bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct cerebellar engrams in short-term and long-term motor learning
Authors: Wang Wen , Nakadate Kazuhiko , Masugi-Tokita Miwako , Shutoh Fumihiro , Aziz Wajeeha , Tarusawa Etsuko , Lorincz Andrea , Molnár Elek , Kesaf Sebnem , Li Yun-Qing , Fukazawa Yugo , Nagao Soichi , Shigemoto Ryuichi
Published: December 2013

Significance

Long-term depression (LTD) of parallel fiber (PF) to Purkinje cell (PC) synapses has been postulated to cause cerebellar motor learning and extensively studied using in vitro preparations. However, there has been no in vivo evidence showing its occurrence after physiological learning, and much controversy on its role has persisted. We demonstrate that LTD as a form of AMPA receptor decrease does occur in PF–PC synapses after adaptation of horizontal optokinetic response. However, it lasted less than a day and was followed by elimination of these synapses. Our findings indicate distinct in vivo engrams for short-term and long-term memory in cerebellar motor learning, and open new mechanistic investigations of how the short-term memory is stabilized through structural reorganization of synaptic connections.
Translational dynamics revealed by genome-wide profiling of ribosome footprints in
Arabidopsis
Authors: Juntawong Piyada , Girke Thomas , Bazin Jérémie , Bailey-Serres Julia
Published: December 2013

Significance

Plant survival in a highly varied environment requires flexibility in gene regulation. To capture dynamics of mRNA translation at the genome scale, we precisely mapped individual ribosomes to mRNAs of whole seedlings under control and low-oxygen conditions. The results demonstrate nearly 100-fold variation in the efficiency of translation of individual mRNAs under both conditions and provide unique insights into posttranscriptional and translational regulation modulated by low-energy stress in
Arabidopsis thaliana
.
Measuring membrane protein stability under native conditions
Authors: Chang Yu-Chu , Bowie James U.
Published: December 2013

Significance

How proteins fold is a fundamental problem in molecular biology and has been the subject of intense study. Membrane protein folding is a particularly thorny challenge because the proteins reside in a complex, nonhomogenous bilayer. As the bilayer has a powerful influence on their structure and stability, new approaches are needed to study folding in their natural environment. Here we describe an approach for driving reversible unfolding of a large membrane protein, which does not require alteration of the environmental properties. Our method therefore provides a general tool to examine the folding of membrane proteins.
Cortical neural populations can guide behavior by integrating inputs linearly, independent of synchrony
Authors: Histed Mark H. , Maunsell John H. R.
Published: December 2013

Significance

The brain performs computations by transforming sensory inputs to make decisions. We study these neuronal computations in the mouse, one of the smallest animals with a cerebral cortex, the part of the human brain that controls complex behavior. We find animals’ behavior can be insensitive to the timing of cortical inputs, depending only on total spike count, even though individual neurons are sensitive to timing. Thus, the cortex can integrate input linearly, or place equal weight on inputs regardless of their arrival time. This emergent linear network behavior may arise from fluctuations in membrane potential generated by background network activity. Brain diseases may arise from dysfunction of these network properties, perhaps by damaging the mechanisms that create this background noise.
Platinum supported on titanium–ruthenium oxide is a remarkably stable electrocatayst for hydrogen fuel cell vehicles
Authors: Parrondo Javier , Han Taehee , Niangar Ellazar , Wang Chunmei , Dale Nilesh , Adjemian Kev , Ramani Vijay
Published: December 2013

Significance

In this study, we showcase titanium–ruthenium oxide (TRO)—a remarkably stable support material, and Pt/TRO, a derivative electrocatalyst that is also extremely stable. These materials have been tested to establish their catalytic activity and stability using accelerated tests that mimic conditions and degradation modes encountered during long-term fuel cell operation. We have evaluated Pt/TRO using these protocols, and provide concrete evidence that this material is far more stable than Pt/C and, would meet the requirements for use in an automotive fuel cell stack. Our cost analysis indicates the use of ruthenium is not a factor given that >90% of catalyst cost resides in the platinum metal; moreover, the exceptional stability of Pt/TRO removes the needs for overdesign or replacement.
Emerging predictable features of replicated biological invasion fronts
Authors: Giometto Andrea , Rinaldo Andrea , Carrara Francesco , Altermatt Florian
Published: December 2013

Significance

Biological dispersal is a key driver of several fundamental processes in nature, crucially controlling the distribution of species and affecting their coexistence. Despite its relevance for important ecological processes, however, the subject suffers an acknowledged lack of experimentation, and current assessments point at inherent limitation to predictability even in the simplest ecological settings. We show, by combining replicated experimentation on the spread of the ciliateTetrahymenasp. with a theoretical approach based on stochastic differential equations, that information on local unconstrained movement and reproduction of organisms (including demographic stochasticity) allows reliable prediction of both the propagation speed and range of variability of invasion fronts over multiple generations.
Representation of interval timing by temporally scalable firing patterns in rat prefrontal cortex
Authors: Xu Min , Zhang Si-yu , Dan Yang , Poo Mu-ming
Published: December 2013

Significance

The ability to estimate time interval in the order of seconds is important for animal behaviors. However, how the brain estimates the passage of time remains mysterious. In the current study, we trained rats to estimate two different time intervals and recorded activities of single neurons from the medial prefrontal cortex (mPFC). We found that some PFC neurons showed activity changes during time estimation by the rat, with the same profile that was temporally scaled by a factor proportional to the estimated time intervals. Local cooling of mPFC slowed the time estimated by the rat. Thus, PFC neuronal activity contributes to time estimation, and temporal scaling of neuronal activity may be a circuit mechanism for estimating different time intervals.
CLASP2 interacts with p120-catenin and governs microtubule dynamics at adherens junctions
Authors: Shahbazi Marta N. , Megias Diego , Epifano Carolina , Akhmanova Anna , Gundersen Gregg G. , Fuchs Elaine , Perez-Moreno Mirna
Published: December 2013

Classical cadherins and their connections with microtubules (MTs) are emerging as important determinants of cell adhesion. However, the functional relevance of such interactions and the molecular players that contribute to tissue architecture are still emerging. In this paper, we report that the MT plus end–binding protein CLASP2 localizes to adherens junctions (AJs) via direct interaction with p120-catenin (p120) in primary basal mouse keratinocytes. Reductions in the levels of p120 or CLASP2 decreased the localization of the other protein to cell–cell contacts and altered AJ dynamics and stability. These features were accompanied by decreased MT density and altered MT dynamics at intercellular junction sites. Interestingly, CLASP2 was enriched at the cortex of basal progenitor keratinocytes, in close localization to p120. Our findings suggest the existence of a new mechanism of MT targeting to AJs with potential functional implications in the maintenance of proper cell–cell adhesion in epidermal stem cells.
Arnaud Echard: Adieu, ma soeur
Authors: Sedwick Caitlin
Published: December 2013

Echard studies membrane trafficking and the cytoskeleton, with a focus on cytokinesis.
Models that include supercoiling of topological domains reproduce several known features of interphase chromosomes
Authors: Benedetti Fabrizio , Dorier Julien , Burnier Yannis , Stasiak Andrzej
Published: December 2013

Understanding the structure of interphase chromosomes is essential to elucidate regulatory mechanisms of gene expression. During recent years, high-throughput DNA sequencing expanded the power of chromosome conformation capture (3C) methods that provide information about reciprocal spatial proximity of chromosomal loci. Since 2012, it is known that entire chromatin in interphase chromosomes is organized into regions with strongly increased frequency of internal contacts. These regions, with the average size of ∼1 Mb, were named topological domains. More recent studies demonstrated presence of unconstrained supercoiling in interphase chromosomes. Using Brownian dynamics simulations, we show here that by including supercoiling into models of topological domains one can reproduce and thus provide possible explanations of several experimentally observed characteristics of interphase chromosomes, such as their complex contact maps.
The family of topological phases in condensed matter†
Authors: Shen Shun-Qing
Published: December 2013

The discovery of topological insulators and superconductors is an important advance in condensed matter physics. Topological phases reflect global properties of the quantum states in materials, and the boundary states are the characteristic of the materials. Such phases constitute a new branch in condensed matter physics. Here a historic development is briefly introduced, and the known family of phases in condensed matter are summarized.
Network mechanisms of grid cells
Authors: Moser Edvard I. , Moser May-Britt , Roudi Yasser
Published: December 2013

One of the major breakthroughs in neuroscience is the emerging understanding of how signals from the external environment are extracted and represented in the primary sensory cortices of the mammalian brain. The operational principles of the rest of the cortex, however, have essentially remained in the dark. The discovery of grid cells, and their functional organization, opens the door to some of the first insights into the workings of the association cortices, at a stage of neural processing where firing properties are shaped not primarily by the nature of incoming sensory signals but rather by internal self-organizing principles. Grid cells are place-modulated neurons whose firing locations define a periodic triangular array overlaid on the entire space available to a moving animal. The unclouded firing pattern of these cells is rare within the association cortices. In this paper, we shall review recent advances in our understanding of the mechanisms of grid-cell formation which suggest that the pattern originates by competitive network interactions, and we shall relate these ideas to new insights regarding the organization of grid cells into functionally segregated modules.
Oscillatory neurocomputing with ring attractors: a network architecture for mapping locations in space onto patterns of neural synchrony
Authors: Blair Hugh T. , Wu Allan , Cong Jason
Published: December 2013

Theories of neural coding seek to explain how states of the world are mapped onto states of the brain. Here, we compare how an animal's location in space can be encoded by two different kinds of brain states:population vectorsstored by patterns of neural firing rates, versussynchronization vectorsstored by patterns of synchrony among neural oscillators. It has previously been shown that a population code stored by spatially tuned ‘grid cells’ can exhibit desirable properties such as high storage capacity and strong fault tolerance; here it is shown that similar properties are attainable with a synchronization code stored by rhythmically bursting ‘theta cells’ that lack spatial tuning. Simulations of a ring attractor network composed from theta cells suggest how a synchronization code might be implemented using fewer neurons and synapses than a population code with similar storage capacity. It is conjectured that reciprocal connections between grid and theta cells might control phase noise to correct two kinds of errors that can arise in the code: path integration and teleportation errors. Based upon these analyses, it is proposed that a primary function of spatially tuned neurons might be to couple the phases of neural oscillators in a manner that allows them to encode spatial locations as patterns of neural synchrony.
Optimal configurations of spatial scale for grid cell firing under noise and uncertainty
Authors: Towse Benjamin W. , Barry Caswell , Bush Daniel , Burgess Neil
Published: December 2013

We examined the accuracy with which the location of an agent moving within an environment could be decoded from the simulated firing of systems of grid cells. Grid cells were modelled with Poisson spiking dynamics and organized into multiple ‘modules’ of cells, with firing patterns of similar spatial scale within modules and a wide range of spatial scales across modules. The number of grid cells per module, the spatial scaling factor between modules and the size of the environment were varied. Errors in decoded location can take two forms: small errors of precision and larger errors resulting from ambiguity in decoding periodic firing patterns. With enough cells per module (e.g. eight modules of 100 cells each) grid systems are highly robust to ambiguity errors, even over ranges much larger than the largest grid scale (e.g. over a 500 m range when the maximum grid scale is 264 cm). Results did not depend strongly on the precise organization of scales across modules (geometric, co-prime or random). However, independent spatial noise across modules, which would occur if modules receive independent spatial inputs and might increase with spatial uncertainty, dramatically degrades the performance of the grid system. This effect of spatial uncertainty can be mitigated by uniform expansion of grid scales. Thus, in the realistic regimes simulated here, the optimal overall scale for a grid system represents a trade-off between minimizing spatial uncertainty (requiring large scales) and maximizing precision (requiring small scales). Within this view, the temporary expansion of grid scales observed in novel environments may be an optimal response to increased spatial uncertainty induced by the unfamiliarity of the available spatial cues.
The development of spatial behaviour and the hippocampal neural representation of space
Authors: Wills Thomas J. , Muessig Laurenz , Cacucci Francesca
Published: December 2013

The role of the hippocampal formation in spatial cognition is thought to be supported by distinct classes of neurons whose firing is tuned to an organism's position and orientation in space. In this article, we review recent research focused on how and when this neural representation of space emerges during development: each class of spatially tuned neurons appears at a different age, and matures at a different rate, but all the main spatial responses tested so far are present by three weeks of age in the rat. We also summarize the development of spatial behaviour in the rat, describing how active exploration of space emerges during the third week of life, the first evidence of learning in formal tests of hippocampus-dependent spatial cognition is observed in the fourth week, whereas fully adult-like spatial cognitive abilities require another few weeks to be achieved. We argue that the development of spatially tuned neurons needs to be considered within the context of the development of spatial behaviour in order to achieve an integrated understanding of the emergence of hippocampal function and spatial cognition.
Exploring community structure in biological networks with random graphs
Authors: Sah Pratha , Singh Lisa O. , Clauset Aaron , Bansal Shweta
Published: December 2013

Background

Community structure is ubiquitous in biological networks. There has been an increased interest in unraveling the community structure of biological systems as it may provide important insights into a system’s functional components and the impact of local structures on dynamics at a global scale. Choosing an appropriate community detection algorithm to identify the community structure in an empirical network can be difficult, however, as the many algorithms available are based on a variety of cost functions and are difficult to validate. Even when community structure is identified in an empirical system, disentangling the effect of community structure from other network properties such as clustering coefficient and assortativity can be a challenge.

Results

Here, we develop a generative model to produce undirected, simple, connected graphs with a specified degrees and pattern of communities, while maintaining a graph structure that is as random as possible. Additionally, we demonstrate two important applications of our model: (a) to generate networks that can be used to benchmark existing and new algorithms for detecting communities in biological networks; and (b) to generate null models to serve as random controls when investigating the impact of complex network features beyond the byproduct of degree and modularity in empirical biological networks.

Conclusion

Our model allows for the systematic study of the presence of community structure and its impact on network function and dynamics. This process is a crucial step in unraveling the functional consequences of the structural properties of biological systems and uncovering the mechanisms that drive these systems.
Methyl Jasmonate-Elicited Transcriptional Responses and Pentacyclic Triterpene Biosynthesis in Sweet Basil
Authors: Misra Rajesh Chandra , Maiti Protiti , Chanotiya Chandan Singh , Shanker Karuna , Ghosh Sumit
Published: December 2013

Sweet basil (Ocimum basilicum) is well known for its diverse pharmacological properties and has been widely used in traditional medicine for the treatment of various ailments. Although a variety of secondary metabolites with potent biological activities are identified, our understanding of the biosynthetic pathways that produce them has remained largely incomplete. We studied transcriptional changes in sweet basil after methyl jasmonate (MeJA) treatment, which is considered an elicitor of secondary metabolites, and identified 388 candidate MeJA-responsive unique transcripts. Transcript analysis suggests that in addition to controlling its own biosynthesis and stress responses, MeJA up-regulates transcripts of the various secondary metabolic pathways, including terpenoids and phenylpropanoids/flavonoids. Furthermore, combined transcript and metabolite analysis revealed MeJA-induced biosynthesis of the medicinally important ursane-type and oleanane-type pentacyclic triterpenes. Two MeJA-responsive oxidosqualene cyclases (ObAS1 and ObAS2) that encode for 761- and 765-amino acid proteins, respectively, were identified and characterized. Functional expressions of ObAS1 and ObAS2 in Saccharomyces cerevisiae led to the production of β-amyrin and α-amyrin, the direct precursors of oleanane-type and ursane-type pentacyclic triterpenes, respectively. ObAS1 was identified as a β-amyrin synthase, whereas ObAS2 was a mixed amyrin synthase that produced both α-amyrin and β-amyrin but had a product preference for α-amyrin. Moreover, transcript and metabolite analysis shed light on the spatiotemporal regulation of pentacyclic triterpene biosynthesis in sweet basil. Taken together, these results will be helpful in elucidating the secondary metabolic pathways of sweet basil and developing metabolic engineering strategies for enhanced production of pentacyclic triterpenes.
Systematic evaluation of bias in microbial community profiles induced by whole genome amplification
Authors: Direito Susana O. L. , Zaura Egija , Little Miranda , Ehrenfreund Pascale , Röling Wilfred F. M.
Published: December 2013

Whole genome amplification methods facilitate the detection and characterization of microbial communities in low biomass environments. We examined the extent to which the actual community structure is reliably revealed and factors contributing to bias. One widely used [multiple displacement amplification (MDA)] and one new primer‐free method [primase‐based whole genome amplification (pWGA)] were compared using a polymerase chain reaction (PCR)‐based method as control. Pyrosequencing of an environmental sample and principal component analysis revealed that MDA impacted community profiles more strongly than pWGA and indicated that this related to species GC content, although an influence of DNA integrity could not be excluded. Subsequently, biases by species GC content, DNA integrity and fragment size were separately analysed using defined mixtures of DNA from various species. We found significantly less amplification of species with the highest GC content for MDA‐based templates and, to a lesser extent, for pWGA. DNA fragmentation also interfered severely: species with more fragmented DNA were less amplified with MDA and pWGA. pWGA was unable to amplify low molecular weight DNA (< 1.5 kb), whereas MDA was inefficient. We conclude that pWGA is the most promising method for characterization of microbial communities in low‐biomass environments and for currently planned astrobiological missions to Mars.
Evolution of salt tolerance in a laboratory reared population of Chlamydomonas reinhardtii
Authors: Perrineau Marie‐Mathilde , Zelzion Ehud , Gross Jeferson , Price Dana C. , Boyd Jeffrey , Bhattacharya Debashish
Published: December 2013

Understanding the genetic underpinnings of adaptive traits in microalgae is important for the study of evolution and for applied uses. We used long‐term selection under a regime of serial transfers with haploid populations of the green alga Chlamydomonas reinhardtii raised in liquid TAP medium containing 200 mM NaCl. After 1255 generations, evolved salt (ES) populations could grow as rapidly in high salt medium as progenitor cells (progenitor light [PL]). Transcriptome data were analysed to elucidate the basis of salt tolerance in ES cells when compared with PL cells and to cells incubated for 48 h in high salt medium (progenitor salt [PS], the short‐term acclimation response). These data demonstrate that evolved and short‐term acclimation responses to salt stress differ fundamentally from each other. Progenitor salt cells exhibit well‐known responses to salt stress such as reduction in photosynthesis, upregulation of glycerophospholipid signaling, and upregulation of the transcription and translation machinery. In contrast, ES cells show downregulation of genes involved in the stress response and in transcription/translation. Our results suggest that gene‐rich mixotrophic lineages such as C. reinhardtii may be able to adapt rapidly to abiotic stress engendered either by a rapidly changing climate or physical vicariance events that isolate populations in stressful environments.
Environmental controls and composition of anoxygenic photoheterotrophs in ultraoligotrophic high‐altitude lakes (Central Pyrenees)
Authors: Caliz Joan , Casamayor Emilio O.
Published: December 2013

The phylogenetic composition of freshwater anoxygenic photoheterotrophs (APs) has been poorly investigated as compared with their marine counterparts. In this study, we explored a set of ultraoligotrophic cold high mountain lakes (Central Pyrenees, Spain) by both pufM gene denaturing gradient gel electrophoresis fingerprinting, and cloning and sequencing of selected lakes samples. Different ranges of limnological and physico‐chemical values were explored as environmental drivers of APs richness and composition. We did not observe significant relationships between richness/diversity of pufM and any of the limnological characteristics measured or trophic status, but a negative correlation with ammonia concentration. Conductivity, pH and nitrate concentration were significantly related to changes in APs community composition, whereas lake area, altitude, temperature and trophic status did not. Most of the sequences (> 85%) had the pufM sequences of Limnohabitans (Betaproteobacteria) as the closest relative in databases, whereas less abundant clones were more closely related to Rhodobacter, Sulfitobacter and Brevundimonas (Alphaproteobacteria), in agreement with 16S rRNA gene sequences previously found in the area. Congregibacter‐like Gammaproteobacteria were not detected. Comparison with available studies in inland waters showed taxonomic partitioning along salinity gradients, and Congregibacter‐like sequences restricted to high saline conditions in continental water bodies.
Blocking initial infiltration of pioneer CD8+T‐cells into the CNS via inhibition of SHP‐2 ameliorates experimental autoimmune encephalomyelitis in mice
Authors: Luo Qiong , Sun Yang , Gong Fang‐Yuan , Liu Wen , Zheng Wei , Shen Yan , Hua Zi‐Chun , Xu Qiang
Published: December 2013

Background and Purpose

In contrast to T‐cell priming in the periphery, therapeutic strategies targeting the initiation step of T‐cell trafficking into the CNS have not been extensively investigated. In this study, we examined the effect of NSC‐87877, a potent Src homology 2‐containing protein tyrosine phosphatase 2 (SHP‐2) inhibitor, on experimental autoimmune encephalomyelitis (EAE) and elucidated its unique mechanism of action.

Experimental Approach

C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein35–55 and monitored for clinical severity of disease and histopathological features in the CNS. Levels of cytokines in serum were measured by elisa. Effects of NSC‐87877 on expressions of chemokines and cytokines in the CNS were determined by quantitative PCR.

Key Results

NSC‐87877‐treated mice developed conventional TH1 and TH17 responses, but were highly resistant to the induction of EAE. NSC‐87877 decreased the accumulation of lymphocytes in the CNS and increased the functional expression of chemokine receptor CXCR7 on CD8+ T‐cells. Adoptive transfer of T‐cells from 2D2‐transgenic mice restored EAE susceptibility in NSC‐87877‐treated mice, indicating that NSC‐87877 only targets the initial migration of pioneer T‐cells. Furthermore, T‐cell‐conditioned SHP‐2‐deficient mice treated with NSC‐87877 were no longer resistant to EAE, suggesting that inhibition of SHP‐2 contributes to the amelioration of EAE by NSC‐87877.

Conclusions and Implications

NSC‐87877 almost completely abolished the development of EAE by blocking the initial infiltration of pioneer CD8+ T‐cells into the uninflamed CNS. These results reveal a critical role for SHP‐2 in regulating EAE pathogenesis and indicate that NSC‐87877 is a potential candidate for the treatment of relapsing‐remitting multiple sclerosis.
The association between oral health literacy and failed appointments in adults attending a university‐based general dental clinic
Authors: Holtzman Jennifer S. , Atchison Kathryn A. , Gironda Melanie W. , Radbod Rebecca , Gornbein Jeffrey
Published: December 2013

Objectives

The purpose of this study is to determine the association between personal characteristics, a person's oral health literacy, and failing to show for dental appointments at a university dental clinic.

Methods

A secondary data analysis was conducted on data collected from 200 adults at a university dental clinic between January 2005 and December 2006. In the original study, an oral health literacy instrument, the Rapid Estimate of Adult Literacy in Medicine and Dentistry (REALM‐D), was administered, sociodemographic and health information seeking behavior was gathered, and electronic records were reviewed.

Results

Descriptive and bivariate analyses and a classification and regression tree (CART) analysis were conducted. Seeking health information through fewer sources vs. multiple sources was the strongest predictor of failing to show. The subjects’ oral health literacy, as measured by the REALM‐D List 3 score, was the next most significant variable. Classification and regression tree analyses also selected gender, chief complaint, age, and payment type as predictor variables.

Conclusions

Multiple factors contribute to failing to show for dental appointments. However, individuals who use fewer sources of oral health information, a subset of health literacy skills, are more likely to fail to show for dental appointments.
Immune priming and experimental glaucoma: the effect of prior systemic lipopolysaccharide challenge on tissue outcomes after optic nerve injury
Authors: Narayan Daniel S , Casson Robert J , Ebneter Andreas , Chidlow Glyn , Grace Peter M , Hutchinson Mark R , Wood John PM
Published: December 2013

Background

Microglial activation is a prominent feature throughout the optic pathway in experimental glaucoma. Pro‐inflammatory microglial activation may contribute to neurodegeneration through the release of pro‐inflammatory cytokines and other inflammatory mediators. Systemic administration of lipopolysaccharide stimulates microglia to produce pro‐inflammatory cytokines and chemoattractants. A preliminary investigation demonstrated pro‐inflammatory microglial activation throughout the optic pathway following systemic lipopolysaccharide challenge. The aim of the current work was to investigate whether microglial priming with lipopolysaccharide would exacerbate optic nerve injury in rats following experimental glaucoma.

Methods

Adult female Sprague‐Dawley rats were divided into lipopolysaccharide treatment (n = 15) and saline treatment groups (n = 15). Microglial priming was induced with a 2.5‐mg/kg intraperitoneal injection of lipopolysaccharide; control animals received saline. Experimental glaucoma was induced 48 h later in the right eyes of animals by laser photocoagulation of the trabecular meshwork. Animals were sacrificed 9 days after laser treatment.

Results

The estimated number of axons per optic nerve was 51 327 ± 3868 (mean ± standard error of the mean) in the lipopolysaccharide group and 54 569 ± 6687 (mean ± standard error of the mean) in the saline group. Optic nerve axon counts were not significantly different between lipopolysaccharide and saline groups (P = 0.67).

Conclusions

Systemic lipopolysaccharide challenge had no discernible effect on optic nerve injury in laser‐induced experimental glaucoma. These findings do not support the hypothesis that this model of experimental glaucoma involves inflammation and instead suggest that microglial activation may occur secondary to chronic neurodegeneration.
Long‐term outcomes in African American kidney transplant recipients under contemporary immunosuppression: a four‐yr analysis of the Mycophenolic acid Observational REnal transplant (MORE) study
Authors: Narayanan Mohanram , Pankewycz Oleh , Shihab Fuad , Wiland Anne , McCague Kevin , Chan Laurence
Published: December 2013

Mycophenolic acid Observational REnal transplant (MORE) was a prospective, observational study of de novo kidney transplant patients receiving mycophenolic acid (MPA). Four‐yr data on 904 patients receiving tacrolimus and enteric‐coated mycophenolate sodium (EC‐MPS) or mycophenolate mofetil (MMF) were analyzed to evaluate immunosuppression and graft outcomes in African American (AA, n = 218) vs. non‐AA (n = 686) patients. Mean tacrolimus dose was higher in AA vs. non‐AA patients but mean tacrolimus trough concentration was similar. Use of the recommended MPA dose in AA patients decreased from 78.9% at baseline to 33.1% at year 3. More AA patients received the recommended MPA dose with EC‐MPS than MMF at month 6 (56.2% vs. 35.7%, p = 0.016) and month 36 (46.6% vs. 16.7%, p = 0.029), with no safety penalty. Significantly, more AA patients received corticosteroids than non‐AA patients. Biopsy‐proven acute rejection was higher in AA vs. non‐AA patients (18.9% vs. 10.7%, p = 0.003), as was graft loss (10.9% vs. 4.4%, p = 0.003); differences were confirmed by Cox regression analysis. Patient survival was similar. Estimated GFR was comparable in AA vs. non‐AA patients. Kidney allograft survival remains lower for AA vs. non‐AA recipients even under the current standard of care.
Changes in Australian attitudes to alcohol policy: 1995–2010
Authors: Callinan Sarah , Room Robin , Livingston Michael
Published: December 2013

Introduction and Aims

In 2009 Wilkinson and colleagues reported a downward trend in support for alcohol policy restrictions in Australia between 1995 and 2004. The aim of the current study is to examine more recent data on policy support in Australia, specifically for policies covering alcohol availability up to 2010, and to examine specific demographic shifts in support.

Design and Methods

Data was taken from the National Drug Strategy Household Surveys from 1995, 1998, 2001, 2004, 2007 and 2010 (n = 80 846), primarily responses to attitude items on policy restriction and demographic questions. The effects of age, sex, drinking patterns and income over time on three items addressing restriction of alcohol availability were assessed using a factorial analysis of variance.

Results

Although availability items are among the less popular policy restrictions put forward in the National Drug Strategy Household Surveys, 2004 actually represented a turning point in the decrease in popularity, with an increase in support since then. Though some groups show consistently higher rates of support than others for policy restrictions, the rate of change in support was fairly uniform across demographic and drinking groups.

Discussion and Conclusions

Despite the lack of an obvious catalyst, there has been an increase in support for alcohol policy restriction as it relates to general availability and accessibility since 2004. Furthermore, this increase does not appear to be a reflection of a change in a specific group of people, but appears to be occurring across the Australian population. [Callinan S, Room R, Livingston M. Changes in Australian attitudes to alcohol policy: 1995–2010. Drug Alcohol Rev 2014;33:227–234]
A Profitability Evaluation of America's Best Hospitals, 2000–2008
Authors: Benton W. C.
Published: December 2013

Each year U.S. News and World Report evaluates more than 5,000 U.S. hospitals, of which approximately 3% are considered the best hospitals in America, and hospital profitability has emerged as a business objective for these hospitals. This study investigates the profitability performance of the best (highest quality) hospitals in the United States. A 9‐year longitudinal investigation of profitability for the best hospitals in the United States is conducted. The results offer evidence that the primary drivers of hospital profitability are the case mix index and daily bed capacity. In terms of hospital profitability, there appears to be a tradeoff between these two factors. Finally, caution must be used when ranking U.S. News and World Report Honor Roll hospitals, in terms of profitability and performance.
APOE*3Leiden.CETP transgenic mice as model for pharmaceutical treatment of the metabolic syndrome
Authors: van den Hoek A. M. , van der Hoorn J. W. A. , Maas A. C. , van den Hoogen R. M. , van Nieuwkoop A. , Droog S. , Offerman E. H. , Pieterman E. J. , Havekes L. M. , Princen H. M. G.
Published: December 2013

Aims

This study aimed to investigate systematically (i) the appropriate dietary conditions to induce the features of the MetS in APOE*3Leiden.humanCholesteryl Ester Transfer Protein (E3L.CETP) mice and (ii) whether the response of this model to different antidiabetic and hypolipidemic drugs is similar as in humans.

Methods

Male obese, IR and dyslipidemic E3L.CETP mice were treated with antidiabetic drugs rosiglitazone, liraglutide or an experimental 11β‐hydroxysteroid‐dehydrogenase‐1 (HSD‐1) inhibitor, or with hypolipidemic drugs atorvastatin, fenofibrate or niacin for 4–6 weeks. The effects on bw, IR and plasma and liver lipids were assessed.

Results

Rosiglitazone, liraglutide and HSD‐1 inhibitor significantly decreased glucose and insulin levels or IR. Liraglutide and HSD‐1 inhibitor also decreased bw. Atorvastatin, fenofibrate and niacin improved the dyslipidemia and fenofibrate and niacin increased high‐density lipoprotein (HDL) cholesterol. In addition, hepatic triglycerides were significantly decreased by treatment with rosiglitazone and liraglutide, while hepatic cholesterol esters were significantly decreased by rosiglitazone and atorvastatin.

Conclusions

We conclude that the E3L.CETP mouse is a promising novel translational model to investigate the effects of new drugs, alone or in combination, that affect IR, diabetic dyslipidemia and non‐alcoholic fatty liver disease (NAFLD).
Persistent Left Superior Vena Cava Draining into Left Atrium as a Cause of Persistent Systemic Desaturation after Surgery
Authors: Agarwal Ashish , K.S. Ravindranath , Agrawal Navin , Patra Soumya , Agarwal Neena , Manjunath C.N.
Published: December 2013

Persistent left superior vena cava (LSVC) is a rare congenital anomaly which usually produces no physiologic derangements if it drains into the right atrium via the coronary sinus, but it may cause significant desaturation when it drains into the left atrium (LA). Failure to diagnose LSVC communicating with the LA preoperatively may lead to serious consequences. We are describing an interesting case of a boy who presented with systemic desaturation due to an undetected LSVC after having undergone corrective surgery for atrioventricular canal defect. We have demonstrated that echocardiography with agitated saline contrast is a simple, accurate, and inexpensive diagnostic modality.
Value of Two‐Dimensional Longitudinal Strains Analysis to Assess the Impact of Thrombus Aspiration during Primary Percutaneous Coronary Intervention on Left Ventricular Function: A Speckle Tracking Imaging Substudy of the EXPIRA Trial
Authors: Cimino Sara , Agati Luciano , Lucisano Luigi , Mancone Massimo , Petronilli Valentina , Cicogna Francesco , Fedele Francesco , Sardella Gennaro
Published: December 2013

Background

Thrombectomy during primary percutaneous coronary intervention (Th‐PCI) improves myocardial reperfusion in the absence of significant changes, in the acute phase, in traditional two‐dimensional (2D) echo indexes of left ventricular (LV) function. The aim of this study was to evaluate the potential of 2D speckle tracking echocardiography (2DSTE) analysis in assessing the efficacy of thrombectomy as compared to standard 2D echo and cardiac magnetic resonance (CMR) data.

Methods

Two‐dimensional speckle tracking echocardiography analysis was performed in 60 anterior ST‐segment elevation myocardial infarction (STEMI) patients to assess global (GLS), segmental (SLS) and regional longitudinal strain (RLS). 2D echo and CMR were performed within 5 days after PCI. Patients were divided into 2 groups according to the different methods of reperfusion used: 28 pts Th‐PCI and 32 pts standard PCI (S‐PCI).

Results

Baseline clinical and angiographic characteristics, 2D echo, and DE‐CMR data before and after PCI were similar in the 2 groups, except for microvascular obstruction (MVO), significantly lower (P = 0.001) in Th‐PCI group. Conversely, GLS was significantly higher in Th‐PCI group (P < 0.001), and in particular in the subset of patients without MVO (P = 0.012). RLS was also significantly higher in Th‐PCI group (P = 0.001). GLS significantly correlates with infarct size, (R = 0.47; P = 0.03) and MVO (R = 0.69, P = 0.001). Finally, SLS was significantly lower in the DE segments (P < 0.001).

Conclusions

Patients treated with Th‐PCI had a more preserved microvascular integrity resulting in a better myocardial longitudinal deformation. 2DSTE analysis adds significant information on the efficacy of thrombus aspiration as compared to standard echocardiography and it is closely related to the extent of microvascular damage.
Nonsymmetric Myocardial Contribution to Supranormal Right Ventricular Function in the Athlete's Heart: Combined Assessment by Speckle Tracking and Real Time Three‐Dimensional Echocardiography
Authors: Esposito Roberta , Galderisi Maurizio , Schiano‐Lomoriello Vincenzo , Santoro Alessandro , De Palma Daniela , Ippolito Renato , Muscariello Riccardo , Santoro Ciro , Guerra Germano , Cameli Matteo , Mondillo Sergio , De Simone Giovanni
Published: December 2013

Purpose

To investigate determinants of right ventricular (RV) function in competitive athletes by a combined assessment of speckle tracking (STE) and real time 3D echocardiography (RT3DE).

Methods

Right ventricular function of 40 top‐level rowers was compared to 43 sedentary normal controls by standard Doppler echocardiography, RT3DE, and STE. RV diameters and wall thickness, tricuspid annular plane systolic excursion (TAPSE), tricuspid E/A ratio, and pulsed tissue Doppler of lateral tricuspid annulus were analyzed. RV volumes, ejection fraction (EF), and stroke volume (SV) were determined. RV global longitudinal strain (GLS) (average of 6 regions), septal strain (average of 3 septal regions, septal longitudinal strain [SLS]), and lateral strain (average of 3 lateral regions, lateral longitudinal strain [LLS]) were estimated by STE.

Results

The 2 groups were comparable for age, body mass index, and blood pressure, but heart rate was lower in rowers. RV diameters were larger and TAPSE, tricuspid E/A ratio, and tissue Doppler‐derived s′ and e′ velocities were higher in rowers. By RT3DE, RV end‐diastolic volume (EDV) and end‐systolic volume were greater in rowers (both P < 0.0001), without difference in EF. GLS (P < 0.005) and LLS (P < 0.001), but not SLS, were greater in rowers. In pooled groups, LLS was related to EDV and SV, even after adjusting for heart rate, body mass index, and RV wall thickness by separate multiple linear regression analyses (β coefficient = 0.247, P < 0.01 and β = 0.225, P < 0.02, respectively).

Conclusions

Right ventricular preload exerts its maximal influence on the longitudinal lateral fibers, which is independent on potential confounders and largely induces RV supranormal function in the athlete's heart.
Empire: An Analytical Category for Educational Research
Authors: Coloma Roland Sintos
Published: December 2013

In this article Roland Sintos Coloma argues for the relevance of empire as an analytical category in educational research. He points out the silence in mainstream studies of education on the subject of empire, the various interpretive approaches to deploying empire as an analytic, and the importance of indigeneity in research on empire and education. Coloma examines three award‐winning books, Lawrence Cremin's The Transformation of the School: Progressivism in American Education, 1876–1957, John Willinsky's Learning to Divide the World: Education at Empire's End, and David Wallace Adams's Education for Extinction: American Indians and the Boarding School Experience, 1875–1928, in order to delineate the heuristic spectrum of the use of empire in educational research. These texts are put in conversation with the interdisciplinary fields of American, postcolonial, race/ethnic, and indigenous studies where questions of empire have received considerable attention. Ultimately, mobilizing empire as an analytical category will enable researchers, policymakers, and educators to establish new connections and dispute long‐standing views about discursive, structural, and affective dynamics at local, national, and global levels.
Chronic desipramine treatment rescues depression‐related, social and cognitive deficits in Engrailed‐2 knockout mice
Authors: Brielmaier J. , Senerth J. M. , Silverman J. L. , Matteson P. G. , Millonig J. H. , DiCicco‐Bloom E. , Crawley J. N.
Published: December 2013

Engrailed‐2 (En2) is a homeobox transcription factor that regulates neurodevelopmental processes including neuronal connectivity and elaboration of monoaminergic neurons in the ventral hindbrain. We previously reported abnormalities in brain noradrenergic concentrations in En2 null mutant mice that were accompanied by increased immobility in the forced swim test, relevant to depression. An EN2 genetic polymorphism has been associated with autism spectrum disorders, and mice with a deletion in En2 display social abnormalities and cognitive deficits that may be relevant to multiple neuropsychiatric conditions. This study evaluated the ability of chronic treatment with desipramine (DMI), a selective norepinephrine (NE) reuptake inhibitor and classical antidepressant, to reverse behavioral abnormalities in En2−/− mice. Desipramine treatment significantly reduced immobility in the tail suspension and forced swim tests, restored sociability in the three‐chambered social approach task and reversed impairments in contextual fear conditioning in En2−/− mice. Our findings indicate that modulation of brain noradrenergic systems rescues the depression‐related phenotype in En2−/− mice and suggest new roles for NE in the pathophysiology of the social and cognitive deficits seen in neuropsychiatric disorders such as autism or schizophrenia.
Time and Organizational Learning: A Review and Agenda for Future Research
Authors: Berends Hans , Antonacopoulou Elena
Published: December 2013

This paper examines the time dimensions of organizational learning. While several recent studies have addressed aspects of time in relation to organizational learning, the topic of time has received little attention in reviews of the field, and this promising domain of research is fragmented. The objective of this paper is to bring these dispersed conceptualizations and findings together and to provide a more solid conceptual foundation for the time dimensions of organizational learning as a new research avenue. Three sets of mechanisms are discerned: concerning time as duration; the timing of organizational learning; and the role of the past, present and future in organizational learning. Each of these perspectives offers unique insights, which when integrated can help map new directions for future research.
“Envelope wages” in the European Union
Authors: WILLIAMS Colin C. , PADMORE Jo
Published: December 2013

This article reveals how many formal employees in the European Union receive from their formal employer not only a declared wage but also an undeclared “envelope wage”. Reporting the results of a 2007 survey involving 26,659 face‐to‐face interviews, the authors find that one in 18 formal employees receives an envelope wage from their formal employer, amounting to 25 per cent of their gross pay on average. Such hybrid wage arrangements are ubiquitous, but are more common in some countries, employee categories and types of firm than others. The authors conclude by discussing the theoretical and policy implications of these findings.
Labour law violations in Chile
Authors: KANBUR Ravi , RONCONI Lucas , WEDENOJA Leigh
Published: December 2013

This empirical contribution to the quantification of labour law violation uses micro survey data to examine compliance with workers' statutory entitlements to a minimum wage, working time limits, a written contract, and pension coverage over the period 1990–2009. One‐third of workers were denied at least one of these entitlements, albeit with significant variations in the incidence of violations over time, across laws and by worker and firm characteristics. The authors' econometric analysis shows that compliance rates are lower for female, foreign‐born, indigenous and less educated workers, and in smaller firms and agricultural regions. Further research, they argue, should focus on enforcement.
Driving forces of informal labour supply and demand in Germany
Authors: HAIGNER Stefan D. , JENEWEIN Stefan , SCHNEIDER Friedrich , WAKOLBINGER Florian
Published: December 2013

The authors empirically investigate people's reasons for supplying or using informal labour, on the basis of data obtained from a 2010 survey of German residents. Building on existing research, they find that being unemployed, or having been unemployed in the past, significantly increases the probability of supplying informal labour. In addition, dissatisfaction with one's relative standing in society, and annoyance at government inefficiency, both have a significant positive effect on male informal labour supply. Informal labour demand, however, is not affected by these factors.