bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of positional candidate genes in the AAA1 susceptibility locus for abdominal aortic aneurysms on chromosome 19
Authors: Lillvis John H , Kyo Yoshiki , Tromp Gerard , Lenk Guy M , Li Ming , Lu Qing , Igo Robert P , Sakalihasan Natzi , Ferrell Robert E , Schworer Charles M , Gatalica Zoran , Land Susan , Kuivaniemi Helena
Published: January 2011

Background

Abdominal aortic aneurysm (AAA) is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA susceptibility locus on chromosome 19q13. This locus has been designated as the AAA1 susceptibility locus in the Online Mendelian Inheritance in Man (OMIM) database.

Methods

Nine candidate genes were selected from the AAA1 locus based on their function, as well as mRNA expression levels in the aorta. A sample of 394 cases and 419 controls was genotyped for 41 SNPs located in or around the selected nine candidate genes using the Illumina GoldenGate platform. Single marker and haplotype analyses were performed. Three genes (CEBPG, PEPD and CD22) were selected for DNA sequencing based on the association study results, and exonic regions were analyzed. Immunohistochemical staining of aortic tissue sections from AAA and control individuals was carried out for the CD22 and PEPD proteins with specific antibodies.

Results

Several SNPs were nominally associated with AAA (p < 0.05). The SNPs with most significant p-values were located near the CCAAT enhancer binding protein (CEBPG), peptidase D (PEPD), and CD22. Haplotype analysis found a nominally associated 5-SNP haplotype in the CEBPG/PEPD locus, as well as a nominally associated 2-SNP haplotype in the CD22 locus. DNA sequencing of the coding regions revealed no variation in CEBPG. Seven sequence variants were identified in PEPD, including three not present in the NCBI SNP (dbSNP) database. Sequencing of all 14 exons of CD22 identified 20 sequence variants, five of which were in the coding region and six were in the 3'-untranslated region. Five variants were not present in dbSNP. Immunohistochemical staining for CD22 revealed protein expression in lymphocytes present in the aneurysmal aortic wall only and no detectable expression in control aorta. PEPD protein was expressed in fibroblasts and myofibroblasts in the media-adventitia border in both aneurysmal and non-aneurysmal tissue samples.

Conclusions

Association testing of the functional positional candidate genes on the AAA1 locus on chromosome 19q13 demonstrated nominal association in three genes. PEPD and CD22 were considered the most promising candidate genes for altering AAA risk, based on gene function, association evidence, gene expression, and protein expression.
Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus
Authors: Dasgupta Sudeshna , Demirci F Yesim , Dressen Amy S , Kao Amy H , Rhew Elisa Y , Ramsey-Goldman Rosalind , Manzi Susan , Kammerer Candace M , Kamboh M Ilyas
Published: January 2011

Background

Low serum paraoxonase (PON) activity is associated with the risk of coronary artery disease, diabetes and systemic lupus erythematosus (SLE). Our prior studies have shown that the PON1/rs662 (p.Gln192Arg), PON1/rs854560 (p.Leu55Met), PON3/rs17884563 and PON3/rs740264 SNPs (single nucleotide polymorphisms) significantly affect serum PON activity. Since PON1, PON2 and PON3 share high degree of structural and functional properties, in this study, we examined the role of PON2 genetic variation on serum PON activity, risk of SLE and SLE-related clinical manifestations in a Caucasian case-control sample.

Methods

PON2 SNPs were selected from HapMap and SeattleSNPs databases by including at least one tagSNP from each bin defined in these resources. A total of nineteen PON2 SNPs were successfully genotyped in 411 SLE cases and 511 healthy controls using pyrosequencing, restriction fragment length polymorphism (RFLP) or TaqMan allelic discrimination methods.

Results

Our pair-wise linkage disequilibrium (LD) analysis, using an r

2
cutoff of 0.7, identified 14 PON2 tagSNPs that captured all 19 PON2 variants in our sample, 12 of which were not in high LD with known PON1 and PON3 SNP modifiers of PON activity. Stepwise regression analysis of PON activity, including the known modifiers, identified five PON2 SNPs [rs6954345 (p.Ser311Cys), rs13306702, rs987539, rs11982486, and rs4729189; P = 0.005 to 2.1 × 10-6] that were significantly associated with PON activity. We found no association of PON2 SNPs with SLE risk but modest associations were observed with lupus nephritis (rs11981433, rs17876205, rs17876183) and immunologic disorder (rs11981433) in SLE patients (P = 0.013 to 0.042).

Conclusions

Our data indicate that PON2 genetic variants significantly affect variation in serum PON activity and have modest effects on risk of lupus nephritis and SLE-related immunologic disorder.
ABI3 ectopic expression reduces in vitro and in vivocell growth properties while inducing senescence
Authors: Latini Flavia RM , Hemerly Jefferson P , Freitas Beatriz CG , Oler Gisele , Riggins Gregory J , Cerutti Janete M
Published: January 2011

Background

Mounting evidence has indicated that ABI3 (ABI family member 3) function as a tumor suppressor gene, although the molecular mechanism by which ABI3 acts remains largely unknown.

Methods

The present study investigated ABI3 expression in a large panel of benign and malignant thyroid tumors and explored a correlation between the expression of ABI3 and its potential partner ABI3-binding protein (ABI3BP). We next explored the biological effects of ABI3 ectopic expression in thyroid and colon carcinoma cell lines, in which its expression was reduced or absent.

Results

We not only observed that ABI3 expression is reduced or lost in most carcinomas but also that there is a positive correlation between ABI3 and ABI3BP expression. Ectopic expression of ABI3 was sufficient to lead to a lower transforming activity, reduced tumor in vitro growth properties, suppressed in vitro anchorage-independent growth and in vivo tumor formation while, cellular senescence increased. These responses were accompanied by the up-regulation of the cell cycle inhibitor p21
WAF1 and reduced ERK phosphorylation and E2F1 expression.

Conclusions

Our result links ABI3 to the pathogenesis and progression of some cancers and suggests that ABI3 or its pathway might have interest as therapeutic target. These results also suggest that the pathways through which ABI3 works should be further characterized.
Intracranial metastasis from primary transitional cell carcinoma of female urethra: case report & review of the literature
Authors: Moon Kyung-Sub , Jung Shin , Lee Kyung-Hwa , Hwang Eu Chang , Kim In-Young
Published: January 2011

Background

Transitional cell carcinoma (TCC) of the female urethra is a rare urological malignancy, and intracranial metastasis of this cancer has not yet been reported in the literature. This review is intended to present a case of multiple intracranial metastasis in a female patient with a remote history of primary urethral TCC.

Case Presentation

A 49-year-old woman, presented with a prolapsed mass in urethral orifice that was diagnosed as primary urethral TCC with distant lung and multiple bone metastases. The patient subsequently underwent chemotherapy under various regimens. A year later, the patient developed headache and vomiting which as was found to be due to multiple intracranial metastasis. The patient underwent surgical resection of the largest lesion located on the cerebellum, and consecutively gamma knife radiosurgery was performed for other small-sized lesions. Pathological examination of the resected mass revealed a metastatic carcinoma from a known urethral TCC. Serial work-up of systemic metastasis revealed concomitant aggravation of lung, spleen, and liver metastasis. The patient died of lung complication 2 months after the diagnosis of brain metastasis.

Conclusion

To the best of our knowledge, this is the first reported case of cerebral metastasis from primary urethral TCC, with pathological confirmation. As shown in intracranial metastasis of other urinary tract carcinoma, this case occurred in the setting of uncontrolled systemic disease and led to dismal prognosis in spite of aggressive interventional modalities.
Physical activity behaviours of Culturally and Linguistically Diverse (CALD) women living in Australia: A qualitative study of socio-cultural influences
Authors: Caperchione Cristina M , Kolt Gregory S , Tennent Rebeka , Mummery W Kerry
Published: January 2011

Background

Australia continues to witness rising levels of immigration by individuals from Culturally and Linguistically Diverse (CALD) origins. With this rapidly growing diverse population, Australia faces a number of population health challenges. In particular, CALD women have been shown to be at an increased risk of chronic diseases such as cardiovascular disease, diabetes, and poor mental health. Despite the high risk of these diseases, women from CALD groups are less likely to be proactive in accessing health care or undertaking preventative behaviours, such as physical activity participation. The purpose of this study was to examine the socio-cultural influences on the physical activity behaviours of CALD women living in Australia by identifing the barriers, constraints and possible enablers to physical activity participation for this population.

Methods

Twelve focus group sessions were undertaken with CALD women (N = 110) from Bosnian, Arabic speaking, Filipino and Sudanese communities in three regions: New South Wales, Victoria, and Queensland. In a semi-structured, open table discussion, participants were encouraged to share their opinions, perceptions and beliefs regarding socio-cultural influences on their physical activity behaviours. Common and ethnic-specific themes emerged from the discussions.

Results

Common themes included: knowledge of physical activity, differing physical activity levels, and the effects of psychological and socio-cultural factors, environmental factors, and perceptions of ill-health and injury, on physical activity behaviours. Ethnic-specific themes indicated that post-war trauma, religious beliefs and obligations, socio-economic status, social isolation and the acceptance of traditional cultural activities, greatly influenced the physical activity behaviours of Bosnian, Arabic speaking, Filipino and Sudanese women living in communities throughout Australia.

Conclusions

This study demonstrates that attitudes and understandings of health and wellbeing are complex, and have a strong socio-cultural influence. The findings of the present study can be used not only to inform further health promotion initiatives, but also as a platform for further research with consumers of these services and with those who deliver such services.
An exploratory cluster randomised controlled trial of knowledge translation strategies to support evidence-informed decision-making in local governments (The KT4LG study)
Authors: Waters Elizabeth , Armstrong Rebecca , Swinburn Boyd , Moore Laurence , Dobbins Maureen , Anderson Laurie , Petticrew Mark , Clark Rachel , Conning Rebecca , Moodie Marj , Carter Robert
Published: January 2011

Background

Childhood overweight and obesity is the most prevalent and, arguably, politically complex child health problem internationally. Governments, communities and industry have important roles to play, and are increasingly expected to deliver an evidence-informed system-wide prevention program. However, efforts are impeded by a lack of organisational access to and use of research evidence. This study aims to identify feasible, acceptable and ideally, effective knowledge translation (KT) strategies to increase evidence-informed decision-making in local governments, within the context of childhood obesity prevention as a national policy priority.

Methods/Design

This paper describes the methods for KT4LG, a cluster randomised controlled trial which is exploratory in nature, given the limited evidence base and methodological advances. KT4LG aims to examine a program of KT strategies to increase the use of research evidence in informing public health decisions in local governments. KT4LG will also assess the feasibility and acceptability of the intervention. The intervention program comprises a facilitated program of evidence awareness, access to tailored research evidence, critical appraisal skills development, networking and evidence summaries and will be compared to provision of evidence summaries alone in the control program. 28 local governments were randomised to intervention or control, using computer generated numbers, stratified by budget tertile (high, medium or low). Questionnaires will be used to measure impact, costs, and outcomes, and key informant interviews will be used to examine processes, feasibility, and experiences. Policy tracer studies will be included to examine impact of intervention on policies within relevant government policy documents.

Discussion

Knowledge translation intervention studies with a focus on public health and prevention are very few in number. Thus, this study will provide essential data on the experience of program implementation and evaluation of a system-integrated intervention program employed within the local government public health context. Standardised programs of system, organisational and individual KT strategies have not been described or rigorously evaluated. As such, the findings will make a significant contribution to understanding whether a facilitated program of KT strategies hold promise for facilitating evidence-informed public health decision making within complex multisectoral government organisations.

Trial registration

Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000953235
Management of osteoporosis and associated quality of life in post menopausal women
Authors: Cortet Bernard , Blotman Francis , Debiais Françoise , Huas Dominique , Mercier Florence , Rousseaux Chantal , Berger Véronique , Gaudin Anne-Françoise , Cotté François-Emery
Published: January 2011

Background

The study aimed to describe the characteristics of women treated for recently-diagnosed osteoporosis, to identify variables associated with different treatment regimens and to assess impact on quality of life.

Methods

This is an observational, cross-sectional pharmacoepidemiological study performed in France. A random sample of 684 general practitioners, gynaecologists and rheumatologists included the first three post-menopausal osteoporotic women consulting in the previous six months on the basis of densitometry or fracture. Data on osteoporosis, fracture risk factors, treatments and comorbidities was collected with a physician questionnaire. Data on quality of life was collected using the SF-12.

Results

Data were analysed for 1,306 patients, of whom 1,117 (85.5%) had been evaluated by densitometry within the previous six months and 554 (42.4%) had experienced a fracture, most frequently of the spine or wrist within the previous six months. Osteoporotic fracture risk factors were reported in 1,028 women (78.7%). 746 women (57.1%) were currently receiving treatment, most frequently weekly or monthly bisphosphonates. Five variables were associated with prescription choice: age (p < 0.0001), physician speciality (p < 0.0001), previous fracture history (p = 0.0002), ongoing treatment at the time of consultation (p = 0.0091) and paraclinical investigations performed in the previous six months (p = 0.0060). SF-12 scores were lower in women complaining of pain, with recent fractures and with spine or hip fractures and in women consulting rheumatologists.

Conclusions

A high proportion of women diagnosed with osteoporosis had been evaluated by densitometry, in agreement with national guidelines. Treatment choice varied between physician groups.
Loss of expression of TGF-βs and their receptors in chronic skin lesions induced by sulfur mustard as compared with chronic contact dermatitis patients
Authors: Khaheshi Isa , Keshavarz Saeed , Imani Fooladi Abbas Ali , Ebrahimi Majid , Yazdani Samaneh , Panahi Yunes , Shohrati Majid , Nourani Mohammad Reza
Published: January 2011

Background

Sulfur mustard (SM) is a blister-forming agent that has been used as a chemical weapon. Sulfur mustard can cause damage in various organs, especially the skin, respiratory system, and eyes. Generally, the multiple complications of mustard gas result from its alkalizing potency; it reacts with cellular components like DNA, RNA, proteins, and lipid membranes.

TGF-β is a multi-functional cytokine with multiple biological effects ranging from cell differentiation and growth inhibition to extracellular matrix stimulation, immunosuppression, and immunomodulation. TGF-β has 3 isoforms (TGF-β 1, 2, 3) and its signaling is mediated by its receptors: R1, R2 and intracellular Smads molecules.

TGF-β has been shown to have anti-inflammatory effects. TGF-βs and their receptors also have an important role in modulation of skin inflammation, proliferation of epidermal cells, and wound healing, and they have been implicated in different types of skin inflammatory disorders.

Methods

Seventeen exposed SM individuals (48.47 ± 9.3 years), 17 chronic dermatitis patients (46.52 ± 14.6 years), and 5 normal controls (44.00 ± 14.6 years) were enrolled in this study.

Evaluation of TGF-βs and their receptors expressions was performed by semiquantitative RT-PCR. Only TGF1was analyzed immunohistochemically.

Results

Our results showed significant decreases in the expression percentages of TGF-β 1, 2 and R1, R2 in chemical victims in comparison with chronic dermatitis and normal subjects and significant decreases in the intensity of R1 and R2 expressions in chemical victims in comparison with chronic dermatitis and normal controls. (P value < 0.05)

Conclusions

TGF-βs and their receptors appear to have a noticeable role in chronic inflammatory skin lesions caused by sulfur mustard.
Cre-LoxP-regulated expression of monoclonal antibodies driven by an ovalbumin promoter in primary oviduct cells
Authors: Oishi Isao , Kim Sungtae , Yoshii Kyoko , Esteban Concepcion Rodriguez , Izpisua Belmonte Juan Carlos
Published: January 2011

Background

A promoter capable of driving high-level transgene expression in oviduct cells is important for developing transgenic chickens capable of producing therapeutic proteins, including monoclonal antibodies (mAbs), in the whites of laid eggs. Ovalbumin promoters can be used as oviduct-specific regulatory sequences in transgenic chickens, but their promoter activities are not high, according to previous reports.

Results

In this study, while using a previously characterized ovalbumin promoter, we attempted to improve the expression level of mAbs using a Cre/loxP-mediated conditional excision system. We constructed a therapeutic mAb expression vector, pBS-DS-hIgG, driven by the CMV and CAG promoters, in which the expression of the heavy and light chains of humanized immunoglobulin G (hIgG) is preceded by two floxed stuffer reporter genes. In the presence of Cre, the stuffer genes were precisely excised and hIgG expression was induced in pBS-DS-hIgG-transfected 293T cells. In chicken oviduct primary culture cells, hIgG was expressed after transfection of pBS-DS-hIgG together with the ovalbumin promoter-driven Cre expression vector. The expression level of hIgG in these cells was increased 40-fold over that induced directly by the ovalbumin promoter. On the other hand, hIgG was not induced by the ovalbumin promoter-driven Cre in chicken embryonic fibroblast cells.

Conclusions

The Cre/loxP-based system could significantly increase ovalbumin promoter-driven production of proteins of interest, specifically in oviduct cells. This expression system could be useful for producing therapeutic mAbs at high level using transgenic chickens as bioreactors.
Systematic cross-validation of 454 sequencing and pyrosequencing for the exact quantification of DNA methylation patterns with single CpG resolution
Authors: Potapova Anna , Albat Cord , Hasemeier Britta , Haeussler Katrin , Lamprecht Stella , Suerbaum Sebastian , Kreipe Hans , Lehmann Ulrich
Published: January 2011

Background

New high-throughput sequencing technologies promise a very sensitive and high-resolution analysis of DNA methylation patterns in quantitative terms. However, a detailed and comprehensive comparison with existing validated DNA methylation analysis methods is not yet available. Therefore, a systematic cross-validation of 454 sequencing and conventional pyrosequencing, both of which offer exact quantification of methylation levels with a single CpG dinucleotide resolution, was performed.

Results

To this end the methylation patterns of 12 loci (GSTπ1, p16

INK4a

, RASSF1A, SOCS1, MAL, hsa-mir-1-1, hsa-mir-9-3, hsa-mir-34a, hsa-mir-596, hsa-mir-663, MINT31, and LINE-1) were analyzed in ten primary hepatocellular carcinoma specimens. After applying stringent quality control criteria, 35749 sequences entered further analysis. The methylation level of individual CpG dinucleotides obtained by 454 sequencing was systematically compared with the corresponding values obtained by conventional pyrosequencing. Statistical analyses revealed an excellent concordance of methylation levels for all individual CpG dinucleotides under study (r2 = 0.927).

Conclusions

Our results confirm that 454 sequencing of bisulfite treated genomic DNA provides reliable high quality quantitative methylation data and identify MAL, hsa-mir-9-3, hsa-mir-596, and hsa-mir-663 as new targets of aberrant DNA methylation in human hepatocelluar carcinoma. In addition, the single molecule resolution of 454 sequencing provides unprecedented information about the details of DNA methylation pattern heterogeneity in clinical samples.
Assessment of antiproliferative and antiplasmodial activities of five selected Apocynaceae species
Authors: Wong Siu Kuin , Lim Yau Yan , Abdullah Noor Rain , Nordin Fariza Juliana
Published: January 2011

Background

Studies have shown that the barks and roots of some Apocynaceae species have anticancer and antimalarial properties. In this study, leaf extracts of five selected species of Apocynaceae used in traditional medicine (Alstonia angustiloba, Calotropis gigantea, Dyera costulata, Kopsia fruticosa and Vallaris glabra) were assessed for antiproliferative (APF) and antiplasmodial (APM) activities, and analysed for total alkaloid content (TAC), total phenolic content (TPC) and radical-scavenging activity (RSA). As V. glabra leaf extracts showed wide spectrum APF and APM activities, they were further screened for saponins, tannins, cardenolides and terpenoids.

Methods

APF and APM activities were assessed using the sulphorhodamine B and lactate dehydrogenase assays, respectively. TAC, TPC and RSA were analysed using Dragendorff precipitation, Folin-Ciocalteu and DPPH assays, respectively. Screening for saponins, tannins, cardenolides and terpenoids were conducted using the frothing, ferric chloride, Kedde and vanillin-H2SO4 tests, respectively.

Results

Leaf extracts of A. angustiloba, C. gigantea and V. glabra displayed positive APF activity. Dichloromethane (DCM) extract of C. gigantea, and DCM and DCM:MeOH extracts of V. glabra showed strong APF activity against all six human cancer cell lines tested. DCM extract of A. angustiloba was effective against three cancer cell lines. Against MCF-7 and MDA-MB-231 cell lines, DCM extract of C. gigantea was stronger than standard drugs of xanthorrhizol, curcumin and tamoxifen. All five species were effective against K1 strain of Plasmodium falciparum and three species (C. gigantea, D. costulata and K. fruticosa) were effective against 3D7 strain. Against K1 strain, all four extracts of V. glabra displayed effective APM activity. Extracts of D. costulata were effective against 3D7 strain. Selectivity index values of extracts of A. angustiloba, C. gigantea and V. glabra suggested that they are potentially safe for use to treat malaria. Extracts of K. fruticosa had the highest TAC while D. costulata had the highest TPC and RSA. Phytochemical screening of extracts of V. glabra also showed the presence of terpenoids, tannins and saponins.

Conclusions

Leaf extracts of C. gigantea and V. glabra showed great promise as potential candidates for anticancer drugs as they inhibited the growth of all six cancer cell lines. Against K1 strain of P. falciparum, all four extracts of V. glabra displayed effective APM activity. The wide spectrum APF and APM activities of V. glabra are reported for the first time and this warrants further investigation into its bioactive compounds.
Spatial and temporal variation in the kdr allele L1014S in Anopheles gambiae s.s. and phenotypic variability in susceptibility to insecticides in Western Kenya
Authors: Mathias Derrick K , Ochomo Eric , Atieli Francis , Ombok Maurice , Nabie Bayoh M , Olang George , Muhia Damaris , Kamau Luna , Vulule John M , Hamel Mary J , Hawley William A , Walker Edward D , Gimnig John E
Published: January 2011

Background

Malaria vector control in Africa depends upon effective insecticides in bed nets and indoor residual sprays. This study investigated the extent of insecticide resistance in Anopheles gambiae s.l., Anopheles gambiae s.s. and Anopheles arabiensis in western Kenya where ownership of insecticide-treated bed nets has risen steadily from the late 1990s to 2010. Temporal and spatial variation in the frequency of a knock down resistance (kdr) allele in A. gambiae s.s. was quantified, as was variation in phenotypic resistance among geographic populations of A. gambiae s.l.

Methods

To investigate temporal variation in kdr frequency, individual specimens of A. gambiae s.s. from two sentinel sites were genotyped using RT-PCR from 1996-2010. Spatial variation in kdr frequency, species composition, and resistance status were investigated in additional populations of A. gambiae s.l. sampled in western Kenya in 2009 and 2010. Specimens were genotyped for kdr as above and identified to species via conventional PCR. Field-collected larvae were reared to adulthood and tested for insecticide resistance using WHO bioassays.

Results

Anopheles gambiae s.s. showed a dramatic increase in kdr frequency from 1996 - 2010, coincident with the scale up of insecticide-treated nets. By 2009-2010, the kdr L1014S allele was nearly fixed in the A. gambiae s.s. population, but was absent in A. arabiensis. Near Lake Victoria, A. arabiensis was dominant in samples, while at sites north of the lake A. gambiae s.s was more common but declined relative to A. arabiensis from 2009 to 2010. Bioassays demonstrated that A. gambiae s.s. had moderate phenotypic levels of resistance to DDT, permethrin and deltamethrin while A. arabiensis was susceptible to all insecticides tested.

Conclusions

The kdr L1014S allele has approached fixation in A. gambiae s.s. populations of western Kenya, and these same populations exhibit varying degrees of phenotypic resistance to DDT and pyrethroid insecticides. The near absence of A. gambiae s.s. from populations along the lakeshore and the apparent decline in other populations suggest that insecticide-treated nets remain effective against this mosquito despite the increase in kdr allele frequency. The persistence of A. arabiensis, despite little or no detectable insecticide resistance, is likely due to behavioural traits such as outdoor feeding and/or feeding on non-human hosts by which this species avoids interaction with insecticide-treated nets.
Genetic and phenotypic variation of the malaria vector Anopheles atroparvus in southern Europe
Authors: Vicente José L , Sousa Carla A , Alten Bulent , Caglar Selim S , Falcutá Elena , Latorre José M , Toty Celine , Barré Hélène , Demirci Berna , Di Luca Marco , Toma Luciano , Alves Ricardo , Salgueiro Patrícia , Silva Teresa L , Bargues Maria D , Mas-Coma Santiago , Boccolini Daniela , Romi Roberto , Nicolescu Gabriela , do Rosário Virgílio E , Ozer Nurdan , Fontenille Didier , Pinto João
Published: January 2011

Background

There is a growing concern that global climate change will affect the potential for pathogen transmission by insect species that are vectors of human diseases. One of these species is the former European malaria vector,Anopheles atroparvus. Levels of population differentiation ofAn. atroparvusfrom southern Europe were characterized as a first attempt to elucidate patterns of population structure of this former malaria vector. Results are discussed in light of a hypothetical situation of re-establishment of malaria transmission.

Methods

Genetic and phenotypic variation was analysed in nine mosquito samples collected from five European countries, using eight microsatellite loci and geometric morphometrics on 21 wing landmarks.

Results

Levels of genetic diversity were comparable to those reported for tropical malaria vectors. Low levels of genetic (0.004 <FST<0.086) and phenotypic differentiation were detected amongAn. atroparvuspopulations spanning over 3,000 km distance. Genetic differentiation (0.202 <FST<0.299) was higher between the sibling speciesAn. atroparvusandAnopheles maculipenniss.s. Differentiation between sibling species was not so evident at the phenotype level.

Conclusions

Levels of population differentiation withinAn. atroparvuswere low and not correlated with geographic distance or with putative physical barriers to gene flow (Alps and Pyrenées). While these results may suggest considerable levels of gene flow, other explanations such as the effect of historical population perturbations can also be hypothesized.
Plasma Lipoprotein-associated Phospholipase A2 in Patients with Metabolic Syndrome and Carotid Atherosclerosis
Authors: Gong Hui-ping , Du Yi-meng , Zhong Li-na , Dong Zhao-qiang , Wang Xin , Mao Yong-jun , Lu Qing-hua
Published: January 2011

Background

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a recently identified and potentially useful plasma biomarker for cardiovascular and atherosclerotic diseases. However, the correlation between the Lp-PLA2 activity and carotid atherosclerosis remains poorly investigated in patients with metabolic syndrome (MetS). The present study aimed to evaluate the potential role of Lp-PLA2 as a comprehensive marker of metabolic syndrome in individuals with and without carotid atherosclerosis.

Methods

We documented 118 consecutive patients with MetS and 70 age- and sex-matched healthy subjects served as controls. The patients were further divided into two groups: 39 with carotid plaques and 79 without carotid plaques to elucidate the influence of Lp-PLA2 on carotid atherosclerosis. The plasma Lp-PLA2 activity was measured by using ELISA method and carotid intimal-media thickness (IMT) was performed by ultrasound in all participants.

Results

Lp-PLA2 activity was significantly increased in MetS subgroups when compared with controls, and was higher in patients with carotid plaques than those without plaques (P < 0.05). Furthermore, we found that significant difference in Lp-PLA2 was obtained between patients with three and four disorders of metabolic syndrome (P < 0.01). Age (β = 0.183, P = 0.029), LDL-cholesterol (β = 0.401, P = 0.000) and waist-hip ratio (β = 0.410, P = 0.000) emerged as significant and independent determinants of Lp-PLA2 activity. Multiple stepwise regression analysis revealed that LDL-cholesterol (β = 0.309, P = 0.000), systolic blood pressure (β = 0.322, P = 0.002) and age (β = 0.235, P = 0.007) significantly correlated with max IMT, and Lp-PLA2 was not an independent predictor for carotid IMT.

Conclusions

Lp-PLA2 may be a modulating factor for carotid IMT via age and LDL-cholesterol, not independent predictor in the pathophysiological process of carotid atherosclerosis in patients with MetS.
The proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations
Authors: Aung Lynn Htet Htet , Yin Rui-Xing , Miao Lin , Hu Xi-Jiang , Yan Ting-Ting , Cao Xiao-Li , Wu Dong-Feng , Li Qing , Pan Shang-Ling , Wu Jin-Zhen
Published: January 2011

Background

Proprotein convertase subtilisin-like kexin type 9 (PCSK9) plays a key role in regulating plasma low-density lipoprotein cholesterol (LDL-C) levels. However, the association of E670G (rs505151) polymorphism in the PCSK9 gene and serum lipid levels is inconsistent in several previous studies. The present study was undertaken to detect the association of PCSK9 E670G polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

Methods

A total of 649 subjects of Bai Ku Yao and 646 participants of Han were randomly selected from our previous samples. Genotypes of the PCSK9 E670G polymorphism were determined via polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.

Results

Serum levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, and apolipoprotein (Apo) AI were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of G allele was 2.00% in Bai Ku Yao and 4.80% in Han (P < 0.01). There was significant difference in the genotypic and allelic frequencies between Bai Ku Yao and Han (P < 0.01); between normal LDL-C (≤ 3.20 mmol/L) and high LDL-C subgroups (> 3.20 mmol/L, P < 0.01) in Bai Ku Yao; and between normal HDL-C (≥ 0.91 mmol/L) and low HDL-C (< 0.91 mmol/L, P < 0.05), between normal ApoAI (≥ 1.00 g/L) and low ApoAI (< 1.00 g/L, P < 0.05), or between normal ApoAI/ApoB ratio (≥ 1.00) and low ApoAI/ApoB ratio (< 1.00, P < 0.01) subgroups in Han. The G allele carriers in Han had higher serum HDL-C levels and the ratio of ApoAI to ApoB than the G allele noncarriers. The G allele carriers in Han had higher serum HDL-C and ApoAI levels than the G allele noncarriers in males (P < 0.05 for each), whereas the G allele carriers had lower serum ApoB levels and higher the ratio of ApoAI to ApoB than the G allele noncarriers in females (P < 0.05 for all). Serum HDL-C and ApoAI levels in Han were correlated with genotypes (P < 0.05) in males, and serum ApoB levels and the ratio of ApoAI to ApoB were associated with genotypes (P < 0.05) in females.

Conclusions

The PCSK9 E670G polymorphism is mainly associated with some serum lipid parameters in the Han population. The G allele carriers had higher serum HDL-C and ApoAI levels in males, and lower serum ApoB levels and higher the ApoAI/ApoB ratio in females than the G allele noncarriers.
Nanometric self-assembling peptide layers maintain adult hepatocyte phenotype in sandwich cultures
Authors: Wu Jonathan , Marí-Buyé Núria , Muiños Teresa Fernández , Borrós Salvador , Favia Pietro , Semino Carlos E
Published: January 2011

Background

Isolated hepatocytes removed from their microenvironment soon lose their hepatospecific functions when cultured. Normally hepatocytes are commonly maintained under limited culture medium supply as well as scaffold thickness. Thus, the cells are forced into metabolic stress that degenerate liver specific functions. This study aims to improve hepatospecific activity by creating a platform based on classical collagen sandwich cultures.

Results

The modified sandwich cultures replace collagen with self-assembling peptide, RAD16-I, combined with functional peptide motifs such as the integrin-binding sequence RGD and the laminin receptor binding sequence YIG to create a cell-instructive scaffold. In this work, we show that a plasma-deposited coating can be used to obtain a peptide layer thickness in the nanometric range, which in combination with the incorporation of functional peptide motifs have a positive effect on the expression of adult hepatocyte markers including albumin, CYP3A2 and HNF4-alpha.

Conclusions

This study demonstrates the capacity of sandwich cultures with modified instructive self-assembling peptides to promote cell-matrix interaction and the importance of thinner scaffold layers to overcome mass transfer problems. We believe that this bioengineered platform improves the existing hepatocyte culture methods to be used for predictive toxicology and eventually for hepatic assist technologies and future artificial organs.
Stable isotope shifted matrices enable the use of low mass ion precursor scanning for targeted metabolite identification
Authors: Reilly Charles B , Ramarathinam Sri H , Williamson Nicholas A , Purcell Anthony W
Published: January 2011

We describe a method to identify metabolites of proteins that eliminates endogenous background by using stable isotope labeled matrices. This technique allows selective screening of the intact therapeutic molecule and all metabolites using a modified precursor ion scan that monitors low molecular weight fragment ions produced during MS/MS. This distinct set of low mass ions differs between isotopically labeled and natural isotope containing species allowing excellent discrimination between endogenous compounds and target analytes. All compounds containing amino acids that consist of naturally abundant isotopes can be selected using this scanning technique for further analysis, including metabolites of the parent molecule. The sensitivity and selectivity of this technique is discussed with specific examples of insulin metabolites identified within a complex matrix using a range of different validated low mass target ions.
PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration
Authors: Chaitanya Ganta Vijay , Alexander Jonathan S , Babu Phanithi Prakash
Published: January 2011

The normal function of poly (ADP-ribose) polymerase-1 (PARP-1) is the routine repair of DNA damage by adding poly (ADP ribose) polymers in response to a variety of cellular stresses. Recently, it has become widely appreciated that PARP-1 also participates in diverse physiological and pathological functions from cell survival to several forms of cell death and has been implicated in gene transcription, immune responses, inflammation, learning, memory, synaptic functions, angiogenesis and aging. In the CNS, PARP inhibition attenuates injury in pathologies like cerebral ischemia, trauma and excitotoxicity demonstrating a central role of PARP-1 in these pathologies. PARP-1 is also a preferred substrate for several 'suicidal' proteases and the proteolytic action of suicidal proteases (caspases, calpains, cathepsins, granzymes and matrix metalloproteinases (MMPs)) on PARP-1 produces several specific proteolytic cleavage fragments with different molecular weights. These PARP-1 signature fragments are recognized biomarkers for specific patterns of protease activity in unique cell death programs. This review focuses on specific suicidal proteases active towards PARP-1 to generate signature PARP-1 fragments that can identify key proteases and particular forms of cell death involved in pathophysiology. The roles played by some of the PARP-1 fragments and their associated binding partners in the control of different forms of cell death are also discussed.
Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion
Authors: Anastasiadis Kyriakos , Antonitsis Polychronis , Argiriadou Helena , Koliakos Georgios , Doumas Argyrios , Khayat Andre , Papakonstantinou Christos , Westaby Stephen
Published: January 2011

We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies.
Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent
Authors: Horibe Tomohisa , Kohno Masayuki , Haramoto Mari , Ohara Koji , Kawakami Koji
Published: January 2011

Background

Despite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.

Methods

We focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.

Results

It was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, and gastric cancer cell linesin vitro. In contrast, Antp-TPR peptide did not affect the viability of normal cells. Moreover, analysisin vivorevealed that Antp-TPR peptide displayed a significant antitumor activity in a xenograft model of human pancreatic cancer in mice.

Conclusion

These results indicate that Antp-TPR peptide would provide a potent and selective anticancer therapy to cancer patients.
HIV, appendectomy and postoperative complications at a reference hospital in Northwest Tanzania: cross-sectional study
Authors: Giiti Geofrey C , Mazigo Humphrey D , Heukelbach Jorg , Mahalu William
Published: January 2011

Background

Appendicitis is a frequent surgical emergency worldwide. The present study was conducted to determine the prevalence of HIV, and the association of infection with clinical, intraoperative and histological findings and outcome, among patients with appendicitis.

Methods

We performed a cross sectional study at Weill-Bugando Medical Centre in northwest Tanzania. In total, 199 patients undergoing appendectomy were included. Demographic characteristics of patients, clinical features, laboratory, intraoperative and histopathological findings, and HIV serostatus were recorded.

Results

In total, 26/199 (13.1%) were HIV-seropositive. The HIV-positive population was significantly older (mean age: 38.4 years) than the HIV-negative population (25.3 years; p < 0.001). Leukocytosis was present in 87% of seronegative patients, as compared to 34% in seropositive patients (p = 0.0001), and peritonitis was significantly more frequent among HIV-positives (31% vs. 2%; p < 0.001). The mean (SD) length of hospital stay was significantly longer in HIV-positives (7.12 ± 2.94 days vs. 4.02 ± 1.14 days; p < 0.001); 11.5% of HIV patients developed surgical site infections, as compared to 0.6% in the HIV-negative group (p = 0.004).

Conclusion

HIV infections are common among patients with appendicitis in Tanzania, and are associated with severe morbidity, postoperative complications and longer hospital stays. Early diagnosis of appendicitis and prompt appendectomy are crucial in areas with high prevalence of HIV infection. Routine pre-test counseling and HIV screening for appendicitis patients is recommended to detect early cases who may benefit from HAART.
Adenovirus serotype 7 associated with a severe lower respiratory tract disease outbreak in infants in Shaanxi Province, China
Authors: Tang Liuying , Wang Li , Tan Xiaojuan , Xu Wenbo
Published: January 2011

Background

Pneumonia caused by adenovirus infection is usually severe especially with adenovirus serotype 7 commonly associated with lower respiratory tract disease outbreaks. We reported an outbreak of 70 cases of severe pneumonia with one death of infants in Shaanxi Province, China. Sampling showed adenovirus 7 (Ad7) as the primary pathogen with some co-infections.

Results

Two strains of adenovirus and two strains of enterovirus were isolated, the 21 pharynx swabs showed 14 positive amplifications for adenovirus; three co-infections with respiratory syncytial virus, two positive for rhinovirus, one positive for parainfluenza 3, and four negative. Adenovirus typing showed nine of the nine adenovirus positive samples were HAdV-7, three were HAdV-3 and two were too weak to perform sequencing. The entire hexon gene of adenovirus was sequenced and analyzed for the two adenovirus serotype 7 isolates, showing the nucleic acid homology was 99.8% between the two strains and 99.5% compared to the reference strain HAdV-7 (GenBank accession number AY769946). For the 21 acute phase serum samples from the 21 patients, six samples had positives results for ELISA detection of HAdV IgA, and the neutralization titers of the convalescent-phase samples were four times higher than those of the acute-phase samples in nine pairs.

Conclusions

We concluded adenovirus was the viral pathogen, primarily HAdV-7, with some co-infections responsible for the outbreak. This is the first report of an infant pneumonia outbreak caused by adenovirus serotype 7 in Shaanxi Province, China.
In-vitro antiviral activity of Solanum nigrum against Hepatitis C Virus
Authors: Javed Tariq , Ashfaq Usman Ali , Riaz Sana , Rehman Sidra , Riazuddin Sheikh
Published: January 2011

Background

Hepatitis C is a major health problem causes liver cirrhosis, hepatocellular carcinoma and death. The current treatment of standard interferon in combination with ribavirin, has limited benefits due to emergence of resistant mutations during long-term treatment, adverse side effects and high cost. Hence, there is a need for the development of more effective, less toxic antiviral agents.

Results

The present study was designed to search anti-HCV plants from different areas of Pakistan. Ten medicinal plants were collected and tested for anti-HCV activity by infecting the liver cells with HCV 3a innoculum. Methanol and chloroform extracts of Solanum nigrum (SN) seeds exhibited 37% and more than 50% inhibition of HCV respectively at non toxic concentration. Moreover, antiviral effect of SN seeds extract was also analyzed against HCV NS3 protease by transfecting HCV NS3 protease plasmid into liver cells. The results demonstrated that chloroform extract of SN decreased the expression or function of HCV NS3 protease in a dose- dependent manner and GAPDH remained constant.

Conclusion

These results suggest that SN extract contains potential antiviral agents against HCV and combination of SN extract with interferon will be better option to treat chronic HCV.