bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenetic relationship of dengue virus type 3 isolated in Brazil and Paraguay and global evolutionary divergence dynamics
Authors: Alfonso Helda Liz , Amarilla Alberto Anastacio , Gonçalves Paula Fernanda , Barros Matheus Takatuba , de Almeida Flavia Tremeschin , Silva Telma R , da Silva Eliana V , Nunes Marcio T , Vasconcelos Pedro F C , Vieira Deusilene S , Batista Weber Cheli , Bobadilla Maria Liz , Vazquez Cynthia , Moran Mirian , Figueiredo Luiz Tadeu Moraes , Aquino Victor Hugo
Published: June 2012

Background

Dengue is the most important mosquito-borne viral disease worldwide. Dengue virus comprises four antigenically related viruses named dengue virus type 1 to 4 (DENV1-4). DENV-3 was re-introduced into the Americas in 1994 causing outbreaks in Nicaragua and Panama. DENV-3 was introduced in Brazil in 2000 and then spread to most of the Brazilian States, reaching the neighboring country, Paraguay in 2002. In this study, we have analyzed the phylogenetic relationship of DENV-3 isolated in Brazil and Paraguay with viruses isolated worldwide. We have also analyzed the evolutionary divergence dynamics of DENV-3 viruses.

Results

The entire open reading frame (ORF) of thirteen DENV-3 isolated in Brazil (n = 9) and Paraguay (n = 4) were sequenced for phylogenetic analysis. DENV-3 grouped into three main genotypes (I, II and III). Several internal clades were found within each genotype that we called lineage and sub-lineage. Viruses included in this study belong to genotype III and grouped together with viruses isolated in the Americas within the lineage III. The Brazilian viruses were further segregated into two different sub-lineage, A and B, and the Paraguayan into the sub-lineage B. All three genotypes showed internal grouping. The nucleotide divergence was in average 6.7% for genotypes, 2.7% for lineages and 1.5% for sub-lineages. Phylogenetic trees constructed with any of the protein gene sequences showed the same segregation of the DENV-3 in three genotypes.

Conclusion

Our results showed that two groups of DENV-3 genotypes III circulated in Brazil during 2002–2009, suggesting different events of introduction of the virus through different regions of the country. In Paraguay, only one group DENV-3 genotype III is circulating that is very closely related to the Brazilian viruses of sub-lineage B. Different degree of grouping can be observed for DENV-3 and each group showed a characteristic evolutionary divergence. Finally, we have observed that any protein gene sequence can be used to identify the virus genotype.
Activation of Extracellular Signal-Regulated Protein Kinase 5 is Essential for Cystitis- and Nerve Growth Factor-Induced Calcitonin Gene-Related Peptide Expression in Sensory Neurons
Authors: Yu Sharon J , Xia Chun-Mei , Kay Jarren C , Qiao Li-Ya
Published: June 2012

Background:

Cystitis causes considerable neuronal plasticity in the primary afferent pathways. The molecular mechanism and signal transduction underlying cross talk between the inflamed urinary bladder and sensory sensitization has not been investigated.

Results:

In a rat cystitis model induced by cyclophosphamide (CYP) for 48 h, the mRNA and protein levels of the excitatory neurotransmitter calcitonin gene-related peptide (CGRP) are increased in the L6 dorsal root ganglia (DRG) in response to bladder inflammation. Cystitis-induced CGRP expression in L6 DRG is triggered by endogenous nerve growth factor (NGF) because neutralization of NGF with a specific NGF antibody reverses CGRP up-regulation during cystitis. CGRP expression in the L6 DRG neurons is also enhanced by retrograde NGF signaling when NGF is applied to the nerve terminals of the ganglion-nerve two-compartmented preparation. Characterization of the signaling pathways in cystitis- or NGF-induced CGRP expression reveals that the activation (phosphorylation) of extracellular signal-regulated protein kinase (ERK)5 but not Akt is involved. In L6 DRG during cystitis, CGRP is co-localized with phospho-ERK5 but not phospho-Akt. NGF-evoked CGRP up-regulation is also blocked by inhibition of the MEK/ERK pathway with specific MEK inhibitors U0126 and PD98059, but not by inhibition of the PI3K/Akt pathway with inhibitor LY294002. Further examination shows that cystitis-induced cAMP-responsive element binding protein (CREB) activity is expressed in CGRP bladder afferent neurons and is co-localized with phospho-ERK5 but not phospho-Akt. Blockade of NGF action in vivo reduces the number of DRG neurons co-expressing CGRP and phospho-CREB, and reverses cystitis-induced increases in micturition frequency.

Conclusions:

A specific pathway involving NGF-ERK5-CREB axis plays an essential role in cystitis-induced sensory activation.
Efficacy of vision restoration therapy after optic neuritis (VISION study): study protocol for a randomized controlled trial
Authors: Schinzel Johann , Schwarzlose Lina , Dietze Holger , Bartusch Karolina , Weiss Susanne , Ohlraun Stephanie , Paul Friedemann , Dörr Jan
Published: June 2012

Background

Optic neuritis is a frequent manifestation of multiple sclerosis. Visual deficits range from a minor impairment of visual functions through to complete loss of vision. Although many patients recover almost completely, roughly 35% of patients remain visually impaired for years, and therapeutic options for those patients hardly exist. Vision restoration therapy is a software-based visual training program that has been shown to improve visual deficits after pre- and postchiasmatic injury. The aim of this pilot study is to evaluate whether residual visual deficits after past or recent optic neuritis can be reduced by means of vision restoration therapy.

Methods/design

A randomized, controlled, patient- and observer-blinded clinical pilot study (VISION study) was designed to evaluate the efficacy of vision restoration therapy in optic neuritis patients. Eighty patients with a residual visual deficit after optic neuritis (visual acuity ≤0.7 and/or scotoma) will be stratified according to the time of optic neuritis onset (manifestation more than 12 months ago (40 patients, fixed deficit) versus manifestation 2 to 6 months ago (40 patients, recent optic neuritis)), and randomized into vision restoration therapy arm or saccadic training arm (control intervention). Patients will be instructed to complete a computer-based visual training for approximately 30 minutes each day for a period of 6 months. Patients and evaluators remain blinded to the treatment allocation throughout the study. All endpoints will be analyzed andP-values < 0.05 will be considered statistically significant. The primary outcome parameter will be the expansion of the visual field after 3 and 6 months of treatment as determined by static visual field perimetry and high resolution perimetry. Secondary outcome variables will include visual acuity at both low and high contrast, glare contrast sensitivity, visually evoked potentials, optical coherence tomography and other functional tests of the visual system, alertness, health-related quality of life, fatigue, and depression.

Discussion

If vision restoration therapy is shown to improve visual function after optic neuritis, this method might be a first therapeutic option for patients with incomplete recovery from optic neuritis.

Trial registration

NCT01274702
Pigmented paraganglioma of the kidney: a case report
Authors: Zhao Ling , Luo Jie , Zhang Honglei , Da Jiping
Published: June 2012

Paragangliomas are rare neoplasms arising from undifferentiated cells of the primitive neural crest. We report a case of a 57-year-old patient with renal pigmented paraganglioma that was an incidental finding. Histopathological examination showed typical morphology of paraganglioma, as well as the unusual feature of large amounts of pigment in the cytoplasm of the tumor cells which was confirmed by bleached Fontana-Masson. Electron microscopy showed abundant, pleomorphic electron-dense granules consistent with neuromelanin. The tumor cells were positive for CD56 and chromogranin A, negative for HMB-45. The unique morphologic appearance represents divergent differentiation from neural crest. To our knowledge, the present case represents the first example of pigmented paraganglioma of the kidney.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2017147293711495.
Use of ex vitro composite plants to study the interaction of cowpea (Vigna unguiculata L.) with the root parasitic angiosperm Striga gesnerioides
Authors: Mellor Karolina E , Hoffman Ava M , Timko Michael P
Published: June 2012

Background

Cowpea (Vigna unguiculata L.) is an important grain and forage legume grown throughout sub-Saharan Africa primarily by subsistence farmers on poor, drought prone soils. Genetic improvement of the crop is being actively pursued and numerous functional genomics studies are underway aimed at characterizing gene controlling key agronomic characteristics for disease and pest resistances. Unfortunately, similar to other legumes, efficient plant transformation technology is a rate-limiting step in analysis of gene function in cowpea.

Results

Here we describe an optimized protocol for the rapid generation of transformed hairy roots on ex vitro composite plants of cowpea using Agrobacterium rhizogenes. We further demonstrate the applicability of cowpea composite plants to study gene expression involved in the resistance response of the plant roots to attack by the root parasitic weed, Striga gesnerioides. The utility of the new system and critical parameters of the method are described and discussed herein.

Conclusions

Cowpea composite plants offer a rapid alternative to methods requiring stable transformation and whole plant regeneration for studying gene expression in resistance or susceptibility responses to parasitic weeds. Their use can likely be readily adapted to look at the effects of both ectopic gene overexpression as well as gene knockdown of root associated defense responses and to the study of a broader range of root associated physiological and aphysiological processes including root growth and differentiation as well as interactions with other root pests, parasites, and symbionts.
Vaccination prepartum enhances the beneficial effects of melatonin on the immune response and reduces platelet responsiveness in sheep
Authors: Regodón Sergio , Ramos Asunción , Míguez María P , Carrillo-Vico Antonio , Rosado Juan A , Jardín Isaac
Published: June 2012

Background

Melatonin regulates several physiological processes and its powerful action as antioxidant has been widely reported. Melatonin acts modulating the immune system, showing a protective effect on the cardiovascular system and improving vaccine administration as an adjuvant-like agent. Here, we have investigated the role of melatonin as an adjuvant of the Clostridium perfringens vaccine in prepartum sheep and whether melatonin modulates platelet physiology during peripartum.

Results

The experiments were carried out in peripartum sheep from a farm located in an area of Mediterranean-type ecosystem. Plasma melatonin levels were determined by ELISA and sheep platelet aggregation was monitored using an aggregometer. Here we demonstrated for the first time that plasma melatonin concentration were higher in pregnant (125 pg/mL) than in non-pregnant sheep (15 pg/mL; P < 0.05). Administration of melatonin prepartum did not significantly modify platelet function but significantly improved the immune response to vaccination against C. perfringens.

Conclusion

Administration of melatonin as an adjuvant provides a significant improvement in the immune response to vaccine administration prepartum against C. perfringens.
Cervical disc herniation presenting with neck pain and contralateral symptoms: a case report
Authors: Yeung Jacky T. , Johnson John I. , Karim Aftab S.
Published: June 2012

Introduction

Cervical disc herniation often results in neck and arm pain in patients as a result of direct impingement of nerve roots and associated inflammatory processes. The clinical presentation usually corresponds with the side of herniation and ipsilateral symptoms predominate the clinical picture.

Case presentation

A 35-year-old Caucasian man presented to our facility with neck pain and left-sided upper and lower extremity pain. A magnetic resonance imaging scan revealed a right paramedian herniated disc at the C5 to C6 level. All other cervical levels were normal without central canal stenosis or neural foraminal stenosis. Results from magnetic reasonance imaging scans of the brain and lumbar spine were negative. An anterior cervical discectomy was performed at the C5 to C6 level, and an inter-body graft and plate were placed. Our patient had complete resolution of his neck and left arm pain.

Conclusions

Anterior discectomy and fusion of the cervical spine resulted in complete resolution of our patient’s neck and left arm symptoms and improvement of his contralateral left leg pain. Cervical disc herniation may present with contralateral symptoms that are different from the current perception of this disease.
Multiple ring-enhancing cerebral lesions in systemic lupus erythematosis: a case report
Authors: Chang Thashi , Rodrigo Chaturaka , Ranawaka Nuwan , Atukorala Inoshi
Published: June 2012

Introduction

Infectious disease in an immunosuppressed patient is a diagnostic challenge. The clinical presentation and the body’s immune response may be quite different from those seen in an immunocompetent patient with the same infection. It is also a race against time to diagnose, as many of these infections can be fatal without timely intervention.

Case presentation

We present the case of a 39-year-old Sri Lankan woman who was on immunosuppressive treatment for systemic lupus erythematosis and who presented with multiple ring-enhancing lesions of the brain. The most likely diagnosis, given the clinical picture, available investigation results, and characteristics of magnetic resonance imaging, was central nervous system tuberculosis. Owing to the small size of the lesions, a tissue biopsy could not be performed. Our patient responded well to a trial of anti-tuberculosis therapy, and there was clinical and radiological evidence of recovery. A paradoxical reaction with the initiation of anti-tuberculosis therapy was observed and this had to be countered with a prolonged course of steroids.

Conclusions

Our experience and previous evidence from case reports suggest that high-dose steroids for a prolonged period (up to eight weeks) should be administered to counter the initial deterioration after starting anti-tuberculous chemotherapy for central nervous system tuberculomas.
Introducing a single secondary alcohol dehydrogenase into butanol-tolerant Clostridium acetobutylicum Rh8 switches ABE fermentation to high level IBE fermentation
Authors: Dai Zongjie , Dong Hongjun , Zhu Yan , Zhang Yanping , Li Yin , Ma Yanhe
Published: June 2012

Background

Previously we have developed a butanol tolerant mutant of Clostridium acetobutylicum Rh8, from the wild type strain DSM 1731. Strain Rh8 can tolerate up to 19 g/L butanol, with solvent titer improved accordingly, thus exhibiting industrial application potential. To test if strain Rh8 can be used for production of high level mixed alcohols, a single secondary alcohol dehydrogenase from Clostridium beijerinckii NRRL B593 was overexpressed in strain Rh8 under the control of thl promoter.

Results

The heterogenous gene sADH was functionally expressed in C. acetobutylicum Rh8. This simple, one-step engineering approach switched the traditional ABE (acetone-butanol-ethanol) fermentation to IBE (isopropanol-butanol-ethanol) fermentation. The total alcohol titer reached 23.88 g/l (7.6 g/l isopropanol, 15 g/l butanol, and 1.28 g/l ethanol) with a yield to glucose of 31.42%. The acid (butyrate and acetate) assimilation rate in isopropanol producing strain Rh8(psADH) was increased.

Conclusions

The improved butanol tolerance and the enhanced solvent biosynthesis machinery in strain Rh8 is beneficial for production of high concentration of mixed alcohols. Strain Rh8 can thus be considered as a good host for further engineering of solvent/alcohol production.
Metabolic syndrome and inflammatory biomarkers: a community-based cross-sectional study at the Framingham Heart Study
Authors: Dallmeier Dhayana , Larson Martin G , Vasan Ramachandran S , Keaney John F , Fontes Joao D , Meigs James B , Fox Caroline S , Benjamin Emelia J
Published: June 2012

Background

Prior studies reported conflicting findings on the association between metabolic syndrome and inflammatory biomarkers. We tested the cross-sectional associations between metabolic syndrome and nine inflammatory markers.

Methods

We measured C-reactive protein, CD40 ligand, interleukin-6, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, osteoprotegerin, P-selectin, tumor necrosis factor-alpha, and tumor necrosis factor receptor-2 in 2570 Framingham Offspring Study participants free of diabetes and cardiovascular disease at examination 7. Metabolic syndrome was defined by National Cholesterol Education Program criteria. We performed multivariable linear regressions for each biomarker with metabolic syndrome as the exposure adjusting for age, sex, smoking, aspirin use, and hormone replacement. We subsequently added to the models components of the metabolic syndrome as continuous traits plus lipid lowering and hypertension treatments. We considered P < 0.05 as statistically significant.

Results

Metabolic syndrome was present in 984 (38%) participants and was statistically significantly associated with each biomarker (all P < 0.02) except osteoprotegerin. After adjusting for its component variables, the metabolic syndrome was associated only with P-selectin (1.06 fold higher in metabolic syndrome, 95% CI 1.02, 1.10, p = 0.005).

Conclusions

Metabolic syndrome was associated with multiple inflammatory biomarkers. However, adjusting for each of its components eliminated the association with most inflammatory markers, except P-selectin. Our results suggest that the relation between metabolic syndrome and inflammation is largely accounted for by its components.
Efficacy of cognitive enhancers for Alzheimer’s disease: protocol for a systematic review and network meta-analysis
Authors: Tricco Andrea C , vanderVaart Sondra , Soobiah Charlene , Lillie Erin , Perrier Laure , Chen Maggie H , Hemmelgarn Brenda , Majumdar Sumit R , Straus Sharon E
Published: June 2012

Background

Approximately 35 million people world-wide have Alzheimer’s disease and this is projected to nearly double by 2030. Cognitive enhancers, including cholinesterase inhibitors (for example, donepezil, galantamine and rivastigmine) and memantine (N-methyl-D-aspartic acid (NMDA) receptor antagonist) have been approved for the treatment of Alzheimer’s disease in many countries. Our objective is to evaluate the comparative effectiveness, safety, and cost of cognitive enhancers for Alzheimer’s disease through a systematic review.

Methods/design

Studies examining the efficacy, safety, and cost of cognitive enhancers compared to placebo, supportive care, and other cognitive enhancers for Alzheimer’s patients will be included. The primary outcome is cognition and secondary outcomes include function, behavior, quality of life, safety, and cost. Experimental studies (randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials), quasi-experimental studies (controlled before-after, interrupted time series), and observational studies (cohort, case–control studies) will be eligible for inclusion. Inclusion will not be limited by publication status, time period or language of dissemination.

We will search electronic databases (for example, MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Ageline) from inception onwards. The electronic database search will be supplemented by searching for grey literature (for example, conference proceedings, searches in Google and relevant organization websites). Two reviewers will independently screen the studies for inclusion using the eligibility criteria established a priori and independently extract data. Risk of bias will be assessed using the Cochrane Risk of Bias tool for experimental and quasi-experimental studies and the Newcastle Ottawa Scale for observational studies. If deemed appropriate, meta-analysis and network (that is, indirect comparisons) meta-analysis will be conducted.

Discussion

Our systematic review will inform the decision of healthcare providers, policy-makers, Alzheimer’s patients and family members about the use of cognitive enhancers, by improving their understanding of the costs, benefits and harms that are associated with these agents.

PROSPERO registry number

CRD42012001948
The role of positron emission tomography/CT imaging in head and neck cancer patients after radical chemoradiotherapy
Authors: Sherriff J M , Ogunremi B , Colley S , Sanghera P , Hartley A
Published: June 2012

Objectives

Positron emission tomography with CT (PET/CT) scanning is increasingly being used in head and neck cancer to assess response after radical concomitant chemoradiotherapy. The purpose of this study was to assess the use of PET/CT following chemoradiotherapy at our institution.

Methods

All patients receiving radical chemoradiotherapy for head and neck cancer over a 9-year period were retrospectively identified. Outcome data including local control and overall survival were collected for all patients. The negative predictive value of PET/CT for local recurrence was calculated. Of those with a reported positive PET/CT scan the maximum standardised uptake values were compared with the incidence of local recurrence.

Results

92 patients were identified having a post-treatment PET/CT from a total of 301 patients receiving radical concomitant chemoradiotherapy. Median time from completion of chemoradiotherapy to PET/CT scan was 3 (range 2–8) months. Median follow-up in surviving patients was 19 and 25 months in the PET/CT and non-PET/CT groups, respectively. The negative predictive value for local recurrence was 91.8%. The median maximum standardised uptake values were 10.2 (range 3.1–33) and 6.89 (range 3.1–30) in those with local recurrence and with no local recurrence, respectively.

Conclusions

Post-chemoradiotherapy PET/CT may aid subsequent management decisions. Patients with a negative PET/CT scan after radical chemoradiotherapy have a 91.8% chance of remaining free of local recurrence 19 months post-treatment. A higher maximum standardised uptake value on the post-chemoradiotherapy PET/CT may predict subsequent local recurrence and warrants further investigation.

Advances in knowledge

Post-chemoradiotherapy PET/CT imaging aids subsequent management decisions.
Disease-linked microRNA-21 exhibits drastically reduced mRNA binding and silencing activity in healthy mouse liver
Authors: Androsavich John R. , Chau B. Nelson , Bhat Balkrishen , Linsley Peter S. , Walter Nils G.
Published: June 2012

MicroRNAs (miRNAs) bind to mRNAs and fine-tune protein output by affecting mRNA stability and/or translation. miR-21 is a ubiquitous, highly abundant, and stress-responsive miRNA linked to several diseases, including cancer, fibrosis, and inflammation. Although the RNA silencing activity of miR-21 in diseased cells has been well documented, the roles of miR-21 under healthy cellular conditions are not well understood. Here, we show that pharmacological inhibition or genetic deletion of miR-21 in healthy mouse liver has little impact on regulation of canonical seed-matched mRNAs and only a limited number of genes enriched in stress response pathways. These surprisingly weak and selective regulatory effects on known and predicted target mRNAs contrast with those of other abundant liver miRNAs such as miR-122 and let-7. Moreover, miR-21 shows greatly reduced binding to polysome-associated target mRNAs compared to miR-122 and let-7. Bioinformatic analysis suggests that reduced thermodynamic stability of seed pairing and target binding may contribute to this deficiency of miR-21. Significantly, these trends are reversed in human cervical carcinoma (HeLa) cells, where miRNAs including miR-21 show enhanced target binding within polysomes and where miR-21 triggers strong degradative activity toward target mRNAs. Taken together, our results suggest that, under normal cellular conditions in liver, miR-21 activity is maintained below a threshold required for binding and silencing most of its targets. Consequently, enhanced association with polysome-associated mRNA is likely to explain in part the gain of miR-21 function often found in diseased or stressed cells.
Nanofluidic Digital PCR for KRAS Mutation Detection and Quantification in Gastrointestinal Cancer
Authors: Azuara Daniel , Ginesta Mireia M , Gausachs Mireia , Rodriguez-Moranta Francisco , Fabregat Joan , Busquets Juli , Pelaez Nuria , Boadas Jaume , Galter Sara , Moreno Victor , Costa Jose , de Oca Javier , Capellá Gabriel
Published: June 2012

BACKGROUND

Concomitant quantification of multiple mutant KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) alleles may provide information in addition to that provided by standard mutation-detection procedures. We assessed the feasibility of a nanofluidic digital PCR array platform to detect and quantify KRAS mutations simultaneously in clinically relevant samples.

METHODS

We assessed 2 groups of patients (colorectal and pancreatic disease): Group 1 consisted of 27 patients with colorectal carcinomas, 14 patients with adenomas, and 5 control individuals; group 2 consisted of 42 patients with pancreatic carcinoma, 4 with adenocarcinomas of the ampulla, and 6 with chronic pancreatitis). Digital PCR was performed with the Digital Array Chip (Fluidigm).

RESULTS

Nanofluidic digital PCR detected mutant alleles at 0.05% to 0.1%, depending on the variant analyzed. For the colorectal disease group, conventional PCR detected 9 (64%) of 14 adenomas that were positive for KRAS mutants, whereas digital PCR increased this number to 11 (79%) of 14. Sixteen (59%) of 27 carcinomas showed KRAS mutation with conventional PCR. Two additional cases were detected with digital PCR. In 5 cases (3 adenomas, 2 carcinomas), the total number of mutant alleles changed. For the pancreatic disease group, digital PCR increased the number of positive cases from 26 to 34 (81%) and identified ≥2 mutant alleles in 25 cases, compared with conventional PCR, which identified multiple KRAS mutant alleles in only 12 cases. A good correlation was observed between results obtained with tumor biopsies and those obtained with pancreatic juice.

CONCLUSIONS

Digital PCR provides a robust, quantitative measure of the proportion of KRAS mutant alleles in routinely obtained samples. It also allows a better classification of tumors, with potential clinical relevance.
Dynamic Effectiveness of Advertising and Word of Mouth in Sequential Distribution of New Products
Authors: Bruce Norris I. , Foutz Natasha Zhang , Kolsarici Ceren
Published: June 2012

Firms in many industries release new products in sequential stages. They also launch separate advertising campaigns at each distribution stage. Thus, communication mix elements—advertising and word of mouth (WOM)—can play important, distinct, and yet interdependent roles in stimulating new product demand. Their effectiveness may fluctuate within and across stages and spill over from earlier to later stages. Thus, the authors construct a dynamic linear model to study the dynamic effects of advertising and WOM on demand for heterogeneous products across stages. They further apply the model to examine a canonical example, the theater-then-video sequential distribution of motion pictures, and estimate the parameters using Kalman filtering/smoothing and Markov chain Monte Carlo methods. The results show that advertising and WOM exert dynamic, yet diverse, influences on demand for new products. For example, while increased ad spending is more effective at an earlier stage due to repetition wear-in and synergy with WOM, increased WOM activities at a later stage could become more powerful in driving demand. Subsequent optimization exercises suggest that films of varied characteristics can potentially re-allocate their advertising budgets and reap additional revenues.
Triangular labyrinth side weirs with one and two cycles
Authors: Borghei S. Mahmood , Nekooie Mohammad Ali , Sadeghian Hadi , Ghazizadeh Mohammad Reza Jalili
Published: June 2012

Labyrinth side weirs provide a potentially effective way to shorten the length of a channel opening with the desired water height, but the discharge coefficient needs to be found experimentally. Experiments were carried out for triangular labyrinth side weirs with one and two cycles in order to obtain the discharge coefficient. The test variables included channel opening, head angle, number of cycles, weir height, upstream water depth and discharge in a subcritical situation. The results show that the discharge coefficient ratio for a triangular labyrinth to a conventional side weir could rise to more than 2 with the same flow and geometric conditions. Relationships for the De Marchi coefficient for subcritical flow in a rectangular channel for triangular labyrinth side weirs (for the two geometries) are introduced as functions of non-dimensional variables of weir and flow. A sensitivity analysis on the measured data is also included.
Using Maximum Entropy modeling to predict the potential distributions of large trees for conservation planning
Authors: Smith Alain , Page Bruce , Duffy Kevin , Slotow Rob
Published: June 2012

Large trees, as keystone structures, are functionally important in savanna ecosystems, and low recruitment and slow growth makes their conservation important. Understanding factors influencing their distribution is essential for mitigation of excessive mortality, for example from management fires or large herbivores. We recorded the locations of large trees in Hluhluwe‐Imfolozi Park (HiP) using GPS to record trees along 43 km of 10 m‐wide transects. Maximum entropy modeling (MaxEnt) uses niche modeling to predict the distribution of a species from the probability of finding it within raster squares, based on environmental variables and recorded locations. MaxEnt is typically applied at a regional spatial scale, and here we assessed its usefulness when predicting the distribution of species at a small (local) scale. HiP has variable topography, heterogeneous soils, and a strong rainfall gradient, resulting in a wide variety of habitat types. We used locations of 179 Acacia nigrescens and 106 Sclerocarya birrea (large trees ≥ 5m), and raster environmental layers for: aspect, elevation, geology, annual rainfall, slope, soil and vegetation. A. nigrescens was largely restricted to the Imfolozi section, while S. birrea had a wider distribution across the reserve. Understanding the interaction of environmental variables dictating tree distribution may facilitate habitat restoration, and will assist planning decisions for persistence of large trees within reserves, including options to reduce fire frequency or herbivore impacts. Though the AUC (Area Under the Curve) values used to test model predictions were high for both species, the ground truthing test data showed that distribution for A. nigrescens was more accurate than that for S. birrea, highlighting the need for independent test data to assess model accuracy. We emphasize that MaxEnt can be used at finer spatial scales than those typically used for species occurrence, but models must be tested using spatially independent test data.
Temporal Changes in Socioeconomic Influences on Health: Maternal Education and Preterm Birth
Authors: El-Sayed Abdulrahman M. , Galea Sandro
Published: June 2012

Objectives. To consider how the relationships between social determinants and health indicators change over time, we assessed the time-varying influence of maternal education on risk of preterm birth (PTB) between 1989 and 2006.

Methods. We used bivariate and multivariable Poisson regression models with robust variation estimates to examine (1) the association between maternal education and PTB risk by year; (2) the relationship between low maternal education and PTB, late PTB, and very PTB risk by year relative to 1989; and (3) the relationship between high maternal education and PTB, late PTB, and very PTB risk by year relative to 1989.

Results. After adjustment, PTB risk increased among the most educated and did not change among the least educated women over time. Risk of PTB among the least educated relative to the most educated women decreased with time. Late PTB risk increased among both the most and the least educated groups but more among the most educated.

Conclusions. Maternal education may be becoming less protective against PTB. The influence of the social determinants of health is dynamic, warranting revisions of our understanding of their roles over time.
Maturation of Human Embryonic Stem Cell–Derived Pancreatic Progenitors Into Functional Islets Capable of Treating Pre-existing Diabetes in Mice
Authors: Rezania Alireza , Bruin Jennifer E. , Riedel Michael J. , Mojibian Majid , Asadi Ali , Xu Jean , Gauvin Rebecca , Narayan Kavitha , Karanu Francis , O’Neil John J. , Ao Ziliang , Warnock Garth L. , Kieffer Timothy J.
Published: June 2012

Diabetes is a chronic debilitating disease that results from insufficient production of insulin from pancreatic β-cells. Islet cell replacement can effectively treat diabetes but is currently severely limited by the reliance upon cadaveric donor tissue. We have developed a protocol to efficiently differentiate commercially available human embryonic stem cells (hESCs) in vitro into a highly enriched PDX1+ pancreatic progenitor cell population that further develops in vivo to mature pancreatic endocrine cells. Immature pancreatic precursor cells were transplanted into immunodeficient mice with streptozotocin-induced diabetes, and glycemia was initially controlled with exogenous insulin. As graft-derived insulin levels increased over time, diabetic mice were weaned from exogenous insulin and human C-peptide secretion was eventually regulated by meal and glucose challenges. Similar differentiation of pancreatic precursor cells was observed after transplant in immunodeficient rats. Throughout the in vivo maturation period hESC-derived endocrine cells exhibited gene and protein expression profiles that were remarkably similar to the developing human fetal pancreas. Our findings support the feasibility of using differentiated hESCs as an alternative to cadaveric islets for treating patients with diabetes.
Diversity and distribution of cyanobacterial toxins in the Italian subalpine lacustrine district
Authors: Cerasino Leonardo , Salmaso Nico
Published: June 2012

Nine lakes (Garda, Maggiore, Como, Iseo, Lugano, Idro, Pusiano, Ledro, and Levico) located in the Italian subalpine lacustrine district were chosen for a comparative study of the diversity and distribution of cyanobacterial toxins. All nine lakes are known to host different toxic cyanobacteria, mainly Planktothrix rubescens. An analytical protocol has been used, based on LC-MS technique, for determining 20 different toxins (14 microcystins, 2 nodularins, anatoxin-a and 3 cylindrospermopsins). In the investigation, microcystins were found in all lakes on all sampling dates. Anatoxin-a could be detected in 6 lakes, but it was only present in 4 lakes on all sampling dates (lakes Garda, Iseo, Como, and Maggiore). Nodularins and cylindrospermopsins were not detected at all. The number of microcystins detected in the survey was 9, but 4 were the most abundant (dmRR, YR, dmLR, and LR); they were differently distributed among the lakes, thus providing each lake a unique toxic potential. Statistical analysis showed positive correlations between total microcystin concentrations and eutrophication indicators and also between anatoxin-a concentrations and water temperature, suggesting that anthropic and climate-related stressors can have different impacts on the presence of different cyanotoxins.
Global Trends in Civic and Citizenship Education: What are the Lessons for Nation States?
Authors: Kennedy Kerry J.
Published: June 2012

Civic and citizenship education is a component of the school curriculum in all nation states. The form it takes, its purposes and the way in which it is implemented differs from jurisdiction to jurisdiction. The pressures of globalization in recent times have meant that citizenship has increasingly come to be seen in global terms brought about by processes such as transnational migration, the homogenization of cultural practices and the development of supranational groupings that often seem to challenge more local versions of citizenship. Despite these pressures, the key responsibility for citizenship continues to rest with nation states. This paper will review issues relating to a more globalized citizenship and outline the strategies that nation states might adopt to ensure they remain capable of creating an active and engaged citizenship.
Introduction to the Special Issue on Recent Advances in Web Services
Authors: Fernandez Eduardo B.
Published: June 2012

We have collected five papers describing different aspects of web services and cloud computing. Cloud computing is the next stage of application interoperability and it is a logical extension of web services, both approaches being a variety of Service-Oriented Architecture. The papers cover security, migration, certification, and application development. Together, these papers provide a useful panorama of some of the issues of these two technologies.
Symptomatological Features of Patients with and without Ecstasy Use during Their First Psychotic Episode
Authors: Rugani Fabio , Bacciardi Silvia , Rovai Luca , Pacini Matteo , Maremmani Angelo Giovanni Icro , Deltito Joseph , Dell’Osso Liliana , Maremmani Icro
Published: June 2012

Background: Ecstasy use is generally chosen by adolescents and young adults for its entactogenic properties (the production of feelings of empathy, love, and emotional closeness to others.) Despite this desired and frequently realized outcome, Ecstasy use has often resulted in the genesis of psychotic symptoms and aggressive behaviors, particularly after chronic and/or intensive use. Methods: To explore the negative consequences of Ecstasy use and to examine the aggressive nature oftentimes seen in many Ecstasy users we employed a case-control study model. We compared, by means of validated psychometric tests, the psychopathological symptoms (BPRS), the aggressiveness (OAS) and the social adjustment (DSM-GAF) of psychotic patients with (n = 23) and without (n = 46) recent user of Ecstasy, during their first psychotic episode and hospitalization. All 23 Ecstasy users were Ecstasy users only. Results: Almost all of the psychotic symptoms were of similar severity in both groups. Blunted affect was milder in users than in non-users, whereas hostility and aggressive behavior was significantly more severe in users than in non-users. Conclusions: psychosis with a high level of aggressiveness and violence constitutes an important ‘side-effect’ that surely runs counter to the expected entactogenic action of Ecstasy. At a patient psycho-educational level, this study suggests that the use of Ecstasy may be counterproductive with respect to user expectations.
DsHsp90 Is Involved in the Early Response of Dunaliella salina to Environmental Stress †
Authors: Wang Si-Jia , Wu Ming-Jie , Chen Xiang-Jun , Jiang Yan , Yan Yong-Bin
Published: June 2012

Heat shock protein 90 (Hsp90) is a molecular chaperone highly conserved across the species from prokaryotes to eukaryotes. Hsp90 is essential for cell viability under all growth conditions and is proposed to act as a hub of the signaling network and protein homeostasis of the eukaryotic cells. By interacting with various client proteins, Hsp90 is involved in diverse physiological processes such as signal transduction, cell mobility, heat shock response and osmotic stress response. In this research, we cloned the dshsp90 gene encoding a polypeptide composed of 696 amino acids from the halotolerant unicellular green algae Dunaliella salina. Sequence alignment indicated that DsHsp90 belonged to the cytosolic Hsp90A family. Further biophysical and biochemical studies of the recombinant protein revealed that DsHsp90 possessed ATPase activity and existed as a dimer with similar percentages of secondary structures to those well-studied Hsp90As. Analysis of the nucleotide sequence of the cloned genomic DNA fragment indicated that dshsp90 contained 21 exons interrupted by 20 introns, which is much more complicated than the other plant hsp90 genes. The promoter region of dshsp90 contained putative cis-acting stress responsive elements and binding sites of transcriptional factors that respond to heat shock and salt stress. Further experimental research confirmed that dshsp90 was upregulated quickly by heat and salt shock in the D. salina cells. These findings suggested that dshsp90 might serve as a component of the early response system of the D. salina cells against environmental stresses.
High Resolution Crystal Structures of the Cerebratulus lacteus Mini-Hb in the Unligated and Carbomonoxy States
Authors: Germani Francesca , Pesce Alessandra , Venturini Andrea , Moens Luc , Bolognesi Martino , Dewilde Sylvia , Nardini Marco
Published: June 2012

The nerve tissue mini-hemoglobin from Cerebratulus lacteus (CerHb) displays an essential globin fold hosting a protein matrix tunnel held to allow traffic of small ligands to and from the heme. CerHb heme pocket hosts the distal TyrB10/GlnE7 pair, normally linked to low rates of O2 dissociation and ultra-high O2 affinity. However, CerHb affinity for O2 is similar to that of mammalian myoglobins, due to a dynamic equilibrium between high and low affinity states driven by the ability of ThrE11 to orient the TyrB10 OH group relative to the heme ligand. We present here the high resolution crystal structures of CerHb in the unligated and carbomonoxy states. Although CO binds to the heme with an orientation different from the O2 ligand, the overall binding schemes for CO and O2 are essentially the same, both ligands being stabilized through a network of hydrogen bonds based on TyrB10, GlnE7, and ThrE11. No dramatic protein structural changes are needed to support binding of the ligands, which can freely reach the heme distal site through the apolar tunnel. A lack of main conformational changes between the heme-unligated and -ligated states grants stability to the folded mini-Hb and is a prerequisite for fast ligand diffusion to/from the heme.
Green Formation of Spherical and Dendritic Silver Nanostructures under Microwave Irradiation without Reducing Agent
Authors: Noroozi Monir , Zakaria Azmi , Moksin Mohd Maarof , Wahab Zaidan Abd , Abedini Alam
Published: June 2012

The rapid and green formation of spherical and dendritic silver nanostructures based on microwave irradiation time was investigated. Silver nanoparticles were successfully fabricated by reduction of Ag+ in a water medium and using polyvinylpyrrolidone (PVP) as the stabilizing agent and without the use of any other reducing agent, and were compared with those synthesized by conventional heating method. UV–vis absorption spectrometry, transmission electron microscopy (TEM), atomic absorption spectroscopy (AAS) and photon correlation spectroscopy (PCS) measurements, indicated that increasing the irradiation time enhanced the concentration of silver nanoparticles and slightly increased the particle size. There was a lack of large silver nanoparticles at a high concentration, but interestingly, the formation and growth of silver dendrite nanostructures appeared. Compared to conventional heating methods, the silver nanoparticle suspension produced by irradiated microwaves was more stable over a six-month period in aqueous solution without any signs of precipitation.
How Varroa Parasitism Affects the Immunological and Nutritional Status of the Honey Bee, Apis mellifera
Authors: Aronstein Katherine A. , Saldivar Eduardo , Vega Rodrigo , Westmiller Stephanie , Douglas Angela E.
Published: June 2012

We investigated the effect of the parasitic mite Varroa destructor on the immunological and nutritional condition of honey bees, Apis mellifera, from the perspective of the individual bee and the colony. Pupae, newly-emerged adults and foraging adults were sampled from honey bee colonies at one site in S. Texas, USA. Varroa‑infested bees displayed elevated titer of Deformed Wing Virus (DWV), suggestive of depressed capacity to limit viral replication. Expression of genes coding three anti-microbial peptides (defensin1, abaecin, hymenoptaecin) was either not significantly different between Varroa-infested and uninfested bees or was significantly elevated in Varroa-infested bees, varying with sampling date and bee developmental age. The effect of Varroa on nutritional indices of the bees was complex, with protein, triglyceride, glycogen and sugar levels strongly influenced by life-stage of the bee and individual colony. Protein content was depressed and free amino acid content elevated in Varroa-infested pupae, suggesting that protein synthesis, and consequently growth, may be limited in these insects. No simple relationship between the values of nutritional and immune-related indices was observed, and colony-scale effects were indicated by the reduced weight of pupae in colonies with high Varroa abundance, irrespective of whether the individual pupa bore Varroa.
Laboratory Study of the Influence of Substrate Type and Temperature on the Exploratory Tunneling by Formosan Subterranean Termite
Authors: Gautam Bal K. , Henderson Gregg
Published: June 2012

Using two-dimensional foraging arenas, laboratory tests were conducted to investigate the effect of soil type, soil moisture level and ambient temperature on the exploratory tunneling by Coptotermes formosanus Shiraki. In choice arenas consisting of two substrate types having two moisture levels each, and conducted at a constant temperature of 22 °C, a significantly greater proportion of termites aggregated in sand than in sandy loam. Similarly, the length of excavated tunnels was also increased in sand. In a given substrate, termite aggregation or tunnel length did not differ between 5% and 15% moisture levels. In no-choice tests, where three different substrates (sand, sandy loam and silt loam) were tested at two temperatures (22 °C and 28 °C), excavations were significantly greater in sand than either sandy loam or silt loam at 22 °C. Fewer primary tunnels were constructed in sandy loam than in sand and fewer branched tunnels than either in sand or silt loam. No significant difference in either tunnel length or number of primary or branched tunnels was found between these two temperatures.
Three New Cembranoids from the Taiwanese Soft Coral Sarcophyton ehrenbergi
Authors: Wang Shang-Kwei , Hsieh Mu-Keng , Duh Chang-Yih
Published: June 2012

In order to search for new bioactive substances from marine organisms, we have investigated the acetone extracts of the soft coral Sarcophyton ehrenbergi collected at San-Hsian-Tai, Taitong County, Taiwan. Chromatographic fractionation of the extracts of the octocoral S. ehrenbergi led to the isolation of three new cembranoids, (+)-12-ethoxycarbonyl-11Z-sarcophine (1), ehrenbergol A and B (2 and 3). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses. Moreover, metabolites 1–3 were evaluated in vitro for their cytotoxicity towards selected cancer cell lines and antiviral activity against human cytomegalovirus (HCMV).