bluuebunny/crossref_metadata_2025 huggingface dataset:
Medieval environmental impacts and feedbacks: The lowland floodplains of England and Wales
Authors: Lewin John
Published: April 2010

Because of their varying channel styles (braided, meandering, and anastomosing) medieval lowland floodplains in England and Wales provided varying opportunities for defense, settlement, river crossing, and resource exploitation. In turn, these activities altered the character of channels and floodplains, with medieval and later development obscuring the former variety of floodplains themselves. The changing nature of river floodplains is reviewed using archaeological, documentary, and geomorphological evidence. Anastomosing channels and floodplain wetlands have now all but disappeared but were formerly of considerable significance; also discussed are interactions involving flooding, fording, bridging, modifications to channels and their dimensions, and those arising from accelerated soil erosion—most of which peaked in the medieval period when floodplains were significantly transformed. Deliberately or inadvertently, dynamic floodplain landforms were interactively involved with human development during a critical time period in a totality of ways not previously fully identified. © 2010 Wiley Periodicals, Inc.
High‐resolution remote sensing and GIS techniques for geobase data supporting archaeological surveys: A case study of ancient Doliche, southeast Turkey
Authors: Prinz Torsten , Lasar Benedikt , Krüger Karl Peter
Published: April 2010

The detection, surveying, and analysis of ancient settlement structures using remote sensing techniques offer a unique opportunity to quickly map the locations of archaeological objects in a relatively short time. High‐resolution images contribute information to the documentation and spatial relation of these objects, especially if Geographic Information Systems (GIS) and Web‐based applications are used. The aim of this study was to assess the potential use of satellite data and aerial imagesacquired by a remote‐controlled balloon to generate geospatial data with a range of resolutions and information depths. The study area was Doliche, in the landscape of ancient Commagene (Turkey), where conventional flight campaigns are impossible or strongly restricted. Recently generated data sets (i.e., topographic maps, ortho‐images, terrain models) were combined with field observations to derive ancient and modern landscape patterns and their possible relation to an assumed “ancient procession road” between the village Doliche (Dülük) and the nearby sanctuary of theRoman divinity Iupiter Dolichenus. © 2010 Wiley Periodicals, Inc.
Estimating gene penetrance from family data
Authors: Gong Gail , Hannon Nathan , Whittemore Alice S.
Published: April 2010

Family data are useful for estimating disease risk in carriers of specific genotypes of a given gene (penetrance). Penetrance is frequently estimated assuming that relatives' phenotypes are independent, given their genotypes for the gene of interest. This assumption is unrealistic when multiple shared risk factors contribute to disease risk. In this setting, the phenotypes of relatives are correlated even after adjustment for the genotypes of any one gene (residual correlation). Many methods have been proposed to address this problem, but their performance has not been evaluated systematically. In simulations we generated genotypes for a rare (frequency 0.35%) allele of moderate penetrance, and a common (frequency 15%) allele of low penetrance, and then generated correlated disease survival times using the Clayton‐Oakes copula model. We ascertained families using both population and clinic designs. We then compared the estimates of several methods to the optimal ones obtained from the model used to generate the data. We found that penetrance estimates for common low‐risk genotypes were more robust to model misspecification than those for rare, moderate‐risk genotypes. For the latter, penetrance estimates obtained ignoring residual disease correlation had large biases. Also biased were estimates based only on families that segregate the risk allele. In contrast, a method for accommodating phenotype correlation by assuming the presence of genetic heterogeneity performed nearly optimally, even when the survival data were coded as binary outcomes. We conclude that penetrance estimates that accommodate residual phenotype correlation (even only approximately) outperform those that ignore it, and that coding censored survival outcomes as binary does not substantially increase the mean‐square errror of the estimates, provided the censoring is not extensive. Genet. Epidemiol. 34: 373–381, 2010. © 2010 Wiley‐Liss, Inc.
Effects of educational interventions on primary dementia care: A systematic review
Authors: Perry M. , Drašković I. , Lucassen P. , Vernooij‐Dassen M. , van Achterberg T. , Rikkert M. Olde
Published: April 2010

Objective

To determine the effects of educational interventions about dementia, directed at primary care providers (PCPs).

Design

We searched Medline, Embase, PsycInfo, Cinahl and the Cochrane library for relevant articles. Two researchers independently assessed the citations identified against the following inclusion criteria: educational intervention on dementia directed at PCPs and study designs being randomized controlled trials (RCTs), controlled clinical trials (CCTs), controlled before and after studies (CBAs) or interrupted time series (ITS) analyses. Outcomes of interest were PCPs' knowledge and attitude on dementia, and quality of dementia care at PCP and patient level.

Results

Of 3953 citations identified, six articles representing five studies (four cluster RCTs and one CBA) were eligible, describing educational interventions directed at 1904 PCPs. Compliance to the interventions varied from 18 to 100%. Systematic review of the studies showed moderate positive results. Five articles reported at least some effects of the interventions. A small group workshop and a decision support system (DSS) increased dementia detection rates. An interactive 2‐h seminar raised GPs' suspicion of dementia. Adherence to dementia guidelines only improved when an educational intervention was combined with the appointment of dementia care managers. This combined intervention also improved patients' and caregivers' quality of life. Effects on knowledge and attitudes were minor.

Conclusion

Educational interventions for PCPs that require active participation improve detection of dementia. Educational interventions alone do not seem to increase adherence to dementia guidelines. To effectively change professionals' performance in primary dementia care, education probably needs to be combined with adequate reimbursement or other organizational incentives. Copyright © 2010 John Wiley & Sons, Ltd.
Effect of mood symptoms on recovery one year after stroke
Authors: Donnellan C. , Hickey A. , Hevey D. , O'Neill D.
Published: April 2010

Background

Depression and anxiety are the most common mood symptoms and psychological consequences of stroke. This study aimed to examine the influence of acute depression and anxiety symptoms on functional recovery and health‐related quality of life (HRQoL) one year after stroke.

Methods

At one month and one year after stroke, the prevalence and severity of depression and anxiety symptoms were examined in consecutively admitted patients, using the Hospital Anxiety and Depression Scale (HADS). Functional recovery was assessed using the Nottingham Extended Activities of Daily Living (NEADL) and HRQoL using the Stroke‐Specific Quality of Life scale (SSQOL).

Results

In 107 patients, the prevalence of depression and anxiety symptoms was 35% at one month and 36% and 34%, respectively, at one year. Depression symptoms were significantly associated with functional ability (r = −0.19, p < 0.05) and HRQoL (r = −0.41, p < 0.001) at one year. Anxiety symptoms were significantly associated with HRQoL (r = −0.33, p < 0.001) only. Multivariate analyses indicated that both depression (β = −0.33, p < 0.001) and anxiety (β = −0.26, p < 0.01) symptoms explained some variance in HRQoL at one month and did not predict functional recovery or HRQoL at one year, after controlling for other independent variables such as stroke severity and pre‐morbid conditions.

Discussion

Mood symptoms following acute stroke were associated with a poorer HRQoL one year later but only depression symptoms influenced functional recovery. Other clinical factors such as pre‐morbid conditions may need to be taken into consideration when determining the effect of mood symptoms on stroke recovery. Copyright © 2010 John Wiley & Sons, Ltd.
Self‐injurious behavior in the nursing home setting
Authors: Mahgoub Nahla , Klimstra Sibel , Kotbi Nabil , Docherty John P
Published: April 2010

Background

Self‐injurious behavior (SIB) in older adults is defined as harm inflicted on oneself without conscious suicidal intent. SIB as a separate entity distinct from suicidal intent is poorly understood. However, it is of great concern to the patients' families and caregivers and it poses serious clinical challenges for clinicians.

Methods

We searched the database of PubMed, Ovid Medline, and ScienceDirect for reports published between 1970 and 2009 using combination of the following keywords: “self‐injurious behavior”, “self‐destructive behavior”, “self‐mutilating behavior”, “older adults”, “geriatric population”, and “nursing homes”. The term “self‐harm behavior” which also appears in the literature is broader in scope than “self‐injurious behavior”. It encompasses high suicide intent and failed suicide attempts; therefore, we excluded this term in order to focus purely on “self‐injurious behavior”. Our search yielded 10 publications concerning SIB in older adults, four of which included studies investigating SIB in nursing homes.

Results

Clinical studies of SIB in older adult nursing home residents are sparse. This limited literature suggests that SIB is a prevalent phenomenon and is reported to be as high as 14% in one study of nursing home subjects aged 65 and older. It is reported to be strongly associated with dementia and a risk of accidental death. It has been suggested that SIB among demented patients occurs in the context of poor impulse control and physical isolation.

Conclusion

SIB is likely a common phenomenon in older adult nursing home residents. There is little evidence‐based treatment guidance for SIB in older population. Copyright © 2010 John Wiley & Sons, Ltd.
Baseline leisure time activity and cognition more than two decades later
Authors: Kåreholt Ingemar , Lennartsson Carin , Gatz Margaret , Parker Marti G.
Published: April 2010

Objective

Many studies of the relation between factors earlier in life and late‐life cognition have a short follow‐up time, often less than 10 years. Since cognitive decline can be present up to 20 years prior to dementia it is difficult to distinguish the direction of the relationships without a long follow‐up. We analyzed the association between different types of leisure time activity at baseline and cognition more than 20 years later. A wide range of activities was included—political, mental, socio‐cultural, social, physical, and organizational activities.

Methods

Baseline studies were random Swedish samples aged 46–75 years (mean 57.4) (n = 1643) interviewed in 1968 or 1981. Activities were measured at baseline. Cognition was measured with items from the Mini‐Mental State Examination in 1992, 2002, or 2004.

Results

There was a significant association between later cognition and earlier political, mental, and socio‐cultural activities controlling for age, age‐square, sex, follow‐up‐time, mobility problems, symptoms of mental distress, employment status, education, adult and childhood socioeconomic status, income, smoking, and drinking. Physical activities had a significant association with cognition only among women. Organizational activities were not significant when controlling for all covariates. Social activities had no significant association. Including all covariates and all leisure activities simultaneously, only mid‐life political and mental activities remained significantly related to later life cognition.

Conclusions

These findings add support to the theory that various forms of engagement in mid‐life can have a protective effect with respect to cognition in later life. Copyright © 2010 John Wiley & Sons, Ltd.
The AddNeuroMed framework for multi‐centre MRI assessment of Alzheimer's disease : experience from the first 24 months
Authors: Simmons Andrew , Westman Eric , Muehlboeck Sebastian , Mecocci Patrizia , Vellas Bruno , Tsolaki Magda , Kłoszewska Iwona , Wahlund Lars‐Olof , Soininen Hilkka , Lovestone Simon , Evans Alan , Spenger Christian
Published: April 2010

Objective

To describe the AddNeuroMed imaging framework for multi‐centre magnetic resonance imaging (MRI) assessment of longitudinal changes in Alzheimer's disease and report on early results from the first 24 months of the project.

Methods

A multi‐centre study similarly to a faux clinical trial has been established to assess longitudinal MRI changes in Alzheimer disease (AD), mild cognitive impairment (MCI) and healthy control subjects using an image acquisition protocol compatible with Alzheimer disease neuroimaging initiative (ADNI). Comprehensive quality control (QC) measures have been established throughout the study. An intelligent web‐accessible database holds details on both the raw images and data processed using a sophisticated image analysis pipeline.

Results

A total of 378 subjects have been recruited (130 AD, 131 MCI, 117 healthy controls) of which a high percentage (97.3%) of the T1‐weighted volumes passed the QC criteria. Measurements of normalized whole brain volume and whole brain cortical thickness showed significant differences between AD and controls, AD and MCI and MCI and controls.

Conclusions

A framework for multi‐centre MRI studies of Alzheimer's disease has been established consisting of a harmonized MRI acquisition protocol across centres, rigorous QC at both the sites and central data analysis hub and an automated image analysis pipeline. Early results demonstrate the high quality of the images acquired and the applicability of the automated image analysis techniques employed. Copyright © 2010 John Wiley & Sons, Ltd.
The effect of memantine on sleep behaviour in dementia with Lewy bodies and Parkinson's disease dementia
Authors: Larsson Victoria , Aarsland Dag , Ballard Clive , Minthon Lennart , Londos Elisabet
Published: April 2010

Objective

Two common and characteristic sleep disturbances have been described in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD); excessive daytime sleepiness and REM sleep behaviour disorder (RBD). This study is an analysis of a secondary outcome measure of a larger study already reported, aimed to determine whether memantine has an effect on the sleep disturbances in DLB and PDD patients.

Methods

Patients with DLB or PDD were included in a placebo‐controlled, randomised controlled study of memantine (20 mg per day) for 24 weeks. The Stavanger Sleep Questionnaire and the Epworth Sleepiness Scale were used to evaluate the effect on sleep disturbances.

Results

Forty two patients started treatment; 20 with memantine and 22 with placebo. The primary analysis was the comparison of change between the two groups during a 24‐week period, using the modified ITT population (last observation carried forward). At 24 weeks, patients treated with memantine were less physically active during sleep while patients in the placebo group worsened. Mean difference between the groups (0.5 [0.05–0.90]) was significant (p = 0.006). No significant change was observed in severity of excessive daytime sleepiness.

Conclusions

Memantine decreases probable REM sleep behaviour disorder in patients with DLB and PDD. Both diagnostic groups contributed equally to the outcome. Copyright © 2010 John Wiley & Sons, Ltd.
The growth of brain tumors can be suppressed by multiple transplantation of mesenchymal stem cells expressing cytosine deaminase
Authors: Chang Da‐Young , Yoo Seung‐Wan , Hong Youngtae , Kim Sujeong , Kim Se Joong , Yoon Sung‐Hwa , Cho Kyung‐Gi , Paek Sun Ha , Lee Young‐Don , Kim Sung‐Soo , Suh‐Kim Haeyoung
Published: April 2010

Suicide genes have recently emerged as an attractive alternative therapy for the treatment of various types of intractable cancers. The efficacy of suicide gene therapy relies on efficient gene delivery to target tissues and the localized concentration of final gene products. Here, we showed a potential ex vivo therapy that used mesenchymal stem cells (MSCs) as cellular vehicles to deliver a bacterial suicide gene, cytosine deaminase (CD) to brain tumors. MSCs were engineered to produce CD enzymes at various levels using different promoters. When co‐cultured, CD‐expressing MSCs had a bystander, anti‐cancer effect on neighboring C6 glioma cells in proportion to the levels of CD enzymes that could convert a nontoxic prodrug, 5‐fluorocytosine (5‐FC) into cytotoxic 5‐fluorouracil (5‐FU) in vitro. Consistent with the in vitro results, for early stage brain tumors induced by intracranial inoculation of C6 cells, transplantation of CD‐expressing MSCs reduced tumor mass in proportion to 5‐FC dosages. However, for later stage, established tumors, a single treatment was insufficient, but only multiple transplantations were able to successfully repress tumor growth. Our findings indicate that the level of total CD enzyme activity is a critical parameter that is likely to affect the clinical efficacy for CD gene therapy. Our results also highlight the potential advantages of autograftable MSCs compared with other types of allogeneic stem cells for the treatment of recurrent glioblastomas through repetitive treatments.
Human papillomavirus genotype in cervical intraepithelial neoplasia grades 2 and 3 of Taiwanese women
Authors: Chao Angel , Jao Mei‐Shan , Huang Chu‐Chun , Huang Huei‐Jean , Cheng Hui‐Hsin , Yang Jung‐Erh , Hsueh Swei , Chen Tse‐Ching , Qiu Jian‐Tai , Lin Cheng‐Tao , Fu Chang‐Jui , Chou Hung‐Hsueh , Lai Chyong‐Huey
Published: April 2010

We aimed to assess the distribution of human papillomavirus (HPV) genotypes in high‐grade cervical lesions in Taiwan. The study included 1,086 paraffin‐embedded, formaldehyde‐fixed cervical intraepithelial neoplasia (CIN) 2/3 specimens. HPV genotyping was performed using polymerase chain reaction (PCR)‐based methods. Multiple HPV types were validated by E6 type‐specific PCR, direct sequencing and/or real‐time PCR. HPV DNA was detected in 995 (91.6%) specimens, and multiple HPV types were identified in 192 (19.3%) samples. The leading HPV types were HPV16 (24%), HPV52 (20%), HPV58 (20%), HPV33 (13%), HPV31 (8%) and HPV18 (4.6%). Although the leading six types consisted of 87.6%, HPV16 or 18 comprised only 30.9%. The prevalence of different HPV types showed a significant association with age. In women older than 50 yr, HPV16 and 18 comprised 21.3% (83/389), while HPV52, 58 and 33 represented 55.5% (216/389). In women aged less than 50 yr, HPV16 and 18 comprised 32.1% (224/697, p < 0.0001), while HPV 52, 58 and 33 represented 47.9% (334/697, p = 0.02). The distribution of HPV genotypes was compared with previously reported findings for Taiwanese women with cervical cancer (CC). The overall HPV16 positivity rate was significantly higher in CC than in CIN 2/3 (odds ratio: 2.14, 95% CI: 1.91–2.40). In addition, HPV18, 39 and 45 were significantly overrepresented in CC, whereas HPV52, 58, 33, 31, 35, 51 and 53 were underrepresented. We concluded that an effective vaccine against the most common HPV types could prevent a significant proportion of cervical cancer cases that occur in Taiwan.
Association of haplotypes of inflammation‐related genes with gastric preneoplastic lesions in African Americans and Caucasians
Authors: Zabaleta Jovanny , Camargo Maria C. , Ritchie Marylyn D. , Piazuelo Maria B. , Sierra Rosa A. , Turner Stephen D. , Delgado Alberto , Fontham Elizabeth T.H. , Schneider Barbara G. , Correa Pelayo , Ochoa Augusto C.
Published: April 2010

Identification of biomarkers is needed for development of screening programs to prevent gastric cancer. Because racial differences exist in cancer rates, we aimed to evaluate the association between polymorphisms in inflammation‐related genes and gastric preneoplastic lesions in African Americans and Caucasians from Louisiana, USA. Gastric biopsies from 569 adults (361 African Americans and 208 Caucasians) undergoing diagnostic endoscopy were used for histological diagnosis and genomic DNA extraction. Polymorphisms within eight genes (IL1B, IL8, IL6, TNF, PTGS2, ARG1, IL10 and TGFB1) were investigated by TaqMan. The cagA status of Helicobacter pylori infection was assessed by PCR. Haplotype logistic regression models were used to identify variables associated with intestinal metaplasia or dysplasia. African Americans carrying the haplotype IL1B‐511T/−31C/+3954T, which includes the three risk‐associated alleles at the IL1B locus, were more likely to being diagnosed with intestinal metaplasia or dysplasia than those carrying the most common haplotype T‐C‐C (adjusted OR: 2.51, 95% CI: 1.1–5.5). None of the polymorphisms were associated with intestinal metaplasia and dysplasia in Caucasians. Age and cagA‐positive status were independent factors associated with these lesions. Haplotypes at the IL1B locus may participate in mediating the susceptibility to gastric carcinogenesis and might be useful as markers of advanced premalignant lesions in African Americans. Interestingly, carriage of IL1B+3954T allele seems to be the key factor, even though the role played by other polymorphisms cannot be excluded.
Higher susceptibility to aflatoxin B1‐related hepatocellular carcinoma in glycine N‐methyltransferase knockout mice
Authors: Liu Shih‐Ping , Li Ying‐Shiuan , Lee Cheng‐Ming , Yen Chia‐Hung , Liao Yi‐Jen , Huang Shiu‐Feng , Chien Chau‐Heng , Chen Yi‐Ming Arthur
Published: April 2010

In both humans and rodents, males are known to be more susceptible than females to hepatocarcinogenesis. We have previously reported that glycine N‐methyltransferase (GNMT) interacts with aflatoxin B1 (AFB1) and reduces both AFB1‐DNA adduct formation and hepatocellular carcinoma (HCC) in mice. We also reported that 50% of the males and 100% of the females in a small group of Gnmt null (Gnmt−/−) mice developed HCC, with first dysplastic hepatocellular nodules detected at mean ages of 17 and 16.5 months, respectively. In our study, we tested our hypothesis that male and female Gnmt−/− mice are susceptible to AFB1 carcinogenesis, and that the absence of Gnmt expression may accelerate AFB1‐induced liver tumorigenesis. We inoculated Gnmt−/− and wild‐type mice intraperitoneally with AFB1 at 7 days and 9 weeks of age and periodically examined them using ultrasound. Dysplastic hepatocellular nodules were detected in six of eight males and five of five females at 12.7 and 12 months of ages, respectively. Dysplastic hepatocellular nodules from 5/8 (62.5%) male and 4/5 (80%) female Gnmt−/− mice were diagnosed as having HCC, ∼6 months earlier than AFB1‐treated wild‐type mice. Results from microarray and real‐time PCR analyses indicate that five detoxification pathway‐related genes were downregulated in AFB1‐treated Gnmt−/− mice: Cyp1a2, Cyp3a44, Cyp2d22, Gsta4 and Abca8a. In summary, we observed overall higher susceptibility to AFB1‐related HCC in Gnmt−/− mice, further evidence that GNMT overexpression is an important contributing factor to liver cancer resistance.
Enhancement of DNA vaccine potency by antigen linkage to IFN‐γ‐inducible protein‐10
Authors: Kang Tae Heung , Kim Keon Woo , Bae Hyun Cheol , Seong Seung‐Yong , Kim Tae Woo
Published: April 2010

DNA vaccines have emerged as an attractive approach to generate antigen‐specific T‐cell immune response. Nevertheless, the potency of DNA vaccines still needs to be improved for cancer immunotherapy. In this study, we explored whether functional linkage of a Th1‐polarizing chemokine, IP‐10, to a model tumor antigen, human papillomavirus type 16 (HPV‐16) E7, enhanced DNA vaccine potency. IP‐10 linkage changed the location of E7 from the nucleus to the endoplasmic reticulum and led to the secretion of functionally chemoattractive chimeric IP‐10/E7 protein. In addition, this linkage drastically enhanced the endogenous processing of E7 antigen through MHC class I. More importantly, we found that C57BL/6 mice intradermally vaccinated with IP‐10/E7 DNA exhibited a dramatic increase in the number of E7‐specific CD4+ Th1 T‐cells and CD8+ T‐cells and, consequently, were strongly resistant over the long term to E7‐expressing tumors compared to mice vaccinated with wild‐type E7 DNA. Thus, because of the increase in tumor antigen‐specific T‐cell immune responses obtained through both enhanced antigen presentation and chemoattraction, vaccination with DNA encoding IP‐10 linked to a tumor antigen holds great promise for treating tumors.
Role of mesenchymal stem cells in tissue engineering of meniscus
Authors: Zellner Johannes , Mueller Michael , Berner Arne , Dienstknecht Thomas , Kujat Richard , Nerlich Michael , Hennemann Burkhard , Koller Michael , Prantl Lukas , Angele Martin , Angele Peter
Published: April 2010

Tissue engineering is a promising approach for the treatment of tissue defects. Mesenchymal stem cells are of potential use as a source of repair cells or of important growth factors for tissue engineering. The purpose of this study was to examine the role of mesenchymal stem cells in meniscal tissue repair. This was tested using several cell and biomaterial‐based treatment options for repair of defects in the avascular zone of rabbit menisci. Circular meniscal punch defects (2 mm) were created in the avascular zone of rabbit menisci and left empty or filled with hyaluronan‐collagen composite matrices without cells, loaded with platelet‐rich plasma, autologous bone marrow, or autologous mesenchymal stem cells. In some experiments, matrices with stem cells were precultured in chondrogenic medium for 14 days before implantation. Rabbits were then allowed free cage movement after surgery for up to 12 weeks. Untreated defects and defects treated with cell‐free implants had muted fibrous healing responses. Neither bone marrow nor platelet‐rich plasma loaded in matrices produced improvement in healing compared with cell‐free implants. The implantation of 14 days precultured chondrogenic stem cell‐matrix constructs resulted in fibrocartilage‐like repair tissue, which was only partially integrated with the native meniscus. Non‐precultured mesenchymal stem cells in hyaluronan‐collagen composite matrices stimulated the development of completely integrated meniscus‐like repair tissue. The study shows the necessity of mesenchymal stem cells for the repair of meniscal defects in the avascular zone. Mesenchymal stem cells seem to fulfill additional repair qualities besides the delivery of growth factors. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Epidermal and dermal integration into sphere‐templated porous poly(2‐hydroxyethyl methacrylate) implants in mice
Authors: Fukano Y. , Usui M. L. , Underwood R. A. , Isenhath S. , Marshall A. J. , Hauch K. D. , Ratner B. D. , Olerud J. E. , Fleckman P.
Published: April 2010

Percutaneous medical devices remain susceptible to infection and failure. We hypothesize that healing of the skin into the percutaneous device will provide a seal, preventing bacterial attachment, biofilm formation, and subsequent device failure. Porous poly(2‐hydroxyethyl methacrylate) [poly(HEMA)] with sphere‐templated pores (40 μm) and interconnecting throats (16 μm) were implanted in normal C57BL/6 mice for 7, 14, and 28 days. Poly(HEMA) was either untreated, keeping the surface nonadhesive for cells and proteins, or modified with carbonyldiimidazole (CDI) or CDI reacted with laminin 332 to enhance adhesion. No clinical signs of infection were observed. Epidermal and dermal response within the poly(HEMA) pores was evaluated using light and transmission electron microscopy. Cells (keratinocytes, fibroblasts, endothelial cells, inflammatory cells) and basement membrane proteins (laminin 332, β4 integrin, type VII collagen) could be demonstrated within the poly(HEMA) pores of all implants. Blood vessels and dermal collagen bundles were evident in all of the 14‐ and 28‐day implants. Fibrous capsule formation and permigration were not observed. Sphere‐templated polymers with 40 μm pores demonstrate an ability to recapitulate key elements of both the dermal and the epidermal layers of skin. Our morphological findings indicate that the implant model can be used to study the effects of biomaterial pore size, pore interconnect (throat) size, and surface treatments on cutaneous biointegration. Further, this model may be used for bacterial challenge studies. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Isolation and characterization of a novel copper‐inducible metallothionein gene of a ciliate, Tetrahymena tropicalis lahorensis
Authors: Chaudhry Raheela , Shakoori Abdul Rauf
Published: April 2010

The two isoforms of copper metallothionein (CuMT) gene of a copper resistant ciliate, Tetrahymena tropicalis lahorensis (Ttl), have been isolated and characterized. The molecular cloning and nucleotide sequencing of cDNAs coding for the two CuMT isoforms revealed that TtlCuMT1 gene has 300, while TtlCuMT2 has 327 nucleotides, both with ATG as the initiation codon and TGA as the translational termination codon. TAG codes for glutamine in TtlCuMT2 gene which is peculiar to Tetrahymena. The deduced or translated TtlCuMT1 and TtlCuMT2 peptide sequences contain 100 and 108 amino acid residues including 28 and 32 cysteine residues, respectively. The amino acid sequences of TtlCuMT1 and TtlCuMT2 have special features of two and three CXCXXCXCXXCXC intragenic tandem repeats with a conserved structural pattern of cysteine, respectively. The predicted tertiary structures of these two isoforms indicate two domains. Domain I and the initial part of domain II showed >98% homology with other Tetrahymena CuMT. On the basis of the differences in the domain II, the metallothionein subfamily 7b can be divided into two groups, one (TtlCuMT1) comprising >100 amino acids and the other (TtlCuMT2) comprising <100 amino acids. This is a novel finding of the present study as no such report on this type of classification exists at the moment. TtlCuMT1 has 95%, while TtlCuMT2 has 97% resemblance with the previously reported CuMT genes of Tetrahymena spp. SDS‐PAGE analysis using fluorescent probe as well as coomassie brilliant blue staining also confirmed the presence of metallothionein. J. Cell. Biochem. 110: 630–644, 2010. © 2010 Wiley‐Liss, Inc.
Carboxylated N‐glycans on RAGE promote S100A12 binding and signaling
Authors: Srikrishna Geetha , Nayak Jonamani , Weigle Bernd , Temme Achim , Foell Dirk , Hazelwood Larnele , Olsson Anna , Volkmann Niels , Hanein Dorit , Freeze Hudson H.
Published: April 2010

The receptor for advanced glycation end products (RAGE) is a signaling receptor protein of the immunoglobulin superfamily implicated in multiple pathologies. It binds a diverse repertoire of ligands, but the structural basis for the interaction of different ligands is not well understood. We earlier showed that carboxylated glycans on the V‐domain of RAGE promote the binding of HMGB1 and S100A8/A9. Here we study the role of these glycans on the binding and intracellular signaling mediated by another RAGE ligand, S100A12. S100A12 binds carboxylated glycans, and a subpopulation of RAGE enriched for carboxylated glycans shows more than 10‐fold higher binding potential for S100A12 than total RAGE. When expressed in mammalian cells, RAGE is modified by complex glycans predominantly at the first glycosylation site (N25IT) that retains S100A12 binding. Glycosylation of RAGE and maximum binding sites for S100A12 on RAGE are also cell type dependent. Carboxylated glycan‐enriched population of RAGE forms higher order multimeric complexes with S100A12, and this ability to multimerize is reduced upon deglycosylation or by using non‐glycosylated sRAGE expressed in E. coli. mAbGB3.1, an antibody against carboxylated glycans, blocks S100A12‐mediated NF‐κB signaling in HeLa cells expressing full‐length RAGE. These results demonstrate that carboxylated N‐glycans on RAGE enhance binding potential and promote receptor clustering and subsequent signaling events following oligomeric S100A12 binding. J. Cell. Biochem. 110: 645–659, 2010. © 2010 Wiley‐Liss, Inc.
Controlled delivery of the heparan sulfate/FGF‐2 complex by a polyelectrolyte scaffold promotes maximal hMSC proliferation and differentiation
Authors: Calarco Anna , Petillo Orsolina , Bosetti Michela , Torpedine Angela , Cannas Mario , Perrone Lorena , Galderisi Umberto , Melone Mariarosa A.B. , Peluso Gianfranco
Published: April 2010

Growth factors and other regulatory molecules are required to direct differentiation of bone marrow‐derived human mesenchymal stem cells (hMSC) along specific lineages. However, the therapeutic use of growth factors is limited by their susceptibility to degradation, and the need to maintain prolonged local release of growth factor at levels sufficient to stimulate hMSC. The aim of this study was to investigate whether a device containing heparan sulfate (HS), which is a co‐factor in growth factor‐mediated cell proliferation and differentiation, could potentiate and prolong the delivery of fibroblast growth factor‐2 (FGF‐2) and thus enhance hMSC stimulation. To this aim, we synthesized cationic polyelectrolyte polymers covalently and non‐covalently anchored to HS and evaluated their effect on hMSC proliferation. Polymers non‐covalently bound to HS resulted in the release of an HS/FGF‐2 complex rather than FGF‐2 alone. The release of this complex significantly restored hMSC proliferation, which was abolished in serum‐free medium and only partially restored by the release of FGF‐2 alone as occurred with polymer covalently bound to HS. We also demonstrate that exposure to HS/FGF‐2 during early growth but not during post‐confluence is essential for hMSC differentiation down the fibroblast lineage, which suggests that both factors are required to establish the correct stem cell commitment that is necessary to support subsequent differentiation. In conclusion, the delivery platform described here is a step towards the development of a new class of biomaterial that enables the prolonged, non‐covalent binding and controlled delivery of growth factors and cofactors without altering their potency. J. Cell. Biochem. 110: ??–??, 2010. © 2010 Wiley‐Liss, Inc.
Biology and pathology of Rho GTPase, PI‐3 kinase‐Akt, and MAP kinase signaling pathways in chondrocytes
Authors: Beier Frank , Loeser Richard F.
Published: April 2010

Chondrocytes provide the framework for the developing skeleton and regulate long‐bone growth through the activity of the growth plate. Chondrocytes in the articular cartilage, found at the ends of bones in diarthroidial joints, are responsible for maintenance of the tissue through synthesis and degradation of the extracellular matrix. The processes of growth, differentiation, cell death and matrix remodeling are regulated by a network of cell signaling pathways in response to a variety of extracellular stimuli. These stimuli consist of soluble ligands, including growth factors and cytokines, extracellular matrix proteins, and mechanical factors that act in concert to regulate chondrocyte function through a variety of canonical and non‐canonical signaling pathways. Key chondrocyte signaling pathways include, but are not limited to, the p38, JNK and ERK MAP kinases, the PI‐3 kinase‐Akt pathway, the Jak‐STAT pathway, Rho GTPases and Wnt‐β‐catenin and Smad pathways. Modulation of the activity of any of these pathways has been associated with various pathological states in cartilage. This review focuses on the Rho GTPases, the PI‐3 kinase‐Akt pathway, and some selected aspects of MAP kinase signaling. Most studies to date have examined these pathways in isolation but it is becoming clear that there is significant cross‐talk among the pathways and that the overall effects on chondrocyte function depend on the balance in activity of multiple signaling proteins. J. Cell. Biochem. 110: 573–580, 2010. © 2010 Wiley‐Liss, Inc.
The development of the conditionally replication‐competent adenovirus: replacement of E4 orf1‐4 region by exogenous gene
Authors: Nam Jae‐Kook , Lee Mi‐Hyang , Seo Hae‐Hyun , Kim Seok‐Ki , Lee Kang‐Huyn , Kim In‐Hoo , Lee Sang‐Jin
Published: April 2010

Background

Tumor or tissue specific replicative adenovirus armed with a therapeutic gene has shown a promising anti‐cancer therapeutic modality. However, because the genomic packaging capacity is constrained, only a few places inside it are available for transgene insertion. In the present study, we introduce a novel strategy utilizing the early E4 region for the insertion of therapeutic gene(s).

Methods

We constructed the conditionally replication‐competent adenovirus (CRAd), Ad5E4(mRFP) by: (i) replacing the E4/E1a promoter by the prostate‐specific enhancer element; (ii) inserting mRFP inside the E4orf1‐4 deletion region; and (iii) sub‐cloning enhanced green fluorescent protein controlled by cytomegalovirus promoter in the left end of the viral genome. Subsequently, we evaluated its replication abilities and killing activities in vitro, as well as its in vivo anti‐tumor efficacy in CWR22rv xenografts.

Results

When infected with Ad5E4(mRFP), the number and intensity of the mRFP gene products increased in a prostate cancer cell‐specific manner as designed, suggesting that the mRFP gene and E4orfs other than E4orf1‐4 were well synthesized from one transcript via alternative splicing as the recombinant adenovirus replicated. As expected from the confirmed virus replication capability, Ad5E4(mRFP) induced cell lysis as potent as the wild‐type adenovirus and effectively suppressed tumor growth when tested in the CWR22rv xenografts in nude mice. Furthermore, Ad5E4(endo/angio) harboring an endostatin‐angiostatin gene in E4orf1‐4 was able to enhance CRAd by replacing mRFP with a therapeutic gene.

Conclusions

The approach employed in the present study for the insertion of a therapeutic transgene in CRAd should facilitate the construction of CRAd containing multiple therapeutic genes in the viral genome that may have the potential to serve as highly potent cancer therapeutic reagents. Copyright © 2010 John Wiley & Sons, Ltd.
Synthesis of new 4‐oxo‐thiazolidine‐5‐ylidenes of antitumor and antioxidant activities
Authors: Aly Ashraf A. , Brown Alan B. , Abdel‐Aziz Mohamed , Abuo‐Rahma Gamal El‐Din A. A. , Radwan Mohamed F. , Ramadan Mohamed , Gamal‐Eldeen Amira M.
Published: April 2010

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Reaction of diacyl thiocarbohydrazides with dimethyl but‐2‐ynedioate in refluxing ethanol led to 4‐oxa‐thiazolidine‐5‐ylidene‐acetates in good yields. Reaction of the newly prepared N‐(2‐(propan‐2‐ylidene) hydrazine‐carbonothioyl)arylhydrazides with dimethyl but‐2‐ynedioate gave the corresponding (Z)‐methyl‐2‐arylhydrazide‐4‐oxo‐3‐(propan‐2‐ylideneamino)thiazolidine‐5‐ylidene)‐acetates. The mechanism is discussed. Antitumor and antioxidant activities have been also investigated. J. Heterocyclic Chem., (2010).
Flux measurements in Cairo. Part 1: in situ measurements and their applicability for comparison with satellite data
Authors: Frey Corinne M. , Parlow Eberhard , Vogt Roland , Harhash Maha , Abdel Wahab Mohammad M.
Published: April 2010

Cairo Air Pollution and Climate (CAPAC) is dedicated to the understanding of the urban energy balance in Cairo, Egypt, through measurements from space and at ground stations. The in situ measurements will provide a focussed insight into three carefully chosen microclimates (urban, suburban‐agriculture, and suburban‐desert) and provide at the same time ground‐truth data for satellite image analysis, which will expand the acquired knowledge into the spatial domain. In situ measurements were made during a field campaign in Greater Cairo from November 2007 to February 2008. In this study, the dataset of the CAPAC measurement campaign will be presented and analysed in terms of use for a remote sensing study. Measured variables complied with our expectations. The urban area featured a distinct nocturnal heat island. During the day the choice of reference station was responsible for the magnitude of the heat island. The diurnal cycle of radiative temperature at the suburban‐desert station clearly exceeded the one at the urban station, thus the urban setting seemed to have a better heat storage than the suburban‐desert. The stations also determined the partitioning of the turbulent heat fluxes. While in Cairo and at the suburban‐desert station most of the available energy was partitioned into the sensible heat flux, the suburban‐agricultural station maintained a high latent heat flux. The radiation and soil heat flux measurements proved to be applicable for comparison with remotely sensed data. However, the analysis of the turbulent heat fluxes showed that several constraints exist: measured fluxes tend to underestimate the actual flux and directional effects complicate the interpretation. An energy balance closure and footprint modelling is necessary to compare measured fluxes with satellite image retrieved products. Finally, turbulent fluxes are time averages, which is contrary to the remote sensing principle. Consequently, a direct use is problematic. Copyright © 2010 Royal Meteorological Society
Urban warming in Japanese cities and its relation to climate change monitoring
Authors: Fujibe Fumiaki
Published: April 2010

This article briefly reviews urban warming studies in Japan, where many of the stations established by the beginning of the 20th century are located in cities that have undergone rapid industrialization. The recorded rate of temperature increase is a few degrees per century in large cities and tends to be larger at night than during the daytime. In some cities, the increase in annual extreme minimum temperature exceeds 10 °C century−1. On the other hand, recent numerical studies have revealed widespread urban warming around Tokyo and other megacities during afternoons of the warm season as a result of extensive urbanization that enhances daytime surface heating. An analysis using data from the dense Automated Meteorological Data Acquisition System network has shown that an urban bias in recent temperature trends is detectable not only in densely inhabited areas but also at slightly urbanized sites with 100–300 people km−2, indicating the need for careful assessment of the background climate change. There is also some evidence of microscale effects on observed temperature, as revealed by an analysis of the relationship between trends in temperature and wind speed. Copyright © 2010 Royal Meteorological Society
Rainfall history for the Hexi Corridor in the arid northwest China during the past 620 years derived from tree rings
Authors: Yang Bao , Qin Chun , Bräuning Achim , Burchardt Iris , Liu Jingjing
Published: April 2010

We present a 620‐year long ring width record from the middle Qilian Mountains, where it is presently controlled by the Westerlies. The chronology was developed from Qilian juniper (Sabina przewalskii) growing at sites near the western distribution limit of the species in the northern Qilian Mountains, Gansu Province, China. A linear regression model between ring width and annual (July to June) precipitation accounts for 34.9% of the observed instrumental precipitation variance during the period 1952 to 2007. Spatial correlation analyses between the reconstruction and gridded precipitation data shows that the annual precipitation reconstruction captures regional climatic variations over the Qilian Mountains and the nearby Hexi Corridor. We also show the scaled standard chronology adjusted to the mean and variance of the instrumental data. Relatively wet periods are identified for AD 1390–1413, 1425–1450, 1530–1649, 1792–1920, 1937–1949 and 1980–1985. Dry conditions prevailed during AD 1414–1424, 1451–1529, 1650–1791, 1921–1936, 1950–1979 and 1986–2007. In comparison with the regression‐based reconstruction, the scaled reconstruction indicates considerably wetter conditions during 1390–1413, 1425–1450, 1570–1630 and 1790–1920. The interval AD 1451–1529 was the most intense and longest drought epoch in the Hexi Corridor over the past six centuries. This drought was not only recorded in the Qilian Mountains but also occurred in northern and eastern China. It might be caused by a substantial weakening of the Asian summer monsoon induced by the joint effects of solar and volcanic activities at that time. Our results also suggest that the Hexi Corridor was under the control of the Asian monsoon circulation on inter‐decadal to centennial timescales in the past centuries. Copyright © 2010 Royal Meteorological Society
Global memory analysis in observed and simulated CAPE and CIN
Authors: Riemann‐Campe Kathrin , Blender Richard , Fraedrich Klaus
Published: April 2010

The memory of convective precipitation is estimated via the analysis of the convective parameters convective available potential energy (CAPE) and convective inhibition (CIN). The variability of mixed layer (ML) CAPE and CIN in present‐day climate is presented in terms of a linear decay time scale for short‐term memory and the Hurst exponent for long‐term memory (determined by detrended fluctuation analysis). Regional and global memory in CAPE and CIN is compared between observations (ECMWF re‐analysis, in 1979–2001) and simulated data (ECHAM5/MPIOM, 20C simulation, in 1900–2001). Both datasets agree on the memory pattern in CAPE and CIN with highest values of the Hurst exponent along the equatorial Pacific which decrease towards higher latitudes; however, longest memory up to decades is found in CAPE south‐east of Greenland. The memory in CIN is weaker than in CAPE regarding strength and spatial extent. To determine the origin of memory in CAPE and CIN, ML temperature and specific humidity, enthalpy, and latent heat equivalent of precipitable water (LPW) are analysed. In the tropics the spatial characteristics of the memory in CAPE coincide with memory in LPW, while in the extra‐tropics ML temperature and humidity have the strongest impact. Copyright © 2010 Royal Meteorological Society