bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of 2‐Naphthoic Acid Monooxygenases by Genome Mining and their Use as Biocatalysts
Authors: Furuya Toshiki , Kino Kuniki
Published: June 2009

The large pool of cytochrome P450 (P450) open‐reading frames identified in genome sequences has attracted much attention as a resource for new oxidation biocatalysts. P450 genes were cloned from genome‐sequenced bacteria and coexpressed with putidaredoxin and its reductase genes to provide the redox partners of P450 in Escherichia coli. Whole‐cell assays were performed with 2‐naphthoic acid as a substrate. Hydroxylated naphthoic acid products were rapidly detected with two reagents showing different colors in the presence of the products. Two P450s, CYP199A1 and CYP199A2, were found to hydroxylate the substrate to 7‐ and 8‐hydroxy‐2‐naphthoic acids. The CYP199A1 whole‐cell biocatalyst converted 1 mM 2‐naphthoic acid to 0.27 mM 7‐hydroxy‐2‐naphthoic acid and 0.53 mM 8‐hydroxy‐2‐naphthoic acid. CYP199A2 exhibited similar regioselectivity to CYP199A1. Furthermore, we found that 8‐hydroxy‐2‐naphthoic acid emits near‐white fluorescence when exposed to UV light. These P450s will provide a facile and environmentally friendly synthetic approach to the hydroxynaphthoic acids.
Morphology of Vapor Deposited Polyimides Containing Copper Phthalocyanine
Authors: Green Zachary I. , Chen Xichong , Papastrat Alexander G. , Zou Lijun , Anthamatten Mitchell
Published: June 2009

A vapor deposition polymerization technique is applied to grow composite films containing polyimide and copper phthalocyanine (CuPc). Specifically, 4,4′‐oxydianiline and 3,3′,4,4′‐biphenyl tetracarboxylic dianhydride are co‐evaporated in the presence of CuPc. Spectroscopy experiments confirm the formation of polyimide segments and suggest that embedded CuPc molecules have less mobility than pure CuPc films. Electron microscopy and X‐ray diffraction (XRD) studies show that the majority of CuPc initially assumes an amorphous phase. Upon curing, partial crystallization of CuPc occurs, forming small crystals (α phase) that are suspended in a polyimide matrix. These crystals exhibit enhanced thermal stability compared to pure vapor‐deposited CuPc.
Special Issue on CVD and Polymeric Materials
Authors: Gleason Karen K.
Published: June 2009

Editorial: CVD of polymeric materials is a field of research that offers tremendous opportunities, combining the controllable deposition of high‐quality, defect‐free films that vapor deposition techniques can provide with the functionality and versatility of polymers. In this editorial, Guest Editor Karen Gleason provides an overview of the fascinating contributions in this Special Issue.
Differential expression of TrkB isoforms switches climbing fiber‐Purkinje cell synaptogenesis to selective synapse elimination
Authors: Sherrard Rachel M. , Dixon Kirsty J. , Bakouche Joëlle , Rodger Jenny , Lemaigre‐Dubreuil Yolande , Mariani Jean
Published: June 2009

Correct neural function depends on precisely organized connectivity, which is refined from broader projections through synaptic/collateral elimination. In the rat, olivocerebellar topography is refined by regression of multiple climbing fiber (CF) innervation of Purkinje cells (PC) during the first two postnatal weeks. The molecules that initiate this regression are not fully understood. We assessed the role of cerebellar neurotrophins by examining tropomycin receptor kinase (Trk) receptor expression in the inferior olive and cerebellum between postnatal days (P)3‐7, when CF‐PC innervation changes from synapse formation to selective synapse elimination, and in a denervation‐reinnervation model when synaptogenesis is delayed. Trks A, B, and C are expressed in olivary neurons; although TrkA was not transported to the cerebellum and TrkC was unchanged during innervation and reinnervation, suggesting that neither receptor is involved in CF‐PC synaptogenesis. In contrast, both total and truncated TrkB (TrkB.T) increased in the olive and cerebellum from P4, whereas full‐length and activated phosphorylated TrkB (phospho‐TrkB) decreased from P4‐5. This reveals less TrkB signaling at the onset of CF regression. This expression pattern was reproduced during CF‐PC reinnervation: in the denervated hemicerebellum phospho‐TrkB decreased as CF terminals degenerated, then increased in parallel with the delayed neosynaptogenesis as new CFs reinnervated the denervated hemicerebellum. In the absence of this signaling, CF reinnervation did not develop. Our data reveal that olivocerebellar TrkB activity parallels CF‐PC synaptic formation and stabilization and is required for neosynaptogenesis. Furthermore, TrkB.T expression rises to reduce TrkB signaling and permit synapse elimination. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009
Rapid, long‐term labeling of cells in the developing and adult rodent visual cortex using double‐stranded adeno‐associated viral vectors
Authors: Lowery Rebecca L. , Zhang Yu , Kelly Emily A. , Lamantia Cassandra E. , Harvey Brandon K. , Majewska Ania K.
Published: June 2009

Chronic in vivo imaging studies of the brain require a labeling method that is fast, long‐lasting, efficient, nontoxic, and cell‐type specific. Over the last decade, adeno‐associated virus (AAV) has been used to stably express fluorescent proteins in neurons invivo. However, AAV's main limitation for many studies (such as those of neuronal development) is the necessity of second‐strand DNA synthesis, which delays peak transgene expression. The development of double‐stranded AAV (dsAAV) vectors has overcome this limitation, allowing rapid transgene expression. Here, we have injected different serotypes (1, 2, 6, 7, 8, and 9) of a dsAAV vector carrying the green fluorescent protein (GFP) gene into the developing and adult mouse visual cortex and characterized its expression. We observed labeling of both neurons and astrocytes with serotype‐specific tropism. dsAAV‐GFP labeling showed high levels of neuronal GFP expression as early as 2 days postinjection and as long as a month, surpassing conventional AAV's onset of expression and matching its longevity. Neurons labeled with dsAAV‐GFP appeared structurally and electrophysiologically identical to nonlabeled neurons, suggesting that dsAAV‐GFP is neither cytotoxic nor alters normal neuronal function. We also demonstrated that dsAAV‐labeled cells can be imaged with subcellular resolution in vivo over multiple days. We conclude that dsAAV is an excellent vector for rapid labeling and long‐term in vivo imaging studies of astrocytes and neurons on the single cell level within the developing and adult visual cortex. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009
Prior use of extreme weight‐control behaviors in a community sample of women with binge eating disorder or subthreshold binge eating disorder: A descriptive study
Authors: Mond Jonathan M. , Peterson Carol B. , Hay Phillipa J.
Published: June 2009

Objective and Method

The prior occurrence of regular extreme weight‐control behaviors was examined in a community sample of women (n = 27) with binge eating disorder (BED) or subthreshold BED.

Results

Approximately two thirds of participants (65.4%) reported the prior use of either purging at least weekly or nonpurging behaviors three or more times per week, for a period of 3 months or more, whereas 38.5% of participants reported either purging at least twice weekly or nonpurging behaviors five or more times per week. Comparatively few participants (11.1%) had ever met formal diagnostic criteria for BN.

Discussion

Considerable overlap be‐tween disorders characterized by binge eating in the absence of extreme weight‐control behaviors and those characterized by extreme weight‐control behaviors in the absence of binge eating may be apparent when a longitudinal perspective is taken. Caution needs to be exercised in drawing conclusions concerning the extent of this overlap based on any one operational definition of the term “regular extreme weight‐control behaviors”. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010
Lack of TNFR2 expression by CD4+ T cells exacerbates experimental colitis
Authors: Dayer Schneider Johanna , Seibold Inge , Saxer‐Sekulic Nikolina , Paredes Bruno E. , Saurer Leslie , Mueller Christoph
Published: June 2009

TNF plays fundamental roles in the induction and perpetuation of inflammation. The effects of TNF are mediated through TNF receptor (TNFR) 1 or 2. As these two receptors mediate different functions, selective targeting of one receptor may represent a more specific treatment for inflammatory disorders than the complete blocking of TNF. TNFR2 expression is up‐regulated in inflammatory bowel disease. Hence, we directly assessed the role of TNFR2 signaling in the CD4+ T‐cell transfer model of colitis using TNFR2−/− or WT mice as donors of colitogenic CD4+CD45RBhi T cells for transfer into syngeneic RAG2−/− or RAG2−/−TNFR2−/− recipient mice. Although the absence of TNFR2 expression by non‐lymphoid cells of the recipient mice does not influence the course of colitis, transfer of TNFR2−/− CD4+ T cells leads to an accelerated onset of disease and to more severe signs of inflammation. The enhanced colitogenic potential of TNFR2−/− CD4+ T cells is associated with reduced activation‐induced cell death, resulting in an increased accumulation of TNFR2−/− CD4+ T cells. Hence, TNFR2 signaling is crucial for the TNF‐dependent contraction of the disease‐inducing T cells. Therefore, a selective blocking of TNFR2 may lead to exacerbation rather than attenuation of T‐cell‐mediated inflammatory disorders.
Determination of 5‐Aminosalicylic Acid by Catalase‐Peroxidase Based Biosensor
Authors: Akkaya Alper , Altug Cagri , Pazarlioglu Nurdan Kasikara , Dinckaya Erhan
Published: June 2009

5‐Aminosalicylic acid is an antiinflammatory drug used to treat inflammation of the digestive tract (Crohn's disease) and mild to moderate ulcerative‐colitis. 5‐Aminosalicylic acid is a bowel‐specific aminosalicylate drug. It was developed an amperometric biosensor for determination of 5‐aminosalicylic acid concentration and measurement technique is based on substrate‐competition. The biosensor is more suitable especially for routine 5‐aminosalicylic acid analysis because it is simple to construct and sensitive, specific and does not require any expensive apparatus. This enzyme based biosensor was made with a couple of enzymes which uses the same substrate. The electrode was developed to determine measurement conditions and also characterized.
Analysis of genomic dose‐response information on arsenic to inform key events in a mode of action for carcinogenicity
Authors: Gentry P. Robinan , McDonald Tracy B. , Sullivan Dexter E. , Shipp Annette M. , Yager Janice W. , Clewell Harvey J.
Published: June 2009

A comprehensive literature search was conducted to identify information on gene expression changes following exposures to inorganic arsenic compounds. This information was organized by compound, exposure, dose/concentration, species, tissue, and cell type. A concentration‐related hierarchy of responses was observed, beginning with changes in gene/protein expression associated with adaptive responses (e.g., preinflammatory responses, delay of apoptosis). Between 0.1 and 10 μM, additional gene/protein expression changes related to oxidative stress, proteotoxicity, inflammation, and proliferative signaling occur along with those related to DNA repair, cell cycle G2/M checkpoint control, and induction of apoptosis. At higher concentrations (10–100 μM), changes in apoptotic genes dominate. Comparisons of primary cell results with those obtained from immortalized or tumor‐derived cell lines were also evaluated to determine the extent to which similar responses are observed across cell lines. Although immortalized cells appear to respond similarly to primary cells, caution must be exercised in using gene expression data from tumor‐derived cell lines, where inactivation or overexpression of key genes (e.g., p53, Bcl‐2) may lead to altered genomic responses. Data from acute in vivo exposures are of limited value for evaluating the dose‐response for gene expression, because of the transient, variable, and uncertain nature of tissue exposure in these studies. The available in vitro gene expression data, together with information on the metabolism and protein binding of arsenic compounds, provide evidence of a mode of action for inorganic arsenic carcinogenicity involving interactions with critical proteins, such as those involved in DNA repair, overlaid against a background of chemical stress, including proteotoxicity and depletion of nonprotein sulfhydryls. The inhibition of DNA repair under conditions of toxicity and proliferative pressure may compromise the ability of cells to maintain the integrity of their DNA. Environ. Mol. Mutagen., 2010. © 2009 Wiley‐Liss, Inc.
Adaptive finite elements with large aspect ratio for mass transport in electroosmosis and pressure‐driven microflows
Authors: Prachittham Virabouth , Picasso Marco , Gijs Martin A. M.
Published: June 2009

A space–time adaptive method is presented for the numerical simulation of mass transport in electroosmotic and pressure‐driven microflows in two space dimensions. The method uses finite elements with large aspect ratio, which allows the electroosmotic flow and the mass transport to be solved accurately despite the presence of strong boundary layers. The unknowns are the external electric potential, the electrical double layer potential, the velocity field and the sample concentration. Continuous piecewise linear stabilized finite elements with large aspect ratio and the Crank–Nicolson scheme are used for the space and time
discretization of the concentration equation. Numerical results are presented showing the efficiency of this approach, first in a straight channel, then in crossing and multiple T‐form configuration channels. Copyright © 2009 John Wiley & Sons, Ltd.
The Laplace transform method for Burgers' equation
Authors: Chen Suqin , Wu Xionghua , Wang Yingwei , Kong Weibin
Published: June 2009

The Laplace transform method (LTM) is introduced to solve Burgers' equation. Because of the nonlinear term in Burgers' equation, one cannot directly apply the LTM. Increment linearization technique is introduced to deal with the situation. This is a key idea in this paper. The increment linearization technique is the following: In time level t, we divide the solution u(x, t) into two parts: u(x, tk) and w(x, t), tk⩽t⩽tk+1, and obtain a time‐dependent linear partial differential equation (PDE) for w(x, t). For this PDE, the LTM is applied to eliminate time dependency. The subsequent boundary value problem is solved by rational collocation method on transformed Chebyshev points. To face the well‐known computational challenge represented by the numerical inversion of the Laplace transform, Talbot's method is applied, consisting of numerically integrating the Bromwich integral on a special contour by means of trapezoidal or midpoint rules. Numerical experiments illustrate that the present method is effective and competitive. Copyright © 2009 John Wiley & Sons, Ltd.
Anterior cingulate cortical volumes and treatment remission of geriatric depression
Authors: Gunning Faith M. , Cheng Janice , Murphy Christopher F. , Kanellopoulos Dora , Acuna Jessica , Hoptman Matthew J. , Klimstra Sibel , Morimoto Shizuko , Weinberg James , Alexopoulos George S.
Published: June 2009

Background

Structural abnormalities of the anterior cingulate cortex (ACC) may interfere with the interaction of cortical and limbic networks involved in emotional regulation and contribute to chronic depressive syndromes in the elderly. This study examined the relationship of regional anterior cingulate cortical volumes with treatment remission of elderly depressed patients. We hypothesized that patients who failed to remit during a 12‐week controlled treatment trial of escitalopram would exhibit smaller anterior cingulate gray matter volumes than patients who remitted.

Methods

The participants were 41 non‐demented individuals with non‐psychotic major depression. After a 2‐week single‐blind placebo period, subjects who still had a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for at least 2 consecutive weeks. The patient sample consisted of 22 depressed patients who achieved remission during the study and 19 depressed patients who remained symptomatic. High‐resolution magnetization‐prepared rapidly acquired gradient echo (MPRAGE) sequences were acquired on a 1.5 T scanner and regional ACC volumes were manually outlined (dorsal, rostral, anterior subgenual, and posterior subgenual).

Results

Repeated measure analyses revealed that patients who failed to remit following escitalopram treatment had smaller dorsal and rostral anterior cingulate gray matter volumes than patients who remitted, whereas subgenual cortical volumes did not differ between the groups.

Conclusions

Structural abnormalities of the dorsal and rostral anterior cingulate may perpetuate late‐life depression. Copyright © 2009 John Wiley & Sons, Ltd.
Disagreement in preference for residential care between family caregivers and elders is greater among cognitively impaired elders group than cognitively intact elders group
Authors: Chau Pui Hing , Kwok Timothy , Woo Jean , Chan Felix , Hui Elsie , Chan Kam Che
Published: June 2009

Objectives

This study examined the predictive factors of preference for residential care in cognitively intact and impaired elders and their family caregivers. It was hypothesized that disagreement in preference for residential care between the elders and their caregivers was greater in the cognitively impaired.

Methods

A cross‐sectional survey was conducted during June 2007 to March 2008 in Hong Kong, and 707 community‐dwelling elders aged 65 and above and 705 family caregivers were interviewed. Cognitively impaired elders were over‐sampled to give reliable estimates for that sub‐group. A structural questionnaire was used to collect data on preference for residential care and potential factors. Logistic regression was used to identify the predictors.

Results

More cognitively impaired elder‐caregiver dyads (37.4%) had disagreement in preference for residential care than cognitively intact elder‐caregiver dyads (20.5%) (p < .001). From the elders' perspective, less preference for residential care was associated with cognitive impairment, whereas greater preference was associated with depression (for cognitively intact elders), more usage of community service and functional impairment. From the caregivers' perspective, greater preference for residential care was associated with greater caregiver burden, or care‐recipients having cognitive or functional impairment, or more usage of community services.

Conclusions

Cognitively intact elders were more likely to indicate preference for residential care than cognitively impaired elders. Elders, both cognitively intact and impaired, were less likely than their caregivers to indicate preference for residential care. Disagreement in preference for residential care between the elders and their caregivers was larger for the cognitively impaired group than the cognitively intact group. Copyright © 2009 John Wiley & Sons, Ltd.
What do Korean American immigrants know about Alzheimer's disease (AD)? The impact of acculturation and exposure to the disease on AD knowledge
Authors: Lee Sang E. , Lee Hee Yun , Diwan Sadhna
Published: June 2009

Objective

The present study examined knowledge of Alzheimer's disease (AD) and factors related to the disease knowledge among Korean American immigrants.

Methods

Two‐hundred and nine middle‐aged and older Korean American immigrants completed a self‐administered questionnaire.

Results

Korean American immigrants had strong stigma about AD and interpreted the disease as a form of insanity. They considered memory loss and AD as a part of the aging process. They seriously lacked knowledge about the treatment, diagnosis and cause of AD. Those who were less acculturated and less exposed to AD were likely to have poorer AD knowledge.

Conclusions

There is a need to expand AD education efforts among Korean American immigrants because the views of stigmatization and normalization of AD combined with certain Asian cultural norms can be barriers to early recognition and intervention. Our study suggests knowledge areas of concentration in AD education and a segment of the population that AD education should target. Further research on symptom knowledge by the disease stages and causal beliefs is needed to better understand the existing views about AD in Korean American immigrants. Copyright © 2009 John Wiley & Sons, Ltd.
Screening for depression in elderly medical inpatients from rural area of Norway: prevalence and associated factors
Authors: Helvik Anne‐Sofie , Skancke Randi H. , Selbæk Geir
Published: June 2009

Aim

The present investigation screened for depression in order to assess the prevalence of depression and to study the associated factors with depression in elderly medically hospitalised patients from a rural area in Norway.

Methods

A cross‐sectional study evaluated 484 (243 women) elderly medical inpatients with age range 65–101 (mean 80.7) years between September 2006 and August 2008 and used the Hospital Anxiety and Depression scale (HAD), Montgomery and Asberg Depression Rating Scale, the Mini‐Mental State Examination, Lawton and Brody's scale for self‐maintaining and instrumental activities of daily living.

Results

The prevalence of current depression, depression score ≥8 at HAD, was for the total sample 10% of whom 78% was previously not diagnosed as having depression. The odds for depression were decreased for women aged 80 years or more while for men at the same age strata it was increased threefold. Age adjusted logistic regression analyses demonstrated an increased odds for depression for those who were in need of nursing assistance before hospitalisation, had lower level of physical functioning, had clinical anxiety symptoms and had higher number of medicaments at inclusion time.

Conclusion

The prevalence of depression in medical hospitalised elderly from rural areas was lower than in most other hospital studies. However, most patients with depression were not previously recognised as being depressed. Copyright © 2009 John Wiley & Sons, Ltd.
Associations between stroke risk and cognition in normal aging and Alzheimer's disease with and without depression
Authors: Bangen Katherine J. , Delano‐Wood Lisa , Wierenga Christina E. , McCauley Ashley , Jeste Dilip V. , Salmon David P. , Bondi Mark W.
Published: June 2009

Background

Stroke risk factors have been increasingly implicated in the development of age‐related cognitive decline, the spectrum of vascular cognitive impairment, and, more recently, Alzheimer's disease (AD). In addition, depression and the apolipoprotein (APOE) ε4 allele have been reported to influence the association between stroke risk and cognition. However, few studies have described the relations among stroke risk, cognition, and APOE genotype in AD, and the findings have been equivocal.

Methods

Thirty cognitively normal older adults, 30 AD patients with depression, and 30 AD patients without depression were administered a comprehensive neuropsychological battery measuring several domains including memory, attention, language, visuospatial skills, executive functions, and speed of information processing. The Framingham Stroke Risk Profile (FSRP), a validated scale that was developed to predict 10‐year probability of stroke, was used to quantify stroke risk burden.

Results

AD patients with depression demonstrated greater stroke risk burden relative to the cognitively normal group and, across all participants, increased stroke risk was associated with poorer performance on memory and processing speed measures. Moreover, stroke risk accurately predicted AD diagnosis. Notably, there were no significant differences in stroke risk or cognitive performance between the AD participants with depression and those without depression.

Conclusion

Given that many markers of stroke risk are modifiable or treatable, our findings have implications for assessment, prevention, and treatment of cognitive decline. Copyright © 2009 John Wiley & Sons, Ltd.
Alcohol use and the labor market in Uruguay
Authors: Balsa Ana I. , French Michael T.
Published: June 2009

This paper is one of only a few studies to examine potential labor market consequences of heavy or abusive drinking in Latin America and the first to focus on Uruguay. We analyzed data from a Uruguayan household survey conducted in 2006 using propensity score matching methods and controlling for a number of socio‐demographic, family, regional, behavioral health, and labor market characteristics. As expected, we found a positive association between heavy drinking and absenteeism, particularly for female employees. Counter to the findings for developed countries, our results revealed a positive relationship between heavy drinking and labor force participation or employment. This result was mostly driven by men and weakened when considering more severe measures of abusive drinking. Possible explanations for these findings are that employment leads to greater alcohol use through an income effect, that the Uruguayan labor market rewards heavy drinking, or that labor market characteristics typical of less developed countries, such as elevated safety risks or job instability, lead to problem drinking. Future research with panel data should explore these possible mechanisms. Copyright © 2009 John Wiley & Sons, Ltd.
Alternative Solid‐Phase Strategies for the Efficient Labelling of Peptides with (Bathophenanthroline)ruthenium(II) Complexes
Authors: Kramer Rolf A. , Bannwarth Willi
Published: June 2009

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To increase the flexibility for the insertion of highly sensitive and robust [RuII(bathophenanthroline)] complexes into peptides, we have evaluated three different solid‐phase strategies (bathophenanthroline=4,7‐diphenyl‐1,10‐phenanthroline). Among these, insertion of the Ru‐complex‐modified lysine building block 9 turned out to be the method of choice (Scheme 5).
1,3‐Dipolar Cycloadditions of a 2‐Oxoethanenitrile Oxide Derived from (2R)‐Bornane‐10,2‐sultam to Electronically Modified 4,4′‐Disubstituted Stilbenes
Authors: Romanski Jan , Chapuis Christian , Jurczak Janusz
Published: June 2009

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Thanks to its type‐II dipole nature, we were able to demonstrate the higher reactivity of the SO2/CO syn‐conformer for the uncatalyzed 1,3‐dipolar cycloaddition of the 2‐oxoethanenitrile oxide 2 derived from bornane‐10,2‐sultam to the symmetric 4,4′‐disubstituted trans‐stilbenes 3a–3i. The C(α)‐si dipolarophile πy approach along the CO bond precludes the use of the steric rules formerly expressed for this pseudo‐C2‐symmetric auxiliary. The observed diastereoselectivity is related to the electronic nature of the dipolarophile and may be predicted on the basis of its σpara Hammett constant. The absolute configuration was based on the X‐ray structure analysis of cycloadduct (4S,5S)‐4b, which exhibits an SO2/CO anti‐conformation. Finally, the results obtained with cis‐stilbene suggest a nonsynchronous mechanism.
Labdane and Tetranorlabdane Diterpenoids from Botryosphaeria sp. MHF, an Endophytic fungus of Maytenus hookeri
Authors: Yuan Lin , Zhao Pei‐Ji , Ma Juan , Lu Chun‐Hua , Shen Yue‐Mao
Published: June 2009

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Five new diterpenoids, named botryosphaerins A–E (1–5, resp.), including one labdane and four tetranorlabdane diterpenes, were isolated from the solid culture of the endophytic fungal strain Botryosphaeria sp. MHF of Maytenus hookeri, together with seven known diterpenoids, namely 13,14,15,16‐tetranorlabd‐7‐ene‐19,6β : 12,17‐diolide (6), acrostalidic acid (7), acrostalic acid (8), agathic acid (9), isocupressic acid (10), LL‐Z1271β (11), and CJ‐14445 (12). The structures of all compounds were established on the basis of comprehensive spectroscopic studies. The relative configurations of 1 and 2 were determined by single‐crystal X‐ray diffraction analyses. All compounds except 4 were evaluated for their inhibitory activities against several pathogenic bacterial and fungal strains. However, only compound 12 showed significant inhibitions against Candida albicans, Saccharomyces cerevisiae, and Penicillium avellaneum UC‐4376 with nystatin as a positive control.
Alkaloids from Aconitum barbatum var. puberulum
Authors: Sun Li‐Mei , Huang Hong‐Li , Li Wen‐Hai , Nan Ze‐Dong , Zhao Gui‐Xia , Yuan Cheng‐Shan
Published: June 2009

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Three new diterpenoid alkaloids, puberulines A–C (1–3, resp.), and three new benzamide derivatives, puberulines D–F (4–6, resp.), as well as 16 known diterpenoid alkaloids were isolated from Aconitum barbatum var. puberulum. The structures of the new compounds were established on the basis of spectral data (IR, EI‐MS, HR‐ESI‐MS, HR‐EI‐MS, 1H‐ and 13C‐NMR, DEPT, NOE, HMQC, 1H,1H‐COSY, HMBC, NOESY, and TOCSY).
Three New Limonoids from Melia toosendan
Authors: Zhou Chun‐Yan , Tang Hai‐Ying , Li Xiang , Sang Yi‐Shu
Published: June 2009

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In order to find new and biologically active compounds, the constituents of the root bark of Melia toosendan were investigated, and three new limonoids, 29‐[(2‐methylbutanoyl)oxy]‐2α‐hydroxyamoorastatone (1), 1,3‐epi‐29‐[(2‐methylbutanoyl)oxy]‐2α‐hydroxyamoorastatone (2), and 1,3‐epi‐29‐[(2‐methylpropanoyl)oxy]‐2α‐hydroxyamoorastatone (3), were isolated from the root bark of Melia toosendan. Their structures were elucidated by means of extensive spectroscopic studies.
Two Novel Resveratrol Trimers from Dipterocarpus grandiflorus
Authors: Ito Tetsuro , Abe Naohito , Oyama Masayoshi , Tanaka Toshiyuki , Murata Jin , Darnaedi Dedy , Iinuma Munekazu
Published: June 2009

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Two new resveratrol (=5‐[(E)‐2‐(4‐hydroxyphenyl)ethenyl]benzene‐1,3‐diol) trimers, grandiphenols C (1) and D (2), were isolated from the stem of Dipterocarpus grandiflorus (Dipterocarpaceae). The structures of 1 and 2 were elucidated by spectral analysis including 1D‐ and 2D‐NMR experiments and by computer‐aided molecular modeling. The NMR characteristics caused by the steric hindrance and the biogenetic relationship of the isolates are also discussed in this work.
Two New Diterpenoid Lactams from Spiraea japonica var. ovalifolia
Authors: Liu Hai‐Yang , Ni Wei , Chen Chang‐Xiang , Di Ying‐Tong , Hao Xiao‐Jiang
Published: June 2009

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Two new diterpenoid alkaloids, spiramilactams A (1) and B (2), were isolated from the basic fraction of a MeOH extract of whole plants of Spiraea japonica var. ovalifolia. Their structures were established on the basis of extensive spectroscopic and mass‐spectrometric analyses.
Lignans and a Sesquiterpene Glucoside from Carissa carandas Stem
Authors: Wangteeraprasert Ruchira , Likhitwitayawuid Kittisak
Published: June 2009

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Two new compounds, the sesquiterpene glucoside carandoside (1) and (6S,7R,8R)‐7a‐[(β‐glucopyranosyl)oxy]lyoniresinol (2), were isolated from the stem of Carissa carandas, together with three known lignans. The structures of the isolated compounds were determined on the basis of spectroscopic evidence. Their DPPH free radical‐scavenging activities were also evaluated.
Oligonucleotide Analogues with Integrated Bases and Backbone. Part 21
Authors: Bogliotti Nicolas , Vasella Andrea
Published: June 2009

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Gelation of organic solvents by the A*[s]U(*) dinucleosides 1 and 2 requires the formation of linear associates cross‐linked by H‐bonding involving either the nucleobase or HOCH2C(6/I). This is evidenced by the absence of gel formation of the N6‐methyladenosine analogue 5 of 1 and the dehydroxy analogue 4 of 2.
Ginkgo biloba: specificity of neuropsychological improvement—a selective review in search of differential effects
Authors: Kaschel Reiner
Published: June 2009

Extracts of Ginkgo biloba are widely used for the treatment of cognitive impairment. Whereas reviews have focused on the question whether ginkgo is effective to enhance cognition in general, little is known about specificity of improvement. This might be crucial for future trials, thus enabling hypotheses about sensitive outcome measures. Therefore, this article summarizes such information, i.e. neuropsychological effects of chronic administration of ginkgo in healthy and cognitively impaired subjects of any age. Objective psychometric test results were considered if they reflected distinct cognitive functions from randomized controlled group‐studies (RCT). We reviewed 29 RCTs yielding 209 placebo‐drug comparisons of psychometric scores in four different cognitive domains comprising 14 sub‐functions. Whereas little specific information can be obtained from trials for treatment of dementia, a pattern of pharmacological actions on cognitive processes emerges here from studies for mild cognitive impairment (MCI), depression, multiple sclerosis and healthy young and elderly subjects. There is consistent evidence that chronic administration improves selective attention, some executive processes and long‐term memory for verbal and non‐verbal material. Further trials should be more comprehensive as there are few data available on some cognitive functions and psychometric flaws in the selection of tests and the interpretation of their results favouring predominantlyβ‐errors. Thus, though this pattern is encouraging it also asks for a cautious interpretation to date. Copyright © 2009 John Wiley & Sons, Ltd.
Oncogenic human papillomaviruses block expression of the B‐cell translocation gene‐2 tumor suppressor gene
Authors: Cullmann Claire , Hoppe‐Seyler Karin , Dymalla Susanne , Lohrey Claudia , Scheffner Martin , Dürst Matthias , Hoppe‐Seyler Felix
Published: June 2009

Human papillomavirus (HPV)‐induced carcinogenesis is critically dependent on the activities of the viral E6 and E7 oncogenes. Here, we demonstrate that expression of the putative tumor suppressor gene B‐cell translocation gene‐2 (BTG2) is reinduced in HPV16‐ and HPV18‐positive cancer cells on silencing of viral oncogene expression, indicating that BTG2 is repressed by oncogenic HPVs. Inhibition of BTG2 expression was mediated by the HPV E6 oncogene and occurred in a p53‐dependent manner. Luciferase reporter gene analyses revealed that BTG2 repression takes place at the transcriptional level and is dependent on the integrity of the major p53‐response element within the BTG2 promoter. Ectopic expression of BTG2 acted antiproliferative in cervical cancer cells. Tissue specimens commonly exhibited reduced BTG2 protein levels in HPV‐positive high‐grade lesions (CIN2/3) and cervical carcinomas, when compared with normal cervical epithelium. These findings identify the antiproliferative BTG2 gene as a novel cellular target blocked by the HPV E6 oncoprotein. © 2009 UICC
Reproductive factors and postmenopausal hormone use in relation to endometrial cancer risk in the Nurses' Health Study cohort 1976–2004
Authors: Karageorgi Stalo , Hankinson Susan E. , Kraft Peter , De Vivo Immaculata
Published: June 2009

Endometrial cancer is a disease primarily driven by cumulative exposure to estrogen unopposed by progesterone. Reproductive factors associated with changes in endogenous hormone levels and use of exogenous hormones such as postmenopausal hormones influence the risk of disease. The authors used the Nurses' Health Study, comprised of 121,700 nurses, to assess the above associations. Over 28 years of follow‐up, 778 adenocarcinoma cases were diagnosed and 1,850,078 person‐years were accumulated. Cox proportional hazards models were used to estimate relative risks (RR) and 95% confidence intervals (CI). A late age at menarche decreased the risk independent of body mass index (BMI) (P‐trend = 0.02). A late age at menopause increased cancer risk (P‐trend = 0.0003). An advanced age at last birth reduced the risk (P‐trend < 0.0001), however, an inverse association with age at first birth and parity diminished after adjustment for age at last birth. Compared with never users, an increased risk was observed among long‐term (≥5 years) users of both estrogen (E) (RR = 7.67, 95% CI: 5.57, 10.57) and combined estrogen plus progesterone (E+P) (RR = 1.52, 95% CI: 1.03, 2.23). Normal‐weight (BMI < 25) women had the highest risk following E or E+P use (P‐interaction‐E = 0.0008, P‐interaction‐E+P = 0.02). The findings from this study underscore the importance of hormonal mechanisms in endometrial carcinogenesis.
Id‐1 promotes tumorigenicity and metastasis of human esophageal cancer cells through activation of PI3K/AKT signaling pathway
Authors: Li Bin , Tsao Sai Wah , Li Yuk Yin , Wang Xianghong , Ling Ming Tat , Wong Yong Chuan , He Qing Yu , Cheung Annie L.M.
Published: June 2009

Id‐1 (inhibitor of differentiation or DNA binding) is a helix‐loop‐helix protein that is overexpressed in many types of cancer including esophageal squamous cell carcinoma (ESCC). We previously reported that ectopic Id‐1 expression activates the phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (AKT) signaling pathway in human esophageal cancer cells. In this study, we confirmed a positive correlation between Id‐1 and phospho‐AKT (Ser473) expressions in ESCC cell lines, as well as in ESCC on a tissue microarray. To investigate the significance of Id‐1 in esophageal cancer progression, ESCC cells with stable ectopic Id‐1 expression were inoculated subcutaneously into the flank of nude mice and were found to form larger tumors that showed elevated Ki‐67 proliferation index and increased angiogenesis, as well as reduced apoptosis, compared with control cells expressing the empty vector.The Id‐1‐overexpressing cells also exhibited enhanced metastatic potential in the experimental metastasis assay. Treatment with the PI3K inhibitor LY294002 attenuated the tumor promotion effects of Id‐1, indicating that the effects were mediated by the PI3K/AKT signaling pathway. In addition, our in vitro experiments showed that ectopic Id‐1 expression altered the expression levels of markers associated with epithelial–mesenchymal transition and enhanced the migration ability of esophageal cancer cells. The Id‐1‐overexpressing ESCC cells also exhibited increased invasive potential, which was in part due to PI3K/AKT‐dependent modulation of matrix metalloproteinase‐9 expression. In conclusion, our results provide the first evidence that Id‐1 promotes tumorigenicity and metastasis of human esophageal cancer in vivo and that the PI3K inhibitor LY294002 can attenuate these effects. © 2009 UICC
Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression
Authors: Bhatia Kishor , Goedert James J. , Modali Rama , Preiss Liliana , Ayers Leona W.
Published: June 2009

Merkel cell polyomavirus (MCPyV) was recently discovered in Merkel cell carcinoma (MCC), a clinically and pathologically heterogeneous malignancy of dermal neuroendocrine cells. To investigate this heterogeneity, we developed a tissue microarray (TMA) to characterize immunohistochemical staining of candidate tumor cell proteins and a quantitative PCR assay to detect MCPyV and measure viral loads. MCPyV was detected in 19 of 23 (74%) primary MCC tumors, but 8 of these had less than 1 viral copy per 300 cells. Viral abundance of 0.06–1.2 viral copies/cell was directly related to presence of retinoblastoma gene product (pRb) and terminal deoxyribonucleotidyl transferase (TdT) by immunohistochemical staining (p ≤ 0.003). Higher viral abundance tumors tended to be associated with less p53 expression, younger age at diagnosis and longer survival (p ≤ 0.08). These data suggest that MCC may arise through different oncogenic pathways, including ones independent of pRb and MCPyV.
Cancer risk among patients with cystic fibrosis and their first‐degree relatives
Authors: Johannesson Marie , Askling Johan , Montgomery Scott M. , Ekbom Anders , Bahmanyar Shahram
Published: June 2009

Patients with cystic fibrosis (CF) are at increased risk of some cancers. Little is known about the cancer risks among carriers heterozygous for the CF mutation and it is hypothesized this may be associated with reduced cancer risk. Using Swedish general population‐based registers, we identified 884 patients with CF from 1968 to 2003 and 3,033 of their first‐degree relatives The subjects were followed from birth of index persons or 1958, whichever came later, until death, emigration or 2003, whichever came first. Cancer risks were compared with the general Swedish population using standardized incidence ratios (SIR) with 95% confidence intervals (CI). Patients, followed for an average of 21 years, were at a higher overall risk of cancer. Some 26 cancer diagnoses, after excluding multiple diagnoses of nonmelanoma skin cancer in one man, produced an overall SIR of 3.2 (95% CI 2.1–4.6). We found statistically significantly increased risks for kidney, thyroid, endocrine, lymphoma and nonmelanoma skin cancer. There was no modification of cancer risk among parents and siblings, with an average of 21 years of follow‐up. This study did not identify a heterozygote advantage for CF gene mutations in relation to cancer risk. © 2009 UICC
Active MMP‐2 effectively identifies the presence of colorectal cancer
Authors: Murnane Mary Jo , Cai Jinguo , Shuja Sania , McAneny David , Klepeis Veronica , Willett John B.
Published: June 2009

Fully active MMP‐2 is expressed at such low levels in human tissues that studies often fail to confirm its value as a cancer marker despite strong associations with malignancy. Our study utilized careful extraction, accurate activity measurements, standardization to purified controls and a new statistical metric to determine whether active MMP‐2 is an effective indicator of colorectal cancer compared to pro‐MMP‐2 or pro‐MMP‐9. MMP‐2 and MMP‐9 activities were analyzed in matched normal and cancer samples from 269 patients by gelatin zymography, computer‐assisted image analysis, serial dilutions of strong samples and standardization to controls. An index of effect size was designed for comparative evaluation of active MMP‐2, pro‐MMP‐2 and pro‐MMP‐9 activities. For each gelatinase, mean activity and protein levels/mg soluble protein in normal mucosa and colorectal cancer were calculated for the first time with respect to commercial standards. Active MMP‐2 activity, detected in 99% of colorectal cancers, was higher in 95% of cancers (on average 10‐fold) than in normal mucosa. Levels of pro‐MMP‐2 and pro‐MMP‐9, but not active MMP‐9, activities were also significantly higher in cancers versus normal. However, active MMP‐2 activity provided the most effective test for the presence of cancer (p < 0.0.0001) with an effect size statistically significantly larger than for either pro‐MMP‐2 or pro‐MMP‐9. Receiver operating characteristic (ROC) curves demonstrated that a cut‐off for active MMP‐2 of >44 SDU activity/mg soluble protein (>180 pg/mg), which is three times mean normal levels, would permit detection of colorectal cancer with an estimated sensitivity of 84% and estimated specificity of 93%. © 2009 UICC
KLF4‐dependent, PPARγ‐induced expression of GPA33 in colon cancer cell lines
Authors: Rageul Julie , Mottier Stéphanie , Jarry Anne , Shah Yatrik , Théoleyre Sandrine , Masson Damien , Gonzalez Frank J. , Laboisse Christian L. , Denis Marc G.
Published: June 2009

The glycoprotein A33 (GPA33) is a colon cancer antigen. Phase I trials with131I and125I monoclonal antibody A33 in colon carcinoma patients showed excellent localization to colorectal cancer and some evidence of tumor response. Using DNA microarrays, we have identified theGPA33gene as a target of PPARγ in HT29‐Cl.16E colon cancer cells. Treatment of HT29‐Cl.16E, Caco2, SW1116 and LS174T colon cancer cells with the PPARγ agonist GW7845 induced a 2‐ to 6‐fold increase in GPA33 mRNA as determined by real‐time PCR. This induction was also found in HT29‐Cl.16E cells treated with rosiglitazone and ciglitazone and was prevented by cotreatment with the PPARγ antagonist GW9662, indicating that this regulation was PPARγ dependent. No canonical PPAR responsive element was found in theGPA33promoter. We therefore analyzed the expression of transcription factors involved in GPA33 expression. CDXl, CDX2 and KLF5 expression was not modified by PPARγ activation. By contrast, a significant increase in KLF4 was seen, both at mRNA and protein levels. Furthermore, chromatin immunoprecipitation studies demonstrated that an increased amount of KLF4 protein was bound to theGPA33promoter in cells treated with rosiglitazone. Finally, downregulation of KLF4 expression by siRNA reduced rosiglitazone‐induced GPA33 expression. This indicates that PPARγ activation induces KLF4 expression, which in turn increases GPA33 expression. We also demonstrate that PPARγ activation leads to increased (p21WAF1/Cip1and keratin 19) or decreased (cyclin D1) expression of known KLF4 targets, suggesting that KLF4 is a nodal player in a network of PPARγ‐regulated genes. © 2009 UICC
BRCA1 modulates malignant cell behavior, the expression of survivin and chemosensitivity in human breast cancer cells
Authors: Promkan Moltira , Liu Guangming , Patmasiriwat Pimpicha , Chakrabarty Subhas
Published: June 2009

BRCA1 is a multifunctional tumor‐suppressive protein. Many functional aspects of BRCA1 are not fully understood. We used a shRNA approach to probe the function of BRCA1 in human breast cancer cells. Knocking down BRCA1 expression by shRNA in the wild‐type BRCA1 human breast cancer MCF‐7 and MDA‐MB‐231 cells resulted in an increase in cell proliferation, anchorage‐independent growth, cell migration, invasion and a loss of p21/Waf1 and p27Kip1 expression. In BRCA1 knocked‐down cells, the expression of survivin was significantly up regulated with a concurrent decrease in cellular sensitivity to paclitaxel. We also found that cells harboring endogenous mutant or defective BRCA1 (MDA‐MB‐436 and HCC1937) were highly proliferative and expressed a relatively low level of p21/Waf1 and p27Kip1 by comparison to wild‐type BRCA1 cells. Cells harboring mutated BRCA1 also expressed a high level of survivin and were relatively resistant to paclitaxel by comparison to wild‐type cells. Increase resistance to paclitaxel was due to an increase in the expression of survivin in both the BRCA1 knocked‐down and mutant BRCA1 cells because knocking down survivin expression by siRNA restored sensitivity to paclitaxel. We conclude that BRCA1 down‐modulates the malignant behavior of breast cancer cells, promotes the expression of p21/Waf1, p27Kip1 and inhibits the expression of survivin. Moreover, loss of BRCA1 expression or function leads to an increase in survivin expression and a reduction in chemosensitivity to paclitaxel. © 2009 UICC