bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired Neurotransmitter Release in Alzheimer’s and Parkinson’s Diseases
Authors: Shen Jie
Published: February 2010

Mutations in several causative genes have been linked to monogenic forms of Alzheimer’s disease (AD) or Parkinson’s disease (PD). To look for possible common pathogenic mechanisms underlying age-related neurodegeneration in AD and PD, we employed genetic approaches to investigate systematically the roles of these gene products (e.g. presenilins (PS) for AD; Parkin, DJ-1, PINK1 and LRRK2 for PD) in the mouse brain, especially in neural circuits that are particularly vulnerable in AD or PD. Our series of genetic studies revealed that PS play cell type-specific roles in the developing brain with the most prominent function in the maintenance of neural progenitor cells. In the adult cerebral cortex, where the pathogenesis of AD occurs, loss of PS results in progressive memory impairment and age-related neurodegeneration. Specifically, PS are involved in the regulation of long-term potentiation and NMDA receptor functions. Interestingly, our further genetic dissection in the hippocampal Schaeffer collateral pathway highlighted the importance of presynaptic PS in the activity-dependent regulation of glutamate release and long-term potentiation induction via modulation of calcium release from intracellular stores. Intriguingly, our independent genetic analysis of Parkin, DJ-1, PINK1 and LRRK2 showed a common defect in activity-dependent dopamine release caused by PD-linked mutations in these genes. Together, our genetic studies suggest that presynaptic dysfunction might be a converging early pathogenic event before neurodegeneration in AD and PD.
Stem Cell Biology in the Study of Pathological Conditions
Authors: Sugaya K.
Published: February 2010

The current focus of researchers is to create certain types of cells in vitroas transplantation materials. The problem of this approach is that terminally differentiated cells may not integrate into the host. To overcome this problem, we may want to transplant premature cells, which can migrate and differentiate due to environmental cues received from the host, allowing for intrinsic proper functioning of the cells. Thus, we have to consider the effects that the pathological environment might have on the transplanted cells. Here, we show the effects of amyloid precursor protein and reelin on neural stem cell (NSC) differentiation, and demonstrate how we have regulated this effect to produce desirable cells under pathological conditions. We found that amyloid precursor protein increases glial differentiation via the notch and cytokine-signaling pathway, while reelin induces radial glial differentiation followed by neuronal differentiation via increasing phosphorylation of adapter protein disabled-1. Since amyloid and reelin are found in plaques within Alzheimer’s disease, these findings may closely associate with NSC biology in the context of its pathology. By regulating these factors in Alzheimer’s disease, we may be able to not only guide differentiation of transplanted NSCs, but also to modify progression of disease by guiding differentiation of endogenous NSCs.
Possible Involvement of Transthyretin in Hippocampal β-Amyloid Burden and Learning Behaviors in a Mouse Model of Alzheimer’s Disease (TgCRND8)
Authors: Doggui Sihem , Brouillette Jonathan , Chabot Jean-Guy , Farso Mark , Quirion Rémi
Published: February 2010

Background: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss, possibly triggered by the accumulation of β-amyloid (Aβ) peptides and the hyperphosphorylation of Tau neurofilament protein. Recent findings have shown that transthyretin (TTR) is a potent scavenger of Aβ peptide deposits, suggesting a possible neuroprotective role for TTR in neurodegenerative processes associated with amyloidogenesis, such as AD. Methods: To investigate the relationship between TTR and Aβ deposition, we crossed mouse carrying a deletion of TTR (TTR–/–) with a transgenic mouse model of AD (TgCRND8), and Aβ burden and spatial learning capacities were evaluated at 4 and 6 months of age (exclusion of the 6 month-old TgCRND8/TTR–/– group due to low survival rate). Results: Rather surprisingly, Aβ plaque burden was significantly reduced in the hippocampus of 4-month-old TgCRND8/TTR+/–, and to a lesser extent in TgCRND8/TTR–/–, as compared to age-matched TgCRND8/TTR+/+. No difference in plaque burden was found between any groups in 6-month-old animals. At 4 and 6 months of age, all populations of these hybrid transgenic mice displayed similar magnitude of spatial memory deficits in the Morris water maze task. Conclusion: Since TgCRND8 mice represent an aggressive model of Aβ deposition with plaques developing as early as 3 months of age, along with spatial learning deficits, it may be already too late at 4 and 6 months of age to observe significant changes due to the deletion of the TTR gene.
Early-Stage Inflammation and Experimental Therapy in Transgenic Models of the Alzheimer-Like Amyloid Pathology
Authors: Cuello A.C. , Ferretti M.T. , Leon W.C. , Iulita M.F. , Melis T. , Ducatenzeiler A. , Bruno M.A. , Canneva F.
Published: February 2010

Background: Intracellular accumulation of β-amyloid (Aβ) is one of the early features in the neuropathology of Alzheimer’s disease (AD) and Down’s syndrome. This can be reproduced in cell and transgenic animal models of the AD-like amyloid pathology. In a transgenic rat model, our lab has previously shown that the intracellular accumulation of Aβ is sufficient to provoke cognitive impairments and biochemical alterations in the cerebral cortex and hippocampus in the absence of amyloid plaques. Objective: To investigate an early, pre-plaque inflammatory process in AD-like transgenic models and establish whether the neurotoxic effects of Aβ oligomers and proinflammatory responses can be arrested with minocycline. Methods: For these studies, we used naïve mice and transgenic animal models of the AD-like amyloid pathology and applied neurochemical, immunohistochemical and behavioral experimental approaches. Results: In the early stages of the AD-like amyloid pathology, intracellular Aβ oligomers accumulate within neurons of the cerebral cortex and hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloid plaques, together with an upregulation of MHC-II, i-NOS and COX-2, well-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, lowered inflammatory markers and levels of Aβ trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatory effects of Aβ might be a promising strategy to prevent or delay the onset of AD.
Generation of Tau Aggregates and Clearance by Autophagy in an Inducible Cell Model of Tauopathy
Authors: Wang Y. , Krüger U. , Mandelkow E. , Mandelkow E.-M.
Published: February 2010

We have studied the mechanism of aggregation in an inducible cell model of Tau pathology. When the repeat domain of human Tau (TauRD) carrying the FTDP-17 mutation ΔK280 is expressed, the cells develop aggregates, as seen by thioflavin S fluorescence, electron microscopy, and sarkosyl extraction methods. By contrast, mutants of TauRD that are unable to generate β-structure do not aggregate. Enhanced aggregation leads to enhanced toxicity, visible by live cell microscopy and LDH release assay. The aggregation process is initiated by the sequential cleavage of TauRD which yields highly amyloidogenic fragments. This cleavage occurs only with proaggregant TauRD, and not with the nonaggregating mutants, indicating that β-structure makes TauRD vulnerable to both proteolytic degradation and aggregation. Aggregation is reversed by switching off the expression of TauRD, by inhibitor compounds, and by certain protease inhibitors. In all cases, the enhanced toxicity is rescued. The clearance of the aggregates involves autophagy, whereas proteasomal degradation plays only a minor role.
Prevalence and Impact of Cerebrovascular Lesions in Alzheimer and Lewy Body Diseases
Authors: Jellinger Kurt A.
Published: February 2010

Background: Data on the prevalence of cerebrovascular lesions (CVLs) and their impact on cognitive decline in Alzheimer disease (AD) and Lewy body disease are conflicting. Objective: Retrospective examination of the prevalence of CVL in a consecutive autopsy series. Material and Methods: 1,339 cases of autopsy-proven AD, Parkinson disease (PD), dementia with Lewy bodies (± AD), and 486 age-matched controls were examined according to standardized neuropathologic methods including immunohistochemistry. Diagnoses followed current consensus criteria, classification of CVLs and of cerebral amyloid angiopathy (CAA) in 5 grades [Acta Neurol Scand 2006;114:38–46; Acta Neuropathol 2005;110:345–359]. Results: Lewy body variant of AD and AD showed significantly more frequent CVLs (91.9 and 67.8%) than the other groups (29.4 to 45.7%), with the highest frequency of severe CVLs (old, recent infarcts and hemorrhages) in AD (23.6%), but 2.0–8.3% in the other groups. Severe CAA was most frequent in AD and the Lewy body variant of AD (97.9 and 85%), less in PD (36%) and controls (30%). CAA was more frequent/severe in demented than in nondemented cases. CVLs in cortico-subcortical and hippocampal areas were most frequent in AD; subcortical CVLs (lacunes) in both AD and PD were more frequent than in controls. The incidence and severity of CVLs significantly correlated with neuritic Braak stages. Cognitive impairment was largely independent of coexisting CVLs, but related to the severity/location of AD and/or Lewy pathology. Conclusions: The present data confirm the importance of CVLs in AD and in dementia with Lewy bodies with severe AD, and the little impact of CVLs alone, but show a close association of CAA with clinical dementia associated with AD pathology.
Vascular Dementia and Alzheimer’s Disease – Are We in a Dead-End Road?
Authors: Cavalieri Margherita , Enzinger Christian , Petrovic Katja , Pluta-Fuerst Aga , Homayoon Nina , Schmidt Helena , Fazekas Franz , Schmidt Reinhold
Published: February 2010

Background: Diagnostic criteria separating vascular dementia from other dementias, particularly Alzheimer’s disease (AD) neglect the real world in which most AD cases present with at least some vascular brain lesions. Most importantly, vascular lesions, even if subtle, exert significant effects on the patients’ cognitive functioning if they coexist with AD pathology. Objectives: To emphasize the need for an integrative dementia concept in which the vascular component represents an important end point in trial planning and a possibility for disease modification along the whole spectrum of combined vascular and primary degenerative pathology. Methods: Review of the literature on possible surrogate markers to study the contribution of vascular brain damage in dementia. Results: The longitudinal change in volume of white matter lesions is the best elaborated putative surrogate marker for the study of the vascular component in dementia. Validation of the role of lacunes and microbleeds as surrogate end points is poor. Loss of brain volume is an important adjunct outcome measure even though the vascular origin of atrophy remains uncertain. Conclusions: A focus on pure vascular dementia distracts from the importance of vascular factors in dementia. Consideration of the vascular component in future clinical trials will improve our pathophysiological understanding and provide options for treatment.
Association of a Peripheral Blood Metabolic Profile With Coronary Artery Disease and Risk of Subsequent Cardiovascular Events
Authors: Shah Svati H. , Bain James R. , Muehlbauer Michael J. , Stevens Robert D. , Crosslin David R. , Haynes Carol , Dungan Jennifer , Newby L. Kristin , Hauser Elizabeth R. , Ginsburg Geoffrey S. , Newgard Christopher B. , Kraus William E.
Published: February 2010

Background—

Molecular tools may provide insight into cardiovascular risk. We assessed whether metabolites discriminate coronary artery disease (CAD) and predict risk of cardiovascular events.

Methods and Results—

We performed mass–spectrometry–based profiling of 69 metabolites in subjects from the CATHGEN biorepository. To evaluate discriminative capabilities of metabolites for CAD, 2 groups were profiled: 174 CAD cases and 174 sex/race-matched controls (“initial”), and 140 CAD cases and 140 controls (“replication”). To evaluate the capability of metabolites to predict cardiovascular events, cases were combined (“event” group); of these, 74 experienced death/myocardial infarction during follow-up. A third independent group was profiled (“event-replication” group; n=63 cases with cardiovascular events, 66 controls). Analysis included principal-components analysis, linear regression, and Cox proportional hazards. Two principal components analysis–derived factors were associated with CAD: 1 comprising branched-chain amino acid metabolites (factor 4, initial
P
=0.002, replication
P
=0.01), and 1 comprising urea cycle metabolites (factor 9, initial
P
=0.0004, replication
P
=0.01). In multivariable regression, these factors were independently associated with CAD in initial (factor 4, odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74;
P
=0.02; factor 9, OR, 0.67; 95% CI, 0.52 to 0.87;
P
=0.003) and replication (factor 4, OR, 1.43; 95% CI, 1.07 to 1.91;
P
=0.02; factor 9, OR, 0.66; 95% CI, 0.48 to 0.91;
P
=0.01) groups. A factor composed of dicarboxylacylcarnitines predicted death/myocardial infarction (event group hazard ratio 2.17; 95% CI, 1.23 to 3.84;
P
=0.007) and was associated with cardiovascular events in the event-replication group (OR, 1.52; 95% CI, 1.08 to 2.14;
P
=0.01).

Conclusions—

Metabolite profiles are associated with CAD and subsequent cardiovascular events.
The Role of the Funny Current in Pacemaker Activity
Authors: DiFrancesco Dario
Published: February 2010

Abstract
:

Pacemaking is a basic physiological process, and the cellular mechanisms involved in this function have always attracted the keen attention of investigators. The “funny” (
I
f
) current, originally described in sinoatrial node myocytes as an inward current activated on hyperpolarization to the diastolic range of voltages, has properties suitable for generating repetitive activity and for modulating spontaneous rate. The degree of activation of the funny current determines, at the end of an action potential, the steepness of phase 4 depolarization; hence, the frequency of action potential firing. Because
I
f
is controlled by intracellular cAMP and is thus activated and inhibited by β-adrenergic and muscarinic M2 receptor stimulation, respectively, it represents a basic physiological mechanism mediating autonomic regulation of heart rate. Given the complexity of the cellular processes involved in rhythmic activity, an exact quantification of the extent to which
I
f
and other mechanisms contribute to pacemaking is still a debated issue; nonetheless, a wealth of information collected since the current was first described more than 30 years ago clearly agrees to identify
I
f
as a major player in both generation of spontaneous activity and rate control.
I
f
- dependent pacemaking has recently advanced from a basic, physiologically relevant concept, as originally described, to a practical concept that has several potentially useful clinical applications and can be valuable in therapeutically relevant conditions. Typically, given their exclusive role in pacemaking, f-channels are ideal targets of drugs aiming to pharmacological control of cardiac rate. Molecules able to bind specifically to and block f-channels can thus be used as pharmacological tools for heart rate reduction with little or no adverse cardiovascular side effects. Indeed a selective f-channel inhibitor, ivabradine, is today commercially available as a tool in the treatment of stable chronic angina. Also, several loss-of-function mutations of HCN4 (hyperpolarization-activated, cyclic-nucleotide gated 4), the major constitutive subunit of f-channels in pacemaker cells, are known today to cause rhythm disturbances, such as for example inherited sinus bradycardia. Finally, gene- or cell-based methods for in situ delivery of f-channels to silent or defective cardiac muscle represent novel approaches for the development of biological pacemakers eventually able to replace electronic devices.
Circadian Rhythms and Metabolic Syndrome
Authors: Maury Eleonore , Ramsey Kathryn Moynihan , Bass Joseph
Published: February 2010

Abstract
:

The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal clock system, and sleep, constitute risk factors for disorders including obesity, diabetes mellitus, cardiovascular disease, thrombosis and even inflammation. An exciting aspect of the field has been the integration of behavioral and physiological approaches, and the emerging insight into both neural and peripheral tissues in disease pathogenesis. Consideration of the cell and molecular links between disorders of circadian rhythms and sleep with metabolic syndrome has begun to open new opportunities for mechanism-based therapeutics.
Decadal Shift in El Niño Influences on Indo–Western Pacific and East Asian Climate in the 1970s*
Authors: Xie Shang-Ping , Du Yan , Huang Gang , Zheng Xiao-Tong , Tokinaga Hiroki , Hu Kaiming , Liu Qinyu
Published: February 2010

El Niño’s influence on the subtropical northwest (NW) Pacific climate increased after the climate regime shift of the 1970s. This is manifested in well-organized atmospheric anomalies of suppressed convection and a surface anticyclone during the summer (June–August) of the El Niño decay year [JJA(1)], a season when equatorial Pacific sea surface temperature (SST) anomalies have dissipated. In situ observations and ocean–atmospheric reanalyses are used to investigate mechanisms for the interdecadal change. During JJA(1), the influence of the El Niño–Southern Oscillation (ENSO) on the NW Pacific is indirect, being mediated by SST conditions over the tropical Indian Ocean (TIO). The results here show that interdecadal change in this influence is due to changes in the TIO response to ENSO.

During the postregime shift epoch, the El Niño teleconnection excites downwelling Rossby waves in the south TIO by anticyclonic wind curls. These Rossby waves propagate slowly westward, causing persistent SST warming over the thermocline ridge in the southwest TIO. The ocean warming induces an antisymmetric wind pattern across the equator, and the anomalous northeasterlies cause the north Indian Ocean to warm through JJA(1) by reducing the southwesterly monsoon winds. The TIO warming excites a warm Kelvin wave in tropospheric temperature, resulting in robust atmospheric anomalies over the NW Pacific that include the surface anticyclone. During the preregime shift epoch, ENSO is significantly weaker in variance and decays earlier than during the recent epoch. Compared to the epoch after the mid-1970s, SST and wind anomalies over the TIO are similar during the developing and mature phases of ENSO but are very weak during the decay phase. Specifically, the southern TIO Rossby waves are weaker, so are the antisymmetric wind pattern and the North Indian Ocean warming during JJA(1). Without the anchor in the TIO warming, atmospheric anomalies over the NW Pacific fail to develop during JJA(1) prior to the mid-1970s. The relationship of the interdecadal change to global warming and implications for the East Asian summer monsoon are discussed.
Near-Ground Pressure and Wind Measurements in Tornadoes*
Authors: Karstens Christopher D. , Samaras Timothy M. , Lee Bruce D. , Gallus William A. , Finley Catherine A.
Published: February 2010

Since the spring of 2002, tornadoes were sampled on nine occasions using Hardened In-Situ Tornado Pressure Recorder probes, video probes, and mobile mesonet instrumentation. This study describes pressure and, in some cases, velocity data obtained from these intercepts. In seven of these events, the intercepted tornadoes were within the radar-indicated or visually identified location of the supercell low-level mesocyclone. In the remaining two cases, the intercepted tornadoes occurred outside of this region and were located along either the rear-flank downdraft gust front or an internal rear-flank downdraft surge boundary.

The pressure traces, sometimes augmented with videography, suggest that vortex structures ranged from single-cell to two-cell, quite similar to the swirl-ratio-dependent continuum of vortex structures shown in laboratory and numerical simulations. Although near-ground tornado observations are quite rare, the number of contemporary tornado measurements now available permits a comparative range of observed pressure deficits for a wide variety of tornado sizes and intensities to be presented.
Modeling the Dependence of Tropical Storm Counts in the North Atlantic Basin on Climate Indices
Authors: Villarini Gabriele , Vecchi Gabriel A. , Smith James A.
Published: February 2010

The authors analyze and model time series of annual counts of tropical storms lasting more than 2 days in the North Atlantic basin and U.S. landfalling tropical storms over the period 1878–2008 in relation to different climate indices. The climate indices considered are the tropical Atlantic sea surface temperature (SST), tropical mean SST, the North Atlantic Oscillation (NAO), and the Southern Oscillation index (SOI). Given the uncertainties associated with a possible tropical storm undercount in the presatellite era, two different time series of counts for the North Atlantic basin are employed: one is the original (uncorrected) tropical storm record maintained by the National Hurricane Center and the other one is with a correction for the estimated undercount associated with a changing observation network. Two different SST time series are considered: the Met Office’s HadISSTv1 and NOAA’s Extended Reconstructed SST.

Given the nature of the data (counts), a Poisson regression model is adopted. The selection of statistically significant covariates is performed by penalizing models for adding extra parameters and two penalty functions are used. Depending on the penalty function, slightly different models, both in terms of covariates and dependence of the model’s parameter, are obtained, showing that there is not a “single best” model. Moreover, results are sensitive to the undercount correction and the SST time series.

Suggestions concerning the model to use are provided, driven by both the outcomes of the statistical analyses and the current understanding of the underlying physical processes responsible for the genesis, development, and tracks of tropical storms in the North Atlantic basin. Although no single model is unequivocally superior to the others, the authors suggest a very parsimonious family of models using as covariates tropical Atlantic and tropical mean SSTs.
Evaluation of Data Reduction Algorithms for Real-Time Analysis
Authors: Lazarus Steven M. , Splitt Michael E. , Lueken Michael D. , Ramachandran Rahul , Li Xiang , Movva Sunil , Graves Sara J. , Zavodsky Bradley T.
Published: February 2010

Data reduction tools are developed and evaluated using a data analysis framework. Simple (nonadaptive) and intelligent (adaptive) thinning algorithms are applied to both synthetic and real data and the thinned datasets are ingested into an analysis system. The approach is motivated by the desire to better represent high-impact weather features (e.g., fronts, jets, cyclones, etc.) that are often poorly resolved in coarse-resolution forecast models and to efficiently generate a set of initial conditions that best describes the current state of the atmosphere. As a precursor to real-data applications, the algorithms are applied to one- and two-dimensional synthetic datasets. Information gleaned from the synthetic experiments is used to create a thinning algorithm that combines the best aspects of the intelligent methods (i.e., their ability to detect regions of interest) while reducing the impacts of spatial irregularities in the data. Both simple and intelligent thinning algorithms are then applied to Atmospheric Infrared Sounder (AIRS) temperature and moisture profiles. For a given retention rate, background, and observation error, the optimal 1D analyses (i.e., lowest MSE) tend to have observations that are near regions of large curvature and gradients. Observation error leads to the selection of spurious data in homogeneous regions of the intelligent algorithms. In the 2D experiments, simple thinning tends to perform better within the homogeneous data regions. Analyses produced using AIRS data demonstrate that observations selected via a combination of the simple and intelligent approaches reduce clustering, provide a more even distribution along the satellite swath edges, and, in general, have lower error and comparable computational requirements compared to standard operational thinning methodologies.
Convection-Allowing and Convection-Parameterizing Ensemble Forecasts of a Mesoscale Convective Vortex and Associated Severe Weather Environment
Authors: Clark Adam J. , Gallus William A. , Xue Ming , Kong Fanyou
Published: February 2010

An analysis of a regional severe weather outbreak that was related to a mesoscale convective vortex (MCV) is performed. The MCV-spawning mesoscale convection system (MCS) formed in northwest Kansas along the southern periphery of a large cutoff 500-hPa low centered over western South Dakota. As the MCS propagated into eastern Kansas during the early morning of 1 June 2007, an MCV that became evident from multiple data sources [e.g., Weather Surveillance Radar-1988 Doppler (WSR-88D) network, visible satellite imagery, wind-profiler data, Rapid Update Cycle 1-hourly analyses] tracked through northwest Missouri and central Iowa and manifested itself as a well-defined midlevel short-wave trough. Downstream of the MCV in southeast Iowa and northwest Illinois, southwesterly 500-hPa winds increased to around 25 m s−1 over an area with southeasterly surface winds and 500–1500 J kg−1 of surface-based convective available potential energy (CAPE), creating a favorable environment for severe weather. In the favorable region, multiple tornadoes occurred, including one rated as a category 3 storm on the enhanced Fujita scale (EF3) that caused considerable damage. In the analysis, emphasis is placed on the role of the MCV in leading to a favorable environment for severe weather. In addition, convection-allowing forecasts of the MCV and associated environmental conditions from the 10-member Storm-Scale Ensemble Forecast (SSEF) system produced for the 2007 NOAA Hazardous Weather Testbed Spring Experiment are compared to those from a similarly configured, but coarser, 30-member convection-parameterizing ensemble. It was found that forecasts of the MCV track and associated environmental conditions (e.g., midlevel winds, low-level wind shear, and instability) were much better in the convection-allowing ensemble. Errors in the MCV track from convection-parameterizing members likely resulted from westward displacement errors in the incipient MCS. Furthermore, poor depiction of MCV structure and maintenance in convection-parameterizing members, which was diagnosed through a vorticity budget analysis, likely led to the relatively poor forecasts of the associated environmental conditions. The results appear to be very encouraging for convection-allowing ensembles, especially when environmental conditions lead to a high degree of predictability for MCSs, which appeared to be the case for this particular event.
Persons with Cleft Lip and Palate Are Looked at Differently
Authors: Meyer-Marcotty P. , Gerdes A.B.M. , Reuther T. , Stellzig-Eisenhauer A. , Alpers G.W.
Published: February 2010

There is evidence that persons with cleft lip and palate (CLP) suffer psychosocial consequences as a result of their facial appearance. However, no data exist on how they are perceived by others. Our hypothesis was that CLP faces were looked at differently compared with faces lacking an anomaly. Eye movements of 30 healthy participants were recorded ( via an eye-tracking camera) while they viewed photographs of faces with/without a CLP. Subsequently, the faces were rated for appearance, symmetry, and facial expression. When the CLP faces were viewed, there were significantly more initial fixations in the mouth and longer fixations in the mouth and nose regions, compared with reactions when control faces were viewed. Moreover, CLP faces were rated more negatively overall. When faces with CLP were viewed, attention was directed to the mouth and nose region. Together with the negative ratings, this may explain at least some of the social deprivations in persons with CLP, probably due to residual asymmetry.
Local Anesthetics Inhibit Ca-ATPase in Masticatory Muscles
Authors: Sánchez G.A. , Takara D. , Alonso G.L.
Published: February 2010

Local anesthetics have myotoxic effects and inhibit Ca-ATPase activity and Ca transport in skeletal muscles. Such effects have not been fully elucidated in masticatory muscles. We tested the hypothesis that local anesthetics increase myoplasmic calcium in masticatory muscles by inhibiting Ca-ATPase at a concentration similar to that of dental cartridges. The effects of lidocaine and bupivacaine on Ca-ATPase from rabbit masseter and medial pterygoid muscles were tested with radioisotopic and colorimetric methods. Bupivacaine had an action similar to that of lidocaine on Ca-ATPase activity, but less effect on calcium transport. The pre-exposure of the membranes to the anesthetics enhanced the Ca-ATPase activity in the absence of calcium ionophore, supporting their permeabilizing effect. The results demonstrate that amide-type anesthetics do not inhibit calcium binding, but do reduce calcium transport and enzyme phosphorylation by ATP, and suggest that the myoplasmic calcium increase induced by lidocaine and bupivacaine might promote masticatory muscle contraction and eventual rigidity.
Neighbourhood Valuation Effects from New Construction of Low-income Housing Tax Credit Projects in Iowa: A Natural Experiment
Authors: Funderburg Richard , MacDonald Heather
Published: February 2010

This paper estimates the valuation effects from new construction of low-income housing tax credit (LIHTC) projects on neighbouring single-family homes in Polk County, Iowa. The evaluative models estimate the impact from LIHTC project locations on assessed values using a 1999—2007 panel of neighbours and their matches, while controlling for unobserved heterogeneity. The results suggest that the siting of new low-rise, concentrated low-income LIHTC projects is associated with a 2—4 per cent slower rate of nearby single-family home valuation and that these effects persisted for five or more years after project approval. On the other hand, no clear valuation effect is detected when the LIHTC project is high quality and targeted to mixed-income groups. It is also found that new construction LIHTC projects serving the elderly, including assisted living, are associated with a 2—4 per cent faster rate of growth in neighbouring single-family home values, although the acceleration appears to be short lived. It is concluded that concentrating low-income renters in subsidised housing projects has negative consequences for neighbouring property values that might be avoided with tenant income mixing and improved site planning and design.
Genetic Variation in Metabolizing Enzyme and Transporter Genes: Comprehensive Assessment in 3 Major East Asian Subpopulations With Comparison to Caucasians and Africans
Authors: Man Michael , Farmen Mark , Dumaual Carmen , Teng Choo Hua , Moser Brian , Irie Shin , Noh Gyu Jeong , Njau Reuben , Close Sandra , Wise Stephen , Hockett Richard
Published: February 2010

The advent of high‐throughput technologies has proven valuable in the assessment of genetic differences and their effects on drug activation, metabolism, disposition, and transport. However, most studies to date have focused on a small number of genes or few alleles, some of which are rare and therefore observed infrequently or lacked rigorous ethnic characterization, thus reducing the ability to extrapolate within and among populations. In this study, the authors comprehensively assessed the allele frequencies of 165 variants comprising 27 drug‐metabolizing enzyme and transporter (DMET) genes from 2188 participants across 3 major ethnic populations: Caucasians, Africans, and East Asians. This sample size was sufficiently large to demonstrate genetic differences among these major ethnic groups while concomitantly confirming similarities among East Asian subpopulations (Korean, Han Chinese, and Japanese). A comprehensive presentation of allele and genotype frequencies is included in the online supplement, and 3 of the most widely studied cytochrome P450 (CYP) genes, CYP2D6, CYP2C19, and CYP2C9; 2 non‐CYP enzymes, NAT1 and TMPT; and 2 transporter genes, SLCO1B1 and SLCO2B1, are presented herein according to ethnic classification.
Single‐ and Multiple‐Dose Pharmacokinetics and Tolerability of Telcagepant, an Oral Calcitonin Gene‐Related Peptide Receptor Antagonist, in Adults
Authors: Han Tae H. , Blanchard Rebecca L. , Palcza John , McCrea Jacqueline B. , Laethem Tine , Willson Kenneth , Xu Yang , Ermlich Susan , Boyle Janet , Lines Christopher , Gutierrez Maria , Van Bortel Luc , Xiao Alan J. , Sinclair Simon , Hickey Lisa , Panebianco Deborah , Murphy M. Gail
Published: February 2010

Telcagepant is a novel, orally active, and selective calcitonin gene‐related peptide receptor antagonist being developed for acute treatment of migraine with and without aura. Three separate clinical studies were conducted to evaluate the pharmacokinetics and tolerability of telcagepant following single oral doses in healthy young and elderly men and women and multiple oral doses in men. Telcagepant was rapidly absorbed with a time to maximum concentration of approximately 1.5 hours. The terminal half‐life was approximately 6 hours. A greater than dose‐proportional increase was observed in the area under the plasma concentration versus time curve from zero to infinity. Following twice‐daily dosing, with each dose separated by 2 hours, steady state was achieved in approximately 3 to 4 days with an accumulation ratio of approximately 2. There were no clinically meaningful pharmacokinetic differences when compared across age and gender. Telcagepant was generally well tolerated up to single doses of 1200 mg and multiple doses of 400 mg twice daily.
The transformation of employee participation: Consequences for the work environment
Authors: Busck Ole , Knudsen Herman , Lind Jens
Published: February 2010

This article reviews the research literature on the relationship between employee participation, influence and the work environment. The main part of the literature points to a positive connection in line with how it has been almost institutionalized in Karasek and Theorell’s demand—control model. However, more recent research into psychosocial work environment problems questions the model’s assumption of high job control compensating for high job demands. Taking its point of departure in a ‘deconstruction’ of the concept of participation based on research on employee participation from the past few decades, the article questions why increased employee participation does not seem to result in a healthy work environment.The article concludes that there are limitations to the demand— control model in modern working life given the contextual changes in the employer—employee relationship, which may mean a transformation of the significance of participation.
The impact of privatization and employee share ownership on employee commitment and citizen behaviour
Authors: McCarthy Dermot , Reeves Eoin , Turner Tom
Published: February 2010

Based on a survey of employees in a large telecommunications company, this article examines the means through which privatization, accompanied by an Employee Share Ownership Plan (ESOP), impact on employee commitment and organizational citizenship behaviour. The findings show that although the ESOP has in some way moderated outcomes, privatization has had negative consequences for commitment. Despite this, 50 percent of respondents report an increased level of citizenship behaviour. In determining changes in employee commitment and behaviour, it was found that an important role is played by how employees perceive changes in conditions of employment, involvement in workplace decision-making and management—union collaboration.
The innovation diffusion paradox in the light of ‘shop-floor games’ and micro-politics
Authors: Koski Pasi , Järvensivu Anu
Published: February 2010

In the literature on workplace innovation or organizational innovation, the concept of high-performance work systems (HPWS) has gained a prominent position. Theoretical and empirical evidence supports the argument that HPWS and their innovative workplace practices can increase firms’ performance. However, several studies have shown that, surprisingly, these practices are only infrequently adopted. Drawing insights from labour process theory and by using an in-depth qualitative approach, this article sheds light on this innovation diffusion paradox. It demonstrates how the realm of micro-politics and related conflicts, resistance and factory games affect the introduction of new practices in two Finnish factories.
Employment status and job insecurity: On the subjective appraisal of an objective status
Authors: Klandermans Bert , Hesselink John Klein , van Vuuren Tinka
Published: February 2010

The article argues that job insecurity has subjective aspects that are not determined by the objective levels of security of someone’s employment status. These subjective aspects can be divided into two elements: the perceived probability and the perceived severity of job loss. The psychological consequences of job insecurity supposedly vary as a function of the objective status and the two constituting elements of subjective job insecurity. Results are reported from a study in the Netherlands among 1706 workers in five employment statuses that differ in degree of security. The perceived probability and severity of job loss were assessed, as were five possible consequences of subjective insecurity. The article shows that (1) job insecurity reflects the ‘objective’ conditions people are in; (2) the appraisal of job insecurity results from the functioning of the probability and severity of job loss; and (3) probability and severity have different consequences depending on employment status.
FRP-confined Concrete Cylinders: Axial Compression Experiments and Strength Model
Authors: Benzaid Riad , Mesbah Habib , Nasr Eddine Chikh
Published: February 2010

The present article deals with the analysis of experimental results, in terms of load-carrying capacity and strain, obtained from tests on plain- and reinforced-concrete (RC) cylinders strengthened with external carbon-fiber-reinforced polymer (CFRP). The parameters considered are the number of composite layers and the compressive strength of unconfined concrete. The effective circumferential FRP failure strain and the effect of the effective lateral confining pressure were investigated. In total, 30 cylinders were subjected to axial compression, which included control specimens. All the test specimens were loaded to failure in axial compression and the behavior of the specimens in the axial and transverse directions was investigated. Test results showed that the CFRP wrap increases the strength and ductility of plain- and RC cylinders significantly. A simple model is presented to predict the compressive strength and axial strain of FRP-confined columns.
The Tribologic and Thermomechanic Properties of Polypropylene Filled with CaCO3 and Anhydrous Borax
Authors: Feyzullahoğlu Erol , Sahin Tülin
Published: February 2010

There are few studies showing the industrial application of boron compounds. In this study, boron compounds are used as fillers in plastic materials in order to increase the use of these raw materials. The effect of anhydrous borax mineral in the thermomechanical and tribologic properties of both calcium carbonate (CaCO3) unfilled and CaCO3 filled polypropylene (PP) material is investigated. Wear and thermomechanical properties of specialized PP material containing additives are examined by using pin-on disc wear tester, DSC, TMA and Shore D hardness testers. This study is the first to use boron (anhydrous borax) compounds as an additive in industrial plastics. As a consequence of the increase in the amount of boron in the samples, the friction coefficient also increases. An increase in the amount of CaCO3 used as an additive in the samples containing the same percentage of boron reduces the friction coefficient. Using anhydrous borax and CaCO3 as additives in a natural PP material did not create a considerable change in the crystalline melting temperature of the material. Weight loss increases for anhydrous borax, while it decreases for CaCO3 compared with natural PPB. If the amount of anhydrous borax is increased, the weight loss increases too. The minimum weight loss is seen for 10% CaCO3. This increases with an increasing amount of CaCO3 and is close to natural PPB.
Implications of Corticotropin Releasing Factor in Targeted Anticancer Therapy
Authors: Kim Byung-Jin , Jones Harlan P.
Published: February 2010

There is a need to develop novel anticancer therapies that eliminate adverse side effects produced by current treatments. Corticotropin releasing factor (CRF), an endogenous neuroedocrine factor, which typically regulates biological and psychological indicators of stress, has recently been found to be expressed by tumor malignancies. Here, we discuss the implications of CRF as a target for antitumor therapy through regulation of tumor immune escape mechanisms.
Obesity, Physical Activity, and Depressive Symptoms in a Cohort of Adults Aged 51 to 61
Authors: Carroll Dianna D. , Blanck Heidi M. , Serdula Mary K. , Brown David R.
Published: February 2010

Objective: To determine associations between changes in obesity and vigorous physical activity (PA) status and depressive symptoms in a cohort aged 51 to 61 years at baseline. Method: Two waves (1992, 1998) of Health and Retirement Study data were used to divide participants into four obesity and four vigorous PA status categories based on change in or maintenance of their 1992 status in 1998. Depressive symptoms were defined as the upper quintile score (women ≥ 4, men ≥ 3) on the eight-item Center for Epidemiologic Studies—Depression Scale. Logistic regression determined adjusted odds ratios for depressive symptoms associated with obesity and vigorous PA status. Results: Among men, no significant associations were found. Among women, decreasing from high vigorous PA status and maintenance of obese status were independently associated with increased odds for depressive symptoms in 1998. Discussion: The findings illustrate the importance of examining gender differences in studies of risk factors for depression.
Neglect of Alternative Causes in Predictive but Not Diagnostic Reasoning
Authors: Fernbach Philip M. , Darlow Adam , Sloman Steven A.
Published: February 2010

People are renowned for their failure to consider alternative hypotheses. We compare neglect of alternative causes when people make predictive versus diagnostic probability judgments. One study with medical professionals reasoning about psychopathology and two with undergraduates reasoning about goals and actions or about causal transmission yielded the same results: neglect of alternative causes when reasoning from cause to effect but not when reasoning from effect to cause. The findings suggest that framing a problem as a diagnostic-likelihood judgment can reduce bias.
Ameliorative effect of DRDE 07 and its analogues on the systemic toxicity of sulphur mustard and nitrogen mustard in rabbit
Authors: Kumar Pravin , Gautam Anshoo , Prakash Chandra Jatav  , kumar Abdhesh , Ganeshan K. , Pathak Uma , Vijayaraghavan R.
Published: February 2010

Despite extensive research efforts, there is no unanimous approval of any animal model to evaluate the toxicity of sulphur mustard [SM; bis (2-chloroethyl) sulphide] or nitrogen mustard [HN-3; tris-(2-chloroethyl) amine] and screening of various prophylactic and therapeutic agents against them. In this study, differential toxicity of mustard agents in higher animal model that is male rabbit was determined. Protective efficacy of DRDE 07 [S-2(2-aminoethylamino) ethyl phenyl sulphide] and its analogues were also evaluated against SM and HN-3 toxicity. Differential toxicity study of SM and HN-3 reveals that both the compounds were more toxic by percutaneous route as compared to subcutaneous route. Till date, there is no recommended drug to counteract SM induced toxicity or mortality in vivo. However, DRDE 07 (an amifostine analogue) and its analogues are found to be very effective protective agents against percutaneously exposed SM in rabbits. The present experiments also showed that SM does not cause skin injury alone but also can cause systemic toxicity as well. DRDE 07 and many of its analogues may prove as prototype compounds for the development of better prophylactic and therapeutic drugs to counter the toxicity of SM or HN-3. In conclusion, rodents and rabbits can be used for the screening of drugs against the blistering agents.
Gender Differences in Incidence Rates of Childhood B-Precursor Acute Lymphocytic Leukemia in Mississippi
Authors: Forsythe Amy , Breland Tobi , Majumdar Suvankar , Elkin T. David , Johnson Dana , Megason Gail
Published: February 2010

The authors studied pediatric patients with B-precursor acute lymphocytic leukemia (ALL) to determine whether Mississippi’s gender incidences correlate with national statistics. Furthermore, data on gender incidences in each of the risk categories of low, standard, and high were collected. A retrospective chart review was performed of pediatric B-precursor ALL patients diagnosed at the Children’s Cancer Clinic at the University of Mississippi Medical Center from 1995 to 2005. The gender incidences in Mississippi were found to be comparable with the national average for ALL (1.34:1 vs 1.3:1) overall. However, the national average includes T-cell ALL, which is known to be significantly more prevalent in boys. Of greater significance, boys were noted to present with high-risk B-precursor ALL 4 times more than girls, suggesting the need for further investigation into possible causes of this phenomenon.
Families of Young Pediatric Cancer Survivors: A Cross-Sectional Survey Examining Physical Activity Behavior and Health-Related Quality of Life
Authors: Norris Jill M. , Moules Nancy J. , Pelletier Guy , Culos-Reed S. Nicole
Published: February 2010

The present study examined physical activity levels within young families of pediatric cancer survivors and the relationship between physical activity and health-related quality of life (HRQL). Nineteen families were recruited, including 33 parents, 17 pediatric cancer survivors, and 10 siblings. Families completed a self-report survey on background information, physical activity levels, and PedsQL generic core scale for child HRQL. Results of this cross-sectional study indicate that families were generally active, with mothers more frequently participating in overall physical activity ( P < .001). Within families, parent—child physical activity levels were associated, but not survivor—sibling physical activity. Survivors and siblings did not differ in their self-reported physical activity levels or HRQL, and no association was observed between physical activity and HRQL. However, discrepancies between sibling self-report and parent proxy-reported HRQL were notable. Overall, results from this exploratory pilot work will assist in further research into physical activity behaviors and HRQL in families of pediatric cancer survivors.The nurse should consider the varied experiences of family members, particularly those of siblings, through long-term follow-up.