bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas‐phase reactivity of protonated 2‐oxazoline derivatives: mass spectrometry and computational studies
Authors: Vessecchi Ricardo , Tomaz José Carlos , Santos Guilherme Purcote dos , de Oliveira Alfredo R. Marques , Lopes Norberto Peporine , Clososki Giuliano Cesar
Published: March 2012

RATIONALE

Oxazolines have attracted the attention of researchers worldwide due to their versatility as carboxylic acid protecting groups, chiral auxiliaries, and ligands for asymmetric catalysis. Electrospray ionization tandem mass spectrometric (ESI‐MS/MS) analysis of five 2‐oxazoline derivatives has been conducted, in order to understand the influence of the side chain on the gas‐phase dissociation of these protonated compounds under collision‐induced dissociation (CID) conditions.

METHODS

Mass spectrometric analyses were conducted in a quadrupole time‐of‐flight (Q‐TOF) spectrometer fitted with electrospray ionization source. Protonation sites have been proposed on the basis of the gas‐phase basicity, proton affinity, atomic charges, and a molecular electrostatic potential map obtained on the basis of the quantum chemistry calculations at the B3LYP/6‐31 + G(d,p) and G2(MP2) levels.

RESULTS

Analysis of the atomic charges, gas‐phase basicity and proton affinities values indicates that the nitrogen atom is a possible proton acceptor site. On the basis of these results, two main fragmentation processes have been suggested: one taking place via neutral elimination of the oxazoline moiety (99 u) and another occurring by sequential elimination of neutral fragments with 72 u and 27 u. These processes should lead to formation of R+.

CONCLUSIONS

The ESI‐MS/MS experiments have shown that the side chain could affect the dissociation mechanism of protonated 2‐oxazoline derivatives. For the compound that exhibits a hydroxyl at the lateral chain, water loss has been suggested to happen through an E2‐type elimination, in an exothermic step. Copyright © 2012 John Wiley & Sons, Ltd.
Gas chromatography/isotope ratio mass spectrometry of recalcitrant target compounds: performance of different combustion reactors and strategies for standardization
Authors: Reinnicke Sandra , Juchelka Dieter , Steinbeiss Sibylle , Meyer Armin , Hilkert Andreas , Elsner Martin
Published: March 2012

RATIONALE

Compound‐specific isotope analysis (CSIA) relies on continuous flow combustion of organic substances to CO2 and N2 in a miniature reactor to measure 13 C/12 C and 15 N/14 N stable isotope ratios. Accurate analysis is well established for many volatile hydrocarbons. In contrast, compounds which contain hetero and halogen atoms are less volatile and may be more recalcitrant to combustion.

METHODS

This study tested carbon and nitrogen isotope analysis of atrazine, desethylatrazine (DEA), dichlobenil and 2,6‐dichlorobenzamide (BAM) by gas chromatography/isotope ratio mass spectrometry (GC/IRMS) with multiple reactor tubes of two different kinds (conventional CuO/NiO/Pt and a NiO tube/CuO‐NiO reactor prototype).

RESULTS

The advantages of the NiO tube/CuO‐NiO reactor were the absence of an additional reduction reactor, the possibility of routine reoxidation in nitrogen isotope analysis, and reliable atrazine and DEA measurements over several hundred injections. In contrast, BAM analysis showed good accuracy for carbon, but notable variations in the trueness of nitrogen isotope ratios. Accurate carbon and nitrogen analysis was nevertheless possible by bracketing samples with external compound‐specific standards and subsequent offset correction.

CONCLUSIONS

We conclude that instrument data should never be taken at its 'face value', but must consistently be validated with compound‐specific standards of the respective analytes. Copyright © 2012 John Wiley & Sons, Ltd.
Laser ablation synthesis of new gold phosphides using red phosphorus and nanogold as precursors. Laser desorption ionisation time‐of‐flight mass spectrometry
Authors: Panyala Nagender Reddy , Peña‐Méndez Eladia María , Havel Josef
Published: March 2012

Gold phosphides show unique optical or semiconductor properties and there are extensive high technology applications, e.g. in laser diodes, etc. In spite of the various AuP structures known, the search for new materials is wide. Laser ablation synthesis is a promising screening and synthetic method. Generation of gold phosphides via laser ablation of red phosphorus and nanogold mixtures was studied using laser desorption ionisation time‐of‐flight mass spectrometry (LDI TOFMS). Gold clusters Aum+ (m = 1 to ~35) were observed with a difference of one gold atom and their intensities were in decreasing order with respect to m. For Pn+ (n = 2 to ~111) clusters, the intensities of odd‐numbered phosphorus clusters are much higher than those for even‐numbered phosphorus clusters. During ablation of P‐nanogold mixtures, clusters Aum+ (m = 1‐12), Pn+ (n = 2‐7, 9, 11, 13–33, 35–95 (odd numbers)), AuPn+ (n = 1, 2–88 (even numbers)), Au2Pn+ (n = 1‐7, 14–16, 21–51 (odd numbers)), Au3Pn+ (n = 1‐6, 8, 9, 14), Au4Pn+ (n = 1‐9, 14–16), Au5Pn+ (n = 1‐6, 14, 16), Au6Pn+ (n = 1‐6), Au7Pn+ (n = 1‐7), Au8Pn+ (n = 1‐6, 8), Au9Pn+ (n = 1‐10), Au10Pn+ (n = 1‐8, 15), Au11Pn+ (n = 1‐6), and Au12Pn+ (n = 1, 2, 4) were detected in positive ion mode. In negative ion mode, Aum– (m = 1–5), Pn– (n = 2, 3, 5–11, 13–19, 21–35, 39, 41, 47, 49, 55 (odd numbers)), AuPn– (n = 4–6, 8–26, 30–36 (even numbers), 48), Au2Pn– (n = 2–5, 8, 11, 13, 15, 17), Au3Pn– (n = 6–11, 32), Au4Pn– (n = 1, 2, 4, 6, 10), Au6P5–, and Au7P8– clusters were observed. In both modes, phosphorus‐rich AumPn clusters prevailed. The first experimental evidence for formation of AuP60 and gold‐covered phosphorus Au12Pn (n = 1, 2, 4) clusters is given. The new gold phosphides generated might inspire synthesis of new Au‐P materials with specific properties. Copyright © 2012 John Wiley & Sons, Ltd.
Contribution of antibody production against neuraminidase to the protection afforded by influenza vaccines
Authors: Marcelin Glendie , Sandbulte Matthew R. , Webby Richard J.
Published: March 2012

Vaccines are instrumental in controlling the burden of influenza virus infection in humans and animals. Antibodies raised against both major viral surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), can contribute to protective immunity. Vaccine‐induced HA antibodies have been characterized extensively, and they generally confer protection by blocking the attachment and fusion of a homologous virus onto host cells. Although not as well characterized, some functions of NA antibodies in influenza vaccine‐mediated immunity have been recognized for many years. In this review, we summarize the case for NA antibodies in influenza vaccine‐mediated immunity. In the absence of well‐matched HA antibodies, NA antibodies can provide varying degrees of protection against disease. NA proteins of seasonal influenza vaccines have been shown in some instances to elicit serum antibodies with cross‐reactivity to avian‐origin and swine‐origin influenza strains, in addition to HA drift variants. NA‐mediated immunity has been linked to (i) conserved NA epitopes amongst otherwise antigenically distinct strains, partly attributable to the segmented influenza viral genome; (ii) inhibition of NA enzymatic activity; and (iii) the NA content in vaccine formulations. There is a potential to enhance the effectiveness of existing and future influenza vaccines by focusing greater attention on the antigenic characteristics and potency of the NA protein. Copyright © 2012 John Wiley & Sons, Ltd.
Practical guidelines for adaptive seamless phase II/III clinical trials that use Bayesian methods
Authors: Kimani Peter K. , Glimm Ekkehard , Maurer Willi , Hutton Jane L. , Stallard Nigel
Published: March 2012

Hommel (Biometrical Journal; 45:581–589) proposed a flexible testing procedure for seamless phase II/III clinical trials. Schmidliet al.(Statistics in Medicine; 26:4925–4938), Kimaniet al.(Statistics in Medicine; 28:917–936) and Brannathet al.(Statistics in Medicine; 28:1445–1463) exploited the flexible testing of Hommel to propose adaptation in seamless phase II/III clinical trials that incorporate prior knowledge by using Bayesian methods. In this paper, we show that adaptation incorporating prior knowledge may lead to higher power. Other important issues to consider in such adaptive designs are the gain in power (or saving in patients) over traditional testing and how utility values used to make the adaptation may be used to stop a trial early. In contrast to the aforementioned authors, we discuss these issues in detail and propose a unified approach to address them so that implementing the aforementioned designs and proposing similar designs is clearer. Copyright © 2012 John Wiley & Sons, Ltd.
Rapid Magnetophoretic Separation of Microalgae
Authors: Lim Jit Kang , Chieh Derek Chan Juinn , Jalak Selah A. , Toh Pey Yi , Yasin Nur Hidayah Mat , Ng Bee Wah , Ahmad Abdul Latif
Published: March 2012

Magnetic collection of the microalgae Chlorella sp. from culture media facilitated by low‐gradient magnetophoretic separation is achieved in real time. A removal efficiency as high as 99% is accomplished by binding of iron oxide nanoparticles (NPs) to microalgal cells in the presence of the cationic polyelectrolyte poly(diallyldimethylammonium chloride) (PDDA) as a binder and subsequently subjecting the mixture to a NdFeB permanent magnet with surface magnetic field ≈6000 G and magnetic field gradient <80 T m−1. Surface functionalization of magnetic NPs with PDDA before exposure to Chlorella sp. is proven to be more effective in promoting higher magnetophoretic removal efficiency than the conventional procedure, in which premixing of microalgal cells with binder is carried out before the addition of NPs. Rodlike NPs are a superior candidate for enhancing the magnetophoretic separation compared to spherical NPs due to their stable magnetic moment that originates from shape anisotropy and the tendency to form large NP aggregates. Cell chaining is observed for nanorod‐tagged Chlorella sp. which eventually fosters the formation of elongated cell clusters.
Pluripotent Stem Cell-Engineered Cell Sheets Reassembled with Defined Cardiovascular Populations Ameliorate Reduction in Infarct Heart Function Through Cardiomyocyte-Mediated Neovascularization
Authors: Masumoto Hidetoshi , Matsuo Takehiko , Yamamizu Kohei , Uosaki Hideki , Narazaki Genta , Katayama Shiori , Marui Akira , Shimizu Tatsuya , Ikeda Tadashi , Okano Teruo , Sakata Ryuzo , Yamashita Jun K.
Published: March 2012

Although stem cell therapy is a promising strategy for cardiac restoration, the heterogeneity of transplanted cells has been hampering the precise understanding of the cellular and molecular mechanisms. Previously, we established a cardiovascular cell differentiation system from mouse pluripotent stem cells, in which cardiomyocytes (CMs), endothelial cells (ECs), and mural cells (MCs) can be systematically induced and purified. Combining this with cell sheet technology, we generated cardiac tissue sheets reassembled with defined cardiovascular populations. Here, we show the potentials and mechanisms of cardiac tissue sheet transplantation in cardiac function after myocardial infarction (MI). Transplantation of the cardiac tissue sheet to a rat MI model showed significant and sustained improvement of systolic function accompanied by neovascularization. Reduction of the infarct wall thinning and fibrotic length indicated the attenuation of left ventricular remodeling. Cell tracing with species-specific fluorescent in situ hybridization after transplantation revealed a relatively early loss of transplanted cells and an increase in endogenous neovascularization in the proximity of the graft, suggesting an indirect angiogenic effect of cardiac tissue sheets rather than direct CM contributions. We prospectively dissected the functional mechanisms with cell type-controlled sheet analyses. Sheet CMs were the main source of vascular endothelial growth factor. Transplantation of sheets lacking CMs resulted in the disappearance of neovascularization and subsequent functional improvement, indicating that the beneficial effects of the sheet were achieved by sheet CMs. ECs and MCs enhanced the sheet functions and structural integration. Supplying CMs to ischemic regions with cellular interaction could be a strategic key in future cardiac cell therapy.

Disclosure of potential conflicts of interest is found at the end of this article.
Place identity and climate change adaptation: a synthesis and framework for understanding
Authors: Fresque‐Baxter Jennifer A. , Armitage Derek
Published: March 2012

Most research on climate change adaptation emphasizes the material and objective assets that build the capacity to adapt. Nonmaterial or ‘subjective’ attributes of adaptation (e.g. identity, beliefs, and values) are more difficult to quantify, and research in this area is less developed. Further effort is required to develop and test frameworks that facilitate a systematic examination of the subjective attributes of climate change adaptation. This article outlines the contribution of place identity theory as a lens through which to systematically examine how person–place bonds influence climate change adaptation. We provide a working typology of three interconnected place identity approaches to help elucidate this relationship. Each has strengths and weaknesses, depending on the theoretical and practical contexts within which they are used. The ‘cognitive‐behavioral approach’ has important utility in addressing how place identity shapes climate change perceptions and behavior; it can, however, be limited due to cognitive complexity and lack of richness from quantitative methodologies. The ‘health and well‐being approach’ addresses the often underemphasized health and well‐being impacts from climate change on place and identity, though the subjective nature of health must be considered in such an approach. The ‘collective action approach’ offers important insight into using place identity as a mechanism to foster collective opportunities for climate change adaptation. With such an approach, however, care must be taken to ensure inclusive representation of subgroup identities. We conclude by reflecting on how place identity theory can foster improved understanding in a critically important and emerging area of climate change adaptation research. WIREs Clim Change 2012. doi: 10.1002/wcc.164

This article is categorized under:

Perceptions, Behavior, and Communication of Climate Change > Behavior Change and Responses

Vulnerability and Adaptation to Climate Change > Values‐Based Approach to Vulnerability and Adaptation
International tourism and climate change
Authors: Scott Daniel , Gössling Stefan , Hall C. Michael
Published: March 2012

Tourism is a major global economic sector that is undergoing tremendous growth in emerging economies and is often touted as salient for development and poverty alleviation in developing countries. Tourism is recognized as a highly climate‐sensitive sector, one that is also strongly influenced by environmental and socioeconomic change influenced by climate change, and is also a growing contributor to anthropogenic climate change. This article outlines the complex interrelationships between climate change and the multiple components of the international tourism system. Five focal themes that have developed within the literature on the consequences of climate change for tourism are then critically reviewed: climatic change and temporal and geographic shifts in tourism demand, climate‐induced environmental change and destination competitiveness within three major market segments (winter sports tourism, coastal tourism, and nature‐based tourism), and mitigation policy developments and future tourist mobility. The review highlights the differential vulnerability of tourism destinations and that the resultant changes in competitiveness and sustainability will transform some international tourism markets. Feedbacks throughout the tourism system mean that all destinations will need to adapt to the risks and opportunities posed by climate change and climate policy. While notable progress has been made in the last decade, a number of important knowledge gaps in each of the major impact areas, key regional knowledge gaps, and both tourist and tourism operator perceptions of climate change risks and adaptive capacity indicate that the tourism sector is not currently well prepared for the challenges of climate change. WIREs Clim Change 2012. doi: 10.1002/wcc.165

This article is categorized under:

Climate and Development > Decoupling Emissions from Development
mGlu receptors in the retina
Authors: Dhingra Anuradha , Vardi Noga
Published: March 2012

Glutamate, a key neurotransmitter in the vertebrate retina, acts via ionotropic and metabotropic receptors. Retina expresses mRNA for all metabotropic glutamate receptors and proteins for all but mGluR3. Every retinal cell class expresses one or more of these receptors. In general, these receptors are present presynaptically and serve to modulate synaptic transmission. While mGluRs on the photoreceptor terminal act as autoreceptors to titer glutamate levels, those on the horizontal cell processes seem to shape the light response. Similarly, autoreceptors on bipolar axon terminals modulate glutamate release and the receptors on amacrine and ganglion cells modulate feedforward signals by modulating K+ or Ca2+current to fine tune light responses. Since most of the mGluR subtypes are present in amacrine and ganglion cells that belong to many cell types, the pathways downstream of mGluRs are highly diverse with primarily modulatory effects. An exception to most mGluRs that have a modulatory function is mGluR6 because it plays a key role in the feedforward transmission from photoreceptors to ON bipolar cells and is also required for the correct localization of the synaptic proteins in the dendritic tips. In humans, mutations in the gene encoding mGluR6 cause autosomal recessive night blindness. In addition, mGluRs appear to play a trophic role in development and after retinal damage, suggesting potential future therapeutic implications. WIREs Membr Transp Signal 2012, 1:641–653. doi: 10.1002/wmts.43

For further resources related to this article, please visit the WIREs website.
Probing strongly interacting W’s at the ILC with polarized beams
Authors: Ananthanarayan B. , Patra Monalisa , Poulose P.
Published: March 2012

Abstract

We study the possibility of fingerprinting a strongly interactingWboson sector which is consistent with present day LHC searches at the ILC with longitudinal as well as transversely polarized electron and positron beams. We account for the final state interaction using a suitable Omnès formalism in terms of a plausible resonance description, and carry out thorough analyses of cross sections, asymmetries and angular distributions of the W′s. We carry out a comparison with other extensions of the Standard Model, where heavy additional Z′bosons arise naturally. We also consider the effect of the strong final state interaction on a correlation that depends on$ \left( {{\phi_{ - }} - {\phi_{ + }}} \right) $, where theϕ∓are the azimuthal angles of decay leptons, and find that it is a useful discriminant.
The off-shell 4D/5D connection
Authors: Banerjee Nabamita , de Wit Bernard , Katmadas Stefanos
Published: March 2012

Abstract

A systematic off-shell reduction scheme from five to four space-time dimensions is presented for supergravity theories with eight supercharges. It is applicable to theories with higher-derivative couplings and it is used to address a number of open questions regarding BPS black holes in five dimensions. Under this reduction the 5D Weyl multiplet becomes reducible and decomposes into the 4D Weyl multiplet and an extra Kaluza-Klein vector multiplet. The emergence of the pseudoscalar field of the latter multiplet and the emergence of the 4D R-symmetry group are subtle features of the reduction. The reduction scheme enables to determine how a 5D supersymmetric Lagrangian with higher-derivative couplings decomposes upon dimensional reduction into a variety of independent 4D supersymmetric invariants, without the need for imposing field equations. In this way we establish, for example, the existence of a new N=2 supersymmetric invariant that involves the square of the Ricci tensor. Finally we resolve the questions associated with the 5D Chern-Simons terms for spinning BPS black holes and their relation to the corresponding 4D black holes.
Pauli-Fierz mass term in modified Plebanski gravity
Authors: Beke David , Palmisano Giovanni , Speziale Simone
Published: March 2012

Abstract

We study SO(4) BF theory plus a general quadratic potential, which describes a bi-metric theory of gravity. We identify the profile of the potential leading to a Pauli-Fierz mass term for the massive graviton, thereby avoiding the linearized ghost. We include the Immirzi parameter in our analysis, and find that the mass of the second graviton depends on it. At the non-perturbative level, we find a situation similar to genuine bi-gravities: even choosing the Pauli-Fierz mass term, the ghost mode propagates through the interactions. We present some simple potentials leading to two and three degrees of freedom, and discuss the difficulties of finding a ghost-free bi-gravity with seven degrees of freedom. Finally, we discuss alternative reality conditions for the case of SO(3,1) BF theory, relevant for Lorentzian signature, and give a new solution to the compatibility equation.
Evaluation of the Appendicitis Inflammatory Response Score for Patients with Acute Appendicitis
Authors: de Castro S. M. M. , Ünlü Ç. , Steller E. Ph. , van Wagensveld B. A. , Vrouenraets B. C.
Published: March 2012

Background

Acute appendicitis is still a difficult diagnosis. Scoring systems are designed to aid in the clinical assessment of patients with acute appendicitis. The Alvarado score is the most well known and best performing in validation studies. The purpose of the present study was to externally validate a recently developed appendicitis inflammatory response (AIR) score and compare it to the Alvarado score.

Methods

The present study selected consecutive patients who presented with suspicion of acute appendicitis between 2006 and 2009. Variables necessary to evaluate the scoring systems were registered. The diagnostic performance of the two scores was compared.

Results

The present study included 941 consecutive patients with suspicion of acute appendicitis. There were 410 male patients (44%) and 531 female patients (56%). The area under the receiver operating characteristic curve of the AIR score was 0.96 and significantly better than the area under the curve of 0.82 of the Alvarado score (p < 0.05). The AIR score also outperformed the Alvarado score when analyzing the more difficult patients, including women, children, and the elderly.

Conclusions

This study externally validates the AIR Score for patients with acute appendicitis. The scoring system has a high discriminating power and outperforms the Alvarado score.
The Role of a State‐Level Prevention Support System in Promoting High‐Quality Implementation and Sustainability of Evidence‐Based Programs
Authors: Rhoades Brittany L. , Bumbarger Brian K. , Moore Julia E.
Published: March 2012

Although numerous evidence‐based programs (EBPs) have been proven effective in research trials and are being widely promoted through federal, state, and philanthropic dollars, few have been “scaled up” in a manner likely to have a measurable impact on today's critical social problems. The Interactive Systems Framework for Dissemination and Implementation (ISF) explicates three systems that are critical in addressing the barriers that prevent these programs from having their intended public health impact. In this article we describe the relevance of these systems in a real‐world context with a specific focus on the Prevention Support System (PSS). We expand on the ISF model by presenting funders and policy‐makers as active and engaged stakeholders, and demonstrate how a state‐level PSS has used empirical evidence to inform general and program‐specific capacity‐building and support interactions among researchers, funders, and practitioners in Pennsylvania. By embracing this expanded ISF framework as a conceptual model for the wide‐scale dissemination and support of EBPs, and recognizing the need for a distinct state‐level PSS, Pennsylvania has created an infrastructure to effectively address the primary barriers to moving from lists of EBPs to achieving population‐level public health improvement.

Special Issue: Advances in Bridging Research and Practice Using the Interactive System Framework for Dissemination and Implementation; Guest Editors: Abraham Wandersman, Paul Flaspohler, Catherine A. Lesesne, Richard Puddy; Action Editor: Emilie Phillips Smith
Establishing and Evaluating the Key Functions of an Interactive Systems Framework Using an Assets‐Getting to Outcomes Intervention
Authors: Chinman Matthew , Acosta Joie , Ebener Patricia , Q Burkhart  , Clifford Michael , Corsello Maryann , Duffey Tim , Hunter Sarah , Jones Margaret , Lahti Michel , Malone Patrick S. , Paddock Susan , Phillips Andrea , Savell Susan , Scales Peter C. , Tellett-Royce Nancy
Published: March 2012

Community practitioners can face difficulty in achieving outcomes demonstrated by prevention science. Building a community practitioner's prevention capacity—the knowledge and skills needed to conduct critical prevention practices—could improve the quality of prevention and its outcomes. The purpose of this article is to: (1) describe how an intervention called Assets‐Getting To Outcomes (AGTO) was used to establish the key functions of the ISF and present early lessons learned from that intervention's first 6 months and (2) examine whether there is an empirical relationship between practitioner capacity at the individual level and the performance of prevention at the program level—a relationship predicted by the ISF but untested. The article describes an operationalization of the ISF in the context of a five‐year randomized controlled efficacy trial that combines two complementary models designed to build capacity: Getting To Outcomes (GTO) and Developmental Assets. The trial compares programs and individual practitioners from six community‐based coalitions using AGTO with programs and practitioners from six similar coalitions that are not. In this article, we primarily focus on what the ISF calls innovation specific capacity and discuss how the combined AGTO innovation structures and uses feedback about its capacity‐building activities, which can serve as a model for implementing the ISF. Focus group discussions used to gather lessons learned from the first 6 months of the AGTO intervention suggest that while the ISF may have been conceptualized as three distinct systems, in practice they are less distinct. Findings from the baseline wave of data collection of individual capacity and program performance suggest that practitioner capacity predicts, in part, performance of prevention programs. Empirically linking practitioner capacity and performance of prevention provides empirical support for both the ISF and AGTO.

Special Issue: Advances in Bridging Research and Practice Using the Interactive System Framework for Dissemination and Implementation; Guest Editors: Abraham Wandersman, Paul Flaspohler, Catherine A. Lesesne, Richard Puddy; Action Editor: Emilie Phillips Smith
Living situation, occupation and health‐related quality of life in adult patients with classic galactosemia
Authors: Hoffmann Björn , Dragano Nico , Schweitzer‐Krantz Susanne
Published: March 2012

Background

Galactose‐1‐phosphate uridyltransferase deficicency is well known as the underlying defect in classic galactosemia. However, little is known about the consequences of this defect beyond physical disease. Aim: To evaluate psychosocial, educational and occupational outcome as well as health‐related quality of life (HRQOL) in adult German patients with galactosemia and to compare information with data from patients with phenylketonuria as well as the general German population.

Methods

Members of the German patient support group for galactosemia received invitation, informed consent form and questionnaires by regular mail from the patient support group. Participation was voluntary.

Results

Forty‐one out of 66 invited patients participated in this study. Nearly 2/3 of the patients were singles, and the majority of patients were still living with their parents. Frequently, patients had no school leaving certificate, and 30% of the patients had never started or never completed an apprenticeship. Getting along with galactosemia was rated as ‘very good’ or ‘good’ although following the diet was a burden. Social well‐being and social functioning was lower compared to patients with PKU.

Discussion

Patients with galactosemia need a multi‐professional team not only focusing on physical and/or biochemical aspects of disease but including also psycho‐social dimensions of life.
Lysosomal delivery of therapeutic enzymes in cell models of Fabry disease
Authors: Marchesan D. , Cox T. M. , Deegan P. B.
Published: March 2012

The success of enzymatic replacement in Gaucher disease has stimulated development of targeted protein replacement for other lysosomal disorders, including Anderson‐Fabry disease, which causes fatal cardiac, cerebrovascular and renal injury: deficiency of lysosomal α‐Galactosidase A induces accumulation of glycosphingolipids. Endothelial cell storage was the primary endpoint in a clinical trial that led to market authorization. Two α‐Galactosidase A preparations are licensed worldwide, but fatal outcomes persist, with storage remaining in many tissues. We compare mechanisms of uptake of α ‐Galactosidase A into cells relevant to Fabry disease, in order to investigate if the enzyme is targeted to the lysosomes in a mannose‐6‐phosphate receptor dependent fashion, as generally believed. α ‐Galactosidase A uptake was examined in fibroblasts, four different endothelial cell models, and hepatic cells in vitro. Uptake of europium‐labeled human α ‐Galactosidase A was measured by time‐resolved fluorescence. Ligand‐specific uptake was quantified in inhibitor studies. Targeting to the lysosome was determined by precipitation and by confocal microscopy. The quantity and location of cation‐independent mannose‐6‐phosphate receptors in the different cell models were investigated using confocal microscopy. Uptake and delivery of α ‐Galactosidase A to lysosomes in fibroblasts is mediated by the canonical mannose‐6‐phosphate receptor pathway, but in endothelial cells in vitro this mechanism does not operate. Moreover, this observation is supported by a striking paucity of expression of cation independent mannose‐6‐phosphate receptors on the plasma membrane of the four endothelial cell models and by little delivery of enzyme to lysosomes, when compared with fibroblasts. If these observations are confirmed in vivo, alternative mechanisms will be needed to explain the ready clearance of storage from endothelial cells in patients undergoing enzyme replacement therapy.
In vivo catecholaminergic metabolism in the medial prefrontal cortex of ENU2 mice: an investigation of the cortical dopamine deficit in phenylketonuria
Authors: Pascucci Tiziana , Giacovazzo Giacomo , Andolina Diego , Conversi David , Cruciani Fabio , Cabib Simona , Puglisi‐Allegra Stefano
Published: March 2012

Objective

Phenylketonuria (PKU) is an inherited metabolic disease characterized by plasma hyperphenylalaninemia and several neurological symptoms that can be controlled by rigorous dietetic treatment. The cellular mechanisms underlying impaired brain functions are still unclear. It has been proposed, however, that phenylalanine interference in cognitive functions depends on impaired dopamine (DA) transmission in the prefrontal cortical area due to reduced availability of the precursor tyrosine. Here, using Pahenu2 (ENU2) mice, the genetic murine model of PKU, we investigated all metabolic steps of catecholamine neurotransmission within the medial preFrontal Cortex (mpFC), availability of the precursor tyrosine, synthesis and release, to find an easy way to reinstate normal cortical DA neurotransmission.

Methods and results

Analysis of blood and brain levels of tyrosine showed reduced plasma and cerebral levels of tyrosine in ENU2 mice. Western blot analysis demonstrated deficient tyrosine hydroxylase (TH) protein levels in mpFC of ENU2 mice. Cortical TH activity, determined in vivo by measuring the accumulation of l‐3,4‐dihydroxyphenylalanine (L‐DOPA) in mpFC after inhibition of L‐aromatic acid decarboxylase with NSD‐1015, was reduced in ENU2 mice. Finally, a very low dose of L‐DOPA, which bypasses the phenylalanine‐inhibited metabolic steps, restored DA prefrontal transmission to levels found in healthy mice.

Conclusion

The data suggests that a strategy of using tyrosine supplementation to treat PKU is unlikely to be effective, whereas small dose L‐DOPA administration is likely to have a positive therapeutic effect.
Clinical characteristics of adults with slowly progressing mucopolysaccharidosis VI: a case series
Authors: Thümler Anke , Miebach Elke , Lampe Christina , Pitz Susanne , Kamin Wolfgang , Kampmann Christoph , Link Bianca , Mengel Eugen
Published: March 2012

Objective

To assess clinical features and general health status of adult patients with mucopolysaccharidosis (MPS) VI.

Methods

This report includes the clinical history of patients older than 18 years with slowly progressing MPS VI and the retrospective analysis of the outcomes of available data collected between September 2003 and October 2008 at the Center of Pediatric and Adolescent Medicine, University Medical Center, Johannes Gutenberg‐University of Mainz, Germany. Variables included were urinary glycosaminoglycan (uGAG) level, mutation analysis, body height, forced vital capacity (FVC), 6‐minute walk test, echocardiographic findings, the need for craniocervical decompression surgery, orthopaedic findings and ophthalmological assessments.

Results

The analysis included nine patients with MPS VI aged 19‐29 years. The median age at diagnosis was 12 (range 6–20) years. At the time of the assessment (median age 25 years), median uGAG was 29 (range 15‐149) μg/mg creatinine and median height 152 (range 136–161) cm. All patients had a FVC below standard values, seven showed reduced endurance in the 6‐minute‐walk test, all had valve changes with valve replacement in three, two underwent craniocervical decompression surgery, two underwent carpal tunnel surgery, five had ear/nose/throat (ENT) interventions, seven had hip pain/dysplasia, seven had corneal clouding and two were visually impaired.

Conclusions

Although patients with slowly progressing MPS VI are a heterogeneous group showing disease manifestations in several organs, they seem to have some typical characteristics in common. Despite the attenuated clinical course, many of these patients show severe morbidity. Therefore, early diagnosis and proper follow‐up and treatment are essential.
Direct‐to‐Consumer Genetic Testing: Introduction to the Special Issue
Authors: Myers Melanie F. , Bernhardt Barbara A.
Published: March 2012

This issue of the Journal of Genetic Counseling is devoted to direct‐to‐consumer (DTC) genetic testing. The 15 articles in this special issue address practice considerations for genetic counselors and other health care professionals; the benefits and limitations of DTC genetic testing; consumer and provider attitudes towards and experience with DTC testing; and the roles and educational needs of genetic counselors and other health care providers in providing and interpreting DTC genetic testing. In this introduction to the special issue, we provide a brief background on DTC genetic testing, summarize the important contribution of the articles included in this issue, and outline the essential work that still needs to be done as genetic counselors are increasingly engaged in discussions, education, and research about DTC genetic testing.
Magnetic tracking in the operation room using the da Vinci® telemanipulator is feasible
Authors: Kenngott H. G. , Wegner I. , Neuhaus J. , Nickel F. , Fischer L. , Gehrig T. , Meinzer H. P. , Müller-Stich B. P.
Published: March 2012

In recent years, robotic assistance for surgical procedures has grown on a worldwide scale, particularly for use in more complex operations. Such operations usually require meticulous handling of tissue, involve a narrow working space and limit the surgeon’s sense of orientation in the human body. Improvement in both tissue handling and working within a narrow working space might be achieved through the use of robotic assistance. Soft tissue navigation might improve orientation by visualizing important target and risk structures intraoperatively, thereby possibly improving patient outcome. Prerequisites for navigation are its integration into the surgical workflow and accurate localization of both the instruments and patient. Magnetic tracking allows for good integration but is susceptible to distortion through metal or electro-magnetic interference, which may be caused by the operation table or a robotic system. We have investigated whether magnetic tracking can be used in combination with the da Vinci® (DV) telemanipulator in terms of stability and precision. We used a common magnetic tracking system (Aurora®, NDI Inc.) with the DV in a typical operation setup. Magnetic field distortion was evaluated using a measuring facility, with the following reference system: without any metal (R), operation table alone (T), DV in standby (D) and DV in motion (Dm). The maximum error of the entire tracking volume for R, T, D and Dm was 9.9, 32.8, 37.9 and 37.2 mm, respectively. Limiting the tracking volume to 190 mm (from cranial to caudal) resulted in a maximum error of 4.0, 8.3, 8.5 and 8.9 mm, respectively. When used in the operation room, magnetic tracking shows high errors, mainly due to the operation table. The target area should be limited to increase accuracy, which is possible for most surgical applications. The use of the da Vinci® telemanipulator only slightly aggravates the distortion and can thus be used in combination with magnetic tracking systems.
Fibrodysplasia ossificans progressiva
Authors: Stefanova I. , Grünberg C. , Gillessen-Kaesbach G.
Published: March 2012

Bei der Fibrodysplasia ossificans progressiva (FOP) handelt es sich um eine sehr seltene, autosomal-dominant vererbbare Erkrankung, die durch Ausbildung von heterotopen Ossifikationen charakterisiert ist, welche zu einer ausgeprägten Mobilitätseinschränkung führen. Angeborene Fehlbildungen von Großzehen im Sinne von Hypoplasie und fibularer Deviation werden bei den meisten Patienten beschrieben. Eine Hypoplasie der Daumen besteht bei etwa der Hälfte der Patienten. Als genetische Ursache der FOP wurden heterozygote Mutationen im ACVR1-Gen identifiziert. Wir berichten über die klinischen und molekulargenetischen Daten von 25 eigenen Patienten (3 bereits veröffentlicht) und weiteren 47 Patienten aus der Literatur mit bekannten Mutationen, bei denen klinische Daten vorlagen und stellen eine Genotyp-Phänotyp-Korrelation dar.
Data interoperability in the future of middleware
Authors: Paolucci Massimo , Souville Berrand
Published: March 2012

Data interoperability is one of the main problems of system interoperability. Indeed, it is estimated that the cost of data interoperability ranges in the billions of dollars every year. The traditional approach to data interoperability is to define mappings between different data structures and different data formats. Whereas this is surely a very important part of the problem, it is not its only aspect. Often systems need to aggregate data coming from different systems, and to reason and derive conclusions from these data. In this paper, we will review the efforts performed in the semantic web to unlock this problem and highlight trends and pitfalls.
microRNA‐210 negatively regulates LPS‐induced production of proinflammatory cytokines by targeting NF‐κB1 in murine macrophages
Authors: Qi Jianni , Qiao Yu , Wang Peng , Li Shuqing , Zhao Wei , Gao Chengjiang
Published: March 2012

Ligation of TLR4 with LPS in macrophages leads to the production of proinflammatory cytokines, which are central to eliminate viral and bacterial infection. However, uncontrolled TLR4 activation may contribute to pathogenesis of inflammatory diseases such as septic shock. In this study, we found microRNA‐210 was induced in murine macrophages by LPS. Transfection of miR‐210 mimics significantly inhibited LPS‐induced production of inflammatory cytokines. In contrast, transfection of anti‐miR‐210 inhibitors increased LPS‐induced expression of proinflammatory cytokines. Furthermore, we demonstrated that miR‐210 targets NF‐κB1. Therefore, our data identify miR‐210 as a very important feedback negative regulator for LPS‐induced production of proinflammatory cytokines.
Zebrafish p53 protein enhances the translation of its own mRNA in response to UV irradiation and CPT treatment
Authors: Zhao Xiangzhong , Wu Ning , Ding Lili , Liu Ming , Liu Haizhou , Lin Xiukun
Published: March 2012

p53 protein is an important regulatory factor involved in cell growth and development. In our previous study, we demonstrated that recombined zebrafish p53 protein could specifically bind to its own mRNA in vitro. To determine if a similar interaction exists in zebrafish and if this interaction affects zebrafish development, in the present study, we investigated the interaction of p53 protein and its mRNA in zebrafish embryos. Our results revealed that expressed zebrafish p53 protein could bind with its own mRNA in zebrafish embryos. Furthermore, the endogenous activated or ectopically expressed p53 protein could enhance the relative activity of Renilla luciferase fused with p53 3′UTR in response to UV irradiation and CPT treatment, and retarded development of zebrafish embryos was observed.
Biogenesis of Y RNA‐derived small RNAs is independent of the microRNA pathway
Authors: Nicolas Francisco Esteban , Hall Adam E. , Csorba Tibor , Turnbull Carly , Dalmay Tamas
Published: March 2012

Y RNAs are approximately 100 nucleotide long conserved cytoplasmic non‐coding RNAs, which produce smaller RNA fragments during apoptosis. Here we show that these smaller RNA molecules are also produced in non‐stressed cells and in a range of human cancerous and non‐cancerous cell types. Recent reports have speculated that the cleavage products of Y RNAs enter the microRNA pathway. We tested this hypothesis and found that Y5 and Y3 RNA fragments are Dicer independent, they are in different complexes than microRNAs and that they are not co‐immunoprecipitated with Ago2. Therefore we conclude that Y RNA fragments do not enter the microRNA pathway.
Dietary fat ingestion activates β‐endorphin neurons in the hypothalamus
Authors: Matsumura Shigenobu , Eguchi Ai , Okafuji Yoko , Tatsu Sotaro , Mizushige Takafumi , Tsuzuki Satoshi , Inoue Kazuo , Fushiki Tohru
Published: March 2012

The opioid system regulates food choice, consumption, and reinforcement processes, especially for palatable meals such as fatty food. β‐Endorphin is known as an endogenous opioid peptide produced in neurons of the hypothalamus. In this study, we found that Intralipid (fat emulsion) ingestion increased c‐fos expression in β‐endorphin neurons. However, intragastric infusion of Intralipid only slightly increased c‐fos expression 2 h after infusion. Further, dissection of glossopharyngeal nerve, innervating posterior tongue taste buds, partially but significantly decreased the Intralipid‐induced c‐fos expression. These results indicate that mainly the orosensory stimulation from fat may activate β‐endorphin neurons, thereby promoting β‐endorphin release.
Biophysical characterization of the isolated C‐terminal region of the transient receptor potential vanilloid 1
Authors: Aguado-Llera David , Bacarizo Julio , Gregorio-Teruel Lucía , Taberner Francisco J. , Cámara-Artigas Ana , Neira José L.
Published: March 2012

C‐TRPV1 and C‐TRPV1 bind by comigration in non‐denaturing gel electrophoresis (View interaction)
A new type of absorbable barbed suture for use in laparoscopic myomectomy
Authors: Angioli Roberto , Plotti Francesco , Montera Roberto , Damiani Patrizio , Terranova Corrado , Oronzi Irma , Luvero Daniela , Scaletta Giuseppe , Muzii Ludovico , Panici Pierluigi B.
Published: March 2012

Objective

To compare effectiveness, feasibility, and suturing time required between an absorbable barbed wire (V‐Loc) uterine suture and a classic continuous suture with intracorporeal knots among women undergoing laparoscopic myomectomy.

Methods

From January 2010 to February 2011, women with single symptomatic intramural myoma were prospectively enrolled in a single‐center study at a university hospital in Rome, Italy. A control group with characteristics meeting the criteria for study inclusion was retrospectively identified from the hospital databases. In the prospective group uterine wall defects were closed with V‐Loc suture, whereas in the control group they were closed by classical continuous suture with intracorporeal knots. Data were analyzed via Student t test, Mann–Whitney U test, and Fisher exact test.

Results

The mean operative time was shorter in the V‐Loc (51 ± 18.1 min) than in the control (58 ± 17.8 min) group. Suturing time was significantly lower in the V‐Loc than in the control (9.9 ± 4.3 versus 15.8 ± 4.7 min; P = 0.0004) group. Both intraoperative bleeding and drop in hemoglobin were significantly lower in the V‐Loc group (P = 0.0076 and P = 0.0176, respectively).

Conclusion

Use of a barbed suture may aid surgeons during laparoscopic suturing by reducing operative time, suturing time, and blood loss.
The Transcript-Centric Mutations in Human Genomes
Authors: Cui Peng , Lin Qiang , Ding Feng , Hu Songnian , Yu Jun
Published: March 2012

Since the human genome is mostly transcribed, genetic variations must exhibit sequence signatures reflecting the relationship between transcription processes and chromosomal structures as we have observed in unicellular organisms. In this study, a set of 646 ubiquitous expression-invariable genes (EIGs) which are present in germline cells were defined and examined based on RNA-sequencing data from multiple high-throughput transcriptomic data. We demonstrated a relationship between gene expression level and transcript-centric mutations in the human genome based on single nucleotide polymorphism (SNP) data. A significant positive correlation was shown between gene expression and mutation, where highly-expressed genes accumulate more mutations than lowly-expressed genes. Furthermore, we found four major types of transcript-centric mutations: C→T, A→G, C→G, and G→T in human genomes and identified a negative gradient of the sequence variations aligning from the 5′ end to the 3′ end of the transcription units (TUs). The periodical occurrence of these genetic variations across TUs is associated with nucleosome phasing. We propose that transcript-centric mutations are one of the major driving forces for gene and genome evolution along with creation of new genes, gene/genome duplication, and horizontal gene transfer.