bluuebunny/crossref_metadata_2025 huggingface dataset:
The selectivity of β‐adrenoceptor agonists at human β1‐, β2‐ and β3‐adrenoceptors
Authors: Baker Jillian G
Published: March 2010

Background and purpose: There are two important properties of receptor–ligand interactions: affinity (the ability of the ligand to bind to the receptor) and efficacy (the ability of the receptor–ligand complex to induce a response). Ligands are classified as agonists or antagonists depending on whether or not they have efficacy. In theory, it is possible to develop selective agonists based on selective affinity, selective intrinsic efficacy or both. This study examined the affinity and intrinsic efficacy of 31 β‐adrenoceptor agonists at the three human β‐adrenoceptors to determine whether the current agonists are subtype selective because of affinity or intrinsic efficacy.

Experimental approach: Stable clonal CHO‐K1 cell lines, transfected with either the human β1, β2or β3‐adrenoceptor, were used, and whole‐cell [3H]‐CGP 12177 radioligand binding and [3H]‐cAMP accumulation were measured.

Key results: Several agonists were found to be highly subtype selective because of selective affinity (e.g. salmeterol and formoterol, for the β2‐adrenoceptor over the β1or β3), while others (e.g. isoprenaline) had little affinity–selectivity. However, the intrinsic efficacy of salmeterol, formoterol and isoprenaline was similar across all three receptor subtypes. Other ligands (e.g. denopamine for β1; clenbuterol, AZ 40140d, salbutamol for β2) were found to have subtype‐selective intrinsic efficacy. Several ligands appeared to activate two agonist conformations of the β1‐ and β3‐adrenoceptors.

Conclusions and implications: There are agonists with subtype selectivity based upon both selective affinity and selective intrinsic efficacy. Therefore, there is scope to develop better selective agonists based upon both selective affinity and selective intrinsic efficacy.

This article is commented on by Kenakin, pp. 1045–1047 of this issue. To view this commentary visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00764.x
Acute administration of cannabidiolin vivosuppresses ischaemia‐induced cardiac arrhythmias and reduces infarct size when given at reperfusion
Authors: Walsh Sarah K , Hepburn Claire Y , Kane Kathleen A , Wainwright Cherry L
Published: March 2010

Background and purpose: Cannabidiol (CBD) is a phytocannabinoid, with anti‐apoptotic, anti‐inflammatory and antioxidant effects and has recently been shown to exert a tissue sparing effect during chronic myocardial ischaemia and reperfusion (I/R). However, it is not known whether CBD is cardioprotective in the acute phase of I/R injury and the present studies tested this hypothesis.

Experimental approach: Male Sprague‐Dawley rats received either vehicle or CBD (10 or 50 µg·kg−1i.v.) 10 min before 30 min coronary artery occlusion or CBD (50 µg·kg−1i.v.) 10 min before reperfusion (2 h). The appearance of ventricular arrhythmias during the ischaemic and immediate post‐reperfusion periods were recorded and the hearts excised for infarct size determination and assessment of mast cell degranulation. Arterial blood was withdrawn at the end of the reperfusion period to assess platelet aggregation in response to collagen.

Key results: CBD reduced both the total number of ischaemia‐induced arrhythmias and infarct size when administered prior to ischaemia, an effect that was dose‐dependent. Infarct size was also reduced when CBD was given prior to reperfusion. CBD (50 µg·kg−1i.v.) given prior to ischaemia, but not at reperfusion, attenuated collagen‐induced platelet aggregation compared with control, but had no effect on ischaemia‐induced mast cell degranulation.

Conclusions and implications: This study demonstrates that CBD is cardioprotective in the acute phase of I/R by both reducing ventricular arrhythmias and attenuating infarct size. The anti‐arrhythmic effect, but not the tissue sparing effect, may be mediated through an inhibitory effect on platelet activation.
The plant cannabinoid Δ9‐tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice
Authors: Bolognini Daniele , Costa Barbara , Maione Sabatino , Comelli Francesca , Marini Pietro , Di Marzo Vincenzo , Parolaro Daniela , Ross Ruth A , Gauson Lisa A , Cascio Maria G , Pertwee Roger G
Published: March 2010

Background and purpose: The phytocannabinoid, Δ9‐tetrahydrocannabivarin (THCV), can block cannabinoid CB1receptors. This investigation explored its ability to activate CB2receptors, there being evidence that combined CB2activation/CB1blockade would ameliorate certain disorders.

Experimental approach: We tested the ability of THCV to activate CB2receptors by determining whether: (i) it inhibited forskolin‐stimulated cyclic AMP production by Chinese hamster ovary (CHO) cells transfected with human CB2(hCB2) receptors; (ii) it stimulated [35S]GTPγS binding to hCB2CHO cell and mouse spleen membranes; (iii) it attenuated signs of inflammation/hyperalgesia induced in mouse hind paws by intraplantar injection of carrageenan or formalin; and (iv) any such anti‐inflammatory or anti‐hyperalgesic effects were blocked by a CB1or CB2receptor antagonist.

Key results: THCV inhibited cyclic AMP production by hCB2CHO cells (EC50= 38 nM), but not by hCB1or untransfected CHO cells or by hCB2CHO cells pre‐incubated with pertussis toxin (100 ng·mL−1) and stimulated [35S]GTPγS binding to hCB2CHO and mouse spleen membranes. THCV (0.3 or 1 mg·kg−1i.p.) decreased carrageenan‐induced oedema in a manner that seemed to be CB2receptor‐mediated and suppressed carrageenan‐induced hyperalgesia. THCV (i.p.) also decreased pain behaviour in phase 2 of the formalin test at 1 mg·kg−1, and in both phases of this test at 5 mg·kg−1; these effects of THCV appeared to be CB1and CB2receptor mediated.

Conclusions and implications: THCV can activate CB2receptorsin vitroand decrease signs of inflammation and inflammatory pain in mice partlyviaCB1and/or CB2receptor activation.

This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x
Differential effects of p38MAP kinase inhibitors on the expression of inflammation‐associated genes in primary, interleukin‐1β‐stimulated human chondrocytes
Authors: Joos H , Albrecht W , Laufer S , Brenner RE
Published: March 2010

Background and purpose:  A main challenge in the therapy of osteoarthritis (OA) is the development of drugs that will modify the disease. Reliable test systems are necessary to enable an efficient screening of therapeutic substances. We therefore established a chondrocyte‐based in vitro cell culture model in order to characterize different p38MAPK inhibitors.

Experimental approach:  Interleukin‐1β (IL‐1β)‐stimulated human OA chondrocytes were treated with the p38MAPK inhibitors Birb 796, pamapimod, SB203580 and the new substance CBS‐3868. Birb 796‐ and SB203580‐treated cells were analysed in a genome‐wide microarray analysis. The efficacy of all inhibitors was characterized by quantitative gene expression analysis and the quantification of PGE2 and NO release.

Key results:  Microarray analysis revealed inhibitor‐specific differences in gene expression. Whereas SB203580 had a broad effect on chondrocytes, Birb 796 counteracted the IL‐1β effect more specifically. All p38MAPK inhibitors significantly inhibited the IL‐1β‐induced gene expression of COX‐2, mPGES1, iNOS, matrix metalloproteinase 13 (MMP13) and TNFRSF11B, as well as PGE2 release. Birb 796 and CBS‐3868 showed a higher efficacy than SB203580 and pamapimod at inhibiting the expression of COX‐2 and MMP13 genes, as well as PGE2 release. In the case of mPGES1 and TNFRSF11B gene expression, CBS‐3868 exceeded the efficacy of Birb 796.

Conclusions and implications:  Our test system could differentially characterize inhibitors of the same primary pharmaceutical target. It reflects processes relevant in OA and is based on chondrocytes that are mainly responsible for cartilage degradation. It therefore represents a valuable tool for drug screening in between functional in vitro testing and in vivo models.
Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase‐9 activation through a calcium and protein kinase Cα‐dependent pathway: phorbol‐12‐myristate‐13‐acetate‐induced/extracellular signal‐regulated kinase/activator protein‐1
Authors: Hwang Yong P , Jeong Hye G
Published: March 2010

Background and purpose: Population studies have revealed that treatment with the anti‐diabetic drug metformin is significantly associated with reduced cancer risk, but the underlying mode of action has not been elucidated. The aim of our study was to determine the effect of metformin on tumour invasion and migration, and the possible mechanisms, using human fibrosarcoma HT‐1080 cells.

Experimental approach: We employed invasion, migration and gelatin zymography assays to characterize the effect of metformin on HT‐1080 cells. Transient transfection assays were performed to gene promoter activities, and immunoblot analysis to study its molecular mechanisms of action.

Key results: Metformin inhibited migration and invasion by HT‐1080 cells at sub‐toxic concentrations. In these cells, metformin also suppressed phorbol‐12‐myristate‐13‐acetate (PMA)‐enhanced levels of matrix metalloproteinases‐9 (MMP‐9) protein, mRNA and transcription activity through suppression of activator protein‐1 (AP‐1) activation. In addition, metformin strongly repressed the PMA‐induced phosphorylation of extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinase (JNK) and protein kinase C(PKC)α, whereas the phosphorylation of p38 mitogen‐activated protein kinase was not affected by metformin. Metformin decreased the PMA‐induced Ca2+influx. Furthermore, treatment with an intracellular Ca2+chelator (BAPTA‐AM) or a selective calmodulin antagonist (W7) markedly decreased PMA‐induced MMP‐9 secretion and cell migration, as well as activation of ERK and JNK/AP‐1.

Conclusions and implications: Metformin inhibited PMA‐induced invasion and migration of human fibrosarcoma cells via Ca2+‐dependent PKCα/ERK and JNK/AP‐1‐signalling pathways. Metformin therefore has the potential to be a potent anti‐cancer drug in therapeutic strategies for fibrosarcoma metastasis.
The Quagga Mussel Crisis at Lake Mead National Recreation Area, Nevada (U.S.A.)
Authors: HICKEY VALERIE
Published: March 2010

Abstract:  Parks are cornerstones of conservation; and non‐native invasive species drive extensive changes to biological diversity in parks. Knowing this, national park staff at Lake Mead National Recreation Area in the southwestern United States had a program in place for early detection of the non‐native, invasive quagga mussel (Dreissena rostriformis bugensis). Upon finding the mussel in January 2007, managers moved quickly to access funding and the best available science to implement a response. Managers considered four options—doing nothing, closing the park, restricting movement on the lakes, and educating and enforcing park visitors—and decided to focus on education and enforcing existing laws. Nonetheless, quagga spread throughout the park and soon began to appear throughout the western United States. I examined why efforts to control the expansion failed and determined the general lessons to be learned from this case. Concentrating human visitation on the lakes through land‐use zoning opened a pathway for invasion, reduced management options, and led to the rapid spread of quagga. To reconcile competing mandates to protect nature and provide recreation, zoning in parks has become a common practice worldwide. It reduces stress on some areas of a park by restricting and thus concentrating human activity in particular areas. Concentrating the human activity in one area does three things: cements pathways that repeatedly import and export vectors of non‐native invasive species; creates the disturbed area necessary to enable non‐native invasive species to gain a foothold; and, establishes a source of invasions that, without appropriate controls, can quickly spread to a park's wilderness areas.
Effects of Drainage‐Basin Geomorphology on Insectivorous Bird Abundance in Temperate Forests
Authors: IWATA TOMOYA , URABE JOTARO , MITSUHASHI HIROMUNE
Published: March 2010

Abstract:  Interfaces between terrestrial and stream ecosystems often enhance species diversity and population abundance of ecological communities beyond levels that would be expected separately from both the ecosystems. Nevertheless, no study has examined how stream configuration within a watershed influences the population of terrestrial predators at the drainage‐basin scale. We examined the habitat and abundance relationships of forest insectivorous birds in eight drainage basins in a cool temperate forest of Japan during spring and summer. Each basin has different drainage‐basin geomorphology, such as the density and frequency of stream channels. In spring, when terrestrial arthropod prey biomass is limited, insectivorous birds aggregated in habitats closer to streams, where emerging aquatic prey was abundant. Nevertheless, birds ceased to aggregate around streams in summer because terrestrial prey became plentiful. Watershed‐scale analyses showed that drainage basins with longer stream channels per unit area sustained higher densities of insectivorous birds. Moreover, such effects of streams on birds continued from spring through summer, even though birds dispersed out of riparian areas in the summer. Although our data are from only a single year, our findings imply that physical modifications of stream channels may reduce populations of forest birds; thus, they emphasize the importance of landscape‐based management approaches that consider both stream and forest ecosystems for watershed biodiversity conservation.
The tectono‐metamorphic evolution of the Balcooma Metamorphic Group, north‐eastern Australia: a multidisciplinary approach
Authors: ALI A.
Published: March 2010

The sequential growth of biotite, garnet, staurolite, kyanite, andalusite, cordierite and fibrolitic sillimanite, their microstructural relationships, foliation intersection axes preserved in porphyroblasts (FIAs), geochronology, P–T pseudosection (MnNCKFMASH system) modelling and geothermobarometry provide evidence for a P–T–t–D path that changes from clockwise to anticlockwise with time for the Balcooma Metamorphic Group. Growth of garnet at ∼530 °C and 4.6 kbar during the N–S‐shortening event that formed FIA 1 was followed by staurolite, plagioclase and kyanite growth. The inclusions of garnet in staurolite porphyroblasts that formed during the development of FIAs 2 and 3 plus kyanite growth during FIA 3 reflect continuous crustal thickening from c. 443 to 425 Ma during an Early Silurian Benambran Orogenic event. The temperature and pressure increased during this time from ∼530 °C and 4.6 kbar to ∼630 °C and 6.2 kbar. The overprinting of garnet‐, staurolite‐ and kyanite‐bearing mineral assemblages by low‐pressure andalusite and cordierite assemblages implies ∼4‐kbar decompression during Early Devonian exhumation of the Greenvale Province.
Modelling grain‐recycling zoning during metamorphism
Authors: PEARCE M. A. , WHEELER J.
Published: March 2010

Chemical zoning, recorded by grain growth during metamorphism, is a key source of information about P–T–t paths. Interpretation of these data must be carried out using appropriate models and recognizing their inherent assumptions. To assist with defining how zoned minerals form, a set of geometric criteria for three types of chemical zoning developed in minerals (diffusion, growth and grain recycling) is outlined. Re‐equilibration of minerals by lattice diffusion causes zoning if the re‐equilibration is incomplete. Growth of porphyroblasts is commonly considered in pelites, but in metagranitoids, large monophase domains undergo coarsening by recycling of material from one grain to another as grain boundaries migrate driven by surface energy. This type of grain size increase is termed here ‘grain recycling’. Zoning developed during grain recycling due to equilibration of the recycled material with grain‐boundary chemistry is termed ‘grain‐recycling zoning’. Furthermore, short lattice diffusion lengths relative to grain sizes cause metamorphic fractionation because material in the grain cores is not in communication thermodynamically with the rest of the rock. A new model is derived for this sort of grain size increase coupled with metamorphic reactions using Theriak–Domino. An example is given of plagioclase undergoing an increase in anorthite content as epidote breaks down during amphibolite facies metamorphism of a metagranitoid. Agreement between naturally occurring zoning profiles and those derived from modelled P–T–t paths shows that this model can be used to extract metamorphic conditions from rocks which are not accessible using conventional thermobarometry.
Relationship Between Fear of Falling and Outcomes of an Inpatient Geriatric Rehabilitation Population—Fear of the Fear of Falling
Authors: Denkinger Michael D. , Igl Wilmar , Lukas Albert , Bader Anne , Bailer Stefanie , Franke Sebastian , Denkinger Claudia M. , Nikolaus Thorsten , Jamour Michael
Published: March 2010

OBJECTIVES: To examine the effects of various risk factors on three functional outcomes during rehabilitation.

SETTING: Geriatric inpatient rehabilitation unit.

DESIGN: Observational longitudinal study.

PARTICIPANTS: One hundred sixty‐one geriatric rehabilitation inpatients (men, women), mean age 82, who were capable of walking at baseline.

MEASUREMENTS: Functional status was assessed weekly between admission and discharge and at a follow‐up 4 months later at home using the function component of the Short Form—Late Life Function and Disability Instrument, the Barthel Index, and Habitual Gait Speed. Various risk factors, such as falls‐related self‐efficacy (Falls Efficacy Scale–International), were measured. Associations between predictors and functional status at discharge and follow‐up were analyzed using linear regression models and bivariate plots.

RESULTS: Fear of falling predicted functioning across all outcomes except for habitual gait speed at discharge and follow‐up. Visual comparison of functional trajectories between subgroups confirmed these findings, with different levels of fear of falling across time in linear plots. Thus, superior ability of this measure to discriminate between functional status at baseline across all outcomes and to discriminate between functional change especially with regard to the performance‐based outcome was demonstrated.

CONCLUSION: Falls‐related self‐efficacy is the only parameter that significantly predicts rehabilitation outcome at discharge and follow‐up across all outcomes. Therefore, it should be routinely assessed in future studies in (geriatric) rehabilitation and considered to be an important treatment goal.
Prevention of Hip Fractures in Long‐Term Care: Relevance of Community‐Derived Data
Authors: Crilly Richard G. , Hillier Loretta M. , Mason Michelle , Gutmanis Iris , Cox Lizebeth
Published: March 2010

Osteoporosis and falling are two major contributing factors to fractures in older persons; the relevant contribution of these may vary according to age, setting, and frailty. The purpose of this review was to examine the existing evidence on osteoporosis treatments to determine whether participants in clinical trials include or resemble the older and frailer adult population living in long‐term care (LTC).

The trials (N=50) used to support major Canadian guidelines for osteoporosis treatment were reviewed because these are used to recommend treatment for all older adults, and several more‐recent studies were added. Trials conducted specifically with participants living in LTC were also reviewed (N=6).

The majority of studies (96.0%) on osteoporosis treatments were conducted with community‐dwelling participants, with many excluding participants resembling the LTC population. Mean ages ranged from 52 to 84, although for the majority of studies, the mean age was younger than 70. Similarly, 80.0% of studies conducted in LTC included only residents who were ambulatory, mobile, able to transfer independently, or not permanently bedridden. Mean ages in these studies ranged from 83 to 85.

These findings suggest that frail older adults, particularly the oldest and frailest adults in LTC, are neglected in clinical trials of osteoporosis fracture prevention. There is little evidence to support the application of community‐based guidelines to the LTC population, and studies directly involving this population are needed. The role of age, frailty, and the mechanics of falls in hip fracture are discussed.
Is There a Natural Rate of Crime?
Authors: Narayan Paresh Kumar , Nielsen Ingrid , Smyth Russell
Published: March 2010

Abstract

Studies in the economics of crime literature have reached mixed conclusions on the deterrence hypothesis. One explanation that has been offered for the failure to find evidence of a deterrent effect in the long run is the natural rate of crime. This article applies univariate unit root tests to crime series for the United Kingdom and United States and panel unit roots to crime rates for a panel of G7 countries to examine whether there is a natural rate of crime. Our main finding is that when we allow for two structural breaks in the univariate unit root test and a structural break in the panel data unit root test, there is strong evidence of a natural rate of crime. The policy implications of our findings is that governments should focus on altering the economic and social structural profile that determines crime in the long run rather than increasing expenditure on law enforcement that will at best reduce crime rates in the short run.
Language Nuances and Socioeconomic Outcomes
Authors: Chong Alberto , Guillen Jorge , Rios Vanessa
Published: March 2010

Abstract

While language enables communication, it also provides a reassuring quality more closely related with issues linked with trust, social capital, and cultural identification. Research on the role of language as a learning process is widespread but there is little evidence on its role as a signal for cultural affinity. We pursue this latter avenue of research and show that subtle language affinity is positively linked with change in socioeconomic outcome variables when using English‐speaking data for cities in the Golden Horseshoe area in Southern Ontario during the period 1991 to 2001.
School Kids and Oil Rigs: Two More Pieces of the Post‐Katrina Puzzle in New Orleans
Authors: Frailing Kelly , Wood Harper, Jr. Dee
Published: March 2010

Abstract

Shortly after Hurricane Katrina's landfall in August 2005 and the reports of rampant looting of businesses in the city, we became curious about the extent of Katrina looting as compared to that after other major storms that hit New Orleans in 1947 and in 1965. Using burglary as a proxy variable for looting, we discovered that the burglary rates in the month before and the month after Katrina were significantly higher than those before and after the other two hurricanes. We then investigated the socioeconomic conditions in the city in an effort to explain these numbers. Population loss and high unemployment rates, coupled with a decline in high‐paying manufacturing jobs and an increase in low‐wage food and hotel service jobs generated severe economic inequality in the city that exacerbated the situation created by Katrina. Our current analysis of the impact of public school desegregation and the oil bust suggests that both events contributed to population loss and the increase in low‐wage jobs prior to the storm. We believe that this type of research can assist in the recovery of New Orleans by providing an understanding of the city's pre‐Katrina social and economic conditions and make clearer which post‐Katrina changes are desirable.
Intrinsic Motivation and the Logic of Collective Action: The Impact of Selective Incentives
Authors: Kyriacou Andreas P.
Published: March 2010

Abstract

I integrate the notion of intrinsic motivation, applied to economics most notably byFrey (1997), into the logic of individual contributions toward collective goods as analyzed sinceOlson ([1965] 1971). This illuminates the many and various ways through which the intrinsic motivation to contribute toward such goods can be crowded out by the application of selective incentives. I suggest that the crowding‐out effect increases the cost to society of organizing the provision of collective goods and argue in favor of designing selective incentives that mitigate this effect.
Motives for Intergenerational Transfers: New Test for Exchange
Authors: Wang Jingshu
Published: March 2010

Abstract

The question of motives for private transfers is one with important policy implications. The evidence from empirical literature has been mixed. This study proposes new tests and evidence of the “exchange motive.” It examines the key assumption on which the exchange motive model is built: that a donor's behavior is determined by his/her own expectation of receiving inter‐vivos transfers or bequests in return. Results from national data show that adult children's time transfers to their aging parents were positively associated with their expectation of inter‐vivos financial transfers, but not with their expectation of receiving bequests.
Central Bank Communication and the Liquidity Trap
Authors: EUSEPI STEFANO
Published: March 2010

Central bank communication plays an important role in shaping market participants' expectations. This paper studies a simple nonlinear model of monetary policy where agents have incomplete information about the economic environment. It shows that agents' learning and the dynamics of the economy are heavily affected by central bank's transparency about its policy rule. A monetary authority that does not communicate its rule can induce “learning equilibria” where the economy experiences prolonged periods of deflation and slow growth. More generally, small expectational errors can result in complex economic dynamics, inducing welfare‐reducing fluctuations. On the contrary, central bank communication helps stabilizing expectations around the inflation target equilibrium.
The Determinants of Future U.S. Monetary Policy: High‐Frequency Evidence
Authors: TAYLOR NICHOLAS
Published: March 2010

This paper examines the determinants of future U.S. monetary policy by studying the relationship between a predictor of the future direction of monetary policy and a pertinent information set. Specifically, we investigate the impact of the surprise component of an array of macro‐economic announcements upon federal funds futures rates. This investigation is conducted using high‐frequency intraday data in order to examine the exact timing of rate reactions to announcements. In doing this, we find that Non‐farm Payrolls and Civilian Unemployment announcements play a dominant role in determining future monetary policy. Moreover, we document evidence that shows that the release of such information is rapidly incorporated into rates, particularly when considering federal funds futures contracts traded via an electronic trading platform (as opposed to an open‐auction trading platform).
Identification‐Robust Minimum Distance Estimation of the New Keynesian Phillips Curve
Authors: MAGNUSSON LEANDRO M. , MAVROEIDIS SOPHOCLES
Published: March 2010

Limited‐information identification‐robust methods on the indexation and price rigidity parameters of the New Keynesian Phillips Curve yield very wide confidence intervals. Full‐information methods impose more restrictions on the reduced‐form dynamics and thus make more efficient use of the information in the data. However, such methods are also subject to weak instrument problems. We propose identification‐robust minimum distance methods for exploiting these additional restrictions and show that they yield considerably smaller confidence intervals for the coefficients of the model compared to their limited‐information generalized method of moments counterparts. In contrast to previous studies, we find evidence of partial but not full indexation, and obtain sharper inference on the degree of price stickiness. However, this parameter remains weakly identified.
Mental Spaces from a Functional Perspective
Authors: Dinsmore John
Published: March 2010

In his book Mental Spaces, Fauconnier develops a powerful theory of human knowledge representation and linguistic processing that handles a variety of problems in linguistics and the philosophy of language in a simple, uniform, and intuitively plausible way. However, he has little to say about the structure or general role of mental spaces in cognition. The present paper proposes that mental spaces are a means of organizing knowledge in support of a general inference method, simulative reasoning, found in various guises both in logic and in Artificial Intelligence. The structuring required to fulfill this role allows us to make a wide variety of predictions which seem to be borne out by evidence from natural language. In attributing a specific function to mental spaces, this paper suggests that the theory of mental spaces defines a potentially significant paradigm for knowledge representation in Artificial Intelligence.
Competitive Learning: From Interactive Activation to Adaptive Resonance
Authors: Grossberg Stephen
Published: March 2010

Functional and mechanistic comparisons are made between several network models of cognitive processing: competitive learning, interactive activation, adaptive resonance, and back propagation. The starting point of this comparison is the article of Rumelhart and Zipser (1985) on feature discovery through competitive learning. All the models which Rumelhart and Zipser (1985) have described were shown in Grossberg (1976b) to exhibit a type of learning which is temporally unstable. Competitive learning mechanisms can be stabilized in response to an arbitrary input environment by being supplemented with mechanisms for learning top‐down expectancies, or templates; for matching bottom‐up input patterns with the top‐down expectancies; and for releasing orienting reactions in a mismatch situation, thereby updating short‐term memory and searching for another internal representation. Network architectures which embody all of these mechanisms were called adaptive resonance models by Grossberg (1976c). Self‐stabilizing learning models are candidates for use in real‐world applications where unpredictable changes can occur in complex input environments. Competitive learning postulates are inconsistent with the postulates of the interactive activation model of McClelland and Rumelhart (1981), and suggest different levels of processing and interaction rules for the analysis of word recognition. Adaptive resonance models use these alternative levels and interaction rules. The self‐organizing learning of an adaptive resonance model is compared and contrasted with the teacher‐directed learning of a back propagation model. A number of criteria for evaluating real‐time network models of cognitive processing are described and applied.
Why a Diagram is (Sometimes) Worth Ten Thousand Words
Authors: Larkin Jill H. , Simon Herbert A.
Published: March 2010

We distinguish diagrammatic from sentential paper‐and‐pencil representations of information by developing alternative models of information‐processing systems that are informationally equivalent and that can be characterized as sentential or diagrammatic. Sentential representations are sequential, like the propositions in a text. Diagrammatic representations are indexed by location in a plane. Diagrammatic representations also typically display information that is only implicit in sentential representations and that therefore has to be computed, sometimes at great cost, to make it explicit for use. We then contrast the computational efficiency of these representations for solving several illustrative problems in mathematics and physics.

When two representations are informationally equivalent, their computational efficiency depends on the information‐processing operators that act on them. Two sets of operators may differ in their capabilities for recognizing patterns, in the inferences they can carry out directly, and in their control strategies (in particular, the control of search). Diagrammatic and sentential representations support operators that differ in all of these respects. Operators working on one representation may recognize features readily or make inferences directly that are difficult to realize in the other representation. Most important, however, are differences in the efficiency of search for information and in the explicitness of information. In the representations we call diagrammatic, information is organized by location, and often much of the information needed to make an inference is present and explicit at a single location. In addition, cues to the next logical step in the problem may be present at an adjacent location. Therefore problem solving can proceed through a smooth traversal of the diagram, and may require very little search or computation of elements that had been implicit.
Fatal Electrocution by a Support Metal Wire
Authors: Shetty B. Suresh Kumar , Kanchan Tanuj , Shetty Mahabalesh , Naik Ramadas , Menezes Ritesh G. , Sameer K. S. Muhammed , Hasan Faisal
Published: March 2010

Abstract:  Electrocution is not an uncommon cause of death. A case of fatal electrocution by a metal wire that was used as a support for the insulated television cable wire is reported. Electric current flowed through the metal wire when it touched the residential power line. Electrical injury caused because of contact with the live metal wire is described with histopathological findings. This case reports the circumstances that led to accidental fatal electrocution in an outdoor setting during the rainy season. Significance of death scene investigation to confirm the cause and manner of death in cases of fatal electrocution is highlighted. Public awareness programs to lay emphasis on electrical safety in domestic environment need to be introduced to prevent fatalities resulting from ignorance and/or negligence.
Elevated CO2 lessens predation of Chrysopa sinica on Aphis gossypii
Authors: Gao Feng , Chen Fajun , Ge Feng
Published: March 2010

Most studies on the effects of elevated atmospheric CO2 on organisms have focused on the performance of plants or herbivores. Few reports have examined the impact on the ability of predators at the third trophic level. In this experiment, we made use of open‐top chambers to quantify the effects of elevated CO2 on growth, development, and predatory ability of two successive generations of Chinese lacewing, Chrysopa sinica (Tjeder) (Neuroptera: Chrysopidae), feeding on cotton aphids, Aphis gossypii (Glover) (Hemiptera: Aphididae), which were reared on cotton, Gossypium hirsutum L. (Malvaceae), grown under elevated CO2 (double ambient vs. ambient). Higher atmospheric CO2 concentrations reduced the duration of larval development and the survival rate of pupae, and caused decreased weight in adult female C. sinica, but had no significant effects on survival rate of each larval stage, female adult fecundity, egg hatch rate, or adult life span. The predatory ability of larvae in the third instar and the total larval stage of C. sinica that fed on A. gossypii were significantly lower in elevated CO2 environments. The number of aphids consumed by first‐generation lacewing population did not change significantly with different CO2 treatments; however, significantly fewer aphids were consumed by the second generation of the lacewing population with elevated CO2. We speculate that A. gossypii may become a more serious pest under an environment with elevated CO2 concentrations because of the reduced predatory ability of C. sinica on A. gossypii.
Is the fast growth of an equatorial Micropterus salmoides population explained by high water temperature?
Authors: Britton J. R. , Harper D. M. , Oyugi D. O.
Published: March 2010

Britton JR, Harper DM, Oyugi DO. Is the fast growth of an equatorial Micropterus salmoides population explained by high water temperature? Ecology of Freshwater Fish 2010: 19: 228–238. © 2010 John Wiley & Sons A/S

Abstract –  Marginal increment analysis of scales collected from the introduced Micropterus salmoides population of Lake Naivasha, Kenya revealed the formation of an annual growth check, validating their use to age individual fish. Subsequent analysis of scales from 372 fish collected between 2002 and 2009 revealed individuals were very fast growing compared with native populations in North America and other introduced populations in Europe, South America, Africa and Asia. This was likely to be as a result of the water temperatures in Lake Naivasha exceeding 20 °C throughout the year. This was corroborated by a meta‐analysis of the growth parameters asymptotic length L∞ and growth coefficient K from across their geographical range that revealed variance was explained by differences in mean annual air temperatures. At a break point of approximately 10 °C, there was a shift to reduced L∞ and increased K, suggesting a temperature driven trade‐off between growth rate and ultimate length. When adjusted for temperature and weighted for sample size, there were significant differences between the growth parameters of the North American and introduced populations, suggesting that other abiotic and biotic variables were also important determinants of the growth of individuals between the two ranges.
Increased susceptibility to Ca2+‐induced permeability transition and to cytochrome c release in rat heart mitochondria with aging: effect of melatonin
Authors: Petrosillo Giuseppe , Moro Nicola , Paradies Valeria , Ruggiero Francesca M. , Paradies Giuseppe
Published: March 2010

Abstract:  Aging is associated with a decline of cardiac function. The mitochondrial permeability transition (MPT) may be a factor in cardiac dysfunction associated with aging. We investigated the effect of aging and long‐term treatment with melatonin (approximately 10 mg/kg b.w./day for 2 months), a known natural antioxidant, on the susceptibility to Ca2+‐induced MPT opening and cytochrome c release in rat heart mitochondria. The mitochondrial content of normal and oxidized cardiolipin as a function of aging and melatonin treatment was also analyzed. Mitochondria from aged rats (24 month old) displayed an increased susceptibility to Ca2+‐induced MPT opening, associated with an elevated release of cytochrome c, when compared with young control animals (5 month old). Melatonin treatment counteracted both these processes. Aging was also associated with an oxidation/depletion of cardiolipin which could be counteracted as well by melatonin. It is proposed that the increased level of oxidized cardiolipin could be responsible, at least in part, for the increased susceptibility to Ca2+‐induced MPT opening and cytochrome c release in rat heart mitochondria with aging. Melatonin treatment counteracts both these processes, most likely, by preventing the oxidation/depletion of cardiolipin. Our results might have implications in the necrotic and apoptotic myocytes cell death in aged myocardium, particularly in ischemia/reperfusion injury.
Prevalence and Diversity of Microbes in the Amniotic Fluid, the Fetal Inflammatory Response, and Pregnancy Outcome in Women with Preterm Pre‐Labor Rupture of Membranes
Authors: DiGiulio Daniel B. , Romero Roberto , Kusanovic Juan Pedro , Gómez Ricardo , Kim Chong Jai , Seok Kimberley S. , Gotsch Francesca , Mazaki‐Tovi Shali , Vaisbuch Edi , Sanders Katherine , Bik Elisabeth M. , Chaiworapongsa Tinnakorn , Oyarzún Enrique , Relman David A.
Published: March 2010

Citation DiGiulio DB, Romero R, Kusanovic JP, Gómez R, Kim CJ, Seok K, Gotsch F, Mazaki‐Tovi S, Vaisbuch E, Sanders K, Bik EM, Chaiworapongsa T, Oyarzún E, Relman DA. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre‐labor rupture of membranes. Am J Reprod Immunol 2010; 64: 38–57

Problem  The role played by microbial invasion of the amniotic cavity (MIAC) in preterm pre‐labor rupture of membranes (pPROM) is inadequately characterized, in part because of reliance on cultivation‐based methods.

Method of study  Amniotic fluid from 204 subjects with pPROM was analyzed with both cultivation and molecular methods in a retrospective cohort study. Broad‐range and group‐specific polymerase chain reaction (PCR) assays targeted small subunit ribosomal DNA (rDNA), or other gene sequences, from bacteria, fungi, and archaea. Results were correlated with measurements of host inflammation, as well as pregnancy and perinatal outcomes.

Results  The prevalence of MIAC was 34% (70/204) by culture, 45% (92/204) by PCR, and 50% (101/204) by both methods combined. The number of bacterial species revealed by PCR (44 species‐level phylotypes) was greater than that by culture (14 species) and included as‐yet uncultivated taxa. Some taxa detected by PCR have been previously associated with the gastrointestinal tract (e.g., Coprobacillus sp.), the mouth (e.g., Rothia dentocariosa), or the vagina in the setting of bacterial vaginosis (e.g., Atopobium vaginae). The relative risk for histologic chorioamnionitis was 2.1 for a positive PCR [95% confidence interval (CI), 1.4–3.0] and 2.0 for a positive culture (95% CI, 1.4–2.7). Bacterial rDNA abundance exhibited a dose relationship with gestational age at delivery (R2 = 0.26; P < 0.01). A positive PCR was associated with lower mean birthweight, and with higher rates of respiratory distress syndrome and necrotizing enterocolitis (P < 0.05 for each outcome).

Conclusion  MIAC in pPROM is more common than previously recognized and is associated in some cases with uncultivated taxa, some of which are typically associated with the gastrointestinal tract. The detection of MIAC by molecular methods has clinical significance.
On Dualism
Authors: Mounce H.O.
Published: March 2010

This is a response to two articles by William Charlton and Nicholas Lash. These authors criticize a view which they attribute to Descartes. According to this view, there is a dualism of mind and body. In this paper it is argued, first, that some form of dualism is intrinsically plausible, second, that the view these authors attribute to Descartes is not one he held and, third, that a dualism of mind or soul and body has always been central to the Christian faith. It concludes by considering Charlton's attempt to elucidate the Christian belief in an after life by reference to what he calls a process of divinisation. The importance of this process is not denied. It is argued, however, that it must itself involve a dualism of mind or soul and body.
Degradation of tropoelastin by matrix metalloproteinases – cleavage site specificities and release of matrikines
Authors: Heinz Andrea , Jung Michael C. , Duca Laurent , Sippl Wolfgang , Taddese Samuel , Ihling Christian , Rusciani Anthony , Jahreis Günther , Weiss Anthony S. , Neubert Reinhard H. H. , Schmelzer Christian E. H.
Published: March 2010

To provide a basis for the development of approaches to treat elastin‐degrading diseases, the aim of this study was to investigate the degradation of the natural substrate tropoelastin by the elastinolytic matrix metalloproteinases MMP‐7, MMP‐9, and MMP‐12 and to compare the cleavage site specificities of the enzymes using complementary MS techniques and molecular modeling. Furthermore, the ability of the three proteases to release bioactive peptides was studied. Tropoelastin was readily degraded by all three MMPs. Eighty‐nine cleavage sites in tropoelastin were identified for MMP‐12, whereas MMP‐7 and MMP‐9 were found to cleave at only 58 and 63 sites, respectively. Cleavages occurred predominantly in the N‐terminal and C‐terminal regions of tropoelastin. With respect to the cleavage site specificities, the study revealed that all three MMPs similarly tolerate hydrophobic and/or aliphatic amino acids, including Pro, Gly, Ile, and Val, at P1′. MMP‐7 shows a strong preference for Leu at P1′, which is also well accepted by MMP‐9 and MMP‐12. Of all three MMPs, MMP‐12 best tolerates bulky charged and aromatic amino acids at P1′. All three MMPs showed a clear preference for Pro at P3 that could be structurally explained by molecular modeling. Analysis of the generated peptides revealed that all three MMPs show a similar ability to release bioactive sequences, with MMP‐12 producing the highest number of these peptides. Furthermore, the generated peptides YTTGKLPYGYGPGG, YGARPGVGVGGIP, and PGFGAVPGA, containing GxxPG motifs that have not yet been proven to be bioactive, were identified as new matrikines upon biological activity testing.

Structured digital abstract

MINT‐7709630: MMP‐7 (uniprotkb:P09237) cleaves (MI:0194) Tropoelastin (uniprotkb:P15502) by protease assay (MI:0435)

MINT‐7709668: MMP‐9 (uniprotkb:P14780) cleaves (MI:0194) Tropoelastin (uniprotkb:P15502) by protease assay (MI:0435)

MINT‐7709289: MMP‐12 (uniprotkb:P39900) cleaves (MI:0194) Tropoelastin (uniprotkb:P15502) by protease assay (MI:0435)
Complementation of coenzyme Q‐deficient yeast by coenzyme Q analogues requires the isoprenoid side chain
Authors: James Andrew M. , Cochemé Helena M. , Murai Masatoshi , Miyoshi Hideto , Murphy Michael P.
Published: March 2010

The ubiquinone coenzyme Q (CoQ) is synthesized in mitochondria with a large, hydrophobic isoprenoid side chain. It functions in mitochondrial respiration as well as protecting membranes from oxidative damage. Yeast that cannot synthesize CoQ (ΔCoQ) are viable, but cannot grow on nonfermentable carbon sources, unless supplied with ubiquinone. Previously we demonstrated that the isoprenoid side chain of the exogenous ubiquinone was important for growth of a ΔCoQ strain on the nonfermentable substrate glycerol [James AM et al. (2005) J Biol Chem280, 21295–21312]. In the present study we investigated the structural requirements of exogenously supplied CoQ2 for growth on glycerol and found that the first double bond of the initial isoprenoid unit is essential for utilization of respiratory substrates. As CoQ2 analogues that did not complement growth on glycerol supported respiration in isolated mitochondria, discrimination does not occur via the respiratory chain complexes. The endogenous form of CoQ in yeast (CoQ6) is extremely hydrophobic and transported to mitochondria via the endocytic pathway when supplied exogenously. We found that CoQ2 does not require this pathway when supplied exogenously and the pathway is unlikely to be responsible for the structural discrimination observed. Interestingly, decylQ, an analogue unable to support growth on glycerol, is not toxic, but antagonizes growth of ΔCoQ yeast in the presence of exogenous CoQ2. Using a ΔCoQ double‐knockout library we identified a number of genes that decrease the ability of yeast to grow on exogenous CoQ. Here we suggest that CoQ or its redox state may be a signal for growth during the shift to respiration.
Effects of a novel arginine methyltransferase inhibitor on T‐helper cell cytokine production
Authors: Bonham Kevin , Hemmers Saskia , Lim Yeon‐Hee , Hill Dawn M. , Finn M. G. , Mowen Kerri A.
Published: March 2010

The protein arginine methyltransferase (PRMT) family of enzymes catalyzes the transfer of methyl groups from S‐adenosylmethionine to the guanidino nitrogen atom of peptidylarginine to form monomethylarginine or dimethylarginine. We created several less polar analogs of the specific PRMT inhibitor arginine methylation inhibitor‐1, and one such compound was found to have improved PRMT inhibitory activity over the parent molecule. The newly identified PRMT inhibitor modulated T‐helper‐cell function and thus may serve as a lead for further inhibitors useful for the treatment of immune‐mediated disease.

Structured digital abstract

MINT‐7710141: Prmt1 (uniprotkb:Q63009) physically interacts (MI:0915) with nip45 (uniprotkb:O09130) by anti tag coimmunoprecipitation (MI:0007)

MINT‐7710127: Prmt1 (uniprotkb:Q63009) physically interacts (MI:0915) with Prmt1 (uniprotkb:Q63009) by anti tag coimmunoprecipitation (MI:0007)