bluuebunny/crossref_metadata_2025 huggingface dataset:
SIS: a program to generate draft genome sequence scaffolds for prokaryotes
Authors: Dias Zanoni , Dias Ulisses , Setubal João C
Published: May 2012

Background

Decreasing costs of DNA sequencing have made prokaryotic draft genome sequences increasingly common. A contig scaffold is an ordering of contigs in the correct orientation. A scaffold can help genome comparisons and guide gap closure efforts. One popular technique for obtaining contig scaffolds is to map contigs onto a reference genome. However, rearrangements that may exist between the query and reference genomes may result in incorrect scaffolds, if these rearrangements are not taken into account. Large-scale inversions are common rearrangement events in prokaryotic genomes. Even in draft genomes it is possible to detect the presence of inversions given sufficient sequencing coverage and a sufficiently close reference genome.

Results

We present a linear-time algorithm that can generate a set of contig scaffolds for a draft genome sequence represented in contigs given a reference genome. The algorithm is aimed at prokaryotic genomes and relies on the presence of matching sequence patterns between the query and reference genomes that can be interpreted as the result of large-scale inversions; we call these patterns inversion signatures. Our algorithm is capable of correctly generating a scaffold if at least one member of every inversion signature pair is present in contigs and no inversion signatures have been overwritten in evolution. The algorithm is also capable of generating scaffolds in the presence of any kind of inversion, even though in this general case there is no guarantee that all scaffolds in the scaffold set will be correct. We compare the performance of sis, the program that implements the algorithm, to seven other scaffold-generating programs. The results of our tests show that sis has overall better performance.

Conclusions

sis is a new easy-to-use tool to generate contig scaffolds, available both as stand-alone and as a web server. The good performance of sis in our tests adds evidence that large-scale inversions are widespread in prokaryotic genomes.
Regulation of ROCK1 via Notch1 during breast cancer cell migration into dense matrices
Authors: Raviraj Vanisri , Fok Sandra , Zhao Jifei , Chien Hsin-Ya , Lyons J Guy , Thompson Erik W , Soon Lilian
Published: May 2012

Background

The behaviour of tumour cells depends on factors such as genetics and the tumour microenvironment. The latter plays a crucial role in normal mammary gland development and also in breast cancer initiation and progression. Breast cancer tissues tend to be highly desmoplastic and dense matrix as a pre-existing condition poses one of the highest risk factors for cancer development. However, matrix influence on tumour cell gene expression and behaviour such as cell migration is not fully elucidated.

Results

We generated high-density (HD) matrices that mimicked tumour collagen content of 20 mg/cm3that were ~14-fold stiffer than low-density (LD) matrix of 1 mg/cm3. Live-cell imaging showed breast cancer cells utilizing cytoplasmic streaming and cell body contractility for migration within HD matrix. Cell migration was blocked in the presence of both the ROCK inhibitor, Y-27632, and the MMP inhibitor, GM6001, but not by the drugs individually. This suggests roles for ROCK1 and MMP in cell migration are complicated by compensatory mechanisms. ROCK1 expression and protein activity, were significantly upregulated in HD matrix but these were blocked by treatment with a histone deacetylase (HDAC) inhibitor, MS-275. In HD matrix, the inhibition of ROCK1 by MS-275 was indirect and relied upon protein synthesis and Notch1. Inhibition of Notch1 using pooled siRNA or DAPT abrogated the inhibition of ROCK1 by MS-275.

Conclusion

Increased matrix density elevates ROCK1 activity, which aids in cell migration via cell contractility. The upregulation of ROCK1 is epigenetically regulated in an indirect manner involving the repression of Notch1. This is demonstrated from inhibition of HDACs by MS-275, which caused an upregulation of Notch1 levels leading to blockade of ROCK1 expression.
Artificial neural networks modeling gene-environment interaction
Authors: Günther Frauke , Pigeot Iris , Bammann Karin
Published: May 2012

Background

Gene-environment interactions play an important role in the etiological pathway of complex diseases. An appropriate statistical method for handling a wide variety of complex situations involving interactions between variables is still lacking, especially when continuous variables are involved. The aim of this paper is to explore the ability of neural networks to model different structures of gene-environment interactions. A simulation study is set up to compare neural networks with standard logistic regression models. Eight different structures of gene-environment interactions are investigated. These structures are characterized by penetrance functions that are based on sigmoid functions or on combinations of linear and non-linear effects of a continuous environmental factor and a genetic factor with main effect or with a masking effect only.

Results

In our simulation study, neural networks are more successful in modeling gene-environment interactions than logistic regression models. This outperfomance is especially pronounced when modeling sigmoid penetrance functions, when distinguishing between linear and nonlinear components, and when modeling masking effects of the genetic factor.

Conclusion

Our study shows that neural networks are a promising approach for analyzing gene-environment interactions. Especially, if no prior knowledge of the correct nature of the relationship between co-variables and response variable is present, neural networks provide a valuable alternative to regression methods that are limited to the analysis of linearly separable data.
Genetic and genome-wide transcriptomic analyses identify co-regulation of oxidative response and hormone transcript abundance with vitamin C content in tomato fruit
Authors: Lima-Silva Viviana , Rosado Abel , Amorim-Silva Vitor , Muñoz-Mérida Antonio , Pons Clara , Bombarely Aureliano , Trelles Oswaldo , Fernández-Muñoz Rafael , Granell Antonio , Valpuesta Victoriano , Botella Miguel Ángel
Published: May 2012

Background

L-ascorbic acid (AsA; vitamin C) is essential for all living plants where it functions as the main hydrosoluble antioxidant. It has diverse roles in the regulation of plant cell growth and expansion, photosynthesis, and hormone-regulated processes. AsA is also an essential component of the human diet, being tomato fruit one of the main sources of this vitamin. To identify genes responsible for AsA content in tomato fruit, transcriptomic studies followed by clustering analysis were applied to two groups of fruits with contrasting AsA content. These fruits were identified after AsA profiling of an F8 Recombinant Inbred Line (RIL) population generated from a cross between the domesticated speciesSolanum lycopersicumand the wild relativeSolanum pimpinellifollium.

Results

We found large variability in AsA content within the RIL population with individual RILs with up to 4-fold difference in AsA content. Transcriptomic analysis identified genes whose expression correlated either positively (PVCgenes) or negatively (NVCgenes) with the AsA content of the fruits. Cluster analysis using SOTA allowed the identification of subsets of co-regulated genes mainly involved in hormones signaling, such as ethylene, ABA, gibberellin and auxin, rather than any of the known AsA biosynthetic genes. Data mining of the correspondingPVCandNVCorthologs in Arabidopis databases identified flagellin and other ROS-producing processes as cues resulting in differential regulation of a high percentage of the genes from both groups of co-regulated genes; more specifically, 26.6% of the orthologous PVC genes, and 15.5% of the orthologous NVC genes were induced and repressed, respectively, under flagellin22 treatment inArabidopsis thaliana.

Conclusion

Results here reported indicate that the content of AsA in red tomato fruit from our selected RILs are not correlated with the expression of genes involved in its biosynthesis. On the contrary, the data presented here supports that AsA content in tomato fruit co-regulates with genes involved in hormone signaling and they are dependent on the oxidative status of the fruit.
The prevalence of Chlamydia trachomatis infection in Australia: a systematic review and meta-analysis
Authors: Lewis Dyani , Newton Danielle C , Guy Rebecca J , Ali Hammad , Chen Marcus Y , Fairley Christopher K , Hocking Jane S
Published: May 2012

Background

Chlamydia trachomatisis a common sexually transmitted infection in Australia. This report aims to measure the burden of chlamydia infection by systematically reviewing reports on prevalence in Australian populations.

Methods

Electronic databases and conference websites were searched from 1997–2011 using the terms ‘Chlamydia trachomatis’ OR ‘chlamydia’ AND ‘prevalence’ OR ‘epidemiology’ AND ‘Australia’. Reference lists were checked and researchers contacted for additional literature. Studies were categorised by setting and participants, and meta-analysis conducted to determine pooled prevalence estimates for each category.

Results

Seventy-six studies met the inclusion criteria for the review. There was a high level of heterogeneity between studies; however, there was a trend towards higher chlamydia prevalence in younger populations, Indigenous Australians, and those attending sexual health centres. In community or general practice settings, pooled prevalence for women <25 years in studies conducted post-2005 was 5.0% (95% CI: 3.1, 6.9; five studies), and for men <30 years over the entire review period was 3.9% (95% CI: 2.7, 5.1; six studies). For young Australians aged <25 years attending sexual health, family planning or youth clinics, estimated prevalence was 6.2% (95% CI: 5.1, 7.4; 10 studies) for women and 10.2% (95% CI: 9.5, 10.9; five studies) for men. Other key findings include pooled prevalence estimates of 22.1% (95% CI: 19.0, 25.3; three studies) for Indigenous women <25 years, 14.6% (95% CI: 11.5, 17.8; three studies) for Indigenous men <25 years, and 5.6% (95% CI: 4.8, 6.3; 11 studies) for rectal infection in men who have sex with men. Several studies failed to report basic demographic details such as sex and age, and were therefore excluded from the analysis.

Conclusions

Chlamydia trachomatisinfections are a significant health burden in Australia; however, accurate estimation of chlamydia prevalence in Australian sub-populations is limited by heterogeneity within surveyed populations, and variations in sampling methodologies and data reporting. There is a need for more large, population-based studies and prospective cohort studies to compliment mandatory notification data.
Prevention and treatment of surgical site infection in HIV-infected patients
Authors: Zhang Lei , Liu Bao-Chi , Zhang Xiao-Yan , Li Lei , Xia Xian-Jun , Guo Rui-Zhang
Published: May 2012

Background

Surgical site infection (SSI) are the third most frequently reported nosocomial infection, and the most common on surgical wards. HIV-infected patients may increase the possibility of developing SSI after surgery. There are few reported date on incidence and the preventive measures of SSI in HIV-infected patients. This study was to determine the incidence and the associated risk factors for SSI in HIV-infected patients. And we also explored the preventive measures.

Methods

A retrospective study of SSI was conducted in 242 HIV-infected patients including 17 patients who combined with hemophilia from October 2008 to September 2011 in Shanghai Public Health Clinical Center. SSI were classified according to Centers for Disease Control and Prevention (CDC) criteria and identified by bedside surveillance and post-discharge follow-up. Data were analyzed using SPSS 16.0 statistical software (SPSS Inc., Chicago, IL).

Results

The SSI incidence rate was 47.5% (115 of 242); 38.4% incisional SSIs, 5.4% deep incisional SSIs and 3.7% organ/space SSIs. The SSI incidence rate was 37.9% in HIV-infected patients undergoing abdominal operation. Patients undergoing abdominal surgery with lower preoperative CD4 counts were more likely to develop SSIs. The incidence increased from 2.6% in clean wounds to 100% in dirty wounds. In the HIV-infected patients combined with hemophilia, the mean preoperative albumin and postoperative hemoglobin were found significantly lower than those in no-SSIs group (P<0.05).

Conclusions

SSI is frequent in HIV-infected patients. And suitable perioperative management may decrease the SSIs incidence rate of HIV-infected patients.
The genetic variants at the HLA-DRB1 gene are associated with primary IgA nephropathy in Han Chinese
Authors: Jiyun Yang , Guisen Li , Li Zhu , Yi Shi , Jicheng Lv , Fang Lu , Xiaoqi Liu , Shi Ma , Cheng Jing , Ying Lin , Haiyan Wang , Li Wang , Hong Zhang , Zhenglin Yang
Published: May 2012

Background

Immunoglobulin A nephropathy (IgAN), an immune-complex-mediated glomerulonephritis defined immunohistologically by the presence of glomerular IgA deposits, is the most common primary glomerular disease worldwide and a significant cause of end-stage renal disease. Familial clustering of patients with IgAN suggests a genetic predisposition.

Methods

In this study, 192 patients with IgAN and 192 normal controls in the Sichuan cohort and 935 patients with IgAN and 2,103 normal controls in the Beijing cohort were investigated. HLA-DRB1*01–DRB1*10 specificities were genotyped by the PCR–SSP technique in both cohorts. Based on the HLA-DRB1*04-positive results, the subtypes of HLA-DRB1*04 were analyzed using sequencing-based typing (SBT) in 291 IgAN cases and 420 matched controls.

Results

The frequency of HLA-DRB1*04 in the IgAN group was significantly higher than that in the control group (0.129 vs. 0.092, P = 8.29 × 10-5, odds ratio (OR) =1.381, 95% confidence interval (CI) 1.178–1.619). Other alleles at the HLA-DRB1 locus were observed with no significant differences between the case and control groups. The dominant alleles of the HLA-DRB1*04 subtypes were DRB1*0405 in both cohorts. The frequencies of HLA-DRB1*0405 and 0403 were significantly increased in the patients compared to healthy subjects.

Conclusion

HLA-DRB1*04 was significantly associated with primary IgAN in Chinese population. This result implies that HLA-DRB1 gene plays a major role in primary IgAN.
Cost-effectiveness of family psychoeducation to prevent relapse in major depression: Results from a randomized controlled trial
Authors: Shimodera Shinji , Furukawa Toshi A , Mino Yoshio , Shimazu Kae , Nishida Atsushi , Inoue Shimpei
Published: May 2012

Background

Family psychoeducation is a relatively simple and straightforward intervention whose prophylactic effectiveness and cost-effectiveness is well-established for schizophrenia. We have recently demonstrated its effectiveness for unipolar depression, but its cost-effectiveness has never been examined. We hereby report a cost-effectiveness analysis alongside a randomized controlled trial in order to assess its cost-effectiveness for preventing relapse/recurrence in depression.

Methods

Fifty-seven patients diagnosed with major depression and undergoing its maintenance treatment, and their primary family members were randomized to treatment as usual (TAU) only or to TAU plus family psychoeducation, which consisted of four 2-hour multiple-family sessions consisting of didactic lectures about depression (30 minutes) and group discussion and problem solving (60–90 minutes). The economic analyses were undertaken from the perspective of the National Health Insurance (NHI), assuming the most reasonable price of US$50 per psychoeducation session per patient. The main outcome measures included relapse-free days and direct costs to the NHI.

Results

The intervention group enjoyed 272 (SD: 7.1) relapse-free days, while the control group spent 214 (SD: 90.8) relapse-free days (Cox proportional hazard ratio = 0.17, 95%CI: 0.04 to 0.75, p = 0.002). Cost-effectiveness acceptability curves suggested that the family psychoeducation has 90% or more chances of being cost-effective if the decision-maker is prepared to pay US$20 for one additional relapse-free day. This cost-effectiveness finding was robust when the price for family psychoeducation ranged between 50% to 150% of the baseline scenario in sensitivity analyses. If a relapse-free day is considered to be worth $30 or more, all the pricing scenarios have a close to 100% probability of being cost-effective.

Conclusion

Family psychoeducation is effective in the relapse prevention of depression and is highly likely to be cost-effective if a relapse-free day is valued as US$20 or more.

Trial registration

UMIN-CTR (UMIN000005555)
Use of glucometer and fasting blood glucose as screening tools for diabetes mellitus type 2 and glycated haemoglobin as clinical reference in rural community primary care settings of a middle income country
Authors: Muktabhant Benja , Sanchaisuriya Pattara , Sarakarn Pongdech , Tawityanon Worawitaya , Trakulwong Mantana , Worawat Songsri , Schelp Frank P
Published: May 2012

Background

Thailand is considered to be a middle income country, and to control and prevent type 2 diabetes mellitus (T2DM) is one of the main concerns of the Thai Ministry of Public Health (MoPH). Screening for T2DM and care for T2DM patients has been integrated into the primary health care system, especially in rural areas. The intention of this investigation is to link public health research at the academic level with the local health authorities of a district of a north-eastern province of the country.

Methods

Epidemiological methods were applied to validate the screening tools fasting capillary blood glucose (CBG), measured by glucometer and venous blood for the determination of plasma glucose (VPG), used for screening for T2DM among asymptomatic villagers. For assessing the validity of these two methods glycated haemoglobin (HbA1c) values were determined and used as the ‘clinical reference’.

Results

All together 669 villagers were investigated. Determinations of CBG and VPG resulted in suspected T2DM cases, with 7.3% when assessed by CBG and 6.4% by VPG using a cutoff point of 7 mmol/L (126 mg/dl). Taking HbA1c determinations with a cutoff point of 7% into account, the proportion of T2DM suspected participants increased to 10.4%. By estimating sensitivity, specificity and the positive predictive value of CBG and VPG against the ‘clinical reference’ of HbA1c, sensitivity below 50% for both screening methods has been observed. The positive predictive value was determined to be 58.5% for CBG and 56.8% for VPG. The specificity of the two screening tests was over 96%.

Conclusions

The low sensitivity indicates that using fasting CBG or VPG as a screening tool in the field results in a high proportion of diseased individuals remaining undetected. The equally low positive predictive values (below 60%) indicate a high working load for the curative sector in investigating suspected T2DM cases to determine whether they are truly diseased or false positive cases according to the screening method. Further implications of the results and the controversial discussion related to the use of HbA1c as clinical evidence for suffering from T2DM are also discussed.
Children eat their school lunch too quickly: an exploratory study of the effect on food intake
Authors: Zandian Modjtaba , Ioakimidis Ioannis , Bergström Jakob , Brodin Ulf , Bergh Cecilia , Leon Michael , Shield Julian , Södersten Per
Published: May 2012

Background

Speed of eating, an important aspect of eating behaviour, has recently been related to loss of control of food intake and obesity. Very little time is allocated for lunch at school and thus children may consume food more quickly and food intake may therefore be affected. Study 1 measured the time spent eating lunch in a large group of students eating together for school meals. Study 2 measured the speed of eating and the amount of food eaten in individual school children during normal school lunches and then examined the effect of experimentally increasing or decreasing the speed of eating on total food intake.

Methods

The time spent eating lunch was measured with a stop watch in 100 children in secondary school. A more detailed study of eating behaviour was then undertaken in 30 secondary school children (18 girls). The amount of food eaten at lunch was recorded by a hidden scale when the children ate amongst their peers and by a scale connected to a computer when they ate individually. When eating individually, feedback on how quickly to eat was visible on the computer screen. The speed of eating could therefore be increased or decreased experimentally using this visual feedback and the total amount of food eaten measured.

Results

In general, the children spent very little time eating their lunch. The 100 children in Study 1 spent on average (SD) just 7 (0.8) minutes eating lunch. The girls in Study 2 consumed their lunch in 5.6 (1.2) minutes and the boys ate theirs in only 6.8 (1.3) minutes. Eating with peers markedly distorted the amount of food eaten for lunch; only two girls and one boy maintained their food intake at the level observed when the children ate individually without external influences (258 (38) g in girls and 289 (73) g in boys). Nine girls ate on average 33% less food and seven girls ate 23% more food whilst the remaining boys ate 26% more food. The average speed of eating during school lunches amongst groups increased to 183 (53)% in the girls and to 166 (47)% in the boys compared to the speed of eating in the unrestricted condition. These apparent changes in food intake during school lunches could be replicated by experimentally increasing the speed of eating when the children were eating individually.

Conclusions

If insufficient time is allocated for consuming school lunches, compensatory increased speed of eating puts children at risk of losing control over food intake and in many cases over-eating. Public health initiatives to increase the time available for school meals might prove a relatively easy way to reduce excess food intake at school and enable children to eat more healthily.
Gender difference in carotid intima-media thickness in type 2 diabetic patients: a 4-year follow-up study
Authors: Zhao Bo , Liu Yanping , Zhang Yifei , Chen Yuhong , Yang Zhifang , Zhu Ying , Zhan Weiwei
Published: May 2012

Background

Different population studies have reported gender difference in carotid intima-media thickness (CIMT), which is proved to be a risk factor of cardiovascular diseases. However, few longitudinal researches examine this gender difference in type 2 diabetes mellitus (T2DM) patients. Therefore, we prospectively analyzed CIMT in T2DM patients over a 4-year follow-up period.

Methods

355 T2DM patients (mean age 59 years; 54.9% women) were included in the present study. CIMT were measured using Color Doppler ultrasound. CIMT was measured at baseline (CIMT) in 2006 and at follow-up in 2010. Biochemical and clinical measurements were collected at baseline.

Results

Mean value of CIMT1 and CIMT2 were 0.740 ± 0.148 mm and 0.842 ± 0.179 mm, respectively. Men had higher CIMT than women both at baseline and at follow-up (CIMT1: 0.762 ± 0.149 vs 0.723 ± 0.146 mm, P = 0.0149; CIMT2: 0.880 ± 0.189 vs 0.810 ± 0.164 mm, P = 0.0002). Mean annual progression of CIMT (dCIMT) was 0.025 ± 0.022 mm/year. dCIMT was larger in men than in women (0.030 ± 0.025 vs 0.022 ± 0.019 mm, P = 0.0006). In multiple regression analyses, age was an independent risk factor of CIMT in both genders, while dCIMT was associated with age only in men.

Conclusions

Gender difference in CIMT was confirmed in T2DM patients. Moreover, impact of ageing on CIMT progression only existed in men, which might be the reason that gender difference in CIMT increased with age.
Expression of lignocellulolytic enzymes in Pichia pastoris
Authors: Mellitzer Andrea , Weis Roland , Glieder Anton , Flicker Karlheinz
Published: May 2012

Background

Sustainable utilization of plant biomass as renewable source for fuels and chemical building blocks requires a complex mixture of diverse enzymes, including hydrolases which comprise the largest class of lignocellulolytic enzymes. These enzymes need to be available in large amounts at a low price to allow sustainable and economic biotechnological processes.

Over the past years Pichia pastoris has become an attractive host for the cost-efficient production and engineering of heterologous (eukaryotic) proteins due to several advantages.

Results

In this paper codon optimized genes and synthetic alcohol oxidase 1 promoter variants were used to generate Pichia pastoris strains which individually expressed cellobiohydrolase 1, cellobiohydrolase 2 and beta-mannanase from Trichoderma reesei and xylanase A from Thermomyces lanuginosus. For three of these enzymes we could develop strains capable of secreting gram quantities of enzyme per liter in fed-batch cultivations. Additionally, we compared our achieved yields of secreted enzymes and the corresponding activities to literature data.

Conclusion

In our experiments we could clearly show the importance of gene optimization and strain characterization for successfully improving secretion levels. We also present a basic guideline how to correctly interpret the interplay of promoter strength and gene dosage for a successful improvement of the secretory production of lignocellulolytic enzymes in Pichia pastoris.
Remote sensing-based time series models for malaria early warning in the highlands of Ethiopia
Authors: Midekisa Alemayehu , Senay Gabriel , Henebry Geoffrey M , Semuniguse Paulos , Wimberly Michael C
Published: May 2012

Background

Malaria is one of the leading public health problems in most of sub-Saharan Africa, particularly in Ethiopia. Almost all demographic groups are at risk of malaria because of seasonal and unstable transmission of the disease. Therefore, there is a need to develop malaria early-warning systems to enhance public health decision making for control and prevention of malaria epidemics. Data from orbiting earth-observing sensors can monitor environmental risk factors that trigger malaria epidemics. Remotely sensed environmental indicators were used to examine the influences of climatic and environmental variability on temporal patterns of malaria cases in the Amhara region of Ethiopia.

Methods

In this study seasonal autoregressive integrated moving average (SARIMA) models were used to quantify the relationship between malaria cases and remotely sensed environmental variables, including rainfall, land-surface temperature (LST), vegetation indices (NDVI and EVI), and actual evapotranspiration (ETa) with lags ranging from one to three months. Predictions from the best model with environmental variables were compared to the actual observations from the last 12 months of the time series.

Results

Malaria cases exhibited positive associations with LST at a lag of one month and positive associations with indicators of moisture (rainfall, EVI and ETa) at lags from one to three months. SARIMA models that included these environmental covariates had better fits and more accurate predictions, as evidenced by lower AIC and RMSE values, than models without environmental covariates.

Conclusions

Malaria risk indicators such as satellite-based rainfall estimates, LST, EVI, and ETa exhibited significant lagged associations with malaria cases in the Amhara region and improved model fit and prediction accuracy. These variables can be monitored frequently and extensively across large geographic areas using data from earth-observing sensors to support public health decisions.
Role of toll-like receptor 4 on the immune escape of human oral squamous cell carcinoma and resistance of cisplatin-induced apoptosis
Authors: Sun Zujun , Luo Qingqiong , Ye Dongxia , Chen Wantao , Chen Fuxiang
Published: May 2012

Background

Toll-like receptor 4 (TLR4) is expressed on immune cells as a sensor that recognizes lipopolysaccharide (LPS), a microbial conserved component. It has recently been determined that the expression of TLR4 is also found in various types of tumor cells. Cisplatin is a widely used chemotherapeutic agent for oral squamous cell carcinoma (OSCC) treatment. However, the mechanisms responsible for cisplatin resistance are not well understood.

Results

The present study was designed to elucidate the role of TLR4 expression in human OSCC regarding immune escape and apoptotic resistance to cisplatin. TLR4 and the myeloid differentiation primary response gene 88 (MyD88) were highly expressed in OSCC cell lines. Upon LPS stimulation both NF-κB and p38 MAPK pathways were activated in OSCC cell lines, followed by the production of large quantities of IL-6, IL-8 and VEGF compared with human immortalized oral epithelia cells (HIOECs). OSCC cell lines were found to be resistant to cisplatin-mediated apoptosis after pretreatment with LPS.

Conclusions

Our results suggested that TLR4 was functionally expressed in human OSCC cells and development of resistance to cisplatin in human OSCC might occur through the mechanism involving TLR4 and its signaling pathway. Suppression of TLR4 and its signaling pathway might thus elevate sensitivity to cisplatin and potentially help improve the prognosis of patients with OSCC.
The isoflavone metabolite 6-methoxyequol inhibits angiogenesis and suppresses tumor growth
Authors: Bellou Sofia , Karali Evdoxia , Bagli Eleni , Al-Maharik Nawaf , Morbidelli Lucia , Ziche Marina , Adlercreutz Herman , Murphy Carol , Fotsis Theodore
Published: May 2012

Background

Increased consumption of plant-based diets has been linked to the presence of certain phytochemicals, including polyphenols such as flavonoids. Several of these compounds exert their protective effect via inhibition of tumor angiogenesis. Identification of additional phytochemicals with potential antiangiogenic activity is important not only for understanding the mechanism of the preventive effect, but also for developing novel therapeutic interventions.

Results

In an attempt to identify phytochemicals contributing to the well-documented preventive effect of plant-based diets on cancer incidence and mortality, we have screened a set of hitherto untested phytoestrogen metabolites concerning their anti-angiogenic effect, using endothelial cell proliferation as an end point. Here, we show that a novel phytoestrogen, 6-methoxyequol (6-ME), inhibited VEGF-induced proliferation of human umbilical vein endothelial cells (HUVE) cells, whereas VEGF-induced migration and survival of HUVE cells remained unaffected. In addition, 6-ME inhibited FGF-2-induced proliferation of bovine brain capillary endothelial (BBCE) cells. In line with its role in cell proliferation, 6-ME inhibited VEGF-induced phosphorylation of ERK1/2 MAPK, the key cascade responsible for VEGF-induced proliferation of endothelial cells. In this context, 6-ME inhibited in a dose dependent manner the phosphorylation of MEK1/2, the only known upstream activator of ERK1/2. 6-ME did not alter VEGF-induced phosphorylation of p38 MAPK or AKT, compatible with the lack of effect on VEGF-induced migration and survival of endothelial cells. Peri-tumor injection of 6-ME in A-431 xenograft tumors resulted in reduced tumor growth with suppressed neovasularization compared to vehicle controls (P < 0.01).

Conclusions

6-ME inhibits VEGF- and FGF2-induced proliferation of ECs by targeting the phosphorylation of MEK1/2 and it downstream substrate ERK1/2, both key components of the mitogenic MAPK pathway. Injection of 6-ME in mouse A-431 xenograft tumors results to tumors with decreased neovascularization and reduced tumor volume suggesting that 6-ME may be developed to a novel anti-angiogenic agent in cancer treatment.
Oleamide activates peroxisome proliferator-activated receptor gamma (PPARγ) in vitro
Authors: Dionisi Mauro , Alexander Stephen PH , Bennett Andrew J
Published: May 2012

Background

Oleamide (ODA) is a fatty acid primary amide first identified in the cerebrospinal fluid of sleep-deprived cats, which exerts effects on vascular and neuronal tissues, with a variety of molecular targets including cannabinoid receptors and gap junctions. It has recently been reported to exert a hypolipidemic effect in hamsters. Here, we have investigated the nuclear receptor family of peroxisome proliferator-activated receptors (PPARs) as potential targets for ODA action.

Results

Activation of PPARα, PPARβ and PPARγ was assessed using recombinant expression in Chinese hamster ovary cells with a luciferase reporter gene assay. Direct binding of ODA to the ligand binding domain of each of the three PPARs was monitored in a cell-free fluorescent ligand competition assay. A well-established assay of PPARγ activity, the differentiation of 3T3-L1 murine fibroblasts into adipocytes, was assessed using an Oil Red O uptake-based assay. ODA, at 10 and 50 μM, was able to transactivate PPARα, PPARβ and PPARγ receptors. ODA bound to the ligand binding domain of all three PPARs, although complete displacement of fluorescent ligand was only evident for PPARγ, at which an IC50value of 38 μM was estimated. In 3T3-L1 cells, ODA, at 10 and 20 μM, induced adipogenesis.

Conclusions

We have, therefore, identified a novel site of action of ODA through PPAR nuclear receptors and shown how ODA should be considered as a weak PPARγ ligandin vitro.
Effect of erythropoietin-stimulating agent on uremic inflammation
Authors: Tanaka Yuri , Joki Nobuhiko , Hase Hiroki , Iwasaki Masaki , Ikeda Masato , Ando Ryoichi , Shinoda Toshio , Inaguma Daijo , Sakaguchi Toshifumi , Komatsu Yasuhiro , Koiwa Fumihiko , Yamaka Toshihiko , Shigematsu Takashi
Published: May 2012

Background

The goal of the present study was to explore the effect of medications that are commonly prescribed for CKD patients on uremic state.

Methods

This was a cross-sectional study. From January 2006 to October 2009, 1,623 patients with end-stage kidney disease (ESKD) commenced hemodialysis (HD) at the 9 participating hospitals. The criteria for exclusion from the database were 1) serum C-reactive protein (CRP) > 3 mg/dL, 2) WBC count > 9,000/mm3 or <4,000/mm3, and 3) patients with cancer, immune complex disease, or vasculitis. A total of 900 patients were entered into the final database. We explored the association of serum CRP just before the first HD session with clinical characteristics, laboratory data, and medications for CKD in the predialysis period.

Results

On univariate analysis, age, CTR, eGFR, and WBC were significantly correlated with CRP. Systolic and diastolic blood pressure, serum albumin, LDL-C, HDL-C, Hb, Cr, and Ca were inversely associated with CRP. Use of erythropoietin-stimulating agents (ESA) using (r = −0.111, p = 0.0015), renin-angiotensin-aldosterone system inhibitors (r = −0.083, p = 0.0154), and calcium channel blockers (r = −0.1, p = 0.0039) was also negatively correlated with CRP. However, only use of ESA showed a significant negative correlation with CRP that was independent of other clinical factors and CKD medications on multiple regression analysis.

Conclusion

ESA may strongly reduce uremic inflammation in addition to improving anemia. To confirm this potential effect, a large-scale longitudinal study would be required.
Hemoglobin A1c improvements and better diabetes-specific quality of life among participants completing diabetes self-management programs: A nested cohort study
Authors: Khanna Abhinav , Bush Amber L , Swint J Michael , Peskin Melissa Fleschler , Street Richard L , Naik Aanand D
Published: May 2012

Background

Numerous primary care innovations emphasize patient-centered processes of care. Within the context of these innovations, greater understanding is needed of the relationship between improvements in clinical endpoints and patient-centered outcomes. To address this gap, we evaluated the association between glycosylated hemoglobin (HbA1c) and diabetes-specific quality of life among patients completing diabetes self-management programs.

Methods

We conducted a retrospective cohort study nested within a randomized comparative effectiveness trial of diabetes self-management interventions in 75 diabetic patients. Multiple linear regression models were developed to examine the relationship between change in HbA1c from baseline to one-year follow-up and Diabetes-39 (a diabetes-specific quality of life measure) at one year.

Results

HbA1c levels improved for the overall cohort from baseline to one-year follow-up (t (74) = 3.09, p = .0029). One-year follow up HbA1c was correlated with worse overall quality of life (r = 0.33, p = 0.004). Improvements in HbA1c from baseline to one-year follow-up were associated with greater D-39 diabetes control (β = 0.23, p = .04) and D-39 sexual functioning (β = 0.25, p = .03) quality of life subscales.

Conclusions

Improvements in HbA1c among participants completing a diabetes self-management program were associated with better diabetes-specific quality of life. Innovations in primary care that engage patients in self-management and improve clinical biomarkers, such as HbA1c, may also be associated with better quality of life, a key outcome from the patient perspective.
Different interface orientations of pentacene and PTCDA induce different degrees of disorder
Authors: Poschlad Angela , Meded Velimir , Maul Robert , Wenzel Wolfgang
Published: May 2012

Organic polymers or crystals are commonly used in manufacturing of today‘s electronically functional devices (OLEDs, organic solar cells, etc). Understanding their morphology in general and at the interface in particular is of paramount importance. Proper knowledge of molecular orientation at interfaces is essential for predicting optoelectronic properties such as exciton diffusion length, charge carrier mobility, and molecular quadrupole moments. Two promising candidates are pentacene and 3,4:9,10-perylenetetracarboxylic dianhydride (PTCDA). Different orientations of pentacene on PTCDA have been investigated using an atomistic molecular dynamics approach. Here, we show that the degree of disorder at the interface depends largely on the crystal orientation and that more ordered interfaces generally suffer from large vacancy formation.
IOP induces upregulation of GFAP and MHC-II and microglia reactivity in mice retina contralateral to experimental glaucoma
Authors: Gallego Beatriz I , Salazar Juan J , de Hoz Rosa , Rojas Blanca , Ramírez Ana I , Salinas-Navarro Manuel , Ortín-Martínez Arturo , Valiente-Soriano Francisco J , Avilés-Trigueros Marcelino , Villegas-Perez Maria P , Vidal-Sanz Manuel , Triviño Alberto , Ramírez Jose M
Published: May 2012

Background

Ocular hypertension is a major risk factor for glaucoma, a neurodegenerative disease characterized by an irreversible decrease in ganglion cells and their axons. Macroglial and microglial cells appear to play an important role in the pathogenic mechanisms of the disease. Here, we study the effects of laser-induced ocular hypertension (OHT) in the macroglia, microglia and retinal ganglion cells (RGCs) of eyes with OHT (OHT-eyes) and contralateral eyes two weeks after lasering.

Methods

Two groups of adult Swiss mice were used: age-matched control (naïve, n = 9); and lasered (n = 9). In the lasered animals, both OHT-eyes and contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against glial fibrillary acid protein (GFAP), neurofilament of 200kD (NF-200), ionized calcium binding adaptor molecule (Iba-1) and major histocompatibility complex class II molecule (MHC-II). The GFAP-labeled retinal area (GFAP-RA), the intensity of GFAP immunoreaction (GFAP-IR), and the number of astrocytes and NF-200 + RGCs were quantified.

Results

In comparison with naïve: i) astrocytes were more robust in contralateral eyes. In OHT-eyes, the astrocyte population was not homogeneous, given that astrocytes displaying only primary processes coexisted with astrocytes in which primary and secondary processes could be recognized, the former having less intense GFAP-IR (P < 0.001); ii) GFAP-RA was increased in contralateral (P <0.05) and decreased in OHT-eyes (P <0.001); iii) the mean intensity of GFAP-IR was higher in OHT-eyes (P < 0.01), and the percentage of the retinal area occupied by GFAP+ cells with higher intensity levels was increased in contralateral (P = 0.05) and in OHT-eyes (P < 0.01); iv) both in contralateral and in OHT-eyes, GFAP was upregulated in Müller cells and microglia was activated; v) MHC-II was upregulated on macroglia and microglia. In microglia, it was similarly expressed in contralateral and OHT-eyes. By contrast, in macroglia, MHC-II upregulation was observed mainly in astrocytes in contralateral eyes and in Müller cells in OHT-eyes; vi) NF-200+RGCs (degenerated cells) appeared in OHT-eyes with a trend for the GFAP-RA to decrease and for the NF-200+RGC number to increase from the center to the periphery (r = −0.45).

Conclusion

The use of the contralateral eye as an internal control in experimental induction of unilateral IOP should be reconsidered. The gliotic behavior in contralateral eyes could be related to the immune response. The absence of NF-200+RGCs (sign of RGC degeneration) leads us to postulate that the MHC-II upregulation in contralateral eyes could favor neuroprotection.
The University Münster model surgery system for Orthognathic surgery. Part I – The idea behind
Authors: Ehmer Ulrike , Joos Ulrich , Flieger Stefanie , Wiechmann Dirk
Published: May 2012

Background

We describe a procedure for diagnosis and planning for orthognatic surgery based on international standards. A special 2D planning based on lateral cephalograms (Axis Orbital Marker Lines System) realize a transmission to the SAM 2P articulator (3D) by means of the Axis Orbital Plane.

Methods

Former intraoperative measurement of the average height of the LeFort I osteotomy plane relative to the molar occlusal plane allow to construct a virtual osteotomy plane in the lateral cephalogram. This is the basis for the development of the Axis Orbital Marker Lines System (AO-MLS).

Results

The AO-MLS is presented graphically, and in detail, with construction guidelines. The system could be integrated into various lateral cephalometric analysis- and surgical prediction schemes. It forms the basis for a standardized transfer of the 2D planning to the 3D planning in the articulator, and vice versa. This procedure makes it possible to generate surgical planning protocols based on the model surgery, which represent the dislocations in the proximity of the real osteotomy planes.

Conclusions

The Axis Orbital Marker Lines System (software component) in conjunction with the University Münster Model Surgery System (hardware system) increases the predictability of model operations in orthognathic surgery.
Behaviour of Sotalia guianensis(van Bénéden, 1864) (Cetacea, Delphinidae) and ethnoecological knowledge of artisanal fishermen from Canavieiras, Bahia, Brazil
Authors: Costa Martha Eloy Bandeira , Le Pendu Yvonnick , Neto Eraldo Medeiros Costa
Published: May 2012

Artisanal fishermen, because of their direct and frequent contact with the aquatic environment, possess a wealth of knowledge about the natural history of the fauna of the region in which they live. This knowledge, both practical and theoretical, has been frequently utilized and integrated into academic research. Taking this into consideration, this study discusses the ethnoecological knowledge of artisanal fishermen from a community in Canavieiras, state of Bahia, Brazil regarding the Guiana dolphin (Sotalia guianensis), a typically costal member of the family Delphinidae that is little studied in this region. To this end, the behaviour ofS. guianensisin Canavieiras was recorded over one year and the data obtained were compared with fishermen’s reports. A total of 609 hours of behavioural observations ofS. guianensiswas conducted from a fixed point in alternate morning and afternoon sessions between October 2009 and September 2010. Observations were conducted from a pier (15°40’59”S and 38°56’38”W) situated on the banks of the Pardo River estuary - the region’s main river - at 5.5 m above water level. For ethnoecological data collection, semi-structured interviews were carried out with 26 fishermen in May, June and September 2010 and January 2011 in the fishing community of Atalaia. Occasional boat expeditions were made with the fishermen to compare their reports with direct observations of the behaviour ofS. guianensis. The results demonstrate that fishermen possess a body of knowledge aboutS. guianensisthat describes in detail the main behavioural aspects of the species. They reported the presence ofS. guianensisin the Pardo River estuary throughout the year and its gregarious behaviour. They cited a relationship between the movement of dolphins and tidal cycles, and their presence in the estuary associated with the search for food. In addition, the fishermen reported that numbers of infants in groups were proportional to group size. Behaviours described were compatible with the observations madein situand with data found in the scientific literature, confirming the importance of traditional knowledge in complementing scientific data. One behaviour mentioned by the fishermen that had no equivalence in the scientific literature was confirmedin situand, therefore, constitutes the first record for this species.
A semi-quantitative assay of overall DNA methylation status using Methyl-CpG binding protein (MBD1)
Authors: Zhang Chunxiao , Li Runsheng , Zhao Ruqian
Published: May 2012

Background

In mammals, DNA methylation at the 5-position of cytosine is the most essential epigenetic modification. Changes in the level of genome-wide DNA methylation (also known as overall DNA methylation) are associated with alterations in gene expression, thereby contributing to the phenotypic and physiological diversity. Current technologies for detecting overall DNA methylation either suffer from low sensitivity or require sophisticated equipment. Studies on domestic animals are hampered by the lack of complete and annotated genomic information.

Results

Here we report a rapid slot blot method using methyl-CpG binding protein (MBD1) to exam the level of overall DNA methylation in pigs and chickens. Using this rapid approach, we determined the methylation status in various DNA samples of a Chinese indigenous (Erhualian) and a Western (Large White) breed of pigs. We also chose day 18 embryos (E18) and newly hatched chicks (D1) of a Chinese indigenous chicken breed (Wen’s yellow-feathered broiler chicken) for genome-wide DNA methylation analysis. The results revealed tissue- and breed-specific differences, as well as age-dependent variations, in the level of overall DNA methylation.

Conclusion

The results showed that the slot blot assay is a sensitive, highly specific and convenient method for semi-quantitative estimation of overall DNA methylation with no species specificity. This method does not require sophisticated equipment, such as high performance liquid chromatography (HPLC), or expensive technologies like sequencing, thus providing a useful tool for overall DNA methylation studies on domestic animals.
Tongue cancer in young patients: case report of a 26-year-old patient
Authors: Credé Aleksandra , Locher Michael , Bredell Marius
Published: May 2012

Introduction

This article presents the case of a 26-year-old woman with tongue cancer. The median age at the diagnosis of the tongue’s cancer is 61 years. Only approximately 2% of patients are diagnosed before the age of 35.

Case presentation

Our patient survived acute myeloid leukemia (AML) before her second year. She had been having recurrent, poorly healing aphtae on the right side of the tongue for a period of months before the symptoms of the tongue cancer appeared. As a treatment a partial glossectomy was conducted on the right side and a neck dissection of levels I-III. Than a reconstruction of the tongue with a radialis free vascularised flap from left side was performed.

Discussion

It should be always looked for the causal factor in young patients with a neoplasm. There is strong evidence for second malignant neoplasms in survivors of childhood cancer.