bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of skeletal muscle lipid metabolism in rat gastrocnemius to hypothyroidism and iodothyronine administration: a putative role for FAT/CD36
Authors: Lombardi Assunta , De Matteis Rita , Moreno Maria , Napolitano Laura , Busiello Rosa Anna , Senese Rosalba , de Lange Pieter , Lanni Antonia , Goglia Fernando
Published: September 2012

Iodothyronines such as triiodothyronine (T3) and 3,5-diiodothyronine (T2) influence energy expenditure and lipid metabolism. Skeletal muscle contributes significantly to energy homeostasis, and the above iodothyronines are known to act on this tissue. However, little is known about the cellular/molecular events underlying the effects of T3and T2on skeletal muscle lipid handling. Since FAT/CD36 is involved in the utilization of free fatty acids by skeletal muscle, specifically in their import into that tissue and presumably their oxidation at the mitochondrial level, we hypothesized that related changes in lipid handling and in FAT/CD36 expression and subcellular redistribution would occur due to hypothyroidism and to T3or T2administration to hypothyroid rats. In gastrocnemius muscles isolated from hypothyroid rats, FAT/CD36 was upregulated (mRNA levels and total tissue, sarcolemmal, and mitochondrial protein levels). Administration of either T3or T2to hypothyroid rats resulted in 1) little or no change in FAT/CD36 mRNA level, 2) a decreased total FAT/CD36 protein level, and 3) further increases in FAT/CD36 protein level in sarcolemma and mitochondria. Thus, the main effect of each iodothyronine seemed to be exerted at the level of FAT/CD36 cellular distribution. The effect of further increases in FAT/CD36 protein level in sarcolemma and mitochondria was already evident at 1 h after iodothyronine administration. Each iodothyronine increased the mitochondrial fatty acid oxidation rate. However, the mechanisms underlying their rapid effects seem to differ; T2and T3each induce FAT/CD36 translocation to mitochondria, but only T2induces increases in carnitine palmitoyl transferase system activity and in the mitochondrial substrate oxidation rate.
Risk of Late Mortality and Second Malignant Neoplasms among 5-Year Survivors of Young Adult Cancer: A Report of the Childhood, Adolescent, and Young Adult Cancer Survivors Research Program
Authors: Zhang Yang , Goddard Karen , Spinelli John J. , Gotay Carolyn , McBride Mary L.
Published: September 2012

We conducted a population-based retrospective study to assess the long-term risks of overall and cause-specific mortality and second malignant neoplasm (SMN) among survivors of young adult cancer compared to the risk in British Columbia (BC) population and to evaluate the effects of demographic and clinical factors on risk. 1248 5-year survivors of young adult cancer diagnosed 1970–1995 between 20 and 24 years of age were identified from the BC Cancer Registry and followed to the end of 2007. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated. The Cox proportional hazards model was used to estimate the effects of different demographic and disease-related characteristics on the risk of death and SMN. A total of 138 deaths and 62 SMNs were observed during follow-up. The overall SMR was 5.9 (95% CI 4.9–6.9) and the absolute excess risk was 5.3 per 1,000 person-years. The overall SIR was 3.0 (95% CI 2.3–3.8). Treatment with radiation resulted in increased risks of death and SMN. These observed increased risks emphasize the importance of prevention, surveillance, and treatment of late effects in survivors of young adult cancers.
Coinhibitory Molecules in Autoimmune Diseases
Authors: Watanabe Norihiko , Nakajima Hiroshi
Published: September 2012

Coinhibitory molecules such as CTLA-4, PD-1 and BTLA negatively regulate immune responses. Multiple studies indicate that the deficiency or mutation of coinhibitory molecules leads to the development of autoimmune diseases in mice and humans, indicating that the negative signals from coinhibitory molecules are crucial for the prevention of autoimmunity. In some conditions, the administration of decoy coinhibitory receptors (e.g., CTLA-4 Ig) or mAb against coinhibitory molecules suppresses the responses of self-reactive T cells in autoimmune diseases. Therefore, modulation of coinhibitory signals seems to be an attractive approach to induce tolerance in autoimmune diseases in humans where the disease-inducing self-antigens are not known. Particularly, administration of CTLA-4 Ig has shown great promise in animal models of autoimmune diseases and has been gaining increasing attention in clinical investigation in several autoimmune diseases in humans.
DNA Repair and Cancer Therapy: Targeting APE1/Ref-1 Using Dietary Agents
Authors: Raffoul Julian J. , Heydari Ahmad R. , Hillman Gilda G.
Published: September 2012

Epidemiological studies have demonstrated the cancer protective effects of dietary agents and other natural compounds isolated from fruits, soybeans, and vegetables on neoplasia. Studies have also revealed the potential for these natural products to be combined with chemotherapy or radiotherapy for the more effective treatment of cancer. In this paper we discuss the potential for targeting the DNA base excision repair enzyme APE1/Ref-1 using dietary agents such as soy isoflavones, resveratrol, curcumin, and the vitamins ascorbate andα-tocopherol. We also discuss the potential role of soy isoflavones in sensitizing cancer cells to the effects of radiotherapy. A comprehensive review of the dual nature of APE1/Ref-1 in DNA repair and redox activation of cellular transcription factors, NF-κB and HIF-1α, is also discussed. Further research efforts dedicated to delineating the role of APE1/Ref-1 DNA repair versus redox activity in sensitizing cancer cells to conventional treatment are warranted.
An Energy-Efficient and Fault-Tolerant Convergecast Protocol in Wireless Sensor Networks
Authors: Yang Ting , Kang ChunJian , Nan Guofang
Published: September 2012

The simple graph theory is commonly employed in wireless sensor networks topology control. An inherent problem of small-granularity algorithms is the high computing complexity and large solution space when managing large-scale WSNs. Computed transmission paths are of low fault tolerance because of unattended sensor nodes and frail wireless transmitting channels. This paper uses hyper-graph theory to solve these practical problems and proposes a spanning hyper-tree algorithm (SHTa) to compute the minimum transmitting power delivery paths set for WSNs convergecast. There are three main contributions of this paper: (1) we present a novel hyper-graph model to abstract large-scale and high connectivity WSNs into a robust hyper-tree infrastructure; (2) we present a precise mathematical derivation that solves the “hyper-tree existence” problem; (3) SHTa is proposed to compute the delivery paths set, which is the minimum power transmitting convergecast hyper-tree. Variable scale hyper-edges represented as computing units limit solution space and reduce computing complexity. Mutual backup delivery paths in one hyper-edge improve the capability of fault tolerance. With experiment results, SHTa computes short latency paths with low energy consumption, compared with previous algorithms. Furthermore, in dynamic experiments scenes, SHTa retains its robust transmitting quality and presents high fault tolerance.
State Feedback Stabilization for Neutral-Type Neural Networks with Time-Varying Discrete and Unbounded Distributed Delays
Authors: Wang Yantao , Lin Xue , Zhang Xian
Published: September 2012

The problem of stabilization for a class of neutral-type neural networks with discrete and unbounded distributed delays is investigated. By introducing an appropriate Lyapunov-Krasovskii functional and using Jensen inequality technique to deal with its derivative, delay-range-dependent and rate-dependent stabilization criteria are presented in the form of LMIs with nonlinear constraints. In order to solve the nonlinear problem, a cone complementarity linearization (CCL) algorithm is offered. In addition, several numerical examples are provided to illustrate the applicability of the proposed approach.
Is Learning in Low Immersive Environments Carried over to High Immersive Environments?
Authors: Lev Dror David , Reiner Miriam
Published: September 2012

One of the more debated issues regarding training simulators is their validity for transfer of skills to sensory environments that differ from the simulator. In two experiments, the advantages of three-dimensional (3D) and collocated (Col) visual displays were evaluated in a realistic and complex visuomotor task. The two factors were evaluated independently, comparing Col-2D with dislocated-2D (experiment 1) and with Col-3D (experiment 2). As expected, in both cases the more immersive presentation condition facilitated better performance. Furthermore, improvement following training in the more immersive condition carried over to the following less immersive condition but there was no carry over in the opposing order of presentation. This is taken as an indication for the differential development of skills conditioned by the level of immersiveness of the training environment. This further suggests that learning of complex realistic tasks is not carried over from less immersive simulator to the complex sensory environment of reality, due to the large gap in sensory patterns.
Community-Based Research among Marginalized HIV Populations: Issues of Support, Resources, and Empowerment
Authors: Brondani Mario , Moniri Nardin R. , Kerston R. Paul
Published: September 2012

A research question was posed to us by a local HIV-resource organization interested in exploring the educational and service needs of those unreached. In order to properly address this inquiry, we developed a community-based participatory research by training peer-led volunteers to facilitate focus-group discussions within Aboriginal and refugees participants following an interview guide. We gathered Aboriginal people and refugees separated into three focus groups each, enrolling a total of 41 self-identified HIV-positive, 38 males. The discussions were tape recorded upon consent and lasted between 59 and 118 minutes. We analyzed the thematic information collected interactively through constant comparison. The qualitative data leading to categories, codes, and themes formed the basis for the spatial representation of a conceptual mapping. Both groups shared similar struggles in living with HIV and in properly accessing local nonmedical HIV resources and discussed their concerns towards the need for empowerment and support to take control of their health.
Osteoarticular Changes in Acromegaly
Authors: Killinger Zdenko , Kužma Martin , Sterančáková Lenka , Payer Juraj
Published: September 2012

Acromegaly is caused by hypersecretion of growth hormone (GH) and consequently of insulin-like growth factor-I (IGF-1) due to pituitary tumor. Other causes, such as increased growth-hormone releasing hormone (GHRH) production, ectopic GHRH production, and ectopic GH secretion, are rare. Growth hormone and IGF-1 play a role in the regulation of bone metabolism, but accurate effect of growth hormone excess on bone is not fully explained. The issue of osteoarticular manifestations is still very actual, due to development of complications in the majority of patients with acromegaly. Traditionally, acromegaly is considered as a cause of secondary osteoporosis. Nowadays, it is discussed if BMD as predictor of osteoporotic fractures in acromegalic patient is decreased or even normal. Thus, bone quality remains to be more important in assessment of fracture risk. GH excess leads to increased bone turnover, defined by changes of bone markers. The articular manifestations are frequent clinical complications and may be present as the earliest symptom in a significant proportion of acromegalic patients. Articular manifestations are the main causes of morbidity and immobility of these patients, and they are persistent even after successful treatment. Quick recognition of osteoarticular changes and aiming the therapy lead to decrease in complication number.
The Antiparkinsonian and Antidyskinetic Mechanisms ofMucuna pruriensin the MPTP-Treated Nonhuman Primate
Authors: Lieu Christopher A. , Venkiteswaran Kala , Gilmour Timothy P. , Rao Anand N. , Petticoffer Andrew C. , Gilbert Erin V. , Deogaonkar Milind , Manyam Bala V. , Subramanian Thyagarajan
Published: September 2012

Chronic treatment with levodopa (LD) in Parkinson's disease (PD) can cause drug induced dyskinesias.Mucuna pruriensendocarp powder (MPEP) contains several compounds including natural LD and has been reported to not cause drug-induced dyskinesias. We evaluated the effects ofMucuna pruriensto determine if its underlying mechanistic actions are exclusively due to LD. We first compared MPEP with and without carbidopa (CD), and LD+CD in hemiparkinsonian (HP) monkeys. Each treatment ameliorated parkinsonism. We then compared the neuronal firing properties of the substantia nigra reticulata (SNR) and subthalamic nucleus (STN) in HP monkeys with MPEP+CD and LD+CD to evaluate basal ganglia circuitry alterations. Both treatments decreased SNR firing rate compared to HP state. However, LD+CD treatments significantly increased SNR bursting firing patterns that were not seen with MPEP+CD treatments. No significant changes were seen in STN firing properties. We then evaluated the effects of a water extract of MPEP. Oral MPWE ameliorated parkinsonism without causing drug-induced dyskinesias. The distinctive neurophysiological findings in the basal ganglia and the ability to ameliorate parkinsonism without causing dyskinesias strongly suggest thatMucuna pruriensacts through a novel mechanism that is different from that of LD.
A New Jacobian‐Like Method for the Polyhedral Cone‐Constrained Eigenvalue Problem
Authors: Sun Guo
Published: September 2012

The eigenvalue problem over a polyhedral cone is studied in this paper. Based on the F‐B NCP function, we reformulate this problem as a system of equations and propose a Jacobian‐like method. The global convergence and local quadratic convergence of the proposed method are established under suitable assumptions. Preliminary numerical experiments for a special polyhedral cone are reported in this paper to show the validity of the proposed method.
Laser Writing of Multiscale Chiral Polymer Metamaterials
Authors: Furlani E. P. , Jee H. S. , Oh H. S. , Baev A. , Prasad P. N.
Published: September 2012

A new approach to metamaterials is presented that involves laser-based patterning of novel chiral polymer media, wherein chirality is realized at two distinct length scales, intrinsically at the molecular level and geometrically at a length scale on the order of the wavelength of the incident field. In this approach, femtosecond-pulsed laser-induced two-photon lithography (TPL) is used to pattern a photoresist-chiral polymer mixture into planar chiral shapes. Enhanced bulk chirality can be realized by tuning the wavelength-dependent chiral response at both the molecular and geometric level to ensure an overlap of their respective spectra. The approach is demonstrated via the fabrication of a metamaterial consisting of a two-dimensional array of chiral polymer-based L-structures. The fabrication process is described and modeling is performed to demonstrate the distinction between molecular and planar geometric-based chirality and the effects of the enhanced multiscale chirality on the optical response of such media. This new approach to metamaterials holds promise for the development of tunable, polymer-based optical metamaterials with low loss.
Radial Artery Free and T Graft Patency as Coronary Artery Bypass Conduit Over a 15-Year Period
Authors: Barner Hendrick B. , Bailey Marci , Guthrie Tracey J. , Pasque Michael K. , Moon Marc R. , Damiano Ralph J. , Lawton Jennifer S.
Published: September 2012

Background—

The radial artery is often used as the second arterial graft for coronary artery bypass grafting. Little is known about the differences in long-term patency between radial free and T grafts. This study was performed to determine long-term radial artery patency over a 15-year period.

Methods and Results—

Radial arteries were used as free grafts or T grafts for coronary artery bypass grafting over a 15-year period. Patients were contacted to determine if postoperative cardiac catheterization was performed and examination of any reports and films was performed. Grafts were graded as patent, luminal irregularity, or occluded. Each sequential graft was counted separately. Between September 1993 and December 2008, 13 926 patients underwent isolated coronary artery bypass grafting and 3248 patients had at least one radial artery graft used as a conduit. Catheterizations were performed at a mean of 7.4±3.8 years (range, 3 days to 14.4 years) on 372 radial artery grafts (103 free and 269 T) in 215 patients. Kaplan-Meier freedom from occlusion for radial free and T grafts at 1 and 10 years was 97.1% and 75.4% and 99.6% and 62.9%, respectively (
P
=0.146 free versus T). Kaplan-Meier survival to 15 years was not statistically different between free and T graft patients (
P
=0.5).

Conclusions—

In 215 patients with postoperative catheterization after coronary artery bypass grafting with a radial artery graft, radial free and T grafts had similar and acceptable long-term patency to support their use as a coronary artery bypass graft conduit.
Modulation of Transforming Growth Factor-β Signaling and Extracellular Matrix Production in Myxomatous Mitral Valves by Angiotensin II Receptor Blockers
Authors: Geirsson Arnar , Singh Mansher , Ali Rahmat , Abbas Hussain , Li Wei , Sanchez Juan A. , Hashim Sabet , Tellides George
Published: September 2012

Background—

Little is known about the pathophysiology of myxomatous degeneration of the mitral valve, the pathological hallmark of mitral valve prolapse, associated with symptomatic mitral regurgitation, heart failure, and death. Excess transforming growth factor (TGF)-β signaling is known to cause mitral valve degeneration and regurgitation in a mouse model of Marfan syndrome. We examined if TGF-β signaling is dysregulated in clinical specimens of sporadic mitral valve prolapse compared with explanted nondiseased mitral valves and we tested the effects of angiotensin II receptor blockers on TGF-β signaling in cultured human mitral valve cells.

Methods and Results—

Operative specimens, cultured valve tissues, and cultured valvular interstitial cells were obtained from patients with mitral valve prolapse undergoing mitral valve repair or from organ donors without mitral valve disease. Increased extracellular matrix in diseased valve tissue correlated with an upregulation of TGF-β expression and signaling as evidenced by SMAD2/3 phosphorylation. Both TGF-β ligand and signaling mediators colocalized primarily to valvular interstitial cells suggesting autocrine/paracrine activation. In cultured valve tissue, exogenous TGF-β increased basal extracellular matrix production, whereas serological neutralization of TGF-β inhibited disease-driven extracellular matrix overproduction. TGF-β-induced extracellular matrix production in cultured valvular interstitial cells was dependent on SMAD2/3 and p38 signaling and was inhibited by angiotensin II receptor blockers.

Conclusions—

TGF-β has a profibrotic role in the pathogenesis of sporadic mitral valve prolapse. Attenuation of TGF-β signaling by angiotensin II receptor blockers may represent a mechanistically based strategy to modulate the pathological progression of mitral valve prolapse in patients.
MicroRNA-145 Targeted Therapy Reduces Atherosclerosis
Authors: Lovren Fina , Pan Yi , Quan Adrian , Singh Krishna K. , Shukla Praphulla C. , Gupta Nandini , Steer Brent M. , Ingram Alistair J. , Gupta Milan , Al-Omran Mohammed , Teoh Hwee , Marsden Philip A. , Verma Subodh
Published: September 2012

Background—

MicroRNA are essential posttranscriptional modulators of gene expression implicated in various chronic diseases. Because microRNA-145 is highly expressed in vascular smooth muscle cells (VSMC) and regulates VSMC fate and plasticity, we hypothesized that it may be a novel regulator of atherosclerosis and plaque stability.

Methods and Results—

Apolipoprotein E knockout mice (
ApoE
−/−
) mice were treated with either a microRNA-145 lentivirus under the control of the smooth muscle cell (SMC)-specific promoter
SM22
α or a
SM22
α control lentivirus before commencing the Western diet for 12 weeks. The SMC-targeted microRNA-145 treatment markedly reduced plaque size in aortic sinuses, ascending aortas, and brachiocephalic arteries. It also significantly increased fibrous cap area, reduced necrotic core area, and increased plaque collagen content. Cellular plaque composition analyses revealed significantly less macrophages in
ApoE
−/−
mice treated with the SMC-specific microRNA-145. These mice also demonstrated marked increases in calponin levels and α-smooth muscle actin–positive SMC areas in their atherosclerotic lesions. Furthermore, lentiviral delivery of microRNA-145 resulted in reduced KLF4 and elevated myocardin expression in aortas from
ApoE
−/−
mice, consistent with an effect of microRNA-145 to promote a contractile phenotype in VSMC.

Conclusions—

VSMC-specific overexpression of microRNA-145 is a novel in vivo therapeutic target to limit atherosclerotic plaque morphology and cellular composition, shifting the balance toward plaque stability vs plaque rupture.
Hybrid Versus Norwood Strategies for Single-Ventricle Palliation
Authors: Baba Kenji , Kotani Yasuhiro , Chetan Devin , Chaturvedi Rajiv R. , Lee Kyong-Jin , Benson Lee N. , Grosse-Wortmann Lars , Van Arsdell Glen S. , Caldarone Christopher A. , Honjo Osami
Published: September 2012

Background—

Hybrid and Norwood strategies differ substantially in terms of stage II palliative procedures. We sought to compare these strategies with an emphasis on survival and reintervention after stage II and subsequent Fontan completion.

Methods and Results—

Of 110 neonates with functionally single-ventricle physiology who underwent stage I palliation between 2004 and 2010, 75 (69%) infants (Norwood, n=43; hybrid, n=32) who subsequently underwent stage II palliation were studied. Survival and reintervention rates after stage II palliation, anatomic and physiologic variables at pre-Fontan assessment, and Fontan outcomes were compared between the groups. Predictors for reintervention were analyzed. Freedom from death/transplant after stage II palliation was equivalent between the groups (Norwood, 80.4% versus hybrid, 85.6% at 3 years,
P
=0.66). Hybrid patients had a higher pulmonary artery (PA) reintervention rate (
P
=0.003) and lower Nakata index at pre-Fontan evaluation (
P
=0.015). Aortic arch and atrioventricular valve reinterventions were not different between the groups. Ventricular end-diastolic pressure, mean PA pressure, and ventricular function were equivalent at pre-Fontan assessment. There were no deaths after Fontan completion in either group (Norwood, n=25, hybrid, n=14).

Conclusions—

Survival after stage II palliation and subsequent Fontan completion is equivalent between the groups. The hybrid group had a higher PA reintervention rate and smaller PA size. Both strategies achieved adequate physiology for Fontan completion. Evolution of the hybrid strategy requires refinement to provide optimal PA growth.
Safe Genetic Modification of Cardiac Stem Cells Using a Site-Specific Integration Technique
Authors: Lan Feng , Liu Junwei , Narsinh Kazim H. , Hu Shijun , Han Leng , Lee Andrew S. , Karow Marisa , Nguyen Patricia K. , Nag Divya , Calos Michele P. , Robbins Robert C. , Wu Joseph C.
Published: September 2012

Background—

Human cardiac progenitor cells (hCPCs) are a promising cell source for regenerative repair after myocardial infarction. Exploitation of their full therapeutic potential may require stable genetic modification of the cells ex vivo. Safe genetic engineering of stem cells, using facile methods for site-specific integration of transgenes into known genomic contexts, would significantly enhance the overall safety and efficacy of cellular therapy in a variety of clinical contexts.

Methods and Results—

We used the phiC31 site-specific recombinase to achieve targeted integration of a triple fusion reporter gene into a known chromosomal context in hCPCs and human endothelial cells. Stable expression of the reporter gene from its unique chromosomal integration site resulted in no discernible genomic instability or adverse changes in cell phenotype. Namely, phiC31-modified hCPCs were unchanged in their differentiation propensity, cellular proliferative rate, and global gene expression profile when compared with unaltered control hCPCs. Expression of the triple fusion reporter gene enabled multimodal assessment of cell fate in vitro and in vivo using fluorescence microscopy, bioluminescence imaging, and positron emission tomography. Intramyocardial transplantation of genetically modified hCPCs resulted in significant improvement in myocardial function 2 weeks after cell delivery, as assessed by echocardiography (
P
=0.002) and MRI (
P
=0.001). We also demonstrated the feasibility and therapeutic efficacy of genetically modifying differentiated human endothelial cells, which enhanced hind limb perfusion (
P
<0.05 at day 7 and 14 after transplantation) on laser Doppler imaging.

Conclusions—

The phiC31 integrase genomic modification system is a safe, efficient tool to enable site-specific integration of reporter transgenes in progenitor and differentiated cell types.
Circulation
Editors' Picks
Authors:   The Editors
Published: September 2012

The following articles are being highlighted as part of
Circulation's
Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in
Circulation
and the
Circulation
subspecialty journals. The studies included in this article represent the most read manuscripts published on the topic of cardiovascular genetics within the last two years.
WRF Simulations of the Urban Circulation in the Salt Lake City Area for CO2 Modeling
Authors: Nehrkorn Thomas , Henderson John , Leidner Mark , Mountain Marikate , Eluszkiewicz Janusz , McKain Kathryn , Wofsy Steven
Published: September 2012

A recent National Research Council report highlighted the potential utility of atmospheric observations and models for detecting trends in concentrated emissions from localized regions, such as urban areas. The Salt Lake City (SLC), Utah, area was chosen for a pilot study to determine the feasibility of using ground-based sensors to identify trends in anthropogenic urban emissions over a range of time scales (from days to years). The Weather Research and Forecasting model (WRF) was combined with a Lagrangian particle dispersion model and an emission inventory to model carbon dioxide (CO2) concentrations that can be compared with in situ measurements. An accurate representation of atmospheric transport requires a faithful modeling of the meteorological conditions. This study examines in detail the ability of different configurations of WRF to reproduce the observed local and mesoscale circulations, and the diurnal evolution of the planetary boundary layer (PBL) in the SLC area. Observations from the Vertical Transport and Mixing field experiment in 2000 were used to examine the sensitivity of WRF results to changes in the PBL parameterization and to the inclusion of an urban canopy model (UCM). Results show that for urban locations there is a clear benefit from parameterizing the urban canopy for simulation of the PBL and near-surface conditions, particularly for temperature evolution at night. Simulation of near-surface CO2 concentrations for a 2-week period in October 2006 showed that running WRF at high resolution (1.33 km) and with a UCM also improves the simulation of observed increases in CO2 during the early evening.
Accommodating Band Students with Visual Impairments
Authors: Coates Rick Lee
Published: September 2012

This article offers a discussion about some of the accommodations and modifications used in music instruction. The focus here is on the musical tasks and challenges faced by band students with visual impairments. Research and literature reveal an interest in the topic but a lack of accessible materials for immediate use in the classroom and rehearsal. The author seeks to broaden the discussion.
Disability in the Classroom
Authors: Abramo Joseph
Published: September 2012

This article covers current trends in disability rights and raises questions about how society’s views of disability influence the music education of students in need of special education services. Brief overviews of the disability-rights movement in the United States and of federal laws pertaining to disabilities and education are included. Next, there is a discussion of the “social model of disability,” which defines disability as a social position rather than a medical condition. Finally, “people-first language” and how it applies to music teaching are examined. The article also offers some suggestions to help educators incorporate these ideas into their teaching.
From the Bandstand to the Classroom
Authors: Baxter Marsha , Santantasio Christopher
Published: September 2012

In this article, narratives of a salsa concert and a lesson with a Native American flute performer provide openings for exploring grooves and their application in the music classroom. The term groove is examined, along with some non-Western ideas about time as represented in the music of the West African Kpelle people. A sixth-grade composition project in upstate New York offers a window on nontraditional notation and compositional models that hold potential to deepen and extend students’ understanding of rhythmic structures and concepts.
Inclusive Music Teaching Strategies for Elementary-Age Children with Developmental Dyslexia
Authors: Heikkila Elizabeth , Knight Andrew
Published: September 2012

Developmental dyslexia (DD) is more prevalent as an “umbrella” disorder than many educators realize. The music educator can play a particularly useful role in helping children in the general or choral classroom cope with DD, given the temporal nature of cognitive issues inherent in the disorder. The purposes of this article are to provide a brief overview of DD and to offer teaching strategies for music educators to assist students with DD in the music classroom. Melodic and rhythmic activities are described and suggested as ways to engage children with DD as part of inclusive general music classrooms.
Quick, “Imputation-free” meta-analysis with proxy-SNPs
Authors: Meesters Christian , Leber Markus , Herold Christine , Angisch Marina , Mattheisen Manuel , Drichel Dmitriy , Lacour André , Becker Tim
Published: September 2012

Background

Meta-analysis (MA) is widely used to pool genome-wide association studies (GWASes) in order to a) increase the power to detect strong or weak genotype effects or b) as a result verification method. As a consequence of differing SNP panels among genotyping chips, imputation is the method of choice within GWAS consortia to avoid losing too many SNPs in a MA. YAMAS (Yet Another Meta Analysis Software), however, enables cross-GWAS conclusions prior to finished and polished imputation runs, which eventually are time-consuming.

Results

Here we present a fast method to avoid forfeiting SNPs present in only a subset of studies, without relying on imputation. This is accomplished by using reference linkage disequilibrium data from 1,000 Genomes/HapMap projects to find proxy-SNPs together with in-phase alleles for SNPs missing in at least one study. MA is conducted by combining association effect estimates of a SNP and those of its proxy-SNPs. Our algorithm is implemented in the MA software YAMAS. Association results from GWAS analysis applications can be used as input files for MA, tremendously speeding up MA compared to the conventional imputation approach. We show that our proxy algorithm is well-powered and yields valuable ad hoc results, possibly providing an incentive for follow-up studies. We propose our method as a quick screening step prior to imputation-based MA, as well as an additional main approach for studies without available reference data matching the ethnicities of study participants. As a proof of principle, we analyzed six dbGaP Type II Diabetes GWAS and found that the proxy algorithm clearly outperforms naïve MA on the p-value level: for 17 out of 23 we observe an improvement on the p-value level by a factor of more than two, and a maximum improvement by a factor of 2127.

Conclusions

YAMAS is an efficient and fast meta-analysis program which offers various methods, including conventional MA as well as inserting proxy-SNPs for missing markers to avoid unnecessary power loss. MA with YAMAS can be readily conducted as YAMAS provides a generic parser for heterogeneous tabulated file formats within the GWAS field and avoids cumbersome setups. In this way, it supplements the meta-analysis process.
Empirical evaluation of scoring functions for Bayesian network model selection
Authors: Liu Zhifa , Malone Brandon , Yuan Changhe
Published: September 2012

In this work, we empirically evaluate the capability of various scoring functions of Bayesian networks for recovering true underlying structures. Similar investigations have been carried out before, but they typically relied on approximate learning algorithms to learn the network structures. The suboptimal structures found by the approximation methods have unknown quality and may affect the reliability of their conclusions. Our study uses an optimal algorithm to learn Bayesian network structures from datasets generated from a set of gold standard Bayesian networks. Because all optimal algorithms always learn equivalent networks, this ensures that only the choice of scoring function affects the learned networks. Another shortcoming of the previous studies stems from their use of random synthetic networks as test cases. There is no guarantee that these networks reflect real-world data. We use real-world data to generate our gold-standard structures, so our experimental design more closely approximates real-world situations. A major finding of our study suggests that, in contrast to results reported by several prior works, the Minimum Description Length (MDL) (or equivalently, Bayesian information criterion (BIC)) consistently outperforms other scoring functions such as Akaike's information criterion (AIC), Bayesian Dirichlet equivalence score (BDeu), and factorized normalized maximum likelihood (fNML) in recovering the underlying Bayesian network structures. We believe this finding is a result of using both datasets generated from real-world applications rather than from random processes used in previous studies and learning algorithms to select high-scoring structures rather than selecting random models. Other findings of our study support existing work, e.g., large sample sizes result in learning structures closer to the true underlying structure; the BDeu score is sensitive to the parameter settings; and the fNML performs pretty well on small datasets. We also tested a greedy hill climbing algorithm and observed similar results as the optimal algorithm.
Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound study
Authors: Griffin Jennifer B , Lokomba Victor , Landis Sarah H , Thorp John M , Herring Amy H , Tshefu Antoinette K , Rogerson Stephen J , Meshnick Steven R
Published: September 2012

Background

During early pregnancy, the placenta develops to meet the metabolic demands of the foetus. The objective of this analysis was to examine the effect of malaria parasitaemia prior to 20 weeks’ gestation on subsequent changes in uterine and umbilical artery blood flow and intrauterine growth restriction.

Methods

Data were analysed from 548 antenatal visits after 20 weeks’ gestation of 128 women, which included foetal biometric measures and interrogation of uterine and umbilical artery blood flow. Linear mixed effect models estimated the effect of early pregnancy malaria parasitaemia on uterine and umbilical artery resistance indices. Log-binomial models with generalized estimating equations estimated the effect of early pregnancy malaria parasitaemia on the risk of intrauterine growth restriction.

Results

There were differential effects of early pregnancy malaria parasitaemia on uterine artery resistance by nutritional status, with decreased uterine artery resistance among nourished women with early pregnancy malaria and increased uterine artery resistance among undernourished women with early pregnancy malaria. Among primigravidae, early pregnancy malaria parasitaemia decreased umbilical artery resistance in the late third trimester, likely reflecting adaptive villous angiogenesis. In fully adjusted models, primigravidae with early pregnancy malaria parasitaemia had 3.6 times the risk of subsequent intrauterine growth restriction (95% CI: 2.1, 6.2) compared to the referent group of multigravidae with no early pregnancy malaria parasitaemia.

Conclusions

Early pregnancy malaria parasitaemia affects uterine and umbilical artery blood flow, possibly due to alterations in placentation and angiogenesis, respectively. Among primigravidae, early pregnancy malaria parasitaemia increases the risk ofintrauterinegrowth restriction. The findings support the initiation of malaria parasitaemia prevention and control efforts earlier in pregnancy.
Effects of amino acid substitutions in the VP2 B-C loop on antigenicity and pathogenicity of serotype Asia1 foot-and-mouth disease virus
Authors: Xue Mei , Wang Haiwei , Li Wan , Zhou Guohui , Tu Yabin , Yu Li
Published: September 2012

Background

Foot-and-mouth disease virus (FMDV) exhibits a high degree of antigenic variability. Studies of the antigenic diversity and determination of amino acid changes involved in this diversity are important to the design of broadly protective new vaccines. Although extensive studies have been carried out to explore the molecular basis of the antigenic variation of serotype O and serotype A FMDV, there are few reports on Asia1 serotype FMDV.

Methods

Two serotype Asia1 viruses, Asia1/YS/CHA/05 and Asia1/1/YZ/CHA/06, which show differential reactivity to the neutralizing monoclonal antibody (nMAb) 1B4, were subjected to sequence comparison. Then a reverse genetics system was used to generate mutant versions of Asia1/YS/CHA/05 followed by comparative analysis of the antigenicity, growth property and pathogenicity in the suckling mice.

Results

Three amino acid differences were observed when the structural protein coding sequences of Asia1/1/YZ/CHA/06 were compared to that of Asia1/YS/CHA/05. Site-directed mutagenesis and Immunofluorescence analysis showed that the amino acid substitution in the B-C loop of the VP2 protein at position 72 is responsible for the antigenic difference between the two Asia1 FMDV strains. Furthermore, alignment of the amino acid sequences of VP2 proteins from serotype Asia1 FMDV strains deposited in GenBank revealed that most of the serotype Asia1 FMDV strains contain an Asn residue at position 72 of VP2. Therefore, we constructed a mutant virus carrying an Asp-to-Asn substitution at position 72 and named it rD72N. Our analysis shows that the Asp-to-Asn substitution inhibited the ability of the rD72N virus to react with the MAb 1B4 in immunofluorescence and neutralization assays. In addition, this substitution decreased the growth rate of the virus in BHK-21 cells and decreased the virulence of the virus in suckling mice compared with the Asia1/YS/CHA/05 parental strain.

Conclusions

These results suggest that variations in domains other than the hyper variable VP1 G-H loop (amino acid 140 to 160) are relevant to the antigenic diversity of FMDV. In addition, amino acid substitutions in the VP2 influenced replicative ability and virulence of the virus. Thus, special consideration should be given to the VP2 protein in research on structure-function relationships and in the development of an FMDV vaccine.
Dietary glycemic index and glycemic load in relation to HbA1c in Japanese obese adults: a cross-sectional analysis of the Saku Control Obesity Program
Authors: Goto Maki , Morita Akemi , Goto Atsushi , Sasaki Satoshi , Aiba Naomi , Shimbo Takuro , Terauchi Yasuo , Miyachi Motohiko , Noda Mitsuhiko , Watanabe Shaw
Published: September 2012

Background

Dietary glycemic index or load is thought to play an important role in glucose metabolism. However, few studies have investigated the relation between glycemic index (GI) or load (GL) and glycemia in Asian populations. In this cross-sectional analysis of a randomized controlled trial, the Saku Control Obesity Program, we examined the relation between the baseline GI or GL and glycemia (HbA1c and fasting plasma glucose [FPG] levels), insulin resistance (HOMA-IR), β-cell function (HOMA-β), and other metabolic risk factors (lipid levels, diastolic and systolic blood pressure, and adiposity measures).

Methods

The participants were 227 obese Japanese women and men. We used multiple linear regression models and logistic regression models to adjust for potential confounding factors such as age, sex, visceral fat area, total energy intake, and physical activity levels.

Results

After adjustments for potential confounding factors, GI was not associated with HbA1c, but GL was positively associated with HbA1c. For increasing quartiles of GI, the adjusted mean HbA1c were 6.3%, 6.7%, 6.4%, and 6.4% (P for trend = 0.991). For increasing quartiles of GL, the adjusted mean HbA1c were 6.2%, 6.2%, 6.6%, and 6.5% (P for trend = 0.044). In addition, among participants with HbA1c ≥ 7.0%, 20 out of 28 (71%) had a high GL (≥ median); the adjusted odds ratio for HbA1c ≥ 7.0% among participants with higher GL was 3.1 (95% confidence interval [CI] = 1.2 to 8.1) compared to the participants with a lower GL (<median). Further, among 16 participants with FPG ≥ 150 mg/dL, 13 participants (81.3%) had a higher GL; the adjusted odds ratio for FPG ≥ 150 mg/dL among participants with a higher GL was 8.5 (95% confidence interval = 1.7 to 43.4) compared to those with a lower GL. In contrast, GI and GL were not associated with metabolic risk factors other than glycemia.

Conclusions

Our findings suggest that participants with poor glycemic control tend to have a higher GL in an obese Japanese population.
Genome-Wide Analysis of Pain-, Nerve- and Neurotrophin -Related Gene Expression in the Degenerating Human Annulus
Authors: Gruber Helen E , Hoelscher Gretchen L , Ingram Jane A , Hanley Edward N
Published: September 2012

Background:

In spite of its high clinical relevance, the relationship between disc degeneration and low back pain is still not well understood. Recent studies have shown that genome-wide gene expression studies utilizing ontology searches provide an efficient and valuable methodology for identification of clinically relevant genes. Here we use this approach in analysis of pain-, nerve-, and neurotrophin-related gene expression patterns in specimens of human disc tissue. Control, non-herniated clinical, and herniated clinical specimens of human annulus tissue were studied following Institutional Review Board approval.

Results:

Analyses were performed on more generated (Thompson grade IV and V) discs vs. less degenerated discs (grades I-III), on surgically operated discs vs. control discs, and on herniated vs. control discs. Analyses of more degenerated vs. less degenerated discs identified significant upregulation of well-recognized pain-related genes (bradykinin receptor B1, calcitonin gene-related peptide and catechol- 0-methyltransferase). Nerve growth factor was significantly upregulated in surgical vs. control and in herniated vs. control discs. All three analyses also found significant changes in numerous proinflammatory cytokine- and chemokine-related genes. Nerve, neurotrophin and pain-ontology searches identified many matrix, signaling and functional genes which have known importance in the disc. Immunohistochemistry was utilized to confirm the presence of calcitonin gene-related peptide, catechol-0-methyltransferase and bradykinin receptor B1 at the protein level in the human annulus.

Conclusions:

Findings point to the utility of microarray analyses in identification of pain-, neurotrophin and nerve-related genes in the disc, and point to the importance of future work exploring functional interactions between nerve and disc cells in vitro and in vivo. Nerve, pain and neurotrophin ontology searches identified numerous changes in proinflammatory cytokines and chemokines which also have significant relevance to disc biology. Since the degenerating human disc is primarily an avascular tissue site into which disc cells have contributed high levels of proinflammatory cytokines, these substances are not cleared from the tissue and remain there over time. We hypothesize that as nerves grow into the human annulus, they encounter a proinflammatory cytokine-rich milieu which may sensitize nociceptors and exacerbate pain production.
Perceptions of neighborhood social environment and drug dependence among incarcerated women and men: a cross-sectional analysis
Authors: Rogers Jessica D , Ramaswamy Megha , Cheng Chin-I , Richter Kimber , Kelly Patricia J
Published: September 2012

Background

Perception of neighborhood social environment can influence an individual’s susceptibility to drug dependence. However, this has never been examined with a jailed sample, where frequent transitions between local jails and disadvantaged neighborhoods are common. Understanding these associations could aid in the design of targeted programs to decrease drug dependence and recidivism among the incarcerated.

Methods

For this study, 596 women and men from three Kansas City jails were surveyed over the course of six months in 2010. Drug dependence was assessed with DSM-IV criteria. Independent variables included fear of one’s neighborhood, perceived level of neighborhood violence, and social capital. All data were self-reported and were analyzed using logistic regression.

Results

Controlling for gender and age, fear of neighborhood violence was associated with increased odds of having drug dependence (OR = 1.27, CI 1.02, 1.58) and a higher level of social capital prior to incarceration was associated with lower odds of drug dependence (OR = 0.65, CI 0.44, 0.96). Mental health problem diagnosis and past year intimate partner violence were significant mediating factors. Gender and race/ethnicity were significant moderating factors between neighborhood disadvantage and drug dependence.

Conclusions

Our study suggests that drug dependence programs for women and men who cycle between jails and communities require both individual- and community-level interventions. To be most effective, programs at the community-level should focus on helping specific groups navigate their communities, as well as address individual health needs associated with drug dependence.