bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Crime Pay? Issue Ownership, Political Opportunity, and the Populist Right in Western Europe
Authors: Smith Jason Matthew
Published: June 2010

This article contributes to the vast literature concerning extreme right parties in Western Europe by examining the effects of crime on the electoral success of these parties. Utilizing theories of issue ownership and political opportunity, this article argues that populist right parties appeal to voters who feel a sense of physical and social insecurity because of higher levels of crime. This hypothesis is tested using a data set covering 18 Western European countries between 1970 and 2005. The results indicate that populist right parties benefit from higher levels of crime as well as linking crime with higher levels of immigration. The article concludes with a discussion of the implications of this analysis.
Who Gets the House? Renegotiating Property Rights in Post-Socialist Urban China
Authors: Davis Deborah
Published: June 2010

Privatization of urban housing in China has altered the basic parameters of household dissolution from those that prevailed before 1980. For several reasons, divorce was rare during the Mao years, but one critical barrier was employer control over urban housing. Thirty years later, employers no longer supply new flats and the majority of urban couples are homeowners. Simultaneous with the privatization of urban real estate has been a divorce revolution. In 1978 there was one divorce for every twenty marriages and courts handled half of the cases. By 2008 there was one divorce for every five marriages and courts finalized less than 30 percent of cases. Through a comparison of the changes in black letter law and arguments made by ordinary citizens in 24 focus groups, the article illustrates how ordinary citizens are negotiating with black letter law to institutionalize post-socialist property rights.
Local Hero
Authors: Flores Borja Carlos
Published: June 2010

Carlos Flores Borja, winner of an Index on Censorship Award, reports from Peru on how his radio station was closed down for reporting a government massacre
Looking for America
Authors: Queenan Joe
Published: June 2010

Talk radio is the right-wing’s battleground for the soul of the USA, but Joe Queenan isn’t listening
Too Free Too Fast
Authors: Waititu Ernest
Published: June 2010

Local language radio stands accused of inciting violence following the elections in Kenya in 2007. Ernest Waititu investigates
Covered Up
Authors: Berer Marge
Published: June 2010

When Marge Berer dedicated an issue of her journal to the trend for cosmetic genital surgery, her choice of cover met with opposition
Deleuzian Thought and Collaborative Writing: A Play in Four Acts
Authors: Wyatt Jonathan , Gale Ken , Gannon Susanne , Davies Bronwyn
Published: June 2010

This article involves four writers exploring together the insights into collaborative writing that Deleuze can offer. Jonathan and Ken in the United Kingdom and Bronwyn and Sue in Australia have separate histories of collaborative writing, and in this collaborative project, they extend their thinking about Deleuze and work reflexively with his concepts to examine their own four-way collaboration. The thoughts of Deleuze provide a means of looking at collaborative writing as performance, as a means of becoming, each for the unknown other; selves as writers and academics but also sexed subjects living complex lives, in this case in worlds many miles apart. The article offers the collective and multiple senses of how the thoughts of Deleuze can be brought to life in collaborative writing.
Majority Rule versus Supermajority Rules: Their Effects on Narrow and Broad Taxes
Authors: Heckelman Jac C. , Dougherty Keith L.
Published: June 2010

Buchanan and Tullock argue that larger supermajority rules reduce tyranny of the majority but should have no effect on the passage of mutually advantageous policies. The authors test this argument by separately analyzing the effect of supermajority requirements on taxes that are targeted toward narrow groups (more redistributive) and taxes targeted toward a broader base (less redistributive), in a panel of fifty states from 1970 to 2008. Regression analysis reveals an inverse relationship between narrow taxes and the size of the majority rule requirement and no relationship between broad taxes and the size of the majority requirement—consistent with the claim of Buchanan and Tullock. The authors also find that Democratic controlled governments have significantly higher tax rates on narrow taxes than Republican controlled governments. The reverse is found for broad taxes, but the result is not as strong.
A clinical trial of peer-based culturally responsive person-centered care for psychosis for African Americans and Latinos
Authors: Tondora Janis , O'Connell Maria , Miller Rebecca , Dinzeo Tom , Bellamy Chyrell , Andres-Hyman Raquel , Davidson Larry
Published: June 2010

Background Providing culturally competent and person-centered care is at the forefront of changing practices in behavioral health. Significant health disparities remain between people of color and whites in terms of care received in the mental health system. Peer services, or support provided by others who have experience in the behavioral health system, is a promising new avenue for helping those with behavioral health concerns move forward in their lives.

Purpose We describe a model of peer-based culturally competent person-centered care and treatment planning, informed by longstanding research on recovery from serious mental illness used in a randomized clinical trial conducted at two community mental health centers.

Methods Participants all were Latino or African American with a current or past diagnosis within the psychotic disorders spectrum as this population is often underserved with limited access to culturally responsive, person-centered services. Study interventions were carried out in both an English-speaking and a Spanish-speaking outpatient program at each study center. Interventions included connecting individuals to their communities of choice and providing assistance in preparing for treatment planning meetings, all delivered by peer-service providers. Three points of evaluation, at baseline, 6 and 18 months, explored the impact of the interventions on areas such as community engagement, satisfaction with treatment, symptom distress, ethnic identity, personal empowerment, and quality of life.

Conclusions Lessons learned from implementation include making cultural modifications, the need for a longer engagement period with participants, and the tension between maintaining strict interventions while addressing the individual needs of participants in line with person-centered principles. The study is one of the first to rigorously test peer-supported interventions in implementing person-centered care within the context of public mental health systems. Clinical Trials 2010; 7: 368—379. http://ctj.sagepub.com
The microvacuolar system: how connective tissue sliding works
Authors: Guimberteau J. C. , Delage J. P. , McGrouther D. A. , Wong J. K. F.
Published: June 2010

The term ‘fascia’ has been applied to a large number of very different tissues within the hand. These range from aligned ligamentous formations such as the longitudinal bands of the palmar fascia or Grayson’s and Cleland’s ligaments, to the loose packing tissues that surround all of the moving structures within the hand. In other parts of the body the terms ‘superficial’ and ‘deep fascia’ are often used but these have little application in the hand and fingers. Fascia can be divided into tissues that restrain motion, act as anchors for the skin, or provide lubrication and gliding. Whereas the deep fascia is preserved and easily characterized in anatomical dissection, the remaining fascial tissue is poorly described. Understanding its structure and dynamic anatomy may help improve outcomes after hand injury and disease. This review describes the sliding tissue of the hand or the ‘microvacuolar system’ and demonstrates how movement of tissues can occur with minimal distortion of the overlying skin while maintaining tissue continuity.
Reversion of epigenetically mediated BIM silencing overcomes chemoresistance in Burkitt lymphoma
Authors: Richter-Larrea Jose A. , Robles Eloy F. , Fresquet Vicente , Beltran Elena , Rullan Antonio J. , Agirre Xabier , Calasanz Maria José , Panizo Carlos , Richter Jose A. , Hernandez Jesus M. , Roman-Gomez Jose , Prosper Felipe , Martinez-Climent Jose A.
Published: June 2010

In Burkitt lymphoma/leukemia (BL), achievement of complete remission with first-line chemotherapy remains a challenging issue, as most patients who respond remain disease-free, whereas those refractory have few options of being rescued with salvage therapies. The mechanisms underlying BL chemoresistance and how it can be circumvented remain undetermined. We previously reported the frequent inactivation of the proapoptotic BIM gene in B-cell lymphomas. Here we show that BIM epigenetic silencing by concurrent promoter hypermethylation and deacetylation occurs frequently in primary BL samples and BL-derived cell lines. Remarkably, patients with BL with hypermethylated BIM presented lower complete remission rate (24% vs 79%; P = .002) and shorter overall survival (P = .007) than those with BIM-expressing lymphomas, indicating that BIM transcriptional repression may mediate tumor chemoresistance. Accordingly, by combining in vitro and in vivo studies of human BL-xenografts grown in immunodeficient RAG2−/−γc−/− mice and of murine B220+IgM+ B-cell lymphomas generated in Eμ-MYC and Eμ-MYC-BIM+/− transgenes, we demonstrate that lymphoma chemoresistance is dictated by BIM gene dosage and is reversible on BIM reactivation by genetic manipulation or after treatment with histone-deacetylase inhibitors. We suggest that the combination of histone-deacetylase inhibitors and high-dose chemotherapy may overcome chemoresistance, achieve durable remission, and improve survival of patients with BL.
Genome size evolution in pufferfish: an insight from BAC clone-based Diodon holocanthus genome sequencing
Authors: Guo Baocheng , Zou Ming , Gan Xiaoni , He Shunping
Published: June 2010

Background

Variations in genome size within and between species have been observed since the 1950 s in diverse taxonomic groups. Serving as model organisms, smooth pufferfish possess the smallest vertebrate genomes. Interestingly, spiny pufferfish from its sister family have genome twice as large as smooth pufferfish. Therefore, comparative genomic analysis between smooth pufferfish and spiny pufferfish is useful for our understanding of genome size evolution in pufferfish.

Results

Ten BAC clones of a spiny pufferfish Diodon holocanthus were randomly selected and shotgun sequenced. In total, 776 kb of non-redundant sequences without gap representing 0.1% of the D. holocanthus genome were identified, and 77 distinct genes were predicted. In the sequenced D. holocanthus genome, 364 kb is homologous with 265 kb of the Takifugu rubripes genome, and 223 kb is homologous with 148 kb of the Tetraodon nigroviridis genome. The repetitive DNA accounts for 8% of the sequenced D. holocanthus genome, which is higher than that in the T. rubripes genome (6.89%) and that in the Te. nigroviridis genome (4.66%). In the repetitive DNA, 76% is retroelements which account for 6% of the sequenced D. holocanthus genome and belong to known families of transposable elements. More than half of retroelements were distributed within genes. In the non-homologous regions, repeat element proportion in D. holocanthus genome increased to 10.6% compared with T. rubripes and increased to 9.19% compared with Te. nigroviridis. A comparison of 10 well-defined orthologous genes showed that the average intron size (566 bp) in D. holocanthus genome is significantly longer than that in the smooth pufferfish genome (435 bp).

Conclusion

Compared with the smooth pufferfish, D. holocanthus has a low gene density and repeat elements rich genome. Genome size variation between D. holocanthus and the smooth pufferfish exhibits as length variation between homologous region and different accumulation of non-homologous sequences. The length difference of intron is consistent with the genome size variation between D. holocanthus and the smooth pufferfish. Different transposable element accumulation is responsible for genome size variation between D. holocanthus and the smooth pufferfish.
Characterization of the equine skeletal muscle transcriptome identifies novel functional responses to exercise training
Authors: McGivney Beatrice A , McGettigan Paul A , Browne John A , Evans Alexander CO , Fonseca Rita G , Loftus Brendan J , Lohan Amanda , MacHugh David E , Murphy Barbara A , Katz Lisa M , Hill Emmeline W
Published: June 2010

Background

Digital gene expression profiling was used to characterize the assembly of genes expressed in equine skeletal muscle and to identify the subset of genes that were differentially expressed following a ten-month period of exercise training. The study cohort comprised seven Thoroughbred racehorses from a single training yard. Skeletal muscle biopsies were collected at rest from thegluteus mediusat two time points: T1- untrained, (9 ± 0.5 months old) and T2- trained (20 ± 0.7 months old).

Results

The most abundant mRNA transcripts in the muscle transcriptome were those involved in muscle contraction, aerobic respiration and mitochondrial function. A previously unreported over-representation of genes related to RNA processing, the stress response and proteolysis was observed. Following training 92 tags were differentially expressed of which 74 were annotated. Sixteen genes showed increased expression, including the mitochondrial genesACADVL,MRPS21andSLC25A29encoded by the nuclear genome. Among the 58 genes with decreased expression,MSTN, a negative regulator of muscle growth, had the greatest decrease.

Functional analysis of all expressed genes using FatiScan revealed an asymmetric distribution of 482 Gene Ontology (GO) groups and 18 KEGG pathways. Functional groups displaying highly significant (P< 0.0001) increased expression included mitochondrion, oxidative phosphorylation and fatty acid metabolism while functional groups with decreased expression were mainly associated with structural genes and included the sarcoplasm, laminin complex and cytoskeleton.

Conclusion

Exercise training in Thoroughbred racehorses results in coordinate changes in the gene expression of functional groups of genes related to metabolism, oxidative phosphorylation and muscle structure.
The proline-rich peptide Bac7(1-35) reduces mortality from Salmonella typhimurium in a mouse model of infection
Authors: Benincasa Monica , Pelillo Chiara , Zorzet Sonia , Garrovo Chiara , Biffi Stefania , Gennaro Renato , Scocchi Marco
Published: June 2010

Background

Bac7 is a proline-rich peptide with a potent in vitro antimicrobial activity against Gram-negative bacteria. Here we investigated its activity in biological fluids and in vivo using a mouse model of S. typhimurium infection.

Results

The efficacy of the active 1-35 fragment of Bac7 was assayed in serum and plasma, and its stability in biological fluids analyzed by Western blot and mass spectrometry. The ability of the peptide to protect mice against Salmonella was assayed in a typhoid fever model of infection by determination of survival rates and bacterial load in liver and spleen of infected animals. In addition, the peptide's biodistribution was evaluated by using time-domain optical imaging. Bac7(1-35) retained a substantial in vivo activity showing a very low toxicity. The peptide increased significantly the number of survivors and the mean survival times of treated mice reducing the bacterial load in their organs despite its rapid clearance.

Conclusions

Our results provide a first indication for a potential development of Bac7-based drugs in the treatment of salmonellosis and, eventually, other Gram-negative infections. The in vivo activity for this peptide might be substantially enhanced by decreasing its excretion rate or modifying the treatment schedule.
Characterization of a diverse secretome generated by the mouse preimplantation embryo in vitro
Authors: Beardsley Amanda J , Li Yan , O'Neill Chris
Published: June 2010

This study investigates the suitability of surface-enhanced laser desorption and ionization time-of-flight (SELDI-TOF) and electrospray ionization (ESI) mass spectrometry for analysis of the proteins released by the mouse preimplantation embryo in vitro. SELDI-TOF analysis with CM10 or IMAC30 (but not Q10) protein chips detected a protein peak at m/z ~8570 released by both C57BL6 and hybrid embryos. No other peaks unique to the presence of the embryo were identified with this method. ESI mass spectrometry of tryptic digests of embryo-conditioned media identified a total of 20 proteins released during development from the zygote to blastocyst stage. Four proteins were expressed in at least 7 out of 8 cultures tested, one of these (lactate dehydrogenase B) was in all cultures. A further five proteins were in at least half of the cultures and 11 more proteins were in at least one culture. The expression of two of these proteins is essential for preimplantation embryo development (NLR family, pyrin domain containing 5 and peptidyl arginine deiminase, type VI). A further four proteins detected have roles in redox regulation of cells, and three others are capable of inducing post-translational modifications of proteins. This study shows the feasibility of ESI mass spectrometry for identifying the proteins secreted by the preimplantation embryo in vitro. This analysis identifies a range of targets that now require detailed functional analysis to assess whether their release by the embryo is an important property of early embryo development.
Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI
Authors: Kim Kyeong-Ae , Yolamanova Maral , Zirafi Onofrio , Roan Nadia R , Staendker Ludger , Forssmann Wolf-Georg , Burgener Adam , Dejucq-Rainsford Nathalie , Hahn Beatrice H , Shaw George M , Greene Warner C , Kirchhoff Frank , Münch Jan
Published: June 2010

Background

HIV-1 is usually transmitted in the presence of semen. We have shown that semen boosts HIV-1 infection and contains fragments of prostatic acid phosphatase (PAP) forming amyloid aggregates termed SEVI (semen-derived enhancer of viral infection) that promote virion attachment to target cells. Despite its importance for the global spread of HIV-1, however, the effect of semen on virus infection is controversial.

Results

Here, we established methods allowing the meaningful analysis of semen by minimizing its cytotoxic effects and partly recapitulating the conditions encountered during sexual HIV-1 transmission. We show that semen rapidly and effectively enhances the infectivity of HIV-1, HIV-2, and SIV. This enhancement occurs independently of the viral genotype and coreceptor tropism as well as the virus producer and target cell type. Semen-mediated enhancement of HIV-1 infection was also observed under acidic pH conditions and in the presence of vaginal fluid. We further show that the potency of semen in boosting HIV-1 infection is donor dependent and correlates with the levels of SEVI.

Conclusions

Our results show that semen strongly enhances the infectivity of HIV-1 and other primate lentiviruses and that SEVI contributes to this effect. Thus, SEVI may play an important role in the sexual transmission of HIV-1 and addition of SEVI inhibitors to microbicides may improve their efficacy.
LICAVAL: combination therapy in acute and maintenance treatment of bipolar disorder
Authors: Campos Rodolfo N , Costa Luis F , Bio Danielle S , Soeiro de Souza Márcio G , Garcia Carla RL , Demétrio Frederico N , Moreno Doris H , Moreno Ricardo A
Published: June 2010

Background

The challenge of Bipolar Disorder (BD) treatment is due to the complexity of the disease. Current guidelines represent an effort to help clinicians in their everyday practice but still have limitations, specially concerning to long term treatment. LICAVAL (efficacy and tolerability of the combination of

LI

thium and

CA

rbamazepine compared to lithium and

VAL

proic acid in the treatment of young bipolar patients) study aim to evaluate acute and maintenance phase of BD treatment with two combined drugs.

Methods

LICAVAL is a single site, parallel group, randomized, outcome assessor blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic,/hypomanic or mixed episode, aged 18 to 35 years are eligible. After the diagnostic assessments, the patients are allocated for one of the groups of treatment (lithium + valproic acid or lithium + carbamazepine). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blind to the treatment. The main outcome is the evaluation of changes in mean scores on CGI-BP-M between baseline and endpoint at the end of each phase of the study.

Results

LICAVAL is currently in progress, with patients in phase I, II or III. It will extended until august 2012.

Conclusions

Trials comparing specific treatments efficacy in BD (head to head) can show relevant information in clinical practice. Long term treatment is an issue of great important and should be evaluated carefully in more studies as long as BD is a chronic disease.

Trial registration

ClinicalTrials.gov Identifier: NCT00976794
Senescent mouse cells fail to overtly regulate the HIRA histone chaperone and do not form robust Senescence Associated Heterochromatin Foci
Authors: Kennedy Alyssa L , McBryan Tony , Enders Greg H , Johnson F Brad , Zhang Rugang , Adams Peter D
Published: June 2010

Background

Cellular senescence is a permanent growth arrest that occurs in response to cellular stressors, such as telomere shortening or activation of oncogenes. Although the process of senescence growth arrest is somewhat conserved between mouse and human cells, there are some critical differences in the molecular pathways of senescence between these two species. Recent studies in human fibroblasts have defined a cell signaling pathway that is initiated by repression of a specific Wnt ligand, Wnt2. This, in turn, activates a histone chaperone HIRA, and culminates in formation of specialized punctate domains of facultative heterochromatin, called S enescence-A ssociated H eterochromatin F oci (SAHF), that are enriched in the histone variant, macroH2A. SAHF are thought to repress expression of proliferation-promoting genes, thereby contributing to senescence-associated proliferation arrest. We asked whether this Wnt2-HIRA-SAHF pathway is conserved in mouse fibroblasts.

Results

We show that mouse embryo fibroblasts (MEFs) and mouse skin fibroblasts, do not form robust punctate SAHF in response to an activated Ras oncogene or shortened telomeres. However, senescent MEFs do exhibit elevated levels of macroH2A staining throughout the nucleus as a whole. Consistent with their failure to fully activate the SAHF assembly pathway, the Wnt2-HIRA signaling axis is not overtly regulated between proliferating and senescent mouse cells.

Conclusions

In addition to the previously defined differences between mouse and human cells in the mechanisms and phenotypes associated with senescence, we conclude that senescent mouse and human fibroblasts also differ at the level of chromatin and the signaling pathways used to regulate chromatin. These differences between human and mouse senescence may contribute to the increased propensity of mouse fibroblasts (and perhaps other mouse cell types) to become immortalized and transformed, compared to human cells.
Digital gangrene associated with anticentromere antibodies: a case report
Authors: Bolster Lauren , Taylor-Gjevre Regina M , Nair Bindu , Gjevre John A
Published: June 2010

Introduction

Anticentromere antibodies have been associated with peripheral vascular occlusive disease, most frequently accompanied by sclerodactyly in the context of a connective tissue disorder. We report a case of digital gangrene with no other clinical associations except positive anticentromere antibodies.

Case presentation

Our patient, a 53-year-old Caucasian woman, non-smoker, presented with progressive pain and blackening of the distal right third finger over the preceding five weeks. No sclerodactyly was evident. She was anticentromere antibody positive at greater than 100 U/mL. Angiography revealed diffuse distal vasculopathy in both upper extremities. Other investigations were unremarkable.

Conclusions

It is rare for anticentromere antibody-associated digital necrosis to develop without concomitant sclerodactyly. However, this patient's case illustrates the need to consider an autoimmune contribution to the pathogenesis of digital ischemia even in the absence of a recognizable connective tissue disease.
The impact of HIV and high‐risk behaviours on the wives of married men who have sex with men and injection drug users: implications for HIV prevention
Authors: Solomon Sunil S , Mehta Shruti H , Latimore Amanda , Srikrishnan Aylur K , Celentano David D
Published: June 2010

Background

HIV/AIDS in India disproportionately affects women, not by their own risks, but by those of their partners, generally their spouses. We address two marginalized populations at elevated risk of acquiring HIV: women who are married to men who also have sex with men (MSM) and wives of injection drug users (IDUs).

Methods

We used a combination of focus groups (qualitative) and structured surveys (quantitative) to identify the risks that high‐risk men pose to their low‐risk wives and/or sexual partners. Married MSM were identified using respondent‐driven recruitment in Tamil Nadu, India, and were interviewed by trainer assessors. A sample of wives of injection drug users in Chennai were recruited from men enrolled in a cohort study of the epidemiology of drug use among IDUs in Chennai, and completed a face‐to‐face survey. Focus groups were held with all groups of study participants, and the outcomes transcribed and analyzed for major themes on family, HIV and issues related to stigma, discrimination and disclosure.

Results

Using mixed‐methods research, married MSM are shown to not disclose their sexual practices to their wives, whether due to internalized homophobia, fear of stigma and discrimination, personal embarrassment or changing sexual mores. Married MSM in India largely follow the prevailing norm of marriage to the opposite sex and having a child to satisfy social pressures. Male IDUs cannot hide their drug use as easily as married MSM, but they also avoid disclosure. The majority of their wives learn of their drug‐using behaviour only after they are married, making them generally helpless to protect themselves. Fear of poverty and negative influences on children were the major impacts associated with continuing drug use.

Conclusions

We propose a research and prevention agenda to address the HIV risks encountered by families of high‐risk men in the Indian and other low‐ and middle‐income country contexts.
Family‐centred HIV interventions: lessons from the field of parental depression
Authors: Tomlinson Mark
Published: June 2010

Traditionally, HIV prevention focuses on individual behaviours that place one at risk for HIV infection. Less widely regarded as a fundamental public health issue is parental depression and the detrimental effects it exerts on infant and child development, as well as its key contribution to non‐fatal burden. Much like many HIV prevention and treatment interventions, programmes for depression focus almost exclusively on individuals and individual behaviour. This paper will use the extensive evidence base from research into parental depression as a model to argue for a family based approach to HIV prevention and treatment. The aim of this will be to make a case for targeting a broader set of behaviours that occur within families when developing and implementing interventions.
Detection and analysis of alternative splicing in Yarrowia lipolytica reveal structural constraints facilitating nonsense-mediated decay of intron-retaining transcripts
Authors: Mekouar Meryem , Blanc-Lenfle Isabelle , Ozanne Christophe , Da Silva Corinne , Cruaud Corinne , Wincker Patrick , Gaillardin Claude , Neuvéglise Cécile
Published: June 2010

Background

Hemiascomycetous yeasts have intron-poor genomes with very few cases of alternative splicing. Most of the reported examples result from intron retention in Saccharomyces cerevisiae and some have been shown to be functionally significant. Here we used transcriptome-wide approaches to evaluate the mechanisms underlying the generation of alternative transcripts in Yarrowia lipolytica, a yeast highly divergent from S. cerevisiae.

Results

Experimental investigation of Y. lipolytica gene models identified several cases of alternative splicing, mostly generated by intron retention, principally affecting the first intron of the gene. The retention of introns almost invariably creates a premature termination codon, as a direct consequence of the structure of intron boundaries. An analysis of Y. lipolytica introns revealed that introns of multiples of three nucleotides in length, particularly those without stop codons, were underrepresented. In other organisms, premature termination codon-containing transcripts are targeted for degradation by the nonsense-mediated mRNA decay (NMD) machinery. In Y. lipolytica, homologs of S. cerevisiaeUPF1 and UPF2 genes were identified, but not UPF3. The inactivation of Y. lipolyticaUPF1 and UPF2 resulted in the accumulation of unspliced transcripts of a test set of genes.

Conclusions

Y. lipolytica is the hemiascomycete with the most intron-rich genome sequenced to date, and it has several unusual genes with large introns or alternative transcription start sites, or introns in the 5' UTR. Our results suggest Y. lipolytica intron structure is subject to significant constraints, leading to the under-representation of stop-free introns. Consequently, intron-containing transcripts are degraded by a functional NMD pathway.
The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle
Authors: Ferrezuelo Francisco , Colomina Neus , Futcher Bruce , Aldea Martí
Published: June 2010

Background

The G1-to-S transition of the cell cycle in the yeast Saccharomyces cerevisiae involves an extensive transcriptional program driven by transcription factors SBF (Swi4-Swi6) and MBF (Mbp1-Swi6). Activation of these factors ultimately depends on the G1 cyclin Cln3.

Results

To determine the transcriptional targets of Cln3 and their dependence on SBF or MBF, we first have used DNA microarrays to interrogate gene expression upon Cln3 overexpression in synchronized cultures of strains lacking components of SBF and/or MBF. Secondly, we have integrated this expression dataset together with other heterogeneous data sources into a single probabilistic model based on Bayesian statistics. Our analysis has produced more than 200 transcription factor-target assignments, validated by ChIP assays and by functional enrichment. Our predictions show higher internal coherence and predictive power than previous classifications. Our results support a model whereby SBF and MBF may be differentially activated by Cln3.

Conclusions

Integration of heterogeneous genome-wide datasets is key to building accurate transcriptional networks. By such integration, we provide here a reliable transcriptional network at the G1-to-S transition in the budding yeast cell cycle. Our results suggest that to improve the reliability of predictions we need to feed our models with more informative experimental data.
Molecular evolution of genes in avian genomes
Authors: Nam Kiwoong , Mugal Carina , Nabholz Benoit , Schielzeth Holger , Wolf Jochen BW , Backström Niclas , Künstner Axel , Balakrishnan Christopher N , Heger Andreas , Ponting Chris P , Clayton David F , Ellegren Hans
Published: June 2010

Background

Obtaining a draft genome sequence of the zebra finch (Taeniopygia guttata), the second bird genome to be sequenced, provides the necessary resource for whole-genome comparative analysis of gene sequence evolution in a non-mammalian vertebrate lineage. To analyze basic molecular evolutionary processes during avian evolution, and to contrast these with the situation in mammals, we aligned the protein-coding sequences of 8,384 1:1 orthologs of chicken, zebra finch, a lizard and three mammalian species.

Results

We found clear differences in the substitution rate at fourfold degenerate sites, being lowest in the ancestral bird lineage, intermediate in the chicken lineage and highest in the zebra finch lineage, possibly reflecting differences in generation time. We identified positively selected and/or rapidly evolving genes in avian lineages and found an over-representation of several functional classes, including anion transporter activity, calcium ion binding, cell adhesion and microtubule cytoskeleton.

Conclusions

Focusing specifically on genes of neurological interest and genes differentially expressed in the unique vocal control nuclei of the songbird brain, we find a number of positively selected genes, including synaptic receptors. We found no evidence that selection for beneficial alleles is more efficient in regions of high recombination; in fact, there was a weak yet significant negative correlation between ω and recombination rate, which is in the direction predicted by the Hill-Robertson effect if slightly deleterious mutations contribute to protein evolution. These findings set the stage for studies of functional genetics of avian genes.
Golgi-to-phagosome transport of acid sphingomyelinase and prosaposin is mediated by sortilin
Authors: Wähe Anna , Kasmapour Bahram , Schmaderer Christoph , Liebl David , Sandhoff Konrad , Nykjaer Anders , Griffiths Gareth , Gutierrez Maximiliano G.
Published: June 2010

Sortilin, also known as neurotensin receptor 3 (NTR3), is a transmembrane protein with a dual function. It acts as a receptor for neuromediators and growth factors at the plasma membrane, but it has also been implicated in binding and transport of some lysosomal proteins. However, the role of sortilin during phagosome maturation has not been investigated before. Here, we show that in macrophages, sortilin is mainly localized in the Golgi and transported to latex-bead phagosomes (LBPs). Using live-cell imaging and electron microscopy, we found that sortilin is delivered to LBPs in a manner that depends on its cytoplasmic tail. We also show that sortilin participates in the direct delivery of acid sphingomyelinase (ASM) and prosaposin (PS) to the phagosome, bypassing fusion with lysosomal compartments. Further analysis confirmed that ASM and PS are targeted to the phagosome by sortilin in a Brefeldin-A-sensitive pathway. Analysis of primary macrophages isolated from Sort1−/− mice indicated that the delivery of ASM and PS, but not pro-cathepsin D, to LBPs was severely impaired. We propose a pathway mediated by sortilin by which selected lysosomal proteins are transported to the phagosome along a Golgi-dependent route during the maturation of phagosomes.
Hepatocytes lacking thioredoxin reductase 1 have normal replicative potential during development and regeneration
Authors: Rollins MaryClare F. , van der Heide Dana M. , Weisend Carla M. , Kundert Jean A. , Comstock Kristin M. , Suvorova Elena S. , Capecchi Mario R. , Merrill Gary F. , Schmidt Edward E.
Published: June 2010

Cells require ribonucleotide reductase (RNR) activity for DNA replication. In bacteria, electrons can flow from NADPH to RNR by either a thioredoxin-reductase- or a glutathione-reductase-dependent route. Yeast and plants artificially lacking thioredoxin reductases exhibit a slow-growth phenotype, suggesting glutathione-reductase-dependent routes are poor at supporting DNA replication in these organisms. We have studied proliferation of thioredoxin-reductase-1 (Txnrd1)-deficient hepatocytes in mice. During development and regeneration, normal mice and mice having Txnrd1-deficient hepatocytes exhibited similar liver growth rates. Proportions of hepatocytes that immunostained for PCNA, phosphohistone H3 or incorporated BrdU were also similar, indicating livers of either genotype had similar levels of proliferative, S and M phase hepatocytes, respectively. Replication was blocked by hydroxyurea, confirming that RNR activity was required by Txnrd1-deficient hepatocytes. Regenerative thymidine incorporation was similar in normal and Txnrd1-deficient livers, further indicating that DNA synthesis was unaffected. Using genetic chimeras in which a fluorescently marked subset of hepatocytes was Txnrd1-deficient while others were not, we found that the multigenerational contributions of both hepatocyte types to development and to liver regeneration were indistinguishable. We conclude that, in mouse hepatocytes, a Txnrd1-independent route for the supply of electrons to RNR can fully support DNA replication and normal proliferative growth.
Thermo-mechanical induced vibration characteristics of shear deformable functionally graded ceramic—metal plates using finite element method
Authors: Talha M , Singh B N
Published: June 2010

This paper deals with the thermomechanical-induced vibration characteristics of shear deformable functionally graded material (FGM) plates. Theoretical formulations are based on higher-order shear deformation theory with a significant improvement in the transverse displacement using finite-element method. The mechanical properties of the plate are assumed to be temperature-dependent and graded in the thickness direction according to a power-law distribution in terms of the volume fractions of the constituents. The temperature field is ascertained to be a uniform distribution over the plate surface and varied in the thickness direction only. The fundamental equations for FGM plates are derived using variational approach by considering traction-free boundary conditions on the top and bottom faces of the plate. A C0 continuous isoparametric Lagrangian finite-element with 13 degrees of freedom (DOF) per node have been used to accomplish the results. Convergence and comparison studies have been performed for square plates to demonstrate the efficiency of the present model. The numerical results are obtained for different thickness ratios, aspect ratios, volume fraction index, and temperature rise with different boundary conditions. The results reveal that the temperature field and the gradient in the material properties have significant effect on the vibration characteristics of the FGM plates.
A method of version merging for computer-aided design files based on feature extraction
Authors: Sun C , Guo D , Gao H , Zou L , Wang H
Published: June 2010

In order to manage the version files and maintain the latest version of the computer-aided design (CAD) files in asynchronous collaborative systems, one method of version merging for CAD files is proposed to resolve the problem based on feature extraction. First of all, the feature information is extracted based on the feature attribute of CAD files and stored in a XML feature file. Then, analyse the feature file, and the feature difference set is obtained by the given algorithm. Finally, the merging result of the difference set and the master files with application programming interface (API) interface functions is achieved, and then the version merging of CAD files is also realized. The application in Catia validated that the proposed method is feasible and valuable in engineering.
Analytical stresses in rough contacts
Authors: Sainsot P
Published: June 2010

The pressure distribution generated by rough surfaces contact induces high stresses just beneath the surface. These stresses are at the origin of several failure mechanisms such as wear, crack initiation, etc. Therefore, it is important to be able to predict these stresses.

This article describes an analytical model to evaluate the near surface stresses below a wavy surface. The originality of this work is to combine Herztian stresses in the general case of elliptical contacts and local stresses due to the pressure fluctuations.

Furthermore, in case of wavy surfaces simple analytical solutions permit the calculation of the maximum shear stress and its location. Compared to a fully numerical method, the time of calculation is negligible; moreover, the analytical expressions give one the possibility of a better understanding of the effect of roughness parameters such as the wavelength of the asperities.

Using a Fourier transform the results can be applied to rough surfaces.
Life Cycle Cost-Driven Innovations for Heavy Haul Turnouts
Authors: Ossberger H , Bishop G
Published: June 2010

Life cycle cost (LCC) considerations are of increasing importance for all organizations making long-term investments. Developments for heavy haul applications were carried out in close cooperation with users identifying the key technical requirements and the overall cost situation.

The design and material specifications of the components within a turnout have to be of the highest level with regards to axle load, dynamic forces, and accelerations to meet the demands for heavy haul.

Aside from the price of a product, the supply-chain, installation, and maintenance costs coupled with the total life expectancy all have a significant impact on the LCC.

Key influencing factors are: (a) initial track quality, (b) delivery logistics - track closing during installation, (c) inspection intervals, (d) time to maintain in track, (e) time for replacement of rails and components, (f) life expectancy of single components.

LCC optimized turnout systems are influenced by the following features: (a) minimizing forces on rails, switches, and crossings by optimizing turnout curvature and contact/transition geometries, (b) providing ideal conditions for maintenance work (e.g. through automatic tamping throughout the whole turnout without dismantling of components), (c) using low-maintenance components in order to minimize costs for inspection and maintenance and to increase availability especially in the field of switching, detecting, and locking of the turnouts. The implementation of LCC philosophy in a state-of-the-art heavy haul turnout technology will be highlighted and demonstrated with examples.
An Ongoing Debate: Should Beta Blockers be Used for Primary Hypertension?
Authors: Howard Patricia A.
Published: June 2010

This continuing feature will update readers on recent developments in cardiovascular pharmacotherapy. Cardiovascular disease remains the number one killer in the United States, and more clinical outcome trials have been conducted in cardiology than in any other field of medicine. Given this rapidly expanding knowledge base, pharmacists can have a significant impact on prevention and treatment—if they keep current with developments in drug therapy.
Developing a Medication Patient Safety Program – Infrastructure and Strategy
Authors: Mark Scott M. , Weber Robert J.
Published: June 2010

The Directors Forum series is written and edited by Robert Weber and Michael Sanborn and is designed to guide pharmacy leaders in establishing patient-centered services in hospitals and health systems. Another specific goal of this column is to address many of the key challenges that pharmacy directors face today, while providing information to foster growth in pharmacy leadership and patient safety. This month's Forum is co-authored by Scott Mark and focuses directly on the importance of a patient safety infrastructure.
Rhabdomyolysis Precipitated by Clopidogrel; Hyponatremia with Duloxetine; Duloxetine Again – Excessive Disturbing and Disabling Yawning; Testicular Pain Attributed to Statin Therapy; Life-Threatening Sensitivity Reaction to Riluzole; Choroidal Detachment Associated with Latanoprost Therapy; Pseudomembranous Colitis Associated with Rifampicin; Long-Term PPI Therapy and the Risk for Hip Fracture
Authors: Shuster Joel
Published: June 2010

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the FDA's medWatch program (800-FDA-1088). If you have reported an interesting preventable ADR to medWatch, please consider sharing the account with our readers. Write to Dr. Shuster at ISMP, 1800 Byberry Road, Suite 810, Huntingdon Valley, PA 19006 (call 215-947-7797; fax 215-914-1492; E-mail: joel.shuster@temple.edu ). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices in cooperation with the FDA's medWatch Program and Temple University School of Pharmacy. ISMP is an FDA medWatch partner.
Pixantrone Nilotinib
Authors: Higdon Jamie E. , Waddell J. Aubrey , Solimando Dominic A.
Published: June 2010

The increasing complexity of cancer chemotherapy increases the requirement that pharmacists be familiar with these highly toxic agents. This column will review various issues related to preparation, dispensing, and administration of cancer chemotherapy, and review various agents, both commercially available and investigational, used to treat malignant diseases.
Impact of Enteric vs Non-Enteric Coated Aspirin Preparations on Efficacy and Toxicity
Authors: Andrle Anne M.
Published: June 2010

This feature examines the impact of pharmacologic interventions on the treatment of the critically ill patient — an area of health care that has become increasingly complex. Recent advances in drug therapy (including evolving and controversial data) for adult intensive-care-unit patients will be reviewed and assessed in terms of clinical, humanistic, and economic outcomes. Direct questions or comments to Gil Fraser, PharmD, at fraseg@mmc.org or Sandra Kane-Gill, PharmD, MSc, at kanesl@upmc.edu .
Tacrolimus (Topical): Vitiligo
Authors: Generali Joyce , Cada Dennis J.
Published: June 2010

Off-Label Drug Uses — This Hospital Pharmacy feature is extracted from Off-Label DrugFacts, a quarterly publication available from Wolters Kluwer Health. Off-Label DrugFacts is a practitioner-oriented resource for information about specific FDA-unapproved drug uses. This new guide to the literature will enable the health care professional/clinician to quickly identify published studies on off-label uses and to determine if a specific use is rational in a patient care scenario. The most relevant data are provided in tabular form, so the reader can easily identify the scope of information available. A summary of the data—including background, study design, patient population, dosage information, therapy duration, results, safety, and therapeutic considerations—precedes each table of published studies. References direct the reader to the full literature for more comprehensive information prior to patient care decisions. Direct questions or comments regarding “Off-Label Drug Uses” to hospitalpharmacy@wolterskluwer.com .