bluuebunny/crossref_metadata_2025 huggingface dataset:
Pacific Walrus and climate change: observations and predictions
Authors: MacCracken James G.
Published: July 2012

The extent and duration of sea‐ice habitats used by Pacific walrus (Odobenus rosmarus divergens) are diminishing resulting in altered walrus behavior, mortality, and distribution. I document changes that have occurred over the past several decades and make predictions to the end of the 21st century. Climate models project that sea ice will monotonically decline resulting in more ice‐free summers of longer duration. Several stressors that may impact walruses are directly influenced by sea ice. How these stressors materialize were modeled as most likely‐case, worst‐case, and best‐case scenarios for the mid‐ and late‐21st century, resulting in four comprehensive working hypotheses that can help identify and prioritize management and research projects, identify comprehensive mitigation actions, and guide monitoring programs to track future developments and adjust programs as needed. In the short term, the most plausible hypotheses predict a continuing northward shift in walrus distribution, increasing use of coastal haulouts in summer and fall, and a population reduction set by the carrying capacity of the near shore environment and subsistence hunting. Alternatively, under worst‐case conditions, the population will decline to a level where the probability of extinction is high. In the long term, walrus may seasonally abandon the Bering and Chukchi Seas for sea‐ice refugia to the northwest and northeast, ocean warming and pH decline alter walrus food resources, and subsistence hunting exacerbates a large population decline. However, conditions that reverse current trends in sea ice loss cannot be ruled out. Which hypothesis comes to fruition depends on how the stressors develop and the success of mitigation measures. Best‐case scenarios indicate that successful mitigation of unsustainable harvests and terrestrial haulout‐related mortalities can be effective. Management and research should focus on monitoring, elucidating effects, and mitigation, while ultimately, reductions in greenhouse gas emissions are needed to reduce sea‐ice habitat losses.
Controls of evapotranspiration during the short dry season in a temperate mixed forest in Northeast China
Authors: Wu Jiabing , Jing Yanli , Guan Dexin , Yang Hong , Niu Lihua , Wang Anzhi , Yuan Fenhui , Jin Changjie
Published: July 2012

The long‐term tower‐based eddy covariance measurements of CO2/H2O fluxes are carried out in a temperate mature forest in Northeast China. The current study investigates the atmospheric (net radiation and vapour pressure deficit) and vegetation (surface conductance) controls of the evapotranspiration (ET) within the two observational years with different water conditions. The results show that the ET during the short dry season of 2004 was higher than that during the wet season of 2005. The ET is mainly driven by the meteorological factor of vapour pressure deficit. The mixed forest did not show clear signs of ET suppression during the summer drought because of its slightly reduced surface conductance, whereas its water demands from the atmosphere significantly increased. Thus, the annual ET slightly varied (416·2 to 462·1 mm) despite the large interannual variation in precipitation (488·7 to 761·6 mm). The 0–100 cm deep soil water storages are important sources of water supply for ET during dry seasons. The findings of this study suggest that the possible reduction in precipitation under future climate change scenarios with invariable or even enhanced ET will decrease the replenishment of groundwater and outflow and, consequently, the downstream water supply. Copyright © 2012 John Wiley & Sons, Ltd.
Active tuberculosis is characterized by an antigen specific and strictly localized expansion of effector T cells at the site of infection
Authors: Nemeth Johannes , Rumetshofer Rudolf , Winkler Heide‐Maria , Burghuber Otto C. , Müller Catharina , Winkler Stefan
Published: July 2012

Mycobacterium tuberculosis (MTB)‐specific cytokine responses in the peripheral blood and at the site of infection may differ significantly within the same individual, but the under‐lying T‐cell subset changes are largely unknown. Here, we measured effector and memory T‐cell markers on CD4+ T cells (CD45RO, cysteine chemokine receptor (CCR)7, and CD27) in peripheral blood and at the site of active tuberculosis (TB). Additionally, T cells were stimulated overnight with purified protein derivative (PPD) and early secretory antigenic target (ESAT)‐6 to determine which T‐cell subset produces MTB‐specific interferon (IFN)‐γ. A striking decrease in CCR7 and CD27 expression on T cells was noted at the site of active TB. Likewise, IFN‐γ expressing, ESAT‐6 specific CD4+CD45RO+CD27− T cells were dramatically increased at the site of infection but were not detectable in peripheral blood. An antigen‐specific expansion of differentiated T cells at the site of active TB infection was poorly reflected in peripheral blood. Insight in these changes in MTB‐specific effector T cells in different compartments of the body could lead to new approaches for immune‐based diagnosis and interventions.
Layered Hydroxide–Porphyrin Hybrid Materials: Synthesis, Structure, and Properties
Authors: Demel Jan , Lang Kamil
Published: July 2012

Layered hydroxide–porphyrin hybrids are attracting attention on account of their possible photophysical, photochemical, catalytic, and sensing applications. In comparison to free porphyrin and phthalocyanine molecules, the hybrids possess several potential advantages such as improved thermal and chemical stability, reduction of aggregation, tuning by layered hydroxide composition, and arrangement in transparent films. This review illustrates recent advances in the design, synthesis, and understanding of the structural alignment of bulky porphyrin‐like molecules in the interlayer space. Special emphasis is placed on the utilization of their spectral and photophysical properties for the possible fabrication of light‐triggered materials for bactericidal purposes. We describe examples from our laboratory and others, review their catalytic and sensing properties, and highlight the potential directions for further developments.
Fused Arene Ring Construction Around Pyrrole To Form 4,7‐Disubstitued Indole (Eur. J. Org. Chem. 22/2012)
Authors: Nojman Elżbieta , Latos‐Grażyński Lechosław , Szterenberg Ludmiła
Published: July 2012

The cover picture shows the original route for the synthesis of indoles. Treatment of the fundamental substrates, disubstituted 2‐butynes, with a stoichiometric amount of trifluoroacetic acid affords 4,7‐disubstituted indoles as the main products. The reported strategy involves attaching the benzene ring onto the existing pyrrole scaffold. Details are discussed in the article by L. Latos‐Grażyński et al. on p. 4115 ff.

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Alpha 1‐antitrypsin: A novel tumor‐associated antigen identified in patients with early‐stage breast cancer
Authors: López‐Árias Eneida , Aguilar‐Lemarroy Adriana , Felipe Jave‐Suárez Luis , Morgan‐Villela Gilberto , Mariscal‐Ramírez Ignacio , Martínez‐Velázquez Moisés , Álvarez Ángel H. , Gutiérrez‐Ortega Abel , Hernández‐ Gutiérrez Rodolfo
Published: July 2012

Several studies have demonstrated that sera from patients with cancer contain antibodies that recognize a unique group of autologous antigens called tumor‐associated antigens (TAA). In the current study, we employed an immunoproteomic approach, combining 2DE, Western blot, and MALDI‐MS to identify TAA in the sera of patients diagnosed with infiltrating ductal or in situ carcinoma breast cancer. Sera obtained from 25 newly diagnosed patients with stage II breast cancer and 20 healthy volunteers was evaluated for the presence of novel TAA. Alpha 1‐antitrypsin (A1AT) antibodies were detected in 24 of 25 patients with breast cancer (96%) and in 2 of 20 controls (10%). Sensitivity of detection of autoantibodies against A1AT in patients with breast cancer was 96%. Our preliminary results suggest that A1AT and autoantibodies against alpha 1 antitrypsin may be useful serum biomarkers for early‐stage breast cancer screening and diagnosis.
The effect of solvent on the morphology of ZnO nanostructure assembly by dielectrophoresis and its device applications
Authors: La Ferrara Vera , Pacheri Madathil Aneesh , De Girolamo Del Mauro Anna , Massera Ettore , Polichetti Tiziana , Rametta Gabriella
Published: July 2012

Different zinc oxide nanostructured morphologies were grown on photolithographically patterned silicon/silicon dioxide substrates by dielectrophoresis technique using different solvents, such as water and ethanol, obtaining rod‐like and net‐like nanostructures, respectively. The formation of continuous nanostructures was confirmed by scanning electron microscopic, atomic force microscopic images, and electrical characterizations. The rod‐like zinc oxide nanostructures were observed in the 10 μm gap between the fingers in the pattern, whereas net‐like nanostructures were formed independently of microgap. A qualitative study about the mechanism for the assembly of zinc oxide continuous nanostructures was presented. Devices were electrically characterized, at room temperature, in controlled environment to measure the conductance behavior in ultraviolet and humidity environment. Devices based on zinc oxide nanostructures grown in ethanol medium show better responses under both ultraviolet and humidity, because of the net‐like structure with high surface‐to‐volume ratio.
Characterization of drug–protein interactions by capillary electrophoresis hyphenated to mass spectrometry
Authors: Vuignier Karine , Veuthey Jean‐Luc , Carrupt Pierre‐Alain , Schappler Julie
Published: July 2012

The demand for analytical techniques to evaluate and measure drug–plasma protein interactions continues to increase. The binding of drugs to plasma proteins is an important parameter to determine during the drug development process because it impacts both pharmacokinetics and pharmacodynamics. Among the numerous methods that have been proposed to perform such studies, CE in frontal analysis mode (CE/FA) is attractive because it consumes a relatively low amount of samples, is fast, and enables analyses under near‐physiological conditions. Most CE/FA applications have been performed with UV detection and often lack sensitivity. In this study, CE was hyphenated to MS to enhance the sensitivity of the method and to evaluate strong drug–plasma protein interactions. To adapt the previously developed CE/FA‐UV method to CE/FA‐MS, different parameters were considered, such as the buffer composition, the rinsing step, and the ESI and MS parameters. The most critical aspect involved obtaining stable MS signals. Good results were achieved due to careful optimization of the ESI and MS parameters, among which the sheath liquid composition appeared to be the most significant. Interactions between six drugs and α1‐acid glycoprotein and three drugs and BSA, including basic, neutral, and acidic drugs, were measured with the optimized CE/FA‐MS method. The obtained affinity constants ranged from 1·10−4 M−1 to 2·10−5 M−1 and were in good agreement with the results that were obtained by CE/FA‐UV and equilibrium dialysis.
Electrophoretically mediated microanalysis for characterization of the enantioselective CYP3A4 catalyzed N‐demethylation of ketamine
Authors: Ying Kwan Hiu , Thormann Wolfgang
Published: July 2012

Execution of an enzymatic reaction performed in a capillary with subsequent electrophoretic analysis of the formed products is referred to as electrophoretically mediated microanalysis (EMMA). An EMMA method was developed to investigate the stereoselectivity of the CYP3A4‐mediated N‐demethylation of ketamine. Ketamine was incubated in a 50 μm id bare fused‐silica capillary together with human CYP3A4 Supersomes using a 100 mM phosphate buffer (pH 7.4) at 37°C. A plug containing racemic ketamine and the NADPH regenerating system including all required cofactors for the enzymatic reaction was injected, followed by a plug of the metabolizing enzyme CYP3A4 (500 nM). These two plugs were bracketed by plugs of incubation buffer to ensure proper conditions for the enzymatic reaction. The rest of the capillary was filled with a pH 2.5 running buffer comprising 50 mM Tris, phosphoric acid, and 2% w/v of highly sulfated γ‐cyclodextrin. Mixing of reaction plugs was enhanced via application of −10 kV for 10 s. After an incubation of 8 min at 37°C without power application (zero‐potential amplification), the capillary was cooled to 25°C within 3 min followed by application of –10 kV for the separation and detection of the formed enantiomers of norketamine. Norketamine formation rates were fitted to the Michaelis–Menten model and the elucidated values for Vmax and Km were found to be comparable to those obtained from the off‐line assay of a previous study.
Paramagnetic particles coupled with an automated flow injection analysis as a tool for influenza viral protein detection
Authors: Krejcova Ludmila , Dospivova Dana , Ryvolova Marketa , Kopel Pavel , Hynek David , Krizkova Sona , Hubalek Jaromir , Adam Vojtech , Kizek Rene
Published: July 2012

Currently, the influenza virus infects millions of individuals every year. Since the influenza virus represents one of the greatest threats, it is necessary to develop a diagnostic technique that can quickly, inexpensively, and accurately detect the virus to effectively treat and control seasonal and pandemic strains. This study presents an alternative to current detection methods. The flow‐injection analysis‐based biosensor, which can rapidly and economically analyze a wide panel of influenza virus strains by using paramagnetic particles modified with glycan, can selectively bind to specific viral A/H5N1/Vietnam/1203/2004 protein‐labeled quantum dots. Optimized detection of cadmium sulfide quantum dots (CdS QDs)‐protein complexes connected to paramagnetic microbeads was performed using differential pulse voltammetry on the surface of a hanging mercury drop electrode (HMDE) and/or glassy carbon electrode (GCE). Detection limit (3 S/N) estimations based on cadmium(II) ions quantification were 0.1 μg/mL or 10 μg/mL viral protein at HMDE or GCE, respectively. Viral protein detection was directly determined using differential pulse voltammetry Brdicka reaction. The limit detection (3 S/N) of viral protein was estimated as 0.1 μg/mL. Streptavidin‐modified paramagnetic particles were mixed with biotinylated selective glycan to modify their surfaces. Under optimized conditions (250 μg/mL of glycan, 30‐min long interaction with viral protein, 25°C and 400 rpm), the viral protein labeled with quantum dots was selectively isolated and its cadmium(II) content was determined. Cadmium was present in detectable amounts of 10 ng per mg of protein. Using this method, submicrogram concentrations of viral proteins can be identified.
A novel XPD mutation in a compound heterozygote; the mutation in the second allele is present in three homozygous patients with mild sun sensitivity
Authors: Falik‐Zaccai Tzipora C. , Erel‐Segal Reut , Horev Liran , Bitterman‐Deutsch Ora , Koka Sivan , Chaim Sara , Keren Zohar , Kalfon Limor , Gross Bella , Segal Zvi , Orgal Shlomi , Shoval Yishay , Slor Hanoch , Spivak Graciela , Hanawalt Philip C.
Published: July 2012

The XPD protein plays a pivotal role in basal transcription and in nucleotide excision repair (NER) as one of the ten known components of the transcription factor TFIIH. Mutations in XPD can result in the DNA repair‐deficient diseases xeroderma pigmentosum (XP), trichothiodystrophy (TTD), cerebro‐oculo‐facial‐skeletal syndrome, and in combined phenotypes such as XP/Cockayne syndrome and XP/TTD. We describe here an 18‐year‐old individual with mild sun sensitivity, no neurological abnormalities and no tumors, who carries a p.R683Q mutation in one allele, and the novel p.R616Q mutation in the other allele of the XPD gene. We also describe four patients from one family, homozygous for the identical p.R683Q mutation in XPD, who exhibit mild skin pigmentation and loss of tendon reflexes. Three homozygous patients presented with late‐onset skin tumors, and two with features of premature aging and moderate cognitive decline. Cells from the compound heterozygous individual and from one of the patients homozygous for p.R683Q exhibited similar responses to UV irradiation: reduced viability and defective overall removal of UV‐induced cyclobutane pyrimidine dimers, implying deficient global genomic NER. Cells from the compound heterozygous subject also failed to recover RNA synthesis after UV, indicating defective transcription‐coupled NER. Mutations affecting codon 616 in XPD generally result in functionally null proteins; we hypothesize that the phenotype of the heterozygous patient results solely from expression of the p.R683Q allele. This study illustrates the importance of detailed follow up with sun sensitive individuals, to ensure appropriate prophylaxis and to understand the mechanistic basis of the implicated hereditary disease. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.
Anaerobic membrane bio‐reactors for waste activated sludge digestion: Tubular versus hollow fiber membrane configurations
Authors: Dagnew M. , Pickel J. , Parker W. , Seto P.
Published: July 2012

This article presents the results of pilot scale studies that examined the use of negative and neutral charged tubular and hollow fiber (HF) anaerobic membrane bio‐reactors (AnMBR) for anaerobic digestion of waste activated sludge. Both AnMBR configurations were operated at a hydraulic retention time of 15 days, a sludge retention time (SRT) of 30 days, and a total solids loading of 1.2–1.3 kg m−3 day−1. The results indicate that both membrane digesters showed comparable total chemical oxygen demand and volatile solids removals of 47.6 and 49.1% respectively while maintaining a throughput that was two times that of the completely stirred tank reactor (CSTR) type digesters. The performance of the AnMBRs was similar to that of CSTRs operating at 30 days SRT. The AnMBRs were operated for 160 days. During this period no significant fouling was observed and membrane cleaning was not required. The average fluxes for the neutral and negative tubular membranes were 32 and 39 LMH when operated at a trans‐membrane pressure TMP of 30 kPa. The HF membranes were operated at a constant flux of 11 LMH and the average TMP was less than 10 kPa. The critical flux measured for the tubular and HF membranes were near to 30 and 18 LMH mark respectively indicating a better performance by the former. However both AnMBR configurations generated comparable net energy. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 598–604, 2013
The Price Discovery Puzzle in Offshore Yuan Trading: Different Contributions for Different Contracts
Authors: Ding David K. , Tse Yiuman , Williams Michael R.
Published: July 2012

The People's Bank of China (PBC) lifted yuan trading restrictions in July of 2010 that led to offshore yuan spot trading in Hong Kong. Based on causality analyses, we find that price discovery is absent between the onshore and offshore spot markets. However, we document the presence of price discovery between onshore spot and offshore nondeliverable forward (NDF) rates. These seemingly inconsistent results present a puzzle wherein one offshore market appears to be more informationally integrated with the onshore market than another. We conclude that price discovery differences in the offshore markets stem from the offshore spot and forward contracts tracking different aspects of yuan rates (e.g., the offshore nondeliverable rate tracks onshore spot rates whereas the offshore spot rate tracks onshore interest rates). Moreover, the introduction of offshore spot trading in Hong Kong has led to an increase in cross‐market price discovery between onshore spot and offshore NDF rates. © 2012 Wiley Periodicals, Inc. Jrl Fut Mark 34:103–123, 2014
Gains in language comprehension relating to working memory training in healthy older adults
Authors: Carretti Barbara , Borella Erika , Zavagnin Michela , de Beni Rossana
Published: July 2012

Objective

A growing number of studies are focusing on cognitive training procedures to delay age‐related decline. Given the crucial role of working memory (WM) in everyday life, some studies have recently analyzed gains deriving from WM training and their transfer and maintenance effects in older adults.

Method

The present study investigates the efficacy of a verbal WM training program in 20 65–75 year old adults with no cognitive impairments, considering the specific training‐related gains in a verbal WM task (criterion) and the transfer effects on measures of WM updating, reasoning, and on abilities related more to daily life, that is language comprehension. Maintenance of training benefits was also assessed after 6 months.

Results

The older adults given training performed better than controls in the criterion task and retained this benefit 6 months later. Immediate transfer effects were seen in most of the abilities considered (reasoning and language comprehension performance) and were substantially maintained at the 6‐month follow‐up.

Conclusion

Our results suggest that WM training is a promising approach for preserving abilities relating to everyday activities, helping to prolong older adults' independence and well‐being. Copyright © 2012 John Wiley & Sons, Ltd.
Longitudinal testing of visual perception in dementia with Lewy bodies and Alzheimer's disease
Authors: Wood Joshua S. , Watson Rosie , Firbank Michael J. , Mosimann Urs P. , Barber Robert , Blamire Andrew M. , O'Brien John T.
Published: July 2012

Objectives

Visuo‐perceptual abnormalities are a prominent feature in dementia with Lewy bodies (DLB) and also occur in Alzheimer's disease (AD) to a lesser extent. We studied the progression of visuo‐perceptual abnormalities over a 12‐month period in DLB and AD by using a novel computerised test battery.

Methods

Following our previous work using the Newcastle Visual Perception (NEVIP) battery, we re‐assessed 16 AD, 12 DLB and 28 similar‐aged comparison participants 12 months after initial baseline assessment.

Results

DLB visual perception at follow‐up showed worse performance than AD (U = 43, p = 0.027); however, there were no significant changes in visuo‐perceptual scores between baseline assessment and 12‐month assessment within groups. A poor baseline score on the NEVIP predicted subsequent deterioration on the Bristol Activities of Daily Living Scale (rs = −0.725, p = 0.014) in DLB participants but not in the AD group.

Conclusions

The NEVIP is a reliable test of visuo‐perception, relatively independent of cognitive decline, with predictive value in identifying DLB participants at risk of functional decline. Visuo‐perceptual dysfunction is a core feature of the disorder for some DLB patients and was stable over the 12‐month period examined here. Copyright © 2012 John Wiley & Sons, Ltd.
Genome-Wide Association Analysis in Primary Sclerosing Cholangitis And Ulcerative Colitis Identifies Risk Loci at Gpr35 And Tcf4
Authors: Ellinghaus David , Folseraas Trine , Holm Kristian , Ellinghaus Eva , Melum Espen , Balschun Tobias , Laerdahl Jon K. , Shiryaev Alexey , Gotthardt Daniel N. , Weismüller Tobias J. , Schramm Christoph , Wittig Michael , Bergquist Annika , Björnsson Einar , Marschall Hanns-Ulrich , Vatn Morten , Teufel Andreas , Rust Christian , Gieger Christian , Wichmann H-Erich , Runz Heiko , Sterneck Martina , Rupp Christian , Braun Felix , Weersma Rinse K. , Wijmenga Cisca , Ponsioen Cyriel Y. , Mathew Christopher G. , Rutgeerts Paul , Vermeire Séverine , Schrumpf Erik , Hov Johannes R. , Manns Michael P. , Boberg Kirsten M. , Schreiber Stefan , Franke Andre , Karlsen Tom H.
Published: July 2012

Approximately 60%-80% of patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). Previous genome-wide association studies (GWAS) in PSC have detected a number of susceptibility loci that also show associations in UC and other immune-mediated diseases. We aimed to systematically compare genetic associations in PSC with genotype data in UC patients with the aim of detecting new susceptibility loci for PSC. We performed combined analyses of GWAS for PSC and UC comprising 392 PSC cases, 987 UC cases, and 2,977 controls and followed up top association signals in an additional 1,012 PSC cases, 4,444 UC cases, and 11,659 controls. We discovered novel genome-wide significant associations with PSC at 2q37 [rs3749171 at G-protein-coupled receptor 35 (GPR35); P = 3.0 × 10−9 in the overall study population, combined odds ratio [OR] and 95% confidence interval [CI] of 1.39 (1.24-1.55)] and at 18q21 [rs1452787 at transcription factor 4 (TCF4); P = 2.61 × 10−8, OR (95% CI) = 0.75 (0.68-0.83)]. In addition, several suggestive PSC associations were detected. The GPR35 rs3749171 is a missense single nucleotide polymorphism resulting in a shift from threonine to methionine. Structural modeling showed that rs3749171 is located in the third transmembrane helix of GPR35 and could possibly alter efficiency of signaling through the GPR35 receptor. Conclusion: By refining the analysis of a PSC GWAS by parallel assessments in a UC GWAS, we were able to detect two novel risk loci at genome-wide significance levels. GPR35 shows associations in both UC and PSC, whereas TCF4 represents a PSC risk locus not associated with UC. Both loci may represent previously unexplored aspects of PSC pathogenesis. (HEPATOLOGY 2013;58:1074–1083)
MicroRNA-221 overexpression accelerates hepatocyte proliferation during liver regeneration
Authors: Yuan Qinggong , Loya Komal , Rani Bhavna , Möbus Selina , Balakrishnan Asha , Lamle Jutta , Cathomen Toni , Vogel Arndt , Manns Michael P. , Ott Michael , Cantz Tobias , Sharma Amar Deep
Published: July 2012

The tightly controlled replication of hepatocytes in liver regeneration and uncontrolled proliferation of tumor cells in hepatocellular carcinoma (HCC) are often modulated by common regulatory pathways. Several microRNAs (miRNAs) are involved in HCC progression by modulating posttranscriptional expression of multiple target genes. miR-221, which is frequently up-regulated in HCCs, delays fulminant liver failure in mice by inhibiting apoptosis, indicating a pleiotropic role of miR-221 in hepatocytes. Here, we hypothesize that modulation of miR-221 targets in primary hepatocytes enhances proliferation, providing novel clues for enhanced liver regeneration. We demonstrate that miR-221 enhances proliferation of in vitro cultivated primary hepatocytes. Furthermore, applying two-thirds partial hepatectomy as a surgically induced liver regeneration model we show that adeno-associated virus-mediated overexpression of miR-221 in the mouse liver also accelerates hepatocyte proliferation in vivo. miR-221 overexpression leads to rapid S-phase entry of hepatocytes during liver regeneration. In addition to the known targets p27 and p57, we identify Aryl hydrocarbon nuclear translocator (Arnt) messenger RNA (mRNA) as a novel target of miR-221, which contributes to the pro-proliferative activity of miR-221. Conclusion: miR-221 overexpression accelerates hepatocyte proliferation. Pharmacological intervention targeting miR-221 may thus be therapeutically beneficial in liver failure by preventing apoptosis and by inducing liver regeneration. (Hepatology 2013;)
Age‐dependent effects of hippocampal neurogenesis suppression on spatial learning
Authors: Martinez‐Canabal Alonso , Akers Katherine G. , Josselyn Sheena A. , Frankland Paul W.
Published: July 2012

Reducing hippocampal neurogenesis sometimes, but not always, disrupts hippocampus‐dependent learning and memory. Here, we tested whether animal age, which regulates rate of hippocampal neurogenesis, is a factor that influences whether deficits in spatial learning are observed after reduction of neurogenesis. We found that suppressing the generation of new hippocampal neurons via treatment with temozolomide, an antiproliferation agent, impaired learning the location of a hidden platform in the water maze in juvenile mice (1–2 months old) but not in adult mice (2–3 months old) or middle‐aged mice (11–12 months old). These findings suggest that during juvenility, suppression of neurogenesis may alter hippocampal development, whereas during adulthood and aging, pre‐existing neurons may compensate for the lack of new hippocampal neurons. © 2012 Wiley Periodicals, Inc.
Combination treatments with ABT‐263 and an immunotoxin produce synergistic killing of ABT‐263‐resistant small cell lung cancer cell lines
Authors: Mattoo Abid R. , Fitzgerald David J.
Published: July 2012

Synergistic killing was achieved when Small Cell Lung Cancer (SCLC) cell lines were incubated with ABT‐263 and an immunotoxin directed to the transferrin receptor. SCLC lines are variably sensitive to the BH‐3 only peptide mimetic, ABT‐263. To determine their sensitivity to toxin‐based reagents, we incubated four representative SCLC lines with a model Pseudomonas exotoxin‐based immunotoxin directed to the transferrin receptor. Remarkably in 4‐of‐4 lines, there was little evidence of immunotoxin‐mediated cytotoxicity despite near complete inhibition of protein synthesis. However, when combinations of ABT‐263 and immunotoxin were added to the ABT‐263‐resistant cell lines (H196 and H69AR), there was synergistic killing as evidenced by increased activation of caspase 3/7, annexin V staining, and loss of cell integrity. Synergistic killing was evident at 6 hr and correlated with loss of Mcl‐1. This synergy was also noted when the closely related compound ABT‐737 was combined with the same immunotoxin. To establish that the synergy seen in tissue culture could be achieved in vivo, H69AR cells were grown as tumors in nude mice and shown to be susceptible to the killing action of an immunotoxin‐ABT‐737 combination but not to either agent alone. When immunotoxin‐ABT combinations were added to ABT‐263‐sensitive lines (H146 and H1417), killing was additive. Our data support combination approaches for treating ABT‐263‐resistant SCLC with ABT‐263 and a second agent that provides synergistic killing action.
Intake of trans fatty acids from partially hydrogenated vegetable and fish oils and ruminant fat in relation to cancer risk
Authors: Laake Ida , Carlsen Monica H. , Pedersen Jan I. , Weiderpass Elisabete , Selmer Randi , Kirkhus Bente , Thune Inger , Veierød Marit B.
Published: July 2012

Intake of trans fatty acids (TFA) may influence systemic inflammation, insulin resistance and adiposity, but whether TFA intake influences cancer risk is insufficiently studied. We examined the association between TFA intake from partially hydrogenated vegetable oils (PHVO‐TFA), partially hydrogenated fish oils (PHFO‐TFA), and ruminant fat (rTFA) and cancer risk in the Norwegian counties study, a large cohort study with a participation rate >80%. TFA intake was assessed three times in 1974–1988 by questionnaire. A total of 77,568 men and women were followed up through 2007, during which time 12,004 cancer cases occurred. Hazard ratios (HRs) and confidence intervals (CIs) were estimated with Cox regression for cancer sites with ≥150 cases during follow‐up. Significantly increased or decreased risks were found when comparing the highest and lowest intake categories (HRs, 95% CIs) for PHVO‐TFA and pancreatic cancer in men (0.52, 0.31–0.87) and non‐Hodgkin lymphoma (NHL) in both genders (0.70, 0.50–0.98); PHFO‐TFA and rectal cancer (1.43, 1.09–1.88), prostate cancer (0.82, 0.69–0.96), and multiple myeloma (2.02, 1.24–3.28); and rTFA and all cancers (1.09, 1.02–1.16), cancer of the mouth/pharynx (1.59, 1.08–2.35), NHL (1.47, 1.06–2.04) and multiple myeloma (0.45, 0.24–0.84). Furthermore, positive trends were found for PHFO‐TFA and stomach cancer (ptrend = 0.01) and rTFA and postmenopausal breast cancer (ptrend = 0.03). Inverse trends were found for PHVO‐TFA and all cancers (ptrend = 0.006) and cancer of the central nervous system in women (ptrend = 0.005). PHFO‐TFA, but not PHVO‐TFA, seemed to increase cancer risk. The increased risks observed for rTFA may be linked to saturated fat.
REST‐dependent expression of TRF2 renders non‐neuronal cancer cells resistant to DNA damage during oxidative stress
Authors: Kwon Jung‐Hee , Shin Ji Hye , Kim Eung‐Sam , Lee Namgyu , Park Jin Young , Koo Bonik Samuel , Hong Sun Mi , Park Chang Wook , Choi Kwan Yong
Published: July 2012

REST is a neuronal gene silencing factor ubiquitously expressed in non‐neuronal tissues. REST is additionally believed to serve as a tumor suppressor in non‐neuronal cancers. Conversely, recent findings on REST‐dependent tumorigenesis in non‐neuronal cells consistently suggest a potential role of REST as a tumor promoter. Here, we have uncovered for the first time the mechanism by which REST contributes to cancer cell survival in non‐neuronal cancers. We observed abundant expression of REST in various types of non‐neuronal cancer cells compared to normal tissues. The delicate roles of REST were further evaluated in HCT116 and HeLa, non‐neuronal cancer cell lines expressing REST. REST silencing resulted in decreased cell survival and activation of the DNA damage response (DDR) through a decrease in the level of TRF2, a telomere‐binding protein. These responses were correlated with reduced colony formation ability and accelerated telomere shortening in cancer cells upon the stable knockdown of REST. Interestingly, REST was down‐regulated under oxidative stress conditions via ubiquitin proteasome system, suggesting that sustainability of REST expression is critical to determine cell survival during oxidative stress in a tumor microenvironment. Our results collectively indicate that REST‐dependent TRF2 expression renders cancer cells resistant to DNA damage during oxidative stress, and mechanisms to overcome oxidative stress, such as high levels of REST or the stress‐resistant REST mutants found in specific human cancers, may account for REST‐dependent tumorigenesis.
Polyvinyl alcohol–polyvinyl pyrrolidone thin films provide local short‐term release of anti‐inflammatory agents post spinal cord injury
Authors: Comolli Noelle , Donaldson Olivia , Grantier Nathan , Zhukareva Victoria , Tom Veronica J.
Published: July 2012

Spinal cord injury (SCI) triggers a large inflammatory response that results in exacerbated tissue damage. Locally delivering anti‐inflammatory drugs could mitigate this secondary wave of degeneration. The mitogen‐activated protein kinase family members p38 and c‐Jun N‐terminal kinase (JNK) play important roles in the inflammatory response and cell death. We propose that the use of polymer thin films, made of polyvinyl alcohol and polyvinyl pyrrolidone blends (PVA–PVP), can be used to provide local release of inhibitors to p38 and JNK post‐SCI. Release studies performed in vitro confirmed the inhibitors could be released from the film for up to 7 days. The thin film was also tested for its surgical feasibility using a cervical contusion model of SCI in adult female rats. Films with or without the inhibitors were placed subdurally over the injury site immediately following SCI. Animals were sacrificed 5 days post‐SCI and spinal cord tissue above and below the injury site was harvested. Additionally, films were removed for analysis. Scanning electron microscopy confirmed the anti‐fouling properties of the PVA–PVP film. Tissue histology confirmed that the films themselves did not generate a large immune response, but they did compress the tissue slightly at its placement above the injury site. Finally, quantitative Western blot analysis determined the films loaded with p38 and JNK inhibitors delivered bioactive agents to the injury site and resulted in a significantly decreased amount of pro‐cell death proteins. These data indicate that PVA–PVP films can be used to effectively deliver drugs to a SCI site. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Effect of load on the repair of osteochondral defects using a porous polymer scaffold
Authors: Hannink Gerjon , de Mulder Eric L.W. , van Tienen Tony G. , Buma Pieter
Published: July 2012

The aim of the present study was to evaluate if a porous polymer scaffold, currently used for partial meniscal replacement in clinical practice, could initiate regeneration and repair of osteochondral defects, and if regeneration and repair were related to mechanical stimulation. Two equally sized osteochondral defects were created bilaterally in each trochlear groove of 16 adult female New Zealand White rabbits. The defects were filled with polycaprolactone–polyurethane scaffolds of either 3 or 4 mm in height. Regeneration and repair of the defects were evaluated after 8 (n = 8) and 14 weeks (n = 8). After 8 weeks of implantation, both the 3‐ and 4‐mm scaffolds were flush with the native cartilage. The amount of cartilaginous tissue was similar in both scaffold types. Pores located in the more central zones of the scaffolds contained less cartilaginous tissue when compared with pores located in the more superficial zones. After 14 weeks, significantly more cartilaginous tissue was present in 4 mm scaffolds when compared with the 3‐mm scaffolds (p = 0.03). In the 4‐mm scaffolds, progression of cartilaginous tissue from the surface of the scaffold toward the center was observed over time, whereas in the 3‐mm scaffold, the percentage of cartilaginous tissue in the central zones was not different from the situation after 8 weeks. Osteochondral defects might be treated using porous polymer scaffolds currently used for partial meniscus replacement, although several limitations need yet to be overcome. The results suggest that mechanical forces may not have to be applied over long periods of time to accelerate tissue formation and increase cartilage repair longevity. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Oxidation‐induced the Formation of Vesicles from Ferrocene Derivative Superamphiphiles
Authors: Li Qiu Hong , Tan Hong Sheng , Li Ai Xiang
Published: July 2012

The stimuli‐responsive vesicles were prepared via electrochemical oxidation on the mixture solution of ferrocenylmethyl‐trimethylammonium iodide (FcMI) and sodium deoxycholate (NaDC). The vesicle structure and morphology are characterized respectively by transmission electron microscopy (TEM), dynamic light scattering (DLS) and atomic force microscopy (AFM). The vesicle shells can be clearly observed by TEM with the thickness ranging from several to several tens of nanometers and their outer diameters at the range of 50‐200 nm. The formation of vesicular structures is also supported via AFM measurements, and the ratio of the diameter and height of the nanospheres was estimated to be ca. 10, indicating the shell collapse. The obtained results are significant for the preparation of smart supramolecular aggregates.
Cellular Uptake of a Polypyridyl Ruthenium Complex Revealed Using a Fluorescent Rhodamine‐modified Ruthenium Complex
Authors: Jhou Yu‐Ru , Chiou Chien‐Hui , Ni Lin‐Kia , Chen Li‐Chou , Chen Yau‐Hung , Chen Chien‐Chung
Published: July 2012

A fluorescent polypyridyl ruthenium complex was successfully prepared using an amide bond linkage to link two rhodamine moieties through bipyridine groups. Although photo‐induced electron transfer (PET) quenched the fluorescent intensity, the quantum yield of the rhodamine‐modified Ru(II) complex was 0.17 in water, sufficient for observing the fluorophore behaviour in biological systems. The rhodaminemodified Ru(II) complex was found to inhibit the bacterial growth of E. coli. In vitro fluorescence images of human hepatoma cells (SK‐Hep1) showed that a fluorescent polypyridyl ruthenium complex not only supported the above observation but also preferably accumulated in the cytoplasmic region inside the cell. These observations suggest that in addition to strong Ru–DNA interactions, Ru‐protein interactions in the cytoplasmic regions are strong and are therefore important to the development of metallopharmaceuticals.
Surface Treatment of Li(Li0.08Ni0.34Co0.08Mn0.5)O2 Oxide for High Voltage Lithium Ion Battery
Authors: Wu Hsin‐Gen , Chandan Prem , Chang Hua‐Shu , Chiu Chui‐Chang , Sheu Hwo‐Shuenn , Tang Horng‐Yi
Published: July 2012

The high capacity cathode materials with charge voltage above 4.5 V are widely being developed. To reduce surface reactivity at high voltage, Al2O3 and pullulan are used for coating on the Li(Li0.08Ni0.34Co0.08Mn0.5)O2 surface and are characterized by electrochemical analysis. Charge/discharge and electrochemical results reveal that the organic coating sustains in high voltage cycles. Ionic conductivity of surface coating plays a key role in the battery performance.
Development and Initial Testing of a Measure of Public and Self‐Stigma in the Military
Authors: Skopp Nancy A. , Bush Nigel E. , Vogel David L. , Wade Nathaniel G. , Sirotin Anton P. , McCann Russell A. , Metzger‐Abamukong Melinda J.
Published: July 2012

Objective

This research developed and tested the Military Stigma Scale (MSS), a 26‐item scale, designed to measure public and self‐stigma, two theorized core components of mental health stigma.

Method

The sample comprised 1,038 active duty soldiers recruited from a large Army installation. Soldiers’ mean age was 26.7 (standard deviation = 5.9) years, and 93.6% were male. The sample was randomly split into a scale development group (n = 520) and a confirmatory group (n = 518).

Results

Factor analysis conducted with the scale development group resulted in the adoption of two factors, named public and self‐stigma, accounting for 52.1% of the variance. Confirmatory factor analysis conducted with the confirmatory group indicated good fit for the two‐factor model. Both factors were components of a higher order stigma factor. The public and self‐stigma scales for the exploratory and confirmatory groups demonstrated good internal consistency (α = .94 and .89; α = .95 and .87, respectively). Demographic differences in stigma were consistent with theory and previous empirical research: Soldiers who had seen a mental health provider scored lower in self‐stigma than those who had not.

Conclusions

The MSS comprises two internally consistent dimensions that appear to capture the constructs of public and self‐stigma. The overall results indicate that public and self‐stigma are dimensions of stigma that are relevant to active duty soldiers and suggest the need to assess these dimensions in future military stigma research.
Intrarenal oxygenation by blood oxygenation level‐dependent MRI in contrast nephropathy model: Effect of the viscosity and dose
Authors: Li Lu‐Ping , Franklin Tammy , Du Hongyan , Papadopoulou‐Rosenzweig Maria , Carbray Joann , Solomon Richard , Prasad Pottumarthi V.
Published: July 2012

Purpose:

To compare the effects of osmolality versus viscosity of radio‐contrast media on intra‐renal oxygenation as determined by blood oxygenation level‐dependent (BOLD) MRI in a model of contrast induced nephropathy (CIN).

Materials and Methods:

Twenty‐four Sprague‐Dawley rats were divided into five groups. Nitric oxide synthase inhibitor L‐NAME (10 mg/kg), cyclooxygenase inhibitor indomethacin (10 mg/kg), or saline, and radio‐contrast iodixanol (high viscosity, 784 or 1600 mg I/kg) or iothalamate (high osmolality, 1600 mg I/kg) were administered. BOLD MRI images were acquired on Siemens 3 Tesla (T) scanner using a multiple gradient recalled echo sequence at baseline, following L‐NAME (or saline), indomethacin (or saline), and radio‐contrast agents. R2* (=1/T2*) was used as the BOLD MRI parameter in renal medulla and cortex. Mixed‐effects models with first order auto‐regressive variance‐covariance models were used to analyze the data.

Results:

The magnitude of change in medullary R2* (MR2*) with same dose of iodine was larger with iodixanol compared with iothalalmate both in pretreated groups (303% versus 225.6%, < 0.01) and the control group (191.6% versus −1.8%, P < 0.01). The MR2* change in high dose iodixanol was approximately twice compared with the low dose (303% versus 133%, P < 0.01).

Conclusion:

The viscosity of radio‐contrast seems to play a more significant role than osmolality in terms of renal oxygenation changes as evaluated by BOLD MRI. Additionally, iodixanol induced a dose‐dependent increase in renal medullary hypoxia. J. Magn. Reson. Imaging 2012;36:1162–1167. © 2012 Wiley Periodicals, Inc.
Recombination and natural selection in hepatitis E virus genotypes
Authors: Chen Xiaoming , Zhang Qian , He Chao , Zhang Lei , Li Jinghua , Zhang Weilu , Cao Wei , Lv Yong‐Gang , Liu Zhengcai , Zhang Jing‐Xia , Shao Zhong‐Jun
Published: July 2012

To gain new insights into the evolutionary processes that created the genetic diversity of the hepatitis E virus (HEV), the Recombination Detection Program (RDP) and SimPlot program were employed to detect recombination events in the genome, then the fixed‐effects likelihood (FEL) method was used to detect natural selection effects on viral proteins. Recombination analysis provided strong evidence for both intergenotype and intragenotype recombination events in the sequences analyzed. Recombination events were found to be distributed non‐randomly, with the highest frequency in the X domain and the helicase. Strain DQ450072 was identified as intergenotype‐recombinant. Natural selection analysis revealed that codons under both negative selection and positive selection were distributed non‐randomly. ORF1 and ORF2 have experienced strong purifying selection across genotypes. Furthermore, potentially important sites were also found under positive selection in the N‐terminal end of ORF2 and the C‐terminal end of ORF3. No significant difference was found among the selective pressures on different genotypes. J. Med. Virol. 84:1396–1407, 2012. © 2012 Wiley Periodicals, Inc.
A diagnostic polymerase chain reaction assay for Zika virus
Authors: Balm Michelle N.D. , Lee Chun Kiat , Lee Hong Kai , Chiu Lily , Koay Evelyn S.C. , Tang Julian W.
Published: July 2012

Zika virus (ZIKV) is a mosquito‐borne flavivirus. Infection results in a dengue‐like illness with fever, headache, malaise, and a maculopapular rash. Nearly all cases are mild and self‐limiting but in 2007, a large outbreak of ZIKV was reported from the island of Yap (in Micronesia, northwest of Indonesia). Singapore is already endemic for dengue, and its impact on public health and economic burden is significant. Other dengue‐like infections (e.g., Chikungunya virus) are present. Yet only 10% of reported dengue cases have laboratory confirmation. The identification and control of other dengue‐like, mosquito‐transmitted infections is thus important for the health of Singapore's population, as well as its economy. Given that ZIKV shares the same Aedes mosquito vector with both dengue and Chikungunya, it is possible that this virus is present in Singapore and causing some of the mild dengue‐like illness. A specific and sensitive one‐step, reverse transcription polymerase chain reaction (RT‐PCR) with an internal control (IC) was designed and tested on 88 archived samples of dengue‐negative, Chikungunya‐negative sera from patients presenting to our hospital with a dengue‐like illness, to determine the presence of ZIKV in Singapore. The assay was specific for detection of ZIKV and displayed a lower limit of detection (LoD) of 140 copies viral RNA/reaction when tested on synthetic RNA standards prepared using pooled negative patient plasma. Of the 88 samples tested, none were positive for ZIKV RNA, however, the vast majority of these were from patients admitted to hospital and further study may be warranted in community‐based environments. J. Med. Virol. 84:1501–1505, 2012. © 2012 Wiley Periodicals, Inc.