bluuebunny/crossref_metadata_2025 huggingface dataset:
The Material Production of the Spiral Jetty: A Study of Culture in the Making
Authors: Rubio Fernando Domínguez
Published: May 2012

The objective of this article is to open the ‘black box’ of artistic production in order to describe, in minute detail, culture in the making, that is, the process through which cultural forms grow into being and are materially accomplished. I will do so through the study of the morphogenetic process through which the Spiral Jetty, an earthwork sculpture created by the American artist Robert Smithson, came into being. This study will show that artistic production constitutes an irreducible form of material practice which cannot be adequately understood as an individual activity or as an activity guided or constrained by ‘external’ social factors. As I shall argue, the attention to the material practice of artistic production reveals a much needed insight into the practices, materials and processes through which culture is actually produced and materially accomplished.
Attached by the Product: A Socio-Material Direction in the Sociology of Art
Authors: Strandvad Sara Malou
Published: May 2012

The sociology of art tends to reduce the cultural product to an outcome of social causality. As an alternative, this article pursues the aim of developing a cultural sociological approach which includes both sociality and materiality. The article builds on an empirical analysis of a case about the development of a film project, which ends in a devastating quarrel and consequently no film. In the analysis, the evolving product is portrayed as a mediator of the social relations around it. The article suggests that the human participants are attached or detached to the project based on their experiences of the evolving product. Thus the argument proposes that the product and the social relations are being co-produced, and that this is overlooked if the product is not included in the socialogical analysis.
What is the evidence for IABP in STEMI with and without cardiogenic shock?
Authors: de Waha Suzanne , Desch Steffen , Eitel Ingo , Fuernau Georg , Lurz Philipp , de Waha Antoinette , Schuler Gerhard , Thiele Holger
Published: May 2012

Intraaortic balloon pump (IABP) is the most widely used left ventricular support device in a variety of indications. This review focuses on the current literature and discusses the evidence of IABP in ST-elevation myocardial infarction (STEMI) with and without cardiogenic shock. In high-risk STEMI patients without cardiogenic shock several randomized clinical trials have been performed. The majority of the studies could not demonstrate an efficacy benefit for IABP as adjunctive therapy in comparison to standard treatment alone. Hence, recent meta-analyses could not reveal diverging mortality rates at a higher incidence of stroke and major bleedings with IABP use independent of the type of reperfusion therapy. IABP in STEMI patients with cardiogenic shock is recommended according to current American College of Cardiology/American Heart Association (AHA/ACC) and European Society of Cardiology (ESC) guidelines. In recent meta-analyses, IABP in cardiogenic shock complicated by STEMI has been shown to be associated with decreased mortality. However, these beneficial effects are limited to patients treated with thrombolysis, whereas in patients undergoing mechanical revascularization IABP therapy is associated with an increase in mortality. Nevertheless, these data only arise from prospective and retrospective cohort studies, as up to date only one very small randomized clinical trial has been completed. In summary, in high-risk STEMI patients without cardiogenic shock, current data do not support the use of IABP and should only be considered as a standby and bailout strategy if patients develop haemodynamic instability. Current data on IABP in patients with cardiogenic shock complicated by STEMI are scarce and highly limited due to the nonrandomized design of previous trials. However, according to current AHA/ACC and ESC guidelines its use is recommended. Although recent meta-analyses challenge current AHA/ACC/ESC guidelines, adequately powered randomized studies are needed to elucidate the role of IABP in patients with acute myocardial infarction complicated by cardiogenic shock.
Clinical and microbiologic characteristics of tcdA-negative variant clostridium difficile infections
Authors: Kim Jieun , Pai Hyunjoo , Seo Mi-ran , Kang Jung Oak
Published: May 2012

Background

The tcdA-negative variant (A-B+) of Clostridium difficile is prevalent in East Asian countries. However, the risk factors and clinical characteristics of A-B+
C. difficile infections (CDI) are not clearly documented. The objective of this study was to investigate these characteristics.

Methods

From September 2008 through January 2010, the clinical characteristics, medication history and treatment outcomes of CDI patients were recorded prospectively. Toxin characterization and antibiotic susceptibility tests were performed on stool isolates of C. difficile.

Results

During the study period, we identified 22 cases of CDI caused by tcdA-negative tcdB-positive (A-B+) strains and 105 cases caused by tcdA-positive tcdB-positive (A+B+) strains. There was no significant difference in disease severity or clinical characteristics between the two groups. Previous use of clindamycin and young age were identified as significant risk factors for the acquisition of A-B+ CDI (OR = 4.738, 95% CI 1.48–15.157, p = 0.009 and OR = 0.966, 95% CI 0.935–0.998, p = 0.038, respectively) in logistic regression.

Rates of resistance to clindamycin were 100% and 69.6% in the A-B+ and A+B+ isolates, respectively (p = 0.006), and the ermB gene was identified in 17 of 21 A-B+ isolates (81%). Resistance to moxifloxacin was also more frequent in the A-B+ than in the A+B+ isolates (95.2% vs. 63.7%, p = 0.004).

Conclusions

The clinical course of A-B+ CDI is not different from that of A+B+ CDI. Clindamycin use is a significant risk factor for the acquisition of tcdA-negative variant strains.
A pragmatic assessment of the relative efficiency of outreach chlamydia screening events conducted in non-clinical settings
Authors: Bowden Francis J , Currie Marian J , Todkill Muareen , Schmidt Mathias , Webeck Sue , Del Rosario Rendry , Bavinton Tim , Tyson Alexandra
Published: May 2012

Background

Opportunistic screening for chlamydia in non-clinical settings is becoming more common, but little is known about which settings (or events) offer the best return on investment. We measured the relative efficiency of each screening site and event during the conduct of a chlamydia education and screening outreach program which used a cash incentive to encourage participation (SOC2).

Methods

SOC2 staff identified sites and organised events in non-clinical sites where young people were likely to congregate. 16 to 30 years olds were offered chlamydia education and a cash reward of AUD10 if they chose to be screened for chlamydia. Data collected during these activities were used to calculated five measures of efficiency: i) screening yield’ (proportion of people providing a sample), ii) proportion of positive tests, iii) ‘event screening tempo’ (number of screens performed for every hour that screening is offered), iv) ‘staff hour screening tempo’ (number of screens performed per hour of staff time) and v) ‘chlamydia detection tempo’ (number of positive tests detected per hour of screening).

Results

3011 people (71% male) were screened during 18 events at 10 venues. Overall ‘screening yield’ was 43.8% (range: 20–77%) and 1.7% (95% CI: 1.1–3.0) of tests were positive (by event range 1–3%). Overall, the ‘event screening tempo’ was 23.7 screens per event hour (range 8.0–79.0), the ‘staff hour screening tempo’ was 6.5 screens per staff hour and the ‘chlamydia detection tempo’ was 0.4 positive tests per hour (range: 0–1.75).

Conclusion

Assessing the efficiency of screening sites and programs should be integral to their conduct. We suggest the use of five measures to enable pragmatic assessment of any screening program. We introduce the terms ‘event screening tempo’, ‘staff hour screening tempo’ and ‘chlamydia detection tempo’ to describe three of these simple measures.
Multi-layer topology control for long-term wireless sensor networks
Authors: Yoon Ikjune , Noh Dong Kun , Shin Heonshik
Published: May 2012

Due to the inefficiency of a flat topology, most wireless sensor networks (WSNs) have a cluster or tree structure; but this causes an imbalance of residual energy between nodes, which gets worse over time as nodes become defunct and replacements are inserted. Multiple layers are better then the typical two-layer cluster-based topology, because it can better accommodate nodes with different levels of residual energy. We propose that each node should periodically determine its own layer, as its situation and the network topology changes. We introduce a topology control scheme for long-term WSNs with these features. Simulations show that this scheme can balance node energy levels, and thus extend network lifetime.
Coupled and tripled coincidence point results without compatibility
Authors: Hussain Nawab , Latif Abdul , Shah Masood Hussain
Published: May 2012

In this article, we introduce a new and simple approach to coupled and tripled coincidence point theory. By using our method, we establish coupled coincidence point results of Lakshmikantham and Ćirić, Binayak et al., Alotaibi and Alsulami without any type of commutativity condition on F and g. We also use our technique to prove tripled coincidence point results of Borcut and Berinde without commutativity of maps. Also, we give a supporting example of non-commuting, non-compatible mappings where the above mentioned results can not be applied.

Mathematics Subject Classification: Primary, 47H10; Secondary, 54H25; 34B15.
Substrate utilization during submaximal exercise in children with a severely obese parent
Authors: Eaves Audrey D , Colon Ashley , DuBose Katrina D , Collier David , Houmard Joseph A
Published: May 2012

Background

We have reported a reduction in fatty acid oxidation (FAO) at the whole-body level and in skeletal muscle in severely obese (BMI ≥ 40 kg/m2) individuals; this defect is retained in cell culture suggesting an inherent component. The purpose of the current study was to determine if an impairment in whole-body fatty acid oxidation (FAO) was also evident in children with a severely obese parent.

Methods

Substrate utilization during submaximal exercise (cycle ergometer) was determined in children ages 8–12 y with a severely obese parent (OP, n = 13) or two lean/non-obese (BMI range of 18 to 28 kg/m2) parents (LP, n = 13). A subgroup of subjects (n = 3/group) performed 4 weeks of exercise training with substrate utilization measured after the intervention.

Results

The children did not differ in age (LP vs. OP, respectively) (10.7 ± 0.5 vs. 10.2 ± 0.5 y), BMI percentile (65.3 ± 5.2 vs. 75.9 ± 7), Tanner Stage (1.4 ± 0.2 vs. 1.5 ± 0.2), VO2peak (40.3 ± 2.7 vs. 35.6 ± 2.6 ml/kg/min) or physical activity levels (accelerometer). At the same absolute workload of 15 W (~38% VO2peak), RER was significantly (P ≤ 0.05) lower in LP vs. OP (0.83 ± 0.02 vs. 0.87 ± 0.01) which was reflected in a reduced reliance on FAO for energy production in the OP group (58.6 ± 5.1 vs. 43.1 ± 4.0% of energy needs during exercise from FAO). At a higher exercise intensity (~65% VO2peak) there were no differences in substrate utilization between LP and OP. After exercise training RER tended to decrease (P = 0.06) at the 15 W workload, suggesting an increased reliance on FAO regardless of group.

Conclusions

These findings suggest that the decrement in FAO with severe obesity has an inherent component that may be overcome with exercise training.
Multi-walled carbon nanotubes induce COX-2 and iNOS expression via MAP Kinase-dependent and -independent mechanisms in mouse RAW264.7 macrophages
Authors: Lee Jong Kwon , Sayers Brian C , Chun Kyung-Soo , Lao Huei-Chen , Shipley-Phillips Jeanette K , Bonner James C , Langenbach Robert
Published: May 2012

Background

Carbon nanotubes (CNTs) are engineered graphene cylinders with numerous applications in engineering, electronics and medicine. However, CNTs cause inflammation and fibrosis in the rodent lung, suggesting a potential human health risk. We hypothesized that multi-walled CNTs (MWCNTs) induce two key inflammatory enzymes in macrophages, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), through activation of extracellular signal-regulated kinases (ERK1,2).

Methods

RAW264.7 macrophages were exposed to MWCNTs or carbon black nanoparticles (CBNPs) over a range of doses and time course. Uptake and subcellular localization of MWCNTs was visualized by transmission electron microscopy (TEM). Protein levels of COX-2, iNOS, and ERK1,2 (total ERK and phosphorylated ERK) were measured by Western blot analysis. Prostaglandin-E2 (PGE2) and nitric oxide (NO) levels in cell supernatants were measured by ELISA and Greiss assay, respectively.

Results

MWCNTs, but not CBNPs, induced COX-2 and iNOS in a time- and dose-dependent manner. COX-2 and iNOS induction by MWCNTs correlated with increased PGE2 and NO production, respectively. MWCNTs caused ERK1,2 activation and inhibition of ERK1,2 (U0126) blocked MWCNT induction of COX-2 and PGE2 production, but did not reduce the induction of iNOS. Inhibition of iNOS (L-NAME) did not affect ERK1,2 activation, nor did L-NAME significantly decrease COX-2 induction by MWCNT. Nickel nanoparticles (NiNPs), which are present in MWCNTs as a residual catalyst, also induced COX-2 via ERK-1,2. However, a comparison of COX-2 induction by MWCNTs containing 4.5 and 1.8% Ni did not show a significant difference in ability to induce COX-2, indicating that characteristics of MWCNTs in addition to Ni content contribute to COX-2 induction.

Conclusion

This study identifies COX-2 and subsequent PGE2 production, along with iNOS induction and NO production, as inflammatory mediators involved in the macrophage response to MWCNTs. Furthermore, our work demonstrates that COX-2 induction by MWCNTs in RAW264.7 macrophages is ERK1,2-dependent, while iNOS induction by MWCNTs is ERK1,2-independent. Our data also suggest contributory physicochemical factors other than residual Ni catalyst play a role in COX-2 induction to MWCNT.
The Arabidopsis thaliana-Alternaria brassicicola pathosystem: A model interaction for investigating seed transmission of necrotrophic fungi
Authors: Pochon Stephanie , Terrasson Emmanuel , Guillemette Thomas , Iacomi-Vasilescu Beatrice , Georgeault Sonia , Juchaux Marjorie , Berruyer Romain , Debeaujon Isabelle , Simoneau Philippe , Campion Claire
Published: May 2012

Background

Seed transmission constitutes a major component of the parasitic cycle for several fungal pathogens. However, very little is known concerning fungal or plant genetic factors that impact seed transmission and mechanisms underlying this key biological trait have yet to be clarified. Such lack of available data could be probably explained by the absence of suitable model pathosystem to study plant-fungus interactions during the plant reproductive phase.

Results

Here we report on setting up a new pathosystem that could facilitate the study of fungal seed transmission. Reproductive organs of Arabidopsis thaliana were inoculated with Alternaria brassicicola conidia. Parameters (floral vs fruit route, seed collection date, plant and silique developmental stages) that could influence the seed transmission efficiency were tested to define optimal seed infection conditions. Microscopic observations revealed that the fungus penetrates siliques through cellular junctions, replum and stomata, and into seed coats either directly or through cracks. The ability of the osmosensitive fungal mutant nik1Δ3 to transmit to A. thaliana seeds was analyzed. A significant decrease in seed transmission rate was observed compared to the wild-type parental strain, confirming that a functional osmoregulation pathway is required for efficient seed transmission of the fungus. Similarly, to test the role of flavonoids in seed coat protection against pathogens, a transparent testa Arabidopsis mutant (tt4-1) not producing any flavonoid was used as host plant. Unexpectedly, tt4-1 seeds were infected to a significantly lower extent than wild-type seeds, possibly due to over-accumulation of other antimicrobial metabolites.

Conclusions

The Arabidopsis thaliana-Alternaria brassicicola pathosystem, that have been widely used to study plant-pathogen interactions during the vegetative phase, also proved to constitute a suitable model pathosystem for detailed analysis of plant-pathogen interactions during the reproductive phase. We demonstrated that it provides an excellent system for investigating the impact of different fungal or plant mutations on the seed transmission process and therefore paves the way towards future high-throughput screening of both Arabidopsis and fungal mutant.
Translating research into practice in Leeds and Bradford (TRiPLaB): a protocol for a programme of research
Authors: Hanbury Andria , Thompson Carl , Wilson Paul M , Farley Kate , Chambers Duncan , Warren Erica , Bibby John , Mannion Russell , Watt Ian S , Gilbody Simon
Published: May 2012

Background

The National Institute for Health Research (NIHR) has funded nine Collaborations for Leadership in Applied Health Research and Care (CLAHRCs). Each CLAHRC is a partnership between higher education institutions (HEIs) and the NHS in nine UK regional health economies. The CLAHRC for Leeds, York, and Bradford comprises two 'research themes' and three 'implementation themes.' One of these implementation themes is Translating Research into Practice in Leeds and Bradford (TRiPLaB). TRiPLaB aims to develop, implement, and evaluate methods for inducing and sustaining the uptake of research knowledge into practice in order to improve the quality of health services for the people of Leeds and Bradford.

Methods

TRiPLaB is built around a three-stage, sequential, approach using separate, longitudinal case studies conducted with collaborating NHS organisations, TRiPLaB will select robust innovations to implement, conduct a theory-informed exploration of the local context using a variety of data collection and analytic methods, and synthesise the information collected to identify the key factors influencing the uptake and adoption of targeted innovations. This synthesis will inform the development of tailored, multifaceted, interventions designed to increase the translation of research findings into practice. Mixed research methods, including time series analysis, quasi-experimental comparison, and qualitative process evaluation, will be used to evaluate the impact of the implementation strategies deployed.

Conclusion

TRiPLaB is a theory-informed, systematic, mixed methods approach to developing and evaluating tailored implementation strategies aimed at increasing the translation of research-based findings into practice in one UK health economy. Through active collaboration with its local NHS, TRiPLaB aims to improve the quality of health services for the people of Leeds and Bradford and to contribute to research knowledge regarding the interaction between context and adoption behaviour in health services.
Neuropsychological testing and biomarkers in the management of brain metastases
Authors: Baschnagel Andrew , Wolters Pamela L , Camphausen Kevin
Published: May 2012

Prognosis for patients with brain metastasis remains poor. Whole brain radiation therapy is the conventional treatment option; it can improve neurological symptoms, prevent and improve tumor associated neurocognitive decline, and prevents death from neurologic causes. In addition to whole brain radiation therapy, stereotactic radiosurgery, neurosurgery and chemotherapy also are used in the management of brain metastases. Radiosensitizers are now currently being investigated as potential treatment options. All of these treatment modalities carry a risk of central nervous system (CNS) toxicity that can lead to neurocognitive impairment in long term survivors. Neuropsychological testing and biomarkers are potential ways of measuring and better understanding CNS toxicity. These tools may help optimize current therapies and develop new treatments for these patients. This article will review the current management of brain metastases, summarize the data on the CNS effects associated with brain metastases and whole brain radiation therapy in these patients, discuss the use of neuropsychological tests as outcome measures in clinical trials evaluating treatments for brain metastases, and give an overview of the potential of biomarker development in brain metastases research.
Assessment of nodal target definition and dosimetry using three different techniques: implications for re-defining the optimal pelvic field in endometrial cancer
Authors: Guo Susan , Ennis Ronald D , Bhatia Stephen , Trichter Frieda , Bashist Benjamin , Shah Jinesh , Chadha Manjeet
Published: May 2012

Purposes

1. To determine the optimal pelvic nodal clinical target volume for post-operative treatment of endometrial cancer. 2. To compare the DVH of different treatment planning techniques applied to this new CTV and the surrounding tissues.

Methods and Materials

Based on the literature, we selected a methodology to delineate nodal target volume to define a NEW-CTV and NEW-PTV. Conventional 2D fields, 3D fields based on anatomic guidelines per RTOG 0418, 3D fields based on our guidelines, and IMRT based on our guidelines were assessed for coverage of NEW-CTV, NEW-PTV, and surrounding structures. CT scans of 10 patients with gynecologic malignancies after TAH/BSO were used. DVHs were compared.

Results

For NEW-PTV, mean V45Gy were 50% and 69% for 2D and RTOG 0418-3DCRT vs. 98% and 97% for NEW-3DCRT and NEW-IMRT (p < 0.0009). Mean V45Gy small bowel were 24% and 20% for 2D and RTOG 0418-3DCRT, increased to 32% with NEW-3DCRT, and decreased to 14% with IMRT (p = 0.005, 0.138, 0.002). Mean V45Gy rectum were 26%, 35%, and 52% for 2D, RTOG 0418-3DCRT, and NEW-3DCRT, and decreased to 26% with NEW-IMRT (p < 0.05). Mean V45Gy bladder were 83%, 51%, and 73% for 2D, RTOG 0418-3DCRT, and NEW-3DCRT, and decreased to 30% with NEW-IMRT (p < 0.002).

Conclusions

Conventional 2D and RTOG 0418-based 3DCRT plans cover only a fraction of our comprehensive PTV. A 3DCRT plan covers this PTV with high doses to normal tissues, whereas IMRT covers the PTV while delivering lower normal tissue doses. Re-consideration of what specifically the pelvic target encompasses is warranted.
Protein sequence and structure alignments within one framework
Authors: Schenk Gundolf , Margraf Thomas , Torda Andrew E
Published: May 2012

Background

Protein structure alignments are usually based on very different techniques to sequence alignments. We propose a method which treats sequence, structure and even combined sequence + structure in a single framework. Using a probabilistic approach, we calculate a similarity measure which can be applied to fragments containing only protein sequence, structure or both simultaneously.

Results

Proof-of-concept results are given for the different problems. For sequence alignments, the methodology is no better than conventional methods. For structure alignments, the techniques are very fast, reliable and tolerant of a range of alignment parameters. Combined sequence and structure alignments may provide a more reliable alignment for pairs of proteins where pure structural alignments can be misled by repetitive elements or apparent symmetries.

Conclusion

The probabilistic framework has an elegance in principle, merging sequence and structure descriptors into a single framework. It has a practical use in fast structural alignments and a potential use in finding those examples where sequence and structural similarities apparently disagree.
Single-stage repair of adult aortic coarctation and concomitant cardiovascular pathologies: a new alternative surgical approach
Authors: Yilmaz Mert , Polat Bulent , Saba Davit
Published: May 2012

Background

Coarctation of the aorta in the adulthood is sometimes associated with additional cardiovascular pathologies that require intervention. Ideal approach in such patients is uncertain. Anatomic left-sided short aortic bypass from the arcus aorta to descending aorta via median sternotomy allows simultaneuos repair of both complex aortic coarctation and concomitant cardiac operation.

Materials

Four adult patients were underwent Anatomic left-sided short aortic bypass operation for complex aortic coarctation through median sternotomy using deep hypothermic circulatory arrest. Concomitant cardiac operations were Bentall procedure for annuloaortic ectasia in one patient, coronary artery bypass grafting for three vessel disease in two patient, and patch closure of ventricular septal defect in one patient.

Results

All patients survived the operation and were alive with patent bypass at a mean follow-up of 36 months. No graft-related complications occurred, and there were no instances of stroke or paraplegia.

Conclusion

We conclude that single-stage repair of adult aortic coarctation with concomitant cardiovascular lesions can be performed safely using this newest technique.
Granulomatous skin lesions complicating Varicella infection in a patient with Rothmund-Thomson syndrome and immune deficiency: case report
Authors: De Somer Lien , Wouters Carine , Morren Marie-Anne , De Vos Rita , Van Den Oord Joost , Devriendt Koenraad , Meyts Isabelle
Published: May 2012

Rothmund-Thomson syndrome (RTS)(OMIM 268400) is a rare autosomal recessive genodermatosis characterized by poikiloderma, small stature, skeletal and dental abnormalities, cataract and an increased risk of cancer. It is caused by mutations in RECQL4 at 8q24. Immune deficiency is not described as a classical feature of the disease. Here we report the appearance of granulomatous skin lesions complicating primary Varicella Zoster Virus infection in a toddler with Rothmund Thomson syndrome and immune deficiency. Although granulomatous disorders are sometimes seen after Herpes zoster, they are even more rare after Varicella primary infection. Granulomas have hitherto not been described in Rothmund-Thomson syndrome. With this report we aim to stress the importance of screening for immune deficiency in patients with Rothmund-Thomson syndrome.
Heat shock protein 90 in neurodegenerative diseases
Authors: Luo Wenjie , Sun Weilin , Taldone Tony , Rodina Anna , Chiosis Gabriela
Published: May 2012

Hsp90 is a molecular chaperone with important roles in regulating pathogenic transformation. In addition to its well-characterized functions in malignancy, recent evidence from several laboratories suggests a role for Hsp90 in maintaining the functional stability of neuronal proteins of aberrant capacity, whether mutated or over-activated, allowing and sustaining the accumulation of toxic aggregates. In addition, Hsp90 regulates the activity of the transcription factor heat shock factor-1 (HSF-1), the master regulator of the heat shock response, mechanism that cells use for protection when exposed to conditions of stress. These biological functions therefore propose Hsp90 inhibition as a dual therapeutic modality in neurodegenerative diseases. First, by suppressing aberrant neuronal activity, Hsp90 inhibitors may ameliorate protein aggregation and its associated toxicity. Second, by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70, Hsp90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity. This mini-review will summarize our current knowledge on Hsp90 in neurodegeneration and will focus on the potential beneficial application of Hsp90 inhibitors in neurodegenerative diseases.
High-risk and multiple human papillomavirus (HPV) infections in cancer-free Jamaican women
Authors: Watt Angela , Garwood David , Jackson Maria , Younger Novie , Ragin Camille , Smikle Monica , Fletcher Horace , McFarlane-Anderson Norma
Published: May 2012

Background

Vaccines, that target human papillomavirus (HPV) high risk genotypes 16 and 18, have recently been developed. This study was aimed at determining genotypes commonly found in high-risk and multiple-HPV infections in Jamaican women. Two hundred and fifty three (253) women were enrolled in the study. Of these, 120 pregnant women, aged 15–44 years, were recruited from the Ante Natal Clinic at the University Hospital of the West Indies and 116 non-pregnant, aged 19–83, from a family practice in Western Jamaica. Cervical cell samples were collected from the women and HPV DNA was detected using Polymerase Chain Reaction and Reverse Line Hybridization. HPV genotypes were assessed in 236 women. Data were collected from January 2003 to October 2006.

Results

HPV DNA was detected in 87.7% (207/236) and of these 80.2% were positive for high-risk types. The most common high-risk HPV types were: HPV 45 (21.7%), HPV 58 (18.8%), HPV 16 (18.4%), HPV 35 (15.0%), HPV 18 (14.5%), HPV 52 (12.0%) and HPV 51(11.1%). Other high-risk types were present in frequencies of 1.4% – 7.2%.

Multivariate regression analyses showed that bacterial vaginosis predicted the presence of multiple infections (OR 3.51; CI, 1.26–9.82) and that alcohol use (OR 0.31; CI, 0.15–0.85) and age at first sexual encounter (12–15 years: OR 3.56; CI, 1.41–9.12; 16–19 years, OR 3.53, CI, 1.22–10.23) were significantly associated with high risk infections. Cervical cytology was normal in the majority of women despite the presence of high-risk and multiple infections.

Conclusion

HPV genotype distribution in this group of Jamaican women differs from the patterns found in Europe, North America and some parts of Asia. It may be necessary therefore to consider development of other vaccines which target genotypes found in our and similar populations. HPV genotyping as well as Pap smears should be considered.
Ethnicity and cancer in Guyana, South America
Authors: Best Plummer Wallis S , Persaud Premini , Layne Penelope J
Published: May 2012

Background

The Cancer Registry of Guyana, a population-based registry was established in 2000. Over the past eight years, data has been collected from the national referral hospital and other public and private institutions.

Methods

A comprehensive review of the Registry's database was undertaken, focusing on the ethnic and site prevalence of the three major reported cancers. The data was then subjected to summary statistics and the frequencies of cases by ethnicity and age-group were subjected to chi squared analysis. A 0.05 level of significance was applied to all tests.

Results

There was a clear ethnic distribution of the three major cancers (breast, cervical and prostate) within the database. Afro-Guyanese men accounted for over 65% of prostate cancers. Among women, Indo-Guyanese presented with the most cases of breast cancer (45%) while Afro-Guyanese had the majority of cervical cancer cases (39%). When the proportion of cervical cancer cases for all cancers in an ethnic group was analysed however, cervical cancer was significantly more common (p < 0.0001) among Indigenous Amerindian women. Similarly, by age-group analysis, there were significantly more cases of cervical than breast cancer (p = 0.014) among women under 30 years of age.

Conclusion

The Cancer Registry of Guyana reflects a high incidence of prostate, cervical and breast cancers among Afro-Guyanese. Socio-economic, dietary and genetic influences on the observed pattern of incidence within this ethnic sub-group, as well as those of Indo-Guyanese and Indigenous Amerindians warrant further investigation.
Thermoanaerobacterium thermosaccharolyticum β-glucosidase: a glucose-tolerant enzyme with high specific activity for cellobiose
Authors: Pei Jianjun , Pang Qian , Zhao Linguo , Fan Song , Shi Hao
Published: May 2012

Background

β-Glucosidase is an important component of the cellulase enzyme system. It does not only participate in cellulose degradation, it also plays an important role in hydrolyzing cellulose to fermentable glucose by relieving the inhibition of exoglucanase and endoglucanase from cellobiose. Therefore, the glucose-tolerant β-glucosidase with high specific activity for cellobiose might be a potent candidate for industrial applications.

Results

The β-glucosidase genebglthat encodes a 443-amino-acid protein was cloned and over-expressed fromThermoanaerobacterium thermosaccharolyticumDSM 571 inEscherichia coli. The phylogenetic trees of β-glucosidases were constructed using Neighbor-Joining (NJ) and Maximum-Parsimony (MP) methods. The phylogeny and amino acid analysis indicated that the BGL was a novel β-glucosidase. By replacing the rare codons for the N-terminal amino acids of the target protein, the expression level ofbglwas increased from 6.6 to 11.2 U/mg in LB medium. Recombinant BGL was purified by heat treatment followed by Ni-NTA affinity. The optimal activity was at pH 6.4 and 70°C. The purified enzyme was stable over pH range of 5.2–7.6 and had a 1 h half life at 68°C. The activity of BGL was significantly enhanced by Fe2+and Mn2+. TheVmaxof 64 U/mg and 120 U/mg were found for p-nitrophenyl-β-D-glucopyranoside (Kmvalue of 0.62 mM) and cellobiose (Kmvalue of 7.9 mM), respectively. It displayed high tolerance to glucose and cellobiose. TheKcatfor cellobiose was 67.7 s-1at 60°C and pH 6.4, when the concentration of cellobiose was 290 mM. It was activated by glucose at concentrations lower that 200 mM. With glucose further increasing, the enzyme activity of BGL was gradually inhibited, but remained 50% of the original value in even as high as 600 mM glucose.

Conclusions

The article provides a useful novel β-glucosidase which displayed favorable properties: high glucose and cellobiose tolerance, independence of metal ions, and high hydrolysis activity on cellobiose.
A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation
Authors: Berendsen Tim A , Bruinsma Bote G , Lee Jungwoo , D’Andrea Vincent , Liu Qiang , Izamis Maria-Louisa , Uygun Korkut , Yarmush Martin L
Published: May 2012

Background

Liver donor shortages stimulate the development of strategies that incorporate damaged organs into the donor pool. Herein we present a simplified machine perfusion system without the need for oxygen carriers or temperature control, which we validated in a model of orthotopic liver transplantation.

Methods

Rat livers were procured and subnormothermically perfused with supplemented Williams E medium for 3 hours, then transplanted into healthy recipients (Fresh-SNMP group). Outcome was compared with static cold stored organs (UW-Control group). In addition, a rat liver model of donation after cardiac death was adapted using a 60-minute warm ischemic period, after which the grafts were either transplanted directly (WI group) or subnormothermically perfused and transplanted (WI-SNMP group).

Results

One-month survival was 100% in the Fresh-SNMP and UW-Control groups, 83.3% in the WI-SNMP group and 0% in the WI group. Clinical parameters, postoperative blood work and histology did not differ significantly between survivors.

Conclusion

This work demonstrates for the first time in an orthotopic transplantation model that ischemically damaged livers can be regenerated effectively using practical subnormothermic machine perfusion without oxygen carriers.
miRNA-dysregulation associated with tenderness variation induced by acute stress in Angus cattle
Authors: Zhao Chunping , Tian Fei , Yu Ying , Liu George , Zan Linsen , Updike M Scott , Song Jiuzhou
Published: May 2012

miRNAs are a class of small, single-stranded, non-coding RNAs that perform post-transcriptional repression of target genes by binding to 3’ untranslated regions. Research has found that miRNAs involved in the regulation of many metabolic processes. Here we uncovered that the beef quality of Angus cattle sharply diversified after acute stress. By performing miRNA microarray analysis, 13 miRNAs were significantly differentially expressed in stressed group compared to control group. Using a bioinformatics method, 135 protein-coding genes were predicted as the targets of significant differentially expressed miRNAs. Gene Ontology (GO) term and Ingenuity Pathway Analysis (IPA) mined that these target genes involved in some important pathways, which may have impact on meat quality and beef tenderness.
Tissue expression and developmental regulation of chicken cathelicidin antimicrobial peptides
Authors: Achanta Mallika , Sunkara Lakshmi T , Dai Gan , Bommineni Yugendar R , Jiang Weiyu , Zhang Guolong
Published: May 2012

Cathelicidins are a major family of antimicrobial peptides present in vertebrate animals with potent microbicidal and immunomodulatory activities. Four cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1, have been identified in chickens. As a first step to understand their role in early innate host defense of chickens, we examined the tissue and developmental expression patterns of all four cathelicidins. Real-time PCR revealed an abundant expression of four cathelicidins throughout the gastrointestinal, respiratory, and urogenital tracts as well as in all primary and secondary immune organs of chickens. Fowlicidins 1 to 3 exhibited a similar tissue expression pattern with the highest expression in the bone marrow and lung, while cathelicidin B1 was synthesized most abundantly in the bursa of Fabricius. Additionally, a tissue-specific regulatory pattern was evident for all four cathelicidins during the first 28 days after hatching. The expression of fowlicidins 1 to 3 showed an age-dependent increase both in the cecal tonsil and lung, whereas all four cathelicidins were peaked in the bursa on day 4 after hatching, with a gradual decline by day 28. An abrupt augmentation in the expression of fowlicidins 1 to 3 was also observed in the cecum on day 28, while the highest expression of cathelicidin B1 was seen in both the lung and cecal tonsil on day 14. Collectively, the presence of cathelicidins in a broad range of tissues and their largely enhanced expression during development are suggestive of their potential important role in early host defense and disease resistance of chickens.
Size-controlled green synthesis of silver nanoparticles mediated by gum ghatti (Anogeissus latifolia) and its biological activity
Authors: Kora Aruna Jyothi , Beedu Sashidhar Rao , Jayaraman Arunachalam
Published: May 2012

Background

Gum ghatti is a proteinaceous edible, exudate tree gum of India and is also used in traditional medicine. A facile and ecofriendly green method has been developed for the synthesis of silver nanoparticles from silver nitrate using gum ghatti (Anogeissus latifolia) as a reducing and stabilizing agent. The influence of concentration of gum and reaction time on the synthesis of nanoparticles was studied. UV–visible spectroscopy, transmission electron microscopy and X-ray diffraction analytical techniques were used to characterize the synthesized nanoparticles.

Results

By optimizing the reaction conditions, we could achieve nearly monodispersed and size controlled spherical nanoparticles of around 5.7 ± 0.2 nm. A possible mechanism involved in the reduction and stabilization of nanoparticles has been investigated using Fourier transform infrared spectroscopy and Raman spectroscopy.

Conclusions

The synthesized silver nanoparticles had significant antibacterial action on both the Gram classes of bacteria. As the silver nanoparticles are encapsulated with functional group rich gum, they can be easily integrated for various biological applications.
Phosphatidylinositol 3-kinases and their roles in phagosome maturation
Authors: Thi Emily P , Reiner Neil E
Published: May 2012

Review on how PI3Ks regulate phagosome maturation downstream of different phagocytic receptors, and their involvement in Rab activation and Ca2+ signaling.

Phagosome maturation is a highly organized and sequential process that results in the formation of a microbicidal phagolysosome. This results in crucial contributions to innate and adaptive immunity through pathogen clearance and antigen presentation. Thus, it is important to understand the regulatory networks that control the extent and nature of phagosome maturation. PI3Ks are lipid kinases that catalyze the phosphorylation of the 3′ position of the inositol ring. This enzyme family is divided into three classes based on structure and substrate preferences. Previously, only the class III PI3K, hVps34, was thought to contribute to phagosome maturation. Recent evidence, however, suggests important contributions by class I PI3Ks in bringing about the diverse phagosome maturation phenotypes. Class I PI3Ks have also been implicated in the activation of Rab GTPases that function in maturation, such as Rab14. In addition, recent studies have illuminated the overlap between phagosome maturation and autophagy, which itself is regulated by multiple classes of PI3K. Taken together, a picture of phagosome maturation is emerging in which multiple classes of PI3Ks are involved in modulating maturation phenotypes. This review summarizes the known contributions of PI3Ks to phagosome maturation. Special emphasis is placed on the impact of PI3Ks on different maturation outcomes stemming from the engagement of diverse phagocytic receptors and on Rab and Ca2+ signaling cascades.
Effects of Liraglutide on β-Cell-Specific Glucokinase-Deficient Neonatal Mice
Authors: Shirakawa Jun , Tanami Ritsuko , Togashi Yu , Tajima Kazuki , Orime Kazuki , Kubota Naoto , Kadowaki Takashi , Goshima Yoshio , Terauchi Yasuo
Published: May 2012

The glucagon-like peptide-1 receptor agonist liraglutide is used to treat diabetes. A hallmark of liraglutide is the glucose-dependent facilitation of insulin secretion from pancreatic β-cells. In β-cells, the glycolytic enzyme glucokinase plays a pivotal role as a glucose sensor. However, the role of glucokinase in the glucose-dependent action of liraglutide remains unknown. We first examined the effects of liraglutide on glucokinase haploinsufficient (Gck+/−) mice. Single administration of liraglutide significantly improved glucose tolerance in Gck+/− mice without increase of insulin secretion. We also assessed the effects of liraglutide on the survival rates, metabolic parameters, and histology of liver or pancreas of β-cell-specific glucokinase-deficient (Gck−/−) newborn mice. Liraglutide reduced the blood glucose levels in Gck−/− neonates but failed to prolong survival, and all the mice died within 1 wk. Furthermore, liraglutide did not improve glucose-induced insulin secretion in isolated islets from Gck−/− neonates. Liraglutide initially prevented increases in alanine aminotransferase, free fatty acids, and triglycerides in Gck−/− neonates but not at 4 d after birth. Liraglutide transiently prevented liver steatosis, with reduced triglyceride contents and elevated glycogen contents in Gck−/− neonate livers at 2 d after birth. Liraglutide also protected against reductions in β-cells in Gck−/− neonates at 4 d after birth. Taken together, β-cell glucokinase appears to be essential for liraglutide-mediated insulin secretion, but liraglutide may improve glycemic control, steatosis, and β-cell death in a glucokinase-independent fashion.
Molecular Cloning and Pharmacological Characterization of Two Novel GnRH Receptors in the Lamprey (Petromyzon marinus)
Authors: Joseph Nerine T. , Aquilina-Beck Allisan , MacDonald Caryn , Decatur Wayne A. , Hall Jeffrey A. , Kavanaugh Scott I. , Sower Stacia A.
Published: May 2012

This paper reports the identification, expression, binding kinetics, and functional studies of two novel type III lamprey GnRH receptors (lGnRH-R-2 and lGnRH-R-3) in the sea lamprey, a basal vertebrate. These novel GnRH receptors share the structural features and amino acid motifs common to other known gnathostome GnRH receptors. The ligand specificity and activation of intracellular signaling studies showed ligands lGnRH-II and -III induced an inositol phosphate (IP) response at lGnRH-R-2 and lGnRH-R-3, whereas the ligand lGnRH-I did not stimulate an IP response. lGnRH-II was a more potent activator of lGnRH-R-3 than lGnRH-III. Stimulation of lGnRH-R-2 and lGnRH-R-3 testing all three lGnRH ligands did not elicit a cAMP response. lGnRH-R-2 has a higher binding affinity in response to lGnRH-III than lGnRH-II, whereas lGnRH-R-3 has a higher binding affinity in response to lGnRH-II than IGnRH-III. lGnRH-R-2 precursor transcript was detected in a wide variety of tissues including the pituitary whereas lGnRH-R-3 precursor transcript was not as widely expressed and primarily expressed in the brain and eye of male and female lampreys. From our phylogenetic analysis, we propose that lGnRH-R-1 evolved from a common ancestor of all vertebrate GnRH receptors and lGnRH-R-2 and lGnRH-R-3 likely occurred due to a gene duplication within the lamprey lineage. In summary, we propose from our findings of receptor subtypes in the sea lamprey that the evolutionary recruitment of specific pituitary GnRH receptor subtypes for particular physiological functions seen in later evolved vertebrates was an ancestral character that first arose in a basal vertebrate.
The Trifunctional Protein Mediates Thyroid Hormone Receptor-Dependent Stimulation of Mitochondria Metabolism
Authors: Chocron E. Sandra , Sayre Naomi L. , Holstein Deborah , Saelim Nuttawut , Ibdah Jamal A. , Dong Lily Q. , Zhu Xuguang , Cheng Sheue-Yann , Lechleiter James D.
Published: May 2012

We previously demonstrated that the thyroid hormone, T3, acutely stimulates mitochondrial metabolism in a thyroid hormone receptor (TR)-dependent manner. T3 has also recently been shown to stimulate mitochondrial fatty acid oxidation (FAO). Here we report that TR-dependent stimulation of metabolism is mediated by the mitochondrial trifunctional protein (MTP), the enzyme responsible for long-chain FAO. Stimulation of FAO was significant in cells that expressed a nonnuclear amino terminus shortened TR isoform (sTR43) but not in adult fibroblasts cultured from mice deficient in both TRα and TRβ isoforms (TRα−/−β−/−). Mouse embryonic fibroblasts deficient in MTP (MTP−/−) did not support T3-stimulated FAO. Inhibition of fatty-acid trafficking into mitochondria using the AMP-activated protein kinase inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine (compound C) or the carnitine palmitoyltransferase 1 inhibitor etomoxir prevented T3-stimulated FAO. However, T3 treatment could increase FAO when AMP-activated protein kinase was maximally activated, indicating an alternate mechanism of T3-stimulated FAO exists, even when trafficking is presumably high. MTPα protein levels and higher molecular weight complexes of MTP subunits were increased by T3 treatment. We suggest that T3-induced increases in mitochondrial metabolism are at least in part mediated by a T3-shortened TR isoform-dependent stabilization of the MTP complex, which appears to lower MTP subunit turnover.