bluuebunny/crossref_metadata_2025 huggingface dataset:
Landscape effects on birds in urban woodlands: an analysis of 34 Swedish cities
Authors: Hedblom Marcus , Söderström Bo
Published: April 2010

Aim  To compare bird abundances in woodlands along gradients from the city centre to the peri‐urban area. To evaluate the importance of the proportion of woodland within the city and in the peri‐urban landscape to forest bird communities breeding in urban woodlands. To test whether fragmentation effects on birds were linked to the type of peri‐urban matrix.

Location  A total of 34 Swedish cities with > 10,000 inhabitants in south‐central Sweden. The study area covered 105,000 km2, in which 84% of the Swedish population of 9.1 million lives.

Methods  Repeated point count surveys were conducted in 2004 in a total of 474 woodlands. General linear models were used to test for possible differences in abundance along urban to peri‐urban gradients, and to regress bird abundances in local urban woodlands on: (1) total woodland cover in the city, (2) total woodland cover in the peri‐urban landscape, (3) the interaction between woodland cover in the city and in the peri‐urban area, (4) region, and (5) human density.

Results  More than 12,000 individuals of 100 forest bird species were recorded. Of the 34 most common species detected, 13 bird species had higher abundances in urban than in peri‐urban woodlands, and seven species showed the opposite trend. The bird community of urban woodlands was characterized by species associated with deciduous forests and tree nesters, whereas the bird community of peri‐urban woodlands was characterized by species associated with coniferous woodland and ground nesters. Twelve species were significantly linearly associated with the proportion of urban woodland and/or the proportion of peri‐urban woodland, and a further eight species were associated with the interaction between these two factors. Local breeding bird abundances of four species were significantly positively associated with the proportion of urban woodland only in farmland‐dominated landscapes.

Main conclusions  Fragmentation effects on some urban birds are linked to the type of peri‐urban matrix. In farmland landscapes, peri‐urban woodlands may have been too scarce to act as a source of bird immigrants to fragmented urban woodlands. To maintain populations of specialized forest birds within cities in landscapes dominated by agriculture, it is of paramount importance to conserve any remaining urban woodlands.
Construct and criterion validity of the SF‐12 health questionnaire in patients with acute myocardial infarction and unstable angina
Authors: Failde Inmaculada , Medina Pilar , Ramirez Carmen , Arana Roque
Published: April 2010

Background  The aim of the study was to determine the construct and criterion validity of the 12‐item short‐form questionnaire (SF‐12) in coronary patients with either acute myocardial infarction or unstable angina in Spain.

Method  A total of 186 patients hospitalized with coronary heart disease have been studied. The construct validity has been analysed by means of the association between the SF‐12v.1 and sociodemographic and clinical variables; and the criterion validity was tested by the correlations between 36‐item short‐form question (SF‐36) and SF‐12 summary scores. The equivalence between both health questionnaires was examined by means of the proportion of variance in the SF‐36 physical and mental component summary (PCS‐36 and MCS‐36) scores explained by the 12 items adjusted by age and sex.

Results  The validation result was as expected: female patients and those with poor education level, worse mental health, unstable angina, cardiovascular risk factor and co‐morbidity obtained a lower score in the SF‐12. The correlations between SF‐36 and SF‐12 summary scores were high. The equivalence between the SF‐12 and SF‐36 was good, because the models explained 87% of the variation in PCS‐36 score and 93% of the variation in MCS‐36.

Conclusion  The SF‐12 is a valid tool in studies assessing health‐related quality of life in coronary patients. The use of the SF‐12 may be especially useful in patients where the clinical situation make difficult the application of the longer instrument.
Host and parasite genomics, an Australasian perspective
Authors: PEACOCK C.
Published: April 2010

The last decade has seen rapid advances in the genetic technology that is allowing researchers to examine host–pathogen interactions at a whole organism level. The advent of ‘affordable’ post‐genomic technology has opened up a world of proteomic, transcriptomic and metabolomic methodologies that have been utilized by research groups in the Australasian region to examine the hosts’ response to parasitic infections. Significant contributions have been made to many areas of parasitic infections with particular strengths being in malaria vaccine development, genetic susceptibility to leishmaniasis, genomic and proteomic analysis of schistosomiasis and genetic determination of resistance to helminthes in domestic animals. This review highlights some of these studies that have made significant contributions to our knowledge of the pathogenesis of parasitic diseases with a particular emphasis placed on studies reported in the last couple of years.
Fact or hypothesis: concomitant immunity in taeniid cestode infections
Authors: LIGHTOWLERS M. W.
Published: April 2010

Sustained research efforts over the last 50 years have revealed a considerable amount of information about immunity to taeniid cestode infections in the parasites’ intermediate hosts. As a product of this research, a series of effective recombinant vaccines have been developed which have no parallel in any other group of parasitic organisms. There are, however, many important aspects relating to immunity that remain to be elucidated. Some concepts have come to be firmly held as facts and yet the supportive data are either conflicting or unconfirmed. This review considers the phenomenon of immunity to re‐infection with taeniid cestodes in their intermediate hosts, examining carefully the nature of the evidence that is available to support conclusions that have been drawn in this area.
Immunological response of sheep to injections of plasmids encoding Toxoplasma gondii SAG1 and ROP1 genes
Authors: LI B. , OLEDZKA G. , McFARLANE R. G. , SPELLERBERG M. B. , SMITH S. M. , GELDER F. B. , KUR J. , STANKIEWICZ M.
Published: April 2010

Infection with the intracellular protozoan parasite Toxoplasma gondii (T. gondii) causes health problems to both humans and livestock and has a large economic impact worldwide. The immune response in sheep following infection with T. gondii was evaluated using six different combinations of plasmid DNA, recombinant antigen and adjuvant. Sheep were generally vaccinated twice by intramuscular injection with plasmid DNA containing gene sequences for either the surface antigen (SAG1) or the rhoptry protein (ROP1) of T. gondii. Two of the groups injected with plasmid DNA SAG1 were boosted with recombinant protein (SAG1). We investigated the efficacy of including oligodeoxynucleotides (ODN) that contain CG motifs (CpG) and the gene coding for ovine granulocyte‐macrophage colony stimulating factor (GM‐CSF) as potential adjuvants. Administration of the plasmid encoding the ROP1 gene significantly enhanced both IFN‐γ production from peripheral blood cells when cultured in vitro with Toxoplasma antigen, and ROP1‐specific IgG1 and IgG2 antibody levels present in serum. However, injection with SAG1 did not stimulate IFN‐γ production. These results indicate the potential of ROP1, given as plasmid DNA, as a potential vaccine candidate to protect sheep against T. gondii infection.
ANCORP: a high‐resolution approach that generates distinct chromatin state models from multiple genome‐wide datasets
Authors: Luo Chongyuan , Lam Eric
Published: April 2010

Chromatin components can be extensively modified and dynamically regulated by a plethora of catalytic complexes. The numerous modifications may form a type of molecular pattern that defines particular local and global ‘chromatin states’ through extensive cross‐talk. Analyses that can integrate multiple genome‐wide datasets are essential to determine the interactions and biological function of chromatin modifications in various contexts. Through a combination of hierarchical clustering and pattern visualization, we categorized all annotated Arabidopsis genes into 16 chromatin state clusters using combinations of four chromatin marks (H3K4me3, H3K36me2, H3K27me3 and cytosine methylation) using publicly available data. Our results suggest that gene length may be an important factor in shaping chromatin states across transcription units. By analysis of two rare chromatin states, we found that the enrichment of H3K36me2 around the transcription start site is negatively correlated with transcriptional activities. High‐resolution association analyses in the context of chromatin states have identified inter‐correlations between chromatin modifications. H3K4me3 were found to be under‐represented in actively transcribed regions that are modified by DNA methylation and the H3K36me2 mark, concomitant with increased nucleosome occupancy in these regions. Lastly, quantitative data from transcriptome analyses and gene ontology partitioning were integrated to determine the possible functional relevance of the corresponding chromatin states. We show that modelling the plant epigenome in terms of chromatin states and combining correlative visualization methods can be a productive approach to unravel complex relationships between epigenomic features and the functional output of the genome.
The Arabidopsis eukaryotic translation initiation factor 3, subunit F (AteIF3f), is required for pollen germination and embryogenesis
Authors: Xia Chuan , Wang Yu‐Jiao , Li Wen‐Qing , Chen Yi‐Ran , Deng Yi , Zhang Xue‐Qin , Chen Li‐Qun , Ye De
Published: April 2010

Previous studies have shown that subunits E (eIF3e), F (eIF3f) and H (elF3h) of eukaryotic translation initiation factor 3 play important roles in cell development in humans and yeast. eIF3e and eIF3h have also been reported to be important for normal cell growth in Arabidopsis. However, the functions of subunit eIF3f remain largely unknown in plant species. Here we report characterization of mutants for the Arabidopsis eIF3f (AteIF3f) gene. AteIF3f encodes a protein that is highly expressed in pollen grains, developing embryos and root tips, and interacts with Arabidopsis eIF3e and eIF3h proteins. A Ds insertional mutation in AteIF3f disrupted pollen germination and embryo development. Expression of some of the genes that are essential for pollen tube growth and embryogenesis is down‐regulated in ateif3f‐1 homozygous seedlings obtained by pollen rescue. These results suggested that AteIF3f might play important roles in Arabidopsis cell growth and differentiation in combination with eIF3e and eIF3h.
Lichen sclerosus of lips: a clinical and histopathologic study of 27 cases
Authors: Attili Venkat Ratnam , Attili Sasi Kiran
Published: April 2010

Background & Methods  Oral lichen sclerosus (LS) has been considered uncommon and involvement of lips extremely rare. We reviewed the clinical and histologic features of 72 cases of LS with oral/genital involvement, seen in our institute from 2002 to 2007.

Results  Lichen sclerosus was diagnosed with exclusive genital lesions in 45, exclusive lip involvement in 20, and orogenital involvement in seven cases. Fifteen of 27 histologically confirmed lip LS lesions were considered as early inflammatory or presclerotic, eight were intermediate/progressive, and four as late resolved lesions. Lip LS presented as asymptomatic vitiligoid lesions in 70% and dermal sclerosis was demonstrable in only 44%, which was limited to the papillary layer. This was in contrast with genital LS lesions which were asymptomatic in only 12% and demonstrated both papillary and reticular dermal sclerosis in 69%.

Conclusion  Lip LS is far less symptomatic and destructive with limited dermal sclerosis compared with genital LS. Greater awareness and histologic assessment are essential for diagnosis because of the misleading vitiligoid appearance. “Vitiligoid LS” a superficial variant proposed by Borda can be aptly applied to lip LS. Dermatologists need to be aware of this rarely reported manifestation of LS as it adds to the spectrum of oral lichenoid lesions and lichenoid dysplasia, which are suspected to have a malignant potential.
Tinea capitis in adults in Tunisia
Authors: Mebazaa Amel , E.L. Oumari Kamel , Ben Said Moncef , Ghariani Najet , Denguezli Mohamed , Mili Akila Fathallah , Kenani Nesrine , Belajouza Colandane , Nouira Rafiaa
Published: April 2010

Objective  To determine the pattern of infectious agents causing tinea capitis (TC) in adult patients in adult patients in Tunisia.

Methods  From January 1990 to December 2005, we retrospectively collected all cases of adult TC, confirmed by the mycological examination.

Results  Sixty patients (18 male, 42 female) with a mean age of 34.5 years were diagnosed as having adult TC among a total number of 1137 cases of TC (5.27%). Clinical features were polymorphic and diagnosis was made on mycological examination. Culture identified Trichophyton violaceum in 36 cases (60%), Microsporum canis in 12 cases (20%), Trichophyton schoenleini in 7 cases (12%), Trichophyton verrucosum in two cases (3.5%), and Trichophyton mentagrophytes and Trichophyton rubrum in one case (each 1.77%). Culture was negative in one case. Treatment consisted of administration of Griseofulvin at the dose of 20–25 mg/kg/d during 6–8 weeks associated with antifungal topics. A complete recovery was noted in 55 cases and relapse occurred in two patients. A scary alopecia was observed in one patient and two patients were lost to follow‐up.

Conclusion  Trichophyton violaceum remains the most common etiological agent of adult TC in Tunisia. Microsporum canis is rising rapidly most notably due to the high frequency of asymptomatic carriage by domestic animals.
Positive concomitant test reactions to allergens in the standard patch test series
Authors: Landeck Lilla , González Ernesto , Baden Lynn , Neumann Konrad , Schalock Peter
Published: April 2010

Background  Patch testing is performed to evaluate suspected allergic contact dermatitis. Common wisdom suggests that various allergens cross‐react but only a few larger studies have published confirmations of this. The purpose of our study was to identify significant correlations between positive test reactions in a screening series.

Methods  A total of 1235 patients undergoing patch testing to the Hermal standard series at the Massachusetts General Hospital, Contact Dermatitis Clinic between 1990 and 2006 were investigated.

Results  Two or more positive reactions were seen in 411 patients (33.3%). Sensitizations to eight pairs of allergens were found to have significant correlation (P ≤ 0.0001). A strong association was observed for cross reactions between formaldehyde and its releasers quaternium 15 and imidazolidinyl urea and between balsam of Peru and fragrance mix. Moreover, significant co‐sensitization was identified for potassium dichromate and colophony. Three significant pairings in our study were associations between fragrances and metals. Our data confirm the previously published cross‐reactions in the literature between fragrance components, and formaldehyde and formaldehyde‐releasing preservatives. The increased numbers of patients with metal and fragrance sensitization can be considered as a random finding due to independent sensitization.

Conclusion  Being aware of cross‐reacting allergens is essential to success in resolving allergic dermatitis when counseling patients.
Acute generalized exanthematous pustulosis: analysis of cases managed in a tertiary hospital in Singapore
Authors: Lee Haur Yueh , Chou Danny , Pang Shiu Ming , Thirumoorthy T
Published: April 2010

Acute generalized exanthematous pustulosis  We reviewed eight cases of acute generalized exanthematous pustulosis managed in a tertiary hospital in Singapore.

Background  Acute generalized exanthematous pustulosis (AGEP) is a pustular reaction characterized by a sudden eruption of widespread nonfollicular sterile pustules associated with systemic symptoms. AGEP is primarily believed to be an adverse reaction to drugs. Outside of Europe, few reports exist on the clinical presentation of AGEP.

Methods  A retrospective review of patients who presented with AGEP to a Singapore tertiary hospital was performed.

Results  Eight patients were diagnosed with AGEP in 2006–2007. All patients presented with a macular, maculopapular eruption prior to the onset of pustules. AGEP was characterized by nonfollicular, pinpoint pustules, which were generalized and accentuated in the flexural areas in seven of the patients. The remaining patient had erythematous patches, and scattered plaques studded with pustules. Other less common features included oral/genital mucositis, blisters and erosions. The mean duration from the cessation of medications to defervescence, resolution of pustules and normalization of leukocytosis was 5, 6, and 7 d, respectively. Despite the resolution of pustules, two patients had protracted clinical courses with evolution to generalized exfoliative dermatitis and Drug rash, eosinophilia, and systemic symptoms (DRESS), respectively. The implicated medications included antibiotics in six patients, morphine and phenytoin in one patient each.

Conclusions  Acute generalized exanthematous pustulosis is generally described as benign and self‐limiting. However, in certain patients, the clinical course is prolonged and may exhibit features that overlap with other forms of cutaneous adverse drug reactions such as toxic epidermal necrolysis and DRESS.
Advanced tools for in vivo skin analysis
Authors: Cal Krzysztof , Zakowiecki Daniel , Stefanowska Justyna
Published: April 2010

A thorough examination of the skin is essential for accurate disease diagnostics, evaluation of the effectiveness of topically applied drugs and the assessment of the results of dermatologic surgeries such as skin grafts. Knowledge of skin parameters is also important in the cosmetics industry, where the effects of skin care products are evaluated. Due to significant progress in the electronics and computer industries, sophisticated analytic devices are increasingly available for day‐to‐day diagnostics. The aim of this article is to review several advanced methods for in vivo skin analysis in humans: magnetic resonance imaging, electron paramagnetic resonance, laser Doppler flowmetry and time domain reflectometry. The molecular bases of these techniques are presented, and several interesting applications in the field are discussed. Methods for in vivo assessment of the biomechanical properties of human skin are also reviewed.
Response to oral cyclosporine therapy and high sensitivity‐CRP level in chronic idiopathic urticaria
Authors: Ohtsuka Tsutomu
Published: April 2010

Background  Chronic idiopathic urticaria (CIU) is often resistant to common treatment of uriticaria.

Objective  To find out clinical and laboratory findings affecting the response of oral cyclosporine therapy in CIU.

Subjects and methods  The response of oral cyclosporine therapy in 15 patients with CIU (male : female = 5 : 10, age 16–60 years old, mean 40.0 years old) was studied. Cyclosporine trough level was measured with an enzyme‐multiplied immunoassay, and high sensitivity‐CRP was measured with a nephelometric assay. The relation between high sensitivity‐CRP level and clinical and laboratory findings in CIU was also studied.

Results  All the 15 CIU patients responded to oral cyclosporine therapy. High sensitivity‐CRP levels before the start of therapy were elevated in nine of 15 CIU patients. The distributions of treatment duration and basophile leukocytes counts in elevated high sensitivity‐CRP patients (8.7 ± 1.3 months, 0.20 ± 0.05%) were significantly shorter and elevated than those in patients showing no elevation (22.7 ± 1.7 months, 0.40 ± 0.05%) (P < 0.05, P < 0.05), respectively. No other clinical and laboratory findings between patients with elevated and not elevated high sensitivity‐CRP showed any significant differences.

Conclusion  Chronic idiopathic urticaria patients with elevated high sensitivity‐CRP showed good response to oral cyclosporine therapy.
Antibody reactivity to Borrelia burgdorferi sensu stricto antigens in patients from the Brazilian Amazon region with skin diseases not related to Lyme disease
Authors: Santos Mônica , Ribeiro‐Rodrigues Rodrigo , Lobo Rogério , Talhari Sinésio
Published: April 2010

In the present study, we report the occurrence of borreliosis in patients from the Brazilian Amazonic region. Nineteen (7.2%) out of 270 dermatological patients with different skin diseases (no one with clinical Lyme disease), tested positive by ELISA for Borrelia burgdorferi. Serum samples from 15 out of the 19 ELISA‐positive patients were further evaluated by Western blot. Presence of Borrelia burgdorferi specific IgG was confirmed in eight (53.3%) out of the 15 patients. All eight patients with ELISA and Western blot positive reactions were treated with doxycycline, according to the Centers for Disease Control and Prevention guidelines. One of them had clinical manifestations of colagenosis and was sent to the Department of Internal Medicine for further investigation. Data presented here suggested that borreliosis “lato sensu” is in the Brazilian Amazon region.
The influence of childhood atopic dermatitis on health of mothers, and its impact on Asian families
Authors: Ho Roger C. M. , Giam Y. C. , Ng T. P. , Mak Anselm , Goh Daniel , Zhang Melvyn W. B. , Cheak Alicia , Van Bever Hugo P.
Published: April 2010

Ho RCM, Giam YC, Ng TP, Mak A, Goh D, Zhang MWB, Cheak A, Van Bever HP. The influence of childhood atopic dermatitis on health of mothers, and its impact on Asian families. Pediatr Allergy Immunol 2010: 21: 501–507. © 2010 John Wiley & Sons A/S

This study examines maternal perceptions of paediatric atopic dermatitis (AD) on family and determines risk factors including severity of AD, maternal physical and mental health (MH), quality of life of patients and sociodemographics which predict a negative family impact. A cross‐sectional assessment using the Dermatitis Family Impact Questionnaire Scale to assess the impact of AD on family, Infant’s Dermatitis Quality of Life Index (<5‐yrs old) or Children’s Dermatitis Life Quality Index (5–17 yrs old) was used to measure health‐related quality of life (HRQOL) of paediatric patients with AD. A 12‐item Short‐Form Health Survey (SF‐12) was used to assess physical and MH of their mothers. Risk factors of adverse family impact were assessed using multiple regression analysis. One hundred and four patients with AD and their mothers were studied. Their mean ages (±s.d.) were respectively 6.4 ± 4.3 and 37.2 ± 6.6 yrs. In multiple regression analysis, Severity Scoring of Atopic Dermatitis (SCORAD) appeared to be associated with negative family impact and the association remained significant after adjustment for bio‐psycho‐social factors and HRQOL of patients. The association remained insignificant after adjustment for physical and MH of the mothers. Our results show that the severity of paediatric AD leads to negative family impact through reduction of physical and MH of the mothers, and is independent of patients’ HRQOL and sociodemographics. The current approach for managing paediatric AD in Asian society could include early multidisciplinary intervention, aiming at enhancing physical and MH of mothers while minimizing negative impact on family and social isolation. Further research will be welcomed as the results of this study mainly applied to Asian society which could be different to populations from other geographic areas.
Intravenous immunoglobulin preparation type: Association with outcomes for patients with acute Kawasaki disease
Authors: Manlhiot Cedric , Yeung Rae S. M. , Chahal Nita , McCrindle Brian W.
Published: April 2010

Manlhiot C, Yeung RSM, Chahal N, McCrindle BW. Intravenous immunoglobulin preparation type: Association with outcomes for patients with acute Kawasaki disease. Pediatr Allergy Immunol 2010: 21: 515–521. © 2010 John Wiley & Sons A/S

To determine whether two different intravenous immunoglobulin (IVIG) preparations were equally efficacious in the treatment of Kawasaki disease (KD). Single centre retrospective review of all patients treated with IVIG for KD between January 1990 and April 2007. Comparison of IVIG (dose 2 g/kg) from two commercial preparations; Iveegam® stabilized with sugar (lyophilized, 5 g/ml glucose, pH 6.4–7.2, IgA 10 μg/ml, 5% IgG/ml) and Gamimune® stabilized through acidification (no sugar, pH 4.0–4.5, IgA 270 μg/ml, 5% 1990–1999, 10% 1999–2007 IgG/ml). Propensity‐adjusted differences in duration of fever after treatment initiation, frequency of retreatment with IVIG, hospital stay and maximum coronary artery z‐score. A total of 954 patients were included, 862 (90%) were treated with Iveegam® and 92 (10%) were treated with Gamimune®. Patients’ demographic, clinical and laboratory characteristics were similar between the two groups. In propensity‐adjusted models, Iveegam® was found to be associated with higher probability of non‐response to IVIG (12% vs. 5%, p = 0.05) and longer median duration of fever after IVIG [1 (1–27) vs. 1 (1–8) days, p = 0.02] than Gamimune®. Nevertheless, Gamimune® was found to be associated with longer median duration of hospital stay [5 (2–49) vs. 4 (2–76) days, p < 0.0001] and higher median maximum coronary artery z‐score both at the end of the acute phase (+1.4 vs. +0.8, p < 0.0001) and 6–8 weeks after the acute phase (+0.7 vs. +0.4, p < 0.0001). IVIG preparations with lower IgA content and stabilized with glucose appear to be associated with improved coronary artery outcomes for patients with KD.
Association between serum levels of soluble CD40/CD40 ligand and organ damage in hypertensive patients
Authors: Yuan Ming , Ohishi Mitsuru , Wang Lin , Raguki Hiromi , Wang Haichang , Tao Ling , Ren Jun
Published: April 2010

1. CD40 and CD40 ligand (CD40L) have a critical role in the pathophysiology and risk prediction of coronary artery syndrome, including atherothrombosis and atherosclerosis. However, the contribution of the CD40/CD40L dyad, especially the soluble form of CD40L (sCD40L), to the pathophysiology of hypertension and associated organ damage remains unknown.

2. In the present study, serum levels of CD40 and sCD40L were measured in 328 hypertensive patients with varying degrees of organ damage. The data revealed that serum levels of CD40 were significantly greater in patients with severe, but not mild, organ damage compared with patients without any organ damage. There were no significant differences in serum concentrations of sCD40L between patients with no, mild and severe organ damage. Concentrations of soluble CD40 were comparable in patients with mild organ damage that included left ventricular hypertrophy, retinal damage, renal dysfunction and proteinuria. In contrast, concentrations of soluble CD40 were increased significantly in patients with certain forms of severe organ damage, specifically stroke, but not coronary and peripheral artery disease.

3. Collectively, our data indicate that upregulation of the CD40 system in hypertensive patients with certain forms of severe end‐organ damage may contribute to the pro‐inflammatory, pro‐atherogenic and prothrombotic milieu in hypertension.
Concomitant inactivation of the epidermal growth factor receptor, phosphatidylinositol 3‐kinase/Akt and Janus tyrosine kinase 2/signal transducer and activator of transcription 3 signalling pathways in cardiotoxin III‐treated A549 cells
Authors: Su Jung‐Chen , Lin Kuei‐Li , Chien Ching‐Ming , Chuang Pei‐Wen , Chang Long‐Sen , Lin Shinne‐Ren
Published: April 2010

1. Cardiotoxin (CTX) III, a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has potential anticancer therapeutic activity. The aim of the present study was to investigate the apoptotic effect (and the underlying mechanism of action) of CTX III in human adenocarcinoma A549 cells.

2. It was found that CTX III induces apoptosis in A549 cells, as indicated by an increase in the sub‐G1 population, phosphatidylserine externalization, loss of mitochondrial membrane potential (Ψm) with cytochrome c release and activation of caspases 9 and 3. These actions were correlated with upregulation of Bax and Bad and downregulation of various anti‐apoptotic proteins, including Bcl‐2, Bcl‐XL, Mcl‐1, X‐linked inhibitor of apoptosis protein (XIAP) and p‐Bad in CTX III‐treated cells.

3. The signal transduction pathways involved in the effects of CTX III in A549 cells were evaluated using 5 μmol/L AG1478, an inhibitor of the epidermal growth factor receptor (EGFR), and exposing cells to the drug for 8 h. The results indicated that CTX III suppresses phosphorylation of EGFR and activation of phosphatidylinositol 3‐kinase (PI3‐K)/Akt and Janus tyrosine kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3, all of which are downstream molecules in the EGFR signalling pathway.

4. Exposure of cells for 8 h to the PI3‐K inhibitor wortmannin (10 μmol/L) blocked JAK2 and STAT3 activation, whereas exposure of cells to the JAK2 inhibitor AG490 (5 μmol/L) decreased levels of phosphorylated (p‐) JAK2 and p‐STAT3 without affecting PI3‐K/Akt activation. These observations suggest that PI3‐K is an upstream activator of JAK2/STAT3. Furthermore, 5 μmol/L AG490 and 10 μmol/L wortmannin treatment of A549 cells for 8 h resulted in upregulation of Bax and Bad and downregulation of Bcl‐2, Bcl‐XL, XIAP and p‐Bad.

5. Together, the results of the present study indicate that CTX III induces apoptosis in A549 cells by inactivating the EGFR, PI3‐K/Akt and JAK2/STAT3 signalling pathways.
Hypothesis: Multiple factors are associated with the lack of any beneficial effects of oestrogen‐replacement therapy in the late postmenopausal stage
Authors: Xiao Ming , Cao Guang‐Liang , Marshall Charles , Hu Gang
Published: April 2010

1. Epidemiological and clinical studies suggest that women may obtain cognitive benefits from oestrogen‐replacement therapy (ERT) during menopause transition rather than in the post‐menopausal stages. However, the underlying mechanisms remain to be determined.

2. We propose that long‐term oestrogen deficiency may result in abnormal distribution and localization of brain oestrogen receptors, brain mitochondrial dysfunction, septohippocampal cholinergic degeneration and reactive gliosis. These multiple pathogenic factors may account for the lack of any beneficial effects of ERT in post‐menopausal women with or without Alzheimer’s disease.
Exercise training attenuates anaphylactic venoconstriction in rat perfused liver, but does not affect anaphylactic hypotension in conscious rats
Authors: Cui Sen , Shibamoto Toshishige , Zhang Wei , Kurata Yasutaka , Kashimura Osamu , Miyamae Shunichi
Published: April 2010

1. Exercise training attenuates circulatory shock due to haemorrhage, endotoxin or heatstroke. However, it remains unknown whether exercise training attenuates anaphylactic shock. Hepatic venoconstriction is involved in rat anaphylactic hypotension. In the present study, we determined the effects of exercise training on both anaphylaxis‐induced segmental venoconstriction in rat perfused livers and systemic anaphylaxis in conscious rats. The role of nitric oxide (NO) in the effect of exercise on the venoconstriction of perfused livers was also examined.

2. Rats were subjected to running training on a motorized treadmill for 4 weeks. Two weeks prior to the anaphylaxis experiment, Sprague‐Dawley rats were actively sensitized with the antigen ovalbumin. In isolated livers perfused portally with blood, the portal venous pressure (Ppv) and sinusoidal pressure were measured to determine the pre‐ and post‐sinusoidal resistances (Rpre and Rpost, respectively). In conscious rats, systemic arterial pressure (SAP) and Ppv were determined.

3. In the perfused livers of sedentary rats, antigen administration led to a predominant presinusoidal constriction, as evidenced by 4.6‐ and 1.7‐fold increases in Rpre and Rpost, respectively. The anaphylaxis‐induced increase in Rpre was significantly attenuated by 24% by exercise training. Inhibition of NO synthase with NG‐nitro‐l‐arginine methyl ester (100 μmol/L) 10 min prior to the injection of antigen enhanced anaphylactic venoconstriction, but did not alter the effect of exercise training on the increase in Rpre. In contrast, exercise training did not attenuate either anaphylactic hypotension or portal hypertension in conscious rats.

4. In conclusion, exercise training attenuates the anaphylaxis‐induced presinusoidal constriction in rat isolated perfused livers, independent of NO production. However, this action is not evident in conscious rats and exercise training does not affect anaphylactic hypotension in conscious rats.
Nestin is a novel marker for renal tubulointerstitial injury in immunoglobulin A nephropathy
Authors: TOMIOKA MAI , HIROMURA KEIJU , SAKAIRI TORU , TAKEUCHI SHIGERU , MAESHIMA AKITO , KANEKO YORIAKI , KUROIWA TAKASHI , TAKEUCHI TOSHIYUKI , NOJIMA YOSHIHISA
Published: April 2010

Aim:  Nestin, an intermediate filament originally identified as a marker of neural progenitor cells, is transiently expressed in endothelial cells and tubuloepithelial cells during kidney development. However, in adult kidneys, podocytes are the only cells that express nestin. In this study, we examined tubulointerstitial nestin expression in human glomerulonephritis.

Methods:  Renal biopsy specimens obtained from 41 adult patients with immunoglobulin (Ig)A nephropathy were studied. Nestin expression was determined by immunohistochemical staining and estimated by digital image analysis. To identify the phenotype of nestin‐positive cells, a double immunofluorescent study was performed for nestin and CD34 (a marker for endothelial cells) or α‐smooth muscle actin (α‐SMA, a marker for myofibroblasts).

Results:  In normal kidney, nestin expression was restricted to the podocytes and was not detected in tubular cells and tubulointerstitial cells. In contrast, increased nestin expression was observed at tubulointerstitial areas of IgA nephropathy. The degree of tubulointerstitial nestin expression was positively correlated with tubulointerstitial fibrosis (r = 0.546, P < 0.001). The double immunofluorescent study showed that most nestin‐positive cells in the interstitium were co‐stained with CD34 or α‐SMA, suggesting that peritubular endothelial cells and tubulointerstitial myofibroblasts express nestin during the progression of tubulointerstitial injury. In addition, strong nestin expression was associated with deterioration of renal function.

Conclusion:  Nestin expression is associated with tubulointerstitial injury and predicts renal prognosis in IgA nephropathy. Nestin could be a new marker for peritubular endothelial cell injury and tubulointerstitial fibrosis.
The ultrastructural distribution of prestin in outer hair cells: a post‐embedding immunogold investigation of low‐frequency and high‐frequency regions of the rat cochlea
Authors: Mahendrasingam Shanthini , Beurg Maryline , Fettiplace Robert , Hackney Carole M.
Published: April 2010

Outer hair cells (OHCs) of the mammalian cochlea besides being sensory receptors also generate force to amplify sound‐induced displacements of the basilar membrane thus enhancing auditory sensitivity and frequency selectivity. This force generation is attributable to the voltage‐dependent contractility of the OHCs underpinned by the motile protein, prestin. Prestin is located in the basolateral wall of OHCs and is thought to alter its conformation in response to changes in membrane potential. The precise ultrastructural distribution of prestin was determined using post‐embedding immunogold labelling and the density of the labelling was compared in low‐frequency and high‐frequency regions of the cochlea. The labelling was confined to the basolateral plasma membrane in hearing rats but declined towards the base of the cells below the nucleus. In pre‐hearing animals, prestin labelling was lower in the membrane and also occurred in the cytoplasm, presumably reflecting its production during development. The densities of labelling in low‐frequency and high‐frequency regions of the cochlea were similar. Non‐linear capacitance, thought to reflect charge movements during conformational changes in prestin, was measured in OHCs in isolated cochlear coils of hearing animals. The OHC non‐linear capacitance in the same regions assayed in the immunolabelling was also similar in both the apex and base, with charge densities of 10 000/μm2 expressed relative to the lateral membrane area. The results suggest that prestin density, and by implication force production, is similar in low‐frequency and high‐frequency OHCs.
Stem and progenitor cell compartments within adult mouse taste buds
Authors: Sullivan Jeremy M. , Borecki Alexander A. , Oleskevich Sharon
Published: April 2010

Adult taste buds are maintained by the lifelong proliferation of epithelial stem and progenitor cells, the identities of which have remained elusive. It has been proposed that these cells reside either within the taste bud (intragemmal) or in the surrounding epithelium (perigemmal). Here, we apply three different in vivo approaches enabling single‐cell resolution of proliferative history to identify putative stem and progenitor cells associated with adult mouse taste buds. Experiments were performed across the circadian peak in oral epithelial proliferation (04:00 h), a time period in which mitotic activity in taste buds has not yet been detailed. Using double label pulse‐chase experiments, we show that defined intragemmal cells (taste and basal) and perigemmal cells undergo rapid, sequential cell divisions and thus represent potential progenitor cells. Strikingly, mitotic activity was observed in taste cells previously thought to be postmitotic (labelled cells occur in 30% of palatal taste buds after 1 h of BrdU exposure). Basal cells showed expression of the transcription factor p63, required for maintaining the self‐renewal potential of various epithelial stem cell types. Candidate taste stem cells were identified almost exclusively as basal cells using the label‐retaining cell approach to localize slow‐cycling cells (0.06 ± 0.01 cells per taste bud; n = 436 taste buds). Together, these results indicate that both stem‐ and progenitor‐like cells reside within the mammalian taste bud.
The effects of aging and chronic fluoxetine treatment on circadian rhythms and suprachiasmatic nucleus expression of neuropeptide genes and 5‐HT1Breceptors
Authors: Duncan Marilyn J. , Hester James M. , Hopper Jason A. , Franklin Kathleen M.
Published: April 2010

Age‐related changes in circadian rhythms, including attenuation of photic phase shifts, are associated with changes in the central pacemaker in the suprachiasmatic nucleus (SCN). Aging decreases expression of mRNA for vasoactive intestinal peptide (VIP), a key neuropeptide for rhythm generation and photic phase shifts, and increases expression of serotonin transporters and 5‐HT1Breceptors, whose activation inhibits these phase shifts. Here we describe studies in hamsters showing that aging decreases SCN expression of mRNA for gastrin‐releasing peptide, which also modulates photic phase resetting. Because serotonin innervation trophically supports SCN VIP mRNA expression, and serotonin transporters decrease extracellular serotonin, we predicted that chronic administration of the serotonin‐selective reuptake inhibitor, fluoxetine, would attenuate the age‐related changes in SCN VIP mRNA expression and 5‐HT1Breceptors.In situhybridization studies showed that fluoxetine treatment does not alter SCN VIP mRNA expression, in either age group, at zeitgeber time (ZT)6 or 13 (ZT12 corresponds to lights off). However, receptor autoradiographic studies showed that fluoxetine prevents the age‐related increase in SCN 5‐HT1Breceptors at ZT6, and decreases SCN 5‐HT1Breceptors in both ages at ZT13. Therefore, aging effects on SCN VIP mRNA and SCN 5‐HT1Breceptors are differentially regulated; the age‐related increase in serotonin transporter sites mediates the latter but not the former. The studies also showed that aging and chronic fluoxetine treatment decrease total daily wheel running without altering the phase of the circadian wheel running rhythm, in contrast to previous reports of phase resetting by acute fluoxetine treatment.
GABAB receptor‐dependent modulation of network activity in the rat prefrontal cortex in vitro
Authors: Wang Ying , Neubauer Florian B. , Lüscher Hans‐Rudolf , Thurley Kay
Published: April 2010

GABA (γ‐aminobutyric acid) can mediate inhibition via pre‐ and post/extrasynaptic GABA receptors. In this paper we demonstrate potentially post/extrasynaptic GABAB receptor‐dependent tonic inhibition in L2/3 pyramidal cells of rat medial prefrontal cortex (mPFC) in vitro. First, we show via voltage‐clamp experiments the presence of a tonic GABAB receptor‐dependent outward current in these neurons. This GABABergic current could be induced by ambient GABA when present at sufficient concentrations. To increase ambient GABA levels in the usually silent slice preparation, we amplified network activity and hence synaptic GABA release with a modified artificial cerebrospinal fluid. The amplitude of tonic GABAB current was similar at different temperatures. In addition to the tonic GABAB current, we found presynaptic GABAB effects, GABAB‐mediated inhibitory postsynaptic currents and tonic GABAA currents. Second, we performed current‐clamp experiments to evaluate the functional impact of GABAB receptor‐mediated inhibition in the mPFC. Activating or inactivating GABAB receptors led to rightward (reduction of excitability) or leftward (increase of excitability) shifts, respectively, of the input–output function of mPFC L2/3 pyramidal cells without effects on the slope. Finally, we showed in electrophysiological recordings and epifluorescence Ca2+‐imaging that GABAB receptor‐mediated tonic inhibition is capable of regulating network activity. Blocking GABAB receptors increased the frequency of excitatory postsynaptic currents impinging on a neuron and prolonged network upstates. These results show that ambient GABA via GABAB receptors is powerful enough to modulate neuronal excitability and the activity of neural networks.
Distinct expression of C1q‐like family mRNAs in mouse brain and biochemical characterization of their encoded proteins
Authors: Iijima Takatoshi , Miura Eriko , Watanabe Masahiko , Yuzaki Michisuke
Published: April 2010

Many members of the C1q family, including complement C1q and adiponectin, and the structurally related tumor necrosis factor family are secreted and play crucial roles in intercellular signaling. Among them, the Cbln (precerebellin) and C1q‐like (C1ql) subfamilies are highly and predominantly expressed in the central nervous system. Although the Cbln subfamily serve as essential trans‐neuronal regulators of synaptic integrity in the cerebellum, the functions of the C1ql subfamily (C1ql1–C1ql4) remain unexplored. Here, we investigated the gene expression of the C1ql subfamily in the adult and developing mouse brain by reverse transcriptase‐polymerase chain reaction and high‐resolution in‐situ hybridization. In the adult brain, C1ql1–C1ql3 mRNAs were mainly expressed in neurons but weak expression was seen in glia‐like structures in the adult brain. The C1ql1 mRNA was predominantly expressed in the inferior olive, whereas the C1ql2 and C1ql3 mRNAs were strongly coexpressed in the dentate gyrus. Although the C1ql1 and C1ql3 mRNAs were detectable as early as embryonic day 13, the C1ql2 mRNA was observed at later embryonic stages. The C1ql1 mRNA was also expressed transiently in the external granular layer of the cerebellum. Biochemical characterization in heterologous cells revealed that all of the C1ql subfamily proteins were secreted and they formed both homomeric and heteromeric complexes. They also formed hexameric and higher‐order complexes via their N‐terminal cysteine residues. These results suggest that, like Cbln, the C1ql subfamily has distinct spatial and temporal expression patterns and may play diverse roles by forming homomeric and heteromeric complexes in the central nervous system.
First diabetes prevalence study in Portugal: PREVADIAB study
Authors: Gardete‐Correia L. , Boavida J. M. , Raposo J. F. , Mesquita A. C. , Fona C. , Carvalho R. , Massano‐Cardoso S.
Published: April 2010

Diabet. Med. 27, 879–881 (2010)

Aims  Diabetes is a growing worldwide problem. Ascertaining its prevalence is vital as a starting point to establish and measure the success of health interventions. This study aimed to determine the prevalence of Type 2 diabetes and ‘pre‐diabetes’, defined as impaired fasting glucose and impaired glucose tolerance, in the Portuguese population aged between 20 and 79 years.

Methods  Considering the number of inhabitants between 20 and 79 years old, statistical units were selected that were representative regionally and nationally. The total sample comprised 5167 subjects. National prevalence was calculated. Analyses were performed on all those without previously known diabetes using World Health Organization reference diagnostic criteria.

Results  We found a diabetes prevalence of 11.7% (95% confidence interval 10.8–12.6%), with a significant difference between men (14.2%; 95% confidence interval 12.5–15.5%) and women (9.5%; 95% confidence interval 8.5–10.6%). While 6.6% of the subjects had previously been diagnosed with diabetes, 5.1% were undiagnosed. By age groups, 2.4% of the population between 20 and 39 years, 12.6% of people from 40 to 59 years old and 26.3% of those aged between 60 and 79 years had diabetes. Prevalence of ‘pre‐diabetes’ (impaired fasting glucose, impaired glucose tolerance or both) in the population was 23.3%.

Conclusions  Diabetes has a high prevalence in Portugal. If ‘pre‐diabetes’ is also considered, about one‐third (34.9%) of the population aged 20–79 years is affected. A greater number of males were found to have diabetes. We detected a high percentage of people with undiagnosed diabetes (43.6%).
EFFICIENT PERSONALIZATION OF E‐LEARNING ACTIVITIES USING A MULTI‐DEVICE DECENTRALIZED RECOMMENDER SYSTEM
Authors: Rosaci Domenico , Sarné Giuseppe M.L.
Published: April 2010

Personalization is becoming a key issue in designing effective e‐learning systems and, in this context, a promising solution is represented by software agents. Usually, these systems provide the student with a student agent that interacts with a site agent associated with each e‐learning site. However, in presence of a large number of students and of e‐learning sites, the tasks of the agents are often onerous, even more if the student agents run on devices with limited resources. To face this problem, we propose a new multiagent learning system, called ISABEL. Our system provides each student, that are using a specific device, with a device agent able to autonomously monitor the student's behavior when accessing e‐learning Web sites. Each site is associated, in its turn, with a teacher agent. When a student visits an e‐learning site, the teacher agent collaborates with some tutor agents associated with the student, to provide him with useful recommendations. We present both theoretical and experimental results to show that this distributed approach introduces significant advantages in quality and efficiency of the recommendation activity with respect to the performances of other past recommenders.