bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of extracellular matrix derived from osteoarthritis subchondral bone osteoblasts on osteocytes: role of integrinβ1 and focal adhesion kinase signaling cues
Authors: Prasadam Indira , Farnaghi Saba , Feng Jian Q , Gu Wenyi , Perry Samuel , Crawford Ross , Xiao Yin
Published: October 2013

Introduction

Our recent study indicated that subchondral bone pathogenesis in osteoarthritis (OA) is associated with osteocyte morphology and phenotypic abnormalities. However, the mechanism underlying this abnormality needs to be identified. In this study we investigated the effect of extracellular matrix (ECM) produced from normal and OA bone on osteocytic cells function.

Methods

De-cellularized matrices, resembling the bone provisional ECM secreted from primary human subchondral bone osteoblasts (SBOs) of normal and OA patients were used as a model to study the effect on osteocytic cells. Osteocytic cells (MLOY4 osteocyte cell line) cultured on normal and OA derived ECMs were analyzed by confocal microscopy, scanning electron microscopy (SEM), cell attachment assays, zymography, apoptosis assays, qRT-PCR and western blotting. The role of integrinβ1 and focal adhesion kinase (FAK) signaling pathways during these interactions were monitored using appropriate blocking antibodies.

Results

The ECM produced by OA SBOs contained less mineral content, showed altered organization of matrix proteins and matrix structure compared with the matrices produced by normal SBOs. Culture of osteocytic cells on these defective OA ECM resulted in a decrease of integrinβ1 expression and the de-activation of FAK cell signaling pathway, which subsequently affected the initial osteocytic cell’s attachment and functions including morphological abnormalities of cytoskeletal structures, focal adhesions, increased apoptosis, altered osteocyte specific gene expression and increased Matrix metalloproteinases (MMP-2) and -9 expression.

Conclusion

This study provides new insights in understanding how altered OA bone matrix can lead to the abnormal osteocyte phenotypic changes, which is typical in OA pathogenesis.
Mapping formation shear-velocity variation by inverting logging-while-drilling quadrupole-wave dispersion data
Authors: Su Yuan-Da , Tang Xiao-Ming , Zhuang Chun-Xi , Xu Song , Zhao Long
Published: October 2013

The logging-while-drilling (LWD) quadrupole wave is a dispersive wave mode guided along the borehole with a drill collar. The wave is sensitive to the formation alteration caused by drilling. We inverted LWD quadrupole-wave dispersion data to estimate a radial shear-velocity profile away from the wellbore. We also explored the nonuniqueness of the inverse problem and solved it by using a constrained inversion method. This was done by constraining the high-frequency portion of the model dispersion curve with another curve calculated using the near-borehole velocity. The constraint condition is based on the physical principle that a high-frequency LWD quadrupole wave has a shallow penetration depth and is therefore sensitive to the near-borehole shear velocity. Particularly, we found that a monotonically continuous velocity profile can be well approximated using a one-zone equivalent model, allowing for a drastic simplification of the inversion process. We used theoretical modeling and real data examples to validate the method for the LWD wave data. The quadrupole dispersion data and the inversion results clearly demonstrated that formation alteration can occur even while the well is being drilled.
Inversion-based petrophysical interpretation of logging-while-drilling nuclear and resistivity measurements
Authors: Ijasan Olabode , Torres-Verdín Carlos , Preeg William E.
Published: October 2013

Interpretation of borehole measurements acquired in high-angle (HA) and horizontal (HZ) wells is challenging due to the significant influence of well trajectory and bed geometrical effects. Experience shows that accurate integrated interpretation of well logs acquired in HA/HZ wells requires explicit consideration of 3D measurement physics. The most reliable alternative for interpretation of well logs in HA/HZ wells is with inversion techniques that correct measurements for shoulder-bed, undulating well trajectory, and bed geometrical effects while taking advantage of high data resolution. We discovered an efficient layer-based inversion workflow for combined, quantitative petrophysical and compositional interpretation of logging-while-drilling sector-based nuclear (density, neutron porosity, photoelectric factor, gamma ray) and array propagation resistivity measurements acquired in HA/HZ wells. A challenging synthetic benchmark example confirmed improved formation evaluation with the layer-based inversion workflow across hydrocarbon-bearing zones in HA/HZ wells, where estimated hydrocarbon pore volume and porosity increased by 10% and 15%, respectively, with respect to conventional interpretation methods. Furthermore, application of the inversion-based method to a field example of HZ well across calcite-cemented siltstone layers confirmed its advantage over conventional interpretation techniques.
Antagonistic Roles of Dmrt1 and Foxl2 in Sex Differentiation via Estrogen Production in Tilapia as Demonstrated by TALENs
Authors: Li Ming-Hui , Yang Hui-Hui , Li Meng-Ru , Sun Yun-Lv , Jiang Xiao-Long , Xie Qing-Ping , Wang Ting-Ru , Shi Hong-Juan , Sun Li-Na , Zhou Lin-Yan , Wang De-Shou
Published: October 2013

Transcription activator-like effector nucleases (TALENs) are a powerful approach for targeted genome editing and have been proved to be effective in several organisms. In this study, we reported that TALENs can induce somatic mutations in Nile tilapia, an important species for worldwide aquaculture, with reliably high efficiency. Six pairs of TALENs were constructed to target genes related to sex differentiation, including dmrt1, foxl2, cyp19a1a, gsdf, igf3, and nrob1b, and all resulted in indel mutations with maximum efficiencies of up to 81% at the targeted loci. Effects of dmrt1 and foxl2 mutation on gonadal phenotype, sex differentiation, and related gene expression were analyzed by histology, immunohistochemistry, and real-time PCR. In Dmrt1-deficient testes, phenotypes of significant testicular regression, including deformed efferent ducts, degenerated spermatogonia or even a complete loss of germ cells, and proliferation of steroidogenic cells, were observed. In addition, disruption of Dmrt1 in XY fish resulted in increased foxl2 and cyp19a1a expression and serum estradiol-17β and 11-ketotestosterone levels. On the contrary, deficiency of Foxl2 in XX fish exhibited varying degrees of oocyte degeneration and significantly decreased aromatase gene expression and serum estradiol-17β levels. Some Foxl2-deficient fish even exhibited complete sex reversal with high expression of Dmrt1 and Cyp11b2. Furthermore, disruption of Cyp19a1a in XX fish led to partial sex reversal with Dmrt1 and Cyp11b2 expression. Taken together, our data demonstrated that TALENs are an effective tool for targeted gene editing in tilapia genome. Foxl2 and Dmrt1 play antagonistic roles in sex differentiation in Nile tilapia via regulating cyp19a1a expression and estrogen production.
Cross-Ethnic Meta-Analysis of Genetic Variants for Polycystic Ovary Syndrome
Authors: Louwers Yvonne V. , Stolk Lisette , Uitterlinden André G. , Laven Joop S. E.
Published: October 2013

Context:

Genome-wide association studies (GWAS) have revealed new susceptibility loci for Chinese patients with polycystic ovary syndrome (PCOS). Because ethnic background adds to phenotypic diversities in PCOS, it seems plausible that genetic variants associated with PCOS act differently in various ethnic populations.

Objective:

We studied cross-ethnic effects of Chinese PCOS loci (ie, LHCGR, THADA, DENND1A, FSHR, c9orf3, YAP1, RAB5B/SUOX, HMGA2, TOX3, INSR, SUMO1P1) in patients of Northern European descent.

Design:

This study was a genetic association study conducted at an University Medical Center.

Patients:

Association was studied in 703 Dutch PCOS patients and 2164 Dutch controls. To assess the cross-ethnic effect, we performed a meta-analysis of the Dutch data combined with results of previously published studies in PCOS patients from China (n = 2254) and the United States (n = 2618). Adjusted for multiple testing, a P value <3.1 × 10−3 was considered statistically significant.

Results:

Meta-analysis of the Chinese, US, and Dutch data resulted in 12 significant variants mapping to the YAP1 (P value = 1.0× 10−9), RAB5B/SUOX (P value = 3.8 × 10−11), LHCGR (P value = 4.1 × 10−4), THADA (P value = 2.2 × 10−4 and P value = 1.3 × 10−3), DENND1A (P value = 2.3 × 10−3 and P value = 2.5 × 10−3), FSHR (P value = 3.8 × 10−5 and P value = 3.6 × 10−4), c9orf3 (P value = 2.0 × 10−6 and P value = 9.2 × 10−6), SUMO1P1 (P value = 2.3 × 10−3) loci with odds ratios ranging from 1.19 to 1.45 and 0.79 to 0.87.

Conclusions:

Overall, we observed for 12 of 17 genetic variants mapping to the Chinese PCOS loci similar effect size and identical direction in PCOS patients from Northern European ancestry, indicating a common genetic risk profile for PCOS across populations. Therefore, it is expected that large GWAS in PCOS patients from Northern European ancestry will partly identify similar loci as the GWAS in Chinese PCOS patients.
The Role of the Parent Compound Vitamin D with Respect to Metabolism and Function: Why Clinical Dose Intervals Can Affect Clinical Outcomes
Authors: Hollis Bruce W. , Wagner Carol L.
Published: October 2013

Context:

There is no doubt that vitamin D must be activated to the hormonal form 1,25-dihydroxyvitamin D to achieve full biological activity or that many tissues participate in this activation process—be it endocrine or autocrine. We believe that not only is 25-hydroxyvitamin D important to tissue delivery for this activation process, but also that intact vitamin D has a pivotal role in this process.

Objective:

In this review, evidence on the vitamin D endocrine/autocrine system is presented and discussed in relation to vitamin D-binding protein affinity, circulating half-lives, and enzymatic transformations of vitamin D metabolites, and how these affect biological action in any given tissue.

Conclusions:

Circulating vitamin D, the parent compound, likely plays an important physiological role with respect to the vitamin D endocrine/autocrine system, as a substrate in many tissues, not originally thought to be important. Based on emerging data from the laboratory, clinical trials, and data on circulating 25-hydroxyvitamin D amassed during many decades, it is likely that for the optimal functioning of these systems, significant vitamin D should be available on a daily basis to ensure stable circulating concentrations, implying that variation in vitamin D dosing schedules could have profound effects on the outcomes of clinical trials because of the short circulating half-life of intact vitamin D.
Immigrants' Labor Supply and Exchange Rate Volatility
Authors: Nekoei Arash
Published: October 2013

Are an immigrant's decisions affected in real time by her home country's economy? I examine this question by exploiting exchange rate variations as exogenous price shocks to immigrants' budget constraints. I find that in response to a 10 percent dollar appreciation, an immigrant decreases her earnings by 0.92 percent, mainly by reducing hours worked. The exchange rate effect is greater for recent immigrants, married immigrants with absent spouses, Mexicans close to the border, and immigrants from countries with higher remittance flows. A neoclassical interpretation of these findings suggests that the income effect exceeds the cross-substitution effect. Remittance targets offer an alternative explanation. (JEL F24, F31, J22, J61)
Information Asymmetries in Consumer Credit Markets: Evidence from Payday Lending
Authors: Dobbie Will , Skiba Paige Marta
Published: October 2013

Information asymmetries are prominent in theory but difficult to estimate. This paper exploits discontinuities in loan eligibility to test for moral hazard and adverse selection in the payday loan market. Regression discontinuity and regression kink approaches suggest that payday borrowers are less likely to default on larger loans. A $50 larger payday loan leads to a 17 to 33 percent drop in the probability of default. Conversely, there is economically and statistically significant adverse selection into larger payday loans when loan eligibility is held constant. Payday borrowers who choose a $50 larger loan are 16 to 47 percent more likely to default. (JEL D14, D82, G21)
Getting Beneath the Veil of Effective Schools: Evidence From New York City
Authors: Dobbie Will , Fryer Roland G
Published: October 2013

In this paper, we collect data on the inner-workings of 39 charter schools and correlate these data with school effectiveness. We find that traditionally collected input measures—class size, per-pupil expenditure, teacher certification, and teacher training—are not correlated with school effectiveness. In stark contrast, we show that an index of five policies suggested by qualitative research—frequent teacher feedback, the use of data to guide instruction, high-dosage tutoring, increased instructional time, and high expectations—explains approximately 45 percent of the variation in school effectiveness. The same index provides similar results in a separate sample of charter schools. (JEL H75, I21, I28)
Synaptic Vesicle Protein 2 (SV2) does not hydrolyze ATP
Authors: Yao Jia , Bajjalieh Sandra M.
Published: October 2013

Synaptic vesicle protein 2 (SV2) is a transporter-like protein specifically expressed in endocrine cells and neurons, where it is localized to vesicles that undergo regulated secretion and plays an essential role in regulating neurotransmitter release. SV2 binds adenine nucleotides including ATP. Analysis of ATP transport revealed that SV2 is not an ATP transporter, nor does it affect ATP transport. As a further step toward understanding how ATP binding contributes to SV2 function, we investigated whether SV2 is an ATPase using an in vitro measure of ATPase activity. The study reported here indicates that SV2 does not have ATPase activity. Thus, binding to adenine nucleotides likely modulates other actions of SV2.
Introduction to the Special Issue on the Environment
Authors: Plambeck Erica L. , Toktay L. Beril
Published: October 2013

Human population growth and increasing consumption per capita are causing environmental impacts that threaten the survival and well-being of humans and other species on Earth. To sustain natural ecosystems and human populations with a high standard of living, humanity must now reinvent our systems for the production and delivery of goods and services to dramatically reduce the environmental impacts associated with consumption. The operations management community can contribute critical know-how to do so, as demonstrated by the papers in this special issue.
Recommendations for the Use of Operational Electronic Health Record Data in
Comparative Effectiveness Research
Authors: Hersh William , Cimino James , Payne Philip R.O. , Embi Peter , Logan Judith , Weiner Mark , Bernstam Elmer V. , Lehmann Harold , Hripcsak George , Hartzog Timothy , Saltz Joel
Published: October 2013

There is an increasing amount of clinical data in operational electronic health
record (EHR) systems. Such data provide substantial opportunities for their re-use for
many purposes, including comparative effectiveness research (CER). In a previous paper,
we identified a number of caveats related to the use of such data, noting that they may
be inaccurate, incomplete, transformed in ways that undermine their meaning,
unrecoverable for research, of unknown provenance, of insufficient granularity, or
incompatible with research protocols. In this paper, we provide recommendations for
overcoming these caveats with the goal of leveraging such data to benefit CER and other
health care activities. These recommendations include adaptation of “best evidence”
approaches to use of data; processes to evaluate availability, completeness, quality,
and transformability of data; creation of tools to manage data and their attributes;
determination of metrics for assessing whether data are “research grade”; development of
methods for comparative validation of data; construction of a methodology database for
methods involving use of clinical data; standardized reporting methods for data and
their attributes; appropriate use of informatics expertise; and a research agenda to
determine biases inherent in operational data and to assess informatics approaches to
their improvement.
Review
Authors: Ralph Susie
Published: October 2013

‘l’eleganza In Esilio: Tra Moda E Costume, Il Tempo Di Djagilev’/‘elegance In Exile: Between Fashion And Costume In The Time Of Diaghilev’, Museo Di Palazzo Mocenigo, Venice, 17 September 2011–6 January 2012
From bag ladies to bathing apes: Japanese interventions in British sartorial culture
Authors: Cambridge Nicolas
Published: October 2013

Since 1980 Japanese designers have built a solid, if understated, presence in the United Kingdom. This chapter examines the country’s interventions in British sartorial culture in the arenas of designer fashion, high-street apparel and sub-cultural style from three inter-related perspectives. The first considers the curatorial context of exhibitions that featured a cohort of avant-garde designers. The second addresses contrasting commercial strategies adopted by Japanese designers that involved mobilizations of traditional culture as ‘unique selling points’ and infiltration of the domestic market through collaborations with British apparel makers. The third documents visual consumption of creative outputs mediated through the styling regimes of the fashion periodical, and identifies a gendered differentiation in representations of Japanese fashion design. The conclusion suggests that, in an increasingly cosmopolitan creative milieu, interpretations of British sartorial heritage have become the province of ‘outsiders looking in’.
From Gallant Little Belgium to Elegant Little Belgium: The creation and marketing of fashions from the flat country
Authors: Dirix Emmanuelle
Published: October 2013

This article examines the enduring myth of the Antwerp Six. By consulting primary sources it revisits the circumstances under which The Six burst onto the international fashion scene and repositions their story into a wider narrative of marketing and branding.
Pre-transnationalism in dress, a methodology: The unique example of Hong Kong’s expatriate western women, 1960–1997
Authors: Trower Valerie Wilson
Published: October 2013

This paper seeks to outline ways in which the topic of transnationalism can be thoroughly explored by other researchers using as an example, research on the Hong Kong fashion system and especially the experience of expatriate Western women in using dress as a means of manifesting identities in the early period of transnationalisn and the period immediately preceding it. Issues of fashion leadership and hegemony are discussed, and particularly expatriate minority dress, together with: the appropriation of regional dress; binge shopping’; and women’s tailoring, all contributing to fashion in one of Asia’s world cities.
The Wigan Dandy: Promenading the dance hall via Detroit and Paris
Authors: Nicholson Sue
Published: October 2013

In this short article, I intend to consider the transnationalism inherent within the Northern Soul movement of the 1970s. By contextualizing the sociocultural climate from which this group emerged, the article will argue that by challenging masculinity through performance and dress practices, Northern Soul devotees borrowed not merely from the disaffected black ghettos of Detroit, but from the streets of nineteenth-century Paris.
Copy Alert: A Method and Metric to Detect Visual Copycat Brands
Authors: Satomura Takuya , Wedel Michel , Pieters Rik
Published: October 2013

The authors propose a method and metric to quantify the consumer confusion between leading brands and copycat brands that results from the visual similarity of their packaging designs. The method has three components. First, image processing techniques establish the objective similarity of the packages of leading and copycat brands on the basis of their colors and textures. Second, a perceptual decision task (triangle test) assesses the accuracy and speed with which consumers can identify differences between brands from rapidly (300 milliseconds) flashed images of their packages. Third, a competing accumulator model describes the buildup of evidence on each of the alternative brands during consumers’ perceptual decisions and predicts the accuracy and response time of brand identification. Jointly, these components establish the impact of copycat packaging's visual features on consumer confusion. The method is applied in a test of experimentally designed copycats and market copycats in 15 product categories. A three-tiered metric (“copy alert,” “copy watch,” and “copy safe”) establishes the extent to which copycat brands imitate the package designs of target brands and identifies which visual features are responsible.
Aristotle on Political Communities: Lessons from Outside the Politics
Authors: Ranger Jean-Philipe
Published: October 2013

This article examines Aristotelian definitions of ‘political community’. Most accounts of this concept focus on the polis, the type of community that features prominently in the Politics. However, if one takes into account passages from the History of Animals and the Nicomachean Ethics VIII-IX, it is possible to uncover a formal definition of ‘political community’. It then becomes clear that other communities, such as those based in virtue-friendship, can be considered political as well according to the criterion set out by Aristotle: a fact which suggests Aristotle has a richer understanding of the concept than scholars usually ascribe to him.
The Tuesday Advantage of Politicians Endorsed by American Newspapers
Authors: Leite Lopez de Leon Fernanda
Published: October 2013

This article documents the electoral advantage of candidates who have a newspaper endorsement published on Election Day compared to other endorsed candidates. I provide evidence that this advantage is not driven by a selection effect, suggesting that it is instead explained by readers deciding how to vote based on endorsements read on Election Day. Moreover, candidates who have a different political orientation from their endorsing newspapers benefit more from this endorsement than other candidates. These results are based on a newly-compiled dataset matching county-level data of 826 endorsed candidates’ election results with newspaper and county characteristics.
Vertical Contracts and Mandatory Universal Distribution
Authors: Karp Larry S. , Perloff Jeffrey M.
Published: October 2013

An upstream monopoly that provides a new good to a downstream oligopoly might prefer to sell to a single rather than to multiple downstream firms. For example, Apple initially sold its iPhone through one vendor. If a monopoly uses a single vendor, the government may impose a mandatory universal distribution (MUD) requirement that forces the monopoly to sell to all downstream vendors. However, if the income elasticity of demand for the new good is greater than the income elasticity of the existing generic good, the MUD requirement leads to a higher equilibrium price for both the new good and the generic and lowers consumer welfare.
Absorptive chemistry based extraction for LC-MS/MS analysis of small molecule analytes from biological fluids – an application for 25-hydroxyvitamin D
Authors: Baecher Silvia , Geyer Roland , Lehmann Christine , Vogeser Michael
Published: October 2013

Background: Already available sample preparation technologies for liquid chromatography-tandem mass spectrometry have substantial shortcomings with respect to automation. A novel approach is based on gel-like polymeric material with defined absorption chemistry, which is immobilized in micro-plate wells. It is referred to as Tecan Immobilized Coating Extraction
™ (TICE
™) technology and it enables easy automation on liquid handling systems. We aimed to study the performance of Tecan AC Extraction Plate
™ based on this principle by addressing 25-hydroxyvitamin D (25OHD) as an exemplary analyte.

Methods: A protocol for extraction of 25OHD from serum samples based on TICE
™ technology was implemented on a robotic liquid handling system Freedom EVO
® (Tecan). An isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry method was used for quantification. Performance was tested according to a comprehensive protocol.

Results: Linearity was found over a range from 4.3 to 65.8 ng/mL for 25OHD3. The coefficients of variation for the intra-day and inter-day precision were <6% and accuracy ranged between 96.9% and 99.8% for 25OHD3. Recovery was 84% and efficient control of matrix effects was verified. High sample throughput could be observed with 96 samples prepared in <60 min. Close agreement of results was found for clinical samples analyzed with a second tandem mass spectrometry method based on protein precipitation and two-dimensional ultra-performance liquid chromatography for sample preparation (r=0.988, n=73).

Conclusions: The new TICE
™ technology was found to be a useful process for sample preparation in clinical mass spectrometry. Full automation suited for routine analysis was achieved.
Urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion increases in normal pregnancy but not in preeclampsia
Authors: Ødum Lars , Andersen Anita Sylvest , Hviid Thomas Vauvert F.
Published: October 2013

Neutrophil gelatinase-associated lipocalin (NGAL) serum values have been shown to increase in preeclampsia. The goal of the present study was to evaluate changes in urinary NGAL concentrations during uncomplicated pregnancy and in cases of preeclampsia and hypertension.

Fifty-one pregnant women who developed preeclampsia and 28 diagnosed with essential or gestational hypertension were investigated for urinary NGAL concentrations during pregnancy. As controls, 100 healthy pregnant women with uncomplicated singleton pregnancies were randomly selected. Urinary NGAL as well as urinary creatinine and albumin were measured by a standardized clinical chemistry platform (ARCHITECT

Urinary NGAL concentrations increased during pregnancy in healthy pregnant women, whereas this increase was not detected in preeclampsia. In order to correct for diuresis, spot urine concentrations were also determined as NGAL/creatinine ratio. NGAL/creatinine ratio in pregnancy week 36–38 was significantly lower in preeclampsia than in healthy pregnant women or pregnant women with hypertension. NGAL urinary concentrations did not correlate with albumin concentration in urine.

Urinary NGAL is not a valuable early biomarker for preeclampsia.
Influence of urine volume on the assessment of intestinal permeability in affected children by multiple sugar probes
Authors: Addobbati Riccardo , Pascolo Lorella , Di Toro Nicola , Sebastiani Giulia B. , Martellossi Stefano , Not Tarcisio
Published: October 2013

In this study we have looked at the reliability of a multi-sugar test in a pediatric patient population and its accuracy at small urine volumes to evaluate intestinal permeability.

Out of 117 subjects enrolled, 31 were healthy and 86 were sick. A solution containing lactulose, rhamnose, sucrose, and sucralose was administered to subjects who were on fasting; the urine excreted during 5 h was collected and measured. Samples were analyzed by gas chromatography-tandem mass spectrometry and results were expressed as percentage of sugar recoveries and lactulose/rhamnose (L/R) ratio.

The analyses showed a clear effect of low urinary volumes (≤240 mL) particularly affecting rhamnose excretion in healthy subjects and sucrose and sucralose recovery in diseased children. Despite the low rhamnose recovery, as lactulose is not similarly affected, the diagnostic reliability of L/R ratio is well preserved at low diuresis conditions. However, this ratio can be useful to discriminate acute conditions vs. clinical remissions only at high urine volumes. Data also suggest potential diagnostic applicability of sucrose and sucralose in children at high urine volumes.

In conclusion, the multi-sugar test has a good predictivity in pediatric subjects but results must be carefully interpreted in the face of reduced diuresis.
Plasma endothelial cell-specific molecule-1 (ESM-1) in management of community-acquired pneumonia
Authors: Kao Shang-Jyh , Chuang Chun-Yi , Tang Chih-Hsin , Lin Chien-Huang , Bien Mauo-Ying , Yu Ming-Chih , Bai Kuan-Jen , Yang Shun-Fa , Chien Ming-Hsien
Published: October 2013

Background: Endothelial cell-specific molecule (ESM)-1 is a soluble proteoglycan expressed by the vascular endothelium and which also circulates in the bloodstream. Inflammatory cytokines and proangiogenic growth factors increase its expression, and increased serum levels are found in immunocompetent patients with sepsis. The aim of this study was to investigate differential changes in plasma levels of ESM-1 before and after antibiotic treatment in hospitalized adult patients with community-acquired pneumonia (CAP).

Methods: Plasma ESM-1 levels were measured in 82 adult patients with CAP and 82 healthy controls using a commercial enzyme-linked immunosorbent assay (ELISA). Upon initial hospitalization, Acute Physiology and Chronic Health Evaluation II (APACHE II), CURB-65, and Pneumonia Severity Index (PSI) scores were determined to assess CAP severity in these patients.

Results: Results showed a decline in the number of white blood cells (WBCs) and neutrophils, and decreases in the concentrations of C-reactive protein (CRP) and ESM-1 after antibiotic treatment. The plasma concentration of ESM-1, but not CRP or the WBC count, was correlated with the severity of CAP based on the PSI (r=0.554, p<0.001), CURB-65 (r=0.510, p<0.001), and APACHE II scores (r=0.447, p<0.001).

Conclusions: Plasma levels of ESM-1 may be able to play a role in the diagnosis and clinical assessment of the severity of CAP, which could potentially guide the development of treatment strategies.
Evaluation of 3-epi-25-hydroxyvitamin D3 cross-reactivity in the Roche Elecsys Vitamin D Total protein binding assay
Authors: van den Ouweland Johannes M.W. , Beijers Antonius M. , van Daal Henny , Elisen Marc G.L.M. , Steen Gerard , Wielders Jos P.M.
Published: October 2013

Background: Presence of the 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3] metabolite affects accurate determination of 25(OH)D3 by most routine liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods and to an unknown extent in present immuno- and protein binding assays. We studied 3-epi-25(OH)D3 cross-reactivity in a competitive protein binding (CPB) assay (Roche Elecsys).

Methods: Neonatal samples, containing up to 58% of 3-epi-25(OH)D3 were used for measurement by the CPB assay and by an LC-MS/MS method separating 25(OH)D3 and 3-epi-25(OH)D3. Analytical recovery was also studied by addition of exogenous 3-epi-25(OH)D3.

Results: The CPB assay showed approximately 51% cross-reactivity to 3-epi-25(OH)D3 at exogenous addition. In contrast, there was minimal 3-epi-25(OH)D3 recognition by the CPB assay when present as the natural endogenous metabolite.

Conclusions: The automated CPB assay displays minimal 3-epi-25(OH)D3 cross-reactivity in samples containing significant concentrations of endogenous 3-epi-25(OH)D3. Exogenous 3-epi-25(OH)D3 added to human serum or plasma seems to behave different from endogenous presence, and caution is warranted when using samples spiked with vitamin D metabolites for testing analytical specificity or external quality assurance in immuno- or protein binding assays.
Beating the bugs: roles of microbial biofilms in corrosion
Authors: Li Kwan , Whitfield Matthew , Van Vliet Krystyn J.
Published: October 2013

Microbiologically influenced corrosion (MIC) is a complex type of environmentally assisted corrosion. Although poorly understood and challenging to ameliorate, it is increasingly appreciated that MIC accelerates failure of metal alloys, including steel pipeline. Historically, this type of material degradation process has been treated from either an electrochemical materials perspective or a microbiological perspective. Here, we review the current understanding of MIC mechanisms for steel – particularly those in sour environments relevant to fossil fuel recovery and processing – and outline the role of the bacterial biofilm in both corrosion processes and mitigation responses.
Dissociable Neural Mechanisms for Goal-Directed Versus Incidental Memory Reactivation
Authors: Kuhl Brice A. , Johnson Marcia K. , Chun Marvin M.
Published: October 2013

Remembering a past event involves reactivation of distributed patterns of neural activity that represent the features of that event—a process that depends on associative mechanisms supported by medial temporal lobe structures. Although efficient use of memory requires prioritizing those features of a memory that are relevant to current behavioral goals (target features) over features that may be goal-irrelevant (incidental features), there remains ambiguity concerning how this is achieved. We tested the hypothesis that although medial temporal lobe structures may support reactivation of both target and incidental event features, frontoparietal cortex preferentially reactivates those features that match current goals. Here, human participants were cued to remember either the category (face/scene) to which a picture belonged (category trials) or the location (left/right) in which a picture appeared (location trials). Multivoxel pattern analysis of fMRI data were used to measure reactivation of category information as a function of its behavioral relevance (target vs incidental reactivation). In ventral/medial temporal lobe (VMTL) structures, incidental reactivation was as robust as target reactivation. In contrast, frontoparietal cortex exhibited stronger target than incidental reactivation; that is, goal-modulated reactivation. Reactivation was also associated with later memory. Frontoparietal biases toward target reactivation predicted subsequent memory for target features, whereas incidental reactivation in VMTL predicted subsequent memory for nontested features. These findings reveal a striking dissociation between goal-modulated reactivation in frontoparietal cortex and incidental reactivation in VMTL.
The Fine-Scale Functional Correlation of Striate Cortex in Sighted and Blind People
Authors: Butt Omar H. , Benson Noah C. , Datta Ritobrato , Aguirre Geoffrey K.
Published: October 2013

To what extent are spontaneous neural signals within striate cortex organized by vision? We examined the fine-scale pattern of striate cortex correlations within and between hemispheres in rest-state BOLD fMRI data from sighted and blind people. In the sighted, we find that corticocortico correlation is well modeled as a Gaussian point-spread function across millimeters of striate cortical surface, rather than degrees of visual angle. Blindness produces a subtle change in the pattern of fine-scale striate correlations between hemispheres. Across participants blind before the age of 18, the degree of pattern alteration covaries with the strength of long-range correlation between left striate cortex and Broca's area. This suggests that early blindness exchanges local, vision-driven pattern synchrony of the striate cortices for long-range functional correlations potentially related to cross-modal representation.
Klotho Regulates Retinal Pigment Epithelial Functions and Protects Against Oxidative Stress
Authors: Kokkinaki Maria , Abu-Asab Mones , Gunawardena Nishantha , Ahern Gerard , Javidnia Monica , Young John , Golestaneh Nady
Published: October 2013

The retinal pigment epithelium (RPE) is a highly specialized CNS tissue that plays crucial roles in retinal homeostasis. Age-related morphological changes in the RPE have been associated with retinal degenerative disorders; our understanding of the underlying molecular mechanisms, however, remains incomplete. Here we report on a key role ofKlotho(Kl), an aging-suppressor gene, in retinal health and RPE physiology.Kl−/−mice show RPE and photoreceptor degeneration, reduced pigment synthesis in the RPE, and impaired phagocytosis of the outer segment of the photoreceptors. Klotho protein (KL) is expressed in primary cultured human RPE, and regulates pigment synthesis by increasing the expression ofMITF(microphthalmia transcription factor) andTYR(tyrosinase), two pivotal genes in melanogenesis. Importantly, KL increases phagocytosis in cultured RPE by inducing gene expression ofMERTK/AXL/TYRO3. These effects of KL are mediated through cAMP-PKA-dependent phosphorylation of transcription factor CREB. In cultured human RPE, KL increases thel-3,4-dihydroxyphenylalanine synthesis and inhibits vascular endothelial growth factor (VEGF) secretion from basal membrane by inhibiting IGF-1 signaling and VEGF receptor 2 phosphorylation. KL also regulates the expression of stress-related genes in RPE, lowers the production of reactive oxygen species, and thereby, protects RPE from oxidative stress. Together, our results demonstrate a critical function for KL in mouse retinal healthin vivo, and a protective role toward human RPE cellsin vitro. We conclude that KL is an important regulator of RPE homeostasis, and propose that an age-dependent decline of KL expression may contribute to RPE degeneration and retinal pathology.
NeonatalE. ColiInfection Causes Neuro-Behavioral Deficits Associated with Hypomyelination and Neuronal Sequestration of Iron
Authors: Lieblein-Boff Jacqueline C. , McKim Daniel B. , Shea Daniel T. , Wei Ping , Deng Zhen , Sawicki Caroline , Quan Ning , Bilbo Staci D. , Bailey Michael T. , McTigue Dana M. , Godbout Jonathan P.
Published: October 2013

Recent evidence indicates that inflammatory insults in neonates significantly influenced white matter development and caused behavioral deficits that manifest in young adulthood. The mechanisms underlying these developmental and behavioral complications, however, are not well understood. We hypothesize that acute brain inflammation caused by neonatal infection reduces the bioavailability of iron required for oligodendrocyte maturation and white matter development. Here, we confirm that peripheralEscherichia coliinfection in neonates at postnatal day 3 (P3) caused acute brain inflammation that was resolved within 72 h. Nonetheless, transient early life infection (ELI) profoundly influenced behavior, white matter development, and iron homeostasis in the brain. For instance, mice exposed toE. colias neonates had increased locomotor activity and impaired motor coordination as juveniles (P35) and young adults (P60). In addition, these behavioral deficits were associated with marked hypomyelination and a reduction of oligodendrocytes in subcortical white matter and motor cortex. Moreover, ELI altered transcripts related to cellular sequestration of iron in the brain including hepcidin, ferroportin, and L-ferritin. For example, ELI increased hepcidin mRNA and decreased ferroportin mRNA and protein in the brain at P4, which preceded increased L-ferritin mRNA at P12. Consistent with the mRNA results, L-ferritin protein was robustly increased at P12 specifically in neurons ofE. coliinfected mice. We interpret these data to indicate that neonatal infection causes significant neuronal sequestration of iron at a time point before myelination. Together, these data indicate a possible role for aberrant neuronal iron storage in neonatal infection-induced disturbances in myelination and behavior.
Prior Expectations Bias Sensory Representations in Visual Cortex
Authors: Kok Peter , Brouwer Gijs Joost , van Gerven Marcel A.J. , de Lange Floris P.
Published: October 2013

Perception is strongly influenced by expectations. Accordingly, perception has sometimes been cast as a process of inference, whereby sensory inputs are combined with prior knowledge. However, despite a wealth of behavioral literature supporting an account of perception as probabilistic inference, the neural mechanisms underlying this process remain largely unknown. One important question is whether top-down expectation biases stimulus representations in early sensory cortex, i.e., whether the integration of prior knowledge and bottom-up inputs is already observable at the earliest levels of sensory processing. Alternatively, early sensory processing may be unaffected by top-down expectations, and integration of prior knowledge and bottom-up input may take place in downstream association areas that are proposed to be involved in perceptual decision-making. Here, we implicitly manipulated human subjects' prior expectations about visual motion stimuli, and probed the effects on both perception and sensory representations in visual cortex. To this end, we measured neural activity noninvasively using functional magnetic resonance imaging, and applied a forward modeling approach to reconstruct the motion direction of the perceived stimuli from the signal in visual cortex. Our results show that top-down expectations bias representations in visual cortex, demonstrating that the integration of prior information and sensory input is reflected at the earliest stages of sensory processing.
Representation of Spatial- and Object-Specific Behavioral Goals in the Dorsal Globus Pallidus of Monkeys during Reaching Movement
Authors: Saga Yosuke , Hashimoto Masashi , Tremblay Léon , Tanji Jun , Hoshi Eiji
Published: October 2013

The dorsal aspect of the globus pallidus (GP) communicates with the prefrontal cortex and higher-order motor areas, indicating that it plays a role in goal-directed behavior. We examined the involvement of dorsal GP neurons in behavioral goal monitoring and maintenance, essential components of executive function. We trained two macaque monkeys to choose a reach target based on relative target position in a spatial goal task or a target shape in an object-goal task. The monkeys were trained to continue to choose a certain behavioral goal when reward volume was constant and to switch the goals when the volume began to decrease. Because the judgment for the next goal was made in the absence of visual signals, the monkeys were required to monitor and maintain the chosen goals during the reaching movement. We obtained three major findings. (1) GP neurons reflected more of the relative spatial position than the shape of the reaching target during the spatial goal task. During the object-goal task, the shape of the reaching object was represented more than the relative position. (2) The selectivity of individual neurons for the relative position was enhanced during the spatial goal task, whereas the object-shape selectivity was enhanced during the object-goal task. (3) When the monkeys switched the goals, the selectivity for either the position or shape also switched. Together, these findings suggest that the dorsal GP is involved in behavioral goal monitoring and maintenance during execution of goal-oriented actions, presumably in collaboration with the prefrontal cortex.
Essential Role of SIRT1 Signaling in the Nucleus Accumbens in Cocaine and Morphine Action
Authors: Ferguson Deveroux , Koo Ja Wook , Feng Jian , Heller Elizabeth , Rabkin Jacqui , Heshmati Mitra , Renthal William , Neve Rachael , Liu Xiaochuan , Shao Ningyi , Sartorelli Vittorio , Shen Li , Nestler Eric J.
Published: October 2013

Sirtuins (SIRTs), class III histone deacetylases, are well characterized for their control of cellular physiology in peripheral tissues, but their influence in brain under normal and pathological conditions remains poorly understood. Here, we establish an essential role for SIRT1 and SIRT2 in regulating behavioral responses to cocaine and morphine through actions in the nucleus accumbens (NAc), a key brain reward region. We show that chronic cocaine administration increases SIRT1 and SIRT2 expression in the mouse NAc, while chronic morphine administration induces SIRT1 expression alone, with no regulation of all other sirtuin family members observed. Drug induction of SIRT1 and SIRT2 is mediated in part at the transcriptional level via the drug-induced transcription factor ΔFosB and is associated with robust histone modifications at theSirt1andSirt2genes. Viral-mediated overexpression of SIRT1 or SIRT2 in the NAc enhances the rewarding effects of both cocaine and morphine. In contrast, the local knockdown of SIRT1 from the NAc of floxedSirt1mice decreases drug reward. Such behavioral effects of SIRT1 occur in concert with its regulation of numerous synaptic proteins in NAc as well as with SIRT1-mediated induction of dendritic spines on NAc medium spiny neurons. These studies establish sirtuins as key mediators of the molecular and cellular plasticity induced by drugs of abuse in NAc, and of the associated behavioral adaptations, and point toward novel signaling pathways involved in drug action.
GDNF Signaling Levels Control Migration and Neuronal Differentiation of Enteric Ganglion Precursors
Authors: Uesaka Toshihiro , Nagashimada Mayumi , Enomoto Hideki
Published: October 2013

Pleiotropic growth factors play a number of critical roles in continuous processes of embryonic development; however, the mechanisms by which a single regulatory factor is able to orchestrate diverse developmental events remain imperfectly understood. In the development of the enteric nervous system (ENS), myenteric ganglia (MGs) form initially, after which the submucosal ganglia (SMGs) develop by radial inward migration of immature ENS precursors from the myenteric layer. Here, we demonstrate that glial cell line-derived neurotrophic factor (GDNF) is essential for the formation not only of the MGs, but the SMGs as well, establishing GDNF as a long-term acting neurotrophic factor for ENS development in a mouse model. GDNF promotes radial migration of SMG precursors. Interestingly, premigratory SMG precursors in the myenteric layer were distinguished from the surrounding neuronally differentiating cells by their lower activation of the GDNF-mediated MAPK pathway, suggesting that low activation of GDNF downstream pathways is required for the maintenance of the immature state. ENS precursors devoid of GDNF signaling during midgestation halt their migration, survive, and remain in an undifferentiated state over the long-termin vivo. Reactivation of GDNF signaling in these dormant precursors restores their migration and neuronal differentiation in gut organ culture. These findings suggest that pleiotropic function of GDNF is at least in part governed by modulating levels of intracellular activation of GDNF downstream pathways; high activation triggers neuronal differentiation, whereas low activation is crucial for the maintenance of progenitor state.
What Does Motor Efference Copy Represent? Evidence from Speech Production
Authors: Niziolek Caroline A. , Nagarajan Srikantan S. , Houde John F.
Published: October 2013

How precisely does the brain predict the sensory consequences of our actions? Efference copy is thought to reflect the predicted sensation of self-produced motor acts, such as the auditory feedback heard while speaking. Here, we use magnetoencephalographic imaging (MEG-I) in human speakers to demonstrate that efference copy prediction does not track movement variability across repetitions of the same motor task. Specifically, spoken vowels were less accurately predicted when they were less similar to a speaker's median production, even though the prediction is thought to be based on the very motor commands that generate each vowel. Auditory cortical responses to less prototypical speech productions were less suppressed, resembling responses to speech errors, and were correlated with later corrective movement, suggesting that the suppression may be functionally significant for error correction. The failure of the motor system to accurately predict less prototypical speech productions suggests that the efferent-driven suppression does not reflect a sensory prediction, but a sensory goal.