuppression by expanding CD14+DCs, which may contribute to HCC progression. This adds new insight to the mechanism for HCC-induced immunosuppression and may also provide a previously unrecognized target of immunotherapy for HCC. (Hepatology 2014;59:567–579)
Chemokine Receptor CCR6-Dependent Accumulation of γδ T Cells in Injured Liver Restricts Hepatic Inflammation and Fibrosis
Authors: Hammerich Linda , Bangen Jörg M. , Govaere Olivier , Zimmermann Henning W. , Gassler Nikolaus , Huss Sebastian , Liedtke Christian , Prinz Immo , Lira Sergio A. , Luedde Tom , Roskams Tania , Trautwein Christian , Heymann Felix , Tacke Frank
Published: August 2013

Chronic liver injury promotes hepatic inflammation, representing a prerequisite for organ fibrosis. We hypothesized a contribution of chemokine receptor CCR6 and its ligand, CCL20, which may regulate migration of T-helper (Th)17, regulatory, and gamma-delta (γδ) T cells. CCR6 and CCL20 expression was intrahepatically up-regulated in patients with chronic liver diseases (n = 50), compared to control liver (n = 5). Immunohistochemistry revealed the periportal accumulation of CCR6+ mononuclear cells and CCL20 induction by hepatic parenchymal cells in liver disease patients. Similarly, in murine livers, CCR6 was expressed by macrophages, CD4 and γδ T-cells, and up-regulated in fibrosis, whereas primary hepatocytes induced CCL20 upon experimental injury. In two murine models of chronic liver injury (CCl4 and methionine-choline-deficient diet),

Ccr6−/−

mice developed more severe fibrosis with strongly enhanced hepatic immune cell infiltration, compared to wild-type (WT) mice. Although CCR6 did not affect hepatic Th-cell subtype composition, CCR6 was explicitly required by the subset of interleukin (IL)-17- and IL-22-expressing γδ T cells for accumulation in injured liver. The adoptive transfer of WT γδ, but not CD4 T cells, into

Ccr6−/−

mice reduced hepatic inflammation and fibrosis in chronic injury to WT level. The anti-inflammatory function of hepatic γδ T cells was independent of IL-17, as evidenced by transfer of

Il-17−/−

cells. Instead, hepatic γδ T cells colocalized with hepatic stellate cells (HSCs)

in vivo

and promoted apoptosis of primary murine HSCs in a cell-cell contact-dependent manner, involving Fas-ligand (CD95L). Consistent with γδ T-cell-induced HSC apoptosis, activated myofibroblasts were more frequent in fibrotic livers of

Ccr6−/−

than in WT mice.

Conclusion

: γδ T cells are recruited to the liver by CCR6 upon chronic injury and protect the liver from excessive inflammation and fibrosis by inhibiting HSCs. (Hepatology 2014;59:630–642)
Comet assay measures of DNA damage are predictive of bladder cancer cell treatment sensitivity in vitro and outcome in vivo
Authors: Bowman Karen J. , Al‐Moneef Manar M. , Sherwood Benedict T. , Colquhoun Alexandra J. , Goddard Jonathan C. , Griffiths T.R. Leyshon , Payne David , Singh Sadmeet , Butterworth Paul C. , Khan Masood A. , Summerton Duncan J. , Steward William P. , McKelvey‐Martin Valerie J. , McKeown Stephanie R. , Kockelbergh Roger C. , Mellon J. Kilian , Symonds R. Paul , Jones George D.D.
Published: August 2013

Bladder cancer patients suffer significant treatment failure, including high rates of recurrence and poor outcomes for advanced disease. If mechanisms to improve tumour cell treatment sensitivity could be identified and/or if tumour response could be predicted, it should be possible to improve local‐control and survival. Previously, we have shown that radiation‐induced DNA damage, measured by alkaline Comet assay (ACA), correlates bladder cancer cell radiosensitivity in vitro. In this study we first show that modified‐ACA measures of cisplatin and mitomycin‐C‐induced damage also correlate bladder cancer cell chemosensitivity in vitro, with essentially the same rank order for chemosensitivity as for radiosensitivity. Furthermore, ACA studies of radiation‐induced damage in different cell‐DNA substrates (nuclei, nucleoids and intact parent cells) suggest that it is a feature retained in the prepared nucleoids that is responsible for the relative damage sensitivity of bladder cancer cells, suggestive of differences in the organisation of DNA within resistant vs. sensitive cells. Second, we show that ACA analysis of biopsies from bladder tumours reveal that reduced DNA damage sensitivity associates with poorer treatment outcomes, notably that tumours with a reduced damage response show a significant association with local recurrence of non‐invasive disease and that reduced damage response was a better predictor of recurrence than the presence of high‐risk histology in this cohort. In conclusion, this study demonstrates that mechanisms governing treatment‐induced DNA damage are both central to and predictive of bladder cancer cell treatment sensitivity and exemplifies a link between DNA damage resistance and both treatment response and tumour aggression.
Short report: Limited effectiveness of screening mammography in addition to clinical breast examination by trained nurse midwives in rural Jakarta, Indonesia
Authors: Kardinah D. , Anderson Benjamin O. , Duggan Catherine , Ali Ibrahim A , Thomas David B
Published: August 2013

Low‐ and middle‐income countries (LMICs) are undergoing an increase in incidence of breast cancer, but have inadequate resources to implement mammographic screening. Clinical breast examination (CBE) has been suggested as an alternative to mammography in these settings. We compared the results of CBE screening by 47 midwives and 15 trained lay health workers to results of independently performed mammographic screening in an unscreened population of 1,179 women in Jakarta, Indonesia. Two hundred and eight‐nine (24.5%) of the screened women had a suspicious finding on CBE and/or mammography. Sixty‐nine (23.9%) of these women had both an abnormal CBE and mammogram; 98 (33.9%) had an abnormal CBE, but a normal mammogram; and 122 (42.2%) had a normal CBE and an abnormal mammogram. Fourteen breast cancers were diagnosed. Of these, 13 were identified by both mammogram and CBE. One breast cancer was identified from an abnormal mammogram, but had a normal CBE. One hundred and sixty‐seven (14.2%) of the CBEs required additional work‐up to diagnose 13 of the 14 cancers detected by mammography. In comparison, 191 (16.2%) of mammograms required additional work‐up to diagnose the 14 cancers. Unfortunately, only 42.8% of the women diagnosed with cancer returned for treatment. In an unscreened population in LMICs such as Indonesia, CBE is nearly as effective as mammography in detecting prevalent breast cancers. However identifying and overcoming barriers to appropriate treatment of women who are identified as having breast cancer are essential to the success of any screening program.
A model of liver carcinogenesis originating from hepatic progenitor cells with accumulation of genetic alterations
Authors: Kim Soo Ki , Nasu Akihiro , Komori Junji , Shimizu Takahiro , Matsumoto Yuko , Minaki Yasuko , Kohno Kenji , Shimizu Kazuharu , Uemoto Shinji , Chiba Tsutomu , Marusawa Hiroyuki
Published: August 2013

Activation‐induced cytidine deaminase (AID) contributes to inflammation‐associated carcinogenesis through its mutagenic activity. In our study, by taking advantage of the ability of AID to induce genetic aberrations, we investigated whether liver cancer originates from hepatic stem/progenitor cells that accumulate stepwise genetic alterations. For this purpose, hepatic progenitor cells enriched from the fetal liver of AID transgenic (Tg) mice were transplanted into recipient “toxin‐receptor mediated conditional cell knockout” (TRECK) mice, which have enhanced liver regeneration activity under the condition of diphtheria toxin treatment. Whole exome sequencing was used to determine the landscape of the accumulated genetic alterations in the transplanted progenitor cells during tumorigenesis. Liver tumors developed in 7 of 11 (63.6%) recipient TRECK mice receiving enriched hepatic progenitor cells from AID Tg mice, while no tumorigenesis was observed in TRECK mice receiving hepatic progenitor cells of wild‐type mice. Histologic examination revealed that the tumors showed characteristics of hepatocellular carcinoma and partial features of cholangiocarcinoma with expression of the AID transgene. Whole exome sequencing revealed that several dozen genes acquired single nucleotide variants in tumor tissues originating from the transplanted hepatic progenitor cells of AID Tg mice. Microarray analyses revealed that the majority of the mutations (>80%) were present in actively transcribed genes in the liver‐lineage cells. These findings provided the evidence suggesting that accumulation of genetic alterations in fetal hepatic progenitor cells progressed to liver cancers, and the selection of mutagenesis depends on active transcription in the liver‐lineage cells.
Bone Strength and Structural Deficits in Children and Adolescents With a Distal Forearm Fracture Resulting From Mild Trauma
Authors: Farr Joshua N , Amin Shreyasee , Melton L Joseph , Kirmani Salman , McCready Louise K , Atkinson Elizabeth J , Müller Ralph , Khosla Sundeep
Published: August 2013

Although distal forearm fractures (DFFs) are common during childhood and adolescence, it is unclear whether they reflect underlying skeletal deficits or are simply a consequence of the usual physical activities, and associated trauma, during growth. Therefore, we examined whether a recent DFF, resulting from mild or moderate trauma, is related to deficits in bone strength and cortical and trabecular bone macro- and microstructure compared with nonfracture controls. High-resolution peripheral quantitative computed tomography was used to assess micro-finite element-derived bone strength (ie, failure load) and to measure cortical and trabecular bone parameters at the distal radius and tibia in 115 boys and girls with a recent (<1 year) DFF and 108 nonfracture controls aged 8 to 15 years. Trauma levels (mild versus moderate) were assigned based on a validated classification scheme. Compared with sex-matched controls, boys and girls with a mild-trauma DFF (eg, fall from standing height) showed significant deficits at the distal radius in failure load (–13% and –11%, respectively; p < 0.05) and had higher (“worse”) fall load-to-strength ratios (both +10%; p < 0.05 for boys and p = 0.06 for girls). In addition, boys and girls with a mild-trauma DFF had significant reductions in cortical area (–26% and –23%, respectively; p < 0.01) and cortical thickness (–14% and –13%, respectively; p < 0.01) compared with controls. The skeletal deficits in the mild-trauma DFF patients were generalized, as similar changes were present at the distal tibia. By contrast, both boys and girls with a moderate-trauma DFF (eg, fall from a bicycle) had virtually identical values for all of the measured bone parameters compared with controls. In conclusion, DFFs during growth have two distinct etiologies: those owing to underlying skeletal deficits leading to fractures with mild trauma versus those owing to more significant trauma in the setting of normal bone strength. © 2014 American Society for Bone and Mineral Research.
3,4‐Dihydroxybenzalacetone Protects Against Parkinson's Disease‐Related Neurotoxin 6‐OHDA Through Akt/Nrf2/Glutathione Pathway
Authors: Gunjima Kei , Tomiyama Ryoichi , Takakura Ken , Yamada Takashi , Hashida Koji , Nakamura Yutaka , Konishi Tetsuya , Matsugo Seiichi , Hori Osamu
Published: August 2013

Oxidative stress is implicated in the pathogenesis of various neurodegenerative diseases including Parkinson's disease (PD). 3,4‐Dihydroxybenzalacetone (DBL) is a small catechol‐containing compound isolated from Chaga (Inonotus obliquus [persoon] Pilat), and has been reported to have beneficial bioactivities, including antioxidative, anti‐inflammatory, and anti‐tumorigenic activities, with a relatively low toxicity to normal cells. We, therefore, investigated the neuroprotective activity of DBL against the PD‐related neurotoxin 6‐hydroxydopamine (6‐OHDA). Pretreatment of human neuroblastoma SH‐SY5Y cells with DBL, but not with another Chaga‐derived catechol‐containing compound, caffeic acid, dose‐dependently improved the survival of 6‐OHDA‐treated cells. Although DBL did not reduce 6‐OHDA‐induced reactive oxygen species in the cell‐free system, it promoted the translocation of Nrf2 to the nucleus, activated the transcription of Nrf2‐dependent antioxidative genes, and increased glutathione synthesis in the cells. Buthionine sulfoximine, an inhibitor of glutathione synthesis, but not Sn‐mesoporphyrin IX, a heme oxygenase‐1 inhibitor, or dicoumarol, an NAD(P)H:quinone oxidoreductase 1 inhibitor, abolished the protective effect of DBL against 6‐OHDA. Furthermore, DBL activated stress‐associated kinases such as Akt, ERK, and p38 MAPK, and PI3K or Akt inhibitors, but not ERK, p38, or JNK inhibitors, diminished DBL‐induced glutathione synthesis and protection against 6‐OHDA. These results suggest that DBL activates the Nrf2/glutathione pathway through PI3K/Akt, and improves survival of SH‐SY5Y cells against 6‐OHDA toxicity. J. Cell. Biochem. 115: 151–160, 2014. © 2013 Wiley Periodicals, Inc.
Eliminative Signaling by Janus Kinases: Role in the Downregulation of Associated Receptors
Authors: Carbone Christopher J. , Fuchs Serge Y.
Published: August 2013

Activation of cytokine receptor‐associated Janus kinases (JAKs) mediates most, if not all, of the cellular responses to peptide hormones and cytokines. Consequently, JAKs play a paramount role in homeostasis and immunity. Members of this family of tyrosine kinases control the cytokine/hormone‐induced alterations in cell gene expression program. This function is largely mediated through an ability to signal toward activation of the signal transducer and activator of transcription proteins (STAT), as well as toward some other pathways. Importantly, JAKs are also instrumental in tightly controlling the expression of associated cytokine and hormone receptors, and, accordingly, in regulating the cell sensitivity to these cytokines and hormones. This review highlights the enzymatic and non‐enzymatic mechanisms of this regulation and discusses the importance of the ambidextrous nature of JAK as a key signaling node that integrates the combining functions of forward signaling and eliminative signaling. Attention to the latter aspect of JAK function may contribute to emancipating our approaches to the pharmacological modulation of JAKs. J. Cell. Biochem. 115: 8–16, 2014. © 2013 Wiley Periodicals, Inc.
Storm time duskside equatorial current and its closure path
Authors: Dubyagin S. , Ganushkina N. , Apatenkov S. , Kubyshkina M. , Ohtani S.‐I. , Singer H. , Liemohn M.
Published: August 2013

We study the closure path of the equatorial current which flows on the duskside in the inner magnetosphere during the moderate two‐dip storm on 22 July 2009. This work was motivated by the result obtained in Tsyganenko and Sitnov (2007) that the prominent part of the duskside equatorial current might close through the dayside magnetopause during magnetic storms. Assuming the electric current conservation, we compared the value of the total downward region 2 current with the intensity of the equatorial current on the duskside to infer what part of the latter closes through the ionosphere. The estimates of the intensity of the equatorial current were based on the THEMIS and GOES magnetic field measurements in the vicinity of geosynchronous orbit. It was found that the duskside equatorial current intensifies simultaneously with Sym‐H∗ decrease. However, unlike the conventional partial ring current, it occupies the region of the highly stretched magnetic configuration (magnetic field inclination ∼24° at r=5.4RE). At the same time, the magnetic field measurements onboard three DMSP satellites showed that the local time distribution of the storm time region 2 currents preserves the pattern typical for more quiet periods with upward (downward) current in the prenoon (afternoon) sector. The peak intensities of the downward region 2 current were recorded within 1 h from the Sym‐H∗ minima in the vicinity of the dusk meridian. The peak values of the total downward region 2 current were found to be within 5–5.8 mA, while the intensity of the equatorial current at R≈5.4–6.6RE was found to be 0.8–1.7 mA per 1RE. Keeping a current continuity, the radial extent of the partial ring current is estimated as 3.4–6RE. This indicates that most of the duskside current was diverted to the ionosphere during the main phase of this storm.
Transport of cold ions from the polar ionosphere to the plasma sheet
Authors: Li Kun , Haaland S. , Eriksson A. , André M. , Engwall E. , Wei Y. , Kronberg E. A. , Fränz M. , Daly P. W. , Zhao H. , Ren Q. Y.
Published: August 2013

Ionospheric outflow is believed to be a significant contribution to the magnetospheric plasma population. Ions are extracted from the ionosphere and transported downtail by the large‐scale convection motion driven by dayside reconnection. In this paper, we use a comprehensive data set of cold ion (total energy less than 70 eV) measurements combined with simultaneous observations from the solar wind to investigate the fate of these ions. By tracing the trajectories of the ions, we are able to find out where in the magnetotail ions end up. By sorting the observation according to geomagnetic activity and solar wind parameters, we then generate maps of the fate regions in the magnetotail and investigate the effects of these drivers. Our results suggest that, on overall, for about 85% of the cases, the outflowing ions are transported to the plasma sheet. The region where the ions are deposited into the plasma sheet is larger during geomagnetic quiet time than during disturbed conditions. A persistent dawn‐dusk asymmetry in the plasma sheet deposition is also observed.
Magnetospheric response to magnetosheath pressure pulses: A low‐pass filter effect
Authors: Archer M. O. , Horbury T. S. , Eastwood J. P. , Weygand J. M. , Yeoman T. K.
Published: August 2013

We present observations from the magnetopause to the ground during periods of large amplitude, transient dynamic pressure pulses in the magnetosheath. While individual magnetosheath pulses are sharp and impulsive, the magnetospheric response is much smoother with frequencies in the Pc5–6 range being excited in the compressional and poloidal components of the magnetic field. We show that the magnetopause acts like a low‐pass filter, suppressing timescales shorter than a few minutes. Further filtering appears to occur locally within the magnetosphere, which may be due to the unusual field line resonance frequency profile on this day. Ground magnetometer and radar data along with equivalent ionospheric currents show signatures of traveling convection vortices, similar to the response from pressure variations of solar wind origin. However, the signatures are associated with groups of magnetosheath pulses rather than individual ones due to the impulsive nature of the pressure variations. Thus, the scale‐dependent magnetospheric response to these transient pressure variations results in coherent signatures on longer timescales than any individual pulse.
Performance of climate field reconstruction methods over multiple seasons and climate variables
Authors: Dannenberg Matthew P. , Wise Erika K.
Published: August 2013

Studies of climate variability require long time series of data but are limited by the absence of preindustrial instrumental records. For such studies, proxy‐based climate reconstructions, such as those produced from tree‐ring widths, provide the opportunity to extend climatic records into preindustrial periods. Climate field reconstruction (CFR) methods are capable of producing spatially‐resolved reconstructions of climate fields. We assessed the performance of three commonly used CFR methods (canonical correlation analysis, point‐by‐point regression, and regularized expectation maximization) over spatially‐resolved fields using multiple seasons and climate variables. Warm‐ and cool‐season geopotential height, precipitable water, and surface temperature were tested for each method using tree‐ring chronologies. Spatial patterns of reconstructive skill were found to be generally consistent across each of the methods, but the robustness of the validation metrics varied by CFR method, season, and climate variable. The most robust validation metrics were achieved with geopotential height, the October through March temporal composite, and the Regularized Expectation Maximization method. While our study is limited to assessment of skill over multidecadal (rather than multi‐centennial) time scales, our findings suggest that the climate variable of interest, seasonality, and spatial domain of the target field should be considered when assessing potential CFR methods for real‐world applications.
Radiolabelling of steroids: the synthesis of 17α‐[4‐14C]trenbolone
Authors: Hendry David , Knagg Eric , Smith Neil A. , Woolley Geoffrey T.
Published: August 2013

17β‐Hydroxyestra‐4,9,11‐trien‐3‐one or trenbolone is an anabolic steroid used in some meat producing countries where its use is licenced. In cattle it is metabolised into 17α‐trenbolone. We were required to make 17α‐[4‐14C]trenbolone for use in environmental fate studies. At the same time we also had a request to make 17α‐[4‐14C]estradiol so we combined the two syntheses and made use of the synergy to allow us to make a batch of 17α‐[4‐14C]estradiol by known methodology and then elaborate a portion of this into 17α‐[4‐14C]trenbolone. The synthesis of 17α‐[4‐14C]trenbolone from 17α‐[4‐14C]estradiol was achieved in 8 steps and 3.1% overall yield to give material with a radiochemical purity of 99.5% and specific activity of 59 mCi/mmol.
Anatomical characterization of athetotic and spastic cerebral palsy using an atlas‐based analysis
Authors: Yoshida Shoko , Faria Andreia V. , Oishi Kenichi , Kanda Toyoko , Yamori Yuriko , Yoshida Naoko , Hirota Haruyo , Iwami Mika , Okano Sozo , Hsu John , Li Xin , Jiang Hangyi , Li Yue , Hayakawa Katsumi , Mori Susumu
Published: August 2013

Purpose

To analyze diffusion tensor imaging (DTI) in two types of cerebral palsy (CP): the athetotic‐type and the spastic‐type, using an atlas‐based anatomical analysis of the entire brain, and to investigate whether these images have unique anatomical characteristics that can support functional diagnoses.

Materials and Methods

We retrospectively analyzed the DTI of seven children with athetotic‐type, 11 children with spastic‐type, and 20 healthy control children, all age‐matched. The severity of motor dysfunction was evaluated with the Gross Motor Function Classification System (GMFCS). The images were normalized using a linear transformation, followed by large deformation diffeomorphic metric mapping. For 205 parcellated brain areas, the volume, fractional anisotropy, and mean diffusivity were measured. Principal component analysis (PCA) was performed for the Z‐scores of these parameters.

Results

The GMFCS scores in athetotic‐type were significantly higher than those in spastic‐type (P < 0.001). PCA extracted anatomical components that comprised the two types of CP, as well as the severity of motor dysfunction. In the athetotic group, the abnormalities were more severe than in the spastic group. In the spastic group, significant changes were concentrated in the lateral ventricle and periventricular structures.

Conclusion

Our results quantitatively delineated anatomical characteristics that reflected the functional findings in two types of CP. J. Magn. Reson. Imaging 2013;38:288–298. © 2013 Wiley Periodicals, Inc.