bluuebunny/crossref_metadata_2025_split huggingface dataset:
More technology, better learning resources, better learning? Lessons from adopting virtual microscopy in undergraduate medical education
Authors: Helle Laura , Nivala Markus , Kronqvist Pauliina 
Published: August 2012

AbstractThe adoption of virtual microscopy at the University of Turku, Finland, created a unique real‐world laboratory for exploring ways of reforming the learning environment. The purpose of this study was to evaluate the students' reactions and the impact of a set of measures designed to boost an experimental group's understanding of abnormal histology through an emphasis on knowledge of normal cells and tissues. The set of measures included (1) digital resources to review normal structures and an entrance examination for enforcement, (2) digital course slides highlighting normal and abnormal tissues, and (3) self‐diagnostic quizzes. The performance of historical controls was used as a baseline, as previous students had never been exposed to the above‐mentioned measures. The students' understanding of normal histology was assessed in the beginning of the module to determine the impact of the first set of measures, whereas that of abnormal histology was assessed at the end of the module to determine the impact of the whole set of measures. The students' reactions to the instructional measures were assessed by course evaluation data. Additionally, four students were interviewed. Results confirmed that the experimental group significantly outperformed the historical controls in understanding normal histology. The students held favorable opinions on the idea of emphasizing normal structures. However, with regards to abnormal histology, the historical controls outperformed the experimental group. In conclusion, allowing students access to high‐quality digitized materials and boosting prerequisite skills are clearly not sufficient to boost final competence. Instead, the solution may lie in making students externally accountable for their learning throughout their training. Anat Sci Educ 6: 73–80. © 2012 American Association of Anatomists.
Repeated dosing of piperine induced gene expression of P‐glycoprotein via stimulated pregnane‐X‐receptor activity and altered pharmacokinetics of diltiazem in rats
Authors: Qiang Fu , Kang Keon‐Wook , Han Hyo‐Kyung 
Published: August 2012

ABSTRACTThis study investigated the effect of piperine on the gene expression of P‐glycoprotein (P‐gp) as well as pregnane‐X‐receptor (PXR) activity and also its implication on the bioavailability of diltiazem, a P‐gp substrate. The effect of piperine on the systemic exposure of diltiazem was examined in rats after the intravenous and oral administration of diltiazem with/without 2 week pretreatment with piperine. Compared with the control group given diltiazem (20 mg/kg) alone, the pretreatment with piperine (10 or 20 mg/kg, once daily for 2 weeks) decreased the oral exposure of diltiazem by 36–48% in rats. Consequently, the bioavailability of oral diltiazem was significantly lower (p < 0.05) after the 2 week pretreatment with piperine. The pretreatment with piperine for 2 weeks also reduced the systemic exposure of desacetyldiltiazem, a major active metabolite of diltiazem by approximately 73%, accompanied by a significant decrease in the metabolite–parent ratio. In contrast to the oral pharmacokinetics, piperine did not affect the intravenous pharmacokinetics of diltiazem in rats. Immunoblot analysis indicated that the protein expression level of intestinal P‐gp was significantly enhanced after the 2 week pretreatment with piperine in rats. In addition, piperine increased the PXR reporter activity in human hepatoma cells. Taken together, the 2 week pretreatment with piperine significantly induced intestinal P‐gp expression in conjunction with stimulated PXR activity and decreased the oral exposure of diltiazem and desacetyldiltiazem in rats. Copyright © 2012 John Wiley & Sons, Ltd.
Reproductive Performance and Early Postnatal Development in Interleukin (IL)‐13‐Deficient Mice
Authors: Wright David J. , Adkins Karissa K. , Minck Daniel R. , Bailey Steven , Warner Garvin , Leach Michael W. 
Published: August 2012

OBJECTIVEThe purpose of this study was to assess the effect of interleukin (IL)‐13 deficiency on fertility and reproductive performance of adult mice and on morphological and behavioral development of the offspring.METHODSWild‐type and homozygous IL‐13‐deficient (KO) mice were grouped by genotype, and male and female mice were mated within each group. Adult (F0) mice were evaluated for reproductive performance, and development was assessed in F1 fetuses on gestation day 18, and in F1 pups to postnatal day 35.RESULTSIn F0 males, there were no differences in the number of males that mated or impregnated females, or in total sperm count or sperm motility, between the wild‐type and KO groups. In F0 females, there were no observed genotype‐related differences in fertility, length of gestation, number of viable fetuses per litter, or viability of offspring. There were no differences in embryo‐fetal development (external/palate, skeletal, visceral) of the F1 fetuses between genotypes. Similarly, IL‐13 deficiency had no impact on any postnatal parameters assessed including reflex, sexual maturation, learning, and memory.CONCLUSIONSIL‐13 deficiency had no observed effect on reproductive performance or morphological and behavioral development in mice.
Production of human cytochrome P450 2D6 drug metabolites with recombinant microbes – a comparative study
Authors: Geier Martina , Braun Andreas , Emmerstorfer Anita , Pichler Harald , Glieder Anton 
Published: August 2012

AbstractThe processes of drug development require efficient strategies to produce the respective drug metabolites, which are often difficult to obtain. Biotransformations employing recombinant microorganisms as whole‐cell biocatalysts have become an attractive alternative to the chemical syntheses of such metabolites. For the first time, the potential of four different microbial systems expressing the human cytochrome P450 2D6 (CYP2D6), which is one of the most important drug‐metabolizing enzymes, were compared and evaluated for such applications. The microbial host Pichia pastoris was the most efficient at expressing CYP2D6. Without additional over‐expression of chaperons, the achieved yield of CYP2D6 was the highest of microbial hosts reported so far. Therefore, the system described in this study outperformed the previously reported expression of the N‐terminally modified enzyme. It was also shown that the activities of the whole‐cell conversions of bufuralol in recombinant P. pastoris were significantly higher than the Escherichia coli catalyst, which expressed the same unmodified gene.
Gene network analysis leads to functional validation of pathways linked to cancer cell growth and survival
Authors: Berger Emmanuelle , Vega Nathalie , Vidal Hubert , Geloën Alain 
Published: August 2012

AbstractHepatocellular carcinoma (HCC) represents one of the most frequently diagnosed human cancers; however, there are currently few treatment alternatives to surgical resection. In this study we performed bioinformatic analysis of previously published transcriptomic data in order to characterize liver specific networks, including biological functions, signaling pathways and transcription factors, potentially dysregulated in HCC. By incorporating specific signaling inhibitors into real‐time proliferation assays using HepG2 cells, we then validated these in silico results. We found that G protein subunits Gi/G0, protein kinase C, Mek1/2, and Erk1/2 (P42/44), JAK1, PPARA and NFκB p65 subunit were the major signaling molecules required for survival and proliferation of human HCC cell lines. We also found that these pathways regulate the expression of key hepatic transcription factors involved in cell differentiation, such as CEBPA, EGR1, FOXM1 and PPARs. By combining bioinformatic and functional analyses, major signaling pathways related to tumorigenicity in HCC are revealed, thereby elucidating potential targets for drug therapies.
Id1 and Id3 expression is associated with increasing grade of prostate cancer: Id3 preferentially regulates CDKN1B
Authors: Sharma Pankaj , Patel Divya , Chaudhary Jaideep 
Published: August 2012

AbstractAs transcriptional regulators of basic helix–oop–helix (bHLH) transcription and non‐bHLH factors, the inhibitor of differentiation (Id1, Id2, Id3, and Id4) proteins play a critical role in coordinated regulation of cell growth, differentiation, tumorigenesis, and angiogenesis. Id1 regulates prostate cancer (PCa) cell proliferation, apoptosis, and androgen independence, but its clinical significance in PCa remains controversial. Moreover, there is lack of evidence on the expression of Id2 and Id3 in PCa progression. In this study we investigated the expression of Id2 and Id3 and reevaluated the expression of Id1 in PCa. We show that increased Id1 and Id3 protein expression is strongly associated with increasing grade of PCa. At the molecular level, we report that silencing either Id1 or Id3 attenuates cell cycle. Although structurally and mechanistically similar, our results show that both these proteins are noncompensatory at least in PCa progression. Moreover, through gene silencing approaches we show that Id1 and Id3 primarily attenuates CDKN1A (p21) and CDKN1B (p27), respectively. We also demonstrate that silencing Id3 alone significantly attenuates proliferation of PCa cells as compared with Id1. We propose that increased Id1 and Id3 expression attenuates all three cyclin‐dependent kinase inhibitors (CDKN2B, ‐1A, and ‐1B) resulting in a more aggressive PCa phenotype.
Iptycene‐Based Fluorescent Sensors for Nitroaromatics and TNT
Authors: Anzenbacher Pavel , Mosca Lorenzo , Palacios Manuel A. , Zyryanov Grigory V. , Koutnik Petr 
Published: August 2012

AbstractSmall‐molecule fluorescent sensors (1–5) for the recognition of nitroaromatic compounds, such as 2,4‐dinitrotoluene and the explosive TNT, were obtained by using a three‐step dehydrohalogenation cycloaddition protocol. The interaction of the receptors and nitroaromatics was studied both in solution and in the solid state by using fluorescence spectroscopy and X‐ray crystallography, respectively. It is shown that the iptycene receptors 1–5 provide a cavity suitable for binding nitroaromatic compounds in an edge‐to‐face mode, rather than simple ring‐stacking interactions. The results obtained inspired us to develop an inexpensive, reliable and robust sensor for vapour detection of explosives. Polymer nanofibres are particularly suitable for the production of such TNT sensors as they accelerate the mass exchange between the polymer and the vapours of TNT. Quenching of the sensors took place within 1 min compared to 10 min for a glass‐slide assay. Hence, the sensor performance can be improved by optimising the matrix material and morphology without resynthesising the sensor moieties.
Exceptional Crystallization Diversity and Solid‐State Conversions of CdII Coordination Frameworks with 5‐Bromonicotinate Directed by Solvent Media
Authors: Li Cheng‐Peng , Wu Jing‐Min , Du Miao 
Published: August 2012

AbstractA series of nine coordination polymers {[Cd(L)2(solvent)x](solvent)y}n have been prepared from Cd(NO3)2 and 5‐bromonicotinic acid (HL) in different solvents through a layered diffusion method. By using CH3OH/H2O at different volume ratios of 1:1 and 1:3, a one‐dimensional (1D) coordination species (1 a) and a three‐dimensional (3D) (3,6)‐connected framework (2 a⋅g1) can be obtained. A similar self‐assembly process in C2H5OH/H2O or H2O/1,4‐dioxane gives 2 a⋅g2 or 2 a⋅g3, which are isomorphic to 2 a⋅g1 but with different lattice solvents. Replacement of the mixed solvents with DMF/H2O (v/v 1:1 or 1:3) also gives a 1D chain complex (1 b) or a 3D microporous framework (2 b⋅g1). Similarly, MOF 2 b⋅g2 can be assembled from CH3CN/H2O as an isomorphic solvate of 2 b⋅g1. Significantly, the 3D MOF families of 2 a⋅gn and 2 b⋅gn are supramolecular isomers even though they are topologically equivalent. Also, if a mixture of CH3OH/CH2Cl2 (v/v 1:1 or 3:1) is used, a pair of distinct MOFs (3 a⋅g) and (3 b) are generated as pseudo‐polymorphs that show a two‐dimensional (2D) sheet and a 3D coordination framework, respectively. Furthermore, mutual solvent‐induced conversions were realized between 1 a and 1 b and between 2 a⋅g1, 2 a⋅g2, and 2 a⋅g3 following the size‐dependent rule of the solvent. These results are of great significance in recognizing the solvent effect upon coordination assemblies and their crystal transformations.
Synthesis of a Library of Fluorescent 2‐Aryl‐3‐trifluoromethylnaphthofurans from Naphthols by Using a Sequential Pummerer‐Annulation/Cross‐Coupling Strategy and their Photophysical Properties
Authors: Ookubo Yuuya , Wakamiya Atsushi , Yorimitsu Hideki , Osuka Atsuhiro 
Published: August 2012

AbstractA library of 2‐aryl‐3‐trifluoromethylnaphthofurans was synthesized with high efficiency from simple naphthols. In this synthesis, the Pummerer‐type annulation of naphthols with 3‐(2,2,2‐trifluoroethylidene)‐2,4‐dithiapentane 2‐oxide was followed by a cross‐coupling of the resulting 2‐methylthio‐3‐trifluoromethylnaphthofurans with a variety of arylzinc reagents. A palladium complex, Pd‐PEPPSI‐IPr, was the most efficient catalyst for the arylation step, which represents the first cross‐coupling of aryl sulfides by using an N‐heterocyclic‐carbene‐ligated palladium complex. This library consists of new π‐expanded molecules, all of which are fluorescent in the solid state as well as in solution. Their photophysical properties, such as absorption and emission, fluorescence quantum yields, and fluorescence lifetimes, were thoroughly investigated. This library was also useful to identify acidochromic molecules.
Influence of Sequential Modifications and Carbohydrate Variations in Synthetic AFGP Analogues on Conformation and Antifreeze Activity
Authors: Nagel Lilly , Budke Carsten , Erdmann Roman S. , Dreyer Axel , Wennemers Helma , Koop Thomas , Sewald Norbert 
Published: August 2012

AbstractCertain Arctic and Antarctic ectotherm species have developed strategies for survival under low temperature conditions that, among others, consist of antifreeze glycopeptides (AFGP). AFGP form a class of biological antifreeze agents that exhibit the ability to inhibit ice growth in vitro and in vivo and, hence, enable life at temperatures below the freezing point. AFGP usually consist of a varying number of (Ala‐Ala‐Thr)n units (n=4–55) with the disaccharide β‐D‐galactosyl‐(1→3)‐α‐N‐acetyl‐D‐galactosamine glycosidically attached to every threonine side chain hydroxyl group. AFGP have been shown to adopt polyproline II helical conformation. Although this pattern is highly conserved among different species, microheterogeneity concerning the amino acid composition usually occurs; for example, alanine is occasionally replaced by proline in smaller AFGP. The influence of minor and major sequence mutations on conformation and antifreeze activity of AFGP analogues was investigated by replacement of alanine by proline and glycosylated threonine by glycosylated hydroxyproline. The target compounds were prepared by using microwave‐enhanced solid phase peptide synthesis. Furthermore, artificial analogues were obtained by copper‐catalyzed azide–alkyne cycloaddition (CuAAC): propargyl glycosides were treated with polyproline helix II‐forming peptides comprising (Pro‐Azp‐Pro)n units (n=2–4) that contained 4‐azidoproline (Azp). The conformations of all analogues were examined by circular dichroism (CD). In addition, microphysical analysis was performed to provide information on their inhibitory effect on ice recrystallization.
Inhibition of Bacterial Dihydrofolate Reductase by 6‐Alkyl‐2,4‐diaminopyrimidines
Authors: Nammalwar Baskar , Bourne Christina R. , Bunce Richard A. , Wakeham Nancy , Bourne Philip C. , Ramnarayan Kal , Mylvaganam Shankari , Berlin K. Darrell , Barrow Esther W. , Barrow William W. 
Published: August 2012

Abstract(±)‐6‐Alkyl‐2,4‐diaminopyrimidine‐based inhibitors of bacterial dihydrofolate reductase (DHFR) have been prepared and evaluated for biological potency against Bacillus anthracis and Staphylococcus aureus. Biological studies revealed attenuated activity relative to earlier structures lacking substitution at C6 of the diaminopyrimidine moiety, though minimum inhibitory concentration (MIC) values are in the 0.125–8 μg mL−1 range for both organisms. This effect was rationalized from three‐ dimensional X‐ray structure studies that indicate the presence of a side pocket containing two water molecules adjacent to the main binding pocket. Because of the hydrophobic nature of the substitutions at C6, the main interactions are with protein residues Leu 20 and Leu 28. These interactions lead to a minor conformational change in the protein, which opens the pocket containing these water molecules such that it becomes continuous with the main binding pocket. These water molecules are reported to play a critical role in the catalytic reaction, highlighting a new area for inhibitor expansion within the limited architectural variation at the catalytic site of bacterial DHFR.
Utilization of NMR spectroscopy to study biological fluids and metabolic processes: Two introductory activities
Authors: Abriata Luciano A. 
Published: August 2012

AbstractThis work describes two activities designed to introduce students into the use of NMR spectroscopy for the analysis of biological fluids. In the first activity, 1H spectra of common beverages are acquired and analyzed to identify their most abundant constituents based on computer‐aided comparison against known spectra of metabolites. In the second activity, the utilization of glucose by yeast is followed by collecting 1H spectra over time, and the evolution of substrates and products is analyzed. The possibility of tailoring these activities to different levels and course scopes is discussed, together with potential alternative experiments and analyses. © 2012 Wiley Periodicals, Inc. Concepts Magn Reson Part A 40A: 171–178, 2012.
Long‐term efficacy and safety of arsenic trioxide for first‐line treatment of elderly patients with newly diagnosed acute promyelocytic leukemia
Authors: Zhang Yingmei , Zhang Zhuo , Li Jinmei , Li Limin , Han Xueying , Han Lina , Hu Longhu , Wang Shuye , Zhao Yanhong , Li Xiaoxia , Zhang Ying , Fan Shengjin , Lv Chengfang , Li Yinghua , Su Yanhua , Zhao Hui , Zhang Xin , Zhou Jin 
Published: August 2012

AbstractBACKGROUND:The prognosis of acute promyelocytic leukemia (APL) in the elderly is poorer than that of younger patients after treatment with all‐trans retinoic acid plus chemotherapy, which is the current standard therapy for APL. A significantly higher mortality during consolidation therapy was found, which is mainly due to deaths from sepsis following chemotherapy‐induced myelosuppression.METHODS:A total of 33 patients aged 60 years or older with de novo APL were treated with single‐agent arsenic trioxide (ATO) for remission induction and postremission therapy. The postremission therapy continued for up to 4 years.RESULTS:Twenty‐nine patients (87.9%) achieved a hematologic complete remission, and the most common adverse event during remission induction was leukocytosis (63.6%). Definite differentiation syndrome was observed in 5 patients. Nonhematologic adverse events were all manageable and reversible. Twenty‐eight patients proceeded to postremission therapy. Adverse effects during postremission therapy were mild, transient, and no treatment was required. No patients died from ATO‐related toxicities. With a median follow‐up of 99 months, the 10‐year cumulative incidence of relapse, overall survival, disease‐free survival, and cause‐specific survival were 10.3%, 69.3%, 64.8%, and 84.8%, respectively, which are comparable with those in the younger APL partners. No significant risks for development of chronic arsenicosis or second malignancy were observed during the follow‐up period.CONCLUSIONS:The results indicate that the single‐agent ATO regimen is safe and effective with long‐term durable remission, and could be used as first‐line treatment for elderly patients with de novo APL. Cancer 2013. © 2012 American Cancer Society.
Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women
Authors: Schwartz Theresa , Stark Azadeh , Pang Judy , Awuah Baffour , Kleer Celina G. , Quayson Solomon , Kingman Stephanie , Aitpillah Francis , Abantanga Francis , Jiagge Evelyn , Oppong Joseph K. , Osei‐Bonsu Ernest , Martin Iman , Yan Xiaowei , Toy Kathy , Adjei Ernest , Wicha Max , Newman Lisa A. 
Published: August 2012

AbstractBACKGROUND:Breast cancers that are negative for the estrogen receptor (ER), the progesterone receptor (PR), and the HER2 (human epidermal growth factor receptor 2) marker are more prevalent among African women, and the biologically aggressive nature of these triple‐negative breast cancers (TNBCs) may be attributed to their mammary stem cell features. Little is known about expression of the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) in African women. Novel data are reported regarding ALDH1 expression in benign and cancerous breast tissue of Ghanaian women.METHODS:Formalin‐fixed, paraffin‐embedded specimens were transported from the Komfo Anoyke Teaching Hospital in Kumasi, Ghana to the University of Michigan for centralized histopathology study. Expression of ER, PR, HER2, and ALDH1 was assessed by immunohistochemistry. ALDH1 staining was further characterized by its presence in stromal versus epithelial and/or tumor components of tissue.RESULTS:A total of 173 women contributed to this study: 69 with benign breast conditions, mean age 24 years, and 104 with breast cancer, mean age 49 years. The proportion of benign breast conditions expressing stromal ALDH1 (n = 40, 58%) was significantly higher than those with cancer (n = 44, 42.3%) (P = .043). Among the cancers, TNBC had the highest prevalence of ALDH1 expression, either in stroma or in epithelial cells. More than 2‐fold higher likelihood of ALDH1 expression was observed in TNBC cases compared with other breast cancer subtypes (odds ratio = 2.38, 95% confidence interval 1.03‐5.52, P = .042).CONCLUSIONS:ALDH1 expression was higher in stromal components of benign compared with cancerous lesions. Of the ER‐, PR‐, and HER2‐defined subtypes of breast cancer, expression of ALDH1 was highest in TNBC. Cancer 2013. © 2012 American Cancer Society.