bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevation of IGF‐2 receptor and the possible underlying implications in end‐stage heart failure patients before and after heart transplantation
Authors: Wei Yingjie , Li Jun , Huang Jie , Zhang Xiaoling , Zhao Hong , Cui Chuanjue , Li Yishi , Hu Shengshou
Published: September 2011

Up‐regulation of insulin‐like growth factor 2 receptor (IGF‐2R) involved in angiotensin II–induced cell apoptosis in cardiomyoblasts, and correlated with cardiomyocyte apoptosis in hypertensive rat hearts. Here, we detected IGF‐2R levels and explored the possible underlying implications in end‐stage heart failure (HF) patients before and after heart transplantation. Western blot and immunohistochemistry were used to measure cardiac IGF‐2R levels. ELISA was used to detect serum IGF‐2R and CD8 levels. Labelling of DNA strand breaks and dihydroethidium detection were used to determine cellular apoptosis and reactive oxygen species, respectively. Cardiac IGF‐2R levels increased in end‐stage HF patients (n = 11) compared with non‐failing control subjects. Leu27‐IGF‐2, an IGF‐2 analogue to activate specially the IGF‐2R, could induce apoptosis and reactive oxygen species production in neonatal rat ventricular myocytes. The serum IGF‐2R levels were significantly higher in HF patients than those in non‐failing control subjects. An unexpected observation is that the serum IGF‐2R levels further increased after heart transplantation, peaked at the first month, and gradually reduced close to the levels before heart transplantation at the 6th months after heart transplantation. Serum CD8, a marker of acute rejection, had no change after heart transplantation, but IGF‐2R and Granzyme B, as a ligand for the IGF‐2R and a marker for CD8 T lymphocyte activation, coexisted in the transplanted hearts. Our preliminary studies suggest that elevation of IGF‐2R may participate in pathological process of end‐stage HF and involved in the acute cellular rejection after heart transplantation.
Etanercept‐induced cutaneous and pulmonary sarcoid‐like granulomas resolving with adalimumab
Authors: Burns Ariel M. , Green Peter J. , Pasternak Sylvia
Published: September 2011

A 59‐year‐old female with rheumatoid arthritis on etanercept therapy presented with a 7‐cm‐large subcutaneous forearm mass. Multiple smaller nodules subsequently developed on the upper and lower extremities. Except for a new cough, the patient was systemically well. Biopsy of the mass showed sarcoidal type granulomatous inflammation with nodular aggregations of non‐necrotizing epithelioid histiocytes in the subcutis. A chest computed tomography (CT) scan showed mediastinal adenopathy consistent with pulmonary sarcoidosis. Etanercept was discontinued, and the patient was started on adalimumab for rheumatoid arthritis control. The cutaneous nodules fully resolved in 6 months with no additional treatment. A 4‐month follow‐up CT scan showed significant regression of mediastinal adenopathy. The patient has since been maintained on adalimumab therapy for 2 years with no recurrence of sarcoid‐like manifestations. Biologic response modifiers targeting tumor necrosis factor alpha (TNFα) are effective treatments of chronic inflammatory conditions such as rheumatoid arthritis and psoriasis. TNFα represents a major cytokine in granuloma formation, and TNFα inhibitors are sometimes efficacious in the treatment of sarcoidosis. Paradoxically, there is a small volume of literature implicating TNFα inhibitors in the development of sarcoid‐like disease. We present this case to promote the recognition of TNFα inhibitor‐induced sarcoidosis and to illustrate the wide clinicopathologic differential of sarcoidal type granulomas.

Burns AM, Green PJ, Pasternak S. Etanercept‐induced cutaneous and pulmonary sarcoid‐like granulomas resolving with adalimumab.
Relaxin‐3 null mutation mice display a circadian hypoactivity phenotype
Authors: Smith C. M. , Hosken I. T. , Sutton S. W. , Lawrence A. J. , Gundlach A. L.
Published: September 2011

Characterizing the neurocircuits and neurotransmitters that underlie arousal and circadian sleep/wake patterns is an important goal of neuroscience research, with potential implications for understanding human mental illnesses, such as major depression. Recent anatomical and functional studies suggest that relaxin‐3 neurons and their ascending projections contribute to these functions via actions on key cortical, limbic and hypothalamic circuits. This study reports the behavioral phenotype of C57BL/6J backcrossed relaxin‐3 knockout (KO) mice. Cohorts of adult, male and female relaxin‐3 KO and wild‐type (WT) littermate mice were subjected to a battery of behavioral tests to assess sensorimotor function and complex behavior. No overt deficits were detected in motor‐coordination, spatial memory, sensorimotor gating, anxiety‐like behavior or locomotor behavior in novel environments; and no marked genotype differences were observed in response to a chronic stress protocol. Notably however, compared to WT mice, relaxin‐3 KO mice displayed robust hypoactivity during the dark/active phase when provided with free home‐cage access to voluntary running wheels. This circadian hypoactivity was reflected by reduced time spent and distance traveled on running wheels, coupled with an increase in the time spent immobile, possibly reflecting increased sleeping. Overall, these studies support a role for relaxin‐3 signaling in the control of arousal and sleep/wakefulness, and identify the relaxin‐3 KO mouse as a useful model to study this role further.
Hybridization and invasion: an experimental test with diffuse knapweed (Centaurea diffusa Lam.)
Authors: Blair Amy C. , Blumenthal Dana , Hufbauer Ruth A.
Published: September 2011

A number of studies have suggested a link between hybridization and invasion. In this study, we experimentally test the potential for hybridization to influence invasion through a greenhouse common garden study. Diffuse knapweed (DK) (Centaurea diffusa Lam.) was introduced to North America with admixture from spotted knapweed (SK) (Centaurea stoebe subsp. stoebe L.). Comparisons between North American DK (including hybrid phenotypes) and native (European) DK in a common garden did not reveal enhanced performance or increased phenotypic variance, suggesting that pre‐introduction hybridization or, more generally, post‐introduction evolutionary change has not significantly contributed to the invasion of DK. In contrast, early generation hybrids [artificially created Backcross 1 (BC1) plants] exhibited increased variance for eight of the examined traits, and greater leaf and reproductive shoot production when compared to North American DK. Individual BC1 lines differed for several traits, suggesting the importance of the cross for drawing conclusions from such comparisons. When compared to the parental species (DK and SK), the BC1 plants were not transgressive for any of the measured traits. Overall, these findings suggest that if diploid SK is introduced to North America, interspecific hybridization has the potential to result in even more aggressive invaders.
Pain Induced by a Minor Medical Procedure (Bone Marrow Aspiration) in Dogs: Comparison of Pain Scales in a Pilot Study
Authors: Guillot M. , Rialland P. , Nadeau M.‐È. , del Castillo J.R.E. , Gauvin D. , Troncy E.
Published: September 2011

Background

Bone marrow aspiration (BMA) is a clinical procedure frequently performed in dogs.

Objective

To compare levels of pain intensity induced by 3 differentBMAprocedures using several pain scoring instruments.

Animals

Sixteen healthy Beagles.

Methods

A prospective experimental pilot study was conducted using blinded observers. Dogs were randomized into 3 groups: iliacBMAunder sedation (Iliac‐Sed, n = 4), sternumBMAunder sedation (Stern‐Sed, n = 4), and sternumBMAon conscious dogs without sedation (Stern‐No‐Sed, n = 8).

Results

Using theSF‐Glasgowpain scale, the overall pain score in the Stern‐No‐Sed group was lower than that in theStern‐Sedgroup (P = 0.04). Using the 4A‐VETpain scale, the effects of procedures over time on pain scores did not differ between and within groups. An inactivity index indicated that the overall score for theStern‐No‐Sedgroup was significantly lower than the scores for theStern‐SedandIliac‐Sedgroups (P ≤ 0.01). There was a significant association in pain assessment using theSF‐Glasgowand 4A‐VETpain scales (P = 0.0004). When comparing theSF‐Glasgowscale to the 4A‐VETpain scale, the scores for theStern‐No‐Sedgroup were lower compared to those of theStern‐Sedscores (P = 0.03). Based on telemetered motor activity, theIliac‐Sedgroup may have experienced more discomfort during the post‐procedural period.

Conclusions and Clinical Importance

Dogs may experience mild to moderate pain afterBMAprocedures, and the sternal site should be preferred. TheSF‐Glasgowpain scale showed better interobserver reliability, but the 4A‐VETscale was less biased by sedation.
Magnetic resonance imaging findings in the carpus and proximal metacarpal region of 50 lame horses
Authors: NAGY A. , DYSON S.
Published: September 2011

Reasons for performing study:There is limited information on magnetic resonance imaging (MRI) findings in the carpus and proximal metacarpal region of lame horses.

Objectives:To document MRI findings in horses with lameness localised to the carpus and/or proximal metacarpal region.

Methods:Clinical records of horses that underwent MRI of the carpus and/or proximal metacarpal region at the Animal Health Trust between January 2003 and September 2010 were reviewed. Magnetic resonance images of all horses and available radiographs, ultrasonographic and scintigraphic images were assessed. When possible, MRI findings were related to the results of other diagnostic imaging techniques.

Results:Seventy‐two MR studies of 58 lame limbs in 50 horses from a broad range of work disciplines and ages were reviewed. The most commonly detected primary abnormality was decreased signal intensity in T1‐ and T2‐weighted images in the medial aspect of the carpal bones and/or the proximomedial aspect of the metacarpal bones (n = 29). Nine horses had syndesmopathy between the second and third metacarpal bones. In 6 horses the primary abnormalities were identified in the palmar cortex of the third metacarpal bone (McIII). Significant abnormalities of the suspensory ligament (SL) with associated lesions in the adjacent palmar cortex of the McIII were seen in 4 limbs. Ligament and associated osseous abnormalities between the second and third carpal bones and second and third metacarpal bones were detected in 4 limbs.

Conclusions and potential relevance:Magnetic resonance imaging enabled diagnosis of a variety of lesions not detected by conventional imaging in horses from a wide range of work disciplines. The distribution of injury types differed considerably from previous studies.
Osteochondrosis and osteochondral fragments in Standardbred trotters: Prevalence and relationships
Authors: LYKKJEN S. , ROED K. H. , DOLVIK N. I.
Published: September 2011

Reasons for performing study:Developmental orthopaedic diseases (DOD) such as osteochondrosis (OC)/osteochondrosis dissecans (OCD), palmar/plantar osteochondral fragments (POF), ununited palmar/plantar eminences (UPE) and dorsoproximal first phalanx fragments are well recognised in the horse. Aetiopathogeneses are controversial and molecular genetic screening of DNA has recently been employed for their elucidation. Precise phenotypic definition and knowledge of breed‐specific prevalence and interrelations are essential for the interpretation of following genomic studies in Standardbred trotters.

Objectives:To assess the prevalence, trend of development and interrelation of DOD in tarsocrural, metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints in Standardbred trotters.

Methods:The tarsocrural and MCP/MTP joints of 464 Norwegian Standardbred yearlings were radiographed and the prevalence and interrelation of osteochondral lesions calculated.

Results:Osteochondral lesions were diagnosed in 50.7% of the horses. The prevalence of tarsocrural OC/OCD at the distal intermediate ridge of the tibia (DIT) and the lateral trochlear ridge of the talus (LTT) was 19.3%. The prevalence of OC/OCD in MCP joints was 3.6%, whereas those of POF and UPE in MCP/MTP joints were 23.1 and 3.9%, respectively. Interrelation was evident for 1) most equivalent lesions in joint homologues, 2) OCD DIT and OCD LTT and 3) POF and UPE. Lesions in hock and fetlock joints were generally not significantly associated.

Conclusions:The prevalence of tarsocrural OC/OCD in Norwegian Standardbreds is apparently increasing, whereas that of other articular DOD appears stable. Association analyses verify bilateralism for most equivalent lesions and suggest aetiological resemblance also between other lesions. The absence of a significant association between tarsocrural OCD and POF implies that the lesions must be considered statistically different disorders.

Potential relevance:The prevalence results emphasise that DOD should be considered in Standardbred breeding regimens (e.g. by sire selection subsequent to progeny testing). Also, improved phenotypic definitions will help elucidate the true causal genes in following genomic studies.
Re‐imagining motor imagery: Building bridges between cognitive neuroscience and sport psychology
Authors: Moran Aidan , Guillot Aymeric , MacIntyre Tadhg , Collet Christian
Published: September 2011

One of the most remarkable capacities of the mind is its ability to simulate sensations, actions, and other types of experience. A mental simulation process that has attracted recent attention from cognitive neuroscientists and sport psychologists is motor imagery or the mental rehearsal of actions without engaging in the actual physical movements involved. Research on motor imagery is important in psychology because it provides an empirical window on consciousness and movement planning, rectifies a relative neglect of non‐visual types of mental imagery, and has practical implications for skill learning and skilled performance in special populations (e.g., athletes, surgeons). Unfortunately, contemporary research on motor imagery is hampered by a variety of semantic, conceptual, and methodological issues that prevent cross‐fertilization of ideas between cognitive neuroscience and sport psychology. In this paper, we review these issues, suggest how they can be resolved, and sketch some potentially fruitful new directions for inter‐disciplinary research in motor imagery.
The influence of sensitivity to reward and punishment, propensity for sensation seeking, depression, and anxiety on the risky behaviour of novice drivers: A path model
Authors: Scott‐Parker Bridie , Watson Barry , King Mark J. , Hyde Melissa K.
Published: September 2011

Young novice drivers are significantly more likely to be killed or injured in car crashes than older, experienced drivers. Graduated driver licensing (GDL), which allows the novice to gain driving experience under less‐risky circumstances, has resulted in reduced crash incidence; however, the driver's psychological traits are ignored. This paper explores the relationships between gender, age, anxiety, depression, sensitivity to reward and punishment, sensation‐seeking propensity, and risky driving. Participants were 761 young drivers aged 17–24 (M= 19.00, SD= 1.56) with a Provisional (intermediate) driver's licence who completed an online survey comprising socio‐demographic questions, the Impulsive Sensation Seeking Scale, Kessler's Psychological Distress Scale, the Sensitivity to Punishment and Sensitivity to Reward Questionnaire, and the Behaviour of Young Novice Drivers Scale. Path analysis revealed depression, reward sensitivity, and sensation‐seeking propensity predicted the self‐reported risky behaviour of the young novice drivers. Gender was a moderator; and the anxiety level of female drivers also influenced their risky driving. Interventions do not directly consider the role of rewards and sensation seeking, or the young person's mental health. An approach that does take these variables into account may contribute to improved road safety outcomes for both young and older road users.
Optimizing Cam Profiles Using the Particle Swarm Technique
Authors: H. Bravo Ramiro , W. Flocker Forrest
Published: September 2011

Cam-follower systems are ideally suited for many machine applications that require a specific and an accurate output motion. The required follower motion is achieved by carefully designing the shape or profile of the cam. Modern profiles are typically synthesized by piecing together a set of trigonometric and/or polynomial functions that satisfy the constraints. For most problems, there are many profile solutions that satisfy the constraints. In this paper, a relatively new optimization technique known as particle swarm optimization (PSO) is applied to the optimization of two different cam problems. The first example is a single-dwell cam in which the magnitude of the negative acceleration is minimized. The second example is a cam with a constant velocity segment in which the cycle time is optimized. The intent is to show the method in two different settings so that the reader can extend it to the optimization of any cam-follower problem. To illustrate the method, first the PSO method is applied to a mathematical function with two independent variables. Then, the method is used to find the cam profile that provides the minimum acceleration in a single-dwell cam using three independent variables. Finally, it is applied to obtain the minimum cycle time of a cam with a constant velocity segment using cubic interpolations and seven or more independent variables. The PSO method was very successful in all the optimization problems discussed in this paper. In the first cam problem, it significantly lowered the level of negative acceleration, while maintaining the positive acceleration at a constrained upper limit. The optimization procedure for the second cam problem found a very elegant five-segment solution. This solution results no matter how many initial segments or independent variables are chosen so long as there are at least five segments. Presented in this paper is the particle swarm optimizing technique that is applicable to many aspects of cam design. Two diverse examples were presented that illustrate how the PSO method can be used effectively in the optimization of cam-follower problems. In both illustrative examples, the PSO method proved to be robust, easy to implement, and suitable for minimizing a wide variety objective functions applicable to the design of cam-follower systems.
Power Flow Analysis of Compound Epicyclic Gear Transmission: Simpson Gear Train
Authors: Chen Chao
Published: September 2011

An analytical expression for the total efficiency of the Simpson gear train is derived using virtual power analysis. This expression is consistent with intuition when the total efficiency is 100%. Power flow analysis shows that there are no internal power circulation and amplification in the Simpson gear train. Analysis based on the derived efficiency formula shows that the total efficiency of the Simpson gear transmission is more sensitive to the individual gear efficiencies when the speed reduction is higher.
Launch of a Vehicle from a Ramp
Authors: Cross Rod
Published: September 2011

Avehicle proceeding up an inclined ramp will become airborne if the ramp comes to a sudden end and if the vehicle fails to stop before it reaches the end of the ramp. A vehicle may also become airborne if it passes over the top of a hill at sufficient speed. In both cases, the vehicle becomes airborne if the point of support underneath the vehicle falls below the trajectory that would be followed by the vehicle in the presence of gravity alone. When the vehicle becomes airborne, the normal reaction force exerted by the ramp or the hill drops to zero, first on the front wheels and then on the rear wheels. Just prior to the vehicle's becoming airborne, the normal reaction force on the rear wheels acts to exert a torque on the vehicle, causing the vehicle to rotate. After the rear wheels become airborne, the vehicle will continue to rotate until it lands some distance from the launch point.
Targeting Intracellular Oncoproteins with Antibody Therapy or Vaccination
Authors: Guo Ke , Li Jie , Tang Jing Ping , Tan Cheng Peow Bobby , Hong Cheng William , Al-Aidaroos Abdul Qader O. , Varghese Leyon , Huang Caixia , Zeng Qi
Published: September 2011

Antibody therapy can target intracellular proteins.
Excretion of Moxidectin into Breast Milk and Pharmacokinetics in Healthy Lactating Women
Authors: Korth-Bradley Joan M. , Parks Virginia , Chalon Stephan , Gourley Ian , Matschke Kyle , Gossart Sophie , Bryson Philip , Fleckenstein Lawrence
Published: September 2011

Moxidectin, registered worldwide as a veterinary antiparasitic agent, is currently under development for humans for the treatment of onchocerciasis in collaboration with the World Health Organization. The objective of this study was to assess the pharmacokinetics of moxidectin in healthy lactating women, including the excretion into breast milk. Twelve women, ages 23 to 38 years, weighing 54 to 79 kg, all more than 5 months postpartum, were enrolled, following their plan to wean their infants and provision of informed consent. A single 8-mg, open-label dose was administered orally after consumption of a standard breakfast. Complete milk collection was done for approximately 28 days, and plasma samples were collected for 90 days. Moxidectin concentrations were measured by high-performance liquid chromatography (HPLC) with fluorescence detection, with a validated range of 0.08 to 120 ng/ml. Noncompartmental pharmacokinetic methods were used to find the following results: peak concentration in plasma (
C
max
), 87 ± 25 ng/ml; time to
C
max
(
t
max
), 4.18 ± 1.59 h; terminal-phase elimination half-life (
t
1/2
), 832 ± 321 h; total area under the concentration-time curve (AUC), 4,046 ± 1,796 ng·h/ml; apparent oral dose clearance (CL/
F
), 2.35 ± 1.07 l/h; ratio of CL/
F
to the terminal-phase disposition rate constant, λ

z

(V
λ

z

/
F
), 2,526 ± 772 liters; percentage of maternal dose excreted in milk, 0.701 ± 0.299%; absolute amount excreted in milk, 0.056 ± 0.024 mg; relative infant dose, 8.73 ± 3.17% of maternal dose assuming complete absorption; clearance in milk (CL
milk
), 0.016 ± 0.009 liter/h. Nine of 12 subjects reported adverse events, all of which were considered treatment emergent but not drug related and were mostly reported during the long outpatient period 8 to 90 days after dose administration. The most frequently reported adverse events were headache and nausea (
n
= 4), oropharyngeal pain (
n
= 2), rhinitis, viral pharyngitis, and viral upper respiratory tract infection (
n
= 2).
Increased
pfmdr1
Copy Number and Sequence Polymorphisms in Plasmodium falciparum Isolates from Sudanese Malaria Patients Treated with Artemether-Lumefantrine
Authors: Gadalla Nahla B. , Adam Ishag , Elzaki Salah-Eldin , Bashir Sahar , Mukhtar Izdihar , Oguike Mary , Gadalla Amal , Mansour Fathi , Warhurst David , El-Sayed Badria B. , Sutherland Colin J.
Published: September 2011

Molecular markers for surveillance of
Plasmodium falciparum
resistance to current antimalarials are sorely needed. A 28-day efficacy study of artemether-lumefantrine in eastern Sudan identified 5 treatment failures among 100 evaluable patients; 9 further individuals were parasite positive by PCR during follow-up. Polymorphisms in
pfatpase6
and
pfmdr1
were evaluated by DNA sequencing. One individual carried parasites with a novel
pfmdr1
polymorphism (F1044L).
pfmdr1
gene amplification in parasites prior to treatment occurred in three individuals who had recurrent infection during follow-up.
Plasma and Intracellular Population Pharmacokinetic Analysis of Tenofovir in HIV-1-Infected Patients
Authors: Baheti Gautam , Kiser Jennifer J. , Havens Peter L. , Fletcher Courtney V.
Published: September 2011

The relationships among the dose of tenofovir disoproxil fumarate (TDF), tenofovir (TFV) plasma concentrations, and intracellular TFV diphosphate (TFV-DP) concentrations are poorly understood. Our objective was to characterize TFV and TFV-DP relationships. Data were pooled from two studies in HIV-infected persons (
n
= 55) on stable antiretroviral therapy. TFV and TFV-DP were measured with validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) methods. Nonlinear mixed effects modeling (NONMEM 7) was used to develop the population model and explore the influence of covariates on TFV. A sequential analysis approach was utilized. A two-compartment model with first-order absorption best described TFV PK (FOCEI). An indirect stimulation of response model best described TFV-DP, where formation of TFV-DP was driven by plasma TFV concentration. Final plasma population estimates were as follows: absorption rate constant, 1.03 h
−1
; apparent clearance (CL/F), 42 liters/h (33.5% interindividual variability [IIV]); intercompartment clearance, 181 liters/h; apparent central distribution volume (Vc/F), 273 liters (64.8% IIV); and apparent peripheral distribution volume (Vp/F), 440 liters (46.5% IIV). Creatinine clearance was the most significant covariate on CL/F and Vc/F. The correlation between CL/F and Vc/F was 0.553. The indirect response model for TFV-DP resulted in estimates of the maximal intracellular concentration (
E
max
), the TFV concentration producing 50% of
E
max
(EC
50
), and the intracellular elimination rate constant (
k
out
) of 300 fmol/10
6
cells (82% IIV), 100 ng/ml (106% IIV), and 0.008 h
−1
, respectively. The estimated
k
out
gave an 87-h TFV-DP half-life. A predictive check assessment indicated satisfactory model performance. This model links formation of TFV-DP with plasma TFV concentrations and should facilitate more informed investigations of TFV clinical pharmacology.
PATRIC: the Comprehensive Bacterial Bioinformatics Resource with a Focus on Human Pathogenic Species
Authors: Gillespie Joseph J. , Wattam Alice R. , Cammer Stephen A. , Gabbard Joseph L. , Shukla Maulik P. , Dalay Oral , Driscoll Timothy , Hix Deborah , Mane Shrinivasrao P. , Mao Chunhong , Nordberg Eric K. , Scott Mark , Schulman Julie R. , Snyder Eric E. , Sullivan Daniel E. , Wang Chunxia , Warren Andrew , Williams Kelly P. , Xue Tian , Seung Yoo Hyun , Zhang Chengdong , Zhang Yan , Will Rebecca , Kenyon Ronald W. , Sobral Bruno W.
Published: September 2011

Funded by the National Institute of Allergy and Infectious Diseases, the
Pat
hosystems
R
esource
I
ntegration
C
enter (PATRIC) is a genomics-centric relational database and bioinformatics resource designed to assist scientists in infectious-disease research. Specifically, PATRIC provides scientists with (i) a comprehensive bacterial genomics database, (ii) a plethora of associated data relevant to genomic analysis, and (iii) an extensive suite of computational tools and platforms for bioinformatics analysis. While the primary aim of PATRIC is to advance the knowledge underlying the biology of human pathogens, all publicly available genome-scale data for bacteria are compiled and continually updated, thereby enabling comparative analyses to reveal the basis for differences between infectious free-living and commensal species. Herein we summarize the major features available at PATRIC, dividing the resources into two major categories: (i) organisms, genomes, and comparative genomics and (ii) recurrent integration of community-derived associated data. Additionally, we present two experimental designs typical of bacterial genomics research and report on the execution of both projects using only PATRIC data and tools. These applications encompass a broad range of the data and analysis tools available, illustrating practical uses of PATRIC for the biologist. Finally, a summary of PATRIC's outreach activities, collaborative endeavors, and future research directions is provided.
Outer Membrane Protein A of Bovine and Ovine Isolates of Mannheimia haemolytica Is Surface Exposed and Contains Host Species-Specific Epitopes
Authors: Hounsome Jonathan D. A. , Baillie Susan , Noofeli Mojtaba , Riboldi-Tunnicliffe Alan , Burchmore Richard J. S. , Isaacs Neil W. , Davies Robert L.
Published: September 2011

Mannheimia haemolyticais the etiological agent of pneumonic pasteurellosis of cattle and sheep; two different OmpA subclasses, OmpA1 and OmpA2, are associated with bovine and ovine isolates, respectively. These proteins differ at the distal ends of four external loops, are involved in adherence, and are likely to play important roles in host adaptation.M. haemolyticais surrounded by a polysaccharide capsule, and the degree of OmpA surface exposure is unknown. To investigate surface exposure and immune specificity of OmpA among bovine and ovineM. haemolyticaisolates, recombinant proteins representing the transmembrane domain of OmpA from a bovine serotype A1 isolate (rOmpA1) and an ovine serotype A2 isolate (rOmpA2) were overexpressed, purified, and used to generate anti-rOmpA1 and anti-rOmpA2 antibodies, respectively. Immunogold electron microscopy and immunofluorescence techniques demonstrated that OmpA1 and OmpA2 are surface exposed, and are not masked by the polysaccharide capsule, in a selection ofM. haemolyticaisolates of various serotypes and grown under different growth conditions. To explore epitope specificity, anti-rOmpA1 and anti-rOmpA2 antibodies were cross-absorbed with the heterologous isolate to remove cross-reacting antibodies. These cross-absorbed antibodies were highly specific and recognized only the OmpA protein of the homologous isolate in Western blot assays. A wider examination of the binding specificities of these antibodies forM. haemolyticaisolates representing different OmpA subclasses revealed that cross-absorbed anti-rOmpA1 antibodies recognized OmpA1-type proteins but not OmpA2-type proteins; conversely, cross-absorbed anti-rOmpA2 antibodies recognized OmpA2-type proteins but not OmpA1-type proteins. Our results demonstrate that OmpA1 and OmpA2 are surface exposed and could potentially bind to different receptors in cattle and sheep.
Comparative Transcriptional Study of the Putative Mannose Donor Biosynthesis Genes in Virulent Mycobacterium tuberculosis and Attenuated Mycobacterium bovis BCG Strains
Authors: Keiser Tracy L. , Azad Abul K. , Guirado Evelina , Bonacci Robert , Schlesinger Larry S.
Published: September 2011

Mycobacterium tuberculosiscontains mannosylated cell wall components which are important in macrophage recognition and response. The building block for the mannosyl constituents of these components is GDP-mannose, which is synthesized through a series of enzymes involved in the mannose donor biosynthesis pathway. Nothing is known about the expression levels of the genes encoding these enzymes during the course of infection. To generate transcriptional profiles for the mannose donor biosynthesis genes from virulentM. tuberculosisand attenuatedMycobacterium bovisBCG, bacteria were grown in broth culture and within human macrophages. Our results with broth-grown bacteria show that there are differences in expression of the selected genes betweenM. tuberculosisand BCG, with increased expression ofmanCinM. tuberculosisandmanAin BCG during stationary-phase growth. Results forM. tuberculosisextracted from within macrophages show thatwhiB2is highly expressed andmanBandmanCare moderately expressed during infection.Rv3256c,Rv3258c, andppm1have high expression levels early and decreased expression as the infection progresses. Results with BCG show that, as inM. tuberculosis,whiB2is highly expressed throughout infection, whereas there is either low expression or little change in expression of the remaining genes studied. Overall, our results show that there is differential regulation of expression of several genes in the mannose donor biosynthesis pathway ofM. tuberculosisand BCG grown in broth and within macrophages, raising the possibility that the level of mannose donors may vary during the course of infection and thereby impact the biosynthesis of mannose-containing cell wall molecules.
Role for the Src Family Kinase Fyn in Sphingolipid Acquisition by Chlamydiae
Authors: Mital Jeffrey , Hackstadt Ted
Published: September 2011

The bacterial obligate intracellular pathogen
Chlamydia trachomatis
replicates within a membrane-bound vacuole termed the inclusion. From within this protective environment, chlamydiae usurp numerous functions of the host cell to promote chlamydial survival and replication. Here we utilized a small interfering RNA (siRNA)-based screening protocol designed to identify host proteins involved in the trafficking of sphingomyelin to the chlamydial inclusion. Twenty-six host proteins whose deficiency significantly decreased sphingomyelin trafficking to the inclusion and 16 proteins whose deficiency significantly increased sphingomyelin trafficking to the inclusion were identified. The reduced sphingomyelin trafficking caused by downregulation of the Src family tyrosine kinase Fyn was confirmed in more-detailed analyses. Fyn silencing did not alter sphingomyelin synthesis or trafficking in the absence of chlamydial infection but reduced the amount of sphingomyelin trafficked to the inclusion in infected cells, as determined by two independent quantitative assays. Additionally, inhibition of Src family kinases resulted in increased cellular retention of sphingomyelin and significantly decreased incorporation into elementary bodies of both
C. trachomatis
and
Chlamydophila caviae
.
Meeting the demand for more sophisticated study designs. A proposal for a new type of clinical trial: the hybrid design
Authors: Soon Guoxing G , Nie Lei , Hammerstrom Thomas , Zeng Wen , Chu Haitao
Published: September 2011

Background

Treatment effect is traditionally assessed through either superiority or non-inferiority clinical trials. Investigators may find that because of safety concerns and/or wide variability across strata of the superiority margin of active controls over placebo, neither a superiority nor a non-inferiority trial design is ethical or practical in some disease populations. Prior knowledge may allow and drive study designers to consider more sophisticated designs for a clinical trial.

Design

In this paper, the authors propose hybrid designs which may combine a superiority design in one subgroup with a non-inferiority design in another subgroup or combine designs with different control regimens in different subgroups in one trial when a uniform design is unethical or impractical. The authors show how the hybrid design can be planned and how inferences can be made. Through two examples, the authors illustrate the scenarios where hybrid designs are useful while the conventional designs are not preferable.

Conclusion

The hybrid design is a useful alternative to current superiority and non-inferiority designs.
Obesity, orbitofrontal structure and function are associated with food choice: a cross-sectional study
Authors: Cohen Jessica I , Yates Kathy F , Duong Michelle , Convit Antonio
Published: September 2011

Objectives

Obesity is on the rise in the US and is linked to the development of type 2 diabetes and cardiovascular disease. Emerging evidence over the last decade suggests that obesity may also adversely affect executive function and brain structure. Although a great deal of research focuses on how diet affects the brain and cognitive performance, no study focuses on how food choice may be associated with brain integrity. Here we investigated how lean and overweight/obese (o/o) adults differed in their food choices and how brain structure and cognition may be associated with those choices.

Design

As part of an ongoing study on diabetes and the brain, participants had routine blood work and a research MRI, received a battery of neurocognitive tests, and were instructed to keep a 3-day food diary.

Results and conclusions

The lean group ate more high quality foods and less low quality foods compared to the o/o group. In the o/o group, high quality food choices were associated with orbitofrontal cortex volume. The lean group performed better than the o/o group on neurocognitive measures of executive function, such as the Stroop Interference Test, the Wisconsin Card Sort Test and the Trail Making Test B-A, and on attention and concentration tasks such as the Digit Symbol Substitution Test. Taken together, these preliminary data suggest that in obesity poor food choices may be associated with frontal cognitive impairments that may be the result of, or contribute to, decreases in orbitofrontal cortex volume. Therefore, longitudinal studies are warranted to investigate a causal link between food choice and executive functioning.
Temporary transvenous pacing: endangered skill
Authors: Sharma Sumeet , Sandler Belinda , Cristopoulos Christos , Saraf Smriti , Markides Vias , Gorog Diana A
Published: September 2011

Background

Temporary cardiac pacing although is an essential requirement for core medical training (CMT) in UK, there are no defined training measures and guidelines available as to who should perform this.

Methods

We conducted an anonymous survey of 300 non-cardiology medical registrars regarding their individual ability, experience and training received in temporary pacing wire (TPW) insertion.

Results

A total of 202 (67%) responses were received. 61% (123) had not performed any TPW insertion before becoming a registrar. Only18% (38) felt confident in inserting a TPW unsupervised and only14 (7%) had ever received any formal training. The majority, 169 (84%), did not feel that their on-call consultant general physician would be able to perform the procedure.

Conclusion

This survey shows that general medical registrars lack a major life-saving skill that is required as part of CMT. Thus, there is now an urgent clinical governance need to either formally train physicians or abandon the concept and practice of general internal medicine-led temporary pacing, and devolve this to cardiologists.
A physiotherapy service to an emergency extended care unit does not decrease admission rates to hospital: a randomised trial
Authors: Jesudason Christabel , Stiller Kathy , McInnes Matthew , Sullivan Thomas
Published: September 2011

Background

One of the reasons physiotherapy services are provided to emergency departments (EDs) and emergency extended care units (EECUs) is to review patients' mobility to ensure they are safe to be discharged home.

Aim

To investigate whether a physiotherapy service to an EECU altered the rate of hospital admission, rate of re-presentation to the ED, visits to community healthcare practitioners, return to usual work/home/leisure activities and patient satisfaction.

Methods

A randomised trial with concealed allocation, assessor blinding and intention-to-treat analysis was undertaken in an EECU. The sample comprised 186 patients (mean age 70 years, 123 (66%) female patients, 130 (70%) trauma) who were referred for physiotherapy assessment/intervention. Referral occurred at any stage of the patients' EECU admission. All participants received medical/nursing care as required. The physiotherapy group also received physiotherapy assessment/intervention.

Results

The physiotherapy group had a 4% (95% CI −18% to 9%) lower rate of admission to hospital than the control group and a 4% (95% CI −6% to 13%) higher rate of re-presentation to the ED, which were statistically non-significant (p≥0.45). Differences between groups for use of community healthcare resources, return to usual work/home/leisure activities and satisfaction with their EECU care were small and not significant.

Conclusion

A physiotherapy service for EECU patients, as provided in this study, did not reduce the rate of hospital admission, rate of re-presentation to the ED, use of community healthcare resources, or improve the rate of return to usual work/home/leisure activities or patient satisfaction.

Trial registration number

ANZCTRN12609000106235.
Psuedotumor cerebri presenting with ataxia and hyper-reflexia in a non-obese woman treated with sinus stenting
Authors: Teleb Mohamed S , Rekate Harold , Chung Steve , Albuquerque Felipe C
Published: September 2011

Aim

To report a successful treatment of an atypical case of pseudotumor cerebri.

Background

Pseudotumor cerebri is a disorder of raised intracranial pressure. Multiple Case Series have been published about its treatment with sinus stenting. All these cases have had typical presentations.

Case

An atypical fulminant case of pseudotumor cerebri which was treated successfully with venous sinus stenting.

Conclusion

Venous sinus stenting can be done effectively in atypical cases of pseudotumor cerebri.
Ameliorative Effects of Ethanolic Leaf Extract ofAzadirachta indicaon Renal Histologic Alterations in Streptozotocin-Induced Diabetic Rats
Authors: Oluwole Busayo Akinola , Laura Zatta , Olufunke Olubusola Dosumu , Oluwafunmike Sharon Akinola , Luciana Dini , Ezekiel Ademola Caxton-Martins
Published: September 2011

We studied the effect of ethanolic leaf extract of Azadirachta indica (AIE) on the microanatomy of the kidney of streptozotocin-induced diabetic rats. Thirty male Wistar rats (161–190 g) were randomly assigned to one of five treatment groups of six animals each: control, diabetic, diabetic + AIE, diabetic + metformin, AIE only. Diabetes was induced with a single intraperitoneal dose of streptozotocin (70 mg/kg body weight). AIE and metformin were administered orally for 50 days (50 d) at 500 mg/kg bw/d and 350 mg/kg bw/d, respectively. Blood glucose was estimated by glucose oxidase method; plasma urea and creatinine were assayed; and paraffin sections of the kidney were stained by periodic acid-Schiff technique. Untreated diabetic rats exhibited marked hyperglycemia. Renal histopathology of these animals showed features of diabetic nephropathy, with nodular glomerulosclerosis and vacuolation of proximal tubule cells (Armanni-Ebstein phenomenon). These feature were absent in the diabetic rats treated with AIE. Besides, plasma urea and creatinine were not significantly different from the control in this group (p > 0.05), in contrast to the untreated diabetic rats, where significant increases in these markers (p < 0.05). These findings showed that the leaf extract of Azadirachta indica ameliorates hyperglycemia and diabetic nephropathy in rats.
Matrine Suppresses Production of IL-23/IL-17 and Ameliorates Experimental Autoimmune Encephalomyelitis
Authors: Zhao Xiaoyu , Kan Quancheng , Zhu Lin , Zhang Guang-Xian
Published: September 2011

Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been suggested to possess immunomodulatory characteristics; however, whether it is effective in multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS), is not known. Our aim was to bridge this gap by investigating the possible therapeutic effects of MAT on experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have found that, compared to the untreated controls, MAT-treated rats showed a significant decrease in clinical scores, in CNS infiltration of inflammatory cells (including CD4+, CD8+ T cells and macrophages) and demyelination. Furthermore, serum levels of IL-23 and IL-17 showed a marked reduction after MAT treatment, particularly in rats treated with higher doses of MAT. This study demonstrates that administration of MAT, as a natural compound, might be a novel therapy for autoimmune disorders such as MS.
Comparative Chemical and Statistical Analysis of Cultivated and Wild Radix Scutellariae
Authors: Chen Cheng-Yu , Chen Jian-Xin , Li Wei , Li Hua , Yang Bin
Published: September 2011

Radix Scutellariae has been widely used to hasten the process of heat clearing and dampness drying in traditional Chinese medicine. The resource of wild Radix Scutellariae is scarce; an increasing amount of cultivated Radix Scutellariae has become available in the market. To determine the clinical effects of Radix Scutellariae, we conducted a comparative analysis of the chemical compositions of cultivated and wild Radix Scutellariae. An HPLC fingerprint method was developed to determine simultaneously the amounts of baicalin, baicalein, and wogonin, which have been identified as active compounds in Radix Scutellariae. Chinese pharmacopoeia methodology was also applied to measure the ethanolic extract content of the wild and cultivated samples. Although the cultivated and wild Radix Scutellariae have similar concentrations of baicalein and wogonin, the concentrations of baicalin and ethanolic extracts are higher in the cultivated samples (i.e., 15.14% ± 1.11% and 56.90% ± 2.83%, respectively, compared to 11.17% ± 1.11%, and 44.16% ± 2.02%, respectively, in the wild Radix Scutellariae). Data from fingerprint analysis were statistically analyzed using the decision tree and hierarchical cluster methods. The study was carried out with 58 samples. Thus, the current study provides significant guidelines for distinguishing cultivated and wild Radix Scutellariae.
HERMITE VARIATIONS OF THE FRACTIONAL BROWNIAN SHEET
Authors: RÉVEILLAC ANTHONY , STAUCH MICHAEL , TUDOR CIPRIAN A.
Published: September 2011

We prove central and non-central limit theorems for the Hermite variations of the anisotropic fractional Brownian sheet Wα, βwith Hurst parameter (α, β) ∈ (0, 1)2. When [Formula: see text] or [Formula: see text] a central limit theorem holds for the renormalized Hermite variations of order q ≥ 2, while for [Formula: see text] we prove that these variations satisfy a non-central limit theorem. In fact, they converge to a random variable which is the value of a two-parameter Hermite process at time (1, 1).
A SUPPORT THEOREM AND A LARGE DEVIATION PRINCIPLE FOR KUNITA FLOWS
Authors: DEREICH STEFFEN , DIMITROFF GEORGI
Published: September 2011

In this paper, stochastic flows driven by Kunita-type stochastic differential equations are studied, focusing on support theorems (ST) and large deviation principles (LDP). We establish a new ST and LDP for Brownian flows with respect to a fine Hölder topology. Our approach is based on recent advances in rough paths theory, which is the natural framework for proving ST and LDP. Nevertheless, while rigorous, our presentation stays rather clear from the rough paths technicalities and is accessible for readers not familiar with them. We view the localized Brownian stochastic flow as a projection of the solution of a rough path differential equation implying the ST and LDP. In a second step the results are generalized for the global flow.
RANDOM ATTRACTORS FOR SECOND ORDER STOCHASTIC LATTICE DYNAMICAL SYSTEMS WITH MULTIPLICATIVE NOISE IN WEIGHTED SPACES
Authors: HAN XIAOYING
Published: September 2011

In this paper, we study the asymptotic behavior of solutions of a second order stochastic lattice differential equation with multiplicative white noise in weighted spaces. We first provide some sufficient conditions for the existence and uniqueness of solutions, and then establish the existence of tempered random bounded absorbing sets and global random attractors.