bluuebunny/crossref_metadata_2025 huggingface dataset:
An evaluation of emerging vaccines for childhood pneumococcal pneumonia
Authors: Webster Julia , Theodoratou Evropi , Nair Harish , Seong Ang Choon , Zgaga Lina , Huda Tanvir , Johnson Hope L , Madhi Shabir , Rubens Craig , Zhang Jian Shayne F , El Arifeen Shams , Krause Ryoko , Jacobs Troy A , Brooks Abdullah W , Campbell Harry , Rudan Igor
Published: April 2011

Background

Pneumonia is the leading cause of child mortality worldwide. Streptococcus pneumoniae (SP) or pneumococcus is estimated to cause 821,000 child deaths each year. It has over 90 serotypes, of which 7 to 13 serotypes are included in current formulations of pneumococcal conjugate vaccines that are efficacious in young children. To further reduce the burden from SP pneumonia, a vaccine is required that could protect children from a greater diversity of serotypes. Two different types of vaccines against pneumococcal pneumonia are currently at varying stages of development: a multivalent pneumococcal conjugate vaccine covering additional SP serotypes; and a conserved common pneumococcal protein antigen (PPA) vaccine offering protection for all serotypes.

Methods

We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging SP vaccines relevant to several criteria of interest: answerability; efficacy and effectiveness; cost of development, production and implementation; deliverability, affordability and sustainability; maximum potential for disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%.

Results

The experts expressed very high level of optimism (over 80%) that low-cost polysaccharide conjugate SP vaccines would satisfy each of the 9 relevant CHNRI criteria. The median potential effectiveness of conjugate SP vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 25% (interquartile range 20-38%, min. 15%, max 45%). For low cost, cross-protective common protein vaccines for SP the experts expressed concerns over answerability (72%) and the level of development costs (50%), while the scores for all other criteria were over 80%. The median potential effectiveness of common protein vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 30% (interquartile range 26-40%, min. 20%, max 45%).

Conclusions

Improved SP vaccines are a very promising investment that could substantially contribute to reduction of child mortality world-wide.
Effectiveness of interventions to screen and manage infections during pregnancy on reducing stillbirths: a review
Authors: Ishaque Sidra , Yakoob Mohammad Yawar , Imdad Aamer , Goldenberg Robert L , Eisele Thomas P , Bhutta Zulfiqar A
Published: April 2011

Background

Infection is a well acknowledged cause of stillbirths and may account for about half of all perinatal deaths today, especially in developing countries. This review presents the impact of interventions targeting various important infections during pregnancy on stillbirth or perinatal mortality.

Methods

We undertook a systematic review including all relevant literature on interventions dealing with infections during pregnancy for assessment of effects on stillbirths or perinatal mortality. The quality of the evidence was assessed using the adapted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach by Child Health Epidemiology Reference Group (CHERG). For the outcome of interest, namely stillbirth, we applied the rules developed by CHERG to recommend a final estimate for reduction in stillbirth for input to the Lives Saved Tool (LiST) model.

Results

A total of 25 studies were included in the review. A random-effects meta-analysis of observational studies of detection and treatment of syphilis during pregnancy showed a significant 80% reduction in stillbirths [Relative risk (RR) = 0.20; 95% confidence interval (CI): 0.12 - 0.34) that is recommended for inclusion in the LiST model. Our meta-analysis showed the malaria prevention interventions i.e. intermittent preventive treatment (IPTp) and insecticide-treated mosquito nets (ITNs) can reduce stillbirths by 22%, however results were not statistically significant (RR = 0.78; 95% CI: 0.59 – 1.03). For human immunodeficiency virus infection, a pooled analysis of 6 radomized controlled trials (RCTs) failed to show a statistically significant reduction in stillbirth with the use of antiretroviral in pregnancy compared to placebo (RR = 0.93; 95% CI: 0.45 – 1.92). Similarly, pooled analysis combining four studies for the treatment of bacterial vaginosis (3 for oral and 1 for vaginal antibiotic) failed to yield a significant impact on perinatal mortality (OR = 0.88; 95% CI: 0.50 – 1.55).

Conclusions

The clearest evidence of impact in stillbirth reduction was found for adequate prevention and treatment of syphilis infection and possibly malaria. At present, large gaps exist in the growing list of stillbirth risk factors, especially those that are infection related. Potential causes of stillbirths including HIV and TORCH infections need to be investigated further to help establish the role of prevention/treatment and its subsequent impact on stillbirth reduction.
The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths
Authors: Imdad Aamer , Yakoob Mohammad Yawar , Bhutta Zulfiqar A
Published: April 2011

Background

Pregnancy is a state of increased requirement of macro- and micronutrients, and malnourishment or inadequate dietary intake before and during pregnancy, can lead to adverse perinatal outcomes including stillbirths. Many nutritional interventions have been proposed during pregnancy according to the nutritional status of the mother and baseline risk factors for different gestational disorders. In this paper, we have reviewed three nutritional interventions including peri-conceptional folic acid supplementation, balanced protein energy supplementation and multiple micronutrients supplementation during pregnancy. This paper is a part of a series to estimate the effect of interventions on stillbirths for input to Live Saved Tool (LiST) model.

Methods

We systematically reviewed all published literature to identify studies evaluating effectiveness of peri-conceptional folic acid supplementation in reducing neural tube defects (NTD), related stillbirths and balanced protein energy and multiple micronutrients supplementation during pregnancy in reducing all-cause stillbirths. The primary outcome was stillbirths. Meta-analyses were generated where data were available from more than one study. Recommendations were made for the Lives Saved Tool (LiST) model based on rules developed by the Child Health Epidemiology Reference Group (CHERG).

Results

There were 18 studies that addressed peri-conceptional folic acid supplementation for prevention of neural tube defects (NTDs). Out of these, 7 studies addressed folic acid supplementation while 11 studies evaluated effect of folic acid fortification. Pooled results from 11 fortification studies showed that it reduces primary incidence of NTDs by 41 % [Relative risk (RR) 0.59; 95 % confidence interval (CI) 0.52-0.68]. This estimate has been recommended for inclusion in the LiST as proxy for reduction in stillbirths. Pooled results from three studies considered to be of low quality and suggest that balanced protein energy supplementation during pregnancy could lead to a reduction of 45% in stillbirths [RR 0.55, 95 % CI 0.31-0.97]. While promising, the intervention needs more effectiveness studies before inclusion in any programs. Pooled results from 13 studies evaluating role of multiple micronutrients supplementation during pregnancy showed no significant effect in reducing stillbirths [RR = 0.98; 95% CI: 0.88 – 1.10] or perinatal mortality [RR = 1.07; 95% CI: 0.92 – 1.25; random model]. No recommendations have been made for this intervention for inclusion in the LiST model.

Conclusions

Peri-conceptional folic acid supplementation reduces stillbirths due to NTDs by approximately 41%, a point estimate recommended for inclusion in LiST.
Elective induction for pregnancies at or beyond 41 weeks of gestation and its impact on stillbirths: a systematic review with meta-analysis
Authors: Hussain Arwa Abbas , Yakoob Mohammad Yawar , Imdad Aamer , Bhutta Zulfiqar A
Published: April 2011

Background

An important determinant of pregnancy outcome is the timely onset of labor and birth. Prolonged gestation complicates 5% to 10% of all pregnancies and confers increased risk to both the fetus and mother. The purpose of this review was to study the possible impact of induction of labour (IOL) for post-term pregnancies compared to expectant management on stillbirths.

Methods

A systematic review of the published studies including randomized controlled trials, quasi- randomized trials and observational studies was conducted. Search engines used were PubMed, the Cochrane Library, the WHO regional databases and hand search of bibliographies. A standardized data abstraction sheet was used. Recommendations have been made for input to the Lives Saved Tool (LiST) model by following standardized guidelines developed by the Child Health Epidemiology Reference Group (CHERG).

Results

A total of 25 studies were included in this review. Meta-analysis of 14 randomized controlled trials (RCTs) suggests that a policy of elective IOL for pregnancies at or beyond 41 weeks is associated with significantly fewer perinatal deaths (RR=0.31; 95% CI: 0.11-0.88) compared to expectant management, but no significant difference in the incidence of stillbirth (RR= 0.29; 95% CI: 0.06-1.38) was noted. The included trials evaluating this intervention were small, with few events in the intervention and control group. There was significant decrease in incidence of neonatal morbidity from meconium aspiration (RR = 0.43, 95% CI 0.23-0.79) and macrosomia (RR = 0.72; 95% CI: 0.54 – 0.98). Using CHERG rules, we recommended 69% reduction as a point estimate for the risk of stillbirth with IOL for prolonged gestation (> 41 weeks).

Conclusions

Induction of labour appears to be an effective way of reducing perinatal morbidity and mortality associated with post-term pregnancies. It should be offered to women with post-term pregnancies after discussing the benefits and risks of induction of labor.
High-fat diet feeding alters metabolic response to fasting/non fasting conditions. Effect on caveolin expression and insulin signalling
Authors: Gómez-Ruiz Ana , Milagro Fermín I , Campión Javier , Martínez J Alfredo , de Miguel Carlos
Published: April 2011

Background

The effect of food intake on caveolin expression in relation to insulin signalling was studied in skeletal muscle and adipocytes from retroperitoneal (RP) and subcutaneous (SC) adipose tissue, comparing fasted (F) to not fasted (NF) rats that had been fed a control or high-fat (HF) diet for 72 days.

Methods

Serum glucose was analysed enzymatically and insulin and leptin by ELISA. Caveolins and insulin signalling intermediaries (IR, IRS-1 and 2 and GLUT4) were determined by RT-PCR and western blotting. Caveolin and IR phosphorylation was measured by immunoprecipitation. Data were analysed with Mann-Whitney U test.

Results

High-fat fed animals showed metabolic alterations and developed obesity and insulin resistance. In skeletal muscle, food intake (NF) induced activation of IR and increased expression of IRS-2 in control animals with normal metabolic response. HF animals became overweight, hyperglycaemic, hyperinsulinemic, hyperleptinemic and showed insulin resistance. In skeletal muscle of these animals, food intake (NF) also induced IRS-2 expression together with IR, although this was not active. Caveolin 3 expression in this tissue was increased by food intake (NF) in animals fed either diet. In RP adipocytes of control animals, food intake (NF) decreased IR and IRS-2 expression but increased that of GLUT4. A similar but less intense response was found in SC adipocytes. Food intake (NF) did not change caveolin expression in RP adipocytes with either diet, but in SC adipocytes of HF animals a reduction was observed. Food intake (NF) decreased caveolin-1 phosphorylation in RP but increased it in SC adipocytes of control animals, whereas it increased caveolin-2 phosphorylation in both types of adipocytes independently of the diet.

Conclusions

Animals fed a control-diet show a normal response to food intake (NF), with activation of the insulin signalling pathway but without appreciable changes in caveolin expression, except a small increase of caveolin-3 in muscle. Animals fed a high-fat diet develop metabolic changes that result in insulin signalling impairment. In these animals, caveolin expression in muscle and adipocytes seems to be regulated independently of insulin signalling.
Protective effect of whey proteins against nonalcoholic fatty liver in rats
Authors: Hamad Essam M , Taha Soad H , Abou Dawood Abdel-Gawad I , Sitohy Mahmoud Z , Abdel-Hamid Mahmoud
Published: April 2011

Background

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and can vary from hepatic steatosis to end-stage liver disease. It is the most common liver disease and its prevalence is increasing worldwide. In the present study, the effect of whey proteins on some parameters of NAFLD was investigated.

Results

Oral administration of the studied whey proteins products reduced the final body weight of rats. There was a significant reduction effect (P < 0.05) of the tested proteins on hepatic triglycerides, liver enzymes (ALT and AST), lipid peroxidation (malondialdehyde level) and serum glucose. Feeding on whey proteins caused an increase in the reduced glutathione. Hepatic content of reduced glutathione was not affected by any of the used whey proteins, but it showed an increasing tendency (P > 0.05). Liver histology showed an improvement of fatty infiltration in hepatocytes from whey protein groups and gives the histology of liver a normal appearance.

Conclusions

The obtained results indicate a possible role for oral administration of whey proteins in the regulation of liver biochemistries in a rat's model of NAFLD. This regulatory effect of whey proteins was accompanied by an improvement in fatty infiltration in hepatocytes and a reduction of oxidative stress parameters.
Association of TRB3 Q84R polymorphism with polycystic ovary syndrome in Chinese women
Authors: Zhang Xue , Fu Li , Zhang Qiufang , Yan Liying , Ma Yanmin , Tu Binbin , Liu Nana , Qiao Jie
Published: April 2011

Background

Tribbles 3 (TRB3) affects insulin signalling by inhibiting insulin-stimulated Akt phosphorylation and subsequent activation. A single nucleotide polymorphism located in the second extron of the human TRB3 gene is thought to be associated with insulin resistance. The latter is a core abnormality in PCOS independent of obesity. The present study was designed to clarify the relationships of TRB3 Q84R polymorphism with PCOS in a Chinese women group.

Methods

A case-control study with two groups: PCOS group (n = 336) and control group of infertility women for tubal and/or male factor (n = 116) was performed. Genotyping of the TRB3 R84 variant was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

The frequency of genotype QQ in PCOS women was significantly lower, while genotype QR and RR were significantly higher than that in control group (p < 0.05). However, the difference disappeared after adjustment for BMI. At glucose1h, glucose2h and insulin2h point, the difference between QQ individuals and R84 allele carriers in PCOS women reached statistical significance during OGTT (p < 0.05).

Conclusions

TRB3 Q84R polymorphism is associated with obesity and especially glucose metabolism and not associated with polycystic ovary syndrome because of compositional characteristics of phenotype in Chinese PCOS women.
On the stability of the exact solutions of the dual-phase lagging model of heat conduction
Authors: Ordonez-Miranda Jose , Alvarado-Gil Juan Jose
Published: April 2011

The dual-phase lagging (DPL) model has been considered as one of the most promising theoretical approaches to generalize the classical Fourier law for heat conduction involving short time and space scales. Its applicability, potential, equivalences, and possible drawbacks have been discussed in the current literature. In this study, the implications of solving the exact DPL model of heat conduction in a three-dimensional bounded domain solution are explored. Based on the principle of causality, it is shown that the temperature gradient must be always the cause and the heat flux must be the effect in the process of heat transfer under the dual-phase model. This fact establishes explicitly that the single- and DPL models with different physical origins are mathematically equivalent. In addition, taking into account the properties of the Lambert W function and by requiring that the temperature remains stable, in such a way that it does not go to infinity when the time increases, it is shown that the DPL model in its exact form cannot provide a general description of the heat conduction phenomena.
A combination of hard and soft templating for the fabrication of silica hollow microcoils with nanostructured walls
Authors: Rodriguez-Abreu Carlos , Vilanova Neus , Solans Conxita , Ujihara Masaki , Imae Toyoko , López-Quintela Arturo , Motojima Seiji
Published: April 2011

Hollow silica microcoils have been prepared by using functionalized carbon microcoils as hard templates and surfactant or amphiphilic dye aggregates as soft templates. The obtained materials have been characterized by electron and optical microscopy, nitrogen sorption and small angle X-ray scattering. The obtained hollow microcoils resemble the original hard templates in shape and size. Moreover, they have mesoporous walls (pore size ≈ 3 nm) with some domains where pores are ordered in a hexagonal array, originated from surfactant micelles. The obtained silica microcoils also show preferential adsorption of cationic fluorescent dyes. A mechanism for the formation of silica microcoils is proposed.
Micro-nano hybrid structures with manipulated wettability using a two-step silicon etching on a large area
Authors: Kim Beom Seok , Shin Sangwoo , Shin Seung Jae , Kim Kyung Min , Cho Hyung Hee
Published: April 2011

Nanoscale surface manipulation technique to control the surface roughness and the wettability is a challenging field for performance enhancement in boiling heat transfer. In this study, micro-nano hybrid structures (MNHS) with hierarchical geometries that lead to maximizing of surface area, roughness, and wettability are developed for the boiling applications. MNHS structures consist of micropillars or microcavities along with nanowires having the length to diameter ratio of about 100:1. MNHS is fabricated by a two-step silicon etching process, which are dry etching for micropattern and electroless silicon wet etching for nanowire synthesis. The fabrication process is readily capable of producing MNHS covering a wafer-scale area. By controlling the removal of polymeric passivation layers deposited during silicon dry etching (Bosch process), we can control the geometries for the hierarchical structure with or without the thin hydrophobic barriers that affect surface wettability. MNHS without sidewalls exhibit superhydrophilic behavior with a contact angle under 10°, whereas those with sidewalls preserved by the passivation layer display more hydrophobic characteristics with a contact angle near 60°.
Functional investigation of grass carp reovirus nonstructural protein NS80
Authors: Cai Lin , Sun Xiaoyun , Shao Ling , Fang Qin
Published: April 2011

Background

Grass Carp Reovirus (GCRV), a highly virulent agent of aquatic animals, has an eleven segmented dsRNA genome encased in a multilayered capsid shell, which encodes twelve proteins including seven structural proteins (VP1-VP7), and five nonstructural proteins (NS80, NS38, NS31, NS26, and NS16). It has been suggested that the protein NS80 plays an important role in the viral replication cycle that is similar to that of its homologous protein μNS in the genus of Orthoreovirus.

Results

As a step to understanding the basis of the part played by NS80 in GCRV replication and particle assembly, we used the yeast two-hybrid (Y2H) system to identify NS80 interactions with proteins NS38, VP4, and VP6 as well as NS80 and NS38 self-interactions, while no interactions appeared in the four protein pairs NS38-VP4, NS38-VP6, VP4-VP4, and VP4-VP6. Bioinformatic analyses of NS80 with its corresponding proteins were performed with all currently available homologous protein sequences in ARVs (avian reoviruses) and MRVs (mammalian reoviruses) to predict further potential functional domains of NS80 that are related to VFLS (viral factory-like structures) formation and other roles in viral replication. Two conserved regions spanning from aa (amino acid) residues of 388 to 433, and 562 to 580 were discovered in this study. The second conserved region with corresponding conserved residues Tyr565, His569, Cys571, Asn573, and Glu576 located between the two coiled-coils regions (aa ~513-550 and aa ~615-690) in carboxyl-proximal terminus were supposed to be essential to form VFLS, so that aa residues ranging from 513 to 742 of NS80 was inferred to be the smallest region that is necessary for forming VFLS. The function of the first conserved region including Ala395, Gly419, Asp421, Pro422, Leu438, and Leu443 residues is unclear, but one-third of the amino-terminal region might be species specific, dominating interactions with other viral components.

Conclusions

Our results in this study together with those from previous investigations indicate the protein NS80 might play a central role in VFLS formation and viral components recruitment in GCRV particle assembly, similar to the μNS protein in ARVs and MRVs.
Management of chest keloids
Authors: Park Tae Hwan , Seo Sang Won , Kim June Kyu , Chang Choong Hyun
Published: April 2011

Keloid formation is one of the most challenging clinical problems in wound healing. With increasing frequency of open heart surgery, chest keloid formations are not infrequent in the clinical practice. The numerous treatment methods including surgical excision, intralesional steroid injection, radiation therapy, laser therapy, silicone gel sheeting, and pressure therapy underscore how little is understood about keloids. Keloids have a tendency to recur after surgical excision as a single treatment. Stretching tension is clearly associated with keloid generation, as keloids tend to occur on high tension sites such as chest region. The authors treated 58 chest keloid patients with surgical excision followed by intraoperative and postoperative intralesional steroid injection. Even with minor complications and recurrences, our protocol results in excellent outcomes in cases of chest keloids.
Impact of concomitant aortic regurgitation on long-term outcome after surgical aortic valve replacement in patients with severe aortic stenosis
Authors: Catovic Suad , Popovic Zoran B , Tasic Nebojsa , Nezic Dusko , Milojevic Predrag , Djukanovic Bosko , Gradinac Sinisa , Angelkov Lazar , Otasevic Petar
Published: April 2011

Background

Prognostic value of concomitant aprtic regurgitation (AR) in patients operated for severe aortic stenosis (AS) is not clarified. The aim of this study was to prospectively examine the impact of presence and severity of concomitant AR in patients operated for severe AS on long-term functional capacity, left ventricular (LV) function and mortality.

Methods

Study group consisted of 110 consecutive patients operated due to severe AS. The patients were divided into AS group (56 patients with AS without AR or with mild AR) and AS+AR group (54 patients with AS and moderate, severe or very severe AR). Follow-up included clinical examination, six minutes walk test (6MWT) and echocardiography 12 and 104 months after AVR.

Results

Patients in AS group had lower LV volume indices throughout the study than patients in AS+AR group. Patients in AS group did not have postoperative decrease in LV volume indices, whereas patients in AS+AR group experienced decrease in LV volume indices at 12 and 104 months. Unlike LV volume indices, LV mass index was significantly lower in both groups after 12 and 104 months as compared to preoperative values. Mean LVEF remained unchanged in both groups throughout the study. NYHA class was improved in both groups at 12 months, but at 104 months remained improved only in patients with AS. On the other hand, distance covered during 6MWT was longer at 104 months as compared to 12 months only in AS+AR group (p = 0,013), but patients in AS group walked longer at 12 months than patients in AS+AR group (p = 0,002). There were 30 deaths during study period, of which 13 (10 due to cardiovascular causes) in AS group and 17 (12 due to cardiovascular causes) in AS+AR group. Kaplan-Meier analysis showed that the survival probability was similar between the groups. Multivariate analysis identified diabetes mellitus (beta 1.78, p = 0.038) and LVEF < 45% (beta 1.92, p = 0.049) as the only independent predictor of long-term mortality.

Conclusion

Our data indicate that the preoperative presence and severity of concomitant AR has no influence on long-term postoperative outcome, LV function and functional capacity in patients undergoing AVR for severe AS.
A Boolean probabilistic model of metabolic adaptation to oxygen in relation to iron homeostasis and oxidative stress
Authors: Achcar Fiona , Camadro Jean-Michel , Mestivier Denis
Published: April 2011

Background

In aerobically grown cells, iron homeostasis and oxidative stress are tightly linked processes implicated in a growing number of diseases. The deregulation of iron homeostasis due to gene defects or environmental stresses leads to a wide range of diseases with consequences for cellular metabolism that remain poorly understood. The modelling of iron homeostasis in relation to the main features of metabolism, energy production and oxidative stress may provide new clues to the ways in which changes in biological processes in a normal cell lead to disease.

Results

Using a methodology based on probabilistic Boolean modelling, we constructed the first model of yeast iron homeostasis including oxygen-related reactions in the frame of central metabolism. The resulting model of 642 elements and 1007 reactions was validated by comparing simulations with a large body of experimental results (147 phenotypes and 11 metabolic flux experiments). We removed every gene, thus generating in silico mutants. The simulations of the different mutants gave rise to a remarkably accurate qualitative description of most of the experimental phenotype (overall consistency > 91.5%). A second validation involved analysing the anaerobiosis to aerobiosis transition. Therefore, we compared the simulations of our model with different levels of oxygen to experimental metabolic flux data. The simulations reproducted accurately ten out of the eleven metabolic fluxes. We show here that our probabilistic Boolean modelling strategy provides a useful description of the dynamics of a complex biological system. A clustering analysis of the simulations of all in silico mutations led to the identification of clear phenotypic profiles, thus providing new insights into some metabolic response to stress conditions. Finally, the model was also used to explore several new hypothesis in order to better understand some unexpected phenotypes in given mutants.

Conclusions

All these results show that this model, and the underlying modelling strategy, are powerful tools for improving our understanding of complex biological problems.
A computational framework for gene regulatory network inference that combines multiple methods and datasets
Authors: Gupta Rita , Stincone Anna , Antczak Philipp , Durant Sarah , Bicknell Roy , Bikfalvi Andreas , Falciani Francesco
Published: April 2011

Background

Reverse engineering in systems biology entails inference of gene regulatory networks from observational data. This data typically include gene expression measurements of wild type and mutant cells in response to a given stimulus. It has been shown that when more than one type of experiment is used in the network inference process the accuracy is higher. Therefore the development of generally applicable and effective methodologies that embed multiple sources of information in a single computational framework is a worthwhile objective.

Results

This paper presents a new method for network inference, which uses multi-objective optimisation (MOO) to integrate multiple inference methods and experiments. We illustrate the potential of the methodology by combining ODE and correlation-based network inference procedures as well as time course and gene inactivation experiments. Here we show that our methodology is effective for a wide spectrum of data sets and method integration strategies.

Conclusions

The approach we present in this paper is flexible and can be used in any scenario that benefits from integration of multiple sources of information and modelling procedures in the inference process. Moreover, the application of this method to two case studies representative of bacteria and vertebrate systems has shown potential in identifying key regulators of important biological processes.
Early finding of chest wall metastasis of hepatocellular carcinoma in a woman by fluorodeoxyglucose-positron emission tomography scan: a case report
Authors: Yang Lixin , Marx Howard , Yen Yun
Published: April 2011

Introduction

The use of fluorodeoxyglucose-positron emission tomography to evaluate well-differentiated hepatocellular carcinomas is facing critical problems. It is reported that the activity of fluorodeoxyglucose-6-phosphatase, which converts fluorodeoxyglucose-6-phosphatase to fluorodeoxyglucose, is high in normal liver cells. However, the enzyme-converting activity of glucose-6-phosphatase of well-differentiated hepatocellular carcinomas is similar to normal liver tissue. Thus, using fluorodeoxyglucose in diagnosing primary hepatocellular carcinomas is difficult. However, using fluorodeoxyglucose to detect extrahepatic metastasis of hepatocellular carcinomas is still possible.

Case presentation

We describe the case of a 45-year-old Chinese woman who developed a recurrent lesion in the chest wall from a previous surgically resected hepatocellular carcinoma. This recurrent lesion was detected first on the basis of a positron emission tomography scan, then on the basis of a computed tomography scan and other clinical tests.

Conclusion

This finding indicates that the positron emission tomography scan is a potentially reliable tool to screen for systemic metastatic disease in patients with hepatocellular carcinomas when other cross-sectional imaging tests such as computed tomography or magnetic resonance imaging are negative.
Babesiosis due to the canine Babesia microti-like small piroplasm in dogs - first report from Portugal and possible vertical transmission
Authors: Simões Paula Brilhante , Cardoso Luís , Araújo Manuela , Yisaschar-Mekuzas Yael , Baneth Gad
Published: April 2011

Background

Canine babesiosis (or piroplasmosis) is endemic in northern Portugal, but molecularly confirmed cases of infection with small piroplasms have not been reported in the country. Three German shepherd dogs - a bitch and its 2-month old pup and an unrelated male - clinically suspected of piroplasmosis were assessed for babesial infection.

Results

Parasitemia with small piroplasms was detected by microscopy in two dogs. All three dogs were positive by PCR and the Babesia microti-like small piroplasm (syn. Theileria annae) was identified by DNA sequencing. These are the first confirmed cases of babesiosis caused by the B. microti-like piroplasm both in dogs from Portugal and in dogs suspected of clinical piroplasmosis outside of Spain.

Conclusions

Although the bitch and the male had visited neighboring Galicia (northwestern Spain), where the disease is endemic, incursion of this piroplasm into northern Portugal is evident and infection of the non-traveled pup was due to either vertical transmission or autochthonous tick infection.
Canine leishmaniosis and its relationship to human visceral leishmaniasis in Eastern Uzbekistan
Authors: Kovalenko Dmitriy A , Razakov Shavkat A , Ponirovsky Evgeny N , Warburg Alon , Nasyrova Rokhat M , Ponomareva Valentina I , Fatullaeva Aziza A , Nasereddin Abdelmajeed , Klement Eyal , Alam Mohammad Z , Schnur Lionel F , Jaffe Charles L , Schönian Gabriele , Baneth Gad
Published: April 2011

Background

The Namangan Region in the Pap District, located in Eastern Uzbekistan is the main focus of visceral leishmaniasis (VL) in Uzbekistan. In total, 28 cases of human VL were registered during 2006-2008 in this region. A study on the epidemiology of VL in this area was carried out in 2007-2008 in the villages of Chodak, Oltinkan, Gulistan and Chorkesar located at elevations of 900-1200 above sea level.

Results

A total of 162 dogs were tested for Leishmania infection. Blood was drawn for serology and PCR. When clinical signs of the disease were present, aspirates from lymph nodes and the spleen were taken. Forty-two dogs (25.9%) had clinical signs suggestive of VL and 51 (31.5%) were sero-positive. ITS-1 PCR was performed for 135 dogs using blood and tissue samples and 40 (29.6%) of them were PCR-positive. Leishmanial parasites were cultured from lymph node or spleen aspirates from 10 dogs.

Eight Leishmania strains isolated from dogs were typed by multi-locus microsatellite typing (MLMT) and by multilocus enzyme electrophoretic analysis (MLEE), using a 15 enzyme system. These analyses revealed that the strains belong to the most common zymodeme of L. infantum, i.e., MON-1, and form a unique group when compared to MON-1 strains from other geographical regions.

Conclusions

The data obtained through this study confirm the existence of an active focus of VL in the Namangan region of Uzbekistan. The fact that L. infantum was the causative agent of canine infection with typical clinical signs, and also of human infection affecting only infants, suggests that a zoonotic form of VL similar in epidemiology to Mediterranean VL is present in Uzbekistan.
Altered protein expression in serum from endometrial hyperplasia and carcinoma patients
Authors: Wang Yi-sheng , Cao Rui , Jin Hong , Huang Yi-ping , Zhang Xiao-yan , Cong Qing , He Yi-feng , Xu Cong-jian
Published: April 2011

Background

Endometrial carcinoma is one of the most common gynecological malignancies in women. The diagnosis of the disease at early or premalignant stages is crucial for the patient's prognosis. To date, diagnosis and follow-up of endometrial carcinoma and hyperplasia require invasive procedures. Therefore, there is considerable demand for the identification of biomarkers to allow non-invasive detection of these conditions.

Methods

In this study, we performed a quantitative proteomics analysis on serum samples from simple endometrial hyperplasia, complex endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma patients, as well as healthy women. Serum samples were first depleted of high-abundance proteins, labeled with isobaric tags (iTRAQ™), and then analyzed via two-dimensional liquid chromatography and tandem mass spectrometry. Protein identification and quantitation information were acquired by comparing the mass spectrometry data against the International Protein Index Database using ProteinPilot software. Bioinformatics annotation of identified proteins was performed by searching against the PANTHER database.

Results

In total, 74 proteins were identified and quantified in serum samples from endometrial lesion patients and healthy women. Using a 1.6-fold change as the benchmark, 12 proteins showed significantly altered expression levels in at least one disease group compared with healthy women. Among them, 7 proteins were found, for the first time, to be differentially expressed in atypical endometrial hyperplasia. These proteins are orosomucoid 1, haptoglobin, SERPINC 1, alpha-1-antichymotrypsin, apolipoprotein A-IV, inter-alpha-trypsin inhibitor heavy chain H4, and histidine-rich glycoprotein.

Conclusions

The differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma.
Gene expression changes with differentiation of cord blood stem cells to respiratory epithelial cells: a preliminary observation
Authors: Berger Michael J , Minnerath Sharon R , Adams Sheryl D , Tigges Barbara M , Sprague Stacey L , McKenna Jr David H
Published: April 2011

Introduction

Owing to wide availability, low cost and avoidance of ethical concerns, umbilical cord blood (UCB) provides an attractive source of stem cells for investigational and therapeutic uses. In this study, we sought to characterize the gene expression changes as stem cells from UCB differentiate toward alveolar type II pneumocytes (ATII).

Methods

Control and experimental cells were cultured in maintenance medium (mesenchymal stem cell growth medium) or differentiation medium (small airway growth medium (SAGM)), respectively, for 8 days. Total RNA was isolated from control and experimental groups for gene expression profiling and real-time polymerase chain reaction assay.

Results

Analysis of only mixed cell lines (n = 2) with parameters including a P value of 0.01 and an intergroup gap of 2.0 yielded a set of 373 differentially expressed genes. Prominently upregulated genes included several genes associated with ATII cells and also lung cancers: ALDH3A1, VDR and CHKA. Several upregulated genes have been shown to be integral or related to ATII functioning: SGK1, HSD17B11 and LEPR. Finally, several upregulated genes appear to play a role in lung cancers, including FDXR and GP96. Downregulated genes appear to be associated with bone, muscle and central nervous system tissues as well as other widespread tissues.

Conclusions

To the best of our knowledge, this accounting of the gene expression changes associated with the differentiation of a human UCB-derived stem cell toward an ATII cell represents the first such effort. Dissecting which components of SAGM affect specific gene regulation events is warranted.
The Coexistence of a Novel Inactivating Mutant Thyrotropin Receptor Allele with Two Thyroid Peroxidase Mutations: A Genotype-Phenotype Correlation
Authors: Sriphrapradang Chutintorn , Tenenbaum-Rakover Yardena , Weiss Mia , Barkoff Marla S. , Admoni Osnat , Kawthar Dallasheh , Caltabiano Gianluigi , Pardo Leonardo , Dumitrescu Alexandra M. , Refetoff Samuel
Published: April 2011

Context:

TSH receptor (TSHR) and thyroid peroxidase (TPO) gene mutations occur independently. This is the first report of their coexistence in the same individuals.

Objectives:

The objective of the study was to evaluate the genotype-phenotype correlations when mutations in both genes are present alone or together in the same individual.

Patients and Methods:

Thirty subjects from an extended Arab kindred underwent clinical investigation and molecular studies of the mutant TSHRs.

Results:

A novel mutant TSHR was identified, involving four nucleotides at three sites on the same allele, c.267G>T (L89L), c.269/270AG>CT (Q90P), and c.790C>T (P264S). In addition, two known TPO gene mutations, G493S and R540X, were identified. Thirteen heterozygotes for the mutant TSHR allele had mild hyperthyrotropinemia. In nine of theses, the coexistence of a TPO mutation in one allele did not magnify the hyperthyrotropinemia. Homozygotes for the mutant TSHR and a compound heterozygote for the TPO mutations presented frank hypothyroidism. In vitro studies showed increasing loss of function for Q90P less than P264S less than Q90P/P264S TSHR mutants, the latter being that expressed in the subjects under investigation. The two interchangeably used WT TSHR vectors, L87 and V87, although functionally identical, differed in structure and function in the presence of the Q90P mutation.

Conclusions:

TSHR and TPO gene mutations were identified alone and together in individuals of a consanguineous kindred. Homozygotes for the TSHR and a compound heterozygote for the TPO mutations were hypothyroid. The mild hyperthyrotropinemia of heterozygotes for the mutant TSHR allele was not aggravated by the coexistence of a TPO defect in one allele.
More on Michigan Listeners' Perceptions of /ɑ/-Fronting
Authors: Rakerd Brad , Plichta Bartłomiej
Published: April 2011

The Northern Cities Vowel Shift (NCVS) is well advanced in southeastern Lower Michigan and largely absent in Michigan's Upper Peninsula. In a previous study, Plichta and Rakerd found evidence that listeners from Lower Michigan make a perceptual adjustment for NCVS /ɑ/-fronting when given acoustical information about a talker's dialect (a sentence-long speech sample), but listeners from the Upper Peninsula do not. The present study further examines this phenomenon. Here, individual differences regarding listeners' vowel categorization judgments indicate that the /ɑ/-fronting perceptual response is consistently present among young adult residents of Lower Michigan, but much more variable among young adults from the Upper Peninsula. There is also evidence that the perceptual effect for Lower Michigan listeners is robust over a number of different stimulus variations. A word-level difference found here suggests that perceptual cues to /ɑ/-fronting may be provided by both static and dynamic vowel formant features. Finally, listeners' decision reaction times provide new evidence of regional differences in sensitivity to NCVS.
Unprincipled Pedagogy
Authors: Lynch Paul
Published: April 2011

Postprocess theory questions the usefulness of pedagogical principles. This article proposes a casuistic pedagogy, which offers a stance rather than a method. Casuistry, the art of case-based reasoning, reframes pedagogy as a series of occasions rather than a system of thought, thus providing grounds for a postprocess pedagogy.
Clarity, George Orwell, and the Pedagogy of Prose Style; Or, How Not to Teach “Shooting an Elephant”
Authors: Clausson Nils
Published: April 2011

Although Orwell's essays—particularly “Shooting an Elephant”—are used in freshman composition classes as stylistic models of clarity for student to imitate, this practice is pedagogically unsound because Orwell's essays are examples of the contemplative essay, whose aims are very different from those of the expository prose students learn to write in composition classes.
Mocking Discourse
Authors: Seitz David
Published: April 2011

Students' writing of parody can provide a more persuasive vehicle than conventional academic writing to move students from their intuitive awareness of irony to critical analysis of rhetorical strategies. Combining parody writing with strong critical reflection can encourage a more complex view of language choices, audience identification, genres, and persuasion.
This One Is for the Groundlings
Authors: McNabb Cameron Hunt
Published: April 2011

Based on Walter Eggers's article “Teaching Drama: a Manifesto,” this article discusses practical ways to emphasize the persistence and popularity of the dramatic tradition in an introduction to drama course. I argue that drama's popularity is an essential tool for teaching the genre to undergraduates in all disciplines, and to demonstrate this tenet in my own experience, I give examples of how I taught formal and thematic elements through their use in contemporary media as well as several assignments that demonstrate the symbiotic relationship between staged theatre and its multimedia counterparts.
The enhancer of trithorax and polycomb gene Caf1/p55 is essential for cell survival and patterning in Drosophila development
Authors: Anderson Aimée E. , Karandikar Umesh C. , Pepple Kathryn L. , Chen Zhihong , Bergmann Andreas , Mardon Graeme
Published: April 2011

In vitro data suggest that the human RbAp46 and RbAp48 genes encode proteins involved in multiple chromatin remodeling complexes and are likely to play important roles in development and tumor suppression. However, to date, our understanding of the role of RbAp46/RbAp48 and its homologs in metazoan development and disease has been hampered by a lack of insect and mammalian mutant models, as well as redundancy due to multiple orthologs in most organisms studied. Here, we report the first mutations in the single Drosophila RbAp46/RbAp48 homolog Caf1, identified as strong suppressors of a senseless overexpression phenotype. Reduced levels of Caf1 expression result in flies with phenotypes reminiscent of Hox gene misregulation. Additionally, analysis of Caf1 mutant tissue suggests that Caf1 plays important roles in cell survival and segment identity, and loss of Caf1 is associated with a reduction in the Polycomb Repressive Complex 2 (PRC2)-specific histone methylation mark H3K27me3. Taken together, our results suggest suppression of senseless overexpression by mutations in Caf1 is mediated by participation of Caf1 in PRC2-mediated silencing. More importantly, our mutant phenotypes confirm that Caf1-mediated silencing is vital to Drosophila development. These studies underscore the importance of Caf1 and its mammalian homologs in development and disease.
The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans
Authors: Neukomm Lukas Jakob , Nicot Anne-Sophie , Kinchen Jason Michael , Almendinger Johann , Pinto Sérgio Morgado , Zeng Sheng , Doukoumetzidis Kimon , Tronchère Hélène , Payrastre Bernard , Laporte Jocelyn Franck , Hengartner Michael Otmar
Published: April 2011

Multicellular organisms use programmed cell death to eliminate unwanted or potentially harmful cells. Improper cell corpse removal can lead to autoimmune diseases. The development of interventional therapies that increase engulfment activity could represent an attractive approach to treat such diseases. Here, we describe mtm-1, the Caenorhabditis elegans homolog of human myotubularin 1, as a potential negative regulator of apoptotic cell corpse clearance. Loss of mtm-1 function leads to substantially reduced numbers of persistent cell corpses in engulfment mutants, which is a result of a restoration of engulfment function rather than of impaired or delayed programmed cell death. Epistatic analyses place mtm-1 upstream of the ternary GEF complex, which consists of ced-2, ced-5 and ced-12, and parallel to mig-2. Over-activation of engulfment results in the removal of viable cells that have been brought to the verge of death under limiting caspase activity. In addition, mtm-1 also promotes phagosome maturation in the hermaphrodite gonad, potentially through CED-1 receptor recycling. Finally, we show that the CED-12 PH domain can bind to PtdIns(3,5)P2 (one target of MTM-1 phosphatase activity), suggesting that MTM-1 might regulate CED-12 recruitment to the plasma membrane.