bluuebunny/crossref_metadata_2025 huggingface dataset:
p130Cas, Crk-Associated Substrate, Plays Important Roles in Osteoclastic Bone Resorption
Authors: Nagai Yoshie , Osawa Kenji , Fukushima Hidefumi , Tamura Yukihiko , Aoki Kazuhiro , Ohya Keiichi , Yasuda Hisataka , Hikiji Hisako , Takahashi Mariko , Seta Yuji , Seo Sachiko , Kurokawa Mineo , Kato Shigeaki , Honda Hiroaki , Nakamura Ichiro , Maki Kenshi , Jimi Eijiro
Published: March 2013

p130Cas, Crk-associated substrate (Cas), is an adaptor/scaffold protein that plays a central role in actin cytoskeletal reorganization. We previously reported that p130Cas is not tyrosine-phosphorylated in osteoclasts derived from Src-deficient mice, which are congenitally osteopetrotic, suggesting that p130Cas serves as a downstream molecule of c-Src and is involved in osteoclastic bone resorption. However, the physiological role of p130Cas in osteoclasts has not yet been confirmed because the p130Cas-deficient mice displayed embryonic lethality. Osteoclast-specific p130Cas conditional knockout (p130CasΔOCL–) mice exhibit a high bone mass phenotype caused by defect in multinucleation and cytoskeleton organization causing bone resorption deficiency. Bone marrow cells from p130CasΔOCL– mice were able to differentiate into osteoclasts and wild-type cells in vitro. However, osteoclasts from p130CasΔOCL– mice failed to form actin rings and resorb pits on dentine slices. Although the initial events of osteoclast attachment, such as β3-integrin or Src phosphorylation, were intact, the Rac1 activity that organizes the actin cytoskeleton was reduced, and its distribution was disrupted in p130CasΔOCL– osteoclasts. Dedicator of cytokinesis 5 (Dock5), a Rho family guanine nucleotide exchanger, failed to associate with Src or Pyk2 in osteoclasts in the absence of p130Cas. These results strongly indicate that p130Cas plays pivotal roles in osteoclastic bone resorption. © 2013 American Society for Bone and Mineral Research.
Free‐energy differences between states with different conformational ensembles
Authors: Garate Jose Antonio , Oostenbrink Chris
Published: March 2013

Multiple conformations separated by high‐energy barriers represent a challenging problem in free‐energy calculations due to the difficulties in achieving adequate sampling. We present an application of thermodynamic integration (TI) in conjunction with the local elevation umbrella sampling (LE/US) method to improve convergence in alchemical free‐energy calculations. TI‐LE/US was applied to the guanosine triphosphate (GTP) to 8‐Br‐GTP perturbation, molecules that present high‐energy barriers between the anti and syn states and that have inverted preferences for those states. The convergence and reliability of TI‐LE/US was assessed by comparing with previous results using the enhanced‐sampling one‐step perturbation (OSP) method. A linear interpolation of the end‐state biasing potentials was sufficient to dramatically improve sampling along the chosen reaction coordinate. Conformational free‐energy differences were also computed for the syn and anti states and compared to experimental and theoretical results. Additionally, a coupled OSP with LE/US was carried out, allowing the calculation of conformational and alchemical free energies of GTP and 8‐substituted GTP analogs. © 2013 Wiley Periodicals, Inc.
Computation of magnetic circular dichroism by sum‐over‐states summations
Authors: Štěpánek Petr , Bouř Petr
Published: March 2013

Magnetic circular dichroism (MCD) spectroscopy has been established as a convenient method to study electronic structure, in particular for small symmetric organic molecules. Newer applications on more complex systems are additionally stimulated by the latest availability of precise quantum‐chemical techniques for the spectral simulations. In this work, a sum over states (SOS) summation is reexamined as an alternative to the derivative techniques for the MCD modeling. Unlike in previous works, the excited electronic states are calculated by the time‐dependent density functional theory (TDDFT). A gradient formulation of the MCD intensities is also proposed, less dependent on the origin choice than the standard expressions. The dependencies of the results on the basis set, number of electronic states, and coordinate origin are tested on model examples, including large symmetric molecules with degenerate electronic states. The results suggest that the SOS/TDDFT approach is a viable and accurate technique for spectral simulation. It may even considerably reduce the computational time, if compared with the traditional MCD computational procedures based on the response theory. © 2013 Wiley Periodicals, Inc.
Atomic force microscopy: High resolution dynamic imaging of cellular and molecular structure in health and disease
Authors: Taatjes Douglas J. , Quinn Anthony S. , Rand Jacob H. , Jena Bhanu P.
Published: March 2013

The atomic force microscope (AFM), invented in 1986, and a member of the scanning probe family of microscopes, offers the unprecedented ability to image biological samples unfixed and in a hydrated environment at high resolution. This opens the possibility to investigate biological mechanisms temporally in a heretofore unattainable resolution. We have used AFM to investigate: (1) fundamental issues in cell biology (secretion) and, (2) the pathological basis of a human thrombotic disease, the antiphospholipid syndrome (APS). These studies have incorporated the imaging of live cells at nanometer resolution, leading to discovery of the “porosome,” the universal secretory portal in cells, and a molecular understanding of membrane fusion from imaging the interaction and assembly of proteins between opposing lipid membranes. Similarly, the development of an in vitro simulacrum for investigating the molecular interactions between proteins and lipids has helped define an etiological explanation for APS. The prime importance of AFM in the success of these investigations will be presented in this manuscript, as well as a discussion of the limitations of this technique for the study of biomedical samples. J. Cell. Physiol. 228: 1949–1955, 2013. © 2013 Wiley Periodicals, Inc.
Hemophagocytosis‐mediated keratinization in oral carcinoma in situ and squamous cell carcinoma: A possible histopathogenesis of keratin pearls
Authors: Al‐Eryani Kamal , Cheng Jun , Abé Tatsuya , Yamazaki Manabu , Maruyama Satoshi , Tsuneki Masayuki , Essa Ahmed , Babkair Hamzah , Saku Takashi
Published: March 2013

Although the histopathogenetic process of keratin pearls is still poorly understood, acceleration of keratinization in squamous cell carcinoma (SCC) cells may represent one possible therapeutic avenue. Based on our histopathological observations, we have hypothesized that SCC cells are keratinized by phagocytosis of extravasated erythrocytes. To confirm this hypothesis, we firstly examined immature keratin pearls in oral carcinoma in situ (CIS) and mature ones in SCC by immunohistochemistry. Concentric dyskeratotic cells in CIS keratin pearls became positive for keratin (K) 10, K17, heme oxygenase‐1 (HO‐1), or protease activated receptor‐2 (PAR‐2), a candidate regulator for hemophagocytosis. When ZK‐1 cells, an SCC cell system, were incubated with human peripheral blood erythrocytes, or with crude and purified hemoglobins (Hbs), their erythro‐hemophagocytotic activities were confirmed by immunofluorescence. Immunofluorescence signals for K10, K17, and HO‐1 were enhanced due to hemophagocytosis in time‐dependent manners. mRNA expression levels for the three molecules were most enhanced by purified Hb, followed by crude Hb and erythrocytes. K17/K10 mRNA expression levels were more elevated when PAR‐2 was activated in ZK‐1 cells. The results indicated that immature and mature keratin pearls in CIS and SCC were generated by oxidative stresses derived from erythro‐hemophagocytosis, which might mediate HO‐1 expression and be regulated by PAR‐2. Thus, hemorrhage from the rupture of blood vessels can be one of the triggers for keratin pearl formation in oral CIS and SCC. J. Cell. Physiol. 228: 1977–1988, 2013. © 2013 Wiley Periodicals, Inc.
Opposite roles of myocardin and atrogin‐1 in L6 myoblast differentiation
Authors: Jiang Yulan , Singh Pavneet , Yin Hao , Zhou Yi‐Xia , Gui Yu , Wang Da‐Zhi , Zheng Xi‐Long ,   Smooth Muscle Research Group,   Libin Cardiovascular Institute of Alberta
Published: March 2013

L6 rat myoblasts undergo differentiation and myotube formation when cultured in medium containing a low‐concentration of serum, but the underlying mechanism is not well understood. The role of atrogin‐1, an E3 ligase with well‐characterized roles in muscle atrophy, has not been defined in muscle differentiation. Myocardin is a coactivator of serum response factor (SRF), which together promotes smooth muscle differentiation. Myocardin is transiently expressed in skeletal muscle progenitor cells with inhibitory effects on the expression of myogenin and muscle differentiation. It remains unknown whether myocardin, which undergoes ubiquitination degradation, plays a role in L6 cell differentiation. The current study aimed to investigate the potential roles of myocardin and atrogin‐1 in differentiation of L6 cells. As reported by many others, shifting to medium containing 2% serum induced myotube formation of L6 cells. Differentiation was accompanied by up‐regulation of atrogin‐1 and down‐regulation of myocardin, suggesting that both may be involved in muscle differentiation. As expected, over‐expression of atrogin‐1 stimulated the expression of troponin T and myogenin and differentiation of the L6 myoblasts. Co‐expression of myocardin with atrogin‐1 inhibited atrogin‐1‐induced myogenin expression. Over‐expression of atrogin‐1 decreased myocardin protein level, albeit without affecting its mRNA level. Small‐interfering RNA‐mediated knockdown of atrogin‐1 increased myocardin protein. Consistently, ectopic expression of myocardin inhibited myogenic differentiation. Unexpectedly, myocardin decreased the expression of atrogin‐1 without involving Foxo1. Taken together, our results have demonstrated that atrogin‐1 plays a positive role in skeletal muscle differentiation through down‐regulation of myocardin. J. Cell. Physiol. 228: 1989–1995, 2013. © 2013 Wiley Periodicals, Inc.
MicroRNA‐195 Chemosensitizes Colon Cancer Cells to the Chemotherapeutic Drug Doxorubicin by Targeting the First Binding Site of BCL2L2 mRNA
Authors: Qu Juan , Zhao Liang , Zhang Pengzhi , Wang Juan , Xu Ning , Mi Wenjuan , Jiang Xingwang , Zhang Changming , Qu Juan
Published: March 2013

The mechanisms underlying doxorubicin (Dox) resistance in colon cancer cells are not fully understood. MicroRNA (miRNA) play important roles in tumorigenesis and drug resistance. However, the relationship between miRNA and Dox resistance in colon cancer cells has not been previously explored. In this study, we utilized microRNA array and real‐time PCR to verify that miR‐127, miR‐195, miR‐22, miR‐137 were significantly down‐regulated, while miR‐21, miR‐592 were up‐regulated in both HT29/DOX and LOVO/DOX cell lines. In vitro cell viability assay showed that knockdown of miR‐195 in HT29 and LOVO cells caused a marked inhibition of Dox‐induced cytotoxicity. Moreover, we explored that miR‐195 is involved in repression of BCL2L2 expression through targeting its 3′‐untranslated region, especially the first binding site within its mRNA. Furthermore, down‐regulation of miR‐195 conferred DOX resistance in parental cells and reduced cell apoptosis activity, while over‐expression of miR‐195 sensitized resistant cells to DOX and enhanced cell apoptosis activity, all of which can be partly rescued by BCL2L2 siRNA and cDNA expression. These results may have implications for therapeutic strategies aiming to overcome colon cancer cell resistance to Dox. J. Cell. Physiol. 230: 535–545, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Acetaminophen attenuates doxorubicin‐induced cardiac fibrosis via osteopontin and GATA4 regulation: Reduction of oxidant levels
Authors: Schunke Kathryn J. , Coyle Luke , Merrill Gary F. , Denhardt David T.
Published: March 2013

It is well documented in animal and human studies that therapy with the anti‐cancer drug doxorubicin (DOX) induces fibrosis, cardiac dysfunction, and cell death. The most widely accepted mechanism of cardiac injury is through production of reactive oxygen species (ROS), which cause mitochondrial damage, sarcomere structural alterations, and altered gene expression in myocytes and fibroblasts. Here we investigated the effects of acetaminophen (APAP, N‐acetyl‐para‐aminophenol) on DOX‐induced cardiac injury and fibrosis in the presence or absence of osteopontin (OPN). H9c2 rat heart‐derived embryonic myoblasts were exposed to increasing concentrations of DOX ± APAP; cell viability, oxidative stress, and OPN transcript levels were analyzed. We found a dose‐dependent decrease in cell viability and a corresponding increase in intracellular oxidants at the tested concentrations of DOX. These effects were attenuated in the presence of APAP. RT‐PCR analysis revealed a small increase in OPN transcript levels in response to DOX, which was suppressed by APAP. When male 10–12‐week‐old mice (OPN+/+ or OPN−/−) were given weekly injections of DOX ± APAP for 4 weeks there was substantial cardiac fibrosis in OPN+/+ and, to a lesser extent, in OPN−/− mice. In both groups, APAP decreased fibrosis to near baseline levels. Activity of the pro‐survival GATA4 transcription factor was diminished by DOX in both mouse genotypes, but retained baseline activity in the presence of APAP. These effects were mediated, in part, by the ability of APAP, acting as an anti‐inflammatory agent, to decrease intracellular ROS levels, consequently diminishing the injury‐induced increase in OPN levels. J. Cell. Physiol. 228: 2006–2014, 2013. © 2013 Wiley Periodicals, Inc.
Network analysis of endogenous gene expression profiles after polyethyleneimine‐mediated DNA delivery
Authors: Martin Timothy M. , Plautz Sarah A. , Pannier Angela K.
Published: March 2013

Background

DNA delivery systems, which transport exogenous DNA to cells, have applications that include gene therapy, tissue engineering and medical devices. Although the cationic nonviral DNA carrier polyethyleneimine (PEI) has been widely studied, the molecular factors and pathways underlying PEI‐mediated DNA transfer remain largely unknown, preventing the design of more efficient delivery systems.

Methods

HEK 293 T cells were treated with polyplexes formed with PEI and pEGFPLuc encoding for green fluorescent protein (GFP). Transfected cells expressing GFP were flow‐separated from treated, untransfected cells. Gene expression profiles were obtained using Affymetrix HG‐U133 2.0 microarrays and differentially expressed genes were identified using R/Bioconductor. Gene network analysis using EGAN (exploratory gene association network) bioinformatics tools was then used to find interaction among genes and enriched gene ontology (GO) terms related to transfection. Genes identified by this method were perturbed using pharmacologic activators or inhibitors to assess their effect on DNA transfer.

Results

Microarray analysis comparing transfected cells to untransfected cells revealed 215 genes to be differentially expressed, with the majority enriched to GO processes including metabolism, response to stimulus, cell cycle, biological regulation and cellular component organization or biogenesis pathways. Gene network analysis revealed a coordinated induction of RAP1A, SCG5, PGAP1, ATF3 and NEB genes implicated in cell stress, cell cycle and cytoskeletal processes. Altering pathways with pharmacologic agents confirmed the potential role of RAP1A, SCG5 and ATF3 in transfection.

Conclusions

Microarray and gene network analyses of the sorted, transfected cell population can identify potential mediators of transfection, providing a basis for the design of improved delivery systems. Copyright © 2013 John Wiley & Sons, Ltd.
TECHNICAL EFFICIENCY IN AFRICAN AGRICULTURE: IS IT CATCHING UP OR LAGGING BEHIND?
Authors: Mugera A. , Ojede A.
Published: March 2013

This article uses recent advances in data envelopment analysis, bootstrap data envelopment analysis, to investigate whether technical efficiency in the agricultural sector of 33 African countries improved (catching up) for the period 1966–2001. We also investigate whether there is evidence of efficiency catching‐up within the five regions of Central, Eastern, Western, Northern and Southern Africa. Overall, the results show no evidence for efficiency catching‐up in the entire sample. However, efficiency differed across countries and regions with evidence of catching‐up within the East African countries. Our analyses point to the need for policies that improve technological uptake in African agriculture. Copyright © 2013 John Wiley & Sons, Ltd.
An improved synthesis of 1′‐[18F]fluoroethyl‐β‐d‐lactose ([18F]‐FEL) for positron emission tomography imaging of pancreatic cancer
Authors: Turkman Nashaat , Gelovani Juri G. , Alauddin Mian M.
Published: March 2013

Introduction

Earlier, we reported syntheses of ethyl‐β‐d‐galactopyranosyl‐(1,4′)‐2′‐deoxy‐2′‐[18F]fluoro‐β‐d‐glucopyranoside (Et‐[18F]FDL) and 1′‐[18F]fluoroethyl‐β‐d‐lactose ([18F]‐FEL) for positron emission tomography (PET) of pancreatic carcinoma. Et‐[18F]FDL requires a precursor, which involves 11 steps to synthesize and produces overall low yields. Synthesis of precursors for [18F]‐FEL requires four steps, but those precursors produced low radiochemical yields. Here, we report new precursors and an improved synthesis of [18F]‐FEL.

Method

Two precursors, 1′‐(methanesulfonyl)ethyl‐2′,3′,6′,2,3,4,6‐hepta‐O‐acetyl‐β‐d‐lactose 2a and 1′‐(p‐nitrophenyl‐sulfonyl)ethyl‐2′,3′,6′,2,3,4,6‐hepta‐O‐acetyl‐β‐d‐lactose 2b, were synthesized from lactose in four steps. Radiofluorination reactions were performed using K18F/kryptofix and the crude product [18F]‐3 was purified by HPLC. Basic hydrolysis of [18F]‐3 produced 1′‐[18F]fluoroethyl‐β‐d‐lactose [18F]‐4, which was neutralized, diluted with saline, filtered on a 0.22‐µm filter, and analyzed by radio‐TLC.

Results

The average radiochemical yields of [18F]‐4 (d. c.) from 2a and 2b were 21% (n = 6) and 65% (n = 6), respectively, with >99% radiochemical purity and specific activity of 55.5 GBq/µmol. Synthesis time was 90–95 min from the end of bombardment.

Conclusion

An improved synthesis of [18F]FEL has been achieved in high yields, with high purity and specific activity. Precursor 2b with this method should be applicable for high yield automated production in a commercial synthesis module for clinical application.
The need for data standards in zoomorphology
Authors: Vogt Lars , Nickel Michael , Jenner Ronald A. , Deans Andrew R.
Published: March 2013

eScience is a new approach to research that focuses on data mining and exploration rather than data generation or simulation. This new approach is arguably a driving force for scientific progress and requires data to be openly available, easily accessible via the Internet, and compatible with each other. eScience relies on modern standards for the reporting and documentation of data and metadata. Here, we suggest necessary components (i.e., content, concept, nomenclature, format) of such standards in the context of zoomorphology. We document the need for using data repositories to prevent data loss and how publication practice is currently changing, with the emergence of dynamic publications and the publication of digital datasets. Subsequently, we demonstrate that in zoomorphology the scientific record is still limited to published literature and that zoomorphological data are usually not accessible through data repositories. The underlying problem is that zoomorphology lacks the standards for data and metadata. As a consequence, zoomorphology cannot participate in eScience. We argue that the standardization of morphological data requires i) a standardized framework for terminologies for anatomy and ii) a formalized method of description that allows computer‐parsable morphological data to be communicable, compatible, and comparable. The role of controlled vocabularies (e.g., ontologies) for developing respective terminologies and methods of description is discussed, especially in the context of data annotation and semantic enhancement of publications. Finally, we introduce the International Consortium for Zoomorphology Standards, a working group that is open to everyone and whose aim is to stimulate and synthesize dialog about standards. It is the Consortium's ultimate goal to assist the zoomorphology community in developing modern data and metadata standards, including anatomy ontologies, thereby facilitating the participation of zoomorphology in eScience. J. Morphol., 2013. © 2013 Wiley Periodicals, Inc.
A comparative analysis of the post‐cranial skeleton of fossorial and non‐fossorial gymnophthalmid lizards
Authors: Roscito Juliana G. , Rodrigues Miguel T.
Published: March 2013

Squamates are found in a wide range of habitats and show a corresponding diversity of morphologies that can often be correlated with locomotor mode. The evolution of a snake‐like body form, frequently associated with fossoriality, from a typical lacertiform morphology involves changes in the morphology of vertebrae, girdles, and limbs; the changes are mainly manifested by the reduction or loss of limbs and body elongation. In this study, we describe the axial and appendicular skeletons of six closely related gymnophthalmid species. Three of them show a lizard‐like morphology, with a four‐digit forelimb and a five‐digit hindlimb, and the other three show a snake‐like morphology associated with a burrowing habit, with reduced limbs and a longer body in comparison to the former three species. We show that vertebral morphology is similar among the six species, with the differences being accounted for by an increase in the number of vertebrae and by the structural reduction of girdles and limbs in the snake‐like species. Skeletal morphology provides valuable information on locomotion type, physiology, diet, and other biological features. The burrowing morphology usually involves accentuated reduction of girdle and limb elements, reflecting an undulating type of locomotion in which the limbs play little or no role in propelling the body; in contrast, well‐developed limbs and girdles indicate a greater reliance on the limbs for body propulsion. Limb reduction is frequent among vertebrates, but many different phenotypes are found in species exhibiting some kind of reduction, indicating that different mechanisms and evolutionary pressures may be involved in generating the diverse morphologies. J. Morphol. 274:845–858, 2013. © 2013 Wiley Periodicals, Inc.
Advanced MR techniques in multicenter clinical trials
Authors: Ashton Edward , Riek Jonathan
Published: March 2013

MRI has had a place in the clinical trials process for more than 20 years. However, for much of that time MRI has been used primarily for subjective interpretation and relatively straightforward structural measurements. More advanced MR techniques have been considered too difficult to implement consistently across multiple sites in a single trial—this despite the fact that these techniques often provide the best window into the direct effects of targeted therapeutics. As an example, numerous compounds are currently under development whose principle effect is to temporarily or permanently alter tumor microvasculature. Changes induced by these compounds typically manifest as reductions in blood flow and vascular permeability within tumors. These changes can be measured directly using dynamic contrast‐enhanced MRI. Early studies using this technique were limited to single centers, limiting both the overall size of the studies and the rate at which they were able to accrue patients. Recent efforts, however, have demonstrated that with sufficient attention to protocol design, imaging site selection and training, and analysis standardization, it is possible to obtain consistent and high quality results using even relatively complex acquisition protocols. This article will briefly review both the benefits and the drawbacks of including advanced MR techniques in clinical trial protocols. It will then review in detail the challenges presented by the need to deploy these techniques both to large research institutions and to community imaging centers which may have little or no familiarity with them at the outset of the trial. J. Magn. Reson. Imaging 2013;37:761–769. © 2012 Wiley Periodicals, Inc.
Proton MRS in mild cognitive impairment
Authors: Kantarci Kejal
Published: March 2013

Mild cognitive impairment (MCI) is a clinical syndrome operationalized for early diagnosis and treatment of Alzheimer's disease (AD). Many individuals with MCI are at the prodromal stage of AD or other dementia. Various quantitative magnetic resonance imaging (MRI) techniques that measure the anatomic, biochemical, microstructural, functional, and blood‐flow changes are being evaluated as possible surrogate measures for early diagnosis and disease progression in MCI. The pathology underlying MCI is heterogeneous, dominated by AD, cerebrovascular disease, Lewy body disease, or a mixture of these pathologies in autopsy cohorts. Proton magnetic resonance spectroscopy (1H MRS) metabolite markers may help identify and track etiologies that typically underlie MCI in the elderly. The role of proton MRS will be critical for pathophysiological processes for which a reliable biomarker does not exist such as neuronal dysfunction, glial and microglial activation in MCI. J. Magn. Reson. Imaging 2013;37:770–777. © 2012 Wiley Periodicals, Inc.
Superselective arterial spin labeling applied for flow territory mapping in various cerebrovascular diseases
Authors: Helle Michael , Rüfer Susanne , van Osch Matthias J.P. , Nabavi Arya , Alfke Karsten , Norris David G. , Jansen Olav
Published: March 2013

In three example patients suffering from internal carotid artery occlusion, intracranial steno‐occlusive disease, and symptomatic arteriovenous malformation (AVM), a new method named superselective pseudo‐continuous arterial spin labeling (pCASL) was used in addition to clinical routine measurements. The capabilities of this method are demonstrated to gain important information in diagnosis, risk analysis, and treatment monitoring that are neither accessible by digital subtraction angiography nor by existing selective arterial spin labeling methods and thus to propose future applications in clinical routine. In all cases superselective pCASL enabled the assessment of tissue viability and of territorial brain perfusion at different levels starting from major brain feeding vessels to collateral circulation at the level of the Circle of Willis to even distal branching arteries. This made it possible to estimate the contribution of an extracranial‐intracranial bypass to the brain perfusion; to depict individual arteries to important functional brain areas; to identify en‐passant feeding vessels of an AVM and to track possible changes in their perfusion territories after intervention. J. Magn. Reson. Imaging 2013;38:496–503. © 2013 Wiley Periodicals, Inc.
Spin echo magnetic resonance imaging
Authors: Jung Bernd André , Weigel Matthias
Published: March 2013

The spin echo sequence is a fundamental pulse sequence in MRI. Many of today's applications in routine clinical use are based on this elementary sequence. In this review article, the principles of the spin echo formation are demonstrated on which the generation of the fundamental image contrasts T1, T2, and proton density is based. The basic imaging parameters repetition time (TR) and echo time (TE) and their influence on the image contrast are explained. Important properties such as the behavior in multi‐slice imaging or in the presence of flow are depicted and the basic differences with gradient echo imaging are illustrated. The characteristics of the spin echo sequence for different magnetic field strengths with respect to clinical applications are discussed. J. Magn. Reson. Imaging 2013;37:805–817. © 2013 Wiley Periodicals, Inc.
BOLD fMRI in infants under sedation: Comparing the impact of pentobarbital and propofol on auditory and language activation
Authors: Di Francesco Mark W. , Robertson Sara A. , Karunanayaka Prasanna , Holland Scott K.
Published: March 2013

Purpose

To elucidate differences in the disruption of language network function, as measured by blood oxygenation level‐dependent (BOLD) contrast functional MRI (fMRI), attributable to two common sedative agents administered to infants under clinical imaging protocols.

Materials and Methods

The sedatives pentobarbital (Nembutal) and Propofol, administered clinically to infants at 1 year of age, were compared with respect to BOLD activation profiles in response to passive story‐listening stimulation. An intermittent event‐related imaging protocol was used with which the temporal evolution of language processing resulting from this stimulation was explored.

Results

Propofol and Nembutal were found to have distinct and complementary responses to story‐listening. Propofol exhibited more activation in higher processing networks with increasing response toward the end of narrative stimulus. Nembutal, in contrast, had much more robust activation of primary and secondary sensory cortices but a decreasing response over time in fronto‐parietal default‐mode regions. This may suggest a breakdown of top‐down feedback for Propofol versus the lack of bottom‐up feed‐forward processing for Nembutal.

Conclusion

Two popular sedative agents for use in children for clinical fMRI were found to induce distinct alteration of activation patterns from a language stimulus. This has ramifications for clinical fMRI of sedated infants and encourages further study to build a framework for more confident interpretation. J. Magn. Reson. Imaging 2013;38:1184–1195. © 2013 Wiley Periodicals, Inc.
Neurogenesis in the circumventricular organs of adult mouse brains
Authors: Hourai Atsushi , Miyata Seiji
Published: March 2013

The circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), median eminence (ME), and area postrema (AP), allow parenchyma cells to sense a variety of blood‐derived substances and/or secreted peptides into blood circulation. In the present study, we examined continuous neurogenesis in the CVOs of adult mice. The immunohistochemistry of neural progenitor cell (NPC) marker proteins revealed that Math1‐ and Mash1‐positive cells were observed in the discrete regions of CVOs, including the capillary plexus in the OVLT, the internal zone of the ME, and the lateral zone in the AP. A few Mash1‐ and Math1‐positive cells were seen throughout the SFO, and many Math1‐ but not Mash1‐positive cells were observed at the arcuate nucleus. Math‐positive cells were often seen to localize in close proximity to the vasculature. Bromodeoxyuridine (BrdU) immunohistochemistry revealed the incorporation of BrdU in a subpopulation of Mash1‐, Math1‐, HuC/D‐, and microtubule‐associated protein 2 (MAP2)‐positive cells. Mash1‐ and Math1‐positive cells expressed exclusively high level of plasminogen, whereas a subpopulation of HuC/D‐ and MAP2‐positive neurons expressed low or undetectable level of plasminogen. Thus, the present study demonstrates that newborn cells express NPC marker proteins and plasminogen to localize closely at vascular matrix and moreover differentiate into neurons expressing mature neuron marker proteins, indicating that new neurons are possibly generated to integrate into new neural circuits. © 2013 Wiley Periodicals, Inc.
Raman characterization of the interactions between gliadins and anthocyanins
Authors: Taddei Paola , Zanna Nicola , Tozzi Silvia
Published: March 2013

Gliadins, the major proteins of the wheat flour, are a family of monomeric and disulphide‐bonded proteins formed by a non‐repetitive domain rich in α‐helix structures and heterogeneous repetitive domains rich in β‐reverse turns.

Gliadins may be strong food allergens, and many studies have explored the mechanisms of gluten allergenicity, with the final aim to properly modify gluten proteins in order to decrease allergen immunoreactivity.

In the present study, Raman spectroscopy was used to gain more insights into the conformational changes of gliadins upon interaction with different anthocyanins (kuromanin, callistephin, oenin, cyanin, pelargonin, malvin). Anthocyanins are powerful antioxidant molecules with anti‐carcinogenic properties and largely widespread natural colorants present in vegetables and flowers.

Raman spectroscopy demonstrated that the anthocyanins under study induce in gliadins conformational changes of different extents. The treatment with malvin, kuromanin and callistephin induced significant changes in the tyrosine environment, while pelargonin, oenin and cyanin did not. The treatment with any of the anthocyanins altered the distribution of the disulphide conformations: the gauche‐gauche‐trans conformation increased at the expenses of the gauche‐gauche‐gauche conformation. Malvin and pelargonin provoked a significant decrease of the β‐turns content. Since both the latter structural elements have been related to gluten allergenicity, anthocyanins appeared interesting molecules, in the context of the attempts to modify gliadins with the aim to decrease allergen immunoreactivity. Copyright © 2013 John Wiley & Sons, Ltd.
Checklists of methodological issues for review authors to consider when including non‐randomized studies in systematic reviews
Authors: Wells George A , Shea Beverley , Higgins Julian PT , Sterne Jonathan , Tugwell Peter , Reeves Barnaby C
Published: March 2013

Background

There is increasing interest from review authors about including non‐randomized studies (NRS) in their systematic reviews of health care interventions. This series from the Ottawa Non‐Randomized Studies Workshop consists of six papers identifying methodological issues when doing this.

Aim

To format the guidance from the preceding papers on study design and bias, confounding and meta‐analysis, selective reporting, and applicability/directness into checklists of issues for review authors to consider when including NRS in a systematic review.

Checklists

Checklists were devised providing frameworks to describe/assess: (1) study designs based on study design features; (2) risk of residual confounding and when to consider meta‐analysing data from NRS; (3) risk of selective reporting based on the Cochrane framework for detecting selective outcome reporting in trials but extended to selective reporting of analyses; and (4) directness of evidence contributed by a study to aid integration of NRS findings into summary of findings tables.

The checklists described will allow review groups to operationalize the inclusion of NRS in systematic reviews in a more consistent way. The next major step is extending the existing Cochrane Risk of Bias tool so that it can assess the risk of bias to NRS included in a review. Copyright © 2013 John Wiley & Sons, Ltd.
Non‐randomized studies as a source of complementary, sequential or replacement evidence for randomized controlled trials in systematic reviews on the effects of interventions
Authors: Schünemann Holger J. , Tugwell Peter , Reeves Barnaby C. , Akl Elie A. , Santesso Nancy , Spencer Frederick A. , Shea Beverley , Wells George , Helfand Mark
Published: March 2013

The terms applicability, generalizability, external validity and transferability are related, sometimes used interchangeably and have in common that they lack a clear and consistent definition in the classic epidemiological literature. However, all of these terms generally describe one overarching theme: whether or not available research evidence can be directly utilized to answer the healthcare questions at hand, ideally supported by a judgment about the degree of confidence for this utilization. This concept has been called directness. The objectives of this paper were to delineate how non‐randomized studies (NRS) inform judgments in relation to directness and the concepts that it encompasses in the context of systematic reviews. We will briefly review what is known and describe the theoretical and practical issues as well as offer guidance to those tackling the challenges of judging directness and using research evidence to answer healthcare questions with evidence from NRS.

In particular, we suggest a framework in which authors can use NRS as a complement, sequence or replacement for randomized controlled trials (RCTs) by focusing on judgments about the population, intervention, comparison and outcomes. Authors of systematic reviews will use NRS to complement judgments about the inconsistencies, the rationale and credibility of subgroup analysis, the baseline risk estimates for the determination of absolute benefits and downsides, and the directness of surrogate outcomes. This evidence includes contextual or supplementary evidence. Authors of systematic review and other summaries of the evidence use NRS as sequential evidence to provide evidence when insufficient evidence is available for an outcome from RCTs, but NRS evidence is available (e.g., long‐term harms). Use of evidence from NRS may also serve to replace RCT evidence when NRS provide equivalent (or potentially higher) confidence in the evidence (i.e. quality) compared to indirect evidence from RCTs. These judgments will be made in the context of other domains that influence the overall quality of the body of evidence, including the risk of bias, publication bias (i.e. limitations in the detailed study design and execution), inconsistency, imprecision and factors that increase our confidence in effects.

This article will support systematic reviewers in their interaction with decision makers, that is, those who use the systematic review to develop guidelines, address health policy makers, and make clinical decisions, by making these judgments transparent. Copyright © 2013 John Wiley & Sons, Ltd.
Psychological and Environmental Correlates of HPA Axis Functioning in Parentally Bereaved Children: Preliminary Findings
Authors: Kaplow Julie B. , Shapiro Danielle N. , Wardecker Britney M. , Howell Kathryn H. , Abelson James L. , Worthman Carol M. , Prossin Alan R.
Published: March 2013

This study examined bereaved children's HPA‐axis functioning (cortisol awakening response; CAR) in relation to psychological distress, coping, and surviving parents' grief reactions. Participants included 38 children (20 girls) with recent parental loss (previous 6 months) and 28 of their surviving caregivers (23 women) who were assessed using self‐report instruments and in‐person, semistructured interviews. Interviews involved discussions about the child's thoughts and feelings related to the loss. Participants provided 3 saliva samples at home (awakening, 30 minutes later, and evening) over 3 successive days, beginning on the day following the interview. Results show a significant relation between dampening of the child's Day 1 CAR and more symptoms of anxiety (r = −.45), depression (r = −.40), posttraumatic stress (r = −.45), and maladaptive grief (r = −.43), as well as higher levels of avoidant coping (r = −.53). Higher levels of parental maladaptive grief were also associated (r = −.47) with a dampening of the child's Day 1 CAR. Our results raise the possibility that blunted CAR may be a result of accumulating allostatic load and/or a result of emotionally challenging events (discussions regarding the deceased) and their subsequent processing (or lack thereof) within the family, which may be particularly stressful for those bereaved children experiencing high levels of psychological distress, avoidant coping, and parental maladaptive grief.
The Associations Between Coping Self‐Efficacy and Posttraumatic Stress Symptoms 10 Years Postdisaster: Differences Between Men and Women
Authors: Bosmans Mark W. G. , Benight Charles C. , van der Knaap Leontien M. , Winkel Frans Willem , van der Velden Peter G.
Published: March 2013

The mediating role of coping self‐efficacy (CSE) perceptions between disaster‐related posttraumatic stress symptoms (PSS) in the intermediate term (4 years postevent) and PSS in the long term (10 years postevent) were examined. Participants were 514 adult Dutch native residents affected by the Enschede fireworks disaster. The disaster (May, 2000) was caused by a massive explosion in a fireworks storage facility that destroyed a residential area. Multiple regression analysis and path analysis were used to examine the mediating role of CSE and whether the mediating role was the same for men and women. Age, education, disaster exposure, home destruction, optimism, and stressful life events were also taken into account. Regression analysis showed that the former variables were not associated with PSS at 10 years postevent, in contrast to PSS at 4 years, and were therefore omitted from the path analyses. CSE assessed at 10 years postdisaster partially mediated the relationship between PSS at 4 and PSS at 10 years postdisaster. Post hoc multigroup analysis showed that this effect was significantly stronger for men, whereas the association between PSS at 4 and 10 years postevent was stronger for women. PSS at 10 years postevent were better predicted among men (explained variance 59.5% vs 50.8%).
Preliminary Evidence for a Unique Role of Disgust‐Based Conditioning in Posttraumatic Stress
Authors: Badour Christal L. , Feldner Matthew T. , Blumenthal Heidemarie , Knapp Ashley
Published: March 2013

Independent lines of evidence have linked posttraumatic stress symptomatology to both peritraumatic disgust (i.e., disgust experienced during a traumatic event) and posttraumatic disgust reactivity in response to traumatic event cues among individuals exposed to traumatic events. Much of this work suggests disgust, defined as a rejection/revulsion response aimed at distancing oneself from a potential source of contamination, may be important in understanding the nature of posttraumatic stress reactions even after accounting for the more frequently studied affective states of fear and anxiety. The current investigation provided a preliminary test of a model of disgust in posttraumatic stress among a sample of 54 community‐recruited women with a history sexual victimization. Both peritraumatic disgust (r = .31) and posttraumatic disgust reactivity (r = .42) in response to an idiographic traumatic event script were significantly associated with posttraumatic stress symptom severity. After accounting for variability‐associated peritraumatic fear and posttraumatic anxious reactivity, an indirect effect of peritraumatic disgust through posttraumatic disgust reactivity also was found, suggesting that one mechanism through which peritraumatic disgust relates to posttraumatic stress is through its relation with increased posttraumatic disgust reactivity. These findings highlight the importance of further elucidating the nature of disgust in relation to traumatic events and subsequent posttraumatic stress reactions.
Effects of Different Forms of Verbal Processing on the Formation of Intrusions
Authors: Luo Pinchao , Jiang Yijie , Dang Xiaojiao , Huang Yuesheng , Chen Xuejun , Zheng Xifu
Published: March 2013

This study used the trauma film paradigm to investigate different forms of posttrauma verbal processing relevant to the formation of intrusive memories. We designed 3 experiments to investigate verbal processing that could help to reduce the formation of posttraumatic intrusions. Experiments 1 and 2 looked at the effect of several forms of verbal processing, varied in emotional foci and vantage points, on the formation of posttraumatic intrusions. Experiment 3 utilized event‐related potential (ERP) technology to control emotional focus and to further examine the effect of verbal processing from different vantage points. Data produced by Experiment 1 showed that the “what‐focus” group had fewer intrusions than the “why‐focus” group. Experiment 2 produced no significant difference between first‐ and third‐person vantage points. Results from the last experiment showed the what‐focus group was faster to judge the colors of the words in the emotional Stroop task, and the amplitude and latency of P2 for negative words were greater than neutral words in the what‐focus group. Based on the results of the experiments, participants who were led to verbalize their traumatic experiences using the what‐focus and the first‐person vantage point ended up with fewer intrusions.
Gender Differences in Posttraumatic Stress Symptoms Among OEF/OIF Veterans: An Item Response Theory Analysis
Authors: King Matthew W. , Street Amy E. , Gradus Jaimie L. , Vogt Dawne S. , Resick Patricia A.
Published: March 2013

Establishing whether men and women tend to express different symptoms of posttraumatic stress in reaction to trauma is important for both etiological research and the design of assessment instruments. Use of item response theory (IRT) can reveal how symptom reporting varies by gender and help determine if estimates of symptom severity for men and women are equally reliable. We analyzed responses to the PTSD Checklist (PCL) from 2,341 U.S. military veterans (51% female) who completed deployments in support of operations in Afghanistan and Iraq (Operation Enduring Freedom/Operation Iraqi Freedom [OEF/OIF]), and tested for differential item functioning by gender with an IRT‐based approach. Among men and women with the same overall posttraumatic stress severity, women tended to report more frequent concentration difficulties and distress from reminders whereas men tended to report more frequent nightmares, emotional numbing, and hypervigilance. These item‐level gender differences were small (on average d = 0.05), however, and had little impact on PCL measurement precision or expected total scores. For practical purposes, men's and women's severity estimates had similar reliability. This provides evidence that men and women veterans demonstrate largely similar profiles of posttraumatic stress symptoms following exposure to military‐related stressors, and some theoretical perspectives suggest this may hold in other traumatized populations.
Use of rifabutin for the treatment of a latent tuberculosis infection in a patient after solid organ transplantation
Authors: Hickey Matthew D. , Quan David J. , Chin-Hong Peter V. , Roberts John P.
Published: March 2013

Latent tuberculosis infection is an important problem for solid organ transplant recipients because of the frequency of its occurrence and its potential for reactivation. Because of the high mortality rate associated with active tuberculosis infections in transplant recipients, guidelines from the American Thoracic Society recommend treatment for latent tuberculosis in this population. However, the choice of treatments is often difficult because liver transplant recipients may be more sensitive to isoniazid hepatotoxicity, and rifampin has significant drug interactions with the calcineurin inhibitors used for immunosuppression. Two prior case reports described success with the use of rifabutin, a rifampin alternative, as part of a multidrug treatment regimen for active tuberculosis in posttransplant patients; however, there is no prior literature describing any experience with rifabutin for the treatment of latent tuberculosis in the posttransplant setting. We present a summary of tacrolimus drug levels and corresponding dose requirements for a single posttransplant patient during the administration of 3 different latent tuberculosis drug regimens: rifampin alone, rifampin plus ketoconazole, and rifabutin. In this patient's case, rifabutin allowed the maintenance of adequate tacrolimus levels, although an approximate 2.5-fold increase in the dose was required. Rifampin alone was associated with inadequate immunosuppressant levels, and rifampin plus ketoconazole was associated with a problematically prolonged QT interval and concerns about inadequate tuberculosis treatment. Liver Transpl 19:457–461, 2013. © 2013 AASLD.