Interstitial Vascularity in Fibrosing Alveolitis

American Journal of Respiratory and Critical Care Medicine. Feb, 2003  |  Pubmed ID: 12406847

The aim of this study was to evaluate interstitial vascularity in cryptogenic fibrosing alveolitis (CFA) and in fibrosing alveolitis associated with systemic sclerosis (FASSc). Open lung biopsies from eight patients with CFA, nine patients with FASSc, and normal lung from 12 patients undergoing surgery for lung cancer were studied. Markers for endothelial cells (CD34) and cell proliferation (proliferating cell nuclear antigen) were localized by sequential immunohistochemistry and quantified using computer-assisted analysis. Vascular distribution was evaluated at increasing distances (up to 160 microm) from the airspaces. Vessel density was markedly reduced in both FASSc (3.9%) and in CFA (4.5%) compared with control samples (20.4%, p < 0.0001). The percentage of tissue occupied by vessels decreased with increasing distance from alveoli in control samples but not in CFA or FASSc samples. Endothelial cell proliferation indices were increased in FASSc but not in CFA, compared with control samples (p = 0.006). In conclusion, there is net vascular ablation and redistribution of blood vessels in areas of interstitial thickening in both CFA and FASSc, which may contribute to gas exchange impairment.

Enhancement of Angiogenesis by Endogenous Substance P Release and Neurokinin-1 Receptors During Neurogenic Inflammation

The Journal of Pharmacology and Experimental Therapeutics. Jul, 2003  |  Pubmed ID: 12660314

Early angiogenesis is a key step in the transition from acute to persistent inflammation. The nervous system has long been known to play a role in inflammation, in part through the release of substance P from peripheral nerve terminals (neurogenic inflammation). Application of substance P can stimulate vessel growth in a variety of angiogenesis assays, although it was previously not known whether endogenous substance P released from sensory nerves could modulate angiogenesis. We hypothesized that endogenous substance P can initiate angiogenesis during acute neurogenic inflammation. Here we show that 10 nmol of substance P can stimulate angiogenesis within the rat knee synovium, as shown by increased endothelial cell proliferation index [PCNA index, 19% (95% confidence interval (CI), 17 to 20%)] compared with saline injected knees [6% (95% CI, 4% to 8%), p < 0.05]. Moreover, this was prevented by coadministration of an antagonist of the neurokinin-1 (NK1) subtype of neurokinin receptor SR140333 (nolpitantium), 1 micro mol [8% (95% CI, 5% to 11%)]. Capsaicin 0.5%, which stimulates release of endogenous substance P from sensory nerves, was also found to enhance synovial angiogenesis, [PCNA index 17% (95% CI, 14% to 19%)] compared with saline injected control knees [2% (95% CI, 1% to 3%), p < 0.05], and this also was inhibited by 1 micro mol of SR140333 [11% (95% CI, 8 to 16%)]. Inhibition of capsaicin-enhanced angiogenesis was incomplete, and this may indicate a contribution of other neuropeptides, in addition to substance P-NK1 receptor interactions, in capsaicin-enhanced angiogenesis. NK1 receptor antagonists could have therapeutic potential in conditions where neurogenic angiogenesis contributes to disease.

Lateral Gene Transfer and the Origins of Prokaryotic Groups

Annual Review of Genetics. 2003  |  Pubmed ID: 14616063

Lateral gene transfer (LGT) is now known to be a major force in the evolution of prokaryotic genomes. To date, most analyses have focused on either (a) verifying phylogenies of individual genes thought to have been transferred, or (b) estimating the fraction of individual genomes likely to have been introduced by transfer. Neither approach does justice to the ability of LGT to effect massive and complex transformations in basic biology. In some cases, such transformation will be manifested as the patchy distribution of a seemingly fundamental property (such as aerobiosis or nitrogen fixation) among the members of a group classically defined by the sharing of other properties (metabolic, morphological, or molecular, such as small subunit ribosomal RNA sequence). In other cases, the lineage of recipients so transformed may be seen to comprise a new group of high taxonomic rank ("class" or even "phylum"). Here we review evidence for an important role of LGT in the evolution of photosynthesis, aerobic respiration, nitrogen fixation, sulfate reduction, methylotrophy, isoprenoid biosynthesis, quorum sensing, flotation (gas vesicles), thermophily, and halophily. Sometimes transfer of complex gene clusters may have been involved, whereas other times separate exchanges of many genes must be invoked.

Combined Effect of Bradykinin B2 and Neurokinin-1 Receptor Activation on Endothelial Cell Proliferation in Acute Synovitis

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. Apr, 2004  |  Pubmed ID: 14766794

During acute synovitis, early angiogenesis may enhance inflammation by facilitating edema formation and cellular infiltration. We have investigated the in vivo modulation by bradykinin of neurally enhanced early angiogenesis in rat models of knee synovitis. The increased endothelial cell proliferation that was observed 24 h after intra-articular injection of substance P (10 nmols) was completely blocked by either NK1 or B2 receptor antagonists (SR140333 or FR172357, respectively). In mild synovitis induced by 0.03% Carrageenan, but not in naïve animals, injection of bradykinin (100 nmols) increased endothelial cell proliferation. In moderate synovitis induced by 3% kaolin and 3% carrageenan, the combined blockade of both NK1 and B2 receptors inhibited 64% of the synovitis-enhanced endothelial cell proliferation. Synovitis-enhanced endothelial cell proliferation was also inhibited by the B2 receptor antagonist alone (27%) but not by the NK1 receptor antagonist alone. B1 receptor agonist (des-Arg9-bradykinin) and antagonist (SR240612A) did not significantly modulate endothelial cell proliferation. B2 receptor mRNA was constitutively expressed in both mild and moderate inflammation, whereas B1 mRNA production was induced in the moderate inflammation model. These findings demonstrate that substance P and bradykinin can act on NK1 and B2 receptors, respectively, to promote endothelial cell proliferation in acute synovitis.

The Effects of Violent Video Game Habits on Adolescent Hostility, Aggressive Behaviors, and School Performance

Journal of Adolescence. Feb, 2004  |  Pubmed ID: 15013257

Video games have become one of the favorite activities of American children. A growing body of research is linking violent video game play to aggressive cognitions, attitudes, and behaviors. The first goal of this study was to document the video games habits of adolescents and the level of parental monitoring of adolescent video game use. The second goal was to examine associations among violent video game exposure, hostility, arguments with teachers, school grades, and physical fights. In addition, path analyses were conducted to test mediational pathways from video game habits to outcomes. Six hundred and seven 8th- and 9th-grade students from four schools participated. Adolescents who expose themselves to greater amounts of video game violence were more hostile, reported getting into arguments with teachers more frequently, were more likely to be involved in physical fights, and performed more poorly in school. Mediational pathways were found such that hostility mediated the relationship between violent video game exposure and outcomes. Results are interpreted within and support the framework of the General Aggression Model.

Angiogenesis in Osteoarthritis and Spondylosis: Successful Repair with Undesirable Outcomes

Current Opinion in Rheumatology. Sep, 2004  |  Pubmed ID: 15314503

Osteoarthritis and spondylosis are frequently described as "wear-and-tear" arthritis, apparently contradicting modern management, which focuses on continuing and progressive exercise. Laboratory findings, including the growth of new blood vessels, encourage comparisons with repair processes. This review aims to place recent evidence in the context of previous work emphasizing the dynamic nature of tissues in these conditions.

Well-child Visits in the Video Age: Pediatricians and the American Academy of Pediatrics' Guidelines for Children's Media Use

Pediatrics. Nov, 2004  |  Pubmed ID: 15520101

The goal of this study was to evaluate awareness of, agreement with, and implementation of the American Academy of Pediatrics (AAP) media use guidelines among pediatricians. Pediatricians' beliefs about several media effects were also measured, as was their own media use. Pediatricians were also asked about how often they make media recommendations as part of anticipatory guidance during well-child visits, as well as the perceived efficacy of and barriers to making such recommendations.

Evolution of the RNA Polymerase B' Subunit Gene (rpoB') in Halobacteriales: a Complementary Molecular Marker to the SSU RRNA Gene

Molecular Biology and Evolution. Dec, 2004  |  Pubmed ID: 15356285

Many prokaryotes have multiple ribosomal RNA operons. Generally, sequence differences between small subunit (SSU) rRNA genes are minor (<1%) and cause little concern for phylogenetic inference or environmental diversity studies. For Halobacteriales, an order of extremely halophilic, aerobic Archaea, within-genome SSU rRNA sequence divergence can exceed 5%, rendering phylogenetic assignment problematic. The RNA polymerase B' subunit gene (rpoB') is a single-copy conserved gene that may be an appropriate alternative phylogenetic marker for Halobacteriales. We sequenced a fragment of the rpoB' gene from 21 species, encompassing 15 genera of Halobacteriales. To examine the utility of rpoB' as a phylogenetic marker in Halobacteriales, we investigated three properties of rpoB' trees: the variation in resolution between trees inferred from the rpoB' DNA and RpoB' protein alignment, the degree of mutational saturation between taxa, and congruence with the SSU rRNA tree. The rpoB' DNA and protein trees were for the most part congruent and consistently recovered two well-supported monophyletic groups, the clade I and clade II haloarchaea, within a collection of less well resolved Halobacteriales lineages. A comparison of observed versus inferred numbers of substitution revealed mutational saturation in the rpoB' DNA data set, particularly between more distant species. Thus, the RpoB' protein sequence may be more reliable than the rpoB' DNA sequence for inferring Halobacteriales phylogeny. AU tests of tree selection indicated the trees inferred from rpoB' DNA and protein alignments were significantly incongruent with the SSU rRNA tree. We discuss possible explanations for this incongruence, including tree reconstruction artifact, differential paralog sampling, and lateral gene transfer. This is the first study of Halobacteriales evolution based on a marker other than the SSU rRNA gene. In addition, we present a valuable phylogenetic framework encompassing a broad diversity of Halobacteriales, in which novel sequences can be inserted for evolutionary, ecological, or taxonomic investigations.

Research Bureaucracy in the United Kingdom: Ethics Committees Have Important Roles in Research

BMJ (Clinical Research Ed.). Sep, 2004  |  Pubmed ID: 15361452

The Real 'domains' of Life

Current Biology : CB. Apr, 2005  |  Pubmed ID: 15823519

Autoradiography of Enzymes, Second Messenger Systems, and Ion Channels

Methods in Molecular Biology (Clifton, N.J.). 2005  |  Pubmed ID: 15867467

Does the 'Ring of Life' Ring True?

Trends in Microbiology. Jun, 2005  |  Pubmed ID: 15936656

In a recent stimulating paper, Rivera and Lake applied a new phylogenetic method to study the evolution of genomes, which challenges the classical representation of the Tree of Life. Acknowledging the evolutionary importance of lateral gene transfer, they used the conditioned genome approach to reconstruct the Tree of Life, and in the end proposed a Ring of Life. They explained that the Ring of Life structure is a result of a single fusion event between two prokaryotic genomes at the base of the eukaryotic tree, probably between the ancestors of a photosynthetic bacterium and an archaeon. Because this constitutes an important conclusion with regards to the evolutionary process and origin of the eukaryotic cell, their work deserves further attention before these conclusions can be accepted. Here we question the reconstruction and the meaning of the Ring of Life. In addition to general problems associated with gene-content-based phylogenetic analyses, we discuss some implicit premises and potential weaknesses of the conditioned genome method and conclude that, although Rivera and Lake's conclusions might be right, they have not been established by their current approach.

Media Ratings for Movies, Music, Video Games, and Television: a Review of the Research and Recommendations for Improvements

Adolescent Medicine Clinics. Jun, 2005  |  Pubmed ID: 16111626

This article review is organized by studies that are relevant for testing the reliability and validity of ratings systems. Specifically, the interrater reliability, consistency, temporal stability, content validity, construct validity, and criterion validity of media ratings systems are reviewed. Data that are related to testing the "forbidden fruit" and "tainted fruit" hypotheses also are reviewed. Several changes are recommended to improve the ratings systems, including the creation of a universal ratings system that could be applied equally to all media. The research reviewed here can provide a guide for how to construct a reliable, valid, and more useful ratings system. This is important because the decisions that parents make regarding their children's media use can be only as good as the information to which the parents have access.

Archaeal Diversity Along a Soil Salinity Gradient Prone to Disturbance

Environmental Microbiology. Oct, 2005  |  Pubmed ID: 16156738

We employed a cultivation-independent approach to examine archaeal diversity along a transient soil salinity gradient at Salt Spring in British Columbia, Canada that is routinely eroded due to heavy, recurrent rainfall. Archaeal 16S rRNA gene libraries were created using DNA extracted from three soil samples collected along this gradient. Statistical comparisons indicated similar archaeal richness across sites but, a significant shift in archaeal community composition along the salinity gradient. Seven distinct phylogenetic groups were represented in soil libraries. Haloarchaea were the most commonly sampled group. Other 16S rRNA sequences were related to uncultured Euryarchaeota and Crenarchaeota or halophilic methanogens. Haloarchaeal diversity was remarkably high in soil of elevated salinity compared with previously characterized haloarchaeal communities. Salt Spring haloarchaea were not closely related to known low-salt adapted/tolerant species, suggesting they may be frequently faced with local mortality as a result of frequent declines in soil salinity. We speculate that ecosystem disturbance -- in the form of salinity fluctuations -- is one mechanism for maintaining a diverse community of haloarchaea at Salt Spring.

Goal Expectations As Predictors of Retirement Intentions

International Journal of Aging & Human Development. 2005  |  Pubmed ID: 16161290

The current study explored the contribution of personal goals to retirement decisions. A SMARTER methodology (to assess multiattribute utility) and taxonomy of human goals were used to investigate the relationship between older workers' personal goals and their retirement intentions. Two hundred and fifty-one employees of a large university, varying in age from 55 to 77, were asked to indicate the relative importance of 29 goals and to indicate the utility they perceived in continued work and retirement as a means to achieve these goals. The results demonstrate that goal evaluations are important predictors of retirement intentions. Furthermore, goal evaluations provide an important and unique contribution to predicting retirement intentions beyond that predicted by personal and demographic variables. These results have implications for pre-retirement education and workplace application.

Synthesis and Inhibitory Activity of Benzoic Acid and Pyridine Derivatives on Influenza Neuraminidase

Bioorganic & Medicinal Chemistry. Apr, 2005  |  Pubmed ID: 15755666

Based upon the activity and X-ray crystallographic studies of tri-substituted benzene derivatives containing carboxylic acid, acetamido and guanidine groups, we investigated the effect of the fourth substituent to fulfill the fourth pocket of neuraminidase enzyme. The groups selected as fourth substituents were hydroxymethyl, hydroxyethyl, oxime and amino. These tetra-substituted benzene derivatives were synthesized and evaluated for neuraminidase inhibitory activity. All these compounds were found to have poorer IC(50) values than the tri-substituted compounds. Further, benzene ring was replaced by pyridine ring and di, tri and tetra-substituted pyridine derivatives were synthesized. The activity of the pyridine derivatives was comparable to benzene derivatives. The fourth substituent seems to disturb the binding of the other three substituents, so the activity is reduced as compared to tri-substituted benzene and pyridine derivatives.

Tachykinins and the Cardiovascular System

Current Drug Targets. Aug, 2006  |  Pubmed ID: 16918331

The tachykinin family of vasoactive peptides comprises the neuropeptides substance P, neurokinin A and neurokinin B, and the newly discovered endokinins and hemokinins. Their cardiovascular effects are predominantly mediated by the family of neurokinin receptors. This review summarises the most recent advances in understanding the effects of tachykinins on the vasculature, and summarises their therapeutic potential. Tachykinins stimulate plasma extravasation, particularly acting through neurokinin-1 receptors in an endothelium-dependent manner. They therefore play prominent roles in tissue oedema and inflammation (called neurogenic inflammation). Pro-inflammatory effects of tachykinins are enhanced by their capacity to stimulate inflammatory cell recruitment, and to initiate angiogenesis. Tachykinins also regulate vascular tone and blood flow, although differences between species and between different vascular beds make this a highly complex area of research. They may relax vessels in some scenarios whilst inducing vasoconstriction in other situations, the state of the endothelium appearing to be of key importance. Tachykinins also modulate blood pressure and heart rate, acting both peripherally, and on the central nervous system. Cardiovascular effects of tachykinins and neurokinin receptors may be important therapeutic targets in diverse disorders such as pulmonary oedema, hypertension, pre-eclampsia, complex regional pain syndrome type 2, stroke and chronic inflammatory diseases such as arthritis. Sophisticated modelling of human disease is required to enable neurokinin receptor antagonists to achieve this therapeutic potential.

Interactions of RadB, a DNA Repair Protein in Archaea, with DNA and ATP

Journal of Molecular Biology. Apr, 2006  |  Pubmed ID: 16516228

The RecA family of recombinases (RecA, Rad51, RadA and UvsX) catalyse strand-exchange between homologous DNA molecules by utilising conserved DNA-binding modules and a common core ATPase domain. RadB was identified in archaea as a Rad51-like protein on the basis of conserved ATPase sequences. However, RadB does not catalyse strand exchange and does not turn over ATP efficiently. RadB does bind DNA, and here we report a triplet of residues (Lys-His-Arg) that is highly conserved at the RadB C terminus, and is crucial for DNA binding. This is consistent with the motif forming a "basic patch" of highly conserved residues identified in an atomic structure of RadB from Thermococcus kodakaraensis. As the triplet motif is conserved at the C terminus of XRCC2 also, a mammalian Rad51-paralogue, we present a phylogenetic analysis that clarifies the relationship between RadB, Rad51-paralogues and recombinases. We investigate interactions between RadB and ATP using genetics and biochemistry; ATP binding by RadB is needed to promote survival of Haloferax volcanii after UV irradiation, and ATP, but not other NTPs, induces pronounced conformational change in RadB. This is the first genetic analysis of radB, and establishes its importance for maintaining genome stability in archaea. ATP-induced conformational change in RadB may explain previous reports that RadB controls Holliday junction resolution by Hjc, depending on the presence or the absence of ATP.

Image Theory, Goal Incompatibility, and Retirement Intent

International Journal of Aging & Human Development. 2007  |  Pubmed ID: 18092668

Identity, as a guiding concept for work and retirement decisions, is explored in the current study. Image theory suggests that actions that "fit" with the goals of the trajectory image are fundamental for maintaining a positive and consistent self-identity (Beach, 1998; Beach & Mitchell, 1987). Incompatibility is the mechanism that evaluates whether retiring or continued work provides sufficient "fit" with the goals one hopes to achieve. In the current study, the "fit" of the trajectory image with retirement and work was measured in 238 full-time employees. Consistent with image theory predictions, individuals' perception of the incompatibility between five personal goals, within the trajectory image, and the choices of working and retiring predicted 25% of their retirement intent. Further support for goal incompatibility as a decision criterion is provided by findings showing it yielded better prediction than an alternative model based on goal facilitation, and equal prediction to an alternative model based on cost/benefit. Overall, the results are consistent with image theory and expand on continuity theory's (Atchley, 1999) concept of identity as fundamental for predicting retirement intent.

Neurovascular Invasion at the Osteochondral Junction and in Osteophytes in Osteoarthritis

Annals of the Rheumatic Diseases. Nov, 2007  |  Pubmed ID: 17446239

Normal adult articular cartilage is thought to be avascular and aneural.

Evolution of Rhodopsin Ion Pumps in Haloarchaea

BMC Evolutionary Biology. 2007  |  Pubmed ID: 17511874

The type 1 (microbial) rhodopsins are a diverse group of photochemically reactive proteins that display a broad yet patchy distribution among the three domains of life. Recent work indicates that this pattern is likely the result of lateral gene transfer (LGT) of rhodopsin genes between major lineages, and even across domain boundaries. Within the lineage in which the microbial rhodopsins were initially discovered, the haloarchaea, a similar patchy distribution is observed. In this initial study, we assess the roles of LGT and gene loss in the evolution of haloarchaeal rhodopsin ion pump genes, using phylogenetics and comparative genomics approaches.

Pathophysiological Mechanisms of Angiogenesis

Advances in Clinical Chemistry. 2007  |  Pubmed ID: 17682343

The growth of new blood vessels may be either beneficial or harmful. The angiogenic process may be measured by a variety of techniques, although it may often be the quality rather than quantity of resulting blood vessels that determines function. Endothelial cells play a key role in the initiation of angiogenesis, and vascular endothelial growth factor (VEGF) may be viewed as a prototypical direct-acting angiogenic factor. VEGF acts through multiple cell surface receptors and signaling pathways to stimulate endothelial cell proliferation, survival, and migration. By inducing other growth factor expression, VEGF stimulates a cascade of angiogenic activity. Different tissues may utilize various angiogenic pathways that are modulated by diverse host tissue responses. Furthermore, a single tissue may progress through a sequence of angiogenic pathways, for example, as acute injury progresses to chronic inflammation. The phenotype of the resulting neovasculature is critically dependent on the context in which it is formed. Biomarkers of angiogenesis are being developed as an aid to assessing human disease. Histological assessment of vascular density and angiogenic factor expression, in vivo imaging, Doppler ultrasound, and biofluid assays each may have clinical utility. Therapeutic targeting of angiogenesis will depend both on the generation of acceptable pharmacological agents and on the identification of patients who may and do gain benefit from such treatments.

Evaluation of Youth Pedometer-determined Physical Activity Guidelines Using Receiver Operator Characteristic Curves

Preventive Medicine. May, 2008  |  Pubmed ID: 18234326

Evidence-based pedometer guidelines have not been sufficiently validated in youth. The purpose of this paper was to evaluate the utility of current pedometer-determined physical activity guidelines for youth.

Combined Influence of Physical Activity and Screen Time Recommendations on Childhood Overweight

The Journal of Pediatrics. Aug, 2008  |  Pubmed ID: 18534231

To examine the combined influence of physical activity and screen time (television and video games) on the odds of being overweight and to evaluate the utility of current public policy recommendations.

SWITCH: Rationale, Design, and Implementation of a Community, School, and Family-based Intervention to Modify Behaviors Related to Childhood Obesity

BMC Public Health. 2008  |  Pubmed ID: 18588706

Although several previous projects have attempted to address the issue of child obesity through school-based interventions, the overall effectiveness of school-based programs on health-related outcomes in youth has been poor. Thus, it has been suggested that multi-level interventions that aim to influence healthy lifestyle behaviors at the community, school and family levels may prove more successful in the prevention of childhood obesity.

Molecular Phylogenetics: Testing Evolutionary Hypotheses

Methods in Molecular Biology (Clifton, N.J.). 2009  |  Pubmed ID: 19082555

A common approach for investigating evolutionary relationships between genes and organisms is to compare extant DNA or protein sequences and infer an evolutionary tree. This methodology is known as molecular phylogenetics and may be the most informative means for exploring phage evolution, since there are few morphological features that can be used to differentiate between these tiny biological entities. In addition, phage genomes can be mosaic, meaning different genes or genomic regions can exhibit conflicting evolutionary histories due to lateral gene transfer or homologous recombination between different phage genomes. Molecular phylogenetics can be used to identify and study such genome mosaicism. This chapter provides a general introduction to the theory and methodology used to reconstruct phylogenetic relationships from molecular data. Also included is a discussion on how the evolutionary history of different genes within the same set of genomes can be compared, using a collection of T4-type phage genomes as an example. A compilation of programs and packages that are available for conducting phylogenetic analyses is supplied as an accompanying appendix.

Evaluation of a Multiple Ecological Level Child Obesity Prevention Program: Switch What You Do, View, and Chew

BMC Medicine. 2009  |  Pubmed ID: 19765270

Schools are the most frequent target for intervention programs aimed at preventing child obesity; however, the overall effectiveness of these programs has been limited. It has therefore been recommended that interventions target multiple ecological levels (community, family, school and individual) to have greater success in changing risk behaviors for obesity. This study examined the immediate and short-term, sustained effects of the Switch program, which targeted three behaviors (decreasing children's screen time, increasing fruit and vegetable consumption, and increasing physical activity) at three ecological levels (the family, school, and community).

Early and Late Retirement Exits

International Journal of Aging & Human Development. 2009  |  Pubmed ID: 20235468

The current study proposes that personal need fulfillment (relatedness, generativity, identity, growth, and finances) predicts early and late retirement intentions. The personal needs of 160 full-time older employees were measured by personal goals, job satisfactions, job characteristics, and intrinsic motivation. Results suggest that the personal needs fulfilled by job employment remain important in retirement. The expectation for personal need fulfillment for identity, growth, and relatedness shifts from work to retirement for those who intend to retire early. The results are discussed in terms of the need for greater study of the relationship between expectations of personal need fulfillment, worker self-concept, and retirement decisions.

Metagenome of a Versatile Chemolithoautotroph from Expanding Oceanic Dead Zones

Science (New York, N.Y.). Oct, 2009  |  Pubmed ID: 19900896

Oxygen minimum zones, also known as oceanic "dead zones," are widespread oceanographic features currently expanding because of global warming. Although inhospitable to metazoan life, they support a cryptic microbiota whose metabolic activities affect nutrient and trace gas cycling within the global ocean. Here, we report metagenomic analyses of a ubiquitous and abundant but uncultivated oxygen minimum zone microbe (SUP05) related to chemoautotrophic gill symbionts of deep-sea clams and mussels. The SUP05 metagenome harbors a versatile repertoire of genes mediating autotrophic carbon assimilation, sulfur oxidation, and nitrate respiration responsive to a wide range of water-column redox states. Our analysis provides a genomic foundation for understanding the ecological and biogeochemical role of pelagic SUP05 in oxygen-deficient oceanic waters and its potential sensitivity to environmental changes.

First-line DMARD Choice in Early Rheumatoid Arthritis--do Prognostic Factors Play a Role?

Rheumatology (Oxford, England). Jul, 2010  |  Pubmed ID: 20008093

To examine if prognostic factors predict the choice of first DMARD for patients with RA.

Angiogenesis and the Persistence of Inflammation in a Rat Model of Proliferative Synovitis

Arthritis and Rheumatism. Jul, 2010  |  Pubmed ID: 20309868

To determine whether blood vessel growth at the onset of resolving synovitis leads to its subsequent persistence and whether inhibiting this angiogenesis at the onset of persistent inflammation leads to its subsequent resolution.

Angiogenesis and Nerve Growth Factor at the Osteochondral Junction in Rheumatoid Arthritis and Osteoarthritis

Rheumatology (Oxford, England). Oct, 2010  |  Pubmed ID: 20581375

Objectives. The osteochondral junction can be a source of pain in both RA and OA. Growth of blood vessels and nerves from the subchondral bone into articular cartilage may mediate the association between joint pathology and symptoms. We have investigated associations between angiogenesis, inflammation and neurovascular growth factor expression at the osteochondral junction in human arthritis. Methods. Osteochondral junctions from medial tibial plateaux of patients undergoing arthroplasty for RA (n = 10) or OA (n = 11), or from non-arthritic post-mortem controls (n = 11) were characterized by immunohistochemistry for CD34 and smooth muscle α-actin (blood vessels), CD68 (macrophages), CD3 (lymphocytes), proliferating cell nuclear antigen, vascular endothelial, platelet-derived and nerve growth factor (NGF). Results. Osteochondral angiogenesis was demonstrated as increased endothelial cell proliferation and vascular density in non-calcified articular cartilage, both in RA and OA. Osteochondral angiogenesis was associated with subchondral bone marrow replacement by fibrovascular tissue expressing VEGF, and with increased NGF expression within vascular channels. RA was characterized by greater lymphocyte infiltration and PDGF expression than OA, whereas chondrocyte expression of VEGF was a particular feature of OA. NGF was observed in vascular channels that contained calcitonin gene-related peptide-immunoreactive sensory nerve fibres. Conclusions. Osteochondral angiogenesis in RA and OA is associated with growth factor expression by cells within subchondral spaces, vascular channels and by chondrocytes. NGF expression and sensory nerve growth may link osteochondral angiogenesis to pain in arthritis.

Intracavity Parametric Generation of Nanosecond Terahertz Radiation Using Quasi-phase-matching

Optics Express. Jun, 2010  |  Pubmed ID: 20588528

We report the use of quasi-phase-matching techniques based on periodically-poled MgO:LiNbO(3) for the generation of nanosecond duration pulses of terahertz radiation in intracavity optical parametric oscillators. Multiple idler-waves are generated with temporal studies indicating that the initiating process is the expected parametric down-conversion, but followed by cascaded difference frequency generation. A number of grating geometries have been explored, revealing the presence of dual solutions for the quasi-phase-matching process in the general case. Choice of grating parameters so as to minimize oscillation threshold while simultaneously ensuring effective extraction of the THz radiation is considered.

Television and Video Game Exposure and the Development of Attention Problems

Pediatrics. Aug, 2010  |  Pubmed ID: 20603258

Television viewing has been associated with greater subsequent attention problems in children. Few studies have examined the possibility of a similar association between video games and attention problems, and none of these has used a longitudinal design.

Media Violence, Physical Aggression, and Relational Aggression in School Age Children: a Short-term Longitudinal Study

Aggressive Behavior. Nov, 2010  |  Pubmed ID: 21105065

Many studies have shown that media violence has an effect on children's subsequent aggression. This study expands upon previous research in three directions: (1) by examining several subtypes of aggression (verbal, relational, and physical), (2) by measuring media violence exposure (MVE) across three types of media, and (3) by measuring MVE and aggressive/prosocial behaviors at two points in time during the school year. In this study, 430 3rd-5th grade children, their peers, and their teachers were surveyed. Children's consumption of media violence early in the school year predicted higher verbally aggressive behavior, higher relationally aggressive behavior, higher physically aggressive behavior, and less prosocial behavior later in the school year. Additionally, these effects were mediated by hostile attribution bias. The findings are interpreted within the theoretical framework of the General Aggression Model. Aggr. Behav. 35:1-14, 2010. © 2010 Wiley-Liss, Inc.

Microbial Community Dynamics in a Seasonally Anoxic Fjord: Saanich Inlet, British Columbia

Environmental Microbiology. Jan, 2010  |  Pubmed ID: 19788414

Dissolved oxygen concentration plays a major role in shaping biotic interactions and nutrient flows within marine ecosystems. Throughout the global ocean, regions of low dissolved oxygen concentration (hypoxia) are a common and expanding feature of the water column, with major feedback on productivity and greenhouse gas cycling. To better understand microbial diversity underlying biogeochemical transformations within oxygen-deficient oceanic waters, we monitored and quantified bacterial and archaeal community dynamics in relation to dissolved gases and nutrients during a seasonal stratification and deep water renewal cycle in Saanich Inlet, British Columbia, a seasonally anoxic fjord. A number of microbial groups partitioned within oxygen-deficient waters including Nitrospina and SAR324 affiliated with the delta-proteobacteria, SAR406 and gamma-proteobacteria related to thiotrophic gill symbionts of deep-sea clams and mussels. Microbial diversity was highest within the hypoxic transition zone decreasing dramatically within anoxic basin waters and temporal patterns of niche partitioning were observed along defined gradients of oxygen and phosphate. These results provide a robust comparative phylogenetic framework for inferring systems metabolism of nitrogen, carbon and sulfur cycling within oxygen-deficient oceanic waters and establish Saanich Inlet as a tractable model for studying the response of microbial communities to changing levels of water column hypoxia.

Media Violence, Physical Aggression, and Relational Aggression in School Age Children: a Short-term Longitudinal Study

Aggressive Behavior. Mar-Apr, 2011  |  Pubmed ID: 21274855

Many studies have shown that media violence has an effect on children's subsequent aggression. This study expands upon previous research in three directions: (1) by examining several subtypes of aggression (verbal, relational, and physical), (2) by measuring media violence exposure (MVE) across three types of media, and (3) by measuring MVE and aggressive/prosocial behaviors at two points in time during the school year. In this study, 430 3rd-5th grade children, their peers, and their teachers were surveyed. Children's consumption of media violence early in the school year predicted higher verbally aggressive behavior, higher relationally aggressive behavior, higher physically aggressive behavior, and less prosocial behavior later in the school year. Additionally, these effects were mediated by hostile attribution bias. The findings are interpreted within the theoretical framework of the General Aggression Model.

Contributions of Angiogenesis to Inflammation, Joint Damage, and Pain in a Rat Model of Osteoarthritis

Arthritis and Rheumatism. Sep, 2011  |  Pubmed ID: 21538326

To determine the contributions of angiogenesis to inflammation, joint damage, and pain behavior in a rat meniscal transection model of osteoarthritis (OA).

Correlation of Protease-activated Receptor-2 Expression and Synovitis in Rheumatoid and Osteoarthritis

Rheumatology International. Sep, 2011  |  Pubmed ID: 21913036

Protease-activated receptor-2 (PAR-2) is known to be pro-inflammatory and increasing evidence points to an inflammatory component in osteoarthritis. This investigation examined the relationship between synovitis and PAR-2 expression, histological and immunohistochemical analysis being performed on synovial samples obtained from OA and RA patients, along with non-arthritic samples obtained by post mortem (PM). Samples were also analysed for PAR-4 expression, this receptor also having putative pro-inflammatory roles. Analysis involved comparison of inflammatory indices (synovial thickness and monocyte infiltration) with expression of PAR-2 and PAR-4. Synovial explants were also analysed for TNFα generation in the presence of a PAR-2 antagonist (ENMD-1068) or vehicle. OA synovia showed heterogeneity of inflammatory indicators, some samples overlapping with those from the RA cohort whilst others appeared similar to the PM cohort. PAR-2 expression, both in the lining layer and the interstitium, correlated strongly and significantly with synovial thickness (r = 0.91) and monocyte infiltration (r = 0.83), respectively (P < 0.001 in both cases), and this remains significant on individual cohort analysis. PAR-2 was co-localised to CD3 and CD68 cells in RA and OA synovium as well as fibroblasts derived from these synovia. PAR-4 was also expressed, but the relationship with inflammatory indicators was substantially weaker. Inflammatory indicators in OA synovia showed considerable variability, but correlated strongly with PAR-2 expression, suggesting PAR-2 upregulation in synovitis. Heterogeneity of inflammatory indicators was paralleled by wide variation in TNFα generation between samples. Secretion of this cytokine was dose-dependently inhibited by ENMD-1068, providing evidence of a functional role for PAR-2 in promoting synovitis.

Bisphosphonates for Osteoarthritis

Arthritis Research & Therapy. Sep, 2011  |  Pubmed ID: 21996085

ABSTRACT: Synovitis and subchondral bone turnover are associated with pain in osteoarthritis. Bisphosphonates provide tools for investigating these pathogenic mechanisms and also may have therapeutic potential. Translating preclinical findings into new treatments for human osteoarthritis requires a critical appraisal and refinement of animal models, identification of those pathogenic mechanisms that are amenable to intervention, and pharmacological targeting of those mechanisms in the right people at the right time.

Osteochondral Alterations in Osteoarthritis

Bone. Oct, 2011  |  Pubmed ID: 22023932

Osteoarthritis (OA) is a major cause of pain and disability in the aging population, but its pathogenesis remains incompletely understood. Alterations beneath the articular cartilage at the osteochondral junction are attracting interest as possible mediators of pain and structural progression in OA. Osteochondral changes occur early during the development of OA and may aggravate pathology elsewhere in the joint. Loss of osteochondral integrity removes the barrier between intra-articular and subchondral compartments, exposing subchondral bone and its nerves to abnormal chemical and biomechanical influence. Osteochondral plasticity results in a merging of tissue compartments across the junction. Loss of the clearly differentiated demarcation between bone and articular cartilage is associated with invasion of articular cartilage by blood vessels and sensory nerves, and advancing endochondral ossification. Increased subchondral bone turnover is intimately associated with these alterations at the osteochondral junction. Cells signal across the osteochondral junction, and this cross-talk may be both a consequence of, and contribute to these pathological changes. Bone turnover, angiogenesis and nerve growth are also features of other diseases such as osteoporosis and cancers, for which therapeutic interventions are already advanced in their development. Here we review pathological changes at the osteochondral junction and explore their potential therapeutic implications for OA. This article is part of a Special Issue entitled .

A Role for the Sensory Neuropeptide Calcitonin Gene-related Peptide in Endothelial Cell Proliferation in Vivo

British Journal of Pharmacology. Jan, 2012  |  Pubmed ID: 22233274

Background and purpos  We have tested the hypothesis that calcitonin gene-related peptide (CGRP) is a mediator of capsaicin-induced angiogenesis in vivo. Experimental approach  In a series of experiments the knee joints of rats were injected with CGRP, capsaicin or vehicle control. Groups of animals (n=6) were treated with the CGRP receptor antagonist BIBN4096BS and/or the NK(1) receptor antagonist SR140333. Endothelium, proliferating endothelial cell nuclei and macrophages were identified 24 h later in the synovium by immunohistochemistry and quantified by image analysis. mRNA for the receptors for CGRP and adrenomedullin were sought in normal and inflamed rat and human synovia using RT-PCR. Key results  Intra-articular CGRP injection increased the endothelial cell proliferation index, whereas macrophage infiltration and knee joint diameters were similar to saline-injected controls. CGRP-induced endothelial cell proliferation was dose-dependently inhibited by BIBN4096BS. mRNA for adrenomedullin and the CGRP receptor subunits were detected in normal and inflamed human and rat synovia. In capsaicin-induced synovitis the increased endothelial cell proliferation index was partially blocked by administration of NK(1) or CGRP antagonists individually, and reduced to the level of saline controls by co-administration of both receptor antagonists. Conclusions and implications  These data support the hypothesis that CGRP stimulates angiogenesis in vivo directly by activating CGRP receptors. Capsaicin-induced endothelial cell proliferation was completely blocked by co-administration of CGRP and NK(1) receptor antagonists, indicating that both CGRP and substance P may contribute to angiogenesis in this model of synovitis.

Remission in Early Rheumatoid Arthritis: Predicting Treatment Response

The Journal of Rheumatology. Jan, 2012  |  Pubmed ID: 22247360

OBJECTIVE: Optimizing therapeutic strategies to induce remission requires an understanding of the initial features predicting remission. Currently no suitable model exists. We aim to develop a remission score using predictors of remission in early rheumatoid arthritis (RA). METHODS: We used a dataset from a UK randomized controlled trial that evaluated intensive treatment with conventional combination therapy, to develop a predictive model for 24-month remission. We studied 378 patients in the trial who received 24 months' treatment. Our model was validated using data from a UK observational cohort (Early RA Network, ERAN). A group of 194 patients was followed for 24 months. Remission was defined as 28-joint Disease Activity Score < 2.6. Logistic regression models were used to estimate the associations between remission and potential baseline predictors. RESULTS: Multivariate logistic regression analyses showed age, sex, and tender joint count (TJC) were independently associated with 24-month remission. The multivariate remission score developed using the trial data correctly classified 80% of patients. These findings were replicated using ERAN. The remission score has high specificity (98%) but low sensitivity (13%). Combining data from the trial and ERAN, we also developed a simplified remission score that showed that younger men with a TJC of 5 or lower were most likely to achieve 24-month remission. Remission was least likely in older women with high TJC. Rheumatoid factor, rheumatoid nodules, and radiographic damage did not predict remission. CONCLUSION: Remission can be predicted using a score based on age, sex, and TJC. The score is relevant in clinical trial and routine practice settings.