bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuité de soins à l’hôpital et médecins étrangers : la régulation d’un système et ses limites en France
Authors: Le Vigouroux Alain
Published: September 2012

Résumé

La démographie médicale est un problème de santé majeur pour la réflexion sur les politiques de santé en France comme ailleurs dans le monde. Les médias se font régulièrement l’écho d’une sous médicalisation de la France. Cette affirmation mérite d’être modulée. Les inégalités de répartition territoriale, déjà importantes, iront en s’aggravant. On sait que la distribution sur le territoire français obéit au tropisme solaire bien connu des professions libérales. Le nord de la France est démographiquement déficitaire en médecins par rapport au sud, et la Champagne-Ardenne n’échappe pas à cette tendance. Cette distribution, loin d’être homogène, concentre les médecins dans les zones citadines, à telle enseigne que l’arrière-pays niçois est une zone aussi désertique que le Santerre picard. Le maintien d’une continuité des soins dans les services de soins continus dans les hôpitaux devient un exercice difficile. Un focus sur la région Champagne Ardenne, région européenne de migration, nous permet de comprendre le rôle des médecins étrangers dans le maintien de la continuité des soins en milieu hospitalier. Les enjeux et limites d’un tel dispositif doivent être perçus à l’échelon européen et mondial. Si les médecins étrangers représentent une manne pour les services des hôpitaux en France et dans d’autres pays d’Europe du Nord, cette migration nécessite d’être mieux régulée afin de freiner une désertification massive en particulier de pays d’Europe de l’Est et d’Afrique sub-saharienne.
The changing landscape in the treatment of metastatic castration-resistant prostate cancer
Authors: El-Amm Joelle , Aragon-Ching Jeanny B.
Published: September 2012

The past few years have brought increasing advances in the therapeutic management of metastatic castration-resistant prostate cancer with the approval of several agents, including vaccine therapy with sipuleucel-T, second-line chemotherapy with cabazitaxel, the bone-targeted pharmaceutical denosumab, and the novel antiandrogen therapy abiraterone acetate. There are ongoing developments with other agents in the pipeline such as MDV3100 and alpharadin that have shown promising results. This review describes the clinical trials that brought about the drug approvals of various agents and offers some insights regarding a rational approach to optimal treatment sequencing for these drugs since national guidelines are currently lacking.
Comparison of whole-genome prediction models for traits with contrasting genetic architecture in a diversity panel of maize inbred lines
Authors: Riedelsheimer Christian , Technow Frank , Melchinger Albrecht E
Published: September 2012

Background

There is increasing empirical evidence that whole-genome prediction (WGP) is a powerful tool for predicting line and hybrid performance in maize. However, there is a lack of knowledge about the sensitivity of WGP models towards the genetic architecture of the trait. Whereas previous studies exclusively focused on highly polygenic traits, important agronomic traits such as disease resistances, nutrifunctional or climate adaptational traits have a genetic architecture which is either much less complex or unknown. For such cases, information about model robustness and guidelines for model selection are lacking. Here, we compared five WGP models with different assumptions about the distribution of the underlying genetic effects. As contrasting model traits, we chose three highly polygenic agronomic traits and three metabolites each with a major QTL explaining 22 to 30% of the genetic variance in a panel of 289 diverse maize inbred lines genotyped with 56,110 SNPs.

Results

We found the five WGP models to be remarkable robust towards trait architecture with the largest differences in prediction accuracies ranging between 0.05 and 0.14 for the same trait, most likely as the result of the high level of linkage disequilibrium prevailing in elite maize germplasm. Whereas RR-BLUP performed best for the agronomic traits, it was inferior to LASSO or elastic net for the three metabolites. We found the approach of genome partitioning of genetic variance, first applied in human genetics, as useful in guiding the breeder which model to choose, if prior knowledge of the trait architecture is lacking.

Conclusions

Our results suggest that in diverse germplasm of elite maize inbred lines with a high level of LD, WGP models differ only slightly in their accuracies, irrespective of the number and effects of QTL found in previous linkage or association mapping studies. However, small gains in prediction accuracies can be achieved if the WGP model is selected according to the genetic architecture of the trait. If the trait architecture is unknowne.g.for novel traits which only recently received attention in breeding, we suggest to inspect the distribution of the genetic variance explained by each chromosome for guiding model selection in WGP.
Drug resistance-conferring mutations in Mycobacterium tuberculosis from Madang, Papua New Guinea
Authors: Ballif Marie , Harino Paul , Ley Serej , Coscolla Mireia , Niemann Stefan , Carter Robyn , Coulter Christopher , Borrell Sonia , Siba Peter , Phuanukoonnon Suparat , Gagneux Sebastien , Beck Hans-Peter
Published: September 2012

Background

Monitoring drug resistance in Mycobacterium tuberculosis is essential to curb the spread of tuberculosis (TB). Unfortunately, drug susceptibility testing is currently not available in Papua New Guinea (PNG) and that impairs TB control in this country. We report for the first time M. tuberculosis mutations associated with resistance to first and second-line anti-TB drugs in Madang, PNG. A molecular cluster analysis was performed to identify M. tuberculosis transmission in that region.

Results

Phenotypic drug susceptibility tests showed 15.7% resistance to at least one drug and 5.2% multidrug resistant (MDR) TB. Rifampicin resistant strains had the rpoB mutations D516F, D516Y or S531L; Isoniazid resistant strains had the mutations katG S315T or inhA promoter C15T; Streptomycin resistant strains had the mutations rpsL K43R, K88Q, K88R), rrs A514C or gidB V77G. The molecular cluster analysis indicated evidence for transmission of resistant strain.

Conclusions

We observed a substantial rate of MDR-TB in the Madang area of PNG associated with mutations in specific genes. A close monitoring of drug resistance is therefore urgently required, particularly in the presence of drug-resistant M. tuberculosis transmission. In the absence of phenotypic drug susceptibility testing in PNG, molecular assays for drug resistance monitoring would be of advantage.
Physiology of deletion mutants in the anaerobic β-myrcene degradation pathway in Castellaniella defragrans
Authors: Lüddeke Frauke , Dikfidan Aytac , Harder Jens
Published: September 2012

Background

Monoterpenes present a large and versatile group of unsaturated hydrocarbons of plant origin with widespread use in the fragrance as well as food industry. The anaerobic β-myrcene degradation pathway in Castellaniella defragrans strain 65Phen differs from well known aerobic, monooxygenase-containing pathways. The initial enzyme linalool dehydratase-isomerase ldi/LDI catalyzes the hydration of β-myrcene to (S)-(+)-linalool and its isomerization to geraniol. A high-affinity geraniol dehydrogenase geoA/GeDH and a geranial dehydrogenase geoB/GaDH contribute to the formation of geranic acid.

A genetic system was for the first time applied for the betaproteobacterium to prove in vivo the relevance of the linalool dehydratase-isomerase and the geraniol dehydrogenase. In-frame deletion cassettes were introduced by conjugation and two homologous recombination events.

Results

Polar effects were absent in the in-frame deletion mutants C. defragrans Δldi and C. defragrans ΔgeoA. The physiological characterization of the strains demonstrated a requirement of the linalool dehydratase-isomerase for growth on acyclic monoterpenes, but not on cyclic monoterpenes. The deletion of geoA resulted in a phenotype with hampered growth rate on monoterpenes as sole carbon and energy source as well as reduced biomass yields. Enzyme assays revealed the presence of a second geraniol dehydrogenase. The deletion mutants were in trans complemented with the broad-host range expression vector pBBR1MCS-4ldi and pBBR1MCS-2geoA, restoring in both cases the wild type phenotype.

Conclusions

In-frame deletion mutants of genes in the anaerobic β-myrcene degradation revealed novel insights in the in vivo function. The deletion of a high-affinity geraniol dehydrogenase hampered, but did not preclude growth on monoterpenes. A second geraniol dehydrogenase activity was present that contributes to the β-myrcene degradation pathway. Growth on cyclic monoterpenes independent of the initial enzyme LDI suggests the presence of a second enzyme system activating unsaturated hydrocarbons.
Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia-Evidence from an updated meta-analysis including 35 studies
Authors: Wang Haigang , Wang Jiali , Zhao Lixia , Liu Xinchun , Mi Wenjie
Published: September 2012

Background

5,10-methylenetetrahydrofolate reductase (MTHFR) variants, C677T and A1298C, have been reported to be associated with decreased risk of acute lymphoblastic leukemia (ALL). However, results derived from individually underpowered studies are conflicting. We carried out an updated meta-analysis on the association betweenMTHFRpolymorphisms and ALL risk.

Methods

Relevant publications were searched through PUBMED and EMBASE databases. The associations betweenMTHFRC677T and A1298C polymorphisms and the risk of ALL were evaluated by odds ratios (ORs). The heterogeneity and publication bias were estimated. Meta-regression analysis was performed to evaluate the potential sources of heterogeneity.

Results

C677T polymorphism was associated with a reduced risk of ALL (allele contrast: ORRE = 0.91, 95% CI: 0.83-0.99). Subgroup analysis showedMTHFRC677T variant was associated with decreased susceptibility to ALL in children and Caucasians. Meta-regression showed the logOR for the association between T allele and ALL increased as sex ratio (M/F) in the case group increased (P = 0.01). Regarding A1298C polymorphism, no significant association was observed (allele contrast: ORRE = 1.01, 95% CI: 0.91-1.11). There was no publication bias for C677T or A1298C polymorphism.

Conclusions

The present meta-analysis suggests that the C677T polymorphism, not A1298C, inMTHFRgene is associated with a decreased risk of ALL, particularly among children and Caucasians subjects. Our findings suggest that the influence of the C677T polymorphism on ALL susceptibility is modified by sex ratio in cases (M/F). Since folate intake may be a possible confounding factor, including this factor in future prospective studies is warranted. Further meta-analysis studies should be at least stratified for folate levels and gender to give more powerful and informative results.
CMV-associated encephalitis and antineuronal autoantibodies - a case report
Authors: Xu Xinling , Bergman Peter , Willows Thomas , Tammik Charlotte , Sund Marie , Hökfelt Tomas , Söderberg-Naucler Cecilia , Varani Stefania
Published: September 2012

Background

Human cytomegalovirus (CMV) is an ubiquitous pathogen capable of modulating the host immune system. Immune dysfunction is common during CMV infection and includes autoimmune phenomena. Here we focus on a case of primary CMV infection associated with encephalopathy in a patient with a rudimentary spleen. We discuss diagnostic challenges and immunological aspects as well as the hypothesis that CMV may break tolerance and induce potentially encephalitogenic autoantibodies.

Case presentation

A 33-year-old woman was admitted with features of encephalitis, rapidly progressing into a catatonic state. The patient tested negative for presence of herpes simplex virus DNA in cerebrospinal fluid (CSF), and had elevated liver enzymes and hepatomegaly at computed tomography scan (CT) examination. CT scan and magnetic resonance imaging (MRI) showed only a rudimentary spleen. Initially, serum was negative for anti-CMV IgM, but borderline for anti-CMV IgG by enzyme-linked immunosorbent assay. However, a more sensitive assay resulted in a positive specific IgM Western blot profile and low IgG avidity, suggesting primary CMV infection. Further, CMV DNA was retrospectively detected in a CSF sample collected at admission. We also detected antineuronal autoantibodies, which stained GAD-positive neurons in the hippocampus. The patient was treated by a combination of prednisone, intravenous immunoglobulins (IVIg) and antivirals, which resulted in a dramatic amelioration of the patient’s neurological status. One year after admission the patient exhibited a nearly complete recovery with mild deficits in attention and memory.

Conclusions

A possible reason for the critical course of CMV infection could be the lack of a functional spleen in this patient, a condition previously associated with severe CMV infection. Prompt treatment with antiviral drugs, steroids and IVIg was most likely important for the positive outcome in this case and should be considered for similar cases of severe primary CMV infection associated with immunopathological phenomena.
Weight- perception in male career firefighters and its association with cardiovascular risk factors
Authors: Baur Dorothee M , Christophi Costas A , Tsismenakis Antonios J , Jahnke Sara A , Kales Stefanos N
Published: September 2012

Background

The prevalence of obesity has reached epidemic proportions worldwide, and is also increasing among public safety professionals like firefighters who are expected to be fit and more active. The present study evaluates the associations among Body Mass Index (BMI), weight perception and cardiovascular risk factors in 768 male career firefighters from two Midwestern states in the United States.

Methods

A physical examination was performed and fasting blood samples were taken. Cardio-respiratory fitness (CRF) was determined from symptom- limited maximal treadmill exercise testing with electrocardiogram (ECG) monitoring and estimation of oxygen consumption (metabolic equivalents, METS) using the Bruce protocol. A health and lifestyle questionnaire was administered with standardized written instructions for completion. Self-reports of weight perception were extracted from responses to the completed multiple choice questionnaire. Baseline characteristics were described using the mean (standard deviation) for continuous variables and frequency for categorical variables. Group comparisons were calculated using analysis of variance (ANOVA). Linear models and logistic regression models were used to adjust for possible confounders. Logistic regression analyses were used to calculate the odds ratios of underestimating one’s weight category.

Results

A high proportion of overweight and obese male career firefighters underestimate their weight categories (68%). The risk of underestimating one’s weight category increased by 24% with each additional unit of increasing BMI after adjustment for age and CRF. When divided into six groups based on combinations of measured BMI category and weight perception, there were significant differences among the groups for most cardiovascular risk factors. After adjustment for age and BMI, these differences remained statistically significant for CRF, amount of weekly exercise, prevalence of Metabolic Syndrome (MetSyn), body fat percentage and cholesterol measurements.

Conclusion

A high proportion of overweight and obese male career firefighters underestimate their measured BMI categories. As a result, they are unlikely to fully appreciate the negative health consequences of their excess weight. The results of this study emphasize the importance of objectively measuring BMI and then informing patients of their actual weight status and the associated disease risks.
Real-time PCR assay for discrimination of Plasmodium ovale curtisi and Plasmodium ovale wallikeri in the Ivory Coast and in the Comoros Islands
Authors: Bauffe Frédérique , Desplans Jérôme , Fraisier Christophe , Parzy Daniel
Published: September 2012

Background

Plasmodium ovale is one of the five malaria species infecting humans. Recent data have shown that the name of this neglected species masks two distinct genotypes also called curtisi and wallikeri. Some authors show that these species could be sympatric. These two subspecies are not differentiated by microscopy techniques and malaria rapid diagnostic tests. This diagnostic defect is the result of low parasitaemia, antigenic polymorphism and absence of antibodies performance and requires the use of sequencing techniques. An accurate and easy discrimination detection method is necessary.

Methods

A new molecular assay was developed to easily identify the two genotypes of P. ovale. This tool allowed the study of 90 blood samples containing P. ovale, confirmed by molecular biology techniques, which were obtained from patients with imported malaria.

Results

The new marker was validated on well genotyped samples. The genotype of 90 P. ovale samples mainly imported from the Ivory Coast and the Comoros Islands was easily and quickly realized. The distribution of the two subspecies was described with a significant number of samples and showed that the two genotypes were present in the studied countries.

Conclusion

This work confirms the presence of the two species in the same country for the first time, in the Ivory Coast and the Comoros Islands. A better genotyping of P. ovale types may improve a better characterization of the clinical pathophysiology for each.
HLA-E expression in cervical adenocarcinomas: association with improved long-term survival
Authors: Spaans Vivian M , Peters Alexander AW , Fleuren Gert Jan , Jordanova Ekaterina S
Published: September 2012

Background

Cervical cancer is the third most common cancer in women worldwide. The most common histopathological subtype is cervical squamous cell carcinoma (SCC, 75-80%), followed by adenocarcinoma (AC) and adenosquamous carcinoma (ASC; together 15-20%). Rising incidence rates of AC have been observed relative and absolute to SCC and evidence is accumulating that cervical AC is a distinct clinical entity. Cervical SCC, ASC, and AC are caused by a persistent infection with high-risk human papillomavirus (HPV) and failed control of the immune system plays a pivotal role in the carcinogenesis of all three histopathological subtypes. Human leukocyte antigen E (HLA-E), a non-classical HLA class Ib molecule, plays an important role in immune surveillance and immune escape of virally infected cells. In this study we investigated HLA-E expression in three well-defined cohorts of cervical AC, ASC, and SCC patients, and determined whether HLA-E expression was associated with histopathological parameters and patient survival.

Methods and results

HLA-E expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections of 79 SCC, 38 ASC, and 75 AC patients. All patients included were International Federation of Gynaecology and Obstetrics stage I-II and underwent radical hysterectomy with lymphadenectomy as primary treatment. Significant differences between the histopathological subgroups were detected for age distribution, HPV positivity, HPV type distribution, tumour size, tumour infiltration depth, lymph-vascular space invasion, and adjuvant radiotherapy. High expression of HLA-E was found in 107/192 (56%) cervical carcinomas, with significantly more overexpression in cervical AC compared to SCC and ASC (37/79 SCC, 18/38 ASC, and 52/75 AC;P = 0.010). High HLA-E expression in cervical AC was associated with favourable long term disease-specific and recurrence-free survival (P = 0.005 andP = 0.001, respectively).

Conclusion

High expression of HLA-E occurred in the majority of all histopathological subtypes of cervical cancer; especially in cervical AC. High HLA-E expression in cervical AC was associated with improved patient survival. This study also highlights the importance of careful evaluation of cervical carcinomas to distinguish histopathological subtypes. In the future, insight into the biological behaviour and distinct molecular carcinogenetic processes of the AC, ASC, and SCC subtypes may contribute to the development of more tumour-specific treatment strategies.
A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: effects of treatment and non-treatment
Authors: Shaw Monica , Hodgkins Paul , Caci Hervé , Young Susan , Kahle Jennifer , Woods Alisa G , Arnold L Eugene
Published: September 2012

Background

In childhood, attention deficit/hyperactivity disorder (ADHD) is characterized by age-inappropriate levels of inattentiveness/disorganization, hyperactivity/impulsiveness, or a combination thereof. Although the criteria for ADHD are well defined, the long-term consequences in adults and children need to be more comprehensively understood and quantified. We conducted a systematic review evaluating the long-term outcomes (defined as 2 years or more) of ADHD with the goal of identifying long-term outcomes and the impact that any treatment (pharmacological, non-pharmacological, or multimodal) has on ADHD long-term outcomes.

Methods

Studies were identified using predefined search criteria and 12 databases. Studies included were peer-reviewed, primary studies of ADHD long-term outcomes published between January 1980 to December 2010. Inclusion was agreed on by two independent researchers on review of abstracts or full text. Published statistical comparison of outcome results were summarized as poorer than, similar to, or improved versus comparators, and quantified as percentage comparisons of these categories.

Results

Outcomes from 351 studies were grouped into 9 major categories: academic, antisocial behavior, driving, non-medicinal drug use/addictive behavior, obesity, occupation, services use, self-esteem, and social function outcomes. The following broad trends emerged: (1) without treatment, people with ADHD had poorer long-term outcomes in all categories compared with people without ADHD, and (2) treatment for ADHD improved long-term outcomes compared with untreated ADHD, although not usually to normal levels. Only English-language papers were searched and databases may have omitted relevant studies.

Conclusions

This systematic review provides a synthesis of studies of ADHD long-term outcomes. Current treatments may reduce the negative impact that untreated ADHD has on life functioning, but does not usually 'normalize' the recipients.
Epidemiological, molecular and clinical features of Enterovirus 109 infection in children and in adult stem cell transplant recipients
Authors: Debiaggi Maurizia , Ceresola Elisa Rita , Sampaolo Michela , Alessandrino Emilio Paolo , Brerra Roberto , Piazza Aurora , Clementi Massimo , Canducci Filippo
Published: September 2012

Background

A novel human enterovirus (HEV) type within the species HEV-C, named EV109, was discovered from cases of respiratory illness in Nicaragua in September 2010. The aim of this study, was to retrospectively examine the presence and the role of EV109 in respiratory samples from two patients populations; infants below the age of 2 years, hospitalized for acute respiratory diseases (ARDs) and adult hematopoietic stem cell transplantation recipients.

Results

A total of 1149 nasopharingeal aspirates were collected and tested for the presence of EV109 by reverse transcription-PCR (RT-PCR). In positive samples, the presence of the most common respiratory viruses was also assayed and clinical symptoms were evaluated. Samples from 2 of the 974 infants tested positive for EV109 RNA (0.2%) and belonged to patients with lower ARDs; co-infection with other viral pathogens under study was observed in both cases. In transplant recipients, one out of the 175 samples analyzed, from a patients with upper respiratory simptoms tested positive for HEV 109 in the absence of co-infecting viruses. Sequence analysis of amplified EV109 genomic regions, showed only a few nucleotide differences when compared with the Nicaraguan strains.

Conclusions

Overall these results indicate that HEV109 variants have circulated and differentiated in different lineages worldwide. Although more cases and larger studies are needed, HEV109 infection may be associated to ARDs both in infants and in hematopoietic stem cell transplantation recipients. If these preliminary observations will be confirmed, improved molecular methods with a wider panel of potential pathogens will be useful for monitoring these categories of patients.
Central and peripheral venous lines-associated blood stream infections in the critically ill surgical patients
Authors: Ugas Mohamed Ali , Cho Hyongyu , Trilling Gregory M , Tahir Zainab , Raja Humaera Farrukh , Ramadan Sami , Jerjes Waseem , Giannoudis Peter V
Published: September 2012

Critically ill surgical patients are always at increased risk of actual or potentially life-threatening health complications. Central/peripheral venous lines form a key part of their care. We review the current evidence on incidence of central and peripheral venous catheter-related bloodstream infections in critically ill surgical patients, and outline pathways for prevention and intervention. An extensive systematic electronic search was carried out on the relevant databases. Articles were considered suitable for inclusion if they investigated catheter colonisation and catheter-related bloodstream infection. Two independent reviewers engaged in selecting the appropriate articles in line with our protocol retrieved 8 articles published from 1999 to 2011. Outcomes on CVC colonisation and infections were investigated in six studies; four of which were prospective cohort studies, one prospective longitudinal study and one retrospective cohort study. Outcomes relating only to PICCs were reported in one prospective randomised trial. We identified only one study that compared CVC- and PICC-related complications in surgical intensive care units. Although our search protocol may not have yielded an exhaustive list we have identified a key deficiency in the literature, namely a paucity of studies investigating the incidence of CVC- and PICC-related bloodstream infection in exclusively critically ill surgical populations. In summary, the diverse definitions for the diagnosis of central and peripheral venous catheter-related bloodstream infections along with the vastly different sample size and extremely small PICC population size has, predictably, yielded inconsistent findings. Our current understanding is still limited; the studies we have identified do point us towards some tentative understanding that the CVC/PICC performance remains inconclusive.
Miliary brain metastasis presenting with calcification in a patient with lung cancer: a case report
Authors: Inomata Minehiko , Hayashi Ryuji , Kambara Kenta , Okazawa Seisuke , Imanishi Shingo , Ichikawa Tomomi , Suzuki Kensuke , Yamada Toru , Miwa Toshiro , Kashii Tatsuhiko , Matsui Shoko , Tobe Kazuyuki , Sasahara Masakiyo
Published: September 2012

Introduction

Miliary brain metastasis is an extremely rare form of brain metastasis which can present with atypical imaging findings. We report the case of a patient with miliary brain metastasis of lung cancer showing calcification in metastatic lesions.

Case presentation

A 68-year-old Japanese woman was diagnosed with lung adenocarcinoma. Brain computed tomography revealed multiple small calcified lesions in both cerebral hemispheres. Mutation of the epidermal growth factor receptor gene (exon 21, L858R) in lung cancer cells was detected, and treatment with gefitinib was initiated. A partial response was observed; however, the patient was readmitted to our hospital because of regrowth of the primary lesion and complaints of nausea, headache, and difficulty walking. Brain magnetic resonance imaging revealed scattered tiny nodules enhanced by gadolinium. A diagnosis of leptomeningeal carcinomatosis was made on the basis of cerebrospinal fluid cytology. The patient’s general status worsened, and she died 356 days after the day of first medical examination. Upon autopsy, the brain was found to be edematous and swollen. Lung carcinoma cells were diffusely disseminated on the meningeal surface. Metastatic foci of small nodular form, accompanied by calcifications, were also found in the brain parenchyma. We diagnosed miliary metastasis of lung carcinoma.

Conclusions

To the best of our knowledge, this is the third report of calcified miliary brain metastasis confirmed by autopsy. We describe calcified lesions that increased in size during the clinical course of nine months. Brain computed tomography findings that reveal multiple small calcified lesions in patients with malignancy should raise suspicion of miliary brain metastasis.
The Constructor: a web application optimizing cloning strategies based on modules from the registry of standard biological parts
Authors: Hesselman Matthijn C , Koehorst Jasper J , Slijkhuis Thijs , Odoni Dorett I , Hugenholtz Floor , van Passel MarkW J
Published: September 2012

Synthetic biology is an emerging field that combines molecular biology with engineering principles, which requires abstraction levels applied to a modular biological componentry. The Registry of Standard Biological Parts harbours such a repository of standardized parts, and thereby facilitates the combination of complex molecular modules to novel genetic circuits and devices. However, since finding the best parts for a pre-determined genetic design can be time consuming, we devised the Constructor, a web tool that recommends the smallest number of cloning steps for pre-designed circuits, and implements user-defined quality checks.

We present the Constructor (http://www.systemsbiology.nl/the_constructor) as a constructive web tool that simplifies the in silico assembly of pre-designed gene circuitries from standard parts, reducing both planning and subsequent cloning time.
Evaluation of high mobility group box 1 protein as a presurgical diagnostic marker reflecting the severity of acute appendicitis
Authors: Wu Chuanxin , Sun Hang , Wang Hongliang , Chi Junmeng , Liu Qi , Guo Hui , Gong Jianping
Published: September 2012

Objectives

To validate the role of high mobility group box-1(HMGB1) in diagnosis of acute appendicitis (AA) with different pathological severity.

Methods

According to the pathologically diagnosis, 150 patients underwent appendectomies between Jan. 2007 and Dec, 2010 were divided into acute simple, acute suppurative and acute gangrenous appendicitis as group 1, 2 and 3, respectively. Each patient group contains 50 sex and age matched cases to make comparison with 50 healthy volunteers. The mRNA and protein expression levels of serum HMGB1 were determined by real-time quantitative PCR and enzyme linked immunosorbent assay (ELISA). Serum High-sensitivity C-reactive protein (hs-CRP) levels were determined by rate nephelometric immunoassay.

Results

In comparison with health volunteers, relative HMGB1 mRNA levels in group 1, 2 and 3 were significantly increased 3.05 ± 0.51,8.33 ± 0.75 and 13.74 ± 1.09 folds, reflecting a tendency of augmented severity. In accordance, serum protein levels of HMGB1 were 10.97 ± 1.64, 14.42 ± 1.56 and 18.08 ± 2.41 ng/ml in 3 patient groups, which are significantly higher than that of healthy volunteers’ 5.47 ± 0.73 ng/ml. hs-CRP levels were 12.85 ± 3.41, 21.04 ± 1.98 and 31.07 ± 5.46 ng/ml in 3 patients groups compared with 2.06 ± 0.77 ng/ml in controls. The concentrations of HMGB1 and hs-CRP were both positively correlated with disease severity.

Conclusion

Serum HMGB1 constitutes as a valuable marker in diagnosis of AA. Positively correlated with hs-CRP level, mRNA and protein expression of HMGB1 to a certain extent reflected the severity of AA.
Evaluation of the Scandinavian guidelines for head injuries based on a consecutive series with computed tomography from a Norwegian university hospital
Authors: Strand Ingrid Haavde , Solheim Ole , Moen Kent Gøran , Vik Anne
Published: September 2012

Background

This study prospectively assesses clinical characteristics and management of consecutive minimal, mild and moderate head injury patients referred for CT scans. Compliance with the Scandinavian head injury guidelines and possible reasons for non-compliance is explored.

Methods

From January 16th 2006 to January 15th 2007, 1325 computed tomography (CT) examinations due to minimal, mild or moderate head injury according to the Head Injury Severity Scale (HISS) were carried out at our University Hospital. When ordering a CT scan due to head trauma, physicians were asked to fill out a questionnaire.

Results

Guideline compliance was impossible to assess in 49.5% of all cases. This was due to non-assessable or missing key variables necessary in the decision making algorithm. One or more key variables for HISS classification were not assessable in 34.4% as it was unknown whether there had been loss of consciousness (LOC), duration of LOC was unknown or it was impossible to assess amnesia or focal neurologic deficits. Definite compliance with both CT and admittance recommendations in guidelines was seen in only 31.2%. In 54.2% of patients with minimal head injuries who underwent CT scans, imaging was not necessary according to guidelines. 59.1% of all patients were admitted to hospital, however only 23.7% of these were admitted because of the head-injury alone. Age < 4 years, possible medical cause of injuries, severe headache/nausea or vomiting and the presence of non-traumatic CT findings were independently associated with non-assessable compliance with Scandinavian guidelines. Suspicion of influence of alcohol was inversely associated to non-compliance.

Conclusions

Despite the prospective study design, guideline compliance was not assessable in nearly half of the patients. Patients with isolated head injuries and available and obtainable complete clinical information necessary for guideline-based decision making are not dominating in a head injury population.
Tamanu oil - an alternative fuel for variable compression ratio engine
Authors: Raj Mohan T , Kandasamy Murugumohan Kumar K
Published: September 2012

Biodiesel can be produced from vegetable oils and also from waste fats. Biodiesel is a mono-alkyl-ester of long chain fatty acids derived from renewable feedstock such as vegetable oils by transesterification process. The esterified cotton seed oil, pungam oil, rice bran oil, and tamanu oil are chosen as the alternative fuels. Among these oils, tamanu oil is considered for the first time as an alternative fuel. An experiment is conducted to obtain the operating characteristics of the variable compression ratio (VCR) engine run by chosen esterified oils, and the results are compared with esterified tamanu oil. From the comparison of results, it is inferred that the engine performance is improved with significant reduction in emissions for the chosen oils without any engine modification. The effective compression ratio can be fixed based on the experimental results obtained in the engine since the findings of the present research work infer that the biodiesel obtained from tamanu oil is a promising alternative fuel for direct-injection four-stroke VCR engine.
The Benefits of Multi-Year Research Experiences: Differences in Novice and Experienced Students’ Reported Gains from Undergraduate Research
Authors: Thiry Heather , Weston Timothy J. , Laursen Sandra L. , Hunter Anne-Barrie
Published: September 2012

This mixed-methods study explores differences in novice and experienced undergraduate students’ perceptions of their cognitive, personal, and professional gains from engaging in scientific research. The study was conducted in four different undergraduate research (UR) programs at two research-extensive universities; three of these programs had a focus on the biosciences. Seventy-three entry-level and experienced student researchers participated in in-depth, semi-structured interviews and completed the quantitative Undergraduate Research Student Self-Assessment (URSSA) instrument. Interviews and surveys assessed students’ developmental outcomes from engaging in UR. Experienced students reported distinct personal, professional, and cognitive outcomes relative to their novice peers, including a more sophisticated understanding of the process of scientific research. Students also described the trajectories by which they developed not only the intellectual skills necessary to advance in science, but also the behaviors and temperament necessary to be a scientist. The findings suggest that students benefit from multi-year UR experiences. Implications for UR program design, advising practices, and funding structures are discussed.
Multiple-Choice Exams: An Obstacle for Higher-Level Thinking in Introductory Science Classes
Authors: Stanger-Hall Kathrin F.
Published: September 2012

Learning science requires higher-level (critical) thinking skills that need to be practiced in science classes. This study tested the effect of exam format on critical-thinking skills. Multiple-choice (MC) testing is common in introductory science courses, and students in these classes tend to associate memorization with MC questions and may not see the need to modify their study strategies for critical thinking, because the MC exam format has not changed. To test the effect of exam format, I used two sections of an introductory biology class. One section was assessed with exams in the traditional MC format, the other section was assessed with both MC and constructed-response (CR) questions. The mixed exam format was correlated with significantly more cognitively active study behaviors and a significantly better performance on the cumulative final exam (after accounting for grade point average and gender). There was also less gender-bias in the CR answers. This suggests that the MC-only exam format indeed hinders critical thinking in introductory science classes. Introducing CR questions encouraged students to learn more and to be better critical thinkers and reduced gender bias. However, student resistance increased as students adjusted their perceptions of their own critical-thinking abilities.
Facilitating Long-Term Changes in Student Approaches to Learning Science
Authors: Buchwitz Brian J. , Beyer Catharine H. , Peterson Jon E. , Pitre Emile , Lalic Nevena , Sampson Paul D. , Wakimoto Barbara T.
Published: September 2012

Undergraduates entering science curricula differ greatly in individual starting points and learning needs. The fast pace, high enrollment, and high stakes of introductory science courses, however, limit students’ opportunities to self-assess and modify learning strategies. The University of Washington's Biology Fellows Program (BFP) intervenes through a 20-session, premajors course that introduces students to the rigor expected of bioscience majors and assists their development as science learners. This study uses quantitative and qualitative approaches to assess whether the 2007–2009 BFP achieved its desired short- and long-term impacts on student learning. Adjusting for differences in students’ high school grade point average and Scholastic Aptitude Test scores, we found that participation in the BFP was associated with higher grades in two subsequent gateway biology courses, across multiple quarters and instructors. Two to 4 yr after participating in the program, students attributed changes in how they approached learning science to BFP participation. They reported having learned to “think like a scientist” and to value active-learning strategies and learning communities. In addition, they reported having developed a sense of belonging in bioscience communities. The achievement of long-term impacts for a short-term instructional investment suggests a practical means to prepare diverse students for the rigors of science curricula.
Cell Biology Apps for Apple Devices
Authors: Stark Louisa A.
Published: September 2012

Apps for touch-pad devices hold promise for guiding and supporting learning. Students may use them in the classroom or on their own for didactic instruction, just-in-time learning, or review. Since Apple touch-pad devices (i.e., iPad and iPhone) have a substantial share of the touch-pad device market ( Campbell, 2012 ), this Feature will explore cell biology apps available from the App Store. My review includes iPad and iPhone apps available in June 2012, but does not include courses, lectures, podcasts, audiobooks, texts, or other books. I rated each app on a five-point scale (1 star = lowest; 5 stars = highest) for educational and production values; I also provide an overall score.
An inwardly rectifying K+ channel is required for patterning
Authors: Dahal Giri Raj , Rawson Joel , Gassaway Brandon , Kwok Benjamin , Tong Ying , Ptáček Louis J. , Bates Emily
Published: September 2012

Mutations that disrupt function of the human inwardly rectifying potassium channel KIR2.1 are associated with the craniofacial and digital defects of Andersen-Tawil Syndrome, but the contribution of Kir channels to development is undefined. Deletion of mouse Kir2.1 also causes cleft palate and digital defects. These defects are strikingly similar to phenotypes that result from disrupted TGFβ/BMP signaling. We use Drosophila melanogaster to show that a Kir2.1 homolog, Irk2, affects development by disrupting BMP signaling. Phenotypes of irk2 deficient lines, a mutant irk2 allele, irk2 siRNA and expression of a dominant-negative Irk2 subunit (Irk2DN) all demonstrate that Irk2 function is necessary for development of the adult wing. Compromised Irk2 function causes wing-patterning defects similar to those found when signaling through a Drosophila BMP homolog, Decapentaplegic (Dpp), is disrupted. To determine whether Irk2 plays a role in the Dpp pathway, we generated flies in which both Irk2 and Dpp functions are reduced. Irk2DN phenotypes are enhanced by decreased Dpp signaling. In wild-type flies, Dpp signaling can be detected in stripes along the anterior/posterior boundary of the larval imaginal wing disc. Reducing function of Irk2 with siRNA, an irk2 deletion, or expression of Irk2DN reduces the Dpp signal in the wing disc. As Irk channels contribute to Dpp signaling in flies, a similar role for Kir2.1 in BMP signaling may explain the morphological defects of Andersen-Tawil Syndrome and the Kir2.1 knockout mouse.
SPACA1-deficient male mice are infertile with abnormally shaped sperm heads reminiscent of globozoospermia
Authors: Fujihara Yoshitaka , Satouh Yuhkoh , Inoue Naokazu , Isotani Ayako , Ikawa Masahito , Okabe Masaru
Published: September 2012

SPACA1 is a membrane protein that localizes in the equatorial segment of spermatozoa in mammals and is reported to function in sperm-egg fusion. We produced a Spaca1 gene-disrupted mouse line and found that the male mice were infertile. The cause of this sterility was abnormal shaping of the sperm head reminiscent of globozoospermia in humans. Disruption of Spaca1 led to the disappearance of the nuclear plate, a dense lining of the nuclear envelope facing the inner acrosomal membrane. This coincided with the failure of acrosomal expansion during spermiogenesis and resulted in the degeneration and disappearance of the acrosome in mature spermatozoa. Thus, these findings clarify part of the cascade leading to globozoospermia.
ISWI contributes to ArsI insulator function in development of the sea urchin
Authors: Yajima Mamiko , Fairbrother William G. , Wessel Gary M.
Published: September 2012

Insulators are genomic elements that regulate transcriptional activity by forming chromatin boundaries. Various DNA insulators have been identified or are postulated in many organisms, and the paradigmatic CTCF-dependent insulators are perhaps the best understood and most widespread in function. The diversity of DNA insulators is, however, understudied, especially in the context of embryonic development, when many new gene territories undergo transitions in functionality. Here we report the functional analysis of the arylsulfatase insulator (ArsI) derived from the sea urchin, which has conserved insulator activity throughout the many metazoans tested, but for which the molecular mechanism of function is unknown. Using a rapid in vivo assay system and a high-throughput mega-shift assay, we identified a minimal region in ArsI that is responsible for its insulator function. We discovered a small set of proteins specifically bound to the minimal ArsI region, including ISWI, a known chromatin-remodeling protein. During embryogenesis, ISWI was found to interact with select ArsI sites throughout the genome, and when inactivated led to misregulation of select gene expression, loss of insulator activity and aberrant morphogenesis. These studies reveal a mechanistic basis for ArsI function in the gene regulatory network of early development.
Dynamic microtubules at the vegetal cortex predict the embryonic axis in zebrafish
Authors: Tran Long Duc , Hino Hiromu , Quach Helen , Lim Shimin , Shindo Asako , Mimori-Kiyosue Yuko , Mione Marina , Ueno Naoto , Winkler Christoph , Hibi Masahiko , Sampath Karuna
Published: September 2012

In zebrafish, as in many animals, maternal dorsal determinants are vegetally localized in the egg and are transported after fertilization in a microtubule-dependent manner. However, the organization of early microtubules, their dynamics and their contribution to axis formation are not fully understood. Using live imaging, we identified two populations of microtubules, perpendicular bundles and parallel arrays, which are directionally oriented and detected exclusively at the vegetal cortex before the first cell division. Perpendicular bundles emanate from the vegetal cortex, extend towards the blastoderm, and orient along the animal-vegetal axis. Parallel arrays become asymmetric on the vegetal cortex, and orient towards dorsal. We show that the orientation of microtubules at 20 minutes post-fertilization can predict where the embryonic dorsal structures in zebrafish will form. Furthermore, we find that parallel microtubule arrays colocalize with wnt8a RNA, the candidate maternal dorsal factor. Vegetal cytoplasmic granules are displaced with parallel arrays by ∼20°, providing in vivo evidence of a cortical rotation-like process in zebrafish. Cortical displacement requires parallel microtubule arrays, and probably contributes to asymmetric transport of maternal determinants. Formation of parallel arrays depends on Ca2+ signaling. Thus, microtubule polarity and organization predicts the zebrafish embryonic axis. In addition, our results suggest that cortical rotation-like processes might be more common in early development than previously thought.
Tooth shape formation and tooth renewal: evolving with the same signals
Authors: Jernvall Jukka , Thesleff Irma
Published: September 2012

Teeth are found in almost all vertebrates, and they therefore provide a general paradigm for the study of epithelial organ development and evolution. Here, we review the developmental mechanisms underlying changes in tooth complexity and tooth renewal during evolution, focusing on recent studies of fish, reptiles and mammals. Mammals differ from other living vertebrates in that they have the most complex teeth with restricted capacity for tooth renewal. As we discuss, however, limited tooth replacement in mammals has been compensated for in some taxa by the evolution of continuously growing teeth, the development of which appears to reuse the regulatory pathways of tooth replacement.