bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinoic Acid Synthesis Promotes Development of Neural Progenitors from Mouse Embryonic Stem Cells by Suppressing Endogenous, Wnt-Dependent Nodal Signaling
Authors: Engberg Nina , Kahn Morten , Petersen Dorthe Rønn , Hansson Mattias , Serup Palle
Published: July 2010

Embryonic stem (ES) cells differentiate spontaneously toward a neuroectodermal fate in serum-free, adherent monocultures. Here, we show that this spontaneous neural fate requires retinoic acid (RA) synthesis. We monitor ES cells containing reporter genes for markers of the early neural plate as well as the primitive streak and its progeny to determine the cell fates induced when RA signaling is perturbed. We demonstrate that the spontaneous neural commitment of mouse ES cells requires endogenous RA production from vitamin A (vitA) in the medium. Formation of neural progenitors is inhibited by removing vitA from the medium, by inhibiting the enzymes that catalyze the synthesis of RA, or by inhibiting RA receptors. We show that subnanomolar concentrations of RA restore neuroectodermal differentiation when RA synthesis is blocked. We demonstrate that a neural to mesodermal fate change occurring when RA signaling is inhibited is dependent on Nodal-, Wnt-, and fibroblast growth factor-signaling. We show that Nodal suppresses neural development in a Wnt-dependent manner and that Wnt-mediated inhibition of neural development is reversed by inhibition of Nodal signaling. Together, our results show that neural induction in ES cells requires RA at subnanomolar levels to suppress Nodal signaling and suggest that the mechanism by which Wnt signaling suppresses neural development is through facilitation of Nodal signaling.
miR-124a Is Important for Migratory Cell Fate Transition During Gastrulation of Human Embryonic Stem Cells
Authors: Ryul Lee Man , Soo Kim Jong , Kim Kye-Seong
Published: July 2010

Precise control of gene expression is of paramount importance for proper embryonic development. Although a number of microRNAs (miRNAs) has been implicated in fine-tuning mRNA translation during development, their exact roles for gastrulation, particularly in connection with functional targets, have yet to be clarified, with regard to stage-specific cell migration to form three embryonic germ layers. We found that miR-124a is expressed in human embryonic stem cells (hESC), but is gradually downregulated during embryoid body (EB) formation in vitro. We also provide evidence that SLUG and IQGAP1, which modulates rearrangement of the migratory cytoskeleton, are specific targets for miR-124a during EB formation. Furthermore, we show that the beginning of cell migration, a hallmark event in gastrulation, is tightly coupled with downregulation of miR-124a during EB formation and induction of SLUG and IQGAP1. Overexpressed miR-124a in hESC reduced expression of SLUG and IQGAP1 and blocked migratory cell behavior in EB. An expression level of MIXL1, associated with gastulation process, was also inversely correlated with expression of miR-124a. Taken together, our results strongly suggest that miR-124a may play an active role in inhibiting hESCs from differentiation into EB by downregulating expression of SLUG and IQGAP1, thereby maintaining stemness.
Mode shape linearization and correction in coupled dynamic analysis of wind‐excited tall buildings
Authors: Huang Mingfeng , Tse Kam‐Tim , Chan Chun‐Man , Kwok Kenny C. S. , Hitchcock Peter A. , Lou Wenjuan
Published: July 2010

The three‐dimensional mode shapes found in modern tall buildings complicate the use of the high‐frequency base balance (HFBB) technique in wind tunnel testing for predicting their wind‐induced loads and effects. The linearized‐mode‐shape (LMS) method was recently proposed to address some of the complications in the calculation of the generalized wind forces, which serve as the input to modal analysis for predicting wind‐induced dynamic responses of tall buildings. An improved LMS method, called the advanced linearized‐mode‐shape (ALMS) method, is developed in this paper by introducing torsional mode shape corrections to account for the partial correlation of torques over building height. The ALMS method has been incorporated into the accurate complete quadratic combination method in the coupled dynamic analysis to form a comprehensive procedure for the determination of equivalent static wind loads (ESWLs) for structural design of complex tall buildings. The improved accuracy in the prediction of generalized forces by the ALMS method has been validated by a 60‐storey benchmark building with multiple‐point simultaneous pressure measurements. A practical 40‐storey residential building with significant swaying and torsional effects is presented to demonstrate the effectiveness of the proposed wind load and response analysis procedure based on the HFBB data. Copyright © 2010 John Wiley & Sons, Ltd.
Long‐term potentiation (LTP) of human sensory‐evoked potentials
Authors: Kirk Ian J. , McNair Nicolas A. , Hamm Jeffrey P. , Clapp Wesley C. , Mathalon Daniel H. , Cavus Idil , Teyler Timothy J.
Published: July 2010

Long‐term potentiation (LTP) is the principal candidate synaptic mechanism underlying learning and memory, and has been studied extensively at the cellular and molecular level in laboratory animals. Inquiry into the functional significance of LTP has been hindered by the absence of a human model as, until recently, LTP has only been directly demonstrated in humans in isolated cortical tissue obtained from patients undergoing surgery, where it displays properties identical to those seen in non‐human preparations. In this brief review, we describe the results of paradigms recently developed in our laboratory for inducing LTP‐like changes in visual‐, and auditory‐evoked potentials. We describe how rapid, repetitive presentation of sensory stimuli leads to a persistent enhancement of components of sensory‐evoked potential in normal humans. Experiments to date, investigating the locus, stimulus specificity, and NMDA receptor dependence of these LTP‐like changes suggest that they have the essential characteristics of LTP seen in experimental animals. The ability to elicit LTP from non‐surgical patients will provide a human model system allowing the detailed examination of synaptic plasticity in normal subjects and may have future clinical applications in the assessment of cognitive disorders. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Psychology > Brain Function and Dysfunction

Neuroscience > Plasticity
Abolition
Authors: Drescher Seymour
Published: July 2010

In one form or another, slavery has existed throughout the world for millennia. It helped to change the world, and the world transformed the institution. In the 1450s, when Europeans from the small corner of the globe least enmeshed in the institution first interacted with peoples of other continents, they created, in the Americas, the most dynamic, productive, and exploitative system of coerced labor in human history. Three centuries later these same intercontinental actions produced a movement that successfully challenged the institution at the peak of its dynamism. Within another century a new surge of European expansion constructed Old World empires under the banner of antislavery. However, twentieth-century Europe itself was inundated by a new system of slavery, larger and more deadly than its earlier system of New World slavery. This book examines these dramatic expansions and contractions of the institution of slavery and the impact of violence, economics, and civil society in the ebb and flow of slavery and antislavery during the last five centuries.
Adaptability to organic farming of lentil (Lens culinarisMedik.) varieties developed from conventional breeding programmes
Authors: VLACHOSTERGIOS D. N. , LITHOURGIDIS A. S. , ROUPAKIAS D. G.
Published: July 2010

The development of organic agriculture has raised the demand for crop varieties well-adapted to organic farming systems. Most of the varieties presently cultivated in organic agriculture were developed from conventional breeding programmes. The objective of the present work was to study the adaptability to organic farming systems of lentil (Lens culinarisMedik.) varieties developed from conventional breeding programmes. Twenty varieties were evaluated over five environments under organic and conventional farming systems from 2005 to 2007. Genotype×system interactions (GSI) for grain yield were significantly different in four out of the five environments and GSI explained 0·03–0·17 of the variance. Spearman's rank correlation index of the 20 varieties between the conventional and organic system ranged from 0·27 to 0·93 in the five environments. Direct selection of the top five varieties in organic systems resulted in significantly higher grain yields than indirect selection in one out of the five environments. However, among the top five varieties, the highest yielding varieties under conventional farming systems were not always the highest yielding varieties under organic farming systems. These results indicate that the demands of organic agriculture for yield performance could be only partially satisfied by varieties developed under conventional breeding programmes.
Quantification of C and N stocks in grassland topsoils in a Dutch region dominated by dairy farming
Authors: SONNEVELD M. P. W. , VAN DEN AKKER J. J. H.
Published: July 2010

Estimates on soil organic carbon (SOC) and nitrogen (N) stocks in soils cannot be directly calculated from routine soil analyses, since these often lack measurements on soil bulk density (Bd). Hence, flexible pedotransfer functions are required that allow the calculation of SOC stocks from gravimetrically determined SOC contents. The present paper aimed to: (1) quantify SOC and N stocks in grassland topsoils for a Northern Dutch region dominated by dairy farming and (2) analyse the relationships between SOC and bulk density at the field level. As estimates of SOC and N stocks are potentially affected by soil compaction, the combined measurements on soil bulk density and soil organic matter (SOM) were also evaluated with respect to critical limits for soil compaction using soil density (Sd) for sandy soils and packing density (Pd) for clay soils. The SOC andBdmeasurements were done in the upper 0·1–0·2 m of grasslands at 18 dairy farms, distributed across sandy, clay and peat soils. Both farm data and grassland management data were collected. Non-linear regressions were used to analyse relationships betweenBdand SOM. Significant non-linear relationships were found between gravimetric SOC contents and bulk density for the 0–0·1 m layer (R2=0·80) and the 0·1–0·2 m layer (R2=0·86). None of the fields on sandy soils or clay soils indicated signs for limited rooting in the topsoil although some fields appear to approach the critical limit for compaction for the 0·1–0·2 m layer. Stocks of SOC in the top 0·2 m at farm level were highest in the peat soils (21·7 kg/m2) and lowest in the sandy soils (9·0 kg/m2). Similarly, N stocks were highest for farms on peat soil (1·30 kg/m2) and lowest for farms on sandy soil (0·60 kg/m2). For the sandy soils, the mean SOC stock was significantly higher in fields with shallow groundwater tables.
Aeromechanics of passive rotation in flapping flight
Authors: WHITNEY J. P. , WOOD R. J.
Published: July 2010

Flying insects and robots that mimic them flap and rotate (or ‘pitch’) their wings with large angular amplitudes. The reciprocating nature of flapping requires rotation of the wing at the end of each stroke. Insects or flapping-wing robots could achieve this by directly exerting moments about the axis of rotation using auxiliary muscles or actuators. However, completely passive rotational dynamics might be preferred for efficiency purposes, or, in the case of a robot, decreased mechanical complexity and reduced system mass. Herein, the detailed equations of motion are derived for wing rotational dynamics, and a blade-element model is used to supply aerodynamic force and moment estimates. Passive-rotation flapping experiments with insect-scale mechanically driven artificial wings are conducted to simultaneously measure aerodynamic forces and three-degree-of-freedom kinematics (flapping, rotation and out-of-plane deviation), allowing a detailed evaluation of the blade-element model and the derived equations of motion. Variations in flapping kinematics, wing-beat frequency, stroke amplitude and torsional compliance are made to test the generality of the model. All experiments showed strong agreement with predicted forces and kinematics, without variation or fitting of model parameters.
In defence of logical nominalism: reply to Leftow
Authors: SWINBURNE RICHARD
Published: July 2010

This paper defends (especially in response to Brian Leftow's recent attack) logical nominalism, the thesis that logically necessary truth belongs primarily to sentences and depends solely on the conventions of human language. A sentence is logically necessary (that is, a priori metaphysically necessary) iff its negation entails a contradiction. A sentence is a posteriori metaphysically necessary iff it reduces to a logical necessity when we substitute for rigid designators of objects or properties canonical descriptions of the essential properties of those objects or properties. The truth-conditions of necessary sentences are not to be found in any transcendent reality, such as God's thoughts. ‘There is a God’ is neither a priori nor a posteriori metaphysically necessary; God is necessary in the sense that His existence is not causally contingent on anything else.
Qualitative Interviews in Applied Linguistics: From Research Instrument to Social Practice
Authors: Talmy Steven
Published: July 2010

Interviews have been used for decades in empirical inquiry across the social sciences as one or the primary means of generating data. In applied linguistics, interview research has increased dramatically in recent years, particularly in qualitative studies that aim to investigate participants’ identities, experiences, beliefs, and orientations toward a range of phenomena. However, despite the proliferation of interview research in qualitative applied linguistics, it has become equally apparent that there is a profound inconsistency in how the interview has been and continues to be theorized in the field. This article critically reviews a selection of applied linguistics research from the past 5 years that uses interviews in case study, ethnographic, narrative, (auto)biographical, and related qualitative frameworks, focusing in particular on the ideologies of language, communication, and the interview, or the communicable cartographies of interviewing, that are evident in them. By contrasting what is referred to as aninterview as research instrumentperspective with aresearch interview as social practiceorientation, the article argues for greater reflexivity about the interview methods that qualitative applied linguists use in their studies, the status ascribed to interview data, and how those data are analyzed and represented.
Current Issues in Heritage Language Acquisition
Authors: Montrul Silvina
Published: July 2010

An increasing trend in many postsecondary foreign language classes in North America is the presence of heritage language learners. Heritage language learners are speakers of ethnolinguistically minority languages who were exposed to the language in the family since childhood and as adults wish to learn, relearn, or improve their current level of linguistic proficiency in their family language. This article discusses the development of the linguistic and grammatical knowledge of heritage language speakers from childhood to adulthood and the conditions under which language learning does or does not occur. Placing heritage language acquisition within current and viable cognitive and linguistic theories of acquisition, I discuss what most recent basic research has so far uncovered about heritage speakers of different languages and their language learning process. I conclude with directions for future research.
Meta-analysis in Second Language Research: Choices and Challenges
Authors: Oswald Frederick L. , Plonsky Luke
Published: July 2010

Applied linguists are increasingly conducting meta-analysis in their substantive domains, because as a quantitative approach for averaging effect sizes across studies, it is more systematic and replicable than traditional, qualitative literature reviews. Additional strengths, such as increased statistical power, moderator analyses, and model testing, have also contributed to its appeal. The current review describes typical stages of a meta-analysis in second language acquisition (SLA) research: (a) defining the research domain, (b) developing a reliable coding scheme, (c) analyzing data, and (d) interpreting results. Each stage has a host of equally reasonable decisions that can be made; each decision will influence the conduct of the meta-analysis, the nature of the results, and the substantive implications of findings for SLA. We highlight a number of benefits and challenges that inform these decisions. In general, when a meta-analysis in applied linguistics is well planned, employs sound statistical methods, and is based on a thorough understanding of relevant theory, it can provide critical information that informs theory as well as future research, practice, and policy.
Effectiveness of village-based marine reserves on reef invertebrates in Emau, Vanuatu
Authors: DUMAS P. , JIMENEZ H. , LÉOPOLD M. , PETRO G. , JIMMY R.
Published: July 2010

Despite the current expansion of community-based marine conservation initiatives in the Pacific, few studies have specifically addressed their ecological efficiency to restore or enhance reef invertebrate resources. This paper investigated the effects of two very small (< 0.05 km2) recent village-based marine reserves (tabu areas) located along the shallow fringing reef of Emau island, Vanuatu. Surveys focused on heavily harvested species (namely trochus, giant clams and green snails) and involved both experienced scientists and local villagers. Abundance, density and individual size data were collected by snorkelling along random transect belts located inside and outside the tabu areas, using simple PVC measuring tools specifically developed for participative monitoring. Habitat was assessed using a photographic method to quantitatively describe varied reef substrata. Resource recovery varied between the areas as a result of species-specific responses to contrasted reserve characteristics and local management practices. Fast-growing mobile Trochus niloticus exhibited strong positive abundance and size responses only within the older larger tabu area through the combined effects of protection from harvesting and translocation actions by local fishers. Similar trends were observed to a lesser extent for sessile slow-growing giant clams (Tridacna spp.), but these were not significant after four years of closure. Despite historical evidence of their presence in the area, surveys emphasized the severe population collapse of the heavily targeted green snail (Turbo marmoratus). Under certain conditions, very small-scale reserves, such as those implemented by village-based conservation initiatives, can rapidly and efficiently enhance local reef invertebrate resources. It is still unclear whether the changes are sufficient to restore critical levels of spawning biomass at larger scale and reverse the severe depletion of invertebrate resources occurring in Vanuatu.
Using connectivity metrics and niche modelling to explore the occurrence of the northern crested newt Triturus cristatus (Amphibia, Caudata) in a traditionally managed landscape
Authors: HARTEL TIBOR , NEMES SZILÁRD , ÖLLERER KINGA , COGĂLNICEANU DAN , MOGA COSMIN , ARNTZEN JAN W.
Published: July 2010

Spatial models are increasingly employed to help understand the distribution of organisms and establish conservation priorities. Classic patch-orientated models may have limited power to accurately predict the organisms' distributions. Pond breeding amphibians are appropriate study organisms because of their complex life cycle, low dispersal and sensitivity to environmental conditions. Here connectivity metrics and niche modelling were used to predict the occurrence of the northern crested newt in a rural landscape from central Romania. Pond-related variables, such as macrophyte cover and the presence of predatory fish, were the most important predictors of newt occurrence, followed by one landscape-related variable (urbanization) and a connectivity metric (nearest neighbouring occupied pond). Most of the landscape and connectivity variables were not adequate predictors, presumably because most of the terrestrial habitats in this traditionally used rural landscape are ecologically optimal for amphibians. Conservation measures for the northern crested newt should promote the preservation of traditional extensive agricultural practices and discourage stocking of ponds with predatory fish.
Human zygote morphological indicators of higher rate of arrest at the first cleavage stage
Authors: Zamora Raquel Blanes , Sánchez Rebeca Vaca , Pérez Jonay González , Díaz Rubí Rodríguez , Quintana Delia Báez , Bethencourt José C. Alberto
Published: July 2010

A little studied aspect of developmental arrest (DA) in ART is zygote arrest (ZA). Etiologically, blockage at the first cleavage stage includes molecular and chromosomal anomalies, some of which manifest morphologically. Given considerations on embryo culture, transfer and cryopreservation, optimal zygote selection is very important. The aim of this study was to ascertain whether zygote morphological features were indicators of increased ZA. In this study we performed a prospective, observational study of 2105 zygotes obtained from consecutive patients who were undergoing IVF/ICSI treatment, of which 43 (2%) suffered ZA. Morphological features observed under the inverted microscope were qualitatively categorized: pronuclear size, nucleolar precursor bodies (NPB) alignment, light and dark halos, polar body placement and fragmentation observed at 16–18 h post-insemination. We compared these features in blocked versus cleaved zygotes at 48 h and found significant correlations (p < 0.05) between ZA and three features: the absence of a light halo (p = 0.001), the absence of a dark halo (p < 0.005), and non-aligned NPB (p < 0.05). We can say that certain morphological features are indicators of significantly increased zygote arrest. These findings may be of utility for optimal zygote selection and culture strategies, especially in countries under restrictive conditions.
Alerting, orienting, and executive attention in older adults
Authors: MAHONEY JEANNETTE R. , VERGHESE JOE , GOLDIN YELENA , LIPTON RICHARD , HOLTZER ROEE
Published: July 2010

The Attention Network Test (ANT) assesses alerting, orienting, and executive attention. The current study was designed to achieve three main objectives. First, we determined the reliability, effects, and interactions of attention networks in a relatively large cohort of non-demented older adults (n= 184). Second, in the context of this aged cohort, we examined the effect of chronological age on attention networks. Third, the effect of blood pressure on ANT performance was evaluated. Results revealed high-reliability for the ANT as a whole, and for specific cue and flanker types. We found significant main effects for the three attention networks as well as diminished alerting but enhanced orienting effects during conflict resolution trials. Furthermore, increased chronological age and low blood pressure were both associated with significantly worse performance on the executive attention network. These findings are consistent with executive function decline in older adults and the plausible effect of reduced blood flow to the frontal lobes on individual differences in attention demanding tasks. (JINS, 2010,16, 877–889.)
Remote sensing of radiative and microphysical properties of clouds during TC4: Results from MAS, MASTER, MODIS, and MISR
Authors: King Michael D. , Platnick Steven , Wind Galina , Arnold G. Thomas , Dominguez Roseanne T.
Published: July 2010

The Moderate Resolution Imaging Spectroradiometer (MODIS) Airborne Simulator (MAS) and MODIS/Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Airborne Simulator (MASTER) were used to obtain measurements of the bidirectional reflectance and brightness temperature of clouds at 50 discrete wavelengths between 0.47 and 14.2 μm (12.9 μm for MASTER). These observations were obtained from the NASA ER‐2 aircraft as part of the Tropical Composition, Cloud and Climate Coupling (TC4) experiment conducted over Central America and surrounding Pacific and Atlantic Oceans between 17 July and 8 August 2007. Multispectral images in eleven distinct bands were used to derive a confidence in clear sky (or alternatively the probability of cloud) over land and ocean ecosystems. Based on the results of individual tests run as part of the cloud mask, an algorithm was developed to estimate the phase of the clouds (liquid water, ice, or undetermined phase). The cloud optical thickness and effective radius were derived for both liquid water and ice clouds that were detected during each flight, using a nearly identical algorithm to that implemented operationally to process MODIS cloud data from the Aqua and Terra satellites (Collection 5). This analysis shows that the cloud mask developed for operational use on MODIS, and tested using MAS and MASTER data in TC4, is quite capable of distinguishing both liquid water and ice clouds during daytime conditions over both land and ocean. The cloud optical thickness and effective radius retrievals use five distinct bands of the MAS (or MASTER), and these results were compared with nearly simultaneous retrievals of marine liquid water clouds from MODIS on the Terra spacecraft. Finally, this MODIS‐based algorithm was adapted to Multiangle Imaging SpectroRadiometer (MISR) data to infer the cloud optical thickness of liquid water clouds from MISR. Results of this analysis are compared and contrasted.
The involvement of sphingosine kinase 1 in LPS‐induced Toll‐like receptor 4‐mediated accumulation of HIF‐1α protein, activation of ASK1 and production of the pro‐inflammatory cytokine IL‐6
Authors: Pchejetski Dmitri , Nunes Joao , Coughlan Karen , Lall Harjinder , Pitson Stuart M , Waxman Jonathan , Sumbayev Vadim V
Published: July 2010

Toll‐like receptors (TLRs) lie in the core of resistance to infectious diseases allowing host immune cells to specifically detect pathogens by recognising their specific molecular patterns. Cell membrane‐associated TLR4 (recognises lipopolysaccharide (LPS) of Gram‐negative bacteria) and endosomal TLR7/8 (recognise viral single‐stranded RNA) are known to activate hypoxia inducible factor‐1α (HIF‐1α) protein (necessary for cellular adaptation to the inflammatory stress) via redox‐dependent mechanism. TLR4 triggers the cross talk between HIF‐1α and apoptosis signal‐regulating kinase 1 (ASK1), whereas TLR7/8 activates HIF‐1α in the ASK1‐independent manner. Here, we report that in THP‐1 and RAW264.7 macrophages, ligand‐induced activation of the TLR4 but not TLR7/8 induces activation and transcriptional upregulation of sphingosine kinase 1 (SphK1) in extracellular signal‐regulating kinase and phospholipase C‐1γ/PI3 kinase‐dependent manner. TLR4‐mediated SphK1 activation was found to be critical for the redox‐dependent activation of HIF‐1α and ASK1, as well as for the prevention of LPS‐induced activation of caspase 3 and the expression of pro‐inflammatory cytokine interleukin‐6.
Synchrotron radiation circular dichroism (SRCD) spectroscopy: an enhanced method for examining protein conformations and protein interactions
Authors: Wallace B.A. , Janes Robert W.
Published: July 2010

CD (circular dichroism) spectroscopy is a well-established technique in structural biology. SRCD (synchrotron radiation circular dichroism) spectroscopy extends the utility and applications of conventional CD spectroscopy (using laboratory-based instruments) because the high flux of a synchrotron enables collection of data at lower wavelengths (resulting in higher information content), detection of spectra with higher signal-to-noise levels and measurements in the presence of absorbing components (buffers, salts, lipids and detergents). SRCD spectroscopy can provide important static and dynamic structural information on proteins in solution, including secondary structures of intact proteins and their domains, protein stability, the differences between wild-type and mutant proteins, the identification of natively disordered regions in proteins, and the dynamic processes of protein folding and membrane insertion and the kinetics of enzyme reactions. It has also been used to effectively study protein interactions, including protein–protein complex formation involving either induced-fit or rigid-body mechanisms, and protein–lipid complexes. A new web-based bioinformatics resource, the Protein Circular Dichroism Data Bank (PCDDB), has been created which enables archiving, access and analyses of CD and SRCD spectra and supporting metadata, now making this information publicly available. To summarize, the developing method of SRCD spectroscopy has the potential for playing an important role in new types of studies of protein conformations and their complexes.
Proteolytic processing of tau
Authors: Wang Yipeng , Garg Sarika , Mandelkow Eva-Maria , Mandelkow Eckhard
Published: July 2010

Tau aggregation is a hallmark of several neurodegenerative diseases, including AD (Alzheimer's disease), although the mechanism underlying tau aggregation remains unclear. Recent studies show that the proteolysis of tau plays an important role in both tau aggregation and neurodegeneration. On one hand, truncation of tau may generate amyloidogenic tau fragments that initiate the aggregation of tau, which in turn can cause toxicity. On the other hand, truncation of tau may result in tau fragments which induce neurodegeneration through unknown mechanisms, independently of tau aggregation. Blocking the truncation of tau thus may represent a promising therapeutic approach for AD or other tauopathies. In the present paper, we summarize our data on tau cleavage in a cell model of tauopathy and major results on tau cleavage reported in the literature.
Pathways linking Aβ and tau pathologies
Authors: LaFerla Frank M.
Published: July 2010

Aβ (amyloid β-peptide) and tau are the main proteins that misfold and accumulate in amyloid plaques and NFTs (neurofibrillary tangles) of Alzheimer's disease and other neurological disorders. Historically, because plaques and NFTs accumulate in diverse cellular compartments, i.e. mainly extracellularly for plaques and intracellularly for NFTs, it was long presumed that the constituent proteins formed these lesions via unrelated pathways. Animal and cell studies over the last decade, however, have provided convincing evidence to show that Aβ can facilitate the development of tau pathology by altering several cell-dependent and -independent mechanisms. In the present article, results are reviewed from several laboratories that show that modulating Aβ pathology can directly affect the development of tau pathology, which has significant implications for the treatment of Alzheimer's disease.
Tau cleavage and tau aggregation in neurodegenerative disease
Authors: Hanger Diane P. , Wray Selina
Published: July 2010

Deposition of highly phosphorylated tau in the brain is the most significant neuropathological and biochemical characteristic of the group of neurodegenerative disorders termed the tauopathies. The discovery of tau fragments in these diseases suggests that tau cleavage and tau phosphorylation, both of which induce conformational changes in tau, could each have roles in disease pathogenesis. The identities of the proteases responsible for degrading tau, resulting in the appearance of truncated tau species in physiological and pathological conditions, are not known. Several fragments of tau are reported to have pro-aggregation properties, but the lack of disease-relevant cell models of tau aggregation has hampered investigation of the effects of tau aggregation on normal cellular functioning. In the present paper, we describe our findings of N-terminally truncated tau in the brain in a subgroup of the tauopathies in which tau isoforms containing four microtubule-binding domains predominate. We also discuss the evidence for the involvement of proteases in the generation of tau pathology in neurodegenerative disease, since these enzymes warrant further investigation as potential therapeutic targets in the tauopathies.
The ground state of pluripotency
Authors: Wray Jason , Kalkan Tuzer , Smith Austin G.
Published: July 2010

Pluripotency is defined as the capacity of individual cells to initiate all lineages of the mature organism in response to signals from the embryo or cell culture environment. A pluripotent cell has no predetermined programme; it is a blank slate. This is the foundation of mammalian development and of ES (embryonic stem) cell biology. What are the design principles of this naïve cell state? How is pluripotency acquired and maintained? Suppressing activation of ERKs (extracellular-signal-regulated kinases) is critical to establishing and sustaining ES cells. Inhibition of GSK3 (glycogen synthase kinase 3) reinforces this effect. We review the effect of selective kinase inhibitors on pluripotent cells and consider how these effects are mediated. We propose that ES cells represent a ground state, meaning a basal proliferative state that is free of epigenetic restriction and has minimal requirements for extrinsic stimuli. The stability of this state is reflected in the homogeneity of ES cell populations cultured in the presence of small-molecule inhibitors of MEK (mitogen-activated protein kinase/ERK kinase) and GSK3.
Imaging-based chemical screens using normal and glioma-derived neural stem cells
Authors: Danovi Davide , Falk Anna , Humphreys Peter , Vickers Richard , Tinsley Jon , Smith Austin G. , Pollard Steven M.
Published: July 2010

The development of optimal culture methods for embryonic, tissue and cancer stem cells is a critical foundation for their application in drug screening. We previously described defined adherent culture conditions that enable expansion of human radial glia-like fetal NS (neural stem) cells as stable cell lines. Similar protocols proved effective in the establishment of tumour-initiating stem cell lines from the human brain tumour glioblastoma multiforme, which we termed GNS (glioma NS) cells. Others have also recently derived more primitive human NS cell lines with greater neuronal subtype differentiation potential than NS cells, which have similarities to the early neuroepithelium, named NES (neuroepithelial stem) cells. In the present paper, we discuss the utility of these cells for chemical screening, and describe methods for a simple high-content live-image-based platform. We report the effects of a panel of 160 kinase inhibitors (Inhibitor Select I and II; Calbiochem) on NES cells, identifying three inhibitors of ROCK (Rho-associated kinase) as promoting the expansion of NES cell cultures. For the GNS cells, we screened a panel of 1000 compounds and confirmed our previous finding of a cytotoxic effect of modulators of neurotransmitter signalling pathways. These studies provide a framework for future higher-throughput screens.
Secondary structure of U6 small nuclear RNA: implications for spliceosome assembly
Authors: Dunn Elizabeth A. , Rader Stephen D.
Published: July 2010

U6 snRNA (small nuclear RNA), one of five RNA molecules that are required for the essential process of pre-mRNA splicing, is notable for its high level of sequence conservation and the important role it is thought to play in the splicing reaction. Nevertheless, the secondary structure of U6 in the free snRNP (small nuclear ribonucleoprotein) form has remained elusive, with predictions changing substantially over the years. In the present review we discuss the evidence for existing models and critically evaluate a fundamental assumption of these models, namely whether the important 3′ ISL (3′ internal stem–loop) is present in the free U6 particle, as well as in the active splicing complex. We compare existing models of free U6 with a newly proposed model lacking the 3′ ISL and evaluate the implications of the new model for the structure and function of U6's base-pairing partner U4 snRNA. Intriguingly, the new model predicts a role for U4 that was unanticipated previously, namely as an activator of U6 for assembly into the splicing machinery.
Muscle Shape as a Predictor of Traumatic Enophthalmos
Authors: Chiasson Genevieve , Matic Damir B.
Published: July 2010

The literature on enophthalmos is reviewed to understand its etiology and its prevention following orbital fractures. Specifically, the importance of muscle shape changes in predicting enophthalmos is discussed. The indications for surgical repair of orbital blowout fractures are well established. However, 7 to 10% of patients still develop enophthalmos despite these criteria. Because late repair of enophthalmos is associated with poor esthetic and functional results, the sensitivity and specificity of the current indications need to be further improved. Increased orbital volumes after fracture together with soft tissue displacement and herniation are the two most important factors causing enophthalmos. The loss of both bone and periorbita as supporting structures is seen on coronal computed tomography scan as changes in shape of the extraocular muscles. In floor fractures, the inferior rectus changes from an ellipse to a more rounded shape. The same is true for the medial rectus in medial wall fractures. It is the degree of rounding measured as a ratio of height to width that has been shown to be predictive of enophthalmos. Therefore, because rounding signifies loss of bone and soft tissue support, it may be a more important indication for surgical intervention than fracture size alone.
Blowout Fractures: Surgical Outcome in Relation to Age, Time of Intervention, and Other Preoperative Risk Factors
Authors: Amrith Shantha , Almousa Radwan , Wong Wan Ling , Sundar Gangadhara
Published: July 2010

We sought to describe outcome of surgical repair in patients presenting with orbital blowout fractures. This noncomparative, retrospective, consecutive case series reviewed the case notes of 63 consecutive patients who underwent surgery for a blowout fracture between November 1992 and March 2005. Risk factors for motility outcome as well as presence of enophthalmos after surgery were analyzed. Children had earlier surgery than adults ( p < 001) and tended to have better motility outcome than adults. Surgery performed within the first week showed a trend for better outcome, but this was not statistically significant ( p = 0.231). Assault had the best motility outcome, compared with other modes of trauma. Patients with worse preoperative motility had better outcome ( p < 0.001). Enophthalmos improved significantly after surgery ( p < 001). Children as compared with adults and surgery performed within the first week tended to have better motility outcome, but this was not statistically significant.
Sinus Preservation Management for Frontal Sinus Fractures in the Endoscopic Sinus Surgery Era: A Systematic Review
Authors: Carter Kenny B. , Poetker David M. , Rhee John S.
Published: July 2010

We systematically reviewed the existing literature supporting the efficacy and safety of sinus preservation management for frontal sinus fractures in the modern era of endoscopic frontal sinus surgery. A systematic review of the English literature for the targeted objective was conducted using the PubMed database between January 1995 and August 2008. The PubMed database was queried using two major search terms of frontal sinus fracture or frontal sinus injury along with manual review of citations within bibliographies. Citations acquired from the primary search were filtered and relevant abstracts were identified that merited full review. Articles were identified that included any cohort of patients with frontal sinus fractures involving the frontal sinus outflow tract or posterior wall with sinus preservation management. A total of 231 citations were generated, and 56 abstracts were identified as potentially relevant articles. Sixteen articles merited full review, with seven articles meeting inclusion criteria for sinus preservation. There were 515 total patients in the studies with 350 patients managed with frontal sinus preservation. Similar short-term complications and effectiveness were found between fractures managed with sinus preservation and those with traditional management. Sinus preservation appears to be a safe and effective management strategy for select frontal sinus fractures. More transparent reporting of management strategies for individual cases or cohorts is needed. A standardized algorithm and categorization framework for future studies are proposed. Longer-term follow-up and larger prospective studies are necessary to assess the safety and efficacy of sinus preservation protocols.
Accounting Executives and it Outsourcing Recommendations: An Experimental Study of the Effect of CIO Skills and Institutional Isomorphism
Authors: Blaskovich Jennifer , Mintchik Natalia
Published: July 2010

Although substantial effort has been devoted to understanding how cost issues drive Information Technology outsourcing (ITO), several researchers have proposed that this narrow focus ignores the role of more subtle factors. This paper addresses this concern by investigating internal and external influences on accounting executives’ recommendations to outsource the IT infrastructure. Using resource-based and institutional theories, we hypothesize that when the chief information officer's (CIO's) skills are strong, accounting executives will more likely advise against outsourcing. But when the skills are weak, accountants are more likely to mimic the outsourcing actions of industry peers. Our findings support this expectation. These results should interest IS, accounting, and general management scholars. Strategic IT choices are a collegial decision which include contributions from multiple members of the top management team. Senior accounting executives are routinely involved in such evaluations, providing initial projections and monitoring the consequent progress. In addition, recent US regulations have made accounting executives personally responsible for the effectiveness of internal controls, including those over the IT infrastructure. The accounting executives’ recommendations on ITO in this context often becomes decisive, and factors behind this recommendation should be fully explored.
Developing Summary Measures of Health-Related Multiple Physical Environmental Deprivation for Epidemiological Research
Authors: Richardson Elizabeth A , Mitchell Richard , Shortt Niamh K , Pearce Jamie , Dawson Terence P
Published: July 2010

Socioeconomic deprivation accounts for much of the spatial inequality in health in the UK, but a significant proportion remains unexplained. It is highly likely that the physical environment is a key factor in this unexplained variation. The role of the socioeconomic environment in health inequalities has been studied using small-area measures of multiple socioeconomic deprivation that capture the burden of socioeconomic adversity. Although similar composite measures of the physical environment would greatly assist investigations of environmental determinants of health no such measures are available. In this study we developed two small-area measures of health-related multiple physical environmental deprivation for the UK. A thorough review and evidence appraisal process was used to identify health-relevant dimensions of physical environmental deprivation. As a result we selected both health-detrimental (air pollution, cold climate, industrial facilities) and health-beneficial (ultraviolet radiation and green space) dimensions. Datasets describing each of the selected dimensions were acquired, and rendered to UK Census Area Statistics wards ( n = 10 654, average population = 5518). We developed two summary measures: the multiple environmental deprivation index (MEDIx) and classification (MEDClass). MEDIx, on an ordinal scale, can be used to distinguish areas exposed to greater or lesser environmental deprivation. MEDClass groups areas with similar environmental characteristics and will be useful for exploring health effects of specific types of environment. Mapping these measures demonstrated a wide variation in physical environmental deprivation across the UK. MEDIx revealed greater environmental deprivation in urban and industrial areas, and at more northerly latitudes. Although created using a different methodology MEDClass also differentiated these environmental types. We concluded that it is possible to capture and characterise multiple attributes of health-related physical environmental deprivation in the UK, at a small area level. The measures we developed offer opportunities to researchers and policy makers for developing our understanding of the role of exposure to multiple dimensions of physical environmental deprivation on health outcomes.
A Psychological–Geographical Approach to Vulnerability: The Example of a Chinese urban Development Project from the Perspective of the Transactional Stress Model
Authors: Lena Bercht Anna , Wehrhahn Rainer
Published: July 2010

Since the 1980s, reform, the open-door policy, and rapid economic growth have encouraged Chinese cities to become fast-growing and highly dynamic urban areas. They are subject to both innovations and international connectivity as well as to rising socioeconomic and ecological vulnerability. In this paper we sketch the main transformation processes of a traditional Chinese village in the megacity Guangzhou, South China, processes that are linked to the construction of a new railway station in its close proximity. Our research addresses the issue of how the inhabitants of this village view the restructuring of their living environment. What kind of demands or opportunities do they perceive? Do they feel stress with regard to ‘harm/loss’, ‘threat’, or ‘challenge’ and how do they cope with the changing structures and processes? People living in the same environment appraise exposure to certain risks differently, which explains varying coping modes. In this context the question is considered as to whether coping necessarily results in ‘visible’ outcomes (eg building houses to rent out and thus benefiting from in-migration) or whether it encompasses ‘invisible’ person-related processes. The primary aim of this paper is to enrich the geographical debate on vulnerability by taking a psychological perspective and presenting and applying the transactional stress model of Lazarus. This conceptual framework from cognitive psychology and schematises person and environment antecedents of stress and coping as well as appraisal and coping as mediating processes between the person and the environment. To facilitate understanding, the transactional stress model is exemplified on the basis of selected research data collected in the transforming village. With reference to different stress appraisals, examples of varying coping modes and coping efficiency are discussed.