bluuebunny/crossref_metadata_2025 huggingface dataset:
A systems biology approach reveals common metastatic pathways in osteosarcoma
Authors: Flores Ricardo J , Li Yiting , Yu Alexander , Shen Jianhe , Rao Pulivarthi H , Lau Serrine S , Vannucci Marina , Lau Ching C , Man Tsz-Kwong
Published: May 2012

Background

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models.

Results

mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest-path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the SaOS-2/LM7 and HOS/143B models was further validated using an orthogonal Reverse Phase Protein Array platform.

Conclusions

In this study, we used a systems biology approach by integrating genomic and proteomic data to identify key and common metastatic mechanisms in OS. The use of the topological analysis revealed hidden biological pathways that are known to play critical roles in metastasis. Wnt signaling has been previously implicated in OS and other tumors, and inhibitors of Wnt signaling pathways are available for clinical testing. Further characterization of this common pathway and other topological pathways identified from this study may lead to a novel therapeutic strategy for the treatment of metastatic OS.
Which characteristic of Natto: appearance, odor, or taste most affects preference for Natto
Authors: Tsumura Yuki , Ohyane Aki , Yamashita Kuniko , Sone Yoshiaki
Published: May 2012

Background

In Japan, consumption of Natto, a fermented bean dish, is recommended because of its high quality protein, digestibility in the gut and its preventive effect on blood clot formation due to high vitamin K content. However, consumption of Natto in Kansai and the Chugoku area (the western part of Honshu) is less than that in the other areas of Japan probably because of a “food related cultural inhibition”. In this study, we determined which characteristic of Natto (appearance, odor or taste) most affect subjects’ perception of sensory attributes by observation of brain hemodynamics in relation to subjects’ preference for Natto.

Findings

In this experiment, we defined each subject’s changes in brain hemodynamics as (+) or (−) corresponding to an increase or a decrease in total hemoglobin concentration after stimuli compared to that before stimuli. As a result, there was no relation between preference for Natto and change in brain hemodynamics by the stimuli of “looking at” or “smelling”, while there was a significant relationship between preference and stimulus of “ingestion”; (+) : (−) = 21:15 in the subjects of the “favorite” group and (+):(−) = 30:7 in the subjects of the “non-favorite” group (P = 0.034).

Conclusion

This result indicated that characteristic “taste” of Natto most affects preference for Natto.
How to set up a low cost tele-ultrasound capable videoconferencing system with wide applicability
Authors: Crawford Innes , McBeth Paul B , Mitchelson Mark , Ferguson James , Tiruta Corina , Kirkpatrick Andrew W
Published: May 2012

Background

Worldwide ultrasound equipment accessibility is at an all-time high, as technology improves and costs decrease. Ensuring that patients benefit from more accurate resuscitation and diagnoses from a user-dependent technology, such as ultrasound, requires accurate examination, typically entailing significant training. Remote tele-mentored ultrasound (RTUS) examination is, however, a technique pioneered in space medicine that has increased applicability on earth. We, thus, sought to create and demonstrate a cost-minimal approach and system with potentially global applicability.

Methods

The cost-minimal RTUS system was constructed by utilizing a standard off-the-shelf laptop computer that connected to the internet through an internal wireless receiver and/or was tethered through a smartphone. A number of portable hand-held ultrasound devices were digitally streamed into the laptop utilizing a video converter. Both the ultrasound video and the output of a head-mounted video camera were transmitted over freely available Voice Over Internet Protocol (VOIP) software to remote experts who could receive and communicate using any mobile device (computer, tablet, or smartphone) that could access secure VOIP transmissions from the internet.

Results

The RTUS system allowed real-time mentored tele-ultrasound to be conducted from a variety of settings that were inside buildings, outside on mountainsides, and even within aircraft in flight all unified by the simple capability of receiving and transmitting VOIP transmissions. . Numerous types of ultrasound examinations were conducted such as abdominal and thoracic examinations with a variety of users mentored who had previous skills ranging from none to expert. Internet connectivity was rarely a limiting factor, with competing logistical and scheduling demands of the participants predominating.

Conclusions

RTUS examinations can educate and guide point of care clinical providers to enhance their use of ultrasound. The scope of the examinations conducted is limited only by the time available and the criticality of the subject being examined. As internet connectivity will only improve worldwide, future developments need to focus on the human factors to optimize tele-sonographic interactions.
Leaky ryanodine receptors in β-sarcoglycan deficient mice: a potential common defect in muscular dystrophy
Authors: Andersson Daniel C , Meli Albano C , Reiken Steven , Betzenhauser Matthew J , Umanskaya Alisa , Shiomi Takayuki , D’Armiento Jeanine , Marks Andrew R
Published: May 2012

Background

Disruption of the sarcolemma-associated dystrophin-glycoprotein complex underlies multiple forms of muscular dystrophy, including Duchenne muscular dystrophy and sarcoglycanopathies. A hallmark of these disorders is muscle weakness. In a murine model of Duchenne muscular dystrophy, mdx mice, cysteine-nitrosylation of the calcium release channel/ryanodine receptor type 1 (RyR1) on the skeletal muscle sarcoplasmic reticulum causes depletion of the stabilizing subunit calstabin1 (FKBP12) from the RyR1 macromolecular complex. This results in a sarcoplasmic reticular calcium leak via defective RyR1 channels. This pathological intracellular calcium leak contributes to reduced calcium release and decreased muscle force production. It is unknown whether RyR1 dysfunction occurs also in other muscular dystrophies.

Methods

To test this we used a murine model of Limb-Girdle muscular dystrophy, deficient in β-sarcoglycan (Sgcb−/−).

Results

Skeletal muscle RyR1 from Sgcb−/− deficient mice were oxidized, nitrosylated, and depleted of the stabilizing subunit calstabin1, which was associated with increased open probability of the RyR1 channels. Sgcb−/− deficient mice exhibited decreased muscle specific force and calcium transients, and displayed reduced exercise capacity. Treating Sgcb−/− mice with the RyR stabilizing compound S107 improved muscle specific force, calcium transients, and exercise capacity. We have previously reported similar findings in mdx mice, a murine model of Duchenne muscular dystrophy.

Conclusions

Our data suggest that leaky RyR1 channels may underlie multiple forms of muscular dystrophy linked to mutations in genes encoding components of the dystrophin-glycoprotein complex. A common underlying abnormality in calcium handling indicates that pharmacological targeting of dysfunctional RyR1 could be a novel therapeutic approach to improve muscle function in Limb-Girdle and Duchenne muscular dystrophies.
Explorative study on patient's perceived knowledge level, expectations, preferences and fear of side effects for treatment for allergic rhinitis
Authors: Hellings Peter W , Dobbels Fabienne , Denhaerynck Kris , Piessens Mark , Ceuppens Jan L , De Geest Sabina
Published: May 2012

Background

In spite of the high prevalence of allergic rhinitis (AR) and the evidence‐based guidelines for treatment, little is known about the patients’ perceived knowledge level, expectations, preferences for treatment, and fear for side effects of treatment for AR. This study aimed at gaining insight into these patient‐related factors.

Methods

This explorative cross‐sectional survey study included a convenience sample of 170 patients with rhinitis and clinical suspicion of allergy at the department of Otorhinolaryngology and Allergology. Patients’ perceived knowledge level, expectations, patient preferences, and fear of side effects of allergy treatment were collected via a self‐report questionnaire developed for the purpose of this study.

Results

22% of all patients (38/170) reported to have knowledge about anti‐allergic treatment. 40% (55/170) of rhinitis patients expected to be cured by the prescribed treatment, whereas 43% (73/170) of patients expected suppression of allergic symptoms. Nasal spray was the preferred route of anti‐allergic drug administration in 30% (52/170) of patients, followed by oral treatment (24%; 42/170), combination therapy (16%; 30/170), and injection therapy (15%; 27/170). More patients would choose a combination treatment with step‐down approach (31%; 53/170) than mono‐therapy with a step‐up approach (20%; 34/170). Fear for side effects was reported mainly for nasal corticosteroids (48%; 81/170) and less for oral antihistamines (33%; 36/170), leucotriene antagonists (21%, 36/170) and immunotherapy (19%, 33/170).

Conclusions

Patients consulting for rhinitis have high expectations of anti‐allergic treatment, prefer a nasal spray above oral treatment, prefer combined treatment rather than monotherapy, and fear adverse events of anti‐allergic treatment.
CD44 enhances invasion of basal-like breast cancer cells by upregulating serine protease and collagen-degrading enzymatic expression and activity
Authors: Montgomery Nicola , Hill Ashleigh , McFarlane Suzanne , Neisen Jessica , O'Grady Anthony , Conlon Susie , Jirstrom Karin , Kay Elaine W , Waugh David JJ
Published: May 2012

Introduction

Basal-like breast cancers (BL-BCa) have the worst prognosis of all subgroups of this disease. Hyaluronan (HA) and the HA receptor CD44 have a long-standing association with cell invasion and metastasis of breast cancer. The purpose of this study was to establish the relation of CD44 to BL-BCa and to characterize how HA/CD44 signaling promotes a protease-dependent invasion of breast cancer (BrCa) cells.

Methods

CD44 expression was determined with immunohistochemistry (IHC) analysis of a breast cancer tissue microarray (TMA). In vitro experiments were performed on a panel of invasive BL-BCa cell lines, by using quantitative polymerase chain reaction (PCR), immunoblotting, protease activity assays, and invasion assays to characterize the basis of HA-induced, CD44-mediated invasion.

Results

Expression of the hyaluronan (HA) receptor CD44 associated with the basal-like subgroup in a cohort of 141 breast tumor specimens (P = 0.018). Highly invasive cells of the representative BL-BCa cell line, MDA-MB-231 (MDA-MB-231Hi) exhibited increased invasion through a basement membrane matrix (Matrigel) and collagen. In further experiments, HA-induced promotion of CD44 signaling potentiated expression of urokinase plasminogen activator (uPA) and its receptor uPAR, and underpinned an increased cell-associated activity of this serine protease in MDA-MB-231Hi and a further BL-BCa cell line, Hs578T cells. Knockdown of CD44 attenuated both basal and HA-stimulated uPA and uPAR gene expression and uPA activity. Inhibition of uPA activity by using (a) a gene-targeted RNAi or (b) a small-molecule inhibitor of uPA attenuated HA-induced invasion of MDA-MB-231Hi cells through Matrigel. HA/CD44 signaling also was shown to increase invasion of MDA-MB-231 cells through collagen and to potentiate the collagen-degrading activity of MDA-MB-231Hi cells. CD44 signaling was subsequently shown to upregulate expression of two potent collagen-degrading enzymes, the cysteine protease cathepsin K and the matrix metalloprotease MT1-MMP. RNAi- or shRNA-mediated depletion of CD44 in MDA-MB-231Hi cells decreased basal and HA-induced cathepsin K and MT1-MMP expression, reduced the collagen-degrading activity of the cell, and attenuated cell invasion through collagen. Pharmacologic inhibition of cathepsin K or RNAi-mediated depletion of MT1-MMP also attenuated MDA-MB-231Hi cell invasion through collagen.

Conclusion

HA-induced CD44 signaling increases a diverse spectrum of protease activity to facilitate the invasion associated with BL-BCa cells, providing new insights into the molecular basis of CD44-promoted invasion.
JMJD6 is a driver of cellular proliferation and motility and a marker of poor prognosis in breast cancer
Authors: Lee Yi Fang , Miller Lance David , Chan Xiu Bin , Black Michael A , Pang Brendan , Ong Chee Wee , Salto-Tellez Manuel , Liu Edison T , Desai Kartiki V
Published: May 2012

Introduction

We developed an analytic strategy that correlates gene expression and clinical outcomes as a means to identify novel candidate oncogenes operative in breast cancer. This analysis, followed by functional characterization, resulted in the identification of Jumonji Domain Containing 6 (JMJD6) protein as a novel driver of oncogenic properties in breast cancer.

Methods

Through microarray informatics, Cox proportional hazards regression was used to analyze the correlation between gene expression and distant metastasis-free survival (DMFS) of patients in 14 independent breast cancer cohorts. JMJD6 emerged as a top candidate gene robustly associated with poor patient survival. Immunohistochemistry, siRNA-mediated silencing, and forced overexpression of JMJD6 in cell-based assays elucidated molecular mechanisms of JMJD6 action in breast cancer progression and shed light on the clinical breast cancer subtypes relevant to JMJD6 action.

Results

JMJD6 was expressed at highest levels in tumors associated with worse outcomes, including ER- and basal-like, Claudin-low, Her2-enriched, and ER+ Luminal B tumors. High nuclear JMJD6 protein was associated with ER negativity, advanced grade, and poor differentiation in tissue microarrays. Separation of ER+/LN- patients that received endocrine monotherapy indicated that JMJD6 is predictive of poor outcome in treatment-specific subgroups. In breast cancer cell lines, loss of JMJD6 consistently resulted in suppressed proliferation but not apoptosis, whereas forced stable overexpression increased growth. In addition, knockdown of JMJD6 in invasive cell lines, such as MDA-MB231, decreased motility and invasion, whereas overexpression in MCF-7 cells slightly promoted motility but did not confer invasive growth. Microarray analysis showed that the most significant transcriptional changes occurred in cell-proliferation genes and genes of the TGF-β tumor-suppressor pathway. High proliferation was characterized by constitutively high cyclin E protein levels. The inverse relation of JMJD6 expression with TGF-β
2
could be extrapolated to the breast cancer cohorts, suggesting that JMJD6 may affect similar pathways in primary breast cancer.

Conclusions

JMJD6 is a novel biomarker of tumor aggressiveness with functional implications in breast cancer growth and migration.
Consensus: a framework for evaluation of uncertain gene variants in laboratory test reporting
Authors: Crockett David K , Ridge Perry G , Wilson Andrew R , Lyon Elaine , Williams Marc S , Narus Scott P , Facelli Julio C , Mitchell Joyce A
Published: May 2012

Accurate interpretation of gene testing is a key component in customizing patient therapy. Where confirming evidence for a gene variant is lacking, computational prediction may be employed. A standardized framework, however, does not yet exist for quantitative evaluation of disease association for uncertain or novel gene variants in an objective manner. Here, complementary predictors for missense gene variants were incorporated into a weighted Consensus framework that includes calculated reference intervals from known disease outcomes. Data visualization for clinical reporting is also discussed.
Editorial: Lipids: fueling the fire in tuberculosis?
Authors: Dixit Vishwa Deep
Published: May 2012

Discussion on Martens et al intriguing initial insights into the potential role of altered cholesterol metabolism in modifying immune response to TB infection.
140 Characters in Search of a Theater
Authors: Muse John H.
Published: May 2012

This article surveys the new forms of drama, performance, and spectatorship created by artists making use of the real-time microblogging website Twitter—as either a forum for performance in itself, or way to extend the boundaries of a more conventionally theatrical performance. He goes on to describe the ways in which social media “are making playwrights, performers, and spectators of us all.”
Let's Put the Seasonality and Trend in Decomposition
Authors: Nydick Robert L. , Weiss Howard J.
Published: May 2012

When discussing forecasting, most textbooks in management science or operations management explain that the values in a time series are a function of seasonality, trend, and random variation. Many textbooks have pictures depicting different patterns of data. We present a workbook that allows the user to manipulate a dynamic picture of these patterns and, in so doing, allows the user to examine the relationship between error measures and forecasting techniques for these different patterns. We also show a result regarding the relationship between the annual trend and the quarterly trend that surprises most of our students.
Teaching Note—Active Learning Exercise: Newspaper Page Layout
Authors: Devia Nelson , Weber Richard
Published: May 2012

This exercise introduces students to the topics of modeling and mixed-integer programming and motivates them to investigate and understand the complexity of day-to-day problems. The activity consists of putting together a sheet of a newspaper using news and advertising items taken from a real newspaper. The objective is to arrive at a layout that has the highest possible value subject to the constraints of space on the sheet and the correct orientation of the items. Thus, the exercise poses a problem of optimization.

The activity has all the necessary elements for use as an introduction to optimization and mixed-integer programming concepts, and it presents the students with a real-world situation that can also be seen as a game or competition. The enthusiasm this creates and the implicit difficulty of the actual problem motivate students to formalize the ideas involved and initiate a study of the basics of optimization techniques.
A. J. Davis’s Belmead
Authors: Bluestone Daniel
Published: May 2012

In 1845 Philip St. George Cocke commissioned Alexander Jackson Davis to design a Gothic revival villa for Belmead. In doing so he radically departed from the tradition of Palladian and classical architecture that had characterized elite Virginia plantations since the mid-eighteenth century. In A. J. Davis’s Belmead: Picturesque Aesthetics in the Land of Slavery, Daniel Bluestone argues that a Davis design resonated differently on the banks of the James River than on the banks of the Hudson. The appeal of Davis’s design lay in its sensitivity to the reciprocity between buildings and landscape, highlighting Cocke’s advocacy of greater stewardship of the land in the place of generations of ruinous agricultural practices. Beyond his villa and his land, Cocke commissioned Davis to design Belmead’s slave quarters. This was an attempt to harmonize himself with his slaves and the nation with an agricultural system based upon chattel slavery rather than yeomen farmers. This essay encourages us to look beyond the universals that often frame architectural history discussions of picturesque aesthetics to situate picturesque designs more precisely within a place-centered context of client vision and socio-cultural meaning.
Amino acid properties may be useful in predicting clinical outcome in patients with Kir6.2 neonatal diabetes
Authors: Fraser Clementine S , Rubio-Cabezas Oscar , Littlechild Jennifer A , Ellard Sian , Hattersley Andrew T , Flanagan Sarah E
Published: May 2012

Background

Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the β-cell KATP channel, are a common cause of neonatal diabetes. The diabetes may be permanent neonatal diabetes mellitus (PNDM) or transient neonatal diabetes mellitus (TNDM), and in ∼20% of patients, neurological features are observed. A correlation between the position of the mutation in the protein and the clinical phenotype has previously been described; however, recently, this association has become less distinct with different mutations at the same residues now reported in patients with different diabetic and/or neurological phenotypes.

Methods

We identified from the literature, and our unpublished series, KCNJ11 mutations that affected residues harbouring various amino acid substitutions (AAS) causing differences in diabetic or neurological status. Using the Grantham amino acid scoring system, we investigated whether the difference in properties between the wild-type and the different AAS at the same residue could predict phenotypic severity.

Results

Pair-wise analysis demonstrated higher Grantham scores for mutations causing PNDM or diabetes with neurological features when compared with mutations affecting the same residue that causes TNDM (P=0.013) or diabetes without neurological features (P=0.016) respectively. In just five of the 25 pair-wise analyses, a lower Grantham score was observed for the more severe phenotype. In each case, the wild-type residue was glycine, the simplest amino acid.

Conclusion

This study demonstrates the importance of the specific AAS in determining phenotype and highlights the potential utility of the Grantham score for predicting phenotypic severity for novel KCNJ11 mutations affecting previously mutated residues.
Robust Estimation of Local Genetic Ancestry in Admixed Populations Using a Nonparametric Bayesian Approach
Authors: Sohn Kyung-Ah , Ghahramani Zoubin , Xing Eric P
Published: May 2012

We present a new haplotype-based approach for inferring local genetic ancestry of individuals in an admixed population. Most existing approaches for local ancestry estimation ignore the latent genetic relatedness between ancestral populations and treat them as independent. In this article, we exploit such information by building an inheritance model that describes both the ancestral populations and the admixed population jointly in a unified framework. Based on an assumption that the common hypothetical founder haplotypes give rise to both the ancestral and the admixed population haplotypes, we employ an infinite hidden Markov model to characterize each ancestral population and further extend it to generate the admixed population. Through an effective utilization of the population structural information under a principled nonparametric Bayesian framework, the resulting model is significantly less sensitive to the choice and the amount of training data for ancestral populations than state-of-the-art algorithms. We also improve the robustness under deviation from common modeling assumptions by incorporating population-specific scale parameters that allow variable recombination rates in different populations. Our method is applicable to an admixed population from an arbitrary number of ancestral populations and also performs competitively in terms of spurious ancestry proportions under a general multiway admixture assumption. We validate the proposed method by simulation under various admixing scenarios and present empirical analysis results from a worldwide-distributed dataset from the Human Genome Diversity Project.
Transvection Is Common Throughout the Drosophila Genome
Authors: Mellert David J , Truman James W
Published: May 2012

Higher-order genome organization plays an important role in transcriptional regulation. In Drosophila, somatic pairing of homologous chromosomes can lead to transvection, by which the regulatory region of a gene can influence transcription in trans. We observe transvection between transgenes inserted at commonly used phiC31 integration sites in the Drosophila genome. When two transgenes that carry endogenous regulatory elements driving the expression of either LexA or GAL4 are inserted at the same integration site and paired, the enhancer of one transgene can drive or repress expression of the paired transgene. These transvection effects depend on compatibility between regulatory elements and are often restricted to a subset of cell types within a given expression pattern. We further show that activated UAS transgenes can also drive transcription in trans. We discuss the implication of these findings for (1) understanding the molecular mechanisms that underlie transvection and (2) the design of experiments that utilize site-specific integration.
Divergent Functions Through Alternative Splicing: The Drosophila
CRMP Gene in Pyrimidine Metabolism, Brain, and Behavior
Authors: Morris Deanna H , Dubnau Josh , Park Jae H , Rawls John M
Published: May 2012

DHP and CRMP proteins comprise a family of structurally similar proteins that perform divergent functions, DHP in pyrimidine catabolism in most organisms and CRMP in neuronal dynamics in animals. In vertebrates, one DHP and five CRMP proteins are products of six genes; however, Drosophila melanogaster has a single CRMP gene that encodes one DHP and one CRMP protein through tissue-specific, alternative splicing of a pair of paralogous exons. The proteins derived from the fly gene are identical over 90% of their lengths, suggesting that unique, novel functions of these proteins derive from the segment corresponding to the paralogous exons. Functional homologies of the Drosophila and mammalian CRMP proteins are revealed by several types of evidence. Loss-of-function CRMP mutation modifies both Ras and Rac misexpression phenotypes during fly eye development in a manner that is consistent with the roles of CRMP in Ras and Rac signaling pathways in mammalian neurons. In both mice and flies, CRMP mutation impairs learning and memory. CRMP mutant flies are defective in circadian activity rhythm. Thus, DHP and CRMP proteins are derived by different processes in flies (tissue-specific, alternative splicing of paralogous exons of a single gene) and vertebrates (tissue-specific expression of different genes), indicating that diverse genetic mechanisms have mediated the evolution of this protein family in animals.
SNP-Ratio Mapping (SRM): Identifying Lethal Alleles and Mutations in Complex Genetic Backgrounds by Next-Generation Sequencing
Authors: Lindner Heike , Raissig Michael T , Sailer Christian , Shimosato-Asano Hiroko , Bruggmann Rémy , Grossniklaus Ueli
Published: May 2012

We present a generally applicable method allowing rapid identification of causal alleles in mutagenized genomes by next-generation sequencing. Currently used approaches rely on recovering homozygotes or extensive backcrossing. In contrast, SNP-ratio mapping allows rapid cloning of lethal and/or poorly transmitted mutations and second-site modifiers, which are often in complex genetic/transgenic backgrounds.
Developing the multitrait concept for functional diversity: lessons from a system rich in functions but poor in species
Authors: Törnroos Anna , Bonsdorff Erik
Published: May 2012

Studies focusing on the linkage between numerical and functional trait diversity frequently consider functional diversity indices but rarely evaluate them empirically or evaluate the use of other than continuous traits such as body size. Here, we present an extensive compilation on functional knowledge of benthic macrofauna using the categorical trait approach and scores of both common and rare species for 25 biological traits, including 102 modalities. We empirically quantify functional trait richness, within‐trait species richness (redundancy), and trait variability on a large regional scale (>1000 km), in three environmentally different areas (basins of a sea), over a long time‐span (10 years). To develop further the usage of multiple categorical traits as an analysis tool, we examine the effect of sampling effort for the understanding of the functional properties of the benthic meta‐assemblages. We also evaluate the relationship between species richness and trait richness in order to understand co‐variation between trait modalities and how traits are packaged within species. Results show that the biological diversity in terms of traits could be distinguished between areas of higher and lower salinity, higher and lower anthropogenic stress, and higher and lower species richness. A considerably lower number of samples are needed to portray the functional structure of an area in relation to the taxonomic structure, thereby demonstrating the advantage of using traits when considering management and conservation issues. Using categorical traits empirically requires, as shown within this study, an understanding of the relationship between species richness and expression of traits, co‐variation of traits at different species richness and composition levels, acknowledgment of differences in trait expressions between common and rare species, and variability in abundance of species. Empirical trait‐based analysis can reveal large‐scale differences and insights into complexities between assemblage structure and function, and simultaneously be a valid tool for finding generalities.
The World Bank's Shift Away from Neoliberal Ideology: Real or Rhetoric?
Authors: Adhikary Rino Wiseman
Published: May 2012

Some literature on World Bank education policies after 1999 tries to project a shift away of the Bank from its 1980s neoliberal mandate. This article argues that the shift is only in the form of rhetoric, which facilitates a hidden agenda of creating a worldwide higher education market, leaving the poor with primary education only. At the rhetorical level there is a greater concern for poverty and equity, showing the importance of primary education for the poor, but at an operational level the policies still are conducive to a market-driven approach to higher education.
Logarithmic Time: Its Role in Current Culture and Education
Authors: Cottey Alan
Published: May 2012

The timescales relevant for human culture cover a very wide range. A better appreciation of these timescales would facilitate an adequate response to humanity's ecological ‘slow reckoning’. This article discusses the use and presentation of simple logarithmic timescales and advocates their widespread use in education.
Mice deficient in p52/NF-κB as a model for studying prion disease
Authors: Poljak Ljiljana
Published: May 2012

A tight functional link between the central nervous and peripheral immune system closely related to the activity of NF-κB transcription factor has been evidenced in numerous brain pathological conditions. One of the most instructive examples is a prion neuroinvasion and the development of transmissible spongioform encephalopathy (TSE) or prion diseases. The failure of peripherally administrated prions to elicit disease in immune-deficient mice indicates that preserved organ microarchitecture is crucial for TSE pathogenesis and it seems to go through topographic relationships between follicular dendritic cells and sympathetic endings in lymphoid organs. New insight into the molecular requirements for follicular dendritic cell (FDC) development in NF-κB p52 deficient mice highlights the role of NF-κB transcription factor in prion disease progression. However, adoptive transfer of wild type bone marrow cells (NF-κB +/+ background) into p52 deficient animals (NF-κB -/- background) does not correct the FDC defect. RT-PCR analysis of the expression level of mRNA for LTa, LTb, TNFRI and BLC of the splenic cells from p52/NF-κB mutant/wt BM chimera did not reveal major changes compared to wt/wt BM chimeras, indicating that their normal expression within splenic tissue does not assure for complete restoration of the FDC network in p52/NF-κB mutant. This implies that the distance between FDCs and splenic nerve terminals around the central arteriole is longer and could interfere with prion spreading in lymphoid organs prior to neuroinvasion. In light of the fact that prion neuroinvasion highly depends on the physical distance between sympathetic nerve endings and FDCs dendritic extensions, it is not hard to imagine that this could be the way to approach the problem of prion diseases development.
Malignant transformation of grade II ganglioglioma to glioblastoma: A case report
Authors: Čupić Hrvoje , Sajko Tomislav , Sesar Nikolina , Ivica Mihovil , Pažanin Leo
Published: May 2012

Gangliogliomas are well differentiated and slowly growing neuroepithelial tumors composed of neoplastic ganglion cells and neoplastic glial cells corresponding mostly to the World Health Organization grade I tumors. However, some of these tumors disclose histologically more malignant glial component and correspond to grade II or grade III tumors. We report a case of left temporal lobe tumor in a 42-year-old woman fulfilling the diagnostic criteria for atypical (grade II) ganglioglioma with high Ki-67 proliferation index and p53 immunoreactive tumor cells. In spite of gross total removal of the tumor, it recurred eight months after surgery. Histopathological examination of the recurrent tumor revealed that it had undergone malignant transformation into a glioblastoma. This case indicates that gangliogliomas with high Ki-67 proliferating index and p53 immunoreactivity should be carefully monitored for recurrence and malignant progression regardless of their morphological grading and seemingly total surgical removal.
PTEN: A molecular target for neurodegenerative disorders
Authors: Ismail Azza , Ning Ke , Al-Hayani Abdulmonem , Sharrack Basil , Azzouz Mimoun
Published: May 2012

PTEN (phosphatase and tensin homologue deleted in chromosome 10) was first identified as a candidate tumour suppressor gene located on chromosome 10q23. It is considered as one of the most frequently mutated genes in human malignancies. Emerging evidence shows that the biological function of PTEN extends beyond its tumour suppressor activity. In the central nervous system PTEN is a crucial regulator of neuronal development, neuronal survival, axonal regeneration and synaptic plasticity. Furthermore, PTEN has been linked to the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Recently increased attention has been focused on PTEN as a potential target for the treatment of brain injury and neurodegeneration. In this review we discuss the essential functions of PTEN in the central nervous system and its involvement in neurodegeneration.
Genetic animal models of Tourette syndrome: The long and winding road from lab to clinic
Authors: Cauchi Ruben , Tárnok Zsanett
Published: May 2012

Tourette syndrome (TS) is a disabling neuropsychiatric disorder characterised by persistent motor and vocal tics. TS is a highly comorbid state, hence, patients might experience anxiety, obsessions, compulsions, sleep abnormalities, depression, emotional liability, learning problems, and attention deficits in addition to tics. In spite of its complex heterogeneous genetic aetiology, recent studies highlighted a strong link between TS and genetic lesions in the HDC (L-histidine decarboxylase) gene, which encodes the enzyme that synthetises histamine, and the SLITRK1 (SLIT and TRK-like family member 1) gene, which encodes a transmembrane protein that was found to regulate neurite outgrowth. In addition to validating the contribution of a specific genetic aberration to the development of a particular pathology, animal models are crucial to dissect the function of disease-linked proteins, expose disease pathways through examination of genetic modifiers and discover as well as assess therapeutic strategies. Mice with a knockout of either Hdc or Slitrk1 exhibit anxiety and those lacking Hdc, display dopamine agonist-triggered stereotypic movements. However, the mouse knockouts do not spontaneously display tics, which are recognised as the hallmark of TS. In this review, we explore the features of the present genetic animal models of TS and identify reasons for their poor resemblance to the human condition. Importantly, we highlight ways forward aimed at developing a valuable genetic model of TS or a model that has good predictive validity in developing therapeutic drugs for the treatment of tics, hence potentially accelerating the arduous journey from lab to clinic.
Attentional biases to threat and serotonin transporter gene promoter (5-HTLPR) polymorphisms: Evidence from a probe discrimination task with endogenous cues
Authors: Miu Andrei , Vulturar Romana , Chiş Adina , Ungureanu Loredana
Published: May 2012

Recent studies have investigated the association between serotonin transporter gene promoter (5-HTTLPR) functional polymorphisms and attentional biases to threat, a cognitive mechanism that probably contributes to the development and maintenance of anxiety. The present study genotyped a sample of N = 141 healthy volunteers for an insertion/deletion polymorphism and the rs25531 single-nucleotide polymorphism in 5-HTTLPR. In order to investigate attentional biases to threat, we used a probe discrimination task in which the gaze direction of centrally presented fearful or neutral faces endogenously cued attention. The results indicated no significant differences in attentional biases to threat between 5-HTTLPR genotype groups. However, we found that carriers of two low-expressing alleles (i.e., S or LG) of 5-HTTLPR displayed a significant slowing of responses across trials with fearful compared to neutral faces. This effect may indicate that fearful faces triggered increased emotional arousal in these genotypes, which may have interfered with the processing of gaze direction and spatial cuing. These results suggest that using fearful faces as endogenous spatial cues may be problematic in genotypes associated with facilitated emotional arousal to these stimuli, and underscore the hypothesis that 5-HTTLPR specifically influences automatic rather than consciously-controlled processes of attention.
Models of CNS injury in the nonhuman primate: A new era for treatment strategies
Authors: Teo Leon , Rosenfeld Jeffrey , Bourne James
Published: May 2012

Central nervous system (CNS) injuries affect all levels of society indiscriminately, resulting in functional and behavioral deficits with devastating impacts on life expectancies, physical and emotional wellbeing. Considerable literature exists describing the pathophysiology of CNS injuries as well as the cellular and molecular factors that inhibit regrowth and regeneration of damaged connections. Based on these data, numerous therapeutic strategies targeting the various factors of repair inhibition have been proposed and on-going assessment has demonstrated some promising results in the laboratory environ. However, several of these treatment strategies have subsequently been taken into clinical trials but demonstrated little to no improvement in patient outcomes. As a result, options for clinical interventions following CNS injuries remain limited and effective restorative treatment strategies do not as yet exist. This review discusses some of the current animal models, with focus on nonhuman primates, which are currently being modeled in the laboratory for the study of CNS injuries. Last, we review the current understanding of the mechanisms underlying repair/regrowth inhibition and the current trends in experimental treatment strategies that are being assessed for potential translation to clinical applications.
Differential optics for illumination design in the presence of caustics
Authors: Ott P. , Yu L.
Published: May 2012

Alternatively to using time-consuming Monte-Carlo simulations the irradiation at a target plane can also be calculated by differential optics methods. In the case of caustics, these methods yield to infinite irradiance and its results are not directly comparable to those of Monte-Carlo simulations. In this paper, a differential based algorithm for an on axis point source and a rotationally symmetric optical system is presented, which yields to the same results as a Monte-Carlo simulation. However, the differential optical methods are about three orders of magnitude faster than the latter one, thus allowing fast trial and error design of such kind of illumination systems. An applet is presented that uses sliders to change the shape of the lens and other properties of the illumination system whereas the irradiance profile is nearly immediately perceived. For beginners in the field, this does not only accelerate the design process itself but also the learning process is improved considerably. Some extensions and special cases are shortly discussed.
The Cost of Providing an Adequate Education to English Language Learners
Authors: Jimenez-Castellanos Oscar , Topper Amelia M.
Published: May 2012

This article systematically reviews the cost study literature as it relates to the treatment of English language learners (ELLs). Despite the substantial number of costing out studies that have been conducted over the past several decades, the school finance literature has failed to focus on ELLs—the fastest growing segment of the school-age population. Little attention has been paid to how ELL students are treated under the various costing out methodologies or which approaches yield the most useful results. The two criterion to select the costing out literature to review included (a) peer-reviewed journal articles and commissioned reports that used one of the four primary cost study methodologies (professional judgment panel, successful school model, evidence-based model, and cost function analysis), and (b) studies published after 1990 that focused on generating statewide funding recommendations at the district level. A total of 70 empirical cost studies met these criteria. The review concludes that there is substantial variability in the treatment of ELLs across cost study methodologies, although all methods agree that current funding levels are insufficient to meet specified performance standards. To comprehensively assess the resource needs of this growing school population, cost studies that specifically focus on ELLs will need to be conducted to improve transparency and representativeness for ELLs.
Reflections on “A Review of Trends in Serious Gaming”
Authors: Tobias Sigmund , Fletcher J. D.
Published: May 2012

This article briefly summarizes findings from a review of 95 empirical studies of games used in instruction. The article suggests that such efforts are best assessed as transfer from game play to performance on external tasks that are targeted by the instruction. Review findings suggest that such transfer may be expected only if the cognitive processes engaged by games and external tasks overlap. Integrating games into a course of study is likely to facilitate such transfer. Research on improvement in cognitive processes as a result of playing “first-person shooter” games is briefly overviewed, and suggestions for similar research not using aggressive content are made. Minimal overlap between this and another research review of the effects of games used in instruction is discussed, and the need for generally accepted definitions and a taxonomy of games is noted.
Culturalisation at an Australian–Swedish Crossroads
Authors: Fornäs Johan , Fredriksson Martin
Published: May 2012

No abstract available.
Whose Canon? Culturalization versus Democratization
Authors: Bjurström Erling
Published: May 2012

Current accounts – and particularly the critique – of canon formation are primarily based on some form of identity politics. In the 20th century a representational model of social identities replaced cultivation as the primary means to democratize the canons of the fine arts. In a parallel development, the discourse on canons has shifted its focus from processes of inclusion to those of exclusion. This shift corresponds, on the one hand, to the construction of so-called alternative canons or counter-canons, and, on the other hand, to attempts to restore the authority of canons considered to be in a state of crisis or decaying. Regardless of the democratic stance of these efforts, the construction of alternatives or the reestablishment of decaying canons does not seem to achieve their aims, since they break with the explicit and implicit rules of canon formation. Politically motivated attempts to revise or restore a specific canon make the workings of canon formation too visible, transparent and calculated, thereby breaking the spell of its imaginary character. Retracing the history of the canonization of the fine arts reveals that it was originally tied to the disembedding of artists and artworks from social and worldly affairs, whereas debates about canons of the fine arts since the end of the 20th century are heavily dependent on their social, cultural and historical reembedding. The latter has the character of disenchantment, but has also fettered the canon debate in notions of “our” versus “their” culture. However, by emphasizing the dedifferentiation of contemporary processes of culturalization, the advancing canonization of popular culture seems to be able to break with identity politics that foster notions of “our” culture in the present thinking on canons, and push it in a more transgressive, syncretic or hybrid direction.
High Performance Shape Memory Polyurethane Synthesized with High Molecular Weight Polyol as the Soft Segment
Authors: Ahmad Manzoor , Xu Bin , Purnawali Hendra , Fu Yongqing , Huang Weimin , Miraftab Mohsen , Luo Jikui
Published: May 2012

Shape memory polyurethanes (SMPUs) are typically synthesized using polyols of low molecular weight (MW~2,000 g/mol) as it is believed that the high density of cross-links in these low molecular weight polyols are essential for high mechanical strength and good shape memory effect. In this study, polyethylene glycol (PEG-6000) with MW ~6000 g/mol as the soft segment and diisocyanate as the hard segment were used to synthesize SMPUs, and the results were compared with the SMPUs with polycaprolactone PCL-2000. The study revealed that although the PEG-6000-based SMPUs have lower maximum elongations at break (425%) and recovery stresses than those of PCL-based SMPUs, they have much better recovery ratios (up to 98%) and shape fixity (up to 95%), hence better shape memory effect. Furthermore, PEG-based SMPUs showed a much shorter actuation time of < 10 s for up to 90% shape recovery compared to typical actuation times of tens of seconds to a few minutes for common SMPUs, demonstrated their great potential for applications in microsystems and other engineering components.