bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Direction for Cardiac Regeneration Therapy
Authors: Winter Elizabeth M. , van Oorschot Angelique A.M. , Hogers Bianca , van der Graaf Linda M. , Doevendans Pieter A. , Poelmann Robert E. , Atsma Douwe E. , Gittenberger-de Groot Adriana C. , Goumans Marie Jose
Published: August 2009

Background—

Adult human epicardium-derived cells (EPDCs), transplanted into the infarcted heart, are known to improve cardiac function, mainly through paracrine protection of the surrounding tissue. We hypothesized that this effect might be further improved if these supportive EPDCs were combined with cells that could possibly supply the ischemic heart with new cardiomyocytes. Therefore, we transplanted EPDCs together with cardiomyocyte progenitor cells that can generate mature cardiomyocytes in vitro.

Methods and Results—

EPDCs and cardiomyocyte progenitor cells were isolated from human adult atrial appendages, expanded in culture, and transplanted separately or together into the infarcted mouse myocardium (total cell number, 4�10
5
). Cardiac function was determined 6 weeks later (9.4T MRI). Coculturing increased proliferation rate and production of several growth factors, indicating a mutual effect. Cotransplantation resulted in further improvement of cardiac function compared with single cell-type recipients (
P
<0.05), which themselves demonstrated better function than vehicle-injected controls (
P
<0.05). However, in contrast to our hypothesis, no graft-derived cardiomyocytes were observed within the 6-week survival, supporting that not only EPDCs but also cardiomyocyte progenitor cells acted in a paracrine manner. Because injected cell number and degree of engraftment were similar between groups, the additional functional improvement in the cotransplantation group cannot be explained by an increased amount of secreted factors but rather by an altered type of secretion.

Conclusion—

EPDCs and cardiomyocyte progenitor cells synergistically improve cardiac function after myocardial infarction, probably instigated by complementary paracrine actions. Our results demonstrate for the first time that synergistically acting cells hold great promise for future clinical regeneration therapy.
Consequences of Intraventricular Hemorrhage in a Rabbit Pup Model
Authors: Chua Caroline O. , Chahboune Halima , Braun Alex , Dummula Krishna , Chua Charles Edrick , Yu Jen , Ungvari Zoltan , Sherbany Ariel A. , Hyder Fahmeed , Ballabh Praveen
Published: August 2009

Background and Purpose—

Intraventricular hemorrhage (IVH) is a common complication of prematurity that results in neurological sequelae, including cerebral palsy, posthemorrhagic hydrocephalus, and cognitive deficits. Despite this, there is no standardized animal model exhibiting neurological consequences of IVH in prematurely delivered animals. We asked whether induction of moderate-to-severe IVH in premature rabbit pups would produce long-term sequelae of cerebral palsy, posthemorrhagic hydrocephalus, reduced myelination, and gliosis.

Methods—

The premature rabbit pups, delivered by cesarean section, were treated with intraperitoneal glycerol at 2 hours postnatal age to induce IVH. The development of IVH was diagnosed by head ultrasound at 24 hours of age. Neurobehavioral, histological, and ultrastructural evaluation and diffusion tensor imaging studies were performed at 2 weeks of age.

Results—

Although 25% of pups with IVH (IVH pups) developed motor impairment with hypertonia and 42% developed posthemorrhagic ventriculomegaly, pups without IVH (non-IVH) were unremarkable. Immunolabeling revealed reduced myelination in the white matter of IVH pups compared with saline- and glycerol-treated non-IVH controls. Reduced myelination was confirmed by Western blot analysis. There was evidence of gliosis in IVH pups. Ultrastructural studies in IVH pups showed that myelinated and unmyelinated fibers were relatively preserved except for focal axonal injury. Diffusion tensor imaging showed reduction in fractional anisotropy and white matter volume confirming white matter injury in IVH pups.

Conclusion—

The rabbit pups with IVH displayed posthemorrhagic ventriculomegaly, gliosis, reduced myelination, and motor deficits, like humans. The study highlights an instructive animal model of the neurological consequences of IVH, which can be used to evaluate strategies in the prevention and treatment of posthemorrhagic complications.
Intense Correlation Between Brain Infarction and Protein-Conjugated Acrolein
Authors: Saiki Ryotaro , Nishimura Kazuhiro , Ishii Itsuko , Omura Tomohiro , Okuyama Shigeru , Kashiwagi Keiko , Igarashi Kazuei
Published: August 2009

Background and Purpose—

We recently found that increases in plasma levels of protein-conjugated acrolein and polyamine oxidases, enzymes that produce acrolein, are good markers for stroke. The aim of this study was to determine whether the level of protein-conjugated acrolein is increased and levels of spermine and spermidine, the substrates of acrolein production, are decreased at the locus of infarction.

Methods—

A unilateral infarction was induced in mouse brain by photoinduction after injection of Rose Bengal. The volume of the infarction was analyzed using the public domain National Institutes of Health image program. The level of protein-conjugated acrolein at the locus of infarction and in plasma was measured by Western blotting and enzyme-linked immunosorbent assay, respectively. The levels of polyamines at the locus of infarction and in plasma were measured by high-performance liquid chromatography.

Results—

The level of protein-conjugated acrolein was greatly increased, and levels of spermine and spermidine were decreased at the locus of infarction at 24 hours after the induction of stroke. The size of infarction was significantly decreased by
N
-acetylcysteine, a scavenger of acrolein. It was also found that the increases in the protein-conjugated acrolein, polyamines, and polyamine oxidases in plasma were observed after the induction of stroke.

Conclusions—

The results indicate that the induction of infarction is well correlated with the increase in protein-conjugated acrolein at the locus of infarction and in plasma.
Consensus Recommendations for Transcranial Color-Coded Duplex Sonography for the Assessment of Intracranial Arteries in Clinical Trials on Acute Stroke
Authors: Nedelmann Max , Stolz Erwin , Gerriets Tibo , Baumgartner Ralf W. , Malferrari Giovanni , Seidel Guenter , Kaps Manfred
Published: August 2009

Background and Purpose—

Transcranial color-coded duplex sonography has become a standard diagnostic technique to assess the intracranial arterial status in acute stroke. It is increasingly used for the evaluation of prognosis and the success of revascularization in multicenter trials. The aim of this international consensus procedure was to develop recommendations on the methodology and documentation to be used for assessment of intracranial occlusion and for monitoring of recanalization.

Methods—

Thirty-five experts participated in the consensus process. The presented recommendations were approved during a meeting of the consensus group in October 2008 in Giessen, Germany. The project was an initiative of the German Competence Network Stroke and performed under the auspices of the Neurosonology Research Group of the World Federation of Neurology.

Results—

Recommendations are given on how examinations should be performed in the time-limited situation of acute stroke, including criteria to assess the quality of the acoustic bone window, the use of echo contrast agents, and the evaluation of intracranial vessel status. The important issues of the examiners’ training and experience, the documentation, and analysis of study results are addressed. One central aspect was the development of standardized criteria for diagnosis of arterial occlusion. A transcranial color-coded duplex sonography recanalization score based on objective hemodynamic criteria is introduced (consensus on grading intracranial flow obstruction [COGIF] score).

Conclusions—

This work presents consensus statements in an attempt to standardize the application of transcranial color-coded duplex sonography in the setting of acute stroke research, aiming to improve the reliability and reproducibility of the results of future stroke studies.
Categorizing Stroke Prognosis Using Different Stroke Scales
Authors: Govan Lindsay , Langhorne Peter , Weir Christopher J.
Published: August 2009

Background and Purpose—

Stroke severity and dependency are often categorized to allow stratification for randomization or analysis. However, there is uncertainty whether the categorizations used for different stroke scales are equivalent. We investigated the amount of information retained by categorizing severity and dependency, and whether the currently used cut-offs are equivalent across different stroke scales.

Methods—

Stroke severity and dependency have been categorized as mild, moderate, or severe. We studied 2 acute stroke unit cohorts, measuring Scandinavian Stroke Scale (SSS), modified Rankin Scale (mRS), Barthel Index (BI), and modified National Institutes of Health Stroke Scale (mNIHSS). Receiver operating characteristic (ROC) curves were examined to determine the ability of full and categorized scales to predict death and dependency. A weighted kappa analysis assessed agreement between the categorized scales.

Results—

When scales are categorized, the area under the ROC curve is significantly reduced; however, the differences are small and may not be practically important. BI, mRS, and SSS all have excellent agreement with each other when categorized, whereas mNIHSS has substantial agreement with mRS and BI.

Conclusions—

Little predictive information is lost when stroke scales are categorized. There is substantial to almost perfect agreement among categorized scales. Therefore the use and categorization of a variety of stroke severity or dependency scales is acceptable in analyses.
Taking Temperature — A Review of European Union Regulation in Nanomedicine
Authors: van Calster Geert , D'Silva Joel
Published: August 2009

Nanomedicine, the application of nanotechnology to healthcare offers numerous improvements to medical diagnosis, drug delivery, therapy and implants. The potential impact of nanomedicine is foreseen radically to change health care; however it also challenges existing perceptions, dynamics and standards relating to ethics, safety and governance. This paper introduces the emerging field of nanomedicine and then proceeds to detail the current regulatory framework and regulatory bodies in the European Union relating to medicinal products, medical devices, biologics and therapies. This is followed by a detailed analysis of two nanomedical applications in the context of regulatory challenges. The paper concludes with a discussion of the adequacy of the current regulatory regime in Europe and where problems are likely to arise as nanomedicine evolves.
The Influence of Loading Rate on the Mode III Interlaminar Fracture Toughness of Composite/Steel Bi-material Systems
Authors: Pennas D. , Cantwell W.J.
Published: August 2009

In this article, the Mode III interlaminar fracture properties of a glass/ epoxy-steel bi-material system are investigated as a function of crosshead displacement rates using the edge crack torsion (ECT) test geometry. For purposes of comparison, tests were also undertaken on the plain glass/epoxy composite. For a given crack length, it has been shown that the interlaminar fracture toughness of the bi-material system was inferior to that offered by the plain composite, an effect that is attributed to the reduced toughness of the interface between the two materials. The Mode III fracture toughness of both the plain composite and the bi-material samples exhibited a crack length dependency, with the measured value of GIIIc increasing with crack length. Verification of the trends in the experimental data was achieved by conducting a finite element analysis of the ECT specimen and good agreement was achieved. Furthermore, the interlaminar fracture toughness of the plain composite remained roughly constant over the range of crosshead displacement rates considered here, suggesting that it does not exhibit a rate-sensitive fracture behavior. In contrast, the bi-material samples exhibited very low values of Mode III fracture toughness at impact rates, associated with extensive debonding of the steel from the composite material.
Dynamic Stability Behavior of 3D Braided Composite Plates Integrated with Piezoelectric Layers
Authors: Yang Jie , Huang Xiaolin
Published: August 2009

This article presents a dynamic stability analysis of a simply supported 3D braided composite laminated plate with surface-bonded piezoelectric layers, subjected to electrical and periodic in-plane mechanical loads. The braided composite plate is produced by the four-step 1 × 1 technique. It is assumed that the yarn is transversely isotropic, and the matrix is isotropic. A fiber inclination model is used to predict the effective stiffness matrices of the braided composite laminates. Theoretical formulations are based on Reddy’s higher order shear deformation plate theory and include piezoelectric effects. Double Fourier series is employed to convert the dynamic governing equations into a linear system of Mathieu—Hill equations from which the boundary points on the unstable regions are determined by Bolotin’s method. Numerical illustrations show the influence of fiber volume fraction, braiding angle, inclination angle, static load level, applied voltage, and aspect ratio on the dynamic stability, buckling and free vibration of the braided composite plate.
Continuum Models for the Analysis of Progressive Failure in Composite Laminates
Authors: Van Der Meer F.P. , Sluys L.J.
Published: August 2009

The performance of continuum material models for mesolevel modeling of progressive failure in composite laminates is examined. Two different continuum models are used: a continuum damage model and a softening plasticity model. It is shown how mesh-independent results can be obtained with both models by introducing a viscosity term. The capability of the models to represent complex intraply failure behavior is assessed by means of an analysis of a notched plate, where interface elements are used to model delamination. Proper results from different modeling approaches are shown, but upon calibration a limitation of the continuum approach in the representation of matrix failure is encountered. With a second example, this limitation is emphasized further and explained as a consequence of the homogenization that is inherent in continuum models, irrespective of the applied failure criteria and material degradation laws.
A Comparison of Various Kinematic Models for Sandwich Shell Panels with Soft Core
Authors: Carrera E. , Brischetto S.
Published: August 2009

A large variety of classical and advanced shell theories are assessed in the present work to evaluate bending response of sandwich shell structures with soft core. The accuracy of classical, higher order, zig-zag, layer-wise, and mixed theories is compared in the case of closed form solutions of simply supported shell panels made by two external skins and an internal soft core. Thickness strain effects have been evaluated too. The various theories have been implemented in a compact and concise form by referring to Carrera’s unified formulation (CUF) for plate/shell analysis that has been, in the recent past, introduced by the first author. Shell theories accuracy has been established with respect to a geometrical parameter (length-to-thickness-ratio) and to a mechanical one (face-to-core-stiffness-ratio). Soft core cases have been mostly analyzed. Two main sources of error have been outlined, which are related to the geometrical parameter and to the mechanical one, respectively. It has been concluded that higher order theories (HOTs) can be conveniently used to reduce the error due to the geometrical parameter in thick shell cases. HOTs are instead not effective to increase the accuracy of classical theories analysis whenever the error is caused by increasing values of the mechanical parameter; layer-wise analysis becomes mandatory in this last case. Among the considered equivalent single layer theories, of particular interest are those zig-zag theories that make use of Murakami’s zig-zag function.
Effects of Modified Vermiculite on Water Absorbency and Swelling Behavior of Chitosan-g-Poly(Acrylic Acid)/Vermiculite Superabsorbent Composite
Authors: Xie Yuntao , Wang Aiqin
Published: August 2009

In this study, a series of chitosan-g-poly(acrylic acid)/vermiculite (CTS-g-PAA/VMT) superabsorbent composites containing VMT, acid-activated, ion-exchanged, and organic modified VMT were synthesized by free-radical graft polymerization in aqueous solution, using N,N’-methylenebisacrylamide as a crosslinker and ammonium persulfate as an initiator. The effects of VMT and modified VMT on equilibrium water absorbency, swelling rate, and swelling behavior in various cationic saline solutions (NaCl, CaCl2, and FeCl 3) and different pH value solution of superabsorbent composites were systematically investigated. FTIR spectroscopy confirmed that acrylic acid had been grafted onto CTS and the -OH groups of VMT participated reaction. The introduction of acid-activated, ion-exchanged, and organic modified VMT into chitosan-g-poly(acrylic acid) polymeric network could improve water absorbency and swelling rate compared with that of VMT. The water-absorbing capacity of superabsorbent composites decrease gradually with the increasing of the concentration of NaCl, CaCl2, and FeCl3 solutions from 0.01 to 10 mM. The all prepared samples have similar swelling behavior in different pH value solution and the equilibrium water absorbencies of samples keep roughly constant in the pH range from 4 to 12.
Strain Rate Effects on the Energy Absorption of Rapidly Manufactured Composite Tubes
Authors: Brighton Aaron , Forrest Mark , Starbuck Mike , Erdman Donald , Fox Bronwyn
Published: August 2009

Quasi-static and intermediate rate axial crush tests were conducted on tubular specimens of Carbon/Epoxy (Toray T700/G83C) and Glass/Polypropylene (Twintex). The quasi-static tests were conducted at 10 mm/min (1.67 × 10—4 m/s); five different crush initiators were used. Tests at intermediate rates were performed at speeds of 0.25, 0.5, 0.75, 1, 2, and 4m/s. Modes of failure and specific energy absorption (SEA) values were studied. The highest SEA measured was 86 kJ/kg. This value was observed using Carbon/Epoxy samples at quasi static rates with a 45° chamfer initiator. The highest energy absorption for Twintex tubes was observed to be 57.56kJ/kg during 45° chamfer initiated tests at 0.25m/s. Compared with steel and aluminium, SEA values of 15 and 30 kJ/kg, respectively, the benefits of using composite materials in crash structures become apparent.
Neural network solution for suboptimal control of non-holonomic chained form system
Authors: Tao Cheng  , Hanxu Sun  , Zhihua Qu  , Lewis Frank L.
Published: August 2009

In this paper, we develop fixed-final time nearly optimal control laws for a class of non-holonomic chained form systems by using neural networks to approximately solve a Hamilton—Jacobi—Bellman equation. A certain time-folding method is applied to recover uniform complete controllability for the chained form system. This method requires an innovative design of a certain dynamic control component. Using this time-folding method, the chained form system is mapped into a controllable linear system for which controllers can systematically be designed to ensure exponential or asymptotic stability as well as nearly optimal performance. The result is a neural network feedback controller that has time-varying coefficients found by a priori offline tuning. The results of this paper are demonstrated in an example.
Community Policing and Community Building
Authors: Glaser Mark A. , Denhardt Janet
Published: August 2009

This research uses the responses from more than 500 officers serving a Midwestern city to understand their perceptions of themselves, fellow officers, the police department, neighborhood organizations, and the larger community in relation to community policing. Based on this data, the authors explore how community policing might be used to create a greater convergence of purpose among citizens, neighborhoods, organizations, and the broader well-being of the community. Findings indicate that officers doubt the ability of citizens to rise above their own self-interest, but they think that they and their fellow officers can do so. Furthermore, findings suggest the need for an overarching community agenda to prevent neighborhoods from becoming “civic cocoons” and to promote convergence of purpose between neighborhoods and the broader community. Finally, this research suggests that police departments that engage in transparent decision making that carefully balances departmental and community interests are better able to encourage this collaboration.
On Men and Work
Authors: Heppner Mary J. , Heppner P. Paul
Published: August 2009

The purpose of this article is to review the literature related to men who pursue nontraditional career choices such as gender atypical occupations outside the home or being stay-at-home fathers. Key foundational findings and current studies that provide information about what factors influence men’s pursuit of nontraditional careers both in the paid labor market and as stay-at-home-fathers, as well as their experience of these important life choices, are reviewed. We then turn to specific recommendations from the literature which can inform the work of future researchers and career counselors in this area.
Sensitivity Analysis of Thickness Assumptions for Piezoelectric Plate Models
Authors: D'Ottavio Michele , Polit Olivier
Published: August 2009

This article compares different axiomatic 2D theories for linear homogeneous piezoelectric plates. Simple actuator and sensor configurations are considered of thin and thick piezoelectric ceramics working either in transverse extension (31 mode) or in shear mode (15 mode). By generalizing a previously established unified formulation, a large number of different through-thickness approximations for the in-plane displacement, the transverse displacement and the electrostatic potential are introduced. Additionally, either full 3D constitutive law or reduced constitutive equations accounting for a vanishing transverse normal stress are employed in these plate theories. By referring to an analytical Naviertype closed-form solution, a systematic assessment of various 2D models is performed. The proposed sensitivity analysis of plate theories with respect to their electromechanical response can serve as a useful guide for choosing appropriate models depending on the piezoelectric polarization scheme, the use as sensor or actuator, and the plate thickness.
When a Student Does Not Want to Be in School
Authors: Johnson Edric C.
Published: August 2009

As Richardson reminds us, “People make sense of their lives, for the most part, in terms of specific events.” The author develops a set of poems based on his autoethnography study on Children of Alcoholics (COA). As the author reads Paulo Freire through alcoholism discourse, he creates a link between COA and his own school experiences. While the author questions his desire for education, he continues to excel in his studies to overcome particular life obstacles. To raise awareness for all educators, his postmodern work attempts to show the dimensions of family alcoholism and how it might impact ones views of their own schooling experience.
Dwelling the Telecare Home
Authors: López Daniel , Sánchez-Criado Tomás
Published: August 2009

Home has become a newly fostered place for care giving in what might be called an aging in place paradigm. As a result, thinking about how the home's spatialities are configured and how they might transform caring has become an important issue for the social sciences. This article is a contribution to this line of thought and looks at being-at-home from a non-anthropocentric point of view. By focusing on the telecare cases of an ongoing ethnographic project and drawing on Heideggerian insights on dwelling and place, we coin the term habitality . We think this term is useful for two purposes: (1) to think about the home as a materially heterogeneous set of spatialities and subjectivities and (2) to understand being-at-home not as a way of living in an enclosed and protected shelter of routine activities, but as a way of combining those spatialities and subjectivities and the differences (and oddities) they might bring.
Blocking aldosterone in heart failure
Authors: Shafiq Moiz M. , Miller Alan B.
Published: August 2009

Fifty years after its discovery, aldosterone continues to stimulate interest as a therapeutic target. Early studies focused on aldosterone’s actions on hypertension, the kidney, and electrolyte handling. More recently, its actions on the heart and cardiovascular system have become more apparent. Aldosterone causes cardiac fibrosis and remodeling, and stimulates neurohormonal systems that adversely affect the cardiovascular system. Aldosterone antagonism attenuates these negative effects. Clinical studies have applied this science and demonstrated improved morbidity and mortality with aldosterone blockade, specifically in patients with chronic heart failure and patients who are postmyocardial infarction and with depressed left ventricular function. This article will address the pathophysiology of aldosterone in cardiac fibrosis and remodeling, review the current clinical trial data, and explore the application of aldosterone blockade in an expanded heart failure population. The Randomized Aldactone Evaluation Study showed that the aldosterone antagonist spironolactone reduced mortality when compared to placebo in patients with chronic advanced heart failure. Similarly, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study demonstrated a significant reduction in mortality and hospitalizations for patients randomized to the aldosterone antagonist eplerenone. A more provocative question is whether aldosterone antagonism will afford the same protection in patient populations with heart failure and preserved left ventricular function. Clinical trials are underway, and results are eagerly awaited.
Crystallization behaviour of the (Mn,Ca)CO3 solid solution in silica gel: nucleation, growth and zoning phenomena
Authors: Katsikopoulos D. , Fernández-González Á. , Prieto M.
Published: August 2009

The nucleation and growth behaviour of the (Mn,Ca)CO3 solid solution from aqueous solutions in silica hydrogel were studied at 25ºC. In order to obtain different levels of supersaturation at nucleation, experiments were carried out in diffusion columns of different lengths. Zoning phenomena, compositional heterogeneity and morphological modifications of the crystals obtained were examined by electron microprobe and scanning electron microscopy and microanalyses. The large difference between the solubility of calcite (CaCO3) and rhodochrosite (MnCO3) implies a significant preferential partitioning of Mn towards the solid. The distribution of Mn2+ and Ca2+ ions between the aqueous and solid phase demonstrates that at elevated supersaturation, this preferential partitioning is softened. The morphologies of experimentally grown individuals show a clear dependence on the composition of the parent solution. Crystals obtained from aqueous solutions with large Mn contents exhibit a relatively sharp concentric zoning along the equatorial sections. On these bases, the roles of multiple kinetic and thermodynamic factors during nucleation and growth are also discussed. Finally, an X-ray diffraction analysis of the precipitates provided no evidence of the formation of the dolomite-type ordered kutnahorite [CaMn(CO3)2] in any of the experimentalsets.
Petrology of low-temperature, ultrahigh-pressure marbles and interlayered coesite eclogites near Sanqingge, Sulu terrane, eastern China
Authors: Zhu Yong-Feng , Massonne H.-J. , Men-Fan Zhu
Published: August 2009

Marbles and interlayered coesite-bearing eclogites near the village ofSanqingge in the Sulu ultrahighpressure (UHP) terrane ofeastern China were studied to estimate their P-T evolution. Using garnet, omphacite and phengite as geothermobarometers, the coesite eclogites are calculated to have experienced P-T conditions of3.4 –3.7 GPa and ~600ºC (stage I), followed by decompression and a slight temperature decrease to 2.7–3.2 GPa and 520–560ºC respectively (stage II) and later to 2.6–2.8 GPa and ~500ºC (stage III). No water influx affected the eclogites until reaching amphibolite facies conditions of 0.5–1.3 Gpa and 595–685ºC (stage IV). As we interpret the occasional appearance ofcalcite with magnesite relics in the core as a reaction ofUHP dolomite and magnesite with Ca-rich fluids at stage IV to form CaCO3, the calculated pressure for stage I could be the maximum pressure experienced by these rocks. Thus, the crustal material ofthe Sanqingge quarry, originally sedimentary carbonates (now marbles) and interstratified basic tuffs (now eclogites), has been buried to a depth of ≥ 120 km at ~600ºC. This burial occurred in a subduction setting along a very low geotherm of 5–6ºC/km. The exhumation possibly occurred in the environment ofa subduction channel.
FcγRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions
Authors: Serezani Carlos H. , Aronoff David M. , Sitrin Robert G. , Peters-Golden Marc
Published: August 2009

Leukotriene (LT) B4 is generated in response to engagement of the Fcγ receptor (FcγR) and potently contributes to FcγR-mediated antimicrobial functions in pulmonary alveolar macrophages. In this study, we report that the LTB4 receptor leukotriene B4 receptor 1 (BLT1) redistributes from nonlipid raft (LR) to LR membrane microdomains upon immunoglobulin G–red blood cell, but not LTB4, challenge. Cholesterol depletion to disrupt LRs abolished LTB4-induced enhancement of phagocytosis, microbicidal activity, and signaling. The dependence on LR integrity for BLT1 signaling correlated with formation of a complex consisting of BLT1, its primary coupled G protein Gαi3, Src kinase, and FcγRI within LRs. This association was dependent on Src-mediated phosphorylation of BLT1. These data identify a novel form of regulation in which engagement of a macrophage immunoreceptor recruits a stimulatory G protein–coupled receptor into a LR microdomain with resultant enhanced antimicrobial signaling.
Whole genome microarray analysis, from neonatal blood cards
Authors: Hardin Jill , Finnell Richard H , Wong David , Hogan Michael E , Horovitz Joy , Shu Jenny , Shaw Gary M
Published: August 2009

Background

Neonatal blood, obtained from a heel stick and stored dry on paper cards, has been the standard for birth defects screening for 50 years. Such dried blood samples are used, primarily, for analysis of small-molecule analytes. More recently, the DNA complement of such dried blood cards has been used for targeted genetic testing, such as for single nucleotide polymorphism in cystic fibrosis. Expansion of such testing to include polygenic traits, and perhaps whole genome scanning, has been discussed as a formal possibility. However, until now the amount of DNA that might be obtained from such dried blood cards has been limiting, due to inefficient DNA recovery technology.

Results

A new technology is employed for efficient DNA release from a standard neonatal blood card. Using standard Guthrie cards, stored an average of ten years post-collection, about 1/40th of the air-dried neonatal blood specimen (two 3 mm punches) was processed to obtain DNA that was sufficient in mass and quality for direct use in microarray-based whole genome scanning. Using that same DNA release technology, it is also shown that approximately 1/250th of the original purified DNA (about 1 ng) could be subjected to whole genome amplification, thus yielding an additional microgram of amplified DNA product. That amplified DNA product was then used in microarray analysis and yielded statistical concordance of 99% or greater to the primary, unamplified DNA sample.

Conclusion

Together, these data suggest that DNA obtained from less than 10% of a standard neonatal blood specimen, stored dry for several years on a Guthrie card, can support a program of genome-wide neonatal genetic testing.
The adult boar testicular and epididymal transcriptomes
Authors: Guyonnet Benoît , Marot Guillemette , Dacheux Jean-Louis , Mercat Marie-José , Schwob Sandrine , Jaffrézic Florence , Gatti Jean-Luc
Published: August 2009

Background

Mammalians gamete production takes place in the testis but when they exit this organ, although spermatozoa have acquired a specialized and distinct morphology, they are immotile and infertile. It is only after their travel in the epididymis that sperm gain their motility and fertility. Epididymis is a crescent shaped organ adjacent to the testis that can be divided in three gross morphological regions, head (caput), body (corpus) and tail (cauda). It contains a long and unique convoluted tubule connected to the testis via the efferent ducts and finished by joining thevas deferensin its caudal part.

Results

In this study, the testis, the efferent ducts (vas efferens, VE), nine distinct successive epididymal segments and the deferent duct (vas deferens, VD) of four adult boars of known fertility were isolated and their mRNA extracted. The gene expression of each of these samples was analyzed using a pig generic 9 K nylon microarray (AGENAE program; GEO accession number: GPL3729) spotted with 8931 clones derived from normalized cDNA banks from different pig tissues including testis and epididymis. Differentially expressed transcripts were obtained with moderated t-tests and F-tests and two data clustering algorithms based either on partitioning around medoid (top down PAM) or hierarchical clustering (bottom up HCL) were combined for class discovery and gene expression analysis. Tissue clustering defined seven transcriptomic units: testis,vas efferensand five epididymal transcriptomic units. Meanwhile transcripts formed only four clusters related to the tissues. We have then used a specific statistical method to sort out genes specifically over-expressed (markers) in testis, VE or in each of the five transcriptomic units of the epididymis (including VD). The specific regional expression of some of these genes was further validated by PCR and Q-PCR. We also searched for specific pathways and functions using available gene ontology information.

Conclusion

This study described for the first time the complete transcriptomes of the testis, the epididymis, thevas efferensand thevas deferenson the same species. It described new genes or genes not yet reported over-expressed in these boar tissues, as well as new control mechanisms. It emphasizes and fulfilled the gap between studies done in rodents and human, and provides tools that will be useful for further studies on the biochemical processes responsible for the formation and maintain of the epididymal regionalization and the development of a fertile spermatozoa.
The steady-state transcriptome of the four major life-cycle stages of Trypanosoma cruzi
Authors: Minning Todd A , Weatherly D Brent , Atwood James , Orlando Ron , Tarleton Rick L
Published: August 2009

Background

Chronic chagasic cardiomyopathy is a debilitating and frequently fatal outcome of human infection with the protozoan parasite, Trypanosoma cruzi. Microarray analysis of gene expression during the T. cruzi life-cycle could be a valuable means of identifying drug and vaccine targets based on their appropriate expression patterns, but results from previous microarray studies in T. cruzi and related kinetoplastid parasites have suggested that the transcript abundances of most genes in these organisms do not vary significantly between life-cycle stages.

Results

In this study, we used whole genome, oligonucleotide microarrays to globally determine the extent to which T. cruzi regulates mRNA relative abundances over the course of its complete life-cycle. In contrast to previous microarray studies in kinetoplastids, we observed that relative transcript abundances for over 50% of the genes detected on the T. cruzi microarrays were significantly regulated during the T. cruzi life-cycle. The significant regulation of 25 of these genes was confirmed by quantitative reverse-transcriptase PCR (qRT-PCR). The T. cruzi transcriptome also mirrored published protein expression data for several functional groups. Among the differentially regulated genes were members of paralog clusters, nearly 10% of which showed divergent expression patterns between cluster members.

Conclusion

Taken together, these data support the conclusion that transcript abundance is an important level of gene expression regulation in T. cruzi. Thus, microarray analysis is a valuable screening tool for identifying stage-regulated T. cruzi genes and metabolic pathways.
Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations
Authors: Illes Sebastian , Theiss Stephan , Hartung Hans-Peter , Siebler Mario , Dihné Marcel
Published: August 2009

Background

The present work was performed to investigate the ability of two different embryonic stem (ES) cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs), progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far.

Results

While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2), only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2-4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated vGlut2 expression within presynaptic vesicles. Also those NPCs that had migrated away from adherent neural aggregates maintained their ability to generate a synchronously oscillating neuronal network, even if they were separated from adherent aggregates, dissociated and re-plated.

Conclusion

These findings suggest that the complex environment within niches and aggregates of heterogeneous neural cell populations support the generation of fully mature neurons and functional neuronal networks from ES cell-derived neural cells. In contrast, homogeneous ES cell-derived NPCs within monolayer cultures exhibited an impaired functional neuronal maturation.
Haloperidol changes mRNA expression of a QKI splice variant in human astrocytoma cells
Authors: Jiang Lin , Saetre Peter , Jazin Elena , Carlström Eva Lindholm
Published: August 2009

Background

The quaking homolog, KH domain RNA binding (mouse) (QKI) is a candidate gene for schizophrenia. Disturbed QKI mRNA expression is observed in the prefrontal cortex of patients, and some of these changes correlate to treatment with antipsychotic drugs.

To test if low doses of antipsychotic drugs can modify QKI mRNA expression, human astrocytoma (U343) and oligodendroglioma (HOG) cell lines were treated with five different antipsychotic drugs including Haloperidol, Aripiprazole, Clozapine, Olanzapine and Risperidone. Messenger RNA expression levels of splice variants QKI-5, QKI-6 and QKI-7 were measured by Real-Time PCR.

Results

Haloperidol treatment (0.2 μM) doubled QKI-7 mRNA levels in U343 cells after 6 hours (p-value < 0.02). The effect was dose dependent, and cells treated with ten times higher concentration (2 μM) responded with a five-fold and three-fold increase in QKI-7, 6 and 24 hours after treatment, respectively (p-values < 0.0001).

Conclusion

The results in U343 cells suggest that QKI-7 mRNA expression in human astrocytes is induced by Haloperidol, at concentrations similar to plasma levels relevant to clinical treatment of schizophrenia. The molecular mechanism of action of antipsychotic drugs after binding to receptors is not well known. We hypothesize that QKI regulation is involved in this mechanism.
Systemic acquired resistance in soybean is regulated by two proteins, Orthologous to Arabidopsis NPR1
Authors: Sandhu Devinder , Tasma I Made , Frasch Ryan , Bhattacharyya Madan K
Published: August 2009

Background

Systemic acquired resistance (SAR) is induced in non-inoculated leaves following infection with certain pathogenic strains. SAR is effective against many pathogens. Salicylic acid (SA) is a signaling molecule of the SAR pathway. The development of SAR is associated with the induction of pathogenesis related (PR) genes. Arabidopsis
n

on-expressor of PR1 (NPR1) is a regulatory gene of the SA signal pathway [1–3]. SAR in soybean was first reported following infection with Colletotrichum trancatum that causes anthracnose disease. We investigated if SAR in soybean is regulated by a pathway, similar to the one characterized in Arabidopsis.

Results

Pathogenesis-related gene GmPR1 is induced following treatment of soybean plants with the SAR inducer, 2,6-dichloroisonicotinic acid (INA) or infection with the oomycete pathogen, Phytophthora sojae. In P. sojae-infected plants, SAR was induced against the bacterial pathogen, Pseudomonas syringae pv. glycinea. Soybean GmNPR1-1 and GmNPR1-2 genes showed high identities to Arabidopsis NPR1. They showed similar expression patterns among the organs, studied in this investigation. GmNPR1-1 and GmNPR1-2 are the only soybean homologues of NPR1and are located in homoeologous regions. In GmNPR1-1 and GmNPR1-2 transformed Arabidopsis npr1-1 mutant plants, SAR markers: (i) PR-1 was induced following INA treatment and (ii) BGL2 following infection with Pseudomonas syringae pv. tomato (Pst), and SAR was induced following Pst infection. Of the five cysteine residues, Cys82, Cys150, Cys155, Cys160, and Cys216 involved in oligomer-monomer transition in NPR1, Cys216 in GmNPR1-1 and GmNPR1-2 proteins was substituted to Ser and Leu, respectively.

Conclusion

Complementation analyses in Arabidopsis npr1-1 mutants revealed that homoeologous GmNPR1-1 and GmNPR1-2 genes are orthologous to Arabidopsis NPR1. Therefore, SAR pathway in soybean is most likely regulated by GmNPR1 genes. Substitution of Cys216 residue, essential for oligomer-monomer transition of Arabidopsis NPR1, with Ser and Leu residues in GmNPR1-1 and GmNPR1-2, respectively, suggested that there may be differences between the regulatory mechanisms of GmNPR1 and Arabidopsis NPR proteins.
Immune correlates of CD4 decline in HIV-infected patients experiencing virologic failure before undergoing treatment interruption
Authors: Huang Kenneth H , Loutfy Mona R , Tsoukas Christos M , Bernard Nicole F
Published: August 2009

Background

The advantage of treatment interruptions (TIs) in salvage therapy remains controversial. Regardless, characterizations of the correlates of CD4 count fall during TI are important to identify since patients with virologic failure commonly stop antiretroviral (ARV) therapy. The objective of this study was to determine the predictive value of pre-TI proliferative capacity and cell surface markers for CD4 count change in HIV-infected patients experiencing virologic failure before undergoing TI.

Methods

Peripheral blood mononuclear cells (PBMCs) from 13 HIV-infected patients experiencing virologic failure at baseline time points before the TI were tested for proliferation using the 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and a Gag p55 peptide pool, staphylococcus enterotoxin B (SEB), cytomegalovirus (CMV) recall antigen, and anti-CD3 antibody as stimuli. CD28 and CD57 expression on CD4+ and CD8+ T-cells was measured.

Results

The median changes in the CD4+ T-cell count and viral load from baseline to the TI time point corresponding to the CD4 count nadir were -44 cells/mm3 {Interquartile range (IQR) -17, -104} and +85,332 copies/mL (IQR +11,198, +283,327), respectively. CD4+ T-cell proliferation to CMV, pre-TI CD4+ T-cell count, and percent CD4+CD57+ cells correlated negatively with CD4 count change during TI (r = -0.59, p = 0.045, r = -0.61, p = 0.030 and r = -0.69, p = 0.0095, respectively; Spearman correlation). The presence of HIV-specific proliferative responses was not associated with a reduced decline in CD4 count during TI.

Conclusion

The use of pre-TI immune proliferative responses and cell surface markers may have predictive value for CD4 count decline during TI.
Abdominal ultrasonography in HIV/AIDS patients in southwestern Nigeria
Authors: Obajimi Millicent O , Atalabi Mojisola O , Ogbole Godwin I , Adeniji-Sofoluwe Adenike T , Agunloye Atinuke M , Adekanmi Ademola J , Osuagwu Yvonne U , Olarinoye Sefiat A , Olusola-Bello Mojisola A , Ogunseyinde Ayotunde O , Aken'Ova Yetunde A , Adewole Isaac F
Published: August 2009

Background

Though the major target of the HIV-virus is the immune system, the frequency of abdominal disorders in HIV/AIDS patients has been reported to be second only to pulmonary disease. These abdominal manifestations may be on the increase as the use of antiretroviral therapy has increased life expectancy and improved quality of life. Ultrasonography is an easy to perform, non invasive, inexpensive and safe imaging technique that is invaluable in Africa where AIDS is most prevalent and where sophisticated diagnostic tools are not readily available. Purpose: To describe the findings and evaluate the clinical utility of abdominal ultrasonography in HIV/AIDS patients in Ibadan, Nigeria

Methods

A Prospective evaluation of the abdominal ultrasonography of 391 HIV-positive patients as well as 391 age and sex-matched HIV-negative patients were carried out at the University College Hospital, Ibadan.

Results

Of the 391 cases studied, 260 (66.5%) were females; the mean age was 38.02 years, (range 15–66 years). The disease was most prevalent in the 4th decade with an incidence of 40.4%. Compared with the HIV-negative individuals, the HIV+ group of patients had a significantly higher proportion of splenomegaly (13.5% vs. 7.7%; p < 0.01), lymphadenopathy (2.0% vs. 1.3%; p < 0.70), and renal abnormalities (8.4% vs. 3.8%; p < 0.02). There were no differences in hepatic and pancreatic abnormalities between the HIV+ and HIV- groups. There were significantly fewer gallstones in the HIV+ group (1.4% vs. 5.1%; p < 0.01).

Conclusion

AIDS is a multi-systemic disease and its demographic and clinical pattern remains the same globally. Ultrasonography is optimally suited for its clinical management especially in Africa. Its accuracy and sensitivity may be much improved with clinico-pathologic correlation which may not be readily available in developing countries; further studies may provide this much needed diagnostic algorithms.