bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential MHC class I expression in distinct leukocyte subsets
Authors: Greene Justin M , Wiseman Roger W , Lank Simon M , Bimber Benjamin N , Karl Julie A , Burwitz Benjamin J , Lhost Jennifer J , Hawkins Oriana E , Kunstman Kevin J , Broman Karl W , Wolinsky Steven M , Hildebrand William H , O'Connor David H
Published: July 2011

Background

MHC class I proteins are partly responsible for shaping the magnitude and focus of the adaptive cellular immune response. In humans, conventional wisdom suggests that the HLA-A, -B, and -C alleles are equally expressed on the majority of cell types. While we currently have a thorough understanding of how total MHC class I expression varies in different tissues, it has been difficult to examine expression of single MHC class I alleles due to the homogeneity of MHC class I sequences. It is unclear how cDNA species are expressed in distinct cell subsets in humans and particularly in macaques which transcribe upwards of 20 distinct MHC class I alleles at variable levels.

Results

We examined MHC gene expression in human and macaque leukocyte subsets. In humans, while we detected overall differences in locus transcription, we found that transcription of MHC class I genes was consistent across the leukocyte subsets we studied with only small differences detected. In contrast, transcription of certain MHC cDNA species in macaques varied dramatically by up to 45% between different subsets. Although the Mafa-B*134:02 RNA is virtually undetectable in CD4+ T cells, it represents over 45% of class I transcripts in CD14+ monocytes. We observed parallel MHC transcription differences in rhesus macaques. Finally, we analyzed expression of select MHC proteins at the cell surface using fluorescent peptides. This technique confirmed results from the transcriptional analysis and demonstrated that other MHC proteins, known to restrict SIV-specific responses, are also differentially expressed among distinct leukocyte subsets.

Conclusions

We assessed MHC class I transcription and expression in human and macaque leukocyte subsets. Until now, it has been difficult to examine MHC class I allele expression due to the similarity of MHC class I sequences. Using two novel techniques we showed that expression varies among distinct leukocyte subsets of macaques but does not vary dramatically in the human cell subsets we examined. These findings suggest pathogen tropism may have a profound impact on the shape and focus of the MHC class I restricted CD8+ T cell response in macaques.
Seven days of doxycycline is an effective treatment for asymptomatic rectal Chlamydia trachomatis infection
Authors: Elgalib A , Alexander S , Tong C Y W , White J A
Published: July 2011

There are no evidence-based guidelines for the specific management of rectal Chlamydia trachomatis (CT) infection. All men who have sex with men (MSM) diagnosed with asymptomatic rectal CT by nucleic acid amplification test (NAAT) at a large London genitourinary (GU) medicine clinic between September 2006 and September 2009 were offered oral doxycycline 100 mg twice daily for seven days and invited for a test of cure (TOC) by CT NAAT four weeks after treatment. A total of 487 asymptomatic rectal CT infections were diagnosed and analysis was restricted to 165 TOCs from men whose only treatment had been doxycycline for seven days. The median time post-treatment for TOC was 45 days (interquartile range [IQR], 34–88). Only two patients tested CT-positive at follow-up. One had taken doxycycline only for three days; the other attended for TOC 240 days after the completion of doxycycline treatment and at this time presented with new symptoms in the context of ongoing high sexual risk. Our findings show that doxycycline 100 mg twice daily for seven days is highly effective treatment for asymptomatic rectal CT infection, achieving clearance of CT in 98.8% (163/165; 95% CI 95.4–99.9%) of cases. We advocate doxycycline for seven days as first-line therapy for asymptomatic rectal CT.
Dynamic Portfolio Optimization with Transaction Costs: Heuristics and Dual Bounds
Authors: Brown David B. , Smith James E.
Published: July 2011

We consider the problem of dynamic portfolio optimization in a discrete-time, finite-horizon setting. Our general model considers risk aversion, portfolio constraints (e.g., no short positions), return predictability, and transaction costs. This problem is naturally formulated as a stochastic dynamic program. Unfortunately, with nonzero transaction costs, the dimension of the state space is at least as large as the number of assets, and the problem is very difficult to solve with more than one or two assets. In this paper, we consider several easy-to-compute heuristic trading strategies that are based on optimizing simpler models. We complement these heuristics with upper bounds on the performance with an optimal trading strategy. These bounds are based on the dual approach developed in Brown et al. (Brown, D. B., J. E. Smith, P. Sun. 2009. Information relaxations and duality in stochastic dynamic programs. Oper. Res. 58(4) 785–801). In this context, these bounds are given by considering an investor who has access to perfect information about future returns but is penalized for using this advance information. These heuristic strategies and bounds can be evaluated using Monte Carlo simulation. We evaluate these heuristics and bounds in numerical experiments with a risk-free asset and 3 or 10 risky assets. In many cases, the performance of the heuristic strategy is very close to the upper bound, indicating that the heuristic strategies are very nearly optimal.

This paper was accepted by Dimitris Bertsimas, optimization.
Mouse models for inherited endocrine and metabolic disorders
Authors: Piret Siân E , Thakker Rajesh V
Published: July 2011

In vivo models represent important resources for investigating the physiological mechanisms underlying endocrine and metabolic disorders, and for pre-clinical translational studies that may include the assessments of new treatments. In the study of endocrine diseases, which affect multiple organs, in vivo models provide specific advantages over in vitro models, which are limited to investigation of isolated systems. In recent years, the mouse has become the popular choice for developing such in vivo mammalian models, as it has a genome that shares ∼85% identity to that of man, and has many physiological systems that are similar to those in man. Moreover, methods have been developed to alter the expression of genes in the mouse, thereby generating models for human diseases, which may be due to loss- or gain-of-function mutations. The methods used to generate mutations in the mouse genome include: chemical mutagenesis; conventional, conditional and inducible knockout models; knockin models and transgenic models, and these strategies are often complementary. This review describes some of the different strategies that are utilised for generating mouse models. In addition, some mouse models that have been successfully generated by these methods for some human hereditary endocrine and metabolic disorders are reviewed. In particular, the mouse models generated for parathyroid disorders, which include: the multiple endocrine neoplasias; hyperparathyroidism-jaw tumour syndrome; disorders of the calcium-sensing receptor and forms of inherited hypoparathyroidism are discussed. The advances that have been made in our understanding of the mechanisms of these human diseases by investigations of these mouse models are described.
Nonparametric Item Response Curve Estimation With Correction for Measurement Error
Authors: Guo Hongwen , Sinharay Sandip
Published: July 2011

Nonparametric or kernel regression estimation of item response curves (IRCs) is often used in item analysis in testing programs. These estimates are biased when the observed scores are used as the regressor because the observed scores are contaminated by measurement error. Accuracy of this estimation is a concern theoretically and operationally. This study investigates the deconvolution kernel estimation of IRCs, which corrects for the measurement error in the regressor variable. A comparison of the traditional kernel estimation and the deconvolution estimation of IRCs is carried out using both simulated and operational data. It is found that, in item analysis, the traditional kernel estimation is comparable to the deconvolution kernel estimation in capturing important features of the IRC.
CGS 21680, an Agonist of the Adenosine (A2A) Receptor, Reduces Progression of Murine Type II Collagen-induced Arthritis
Authors: MAZZON EMANUELA , ESPOSITO EMANUELA , IMPELLIZZERI DANIELA , DI PAOLA ROSANNA , MELANI ALESSIA , BRAMANTI PLACIDO , PEDATA FELICITA , CUZZOCREA SALVATORE
Published: July 2011

Objective.

The aim of our study was to investigate the effect of an adenosine A2A receptor agonist, 2-[p-(2-carboxyethyl)phenylethylamino]-50 ethylcarboxamidoadenosine (CGS 21680), on modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA).

Methods.

CIA was induced by intradermal injection of 100 μl of emulsion containing 100 μg of bovine type II collagen (CII) and complete Freund’s adjuvant (CFA) at the base of the tail. On Day 21, a second injection of CII in CFA was administered. Immunized mice developed erosive hind paw arthritis. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by Day 27 in the CII challenged mice and the severity of CIA progressed over a 35-day period, with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of cartilage at the joint margins.

Results.

Treatment of mice with CGS 21680 starting at the onset of arthritis (Day 25) ameliorated the clinical signs at Days 26–35 and improved histological status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in CGS 21680-treated mice as indicated by elevated levels of malondialdehyde, formation of nitrotyrosine, and activation of poly(ADP-ribose) polymerase. Plasma levels of proinflammatory cytokines such as tumor necrosis factor, interleukin 1ß (IL-1ß) and IL-6 were also reduced by CGS 21680. Treatment with CGS 21680 also decreased the expression of inducible nitric oxide synthase and cyclooxygenase-2.

Conclusion.

We demonstrate that CGS 21680 exerts an antiinflammatory effect during chronic inflammation and ameliorates the tissue damage associated with CIA.
25-Hydroxyvitamin D Levels and Vitamin D Deficiency in Children with Rheumatologic Disorders and Controls
Authors: PELAJO CHRISTINA F. , LOPEZ-BENITEZ JORGE M. , MILLER LAURIE C.
Published: July 2011

Objective.

To evaluate the prevalence of vitamin D deficiency, as well as factors associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in children attending a pediatric rheumatology clinic, and to determine whether there was a difference in serum 25(OH)D levels and in vitamin D deficiency between children with autoimmune disorders and nonautoimmune conditions.

Methods.

Cross-sectional analysis of serum 25(OH)D levels of patients between the ages of 2 and 19 years, seen between November 2008 and October 2009.

Results.

A total of 254 patients were studied (169 autoimmune disorders, 85 nonautoimmune conditions). The mean age of study patients was 12.3 years; 67% were female and 80% were white. In the autoimmune disorders group, 23% had vitamin D deficiency [serum 25(OH)D < 20 ng/ml], and in the nonautoimmune conditions group 14% were vitamin D deficient. The average level of serum 25(OH)D was 28.6 (± 11) ng/ml (range 2 to 59). Age, ethnicity, body mass index, use of supplements, and season were significantly associated with serum levels of 25(OH)D (all p ≤ 0.02). The OR of patients with autoimmune disorders being vitamin D deficient was 2.3, in relation to patients with nonautoimmune conditions (p = 0.04).

Conclusion.

Twenty percent of patients attending a pediatric rheumatology clinic were vitamin D deficient. Patients with autoimmune disorders were more likely to be vitamin D deficient than patients with nonautoimmune conditions. Screening of serum 25(OH)D levels should be performed for patients with autoimmune disorders.
Canadian Recommendations for Clinical Trials of Pharmacologic Interventions in Rheumatoid Arthritis: Inclusion Criteria and Study Design: Table 1.
Authors: KARSH JACOB , KEYSTONE EDWARD C. , HARAOUI BOULOS , THORNE J. CARTER , POPE JANET E. , BYKERK VIVIAN P. , MAKSYMOWYCH WALTER P. , ZUMMER MICHEL , BENSEN WILLIAM G. , KRAISHI MAJED M.
Published: July 2011

Objective.

Current clinical trial designs for pharmacologic interventions in rheumatoid arthritis (RA) do not reflect the innovations in RA diagnosis, treatment, and care in countries where new drugs are most often used. The objective of this project was to recommend revised entry criteria and other study design features for RA clinical trials.

Methods.

Recommendations were developed using a modified nominal group consensus method. Canadian Rheumatology Research Consortium (CRRC) members were polled to rank the greatest challenges to clinical trial recruitment in their practices. Initial recommendations were developed by an expert panel of rheumatology trialists and other experts. A scoping study methodology was then used to examine the evidence available to support or refute each initial recommendation. The potential influence of CRRC recommendations on primary outcomes in future trials was examined. Recommendations were finalized using a consensus process.

Results.

Recommendations for clinical trial inclusion criteria addressed measures of disease activity [Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) > 3.2 PLUS ≥ 3 tender joints using 28-joint count (TJC28) PLUS ≥ 3 swollen joint (SJC28) OR C-reactive protein (CRP) or ESR > upper limit of normal PLUS ≥ 3 TJC28 PLUS ≥ 3 SJC28], functional classification, disease classification and duration, and concomitant RA treatments. Additional recommendations regarding study design addressed rescue strategies and longterm extension.

Conclusion.

There is an urgent need to modify clinical trial inclusion criteria and other study design features to better reflect the current characteristics of people living with RA in the countries where the new drugs will be used.
Role of IL-17 and Th17 Cells in Herpes Simplex Virus-Induced Corneal Immunopathology
Authors: Suryawanshi Amol , Veiga-Parga Tamara , Rajasagi Naveen K. , Reddy Pradeep Babu Jagdeesh , Sehrawat Sharvan , Sharma Shalini , Rouse Barry T.
Published: July 2011

HSV-1 infection of the cornea leads to a blinding immunoinflammatory lesion of the eye termed stromal keratitis (SK). Recently, IL-17–producing CD4+ T cells (Th17 cells) were shown to play a prominent role in many autoimmune conditions, but the role of IL-17 and/or of Th17 cells in virus immunopathology is unclear. In this study, we show that, after HSV infection of the cornea, IL-17 is upregulated in a biphasic manner with an initial peak production around day 2 postinfection and a second wave starting from day 7 postinfection with a steady increase until day 21 postinfection, a time point when clinical lesions are fully evident. Further studies demonstrated that innate cells, particularly γδ T cells, were major producers of IL-17 early after HSV infection. However, during the clinical phase of SK, the predominant source of IL-17 was Th17 cells that infiltrated the cornea only after the entry of Th1 cells. By ex vivo stimulation, the half fraction of IFN-γ–producing CD4+ T cells (Th1 cells) were HSV specific, whereas very few Th17 cells responded to HSV stimulation. The delayed influx of Th17 cells in the cornea was attributed to the local chemokine and cytokine milieu. Finally, HSV infection of IL-17R knockout mice as well as IL-17 neutralization in wild-type mice showed diminished SK severity. In conclusion, our results show that IL-17 and Th17 cells contribute to the pathogenesis of SK, the most common cause of infectious blindness in the Western world.
Role of Zooplankton Diversity in Vibrio cholerae Population Dynamics and in the Incidence of Cholera in the Bangladesh Sundarbans
Authors: de Magny Guillaume Constantin , Mozumder Pronob K. , Grim Christopher J. , Hasan Nur A. , Naser M. Niamul , Alam Munirul , Sack R. Bradley , Huq Anwar , Colwell Rita R.
Published: July 2011

Vibrio cholerae
, a bacterium autochthonous to the aquatic environment, is the causative agent of cholera, a severe watery, life-threatening diarrheal disease occurring predominantly in developing countries.
V. cholerae
, including both serogroups O1 and O139, is found in association with crustacean zooplankton, mainly copepods, and notably in ponds, rivers, and estuarine systems globally. The incidence of cholera and occurrence of pathogenic
V. cholerae
strains with zooplankton were studied in two areas of Bangladesh: Bakerganj and Mathbaria. Chitinous zooplankton communities of several bodies of water were analyzed in order to understand the interaction of the zooplankton population composition with the population dynamics of pathogenic
V. cholerae
and incidence of cholera. Two dominant zooplankton groups were found to be consistently associated with detection of
V. cholerae
and/or occurrence of cholera cases, namely, rotifers and cladocerans, in addition to copepods. Local differences indicate there are subtle ecological factors that can influence interactions between
V. cholerae
, its plankton hosts, and the incidence of cholera.
Ligands of Thermophilic ABC Transporters Encoded in a Newly Sequenced Genomic Region of Thermotoga maritima MSB8 Screened by Differential Scanning Fluorimetry
Authors: Boucher Nathalie , Noll Kenneth M.
Published: July 2011

The chromosome of
Thermotoga maritima
strain MSB8 was found to have an 8,870-bp region that is not present in its published sequence. The isolate that was sequenced by The Institute for Genomic Research (TIGR) in 1999 is apparently a laboratory variant of the isolate deposited at the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSM 3109) in 1986. This newly sequenced region from the DSMZ culture was located between TM1848 (
cbp
, cellobiose phosphorylase) and TM1847 (the 3′ end of a truncated ROK regulator). The new region contained seven genes: a beta glucosidase gene (
bglA
), three trehalose ABC transporter genes (
treEFG
), three xylose ABC transporter genes (
xylE2F2K2
), and the 5′ end of a gene encoding the ROK regulator TM1847. We present a new differential scanning fluorimetry method using a low pH that was necessary to screen potential ligands of these exceptionally thermostable periplasmic substrate-binding proteins. This method showed that trehalose, sucrose, and glucose stabilized TreE, and their binding was confirmed by measuring changes in intrinsic fluorescence upon ligand binding. Binding constants of 0.024 μM, 0.300 μM, and 56.78 μM at 60°C, respectively, were measured. XylE2 ligands were similarly determined and xylose, glucose, and fucose bound with

K
d

(dissociation constant) values of 0.042 μM, 0.059 μM, and 1.436 μM, respectively. Since there is no discernible phenotypic difference between the TIGR isolate and the DSMZ isolate despite the variance in their genomes, we propose that they be called genomovars:
T. maritima
MSB8 genomovar TIGR and
T. maritima
MSB8 genomovar DSM 3109, respectively.
Reinventing Heterochromatin in Budding Yeasts: Sir2 and the Origin Recognition Complex Take Center Stage
Authors: Hickman Meleah A. , Froyd Cara A. , Rusche Laura N.
Published: July 2011

The transcriptional silencing of the cryptic mating-type loci in
Saccharomyces cerevisiae
is one of the best-studied models of repressive heterochromatin. However, this type of heterochromatin, which is mediated by the Sir proteins, has a distinct molecular composition compared to the more ubiquitous type of heterochromatin found in
Schizosaccharomyces pombe
, other fungi, animals, and plants and characterized by the presence of HP1 (heterochromatin protein 1). This review discusses how the loss of important heterochromatin proteins, including HP1, in the budding yeast lineage presented an evolutionary opportunity for the development and diversification of alternative varieties of heterochromatin, in which the conserved deacetylase Sir2 and the replication protein Orc1 play key roles. In addition, we highlight how this diversification has been facilitated by gene duplications and has contributed to adaptations in lifestyle.
Antibiotic Production by Myxobacteria Plays a Role in Predation
Authors: Xiao Yao , Wei Xueming , Ebright Richard , Wall Daniel
Published: July 2011

Myxobacteria are predatory and are prolific producers of secondary metabolites. Here, we tested a hypothesized role that secondary metabolite antibiotics function as weapons in predation. To test this, a
Myxococcus xanthus
Δta1
mutant, blocked in antibiotic TA (myxovirescin) production, was constructed. This TA
−
mutant was defective in producing a zone of inhibition (ZOI) against
Escherichia coli
. This shows that TA is the major
M. xanthus
-diffusible antibacterial agent against
E. coli
. Correspondingly, the TA
−
mutant was defective in
E. coli
killing. Separately, an engineered
E. coli
strain resistant to TA was shown to be resistant toward predation. Exogenous addition of spectinomycin, a bacteriostatic antibiotic, rescued the predation defect of the TA
−
mutant. In contrast, against
Micrococcus luteus
the TA
−
mutant exhibited no defect in ZOI or killing. Thus, TA plays a selective role on prey species. To extend these studies to other myxobacteria, the role of antibiotic corallopyronin production in predation was tested and also found to be required for
Corallococcus coralloides
killing on
E. coli
. Next, a role of TA production in myxobacterial fitness was assessed by measuring swarm expansion. Here, the TA
−
mutant had a specific swarm rate reduction on prey lawns, and thus reduced fitness, compared to an isogenic TA
+
strain. Based on these observations, we conclude that myxobacterial antibiotic production can function as a predatory weapon. To our knowledge, this is the first report to directly show a link between secondary metabolite production and predation.
Metabolomics Reveals Phospholipids as Important Nutrient Sources during Salmonella Growth in Bile In Vitro and
In Vivo
Authors: Antunes L. Caetano. M. , Andersen Sarah K. , Menendez Alfredo , Arena Ellen T. , Han Jun , Ferreira Rosana B. R. , Borchers Christoph H. , Finlay B. Brett
Published: July 2011

During the colonization of hosts, bacterial pathogens are presented with many challenges that must be overcome for colonization to occur successfully. This requires the bacterial sensing of the surroundings and adaptation to the conditions encountered. One of the major impediments to the pathogen colonization of the mammalian gastrointestinal tract is the antibacterial action of bile.
Salmonella enterica
serovar Typhimurium has specific mechanisms involved in resistance to bile. Additionally,
Salmonella
can successfully multiply in bile, using it as a source of nutrients. This accomplishment is highly relevant to pathogenesis, as
Salmonella
colonizes the gallbladder of hosts, where it can be carried asymptomatically and promote further host spread and transmission. To gain insights into the mechanisms used by
Salmonella
to grow in bile, we studied the changes elicited by
Salmonella
in the chemical composition of bile during growth
in vitro
and
in vivo
through a metabolomics approach. Our data suggest that phospholipids are an important source of carbon and energy for
Salmonella
during growth in the laboratory as well as during gallbladder infections of mice. Further studies in this area will generate a better understanding of how
Salmonella
exploits this generally hostile environment for its own benefit.
Genetic Regulation of the
yefM-yoeB
Toxin-Antitoxin Locus of Streptococcus pneumoniae
Authors: Chan Wai Ting , Nieto Concha , Harikrishna Jennifer Ann , Khoo Seok Kooi , Othman Rofina Yasmin , Espinosa Manuel , Yeo Chew Chieng
Published: July 2011

Type II (proteic) toxin-antitoxin systems (TAS) are ubiquitous among bacteria. In the chromosome of the pathogenic bacterium
Streptococcus pneumoniae
, there are at least eight putative TAS, one of them being the

yefM-yoeB
Spn

operon studied here. Through footprinting analyses, we showed that purified YefM
Spn
antitoxin and the YefM-YoeB
Spn
TA protein complex bind to a palindrome sequence encompassing the −35 region of the main promoter (P

yefM2

) of the operon. Thus, the locus appeared to be negatively autoregulated with respect to P

yefM2

, since YefM
Spn
behaved as a weak repressor with YoeB
Spn
as a corepressor. Interestingly, a BOX element, composed of a single copy (each) of the boxA and boxC subelements, was found upstream of promoter P

yefM2

. BOX sequences are pneumococcal, perhaps mobile, genetic elements that have been associated with bacterial processes such as phase variation, virulence regulation, and genetic competence. In the

yefM-yoeB
Spn

locus, the boxAC element provided an additional weak promoter, P

yefM1

, upstream of P

yefM2

which was not regulated by the TA proteins. In addition, transcriptional fusions with a
lacZ
reporter gene showed that P

yefM1

was constitutive albeit weaker than P

yefM2

. Intriguingly, the coupling of the boxAC element to P

yefM1

and

yefM
Spn

in
cis
(but not in
trans
) led to transcriptional activation, indicating that the regulation of the

yefM-yoeB
Spn

locus differs somewhat from that of other TA loci and may involve as yet unidentified elements. Conservation of the boxAC sequences in all available sequenced genomes of
S. pneumoniae
which contained the

yefM-yoeB
Spn

locus suggested that its presence may provide a selective advantage to the bacterium.
Chronic skeletal muscle ischemia preserves coronary flow in the ischemic rat heart
Authors: Varnavas Varnavas C. , Kontaras Konstantinos , Glava Chryssoula , Maniotis Christos D. , Koutouzis Michael , Baltogiannis Giannis G. , Papalois Apostolos , Kolettis Theofilos M. , Kyriakides Zenon S.
Published: July 2011

Chronic skeletal muscle ischemia confers cytoprotection to the ventricular myocardium during infarction, but the underlying mechanisms remain unclear. Although neovascularization in the left ventricular myocardium has been proposed as a possible mechanism, the functional capacity of such vessels has not been studied. We examined the effects of chronic limb ischemia on infarct size, coronary blood flow, and left ventricular function after ischemia-reperfusion. Hindlimb ischemia was induced in 65 Wistar rats by excision of the left femoral artery, whereas 65 rats were sham operated. After 4 wk, myocardial infarction was generated by permanent coronary artery ligation. Infarct size was measured 24 h postligation. Left ventricular function was evaluated in isolated hearts after ischemia-reperfusion, 4 wk after limb ischemia. Neovascularization was assessed by immunohistochemistry, and coronary flow was measured under maximum vasodilatation at different perfusion pressures before and after coronary ligation. Infarct size was smaller after limb ischemia compared with controls (24.4 ± 8.1% vs. 46.2 ± 9.5% of the ventricle and 47.6 ± 8.7% vs. 80.1 ± 9.3% of the ischemic area, respectively). Indexes of left ventricular function at the end of reperfusion (divided by baseline values) were improved after limb ischemia (developed pressure: 0.68 ± 0.06 vs. 0.59 ± 0.05, P = 0.008; maximum +dP/d t: 0.70 ± 0.08 vs. 0.59 ± 0.04, P = 0.004; and maximum −dP/d t: 0.86 ± 0.14 vs. 0.72 ± 0.10, P = 0.041). Coronary vessel density was markedly higher ( P = 0.00021) in limb ischemic rats. In contrast to controls ( F = 5.65, P = 0.00182), where coronary flow decreased, it remained unchanged ( F = 1.36, P = 0.28) after ligation in limb ischemic rats. In conclusion, chronic hindlimb ischemia decreases infarct size and attenuates left ventricular dysfunction by increasing coronary collateral vessel density and blood flow.
Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress
Authors: Terasaki Yasuhiro , Ohsawa Ikuroh , Terasaki Mika , Takahashi Mikiko , Kunugi Shinobu , Dedong Kang , Urushiyama Hirokazu , Amenomori Shunsuke , Kaneko-Togashi Mayuko , Kuwahara Naomi , Ishikawa Arimi , Kamimura Naomi , Ohta Shigeo , Fukuda Yuh
Published: July 2011

Molecular hydrogen (H2) is an efficient antioxidant that diffuses rapidly across cell membranes, reduces reactive oxygen species (ROS), such as hydroxyl radicals and peroxynitrite, and suppresses oxidative stress-induced injury in several organs. ROS have been implicated in radiation-induced damage to lungs. Because prompt elimination of irradiation-induced ROS should protect lung tissue from damaging effects of irradiation, we investigated the possibility that H2 could serve as a radioprotector in the lung. Cells of the human lung epithelial cell line A549 received 10 Gy irradiation with or without H2 treatment via H2-rich PBS or medium. We studied the possible radioprotective effects of H2 by analyzing ROS and cell damage. Also, C57BL/6J female mice received 15 Gy irradiation to the thorax. Treatment groups inhaled 3% H2 gas and drank H2-enriched water. We evaluated acute and late-irradiation lung damage after H2 treatment. H2 reduced the amount of irradiation-induced ROS in A549 cells, as shown by electron spin resonance and fluorescent indicator signals. H2 also reduced cell damage, measured as levels of oxidative stress and apoptotic markers, and improved cell viability. Within 1 wk after whole thorax irradiation, immunohistochemistry and immunoblotting showed that H2 treatment reduced oxidative stress and apoptosis, measures of acute damage, in the lungs of mice. At 5 mo after irradiation, chest computed tomography, Ashcroft scores, and type III collagen deposition demonstrated that H2 treatment reduced lung fibrosis (late damage). This study thus demonstrated that H2 treatment is valuable for protection against irradiation lung damage with no known toxicity.
Meniscal Root Suturing Techniques
Authors: Kopf Sebastian , Colvin Alexis Chiang , Muriuki Muturi , Zhang Xudong , Harner Christopher Dechant
Published: July 2011

Background: Meniscal root tears have attracted increasing interest in recent years. Fixation is an important factor for rehabilitation and avoidance of early failure. Suture fixations have been the most commonly used techniques. The current study aimed to evaluate the maximum failure load of the native meniscal roots (anteromedial, posteromedial, anterolateral, and posterolateral) and of 3 commonly used meniscal root fixation techniques (2 simple stitches, modified Kessler stitch, and loop stitch).

Hypotheses: (1) There will be no difference in maximum failure load between the native meniscal roots. (2) The loop stitch will sustain the greatest maximum load to failure, followed by the modified Kessler stitch and the 2 simple stitches. (3) The maximum failure load of the native meniscal roots will not be restored by the tested fixation methods.

Study Design: Controlled laboratory study.

Methods: The maximum failure load of the 4 human native meniscal roots was evaluated using 64 human meniscal roots. Additionally, the maximum failure load of the 3 fixation techniques was evaluated on 24 meniscal roots: (1) 2 simple stitches, (2) modified Kessler stitch, and (3) loop stitch using a suture shuttle.

Results: The average maximum failure load of the native meniscal roots was 594 ± 241 N (anterolateral: 692 ± 304 N; posterolateral: 648 ± 140 N; anteromedial: 407 ± 180 N; posteromedial: 678 ± 200 N). The anteromedial root was significantly weaker than the posterolateral and posteromedial roots ( P = .04 and P = .01, respectively). Regarding fixation techniques, the maximum failure load of the 2 simple stitches was 64.1 ± 22.5 N, the modified Kessler stitch was 142.6 ± 33.3 N, and the loop was 100.9 ± 41.6 N. None of the fixation techniques recreated the strength of the native roots.

Conclusion: The native anterolateral root was the strongest meniscal root, and the anteromedial root was the weakest meniscal root. Regarding primary fixation strength, the modified Kessler stitch was the strongest technique compared with the loop and the 2 simple stitches.

Clinical Relevance: None of our tested fixation methods restored the strength of native meniscal roots. Thus, rehabilitation after meniscal root fixation should proceed cautiously.
Ironic Effects of Dietary Supplementation
Authors: Chiou Wen-Bin , Yang Chao-Chin , Wan Chin-Sheng
Published: July 2011

The use of dietary supplements and the health status of individuals have an asymmetrical relationship: The growing market for dietary supplements appears not to be associated with an improvement in public health. Building on the notion of licensing, or the tendency for positive choices to license subsequent self-indulgent choices, we argue that because dietary supplements are perceived as conferring health advantages, use of such supplements may create an illusory sense of invulnerability that disinhibits unhealthy behaviors. In two experiments, participants who took placebo pills that they believed were dietary supplements exhibited the licensing effect across multiple forms of health-related behavior: They expressed less desire to engage in exercise and more desire to engage in hedonic activities (Experiment 1), expressed greater preference for a buffet over an organic meal (Experiment 1), and walked less to benefit their health (Experiment 2) compared with participants who were told the pills were a placebo. A mediational analysis indicated that perceived invulnerability was an underlying mechanism for these effects. Thus, a license associated with the use of dietary supplements may operate within cycles of behaviors that alternately protect and endanger health.
Evolution and Current Role of Autologous Chondrocyte Implantation for Treatment of Articular Cartilage Defects in the Football (Soccer) Player
Authors: Mithoefer Kai , Peterson Lars , Saris Daniel B.F. , Mandelbaum Bert R.
Published: July 2011

Background: Autologous chondrocyte implantation (ACI) continues to technically evolve, but how the technical innovations affect the ability to participate in high-impact sports such as football is unknown. Methods: Clinical studies describing athletes treated with first-, second-, or third-generation ACI techniques were reviewed. The technical developments of ACI were evaluated, and the results in athletes and specifically football (soccer) players were analyzed. Results: Football players reported 72% good to excellent results with significant overall improvement of knee function and activity scores. Return to football was 83% in competitive players but lower in recreational players. Eighty percent of players returned to the same competitive level after ACI, and 87% to 100% maintained their ability to play sports at 5 years postoperatively. Return to sport was better for younger, competitive players with shorter intervals between injury and ACI. New developments of the surgical technique and postoperative rehabilitation were able to reduce the limitations associated with first-generation ACI including invasiveness, graft hypertrophy, and particularly long postoperative rehabilitation. This allowed for faster return to sports like football without compromising the ability for continued competition over time. Conclusion: Articular cartilage repair in football players often allows for successful return to this high-impact sport with excellent durability. The continued evolution of this technique has improved initial shortcomings with important implications for both the professional and recreational athlete.
Monoclonal and polyclonal serum free light chains and clinical outcome in chronic lymphocytic leukemia
Authors: Maurer Matthew J. , Cerhan James R. , Katzmann Jerry A. , Link Brian K. , Allmer Cristine , Zent Clive S. , Call Timothy G. , Rabe Kari G. , Hanson Curtis A. , Kay Neil E. , Slager Susan L. , Witzig Thomas E. , Shanafelt Tait D.
Published: July 2011

Free light chains (FLCs) are the most commonly detected paraproteins in chronic lymphocytic leukemia (CLL). We examined the types of FLC abnormalities and prognostic utility of the FLC assay compared with standard prognostic biomarkers in a prospective cohort of 339 patients with newly diagnosed CLL. Three types of FLC abnormalities were identified: monoclonal elevated FLC (elevated κ and/or λ with abnormal FLC ratio), polyclonal elevated FLC (elevated κ and/or λ with normal FLC ratio), and ratio-only FLC abnormality (normal range κ and λ with abnormal FLC ratio). One hundred sixty-five patients (49%) had a FLC abnormality with approximately equal distribution among monoclonal elevation, polyclonal elevation, and ratio-only abnormality. All FLC abnormalities were associated with poor time to first treatment: monoclonal FLC (hazard ratio [HR], 4.99; 95% confidence interval [CI], 2.94-8.48), polyclonal FLC (HR, 2.40; 95% CI, 1.24-4.64), ratio-only FLC (HR, 2.57; 95% CI, 1.40-4.69). Monoclonal FLC and polyclonal FLC were associated with poor overall survival compared with patients with normal FLC. Results remained significant after adjusting for Rai stage. The FLC assay is a simple, widely available clinical test with similar prognostic utility as routinely used prognostic biomarkers for CLL. Among persons with FLC abnormalities, the type of abnormality affects prognostic significance.
Comparative Proteomic Analysis of saccharopolyspora spinosa SP06081 and PR2 strains reveals the differentially expressed proteins correlated with the increase of spinosad yield
Authors: Luo Yushuang , Ding Xuezhi , Xia Liqiu , Huang Fan , Li Wenping , Huang Shaoya , Tang Ying , Sun Yunjun
Published: July 2011

Background

Saccharopolyspora spinosa produces the environment-friendly biopesticide spinosad, a mixture of two polyketide-derived macrolide active ingredients called spinosyns A and D. Therefore considerable interest is in the improvement of spinosad production because of its low yield in wild-type S. spinosa. Recently, a spinosad-hyperproducing PR2 strain with stable heredity was obtained from protoplast regeneration of the wild-type S. spinosa SP06081 strain. A comparative proteomic analysis was performed on the two strains during the first rapid growth phase (RG1) in seed medium (SM) by using label-free quantitative proteomics to investigate the underlying mechanism leading to the enhancement of spinosad yield.

Results

In total, 224 proteins from the SP06081 strain and 204 proteins from the PR2 strain were unambiguously identified by liquid chromatography-tandem mass spectrometry analysis, sharing 140 proteins. A total of 12 proteins directly related to spinosad biosynthesis were identified from the two strains in RG1. Comparative analysis of the shared proteins revealed that approximately 31% of them changed their abundance significantly and fell in all of the functional groups, such as tricarboxylic acid cycles, glycolysis, biosynthetic processes, catabolic processes, transcription, translation, oxidation and reduction. Several key enzymes involved in the synthesis of primary metabolic intermediates used as precursors for spinosad production, energy supply, polyketide chain assembly, deoxysugar methylation, and antioxidative stress were differentially expressed in the same pattern of facilitating spinosad production by the PR2 strain. Real-time reverse transcriptase polymerase chain reaction analysis revealed that four of five selected genes showed a positive correlation between changes at the translational and transcriptional expression level, which further confirmed the proteomic analysis.

Conclusions

The present study is the first comprehensive and comparative proteome analysis of S. spinosa strains. Our results highlight the differentially expressed proteins between the two S. spinosa strains and provide some clues to understand the molecular and metabolic mechanisms that could lead to the increased spinosad production yield.
Evaluation of 19 Autoimmune Disease-associated Loci with Rheumatoid Arthritis in a Colombian Population: Evidence for Replication and Gene-Gene Interaction
Authors: DESHMUKH HARSHAL A. , MAITI AMIT K. , KIM-HOWARD XANA R. , ROJAS-VILLARRAGA ADRIANA , GUTHRIDGE JOEL M. , ANAYA JUAN-MANUEL , NATH SWAPAN K.
Published: July 2011

Objective.

Recent studies have identified several common genes associated with multiple autoimmune diseases that support the hypothesis of the presence of shared or general autoimmunity genes. However, most of this work has been performed in populations of white origin. The main objectives of this study are to replicate the genotype-phenotype correlation between 19 such variants and rheumatoid arthritis (RA), and to evaluate gene-gene interactions between these genes in individuals from an ethnically homogenous nonwhite Colombian population.

Methods.

Nineteen single-nucleotide polymorphisms (SNP) from 16 genes/loci were genotyped in 353 RA cases and 368 controls. For each SNP, allelic and genotype-based association tests were applied to evaluate genotype-phenotype correlation. Permutation-based tests were used to validate the statistical significance. Gene-gene interactions were assessed by logistic regression.

Results.

We replicated the genetic association with rs13277113 (p = 0.0009, OR 1.46) and rs2736340 (p = 0.0001, OR 1.63) from C8orf13-BLK (8p23.1, associated with RA and systemic lupus erythematosus), and rs763361 (p = 0.03) from CD226 (18q22.3, associated with multiple sclerosis and type 1 diabetes) in the Colombian population. The population-attributable risks were estimated as 27%, 34%, and 16% for rs13277113, rs2736340, and rs763361, respectively. We also detected evidence for gene-gene interaction between SNP in MMEL1 (rs3890745) and C80rf13-BLK (rs13277113; p = 0.0002).

Conclusion.

Our results demonstrate that the IL2/IL21 region, C8orf13-BLK, and CD226 influence RA in Colombians, and RA shares some of the pathogenic mechanisms associated with other autoimmune diseases.
High-temperature x-ray characterization of GaN epitaxially grown on Sc2O3/Y2O3/Si(1 1 1) heterostructures
Authors: Zaumseil P , Tarnawska L , Storck P , Schroeder T
Published: July 2011

The thermal behaviour of GaN epitaxially grown on a Sc2O3/Y2O3 bilayer buffer on the Si(1 1 1) substrate is studied between room temperature (RT) and 800 °C by x-ray diffraction of symmetrical and asymmetrical reflections. It is found that the GaN layer is in-plane mediated by the oxide buffer completely fixed to the Si substrate, which indicates the absence of any temperature related compliance behaviour of the oxide buffer. The GaN grows at 720 °C already slightly tensile strained on top of the larger Sc2O3 lattice, and this strain increases further during cooling down to RT due to different coefficients of thermal expansion of GaN and the Si substrate.
Multi-parameter scaling of divertor power load profiles in D, H and He plasmas on JET and implications for ITER
Authors: Fundamenski W. , Eich T. , Devaux S. , Jachmich S. , Jakubowski M. , Thomsen H. , Arnoux G. , Militello F. , Havlickova E. , Moulton D. , Brezinsek S. , Maddison G. , McCormick K. , Huber A.
Published: July 2011

Inter-ELM and ELM divertor power loads were measured on JET in dedicated deuterium, hydrogen and helium discharges. Matched triplets (D, H, He) were obtained for different values of magnetic field, B, plasma current, I
p, line average plasma density, n, and heating power, P. In this paper, the above experiments are described and the results are presented in terms of empirical scalings of inter-ELM and ELM wetted areas (power widths) versus engineering parameters. The inter-ELM wetted area on the outer target is found to scale roughly as
, where A and Z and the fuel ion mass and charge numbers, and q
cyl is the cylindrical safety factor, and the ELM wetted area as
. The obtained inter-ELM scalings are then compared with those previously reported in the literature and with a wide range of 0D theoretical predictions. For this purpose a family of scrape-off layer power width models was constructed based on a permutation of different assumptions for parallel and perpendicular transport. It is found that a combination of parallel electron conduction and drift-ordered radial convection offers the best overall match to the empirical data, closely followed by models based on marginal stability to interchange/ballooning modes and ion convection with transport ordered radial velocity. Finally, implications for ITER are tentatively drawn, and a revised estimate for the power width in ITER is proposed. Extrapolating to ITER based on the empirical JET scaling and the optimum size scaling of R
0.7±0.6, obtained based on comparison with simple models, yields a median outer target inter-ELM power width of ∼5.5 ± 2 mm (mapped to the outer mid-plane), in close agreement with previous estimates and the ITER design value. The most pessimistic forecasts (little or no size scaling and inverse linear B dependence, i.e. pure inverse current scaling) yield values as small as 2 mm. The resolution of the size scaling issue calls for additional inter-machine comparisons.
Experimental study of the poloidal flow effect on magnetic island dynamics in LHD and TJ-II
Authors: Narushima Y. , Castejón F. , Sakakibara S. , Watanabe K.Y. , Ohdachi S. , Suzuki Y. , Estrada T. , Medina F. , López-Bruna D. , Yokoyama M. , Yoshinuma M. , Ida K. , Nishimura S.
Published: July 2011

The dynamics of a magnetic island is studied by focusing on the poloidal flows in the helical devices LHD and TJ-II. An experimental result implying the temporal increment of the
E
×
B
poloidal flow prior to the magnetic island transition from growth to healing is observed. The direction of the poloidal flow is in the electron-diamagnetic direction in LHD and in the ion-diamagnetic direction in TJ-II. From the magnetic diagnostics, it is observed that a current structure flowing in the plasma moves ∼π rad poloidally in the electron-diamagnetic direction during the transition in LHD experiments. These experimental observations from LHD and TJ-II show that the temporal increment of the poloidal flow is followed by the transition (growth to healing) of the magnetic island regardless of the flow direction and suggests the fact that a significant poloidal flow affects the magnetic island dynamics.
Amycolatopsis granulosa sp. nov., Amycolatopsis ruanii sp. nov. and Amycolatopsis thermalba sp. nov., thermophilic actinomycetes isolated from arid soils
Authors: Zucchi Tiago Domingues , Tan Geok Yuan Annie , Bonda Avinash Naga Venkata , Frank Sarah , Kshetrimayum Jenileima Devi , Goodfellow Michael
Published: July 2011

The taxonomic positions of three thermophilic actinomycetes isolated from arid soil samples were established by using a polyphasic approach. The organisms had chemical and morphological features that were consistent with their classification in the genus

Amycolatopsis

. 16S rRNA gene sequence data supported the classification of the isolates in the genus

Amycolatopsis

and showed that they formed distinct branches in the

Amycolatopsis methanolica

subclade. DNA–DNA relatedness studies between the isolates and their phylogenetic neighbours showed that they belonged to distinct genomic species. The three isolates were readily distinguished from one another and from the type strains of species classified in the

A. methanolica

subclade based on a combination of phenotypic properties and by genomic fingerprinting. Consequently, it is proposed that the three isolates be classified in the genus

Amycolatopsis

as representatives of Amycolatopsis granulosa sp. nov. (type strain GY307T = NCIMB 14709T = NRRL B-24844T), Amycolatopsis ruanii sp. nov. (type strain NMG112T = NCIMB 14711T = NRRL B-24848T) and Amycolatopsis thermalba sp. nov. (type strain SF45T = NCIMB 14705T = NRRL B-24845T).