bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of saline fluids in deep‐crustal and upper‐mantle metasomatism: insights from experimental studies
Authors: NEWTON R. C. , MANNING C. E.
Published: March 2010

Geofluids (2010) 10, 58–72

Chloride‐rich brines are increasingly recognized as playing an important role in high pressure and temperature metamorphic and magmatic systems. The origins of these saline multicomponent fluids are debated, but experimental evidence suggests that regardless of their origin they must be important agents of rock alteration and mass transfer wherever they occur. Studies of the solubility of quartz in H2O, CO2–H2O and salt–H2O solutions provide a framework for understanding the role of brines in the deep crust and upper mantle. While quartz solubility in the system SiO2–H2O–NaCl–CO2 is maximal at a given high pressure and temperature if the solvent is pure H2O, the decline in quartz solubility with NaCl content (salting‐out) is less severe than in CO2–H2O fluids at comparable H2O activities. Moreover, at lower pressures, quartz solubility initially salts in at low salt contents, before reaching a maximum and then declining. The behavior of quartz solubility in salt–H2O solutions has not yet been fully explained and is the subject of active debate. Experimental investigations of the solubility of some other rock‐forming oxides and silicates show enhancements due to NaCl addition. As illustrated by the well‐studied CaO–Al2O3–SiO2–NaCl–H2O system, enhancements initially increase to maxima, and then decline. This behavior can be explained by formation of a range of hydrated aqueous complexes and clusters with specific NaCl:H2O stoichiometries. In contrast, solubilities of calcium salts, including calcite, fluorite, fluorapatite and anhydrite, rise monotonically with increasing NaCl, implying complexing to form anhydrous ionic solutes and/or ion pairs. The experimental studies offer new insights into fluid‐rock interaction in a range of settings, including carbonatite–fenite complexes, granulite‐facies metamorphism, porphyry ore deposits and aluminum‐silicate vein complexes in high‐grade metamorphic terranes.
Modulation of bone morphogenic protein signalling alters numbers of astrocytes and oligodendroglia in the subventricular zone during cuprizone‐induced demyelination
Authors: Cate Holly S. , Sabo Jennifer K. , Merlo Daniel , Kemper Dennis , Aumann Tim D. , Robinson Julien , Merson Toby D. , Emery Ben , Perreau Victoria M. , Kilpatrick Trevor J.
Published: February 2010

J. Neurochem. (2010) 115, 11–22.

The adult subventricular zone (SVZ) is a potential source of precursor cells to replace neural cells lost during demyelination. To better understand the molecular events that regulate neural precursor cell responsiveness in this context we undertook a microarray and quantitative PCR based analysis of genes expressed within the SVZ during cuprizone‐induced demyelination. We identified an up‐regulation of the genes encoding bone morphogenic protein 4 (BMP4) and its receptors. Immunohistochemistry confirmed an increase in BMP4 protein levels and also showed an increase in phosphorylated SMAD 1/5/8, a key component of BMP4 signalling, during demyelination. In vitro analysis revealed that neural precursor cells isolated from demyelinated animals, as well as those treated with BMP4, produce more astrocytes. Similarly, there were increased numbers of astrocytes in vivo within the SVZ during demyelination. Intraventricular infusion of Noggin, an endogenous antagonist of BMP4, during cuprizone‐induced demyelination reduced pSMAD1/5/8, decreased astrocyte numbers and increased oligodendrocyte numbers in the SVZ. Our results suggest that lineage commitment of SVZ neural precursor cells is altered during demyelination and that BMP signalling plays a role in this process.
Increased expression of cholesterol 24S‐hydroxylase results in disruption of glial glutamate transporter EAAT2 association with lipid rafts: a potential role in Alzheimer’s disease
Authors: Tian Guilian , Kong Qiongman , Lai Liching , Ray‐Chaudhury Abhik , Lin Chien‐liang G.
Published: February 2010

J. Neurochem. (2010) 113, 978–989.

The glial glutamate transporter EAAT2 (excitatory amino acid transporter 2) is the major mediator of glutamate clearance that terminates glutamate‐mediated neurotransmission. Loss of EAAT2 and associated glutamate uptake function has been reported in the brains of patients with Alzheimer’s disease (AD). We previously reported that EAAT2 is associated with lipid raft microdomains of the plasma membrane. In the present study, we demonstrated that association of EAAT2 with lipid rafts is disrupted in AD brains. This abnormality is not a consequence of neuron degeneration, oxidative stress, or amyloid beta toxicity. In AD brains, cholesterol 24S‐hydroxylase (CYP46), a key enzyme in maintenance of cholesterol homeostasis in the brain, is markedly increased in astrocytes but decreased in neurons. We demonstrated that increased expression of CYP46 in primary astrocytes results in a reduction of membrane cholesterol levels and leads to the dissociation of EAAT2 from lipid rafts and the loss of EAAT2 and associated glutamate uptake function. These results suggest that a disturbance of cholesterol metabolism may contribute to loss of EAAT2 in AD.
Human TrkB gene: novel alternative transcripts, protein isoforms and expression pattern in the prefrontal cerebral cortex during postnatal development
Authors: Luberg Kristi , Wong Jenny , Weickert Cynthia Shannon , Timmusk Tõnis
Published: February 2010

J. Neurochem. (2010) 113, 952–964.

Brain‐derived neurotrophic factor and neurotrophin‐4 high‐affinity receptor tropomyosine related kinase (Trk) B is required for the differentiation and maintenance of specific neuron populations. Misregulation of TrkB has been reported in many human diseases, including cancer, obesity and neurological and psychiatric disorders. Alternative splicing that generates receptor isoforms with different functional properties also regulates TrkB function. Here, we describe numerous novel isoforms of TrkB proteins, including isoforms generated by alternative splicing of cassette exons in the regions encoding both the extracellular and intracellular domain and also N‐terminally truncated isoforms encoded by novel 5′ exon‐containing transcripts. We also characterize the intracellular localization and phosphorylation potential of novel TrkB isoforms and find that these proteins have unique properties. In addition, we describe the expression profiles of all the known human TrkB transcripts in adult tissues and also during postnatal development in the human prefrontal cortex. We show that transcripts encoding the full‐length TrkB receptor and the C‐terminally truncated TrkB‐T1 have different expression profiles as compared to the proteins they encode. Identification of 36 potential TrkB protein isoforms suggests high complexity in the synthesis, regulation and function of this important neurotrophin receptor emphasizing the need for further study of these novel TrkB variants.
Drosophila models of human tauopathies indicate that Tau protein toxicity in vivo is mediated by soluble cytosolic phosphorylated forms of the protein
Authors: Feuillette Sébastien , Miguel Laetitia , Frébourg Thierry , Campion Dominique , Lecourtois Magalie
Published: February 2010

J. Neurochem. (2010) 113, 895–903.

Tau is a neuronal microtubule‐associated protein involved in microtubules assembly and stabilization. Tauopathies, including Alzheimer’s disease and fronto‐temporal dementia with parkinsonism linked to chromosome 17, are a group of neurodegenerative disorders characterized by the presence of intraneuronal filamentous inclusions of abnormally and hyperphosphorylated Tau. Currently, the molecular mechanisms underlying Tau‐mediated cellular toxicity remain elusive. To address the determinants of Tau neurotoxicity, we used Drosophila models of human tauopathies to study the microtubule‐binding properties of human Tau proteins in vivo. We showed that, in contrast to endogenous Drosophila Tau, human Tau proteins bind very poorly to microtubules in Drosophila, and are mostly recovered as soluble cytosolic hyperphosphorylated species. This weak binding of human Tau to microtubules is neither because of microtubules saturation nor competition with endogenous Drosophila Tau, but clearly depends on its phosphorylation degree. We also reported that accumulation of cytosolic hyperphosphorylated forms of human Tau proteins correlates with human Tau‐mediated neurodegeneration in flies, supporting the key role of soluble cytosolic hyperphosphorylated Tau proteins as toxic species in vivo.
Systemic polarisation and spatial voting
Authors: PARDOS‐PRADO SERGI , DINAS ELIAS
Published: March 2010

The controversy between proximity and directional models of issue voting has not been settled. Instead of appointing an ultimate winner, this article explores the conditioning impact of the level of systemic polarisation and provides evidence that proximity is a more relevant determinant of voter behaviour in less polarised systems, whereas there is a centrifugal and directional dynamic in more polarised contexts. By so doing, the article shows how a largely forgotten notion – namely Sartori's idea of the spatial elasticity of the political spectrum – leads to different spatial viewpoints. In distinguishing between party (supply side) and voter (demand side) polarisation, this framework provides a comprehensive picture about the conditions that turn a centripetal electoral dynamic into a purely centrifugal one.
A monobromobimane‐based assay to measure the pharmacokinetic profile of reactive sulphide species in blood
Authors: Wintner Edward A , Deckwerth Thomas L , Langston William , Bengtsson Asa , Leviten Dina , Hill Paul , Insko Michael A , Dumpit Ronald , VandenEkart Emily , Toombs Christopher F , Szabo Csaba
Published: March 2010

Background and purpose: Hydrogen sulphide (H2S) is a labile, endogenous metabolite of cysteine, with multiple biological roles. The development of sulphide‐based therapies for human diseases will benefit from a reliable method of quantifying H2S in blood and tissues.

Experimental approach: Concentrations of reactive sulphide in saline and freshly drawn whole blood were quantified by reaction with the thio‐specific derivatization agent monobromobimane, followed by reversed‐phase fluorescence HPLC and/or mass spectrometry. In pharmacokinetic studies, male rats were exposed either to intravenous infusions of sodium sulphide or to H2S gas inhalation, and levels of available blood sulphide were measured. Levels of dissolved H2S/HS‐were concomitantly measured using an amperometric sensor.

Key results: Monobromobimane was found to rapidly and quantitatively derivatize sulphide in saline or whole blood to yield the stable small molecule sulphide dibimane. Extraction and quantification of this bis‐bimane derivative were validated via reversed‐phase HPLC separation coupled to fluorescence detection, and also by mass spectrometry. Baseline levels of sulphide in blood were in the range of 0.4–0.9 µM. Intravenous administration of sodium sulphide solution (2–20 mg·kg−1·h−1) or inhalation of H2S gas (50–400 ppm) elevated reactive sulphide in blood in a dose‐dependent manner. Each 1 mg·kg−1·h−1of sodium sulphide infusion into rats was found to be pharmacokinetically equivalent to approximately 30 ppm of H2S gas inhalation.

Conclusions and implications: The monobromobimane derivatization method is a sensitive and reliable means to measure reactive sulphide species in whole blood. Using this method, we have established a bioequivalence between infused sodium sulphide and inhaled H2S gas.
Women’s Labour Contribution to Productivity and Efficiency in Agriculture: Empirical Evidence From Bangladesh
Authors: Rahman Sanzidur
Published: March 2010

This article examines the contribution of women’s labour input to productivity and efficiency in crop farming using a large survey dataset of 1,839 households from 16 villages in two agro‐ecological regions of Bangladesh. Results reveal that female labour accounts for a substantial 28% of total labour use (mainly supplied from the family) and contributes significantly to productivity as well as technical efficiency. Contrary to expectation, the cost share of female labour input is significantly higher than the male share, and has a substitution relationship with all other inputs, including male labour. The estimated mean level of technical efficiency is 0.90, implying that crop output might be increased by 10% by eliminating technical inefficiency. Both male and female education have a significant impact on improving technical efficiency. Other significant technical efficiency shifters are farming experience, family size and crop diversification. Owner operators are found to be technically inefficient relative to the tenants. Policy implications include creation of a hired labour market for female labour so that more women can be involved in the production process, and can contribute to towards improving productivity and efficiency. In addition, investment in education for both men and women, strategies to promote crop diversification and effective regulation/modification of the tenancy market will significantly improve technical efficiency in this case.
What Do Farmers Want From Agri‐Environmental Scheme Design? A Choice Experiment Approach
Authors: Espinosa‐Goded Maria , Barreiro‐Hurlé Jesús , Ruto Eric
Published: March 2010

Agri‐environmental schemes (AES) have had a limited effect on European agriculture due to farmers’ reluctance to participate. Information on how farmers react when AES characteristics are modified can be an important input to the design of such policies. This article investigates farmers’ preferences for different design options in a specific AES aimed at encouraging nitrogen fixing crops in marginal dry‐land areas in Spain. We use a choice experiment survey conducted in two regions (Aragón and Andalusia). The analysis employs an error component random parameter logit model allowing for preference heterogeneity and correlation amongst the non‐status quo alternatives. Farmers show a strong preference for maintaining their current management strategies; however, significant savings in cost or increased participation can be obtained by modifying some AES attributes.
Increased Activation of the ACC During a Spatial Working Memory Task in Alcohol‐Dependence Versus Heavy Social Drinking
Authors: Vollstädt‐Klein Sabine , Hermann Derik , Rabinstein Juri , Wichert Svenja , Klein Oliver , Ende Gabriele , Mann Karl
Published: March 2010

Background:  Activation of the anterior cingulate cortex (ACC) in a spatial working memory task has been associated with risk factors for alcohol use disorders such as low alcohol effects and positive alcohol expectations in adolescents. To transfer these results into adults, we used the same task in adults.

Methods:  During functional magnetic resonance imaging, 12 light social, 7 heavy social, and 11 non‐abstinent‐dependent alcohol drinkers performed a spatial working memory task and completed measures of automatic alcohol‐related thoughts and behavior (Obsessive–Compulsive Drinking Scale—OCDS), alcohol use of the last 90 days, and general intelligence.

Results:  Behavioral performance in the spatial working memory task was not significantly different in all 3 groups. Controlling for differences in general intelligence alcohol‐dependent participants showed a higher task‐related activation of the dorsal ACC (dACC) in comparison with light and heavy social drinkers. Measures of the OCDS were positively correlated with the activation in the left hippocampus and right thalamus in all participants.

Conclusions:  Our results support the findings of increased dACC activation during a spatial working memory task as a risk factor for alcohol dependence. Increased task‐related activation in the dACC was only observed in alcohol‐dependent participants and not in heavy social drinkers with comparable alcohol consumption. Furthermore, the absence of behavioral performance differences between groups as well as an association between dACC activation and working memory performance indicates subtle working memory deficits. Low capacity of working memory has been linked to more automatic and less self‐regulated behavior in studies on natural reward processing. Therefore, additional neural activation during performance of the non‐alcohol‐related working memory task in participants with higher OCDS values in the left hippocampus and the right thalamus may be a consequence of decreased neural capacity because of distracting alcohol‐related thoughts.
Effect of Establishing Guidelines on Appropriate Urinary Catheter Placement
Authors: Fakih Mohamad G. , Pena Margarita E. , Shemes Stephen , Rey Janice , Berriel‐Cass Dorine , Szpunar Susan M. , Savoy‐Moore Ruth T. , Saravolatz Louis D.
Published: March 2010

Objectives:  Avoiding placement of unnecessary urinary catheters (UCs) in the emergency department (ED) affects UC utilization during hospitalization. The authors sought to evaluate the effect of establishing institutional guidelines for appropriate UC placement coupled with emergency physician (EP) education on UC utilization.

Methods:  Urinary catheter utilization was measured before and after the establishment of guidelines and EP education. Data collected included the presence of a UC on ED arrival, placement of a UC in the ED, documentation of a physician order for UC placement, reasons for placement, and compliance with the guidelines. Chi‐square analyses were used to study the association between pre‐ and postintervention time periods and catheter use.

Results:  A total of 377 (15%) patients had UCs; only 151 (47%) UCs initially placed in the ED had a physician order documented. UC placement was appropriately indicated in 75.5% of patients with a documented physician order, but in only 52% of cases without a documented physician order (p < 0.001). The physician intervention was associated with an overall reduction in UC utilization from 16.4% to 13% (p = 0.018). Physicians ordered 40% fewer UCs postintervention compared to preintervention. Preintervention, a physician order for UC placement was found indicated in 72.6% patients, compared to 82.2% patients with UC placed postintervention (p = 0.21).

Conclusions:  Establishing guidelines for UC placement and physician education in the ED were associated with a marked reduction in utilization. However, addressing appropriate UC utilization may require evaluating other factors such as nursing influence on utilization.

ACADEMIC EMERGENCY MEDICINE 2010; 17:337–340 © 2010 by the Society for Academic Emergency Medicine
Potentially Inappropriate Medication Utilization in the Emergency Department Visits by Older Adults: Analysis From a Nationally Representative Sample
Authors: Meurer William J. , Potti Tommy A. , Kerber Kevin A. , Sasson Comilla , Macy Michelle L. , West Brady T. , Losman Eve D.
Published: March 2010

Objectives:  The objectives were to determine the frequency of administration of potentially inappropriate medications (PIMs) to older emergency department (ED) patients and to examine recent trends in the rates of PIM usage.

Methods:  The data examined during the study were obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS). This study utilized the nationally representative ED data from 2000–2006 NHAMCS surveys. Our sample included older adults (age 65 years and greater) who were treated in the ED and discharged home. Estimated frequencies of PIM‐associated ED visits were calculated. A multivariable logistic regression model was created to assess demographic, clinical, and hospital factors associated with PIM administration and to assess temporal trends.

Results:  Approximately 19.5 million patients, or 16.8% (95% confidence interval [CI] = 16.1% to 17.4%) of eligible ED visits, were associated with one or more PIMs. The five most common PIMs were promethazine, ketorolac, propoxyphene, meperidine, and diphenhydramine. The total number of medications prescribed or administered during the ED visit was most strongly associated with PIM use. Other covariates associated with PIM use included rural location outside of the Northeast, being seen by a staff physician only (and not by a resident or intern), presenting with an injury, and the combination of female sex and age 65–74 years. There was a small but significant decrease in the proportion of visits associated with a PIM over the study period.

Conclusions:  Potentially inappropriate medication administration in the ED remains common. Given rising concerns about preventable complications of medical care, this area may be of high priority for intervention. Substantial regional and hospital type (teaching versus nonteaching) variability appears to exist.

ACADEMIC EMERGENCY MEDICINE 2010; 17:231–237 © 2010 by the Society for Academic Emergency Medicine
Development of Geriatric Competencies for Emergency Medicine Residents Using an Expert Consensus Process
Authors: Hogan Teresita M. , Losman Eve D. , Carpenter Christopher R. , Sauvigne Karen , Irmiter Cheryl , Emanuel Linda , Leipzig Rosanne M.
Published: March 2010

Background:  The emergency department (ED) visit rate for older patients exceeds that of all age groups other than infants. The aging population will increase elder ED patient utilization to 35% to 60% of all visits. Older patients can have complex clinical presentations and be resource‐intensive. Evidence indicates that emergency physicians fail to provide consistent high‐quality care for elder ED patients, resulting in poor clinical outcomes.

Objectives:  The objective was to develop a consensus document, “Geriatric Competencies for Emergency Medicine Residents,” by identified experts. This is a minimum set of behaviorally based performance standards that all residents should be able to demonstrate by completion of their residency training.

Methods:  This consensus‐based process utilized an inductive, qualitative, multiphase method to determine the minimum geriatric competencies needed by emergency medicine (EM) residents. Assessments of face validity and reliability were used throughout the project.

Results:  In Phase I, participants (n = 363) identified 12 domains and 300 potential competencies. In Phase II, an expert panel (n = 24) clustered the Phase I responses, resulting in eight domains and 72 competencies. In Phase III, the expert panel reduced the competencies to 26. In Phase IV, analysis of face validity and reliability yielded a 100% consensus for eight domains and 26 competencies. The domains identified were atypical presentation of disease; trauma, including falls; cognitive and behavioral disorders; emergent intervention modifications; medication management; transitions of care; pain management and palliative care; and effect of comorbid conditions.

Conclusions:  The Geriatric Competencies for EM Residents is a consensus document that can form the basis for EM residency curricula and assessment to meet the demands of our aging population.

ACADEMIC EMERGENCY MEDICINE 2010; 17:316–324 © 2010 by the Society for Academic Emergency Medicine
Vitamin D deficiency does not alter biochemical markers of bone metabolism before or after autograft in patients with multiple myeloma
Authors: Laroche Michel , Lemaire Olivia , Attal Michel
Published: February 2010

So far, only one study has demonstrated a high incidence of vitamin D deficiency in patients with multiple myeloma. Vitamin D deficiency may alter bone remodelling in myeloma. In this study, we aimed to determine the prevalence of vitamin D deficiency and to assess its impact on bone remodelling and bone mineral density before and after autologous stem cell transplantation (ASCT). Patients and methods: In 39 consecutive patients receiving high‐dose chemotherapy (melphalan 200 mg/m2) followed by ASCT for multiple myeloma, we measured before (T0) and 12 months after ASCT (T12) serum calcium, 25‐OH‐D, PTH 1‐84, bone alkaline phosphatase (bALP), serum C‐terminal cross‐linking telopeptide and lumbar spine bone mineral density (BMD). Results: Mean vitamin D levels were low: 15 ± 5 ng/mL (9–18) at T0 and 16 ± 5 ng/mL (14–22) at T12. Twenty‐six patients (68%) had vitamin D deficiency (25‐OH‐D < 20 ng/mL) at T0 and 58% at T12. Patients in the vitamin D‐deficient group had higher serum PTH levels than those in the vitamin D‐sufficient group : 71 ± 24 pg/mL vs. 52 ± 18 pg/mL (P = 0.04). Biochemical bone markers were identical in both groups at T0 and T12. Z‐score values did not significantly differ between the two groups at T0 and T12. There were no correlations between 25‐OH‐D and BMD or bone marker levels. Conclusion: Vitamin D deficiency does not impair biochemical markers of bone metabolism in patients with multiple myeloma, before or after ASCT.
Association of AKT1 gene variants and protein expression in both schizophrenia and bipolar disorder
Authors: Karege F. , Perroud N. , Schürhoff F. , Méary A. , Marillier G. , Burkhardt S. , Ballmann E. , Fernandez R. , Jamain S. , Leboyer M. , La Harpe R. , Malafosse A.
Published: February 2010

The AKT1 gene has been associated with the genetic aetiology of schizophrenia. Following the overlap model of bipolar disorder and schizophrenia, we aimed to investigate AKT1 genetic variants and protein expression in both diseases. A total of 679 subjects with European ancestry were included: 384 with schizophrenia, 130 with bipolar disorder and 165 controls. Six single nucleotide polymorphisms (SNPs) were investigated for association with the diseases using single‐ and multi‐locus analyses. AKT1 and AKT2 protein levels were measured in post‐mortem brain tissues from ante‐mortem diagnosed schizophrenia (n = 30) and bipolar disorder subjects (n = 12) and matched controls. The analysis identified a significant global distortion in schizophrenia (P = 0.0026) and a weak association in bipolar disorder (P = 0.046). A sliding window procedure showed a five‐SNP haplotype (TCGAG) to be associated with schizophrenia (P = 1.22 × 10−4) and bipolar disorder (P = 0.0041) and a four‐SNP haplotype (TCGA) with the combined sample (1.73 × 10−5). On the basis of selected genotypes, a significant difference in protein expression emerged between subjects (P < 0.02). In conclusion, our findings, by showing the involvement of the AKT1 gene in both schizophrenia and bipolar disorder, support the role of AKT1 in the genetics of both disorders and add support to the view that there is some genetic overlap between them.
Decreased cardiac parasympathetic nerve activity of pregnant women during foot baths
Authors: MIYAZATO Kuniko , MATSUKAWA Kanji
Published: March 2010

Aim:  This study aimed to examine the effect of foot baths on the cardiac parasympathetic outflow of five pregnant (31–32 weeks; mid‐pregnancy) women and 16 non‐pregnant women.

Methods:  The cardiac parasympathetic outflow was assessed by using the respiratory variability of the R‐R interval under controlled breathing according to three different methods: (i) respiratory sinus arrhythmia; (ii) a respiratory‐synchronized component of the power spectrum of R‐R interval variability with a fast Fourier transform; and (iii) a high‐frequency component (HF at 0.15–0.40 Hz) of the power spectrum of R‐R interval variability with a maximum entropy method.

Results:  The rate and amplitude of spontaneous respiration and arterial blood pressure at rest were the same between the non‐pregnant and pregnant women. However, the baseline R‐R interval was shorter and the respiratory‐synchronized and HF components of the power spectrum of R‐R interval variability were smaller in the pregnant women, indicating a decreased baseline cardiac parasympathetic outflow with mid‐pregnancy. Although a foot bath for 15 min did not significantly affect the systemic hemodynamics and body temperature of both groups, the foot bath reduced the respiratory arrhythmia and the respiratory‐synchronized and HF components of the power spectrum of R‐R interval variability in both groups. The reduction in the respiratory R‐R interval became more prominent in the pregnant group.

Conclusion:  A foot bath, used as part of midwives' daily nursing care, is able to decrease the cardiac parasympathetic outflow of pregnant women.
Continuing Medical Education: Vulvovaginal Atrophy: Current and Future Therapies (CME)
Authors: Ibe Comfort , Simon James A.
Published: March 2010

Introduction

Vulvovaginal atrophy results from estrogen deficiency and affects a large number of postmenopausal women. Symptoms include vaginal dryness, itching, irritation, and dyspareunia.

Aim

The purpose of this review is to evaluate the efficacy, safety and acceptability of current treatment methods for vulvovaginal atrophy, as well as highlight evolving new treatment methods.

Method

We conducted a review of the literature concerning treatment of vulvovaginal atrophy.

Results

All currently available low-dose local estrogen formulations are effective and yield few side effects. Fears sparked by the Women’s Health Initiative, as well as recommendations by the FDA, have generated interest in the development of new treatment methods. Lower doses of existing formulations have proven to be efficacious. The use of estrogen agonists/antagonists and intravaginal dehydroepiandrosterone (DHEA) have both been shown to positively affect vaginal atrophy symptoms without inducing endometrial proliferation.

Conclusion

Potential new treatment methods show promise to provide efficacy in treatment while avoiding unwanted side effects. Further research is needed to establish optimal treatment formulations.
Overcoming immunological tolerance to melanoma: Targeting CTLA‐4
Authors: HODI F Stephen
Published: March 2010

The use of immunotherapeutics in melanoma has received much attention, and recent advances to further characterize the regulatory components of the immune system and the importance of co‐stimulatory molecules have opened a new area for clinical investigation. Cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) serves as a negative regulator of immunity. Recent trials administering fully human anti‐CTLA‐4 monoclonal antibodies to melanoma patients have demonstrated clinically meaningful responses. Treatment with CTLA‐4 blocking antibodies, however, is not without potential toxicities. Autoimmune side‐effects, the most common being colitis‐associated diarrhea, are frequently associated with clinical responses. In efforts to build upon prior vaccination efforts as well as attempt to offer patients clinically meaningful immune responses with a CTLA‐4 blockade but without significant toxicities, we conducted a clinical trial in patients who previously received autologous tumor cells engineered to secrete granulocyte‐macrophage colony stimulating factor (GVAX; Cell Genesys, South San Francisco, CA, USA) with periodic infusions of CTLA‐4 blocking antibodies. This sequential treatment resulted in clinically significant anti‐tumor immunity without grade 3 or 4 toxicity in most patients. Pathological analyses following treatment of pre‐existing tumors revealed a linear correlation between tumor necrosis and the ratio of intra‐tumoral CD8+ effector cells to FoxP3+ regulatory cells (Tregs). Effective anti‐tumor immunity and serious autoimmunity can be disassociated. Further targeting of anti‐tumor Tregsin combinatorial therapy approaches may be a rich avenue of future investigation.
Phosphate treatment to reduce plumbosolvency of drinking water also reduces discharges of copper into environmental surface waters
Authors: Comber Sean , Cassé Franck , Brown Bruce , Martin John , Hillis Peter , Gardner Mike
Published: March 2010

The majority of drinking water supply zones in the United Kingdom are currently dosed with phosphate in order to meet the drinking water quality standards for lead. Consequent reductions in other metals released from domestic plumbing might be expected. Lead, copper, zinc and nickel concentrations in the tap water of supply zones and in effluents from related sewage works were examined to assess reductions in the concentrations of these metals associated with the dosing of orthophosphate. This paper provides an analysis of the impact of phosphate dosing of drinking water on the metal concentrations in drinking water and sewage work effluents and the potential impacts in relation to the Water Framework Directive. Phosphate treatment the reduced average copper concentrations in drinking water by around 40% from 65 to 35 μg/L; the reduction is proportional to the phosphate dose. A corresponding 30% decrease in wastewater treatment work effluent concentrations is observed. No significant changes are evident in the zinc and nickel concentrations.
Basic aspects of phase changes under high pressure
Authors: Delgado Antonio , Kulisiewicz Leszek , Rauh Cornelia , Benning Rainer
Published: March 2010

Some substances of technological importance reveal phase change phenomena in the pressure and temperature range typically applied in biotechnology and food processing. For example, media with high molar volumes like edible oils and fats undergo liquid–solid phase transition at pressure increases up to several hundred megapascals. This article is concerned with theoretical considerations of the line of coexistence of solid and liquid phases in the pressure and temperature domain that corresponds to the phase boundary as a function of temperature and pressure. A universal model equation based on the equilibrium thermodynamics allowing prediction of the phase transition line of homogeneous media with high molar volume is presented. Approximate solutions of the model equation are discussed, which allow the phase boundary of substances with high molar volume to be described by a linear relation at least sequentially. The methods of experimental determination of the phase boundary under high pressure are presented and an attempt is made to validate the theoretical model with respect to the experimental data.
Molecular effects of high‐pressure processing on food studied by resonance Raman
Authors: Tintchev Filip , Wackerbarth Hainer , Kuhlmann Uwe , Toepfl Stefan , Knorr Dietrich , Hildebrandt Peter , Heinz Volker
Published: March 2010

Pressurization may cause unwanted side effects including color or texture changes of fish and meat. The color changes of poultry, pork, and smoked salmon were studied by CIE L*, a*, b* system, and resonance Raman (RR). High‐pressure processing (HPP) of pork and chicken meat resulted in significant color modification at pressures higher than 270 and 280 MPa, respectively. RR spectra were taken after a high‐pressure treatment of pork meat. According to the RR‐data, deoxymyoglobin is the dominating myoglobin species in pork meat. High‐pressure treatment causes conformational changes resulting in a stabile nonnative ferrous myoglobin species while the ferrous myoglobin state is maintained. High‐pressure treatment causes a decrease of the relative RR intensities of astaxanthin by salmon as probed with 514 nm. RR spectra excited at 413 nm revealed a heterogeneous broadening of astaxanthin bands accompanied by the formation of deoxymyoglobin or deoxyhemoglobin. The broadening is interpreted as the degradation products of astaxanthin. Obviously, the high‐pressure treatment of smoked salmon triggers redox processes of astaxanthin and the heme protein.
Microtubule depolymerization at high pressure
Authors: Nishiyama Masayoshi , Shimoda Yoshiki , Hasumi Manabu , Kimura Yoshifumi , Terazima Masahide
Published: March 2010

We performed in vitro assays to visualize the effects of pressure on the filamentous structure of microtubules. Taxol‐stabilized microtubules were tethered to kinesin motors on the observation window of a high‐pressure chamber. When pressure was applied to the sample solution, all of the microtubules started to shorten from both ends. The length changes were constant over time, irrespective of the microtubule polarity. The shortening rate of microtubules increased exponentially with pressure, and the activation volume was −100 mL/mol, consistent with in vivo studies. These results show that application of pressure works directly to weaken the intermolecular interactions between tubulin molecules.
Introduction to High‐Pressure Bioscience and Biotechnology
Authors: Bartlett Douglas H.
Published: March 2010

The manipulation of biological materials using elevated pressure is providing an ever‐growing number of opportunities in both the applied and basic sciences. Manipulation of pressure is a useful parameter for enhancing food quality and shelf life; inactivating microbes, viruses, prions, and deleterious enzymes; affecting recombinant protein production; controlling DNA hybridization; and improving vaccine preparation. In biophysics and biochemistry, pressure is used as a tool to study intermediates in protein folding, enzyme kinetics, macromolecular interactions, amyloid fibrous protein aggregation, lipid structural changes, and to discern the role of solvation and void volumes in these processes. Biologists, including many microbiologists, examine the utility and basis of pressure inactivation of cells and cellular processes, and conversely seek to discover how deep‐sea life has evolved a preference for high‐pressure environments. This introduction and the papers that follow provide information on the nature and promise of the highly interdisciplinary field of high‐pressure bioscience and biotechnology (HPBB).
Der Umverteilungseffekt öffentlicher bzw. privater Sozialprogramme: Eine internationale Querschnittstudie
Authors: Goudswaard Kees , Caminada Koen
Published: March 2010

Auszug

Eine Aufgabe vieler nationaler Sozialschutzsysteme ist es, Einkommen nachhaltig umzuverteilen. Umfang und Art der angebotenen Sozialschutzprogramme befinden sich jedoch in einem Wandel. In einigen Ländern ist eine Verlagerung von öffentlichen zu privatwirtschaftlichen Sozialschutzplänen zu beobachten, wobei Letztere die öffentlichen Programme oft ergänzen oder ersetzen. Aufbauend auf früheren Arbeiten, untersucht der vorliegende Artikel die Umverteilungswirkung von öffentlichen bzw. privaten Sozialschutzprogrammen auf die Einkommen. Anhand neuerer Daten der Organisation für wirtschaftliche Zusammenarbeit und Entwicklung (OECD) finden wir länderübergreifend eine starke positive Korrelation zwischen den öffentlichen Sozialausgaben und der Einkommensumverteilung. Bei den privatwirtschaftlichen Sozialausgaben finden wir eine schwache, aber statistisch signifikante, negative Korrelation mit der Umverteilungswirkung. In Ländern, in denen der Großteil der gesamten Sozialausgaben in private Sozialpläne fließt, ist die Einkommensumverteilung also geringer. Wir kommen zum Schluss, dass der Entscheid, den Sozialschutz stärker öffentlich oder stärker privatwirtschaftlich auszurichten, die Umverteilungswirkung des Wohlfahrtsstaats beeinflusst.
Aktuelle Belege für die Ausweitung der Deckung durch die soziale Sicherheit
Authors: Van Ginneken Wouter
Published: March 2010

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Dieser Beitrag basiert auf den Ergebnissen von 13 Studien, die im Rahmen eines Projekts der Internationalen Vereinigung für Soziale Sicherheit (IVSS) zur Ausweitung der Deckung („Examining the existing knowledge on coverage extension“—„Untersuchung des bestehenden Wissens über die Ausweitung der Deckung“) durchgeführt wurden. Er befasst sich mit neueren Belegen, die zeigen, wie aus Beiträgen oder Steuermitteln bzw. beidem finanzierte Geldleistungen und Krankenversicherungen in Ländern mit niedrigen, mittleren und hohen Einkommen ausgedehnt und erhalten werden können. Der Artikel wirft auch ein Schlaglicht auf eine Reihe von Prioritäten und Fragen bezüglich der Ausweitung der Deckung, darunter die Verbesserung des Schutzes für Wanderarbeitnehmer und solche in der informellen Wirtschaft.
Sensitivity study of micro four-point probe measurements on small samples
Authors: Wang Fei , Petersen Dirch H. , Hansen Torben M. , Henriksen Toke R. , Bøggild Peter , Hansen Ole
Published: March 2010

The authors calculate the sensitivities of micro four-point probe sheet resistance and Hall effect measurements to the local transport properties of nonuniform material samples. With in-line four-point probes, the measured dual configuration sheet resistance is more sensitive near the inner two probes than near the outer ones. The sensitive area is defined for infinite film, circular, square, and rectangular test pads, and convergent sensitivities are observed for small samples. The simulations show that the Hall sheet resistance RH in micro Hall measurements with position error suppression is sensitive to both local carrier density and local carrier mobility because the position calculation is affected in the two pseudo-sheet-resistance measurements needed for the position error suppression. Furthermore, they have also simulated the sensitivity for the resistance difference ΔRBB′ of two specific configurations to clarify the effect of the calculated position, which results in an unexpected sensitivity to the local carrier mobility.
Identification of the Biosynthetic Gene Cluster for 3-Methylarginine, a Toxin Produced by
Pseudomonas syringae
pv. syringae 22d/93
Authors: Braun S. D. , Hofmann J. , Wensing A. , Ullrich M. S. , Weingart H. , Völksch B. , Spiteller D.
Published: February 2010

The epiphyte
Pseudomonas syringae
pv. syringae 22d/93 (Pss22d) produces the rare amino acid 3-methylarginine (MeArg), which is highly active against the closely related soybean pathogen
Pseudomonas syringae
pv. glycinea. Since these pathogens compete for the same habitat, Pss22d is a promising candidate for biocontrol of
P. syringae
pv. glycinea. The MeArg biosynthesis gene cluster codes for the
S
-adenosylmethionine (SAM)-dependent methyltransferase MrsA, the putative aminotransferase MrsB, and the amino acid exporter MrsC. Transfer of the whole gene cluster into
Escherichia coli
resulted in heterologous production of MeArg. The methyltransferase MrsA was overexpressed in
E. coli
as a His-tagged protein and functionally characterized (

K
m

, 7 mM;
k
cat
, 85 min
−1
). The highly selective methyltransferase MrsA transfers the methyl group from SAM into 5-guanidino-2-oxo-pentanoic acid to yield 5-guanidino-3-methyl-2-oxo-pentanoic acid, which then only needs to be transaminated to result in the antibiotic MeArg.
Metabolomic Characterization of the Salt Stress Response in
Streptomyces coelicolor
Authors: Kol Stefan , Merlo M. Elena , Scheltema Richard A. , de Vries Marcel , Vonk Roel J. , Kikkert Niels A. , Dijkhuizen Lubbert , Breitling Rainer , Takano Eriko
Published: February 2010

The humicolous actinomycete
Streptomyces coelicolor
routinely adapts to a wide variety of habitats and rapidly changing environments. Upon salt stress, the organism is also known to increase the levels of various compatible solutes. Here we report the results of the first high-resolution metabolomics time series analysis of various strains of
S. coelicolor
exposed to salt stress: the wild type, mutants with progressive knockouts of the ectoine biosynthesis pathway, and two stress regulator mutants (with disruptions of the
sigB
and
osaB
genes). Samples were taken from cultures at 0, 4, 8, and 24 h after salt stress treatment and analyzed by liquid chromatography-mass spectrometry with an LTQ Orbitrap XL mass spectrometer. The results suggest that a large fraction of amino acids is upregulated in response to the salt stress, as are proline/glycine-containing di- and tripeptides. Additionally we found that 5′-methylthioadenosine, a known inhibitor of polyamine biosynthesis, is downregulated upon salt stress. Strikingly, no major differences between the wild-type cultures and the two stress regulator mutants were found, indicating a considerable robustness of the metabolomic response to salt stress, compared to the more volatile changes in transcript abundance reported earlier.
Biofilm Formation on Reverse Osmosis Membranes Is Initiated and Dominated by
Sphingomonas
spp
Authors: Bereschenko L. A. , Stams A. J. M. , Euverink G. J. W. , van Loosdrecht M. C. M.
Published: February 2010

The initial formation and spatiotemporal development of microbial biofilm layers on surfaces of new and clean reverse osmosis (RO) membranes and feed-side spacers were monitored
in situ
using flow cells placed in parallel with the RO system of a full-scale water treatment plant. The feed water of the RO system had been treated by the sequential application of coagulation, flocculation, sand filtration, ultrafiltration, and cartridge filtration processes. The design of the flow cells permitted the production of permeate under cross-flow conditions similar to those in spiral-wound RO membrane elements of the full-scale system. Membrane autopsies were done after 4, 8, 16, and 32 days of flow-cell operation. A combination of molecular (fluorescence
in situ
hybridization [FISH], denaturing gradient gel electrophoresis [DGGE], and cloning) and microscopic (field emission scanning electron, epifluorescence, and confocal laser scanning microscopy) techniques was applied to analyze the abundance, composition, architecture, and three-dimensional structure of biofilm communities. The results of the study point out the unique role of
Sphingomonas
spp. in the initial formation and subsequent maturation of biofilms on the RO membrane and feed-side spacer surfaces.
Impact of Molecular Hydrogen on Chalcopyrite Bioleaching by the Extremely Thermoacidophilic Archaeon
Metallosphaera sedula
Authors: Auernik Kathryne S. , Kelly Robert M.
Published: February 2010

Hydrogen served as a competitive inorganic energy source, impacting the CuFeS

2

bioleaching efficiency of the extremely thermoacidophilic archaeon
Metallosphaera sedula
. Open reading frames encoding key terminal oxidase and electron transport chain components were triggered by CuFeS
2
. Evidence of heterotrophic metabolism was noted after extended periods of bioleaching, presumably related to cell lysis.
Identification of a Dehydrogenase Required for Lactose Metabolism inCaulobacter crescentus
Authors: Arellano Benjamin H. , Ortiz Janett D. , Manzano Janet , Chen Joseph C.
Published: February 2010

Caulobacter crescentus, which thrives in freshwater environments with low nutrient levels, serves as a model system for studying bacterial cell cycle regulation and organelle development. We examined its ability to utilize lactose (i) to gain insight into the metabolic capacities of oligotrophic bacteria and (ii) to obtain an additional genetic tool for studying this model organism, aiming to eliminate the basal enzymatic activity that hydrolyzes the chromogenic substrate 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal). Using a previously isolated transposon mutant, we identified a gene,lacA, that is required for growth on lactose as the sole carbon source and for turning colonies blue in the presence of X-gal. LacA, which contains a glucose-methanol-choline (GMC) oxidoreductase domain, has homology to the flavin subunit ofPectobacterium cypripedii's gluconate dehydrogenase. Sequence comparisons indicated that two genes nearlacA,lacBandlacC, encode the other subunits of the membrane-bound dehydrogenase. In addition to lactose, all threelacgenes are involved in the catabolism of three other β-galactosides (lactulose, lactitol, and methyl-β-d-galactoside) and two glucosides (salicin and trehalose). Dehydrogenase assays confirmed that thelacgene products oxidize lactose, salicin, and trehalose. This enzymatic activity is inducible, and increasedlacexpression in the presence of lactose and salicin likely contributes to the induction. Expression oflacAalso depends on the presence of thelacgenes, implying that the dehydrogenase participates in induction. The involvement of a dehydrogenase suggests that degradation of lactose and other sugars inC. crescentusmay resemble a proposed pathway inAgrobacterium tumefaciens.