bluuebunny/crossref_metadata_2025 huggingface dataset:
Private and Public Ageing in the UK
Authors: Ballard Karen D. , Elston Mary Ann , Gabe Jonathan
Published: February 2009

Sociological discussions of the menopause have focused largely on the ways in which women's experiences are socially and culturally shaped, with second wave feminists resisting a biomedical model of the menopause as a deficiency disease. Yet in emphasizing the social and cultural meaning, little attention has been given to women's experiences of the menopause as an embodied transition. This article presents findings from a qualitative data analysis. The authors draw on their previous findings of private and public ageing and show how British women experience both `public', visible age-related changes in body appearance and `private', invisible age-related physiological body changes that they attribute to the menopause. Within private ageing, women report the changes in ovarian physiology as altering their reproductive status, and they thus experience the emergence of a new identity.
Finnish Commercial Web-Based Information on Male Menopause and Male Hormone Therapy
Authors: Vainionpää Kirsi J.
Published: February 2009

The Internet is used by lay people interested in their well-being and health. The objective in this article is to study male menopause by analysing the themes the Internet provides about male menopause and its treatments and to evaluate the quality of commercial web-based information by comparing it to the scientific information. The data were drawn from a selection of Finnish websites that Finnish men would be able to access. Seven different themes emerged in the material: healthism, a quasi-professional attitude, uncertainty, risk, mood-enhancement effects, good sex and similarity to women. The online information did not correspond to current scientific medical information. These seven themes produce a new form of illness — male menopause — and its treatment with male hormone therapy. The themes contribute to the constitution of medicalized bodies by encouraging men to use testosterone medication.
Ikajarutit: delivering legislative library services in an Inuktitut language environment
Authors: Earle Yvonne
Published: February 2009

Nunavut Territory came into existence April 1, 1999. From the outset it was seen as a chance to shape institutions to preserve Inuit language, culture and tradition. No other Canadian province or territory has a majority of people speaking a single aboriginal language and it is a goal of the Government of Nunavut that by 2020 Inuktitut will be the working language of government. In this environment, the Legislative Library works to build collections, deliver services and develop staff competencies in Inuktitut language and library skills.
Between National Security and Ethno-nationalism
Authors: McDuie-RA Duncan
Published: February 2009

Although scholarly interest in Northeast India is growing there is still relatively little discussion of the high levels of poverty in the region and the failures of development. When mentioned they are viewed instrumentally as causes and/or symptoms of ongoing insurgency and counter-insurgency. However this does not fully explain how a region that receives an extraordinarily large amount of development funding from the Indian Government, has its own development ministry, has some of India’s highest human development indicators, and has an array of institutional layers assuring autonomy and decentralisation has poverty levels well above the Indian national average. Using the state of Meghalaya, this article examines the factors underpinning the development agenda in the region and the political space for contesting this agenda. The argument presented is three-fold; the regional development agenda is underpinned by national security imperatives which characterise relations between the various levels of governance ensuring minimal deviation, contestation of the development agenda is limited by national security from above and ethno-nationalism from below narrowing the political space for negotiating development alternatives, and this situation is the result of material and ideational factors embedding development in the politics of state-formation and ethnic identity.
Ownership and Performance of the Indian Banking Industry
Authors: Bhaduri Saumitra N , Shanmugam KR
Published: February 2009

This study contributes to the ownership–performance literature by analysing the issue for the Indian banking sector during the post reform period (1992–2007). Results indicate that both foreign and domestic private banks are superior to their public counterparts with respect to four performance indicators namely, Return on Asset, Operating Profit Ratio, Operating Cost Ratio and Staff Expense Ratio. The one indicator in which the private banks are less efficient than their counterpart is Net Interest Margin. Furthermore, the foreign banks seem to be superior among the private banks, while the State bank group shows better performance among the public banks. The results also highlight a convergence in the performances across various ownership groups over the reform period. The competitiveness due to reform measures seems to help the poor performing banks in reducing the performance gap. Since publicly owned banks still perform poorly, privatisation seems to be an effective policy in improving the performance of Indian banks.
The diversity of youth citizenships in the European Union
Authors: Hoikkala Tommi
Published: February 2009

The aim of this article is to demonstrate the diversity of youth civic action by pre-senting several examples of what young citizenship concretely is and can be in the European Union (EU). This will be done by placing Theodore Marshall's (1950) classical, modern formulation of citizenship in different contemporary contexts, and thus also going beyond the modern conception of citizenship. Contexts such as the globalizing world, new conditions for transitions into adulthoods, new forms of political participation of youth, and the transformation of politics (media politics) as well as consumption will be elaborated upon. In addition to Marshall's triad — civic, political and social — media citizenship, consumer citizenship, cosmopolitan and global citizenship will be discussed as new types of civic virtue (late modern civic virtue). The genre of the article falls into the special category of reflectively open research texts with a touch of a criticism and politicization. The text is not based on any specific empirical corpus as research texts conventionally are.
Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease
Authors: Sato Kaori , Eizumi Kawori , Fukaya Tomohiro , Fujita Shigeharu , Sato Yumiko , Takagi Hideaki , Yamamoto Mai , Yamashita Naohide , Hijikata Atsushi , Kitamura Hiroshi , Ohara Osamu , Yamasaki Sho , Saito Takashi , Sato Katsuaki
Published: February 2009

Chronic graft-versus-host disease (cGVHD) is a limiting factor in allogeneic hematopoietic stem cell transplantation (alloHSCT) for the treatment of leukemia and other malignancies. Relative to the process that initiates and promotes cGVHD, the regulation is poorly understood. In this study, we examined the role of naturally occurring regulatory dendritic cells (DCregs) in murine major histocompatibility complex (MHC)-compatible and multiple minor histocompatibility antigen (miHAg)–incompatible model of cGVHD in alloHSCT. DCregs generated from bone marrow in vitro (BM-DCregs) exclusively expressed CD200 receptor 3 (CD200R3), which exerted a suppressive function in the Ag-specific CD4+ T-cell response. CD49+CD200R3+ cells showed similarities in phenotype and function to BM-DCregs, which formally distinguishes them from other leukocytes, suggesting that they are the natural counterpart of BM-DCregs. Treatment of the recipient mice after alloHSCT with the recipient-type CD49+CD200R3+ cells as well as BM-DCregs protected against cGVHD, and the protection was associated with the generation of Ag-specific anergic CD4+ T cells as well as CD4+CD25+Foxp3+ regulatory T cells (Tregs) from donor-derived alloreactive CD4+CD25−Foxp3− T cells. In addition, the depletion of CD49+CD200R3+ cells before alloHSCT enhanced the progression of cGVHD. In conclusion, CD49+CD200R3+ cells act as naturally occurring DCregs to regulate the pathogenesis of cGVHD in alloHSCT mediated through the control of the transplanted alloreactive CD4+ T cells.
Common processes in pathogenesis by fungal and oomycete plant pathogens, described with Gene Ontology terms
Authors: Meng Shaowu , Torto-Alalibo Trudy , Chibucos Marcus C , Tyler Brett M , Dean Ralph A
Published: February 2009

Plant diseases caused by fungi and oomycetes result in significant economic losses every year. Although phylogenetically distant, the infection processes by these organisms share many common features. These include dispersal of an infectious particle, host adhesion, recognition, penetration, invasive growth, and lesion development. Previously, many of these common processes did not have corresponding Gene Ontology (GO) terms. For example, no GO terms existed to describe processes related to the appressorium, an important structure for infection by many fungi and oomycetes. In this mini-review, we identify common features of the pathogenic processes of fungi and oomycetes and create a pathogenesis model using 256 newly developed and 38 extant GO terms, with an emphasis on the appressorium and signal transduction. This set of standardized GO terms provides a solid base to further compare and contrast the molecular underpinnings of fungal and oomycete pathogenesis.
Removal of Hsf4 leads to cataract development in mice through down-regulation of γS-crystallin and Bfsp expression
Authors: Shi Xiaohe , Cui Bin , Wang Zhugang , Weng Lin , Xu Zhongping , Ma Jinjin , Xu Guotong , Kong Xiangyin , Hu Landian
Published: February 2009

Background

Heat-shock transcription factor 4 (HSF4) mutations are associated with autosomal dominant lamellar cataract and Marner cataract. Disruptions of the Hsf4 gene cause lens defects in mice, indicating a requirement for HSF4 in fiber cell differentiation during lens development. However, neither the relationship between HSF4 and crystallins nor the detailed mechanism of maintenance of lens transparency by HSF4 is fully understood.

Results

In an attempt to determine how the underlying biomedical and physiological mechanisms resulting from loss of HSF4 contribute to cataract formation, we generated an Hsf4 knockout mouse model. We showed that the Hsf4 knockout mouse (Hsf4
-/-) partially mimics the human cataract caused by HSF4 mutations. Q-PCR analysis revealed down-regulation of several cataract-relevant genes, including γS-crystallin (Crygs) and lens-specific beaded filament proteins 1 and 2 (Bfsp1 and Bfsp2), in the lens of the Hsf4
-/- mouse. Transcription activity analysis using the dual-luciferase system suggested that these cataract-relevant genes are the direct downstream targets of HSF4. The effect of HSF4 on γS-crystallin is exemplified by the cataractogenesis seen in the Hsf4
-/-,rncat intercross. The 2D electrophoretic analysis of whole-lens lysates revealed a different expression pattern in 8-week-old Hsf4
-/- mice compared with their wild-type counterparts, including the loss of some αA-crystallin modifications and reduced expression of γ-crystallin proteins.

Conclusion

Our results indicate that HSF4 is sufficiently important to lens development and disruption of the Hsf4 gene leads to cataracts via at least three pathways: 1) down-regulation of γ-crystallin, particularly γS-crystallin; 2) decreased lens beaded filament expression; and 3) loss of post-translational modification of αA-crystallin.
The sweet taste quality is linked to a cluster of taste fibers in primates: lactisole diminishes preference and responses to sweet in S fibers (sweet best) chorda tympani fibers of M. fascicularis monkey
Authors: Wang Yiwen , Danilova Vicktoria , Cragin Tiffany , Roberts Thomas W , Koposov Alexey , Hellekant Göran
Published: February 2009

Background

Psychophysically, sweet and bitter have long been considered separate taste qualities, evident already to the newborn human. The identification of different receptors for sweet and bitter located on separate cells of the taste buds substantiated this separation. However, this finding leads to the next question: is bitter and sweet also kept separated in the next link from the taste buds, the fibers of the taste nerves? Previous studies in non-human primates, P. troglodytes, C. aethiops, M. mulatta, M. fascicularis and C. jacchus, suggest that the sweet and bitter taste qualities are linked to specific groups of fibers called S and Q fibers. In this study we apply a new sweet taste modifier, lactisole, commercially available as a suppressor of the sweetness of sugars on the human tongue, to test our hypothesis that sweet taste is conveyed in S fibers.

Results

We first ascertained that lactisole exerted similar suppression of sweetness in M. fascicularis, as reported in humans, by recording their preference of sweeteners and non- sweeteners with and without lactisole in two-bottle tests. The addition of lactisole significantly diminished the preference for all sweeteners but had no effect on the intake of non-sweet compounds or the intake of water. We then recorded the response to the same taste stimuli in 40 single chorda tympani nerve fibers. Comparison between single fiber nerve responses to stimuli with and without lactisole showed that lactisole only suppressed the responses to sweeteners in S fibers. It had no effect on the responses to any other stimuli in all other taste fibers.

Conclusion

In M. fascicularis, lactisole diminishes the attractiveness of compounds, which taste sweet to humans. This behavior is linked to activity of fibers in the S-cluster. Assuming that lactisole blocks the T1R3 monomer of the sweet taste receptor T1R2/R3, these results present further support for the hypothesis that S fibers convey taste from T1R2/R3 receptors, while the impulse activity in non-S fibers originates from other kinds of receptors. The absence of the effect of lactisole on the faint responses in some S fibers to other stimuli as well as the responses to sweet and non-sweet stimuli in non-S fibers suggest that these responses originate from other taste receptors.
Vitrification of isolated mice blastomeres using a closed loading device
Authors: Kader Amr , Agarwal Ashok , Sharma Rakesh , Falcone Tommaso
Published: February 2009

Isolated blastomeres obtained by embryo biopsy serve mainly for preimplantation genetic screening. Blastomeres are undifferentiated embryonic cells that include all the embryo genetic information. A lot of developing technologies may benefit by the efficient cryopreservation of blastomeres for future potential use, especially for stem cell culture and differentiation control. We are hereby reporting for the first time the feasibility of preserving individual isolated blastomeres in microvolumes in a closed vitrification system. Using a cryotip and propagation in microvolumes, isolated mice blastomeres were vitrified and warmed with 100% post-warming survival.
Ejaculate collection efficiency and post-thaw semen quality in wild-caught Griffon vultures from the Sardinian population
Authors: Madeddu Manuela , Berlinguer Fiammetta , Ledda Massimo , Leoni Giovanni G , Satta Valentina , Succu Sara , Rotta Andrea , Pasciu Valeria , Zinellu Angelo , Muzzeddu Marco , Carru Ciriaco , Naitana Salvatore
Published: February 2009

This study aimed to test the feasibility of a programme of semen collection and cryopreservation in Griffon vultures. Four wild-caught individuals kept in captivity because of unrecoverable traumas were used. Semen collection attempts were made twice a week during three consecutive reproductive seasons (December – March) using the abdominal massage method. Ejaculation was successfully induced between late January and late February. Semen collection efficiency was rather low (27.9%) and it did not vary among individuals (p > 0.05). No differences were found in ejaculate volumes (12.5 +/- 9.1 μl), spermatozoa concentration (28.4 +/- 30.9 million cells/ml) and viability (61.3 +/- 13.9%) among the 4 vultures. ATP values differed among the four vultures (p < 0.001); B showed higher nucleotide concentration than both C and D, while it did not differ form A, whose values were higher compared with D. After freezing and thawing, semen in vitro viability, DNA integrity and ATP intracellular concentration were determined. Spermatozoa viability after thawing did not differ among the four individuals (52.6 +/- 5.8 in A, 53.4 +/- 4.6 in B, 50.4 +/- 3.2 in C, 42.5 +/- 2.7 in D), but it decreased significantly compared to fresh semen (p < 0.05). During 4 hrs in vitro culture, spermatozoa collected from B maintained over time a higher viability in vitro when compared to A, C and D. As evaluated by the comet assay method, DNA fragmentation after freezing and thawing did not differ in the 4 vultures. ATP concentration in frozen/thawed semen was significantly lower than in fresh semen (p < 0.0001). This study indicates that semen cryopreservation can be considered as a useful tool in the conservation of Griffon vulture genetic resources, but further studies are needed to optimize this technique.
Attention Deficit Hyperactivity Disorder comorbid oppositional defiant disorder and its predominately inattentive type: evidence for an association with COMT but not MAOA in a Chinese sample
Authors: Qian Qiu-Jin , Liu Jin , Wang Yu-Feng , Yang Li , Guan Li-Li , Faraone Stephen V
Published: February 2009

Background

There are three childhood disruptive behavior disorders (DBDs), attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). The most common comorbid disorder in ADHD is ODD. DSM-IV describes three ADHD subtypes: predominantly inattentive type (ADHD-IA), predominantly hyperactive-impulsive type (ADHD-HI), and combined type (ADHD-C). Prior work suggests that specific candidate genes are associated with specific subtypes of ADHD in China. Our previous association studies between ADHD and functional polymorphisms of COMT and MAOA, consistently showed the low transcriptional activity alleles were preferentially transmitted to ADHD-IA boys. Thus, the goal of the present study is to test the hypothesis that COMT Val158Met and MAOA-uVNTR jointly contribute to the ODD phenotype among Chinese ADHD boys.

Methods

171 Chinese boys between 6 and 17.5 years old (mean = 10.3, SD = 2.6) with complete COMT val158met and MAOA-uVNTR genotyping information were studied. We used logistic regression with genotypes as independent variables and the binary phenotype as the dependent variable. We used p < 0.05 as the level of nominal statistical significance. Bonferroni correction procedures were used to adjust for multiple comparisons.

Results

Our results highlight the potential etiologic role of COMT in the ADHD with comorbid ODD and its predominately inattentive type in male Chinese subjects. ADHD with comorbid ODD was associated with homozygosity of the high-activity Val allele, while the predominantly inattentive ADHD subtype was associated with the low-activity Met allele. We found no evidence of association between the MAOA-uVNTR variant and ADHD with comorbid ODD or the ADHD-IA subtype.

Conclusion

Our study of attention deficit hyperactivity disorder comorbid oppositional defiant disorder and its predominately inattentive type highlights the potential etiologic role of COMT for ADHD children in China. But we failed to observe an interaction between COMT and MAOA, which suggests that epistasis between COMT and MAOA genes does not influence the phenotype of ADHD-IA with comorbid ODD in a clinical sample of Chinese male subjects. To confirm our findings further studies with a larger number of subjects and healthy controls are needed.
High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays
Authors: Wang Yuker , Carlton Victoria EH , Karlin-Neumann George , Sapolsky Ronald , Zhang Li , Moorhead Martin , Wang Zhigang C , Richardson Andrea L , Warren Robert , Walther Axel , Bondy Melissa , Sahin Aysegul , Krahe Ralf , Tuna Musaffe , Thompson Patricia A , Spellman Paul T , Gray Joe W , Mills Gordon B , Faham Malek
Published: February 2009

Background

A major challenge facing DNA copy number (CN) studies of tumors is that most banked samples with extensive clinical follow-up information are Formalin-Fixed Paraffin Embedded (FFPE). DNA from FFPE samples generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking during FFPE fixation and processing. As FFPE protocols may vary widely between labs and samples may be stored for decades at room temperature, an ideal FFPE CN technology should work on diverse sample sets. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from cell line and frozen tumor DNA. Since the MIP probes require only a small (~40 bp) target binding site, we reasoned they may be well suited to assess degraded FFPE DNA. We assessed CN with a MIP panel of 50,000 markers in 93 FFPE tumor samples from 7 diverse collections. For 38 FFPE samples from three collections we were also able to asses CN in matched fresh frozen tumor tissue.

Results

Using an input of 37 ng genomic DNA, we generated high quality CN data with MIP technology in 88% of FFPE samples from seven diverse collections. When matched fresh frozen tissue was available, the performance of FFPE DNA was comparable to that of DNA obtained from matched frozen tumor (genotype concordance averaged 99.9%), with only a modest loss in performance in FFPE.

Conclusion

MIP technology can be used to generate high quality CN and genotype data in FFPE as well as fresh frozen samples.
Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability
Authors: Pascual-Ramos Virginia , Contreras-Yáñez Irazú , Villa Antonio R , Cabiedes Javier , Rull-Gabayet Marina
Published: February 2009

Introduction

Aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators.

Methods

Charts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Student's t test, the chi-squared test, and logistic regression analyses were used.

Results

The proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P ≤ 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (≥ 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 ± 4.6 versus 13.6 ± 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P ≤ 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age at baseline was associated with therapy discontinuation (odds ratio = 1.1, 95% confidence interval = 1.007 to 1.103, P = 0.02).

Conclusions

Discontinuation of DMARDs was frequent and progressive in an early RA cohort. Patients with persistence on therapy were younger, had lower disease activity and disability during follow-up, and reached sustained remission more frequently and earlier than patients without it. MP should intentionally be evaluated during follow-up of early RA patients, as it seems to play a major role in outcome.
Global analysis of alternative splicing regulation by insulin and wingless signaling in Drosophilacells
Authors: Hartmann Britta , Castelo Robert , Blanchette Marco , Boue Stephanie , Rio Donald C , Valcárcel Juan
Published: February 2009

Background

Despite the prevalence and biological relevance of both signaling pathways and alternative pre-mRNA splicing, our knowledge of how intracellular signaling impacts on alternative splicing regulation remains fragmentary. We report a genome-wide analysis using splicing-sensitive microarrays of changes in alternative splicing induced by activation of two distinct signaling pathways, insulin and wingless, in Drosophila cells in culture.

Results

Alternative splicing changes induced by insulin affect more than 150 genes and more than 50 genes are regulated by wingless activation. About 40% of the genes showing changes in alternative splicing also show regulation of mRNA levels, suggesting distinct but also significantly overlapping programs of transcriptional and post-transcriptional regulation. Distinct functional sets of genes are regulated by each pathway and, remarkably, a significant overlap is observed between functional categories of genes regulated transcriptionally and at the level of alternative splicing. Functions related to carbohydrate metabolism and cellular signaling are enriched among genes regulated by insulin and wingless, respectively. Computational searches identify pathway-specific sequence motifs enriched near regulated 5' splice sites.

Conclusions

Taken together, our data indicate that signaling cascades trigger pathway-specific and biologically coherent regulatory programs of alternative splicing regulation. They also reveal that alternative splicing can provide a novel molecular mechanism for crosstalk between different signaling pathways.
La Citoyenne in the World: Hubertine Auclert and Feminist Imperialism
Authors: Eichner Carolyn J.
Published: February 2009

Hubertine Auclert founded the feminist newspaper La citoyenne in 1881, primarily to advocate French women's suffrage and full citizenship. The periodical also looked beyond national borders, presaging later feminists' interest in women and empire. The publication compared the circumstances of French women with those of women in other nations and cultures and in the colonies. Frequently concluding that French women held a preferable position, Auclert and her fellow writers also emphasized aspects of “uncivilized” women's lives and status that compared positively to those in the metropole. La citoyenne questioned France's level of civilization under a legal code that disenfranchised and subjugated its entire female population. The journalists thus disrupted the absolutes of supposedly civilized France and uncivilized colonies. Appropriating and adapting the era's anthropological hierarchies of civilization and race, Auclert and her contributors developed a feminist imperialism that challenged women's oppression both in the metropole and in the colonies, striving to subsume cultural differences into a feminist-influenced, universalized French identity.
The Wnt antagonists Frzb-1 and Crescent locally regulate basement membrane dissolution in the developing primary mouth
Authors: Dickinson Amanda J. G. , Sive Hazel L.
Published: February 2009

The primary mouth forms from ectoderm and endoderm at the extreme anterior of the embryo, a conserved mesoderm-free region. In Xenopus, a very early step in primary mouth formation is loss of the basement membrane between the ectoderm and endoderm. In an unbiased microarray screen, we defined genes encoding the sFRPs Frzb-1 and Crescent as transiently and locally expressed in the primary mouth anlage. Using antisense oligonucleotides and `face transplants', we show that frzb-1 and crescent expression is specifically required in the primary mouth region at the time this organ begins to form. Several assays indicate that Frzb-1 and Crescent modulate primary mouth formation by suppressing Wnt signaling, which is likely to be mediated by β-catenin. First, a similar phenotype (no primary mouth) is seen after loss of Frzb-1/Crescent function to that seen after temporally and spatially restricted overexpression of Wnt-8. Second, overexpression of either Frzb-1 or Dkk-1 results in an enlarged primary mouth anlage. Third,overexpression of Dkk-1 can restore a primary mouth to embryos in which Frzb-1/Crescent expression has been inhibited. We show that Frzb-1/Crescent function locally promotes basement membrane dissolution in the primary mouth primordium. Consistently, Frzb-1 overexpression decreases RNA levels of the essential basement membrane genes fibronectin and laminin,whereas Wnt-8 overexpression increases the levels of these RNAs. These data are the first to connect Wnt signaling and basement membrane integrity during primary mouth development, and suggest a general paradigm for the regulation of basement membrane remodeling.
Scheduling Medical Residents at Boston University School of Medicine
Authors: Cohn Amy , Root Sarah , Kymissis Carisa , Esses Justin , Westmoreland Niesha
Published: February 2009

The chief residents in the psychiatry program at Boston University School of Medicine (BUSM) must construct a schedule that simultaneously assigns residents to five types of call shifts, spanning three different hospitals, over a 365-day planning horizon. We show how user expertise and heuristic approaches alone fail to find acceptable solutions to this complex combinatorial problem; likewise, mathematical programming techniques alone are inadequate, largely because they lack a clearly definable objective function. However, by combining both approaches, we were able to find high-quality solutions in a very short time. The resulting schedule, which BUSM uses currently, has yielded substantial benefits; the solution quality has improved, and the effort required to develop the solution has been reduced.
Scheduling the Belgian Soccer League
Authors: Goossens Dries , Spieksma Frits
Published: February 2009

Every sports league needs a game schedule; such a schedule is important because it influences all parties involved and even the outcome of the sports competition. Interest in Belgian soccer has increased during recent years, as has interest in sports leagues in other countries. This paper describes our experiences in scheduling the highest division in the Belgian soccer league. We describe how we automated and improved the development of the 2006–2007 season schedule, and explain how we achieved additional improvement by dividing the scheduling problem into two problems. The resulting calendar has been accepted for the 2007–2008 season. We also compare the quality of the schedules generated using different scheduling methods.
Long-Range Planning for a West Texas Catholic Diocese
Authors: Butler John C. , Lasdon Leon S. , Dyer James S. , Maiman Leslie T.
Published: February 2009

This paper describes a decision-support system (DSS) implemented for the Roman Catholic diocese of San Angelo, Texas. The objective of this DSS is to support long-range diocese planning with a focus on the impact of a decreasing number of available priests and with changes in the mix of languages that the available priests speak. The key component of the DSS is a mixed-integer programming optimization model; although our problem is similar to a location-routing problem, our model has some noteworthy differences. We implemented this model using the General Algebraic Modeling System with an Excel interface to make it more adaptable to the needs of the chancellor of the diocese. The chancellor used this model to explore the impact of a decrease in the availability of priests in the region, and the diocese's Priest Personnel Board has adopted it for use in additional studies.
Secondary CD5+ Diffuse Large B-Cell Lymphoma Not Associated With Transformation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Richter Syndrome)
Authors: Maeshima Akiko Miyagi , Taniguchi Hirokazu , Nomoto Junko , Maruyama Dai , Kim Sung-Won , Watanabe Takashi , Kobayashi Yukio , Tobinai Kensei , Matsuno Yoshihiro
Published: February 2009

Few cases of secondary CD5+ diffuse large B-cell lymphoma (DLBCL) that are not Richter syndrome have been reported previously. We report 9 cases of non–Richter syndrome secondary CD5+ DLBCL. Among 529 cases of DLBCL, 38 (7.2%) were CD5+ DLBCL, including 9 of secondary CD5+ DLBCL. Five cases gained CD5 expression during the clinical course of DLBCL (group 1). Three cases showed transformation from CD5− low-grade B-cell lymphoma to CD5+ DLBCL (group 2). The remaining case showed coexistence of CD5+ DLBCL and CD5+ follicular lymphoma. The clonal relationships of CD5− and CD5+ tumors were confirmed in all 4 available cases. Cases of secondary CD5+ DLBCL that were not Richter syndrome were classifiable into 3 groups. Groups 1 and 2 showed the gain of CD5 during the clinical course or transformation of the tumors, suggesting that CD5 expression is closely associated with the progression of B-cell lymphoma.
PAX-2 in the Diagnosis of Primary Renal Tumors
Authors: Ozcan Ayhan , Zhai Jim , Hamilton Candice , Shen Steven S. , Ro Jae Y. , Krishnan Bhuvaneswari , Truong Luan D.
Published: February 2009

The diagnosis of renal cell carcinoma (RCC) remains problematic, especially in the context of metastasis or small needle biopsy specimens. The renal cell carcinoma marker (RCCM) and kidney-specific cadherin (KSC) are considered specific markers for RCC but are expressed preferentially in specific subtypes of RCC of lower grades. This study was aimed at evaluating the usefulness of PAX-2 in the diagnosis of renal tumors and comparing it with that of RCCM and KSC. Immunostaining for PAX-2, RCCM, and KSC was performed on consecutive tissue sections of 130 renal tumors.

PAX-2 was successfully detected in routine tissue specimens. Although PAX-2 seems to be more sensitive than RCCM and KSC, there is significant staining overlap in relation to histologic subtypes, justifying the use of all 3 markers, which helps detect the vast majority of renal neoplasms. PAX-2 seems to have a significant role in renal neogenesis and may represent a novel therapeutic target.
Development of Spontaneous Recurrent Seizures after Kainate-Induced Status Epilepticus
Authors: Williams Philip A. , White Andrew M. , Clark Suzanne , Ferraro Damien J. , Swiercz Waldemar , Staley Kevin J. , Dudek F. Edward
Published: February 2009

Acquired epilepsy (i.e., after an insult to the brain) is often considered to be a progressive disorder, and the nature of this hypothetical progression remains controversial. Antiepileptic drug treatment necessarily confounds analyses of progressive changes in human patients with acquired epilepsy. Here, we describe experiments testing the hypothesis that development of acquired epilepsy begins as a continuous process of increased seizure frequency (i.e., proportional to probability of a spontaneous seizure) that ultimately plateaus. Using nearly continuous surface cortical and bilateral hippocampal recordings with radiotelemetry and semiautomated seizure detection, the frequency of electrographically recorded seizures (both convulsive and nonconvulsive) was analyzed quantitatively for ∼100 d after kainate-induced status epilepticus in adult rats. The frequency of spontaneous recurrent seizures was not a step function of time (as implied by the “latent period”); rather, seizure frequency increased as a sigmoid function of time. The distribution of interseizure intervals was nonrandom, suggesting that seizure clusters (i.e., short interseizure intervals) obscured the early stages of progression, and may have contributed to the increase in seizure frequency. These data suggest that (1) the latent period is the first of many long interseizure intervals and a poor measure of the time frame of epileptogenesis, (2) epileptogenesis is a continuous process that extends much beyond the first spontaneous recurrent seizure, (3) uneven seizure clustering contributes to the variability in occurrence of epileptic seizures, and (4) the window for antiepileptogenic therapies aimed at suppressing acquired epilepsy probably extends well past the first clinical seizure.
Neprilysin Overexpression Inhibits Plaque Formation But Fails to Reduce Pathogenic Aβ Oligomers and Associated Cognitive Deficits in Human Amyloid Precursor Protein Transgenic Mice
Authors: Meilandt William J. , Cisse Moustapha , Ho Kaitlyn , Wu Tiffany , Esposito Luke A. , Scearce-Levie Kimberly , Cheng Irene H. , Yu Gui-Qiu , Mucke Lennart
Published: February 2009

The accumulation of amyloid-β (Aβ) peptides in the brain of patients with Alzheimer's disease (AD) may arise from an imbalance between Aβ production and clearance. Overexpression of the Aβ-degrading enzyme neprilysin in brains of human amyloid precursor protein (hAPP) transgenic mice decreases overall Aβ levels and amyloid plaque burdens. Because AD-related synaptic and cognitive deficits appear to be more closely related to Aβ oligomers than to plaques, it is important to determine whether increased neprilysin activity also diminishes the levels of pathogenic Aβ oligomers and related neuronal deficitsin vivo. To address this question, we crossed hAPP transgenic mice with neprilysin transgenic mice and analyzed their offspring. Neprilysin overexpression reduced soluble Aβ levels by 50% and effectively prevented early Aβ deposition in the neocortex and hippocampus. However, it did not reduce levels of Aβ trimers and Aβ*56 or improve deficits in spatial learning and memory. The differential effect of neprilysin on plaques and oligomers suggests that neprilysin-dependent degradation of Aβ affects plaques more than oligomers and that these structures may form through distinct assembly mechanisms. Neprilysin's inability to prevent learning and memory deficits in hAPP mice may be related to its inability to reduce pathogenic Aβ oligomers. Reduction of Aβ oligomers will likely be required for anti-Aβ treatments to improve cognitive functions.
A Switch from Cycloheximide-Resistant Consolidated Memory to Cycloheximide-Sensitive Reconsolidation and Extinction inDrosophila
Authors: Lagasse Fabrice , Devaud Jean-Marc , Mery Frederic
Published: February 2009

It is generally accepted that, after learning, memories stabilize over time and integrate into long-term memory (LTM) through the process of consolidation, which depends onde novoprotein synthesis. Besides, studies on several species have shown that reactivation of already stabilized LTM can either make this memory labile and then restabilize it (a process called reconsolidation) or inhibit it (extinction). However, the identity of both processes and their interactions with consolidation are still under debate. Regarding memory stabilization,Drosophilaoffers a striking exception since, in this species, LTM is not the sole stable form of memory. Under specific learning conditions, anesthesia-resistant memory (ARM) can be formed through processes yet unknown but that are resistant to cycloheximide, a classical protein synthesis inhibitor that impairs LTM. Here, we took advantage of this dichotomy to ask whether both ARM and LTM could be extinguished and/or reconsolidated. We also studied whether two forms of memory extinction and reconsolidation exist in flies, as for memory stabilization. We show that either reconsolidation or extinction can be induced after olfactory conditioning inDrosophila, depending on the number of reactivations as in other species. Furthermore, regarding the effect of cycloheximide, the ARM/LTM dichotomy for stabilization does not apply to extinction and reconsolidation. Blocking protein synthesis interfered with both processes regardless of whether initial stabilization was sensitive (LTM) or not (ARM) to cycloheximide. These results thus show thatDrosophilais a useful model to tackle these questions and that reconsolidation is not necessarily a mere repetition of consolidation.
Carriers of RecessiveWNK1/HSN2Mutations for Hereditary Sensory and Autonomic Neuropathy Type 2 (HSAN2) Are More Sensitive to Thermal Stimuli
Authors: Loggia Marco L. , Bushnell M. Catherine , Tétreault Martine , Thiffault Isabelle , Bhérer Claude , Mohammed Nazma K. , Kuchinad Anil A. , Laferrière Audrey , Dicaire Marie-Josée , Loisel Lina , Mogil Jeffrey S. , Brais Bernard
Published: February 2009

Hereditary sensory and autonomic neuropathy type 2 (HSAN2) is a rare recessive genetic disorder characterized by severe sensory loss affecting the tactile, thermal and nociceptive modalities. Although heterozygous carriers of nonsense mutations in theHSN2gene, called with-no-lysine(K)-1 (WNK1), do not develop the disease, historical and experimental evidence suggests that these individuals might perceive somatosensory stimuli differently from others. Using the method-of-limits, we assessed the thresholds for warmth detection, cool detection, heat pain and cold pain in 25 mutation carriers and 35 controls. In group analyses, carriers displayed significantly lower warmth (p< 0.001) and cool (p< 0.05) difference thresholds, and also tended to report cold pain at higher temperatures (p= 0.095), than controls. Similarly, matched-pair analyses showed that carriers are significantly more sensitive to warm stimuli (p< 0.01) and cold pain stimuli (p< 0.05), and tend to be more sensitive to cool stimuli (p= 0.11). Furthermore, the differences between the warmth detection thresholds of the carriers and those of gender- and sex-matched wild types significantly increased with age (r= 0.76,p= 0.02), and in carriers cool detection thresholds did not increase with age (r= 0.27,p= 0.24) as expected and observed in controls (r= 0.34,p= 0.05). This study demonstrates that the carriers of a recessive mutation for HSAN2 display greater sensitivity to innocuous thermal stimuli, as well as for cold pain, suggesting a possible environmental adaptive advantage of the heterozygous state.
Interdependent Encoding of Pitch, Timbre, and Spatial Location in Auditory Cortex
Authors: Bizley Jennifer K. , Walker Kerry M. M. , Silverman Bernard W. , King Andrew J. , Schnupp Jan W. H.
Published: February 2009

Because we can perceive the pitch, timbre, and spatial location of a sound source independently, it seems natural to suppose that cortical processing of sounds might separate out spatial from nonspatial attributes. Indeed, recent studies support the existence of anatomically segregated “what” and “where” cortical processing streams. However, few attempts have been made to measure the responses of individual neurons in different cortical fields to sounds that vary simultaneously across spatial and nonspatial dimensions. We recorded responses to artificial vowels presented in virtual acoustic space to investigate the representations of pitch, timbre, and sound source azimuth in both core and belt areas of ferret auditory cortex. A variance decomposition technique was used to quantify the way in which altering each parameter changed neural responses. Most units were sensitive to two or more of these stimulus attributes. Although indicating that neural encoding of pitch, location, and timbre cues is distributed across auditory cortex, significant differences in average neuronal sensitivity were observed across cortical areas and depths, which could form the basis for the segregation of spatial and nonspatial cues at higher cortical levels. Some units exhibited significant nonlinear interactions between particular combinations of pitch, timbre, and azimuth. These interactions were most pronounced for pitch and timbre and were less commonly observed between spatial and nonspatial attributes. Such nonlinearities were most prevalent in primary auditory cortex, although they tended to be small compared with stimulus main effects.
Role of the Superior Colliculus in Choosing Mixed-Strategy Saccades
Authors: Thevarajah Dhushan , Mikulić Areh , Dorris Michael C.
Published: February 2009

Game theory outlines optimal response strategies during mixed-strategy competitions. The neural processes involved in choosing individual strategic actions, however, remain poorly understood. Here, we tested whether the superior colliculus (SC), a brain region critical for generating sensory-guided saccades, is also involved in choosing saccades under strategic conditions. Monkeys were free to choose either of two saccade targets as they competed against a computer opponent during the mixed-strategy game “matching pennies.” The accuracy with which presaccadic SC activity predicted upcoming choice gradually increased in the time leading up to the saccade. Probing the SC with suprathreshold stimulation demonstrated that these evolving signals were functionally involved in preparing strategic saccades. Finally, subthreshold stimulation of the SC increased the likelihood that contralateral saccades were selected. Together, our results suggest that motor regions of the brain play an active role in choosing strategic actions rather than passively executing those prespecified by upstream executive regions.
Thick Visual Cortex in the Early Blind
Authors: Jiang Jiefeng , Zhu Wanlin , Shi Feng , Liu Yong , Li Jun , Qin Wen , Li Kuncheng , Yu Chunshui , Jiang Tianzi
Published: February 2009

We investigated the key neurodevelopmental factors that determine cortical thickness, namely synaptogenesis and regression, by analyzing the thickness of the visual cortex in humans with early- and late-onset blindness. The bilateral visual cortices of the early blind were significantly thicker than those of the late blind and the sighted controls, but the latter two groups did not differ significantly. This suggests reduced “pruning” of synapses in the visual cortex, which may be due to a lack of visual experience during a critical developmental period. These findings support the hypothesis that sensory experience is necessary for an appropriate regression and remodeling of neuronal processes and that synaptic regression might be a major determinant of macroscopic anatomical features like cortical thickness.