bluuebunny/crossref_metadata_2025 huggingface dataset:
Sport, Intellectuals and Public Sociology
Authors: Bairner Alan
Published: July 2009

This article seeks to explain why it has proved so difficult for sociologists of sport to assume the mantle of public intellectuals even in relation to sport itself. Using a case study relating to sport in Northern Ireland and rooted in personal experience, the article examines alternative ways in which intellectual activity, albeit unconventionally understood, can influence the world of sport. Specifically, the analysis draws upon Antonio Gramsci's distinction between traditional and organic intellectuals. It is argued that only through engagement with organic intellectuals who exercise authority within the subcultures of sport can critical sociologists hope to influence sporting practices.
Reputation and Reliability in Collective Goods
Authors: Anthony Denise , Smith Sean W. , Williamson Timothy
Published: July 2009

An important organizational innovation enabled by the revolution in information technologies is `open source' production which converts private commodities into essentially public goods. Similar to other public goods, incentives for reputation and group identity appear to motivate contributions to open source projects, overcoming the social dilemma inherent in producing such goods. In this paper we examine how contributor motivations affect the type of contributions made to the open source online encyclopedia Wikipedia. As expected, we find that registered participants, motivated by reputation and commitment to the Wikipedia community, make many contributions with high reliability. Surprisingly, however, we find the highest reliability from the vast numbers of anonymous `Good Samaritans' who contribute only once. Our findings of high reliability in the contributions of both Good Samaritans and committed `zealots' suggest that open source production succeeds by altering the scope of production such that a critical mass of contributors can participate.
Higher Punishment, Less Control?
Authors: Rauhut Heiko
Published: July 2009

Rational choice theory predicts for higher punishment less crime. However, many field studies could not support this conclusion. A game theoretic approach can explain these puzzling findings because it takes not only criminals' but also control agents' rationality into account. Mixed Nash equilibria predict for higher punishment less control and no effect on crime rates. A new experimental design is introduced to test game theoretic hypotheses. 196 subjects have been partitioned into `inspectees' who can steal money from each other and `inspectors' who can invest in control activities to catch inspectees. Static and dynamic analyses show that strategic interaction plays an important role for crime and punishment. However, effects are not as strong as predicted. Higher punishment indeed causes less control, but crime is deterred as well. Furthermore, dynamical analyses with the learning model fictitious play reveal that humans learn only slowly in inspection situations.
Adaptive Fault Tolerance for Scalable Cluster Computing in Space
Authors: James Mark L. , Shapiro Andrew A. , Springer Paul L. , Zima Hans P.
Published: July 2009

Future missions of deep-space exploration face the challenge of building more capable autonomous spacecraft and planetary rovers. Given the communication latencies and bandwidth limitations for such missions, the need for increased autonomy becomes mandatory, along with the requirement for enhanced on-board computational capabilities while in deep-space or time-critical situations. This will result in dramatic changes in the way missions are conducted and supported by on-board computing systems. Specifically, the traditional approach of relying exclusively on radiation-hardened hardware and modular redundancy will not be able to deliver the required computational power. As a consequence, such systems are expected to include high-capability low-power components based on emerging commercial-off-the-shelf (COTS) multi-core technology. In this paper we describe the design of a generic framework for introspection that supports runtime monitoring and analysis of program execution as well as a feedback-oriented recovery from faults. Our focus is on providing flexible software fault tolerance matched to the requirements and properties of applications by exploiting knowledge that is either contained in an application knowledge base, provided by users, or automatically derived from specifications. A prototype implementation is currently in progress at the Jet Propulsion Laboratory, California Institute of Technology, targeting a cluster of cell broadband engines.
Risk-Taking Behaviors Among Vertically HIV-Infected Adolescents in Northern Thailand
Authors: Lee Benjamin , Oberdorfer Peninnah
Published: July 2009

Purpose. To examine risk-taking behaviors and HIV self-disclosure among vertically HIV-infected adolescents in northern Thailand. Methods. A quantitative survey was conducted from 2007 to 2008 at 2 pediatric HIV clinics in northern Thailand among vertically HIV-infected adolescents aged ≥13 years, with disclosed HIV status. The survey assessed sociodemographics, substance use, sexual behavior, peer behaviors, knowledge, and attitudes regarding HIV disclosure. Results. Fifty-four adolescents (median age 14.6 years) participated; 18.5% reported previous alcohol use but none reported drug use; 35.2% reported presexual activity, and 3.7% reported sexual activity. Nearly all (96.3%) knew that HIV could be transmitted sexually, but knowledge regarding other sexually transmitted infections (STIs) was poor. Nearly half (48.1%) had never disclosed their status to anyone. Conclusions. Rates of substance use and sexual activity were low in this population. STI knowledge was poor and diagnosis self-disclosure was infrequent. Improved sexual education and self-disclosure skills are needed among vertically HIV-infected adolescents in Thailand.
B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders
Authors: Wilcox Ryan A. , Feldman Andrew L. , Wada David A. , Yang Zhi-Zhang , Comfere Nneka I. , Dong Haidong , Kwon Eugene D. , Novak Anne J. , Markovic Svetomir N. , Pittelkow Mark R. , Witzig Thomas E. , Ansell Stephen M.
Published: July 2009

Stromal elements present within the tumor microenvironment may suppress host immunity and promote the growth of malignant lymphocytes in B cell–derived non-Hodgkin lymphoma (NHL). In contrast, little is known about the microenvironment's role in T cell–derived NHL. B7-H1 (PD-L1, CD274), a member of the B7 family of costimulatory/coinhibitory ligands expressed by both malignant cells and stromal cells within the tumor microenvironment, has emerged as an important immune modulator capable of suppressing host immunity. Therefore, B7-H1 expression and function were analyzed in cutaneous and peripheral T-cell NHL. B7-H1 was expressed by tumor cells, monocytes, and monocyte-derived cells within the tumor microenvironment in T-cell NHL and was found to inhibit T-cell proliferation and promote the induction of FoxP3+ regulatory T cells. Collectively, the data presented provide the first evidence implicating B7-H1 in the suppression of host immunity in T-cell lymphoproliferative disorders and suggest that the targeting of B7-H1 may represent a novel therapeutic approach.
Significance of common variants on human chromosome 8q24 in relation to the risk of prostate cancer in native Japanese men
Authors: Liu Miao , Kurosaki Takayuki , Suzuki Motofumi , Enomoto Yutaka , Nishimatsu Hiroaki , Arai Tomio , Sawabe Motoji , Hosoi Takayuki , Homma Yukio , Kitamura Tadaichi
Published: July 2009

Background

Common variants on human chromosome 8q24, rs1447295 (C/A) and rs6983267 (T/G), have been recently linked to the prevalence of prostate cancer in European and American populations. Here, we evaluated whether the single-nucleotide polymorphisms rs1447295 and rs6983267 were associated with the risk of sporadic prostate cancer as well as latent prostate cancer in a native Japanese population.

Results

We analyzed genomic DNA samples from 391 sporadic prostate cancer patients, 323 controls who had died from causes unrelated to cancer and 112 Japanese men who were diagnosed as having latent prostate cancer based on autopsy results. The polymorphisms were determined by allelic discrimination using a fluorescent-based TaqMan assay. The A allele of rs1447295 was significantly associated with the risk of sporadic prostate cancer (p = 0.04; age-adjusted OR, 1.34), while the G allele of rs6983267 showed a trend towards being a high-risk allele (p = 0.06; age-adjusted OR, 1.27). No significant difference between these two polymorphisms and the risk of latent prostate cancer was observed in the present Japanese population.

Conclusion

Known variants on human chromosome 8q24 may be risk factors for sporadic prostate cancer in native Japanese men.
Genome wide analysis of human genes transcriptionally and post-transcriptionally regulated by the HTLV-I protein p30
Authors: Taylor John M , Ghorbel Sofiane , Nicot Christophe
Published: July 2009

Background

Human T-cell leukemia virus type 1 (HTLV-I) is a human retrovirus that is etiologically linked to adult T-cell leukemia (ATL), an aggressive and fatal lymphoproliferative disease. The viral transactivator, Tax, is thought to play an important role during the initial stages of CD4+T-cell immortalization by HTLV-1. Tax has been shown to activate transcription through CREB/ATF and NF-KB, and to alter numerous signaling pathways. These pleiotropic effects of Tax modify the expression of a wide array of cellular genes. Another viral protein encoded by HTLV-I, p30, has been shown to affect virus replication at the transcriptional and posttranscriptional levels. Little is currently known regarding the effect of p30 on the expression and nuclear export of cellular host mRNA transcripts. Identification of these RNA may reveal new targets and increase our understanding of HTLV-I pathogenesis. In this study, using primary peripheral blood mononuclear cells, we report a genome wide analysis of human genes transcriptionally and post-transcriptionally regulated by the HTLV-I protein p30.

Results

Using microarray analysis, we analyzed total and cytoplasmic cellular mRNA transcript levels isolated from PBMCs to assess the effect of p30 on cellular RNA transcript expression and their nuclear export. We report p30-dependent transcription resulting in the 2.5 fold up-regulation of 15 genes and the down-regulation of 65 human genes. We further tested nuclear export of cellular mRNA and found that p30 expression also resulted in a 2.5 fold post-transcriptional down-regulation of 90 genes and the up-regulation of 33 genes.

Conclusion

Overall, our study describes that expression of the HTLV-I protein p30 both positively and negatively alters the expression of cellular transcripts. Our study identifies for the first time the cellular genes for which nuclear export is affected by p30. These results suggest that p30 may possess a more global function with respect to mRNA transcription and the nuclear shuttling of cellular mRNA transcripts. In addition, these alterations in gene expression may play a role in cell transformation and the onset of leukemia.
Extent and consistency of linkage disequilibrium and identification of DNA markers for production and egg quality traits in commercial layer chicken populations
Authors: Abasht Behnam , Sandford Erin , Arango Jesus , Settar Petek , Fulton Janet E , O'Sullivan Neil P , Hassen Abebe , Habier David , Fernando Rohan L , Dekkers Jack CM , Lamont Susan J
Published: July 2009

Background

The genome sequence and a high-density SNP map are now available for the chicken and can be used to identify genetic markers for use in marker-assisted selection (MAS). Effective MAS requires high linkage disequilibrium (LD) between markers and quantitative trait loci (QTL), and sustained marker-QTL LD over generations. This study used data from a 3,000 SNP panel to assess the level and consistency of LD between single nucleotide polymorphisms (SNPs) over consecutive years in two egg-layer chicken lines, and analyzed one line by two methods (SNP-wise association and genome-wise Bayesian analysis) to identify markers associated with egg-quality and egg-production phenotypes.

Results

The LD between markers pairs was high at short distances (r2 > 0.2 at < 2 Mb) and remained high after one generation (correlations of 0.80 to 0.92 at < 5 Mb) in both lines. Single- and 3-SNP regression analyses using a mixed model with SNP as fixed effect resulted in 159 and 76 significant tests (P < 0.01), respectively, across 12 traits. A Bayesian analysis called BayesB, that fits all SNPs simultaneously as random effects and uses model averaging procedures, identified 33 SNPs that were included in the model >20% of the time (φ > 0.2) and an additional ten 3-SNP windows that had a sum of φ greater than 0.35. Generally, SNPs included in the Bayesian model also had a small P-value in the 1-SNP analyses.

Conclusion

High LD correlations between markers at short distances across two generations indicate that such markers will retain high LD with linked QTL and be effective for MAS. The different association analysis methods used provided consistent results. Multiple single SNPs and 3-SNP windows were significantly associated with egg-related traits, providing genomic positions of QTL that can be useful for both MAS and to identify causal mutations.
DNA-binding by Haemophilus influenzae and Escherichia coli YbaB, members of a widely-distributed bacterial protein family
Authors: Cooley Anne E , Riley Sean P , Kral Keith , Miller M Clarke , DeMoll Edward , Fried Michael G , Stevenson Brian
Published: July 2009

Background

Genes orthologous to the ybaB loci of Escherichia coli and Haemophilus influenzae are widely distributed among eubacteria. Several years ago, the three-dimensional structures of the YbaB orthologs of both E. coli and H. influenzae were determined, revealing a novel "tweezer"-like structure. However, a function for YbaB had remained elusive, with an early study of the H. influenzae ortholog failing to detect DNA-binding activity. Our group recently determined that the Borrelia burgdorferi YbaB ortholog, EbfC, is a DNA-binding protein. To reconcile those results, we assessed the abilities of both the H. influenzae and E. coli YbaB proteins to bind DNA to which B. burgdorferi EbfC can bind.

Results

Both the H. influenzae and the E. coli YbaB proteins bound to tested DNAs. DNA-binding was not well competed with poly-dI-dC, indicating some sequence preferences for those two proteins. Analyses of binding characteristics determined that both YbaB orthologs bind as homodimers. Different DNA sequence preferences were observed between H. influenzae YbaB, E. coli YbaB and B. burgdorferi EbfC, consistent with amino acid differences in the putative DNA-binding domains of these proteins.

Conclusion

Three distinct members of the YbaB/EbfC bacterial protein family have now been demonstrated to bind DNA. Members of this protein family are encoded by a broad range of bacteria, including many pathogenic species, and results of our studies suggest that all such proteins have DNA-binding activities. The functions of YbaB/EbfC family members in each bacterial species are as-yet unknown, but given the ubiquity of these DNA-binding proteins among Eubacteria, further investigations are warranted.
Yersinia outer protein YopE affects the actin cytoskeleton in Dictyostelium discoideumthrough targeting of multiple Rho family GTPases
Authors: Vlahou Georgia , Schmidt Oxana , Wagner Bettina , Uenlue Handan , Dersch Petra , Rivero Francisco , Weissenmayer Barbara A
Published: July 2009

Background

All human pathogenic Yersinia species share a virulence-associated type III secretion system that translocates Yersinia effector proteins into host cells to counteract infection-induced signaling responses and prevent phagocytosis. Dictyostelium discoideum has been recently used to study the effects of bacterial virulence factors produced by internalized pathogens. In this study we explored the potential of Dictyostelium as model organism for analyzing the effects of ectopically expressed Yersinia outer proteins (Yops).

Results

The Yersinia pseudotuberculosis virulence factors YopE, YopH, YopM and YopJ were expressed de novo within Dictyostelium and their effects on growth in axenic medium and on bacterial lawns were analyzed. No severe effect was observed for YopH, YopJ and YopM, but expression of YopE, which is a GTPase activating protein for Rho GTPases, was found to be highly detrimental. GFP-tagged YopE expressing cells had less conspicuous cortical actin accumulation and decreased amounts of F-actin. The actin polymerization response upon cAMP stimulation was impaired, although chemotaxis was unaffected. YopE also caused reduced uptake of yeast particles. These alterations are probably due to impaired Rac1 activation. We also found that YopE predominantly associates with intracellular membranes including the Golgi apparatus and inhibits the function of moderately overexpressed RacH.

Conclusion

The phenotype elicited by YopE in Dictyostelium can be explained, at least in part, by inactivation of one or more Rho family GTPases. It further demonstrates that the social amoeba Dictyostelium discoideum can be used as an efficient and easy-to-handle model organism in order to analyze the function of a translocated GAP protein of a human pathogen.
Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemia
Authors: Hu Xiaohan , Wu Xiangyang , Xu Jiali , Zhou Jin , Han Xiao , Guo Jun
Published: July 2009

Background

The regulation of protein phosphorylation requires a balance in the activity of protein kinases and protein phosphatases. Our previous data indicates that Src can increase ERK activity through Raf kinase in response to ischemic stimuli. This study examined the molecular mechanisms by which Src activates ERK cascade through protein phosphatases following cerebral ischemia.

Results

Ischemia-induced Src activation is followed by phosphorylation of PP2A at Tyr307 leading to its inhibition in the rat hippocampus. SU6656, a Src inhibitor, up-regulates PP2A activity, resulting in a significant decreased activity in ERK and its targets, CREB and ERα. In addition, the PP2A inhibitor, cantharidin, led to an up-regulation of ERK activity and was able to counteract Src inhibition during ischemia.

Conclusion

Src induces up-regulation of ERK activity and its target transcription factors, CREB and ERα, through attenuation of PP2A activity. Therefore, activation of ERK is the result of a crosstalk between two pathways, Raf-dependent positive regulators and PP2A-dependent negative regulators.
Activation of the pre-supplementary motor area but not inferior prefrontal cortex in association with short stop signal reaction time – an intra-subject analysis
Authors: Chao Herta HA , Luo Xi , Chang Jeremy LK , Li Chiang-shan R
Published: July 2009

Background

Our previous work described the neural processes of motor response inhibition during a stop signal task (SST). Employing the race model, we computed the stop signal reaction time (SSRT) to index individuals' ability in inhibitory control. The pre-supplementary motor area (preSMA), which shows greater activity in individuals with short as compared to those with long SSRT, plays a role in mediating response inhibition. In contrast, the right inferior prefrontal cortex (rIFC) showed greater activity during stop success as compared to stop error. Here we further pursued this functional differentiation of preSMA and rIFC on the basis of an intra-subject approach.

Results

Of 65 subjects who participated in four sessions of the SST, we identified 30 individuals who showed a difference in SSRT but were identical in other aspects of stop signal performance between the first ("early") and last two ("late") sessions. By comparing regional brain activation between the two sessions, we confirmed greater preSMA but not rIFC activity during short as compared to long SSRT session within individuals. Furthermore, putamen, anterior cerebellum and middle/posterior cingulate cortex also showed greater activity in association with short SSRT.

Conclusion

These results are consistent with a role of medial prefrontal cortex in controlled action and inferior frontal cortex in orienting attention. We discussed these findings with respect to the process of attentional monitoring and inhibitory motor control during stop signal inhibition.
Closing the osteoporosis care gap – Increased osteoporosis awareness among geriatrics and rehabilitation teams
Authors: Haaland Derek A , Cohen Dana R , Kennedy Courtney C , Khalidi Nader A , Adachi Jonathan D , Papaioannou Alexandra
Published: July 2009

Background

A care gap exists between recommendations and practice regarding the diagnosis and treatment of osteoporosis in fracture patients. The current study was designed to determine rates and predictors of in-hospital diagnosis and treatment of osteoporosis in patients admitted with fragility hip fractures, and to assess differences in these rates since the outset of the multipronged "Fracture? Think Osteoporosis" (FTOP) Program, which includes education of geriatrics and rehabilitation teams.

Methods

This is a retrospective cohort study conducted with data from two Hamilton, Ontario, university-based tertiary-care hospitals, and represents a follow-up to a previous study conducted 8 years earlier. Data pertaining to all 354 patients, age >/= 50, admitted between March 2003 and April 2004, inclusive, with a diagnosis of fragility hip fracture were evaluated. Twelve patients were excluded leaving 342 patients for analysis, with 75% female, mean age 81.

Outcomes included: Primary – In-hospital diagnosis of osteoporosis and/or initiation of anti-resorptive treatment ("new osteoporosis diagnosis/treatment"). Secondary – In-hospital mortality, BMD referrals, pre-admission osteoporosis diagnosis and treatment.

Results

At admission, 27.8% of patients had a pre-existing diagnosis of osteoporosis and/or were taking anti-resorptive treatment. Among patients with no previous osteoporosis diagnosis/treatment: 35.7% received a new diagnosis of osteoporosis, 21% were initiated on anti-resorptive treatment, and 14.3% received a BMD referral. The greatest predictor of new osteoporosis diagnosis/treatment was transfer to a rehabilitation or geriatrics unit: 79.5% of rehabilitation/geriatrics versus 18.5% of patients receiving only orthopedics care met this outcome (p < 0.001).

Conclusion

New diagnosis of osteoporosis among patients admitted with hip fracture has improved from 1.8% in the mid 1990's to 35.7%. Initiation of bisphosphonate therapy has likewise improved from 0% to 21%. Although multiple factors have likely contributed, the differential response between rehabilitation/geriatrics versus orthopedics patients suggests that education of the geriatric and rehabilitation teams, including one-on-one and group-based sessions, implemented as part of the FTOP Program, has played a role in this improvement. A significant care gap still exists for patients discharged directly from orthopedic units. The application of targeted inpatient and post-discharge initiatives, such as those that comprise the entire FTOP Program, may be of particular value in this setting.
Association between a rare SNP in the second intron of human Agouti related protein gene and increased BMI
Authors: Kalnina Ineta , Kapa Ivo , Pirags Valdis , Ignatovica Vita , Schiöth Helgi B , Klovins Janis
Published: July 2009

Background

The agouti related protein (AGRP) is an endogenous antagonist of the melanocortin 4 receptor and is one of the most potent orexigenic factors. The aim of the present study was to assess the genetic variability of AGRP gene and investigate whether the previously reported SNP rs5030980 and the rs11575892, a SNP that so far has not been studied with respect to obesity is associated with increased body mass index (BMI).

Methods

We determined the complete sequence of the AGRP gene and upstream promoter region in 95 patients with severe obesity (BMI > 35 kg/m2). Three polymorphisms were identified: silent mutation c.123G>A (rs34123523) in the second exon, non-synonymous mutation c.199G>A (rs5030980) and c.131-42C>T (rs11575892) located in the second intron. We further screened rs11575892 in a selected group of 1135 and rs5030980 in group of 789 participants from the Genome Database of Latvian Population and Latvian State Research Program Database.

Results

The CT heterozygotes of rs11575892 had significantly higher mean BMI value (p = 0.027). After adjustment for age, gender and other significant non-genetic factors (presence of diseases), the BMI levels remained significantly higher in carriers of the rs11575892 T allele (p = 0.001). The adjusted mean BMI value of CC genotype was 27.92 ± 1.01 kg/m2 (mean, SE) as compared to 30.97 ± 1.03 kg/m2 for the CT genotype. No association was found between rs5030980 and BMI.

Conclusion

This study presents an association of rare allele of AGRP polymorphism in heterozygous state with increased BMI. The possible functional effects of this polymorphism are unclear but may relate to splicing defects.
Factors associated with improved survival among older colorectal cancer patients in the US: a population-based analysis
Authors: Lang Kathleen , Korn Jonathan R , Lee David W , Lines Lisa M , Earle Craig C , Menzin Joseph
Published: July 2009

Background

The purpose of this study was to estimate the relative impact of changes in demographics, stage at detection, treatment mix, and medical technology on 5-year survival among older colorectal cancer (CRC) patients.

Methods

We selected older patients diagnosed with CRC between 1992 and 2000 from the SEER-Medicare database and followed them through 2005. Trends in demographic characteristics, stage at detection and initial treatment mix were evaluated descriptively. Separate multivariate logistic regression models for colon (CC) and rectal cancer (RC) patients were estimated to isolate the independent effects of these factors along with technological change (proxied by cohort year) on 5-year survival.

Results

Our sample included 37,808 CC and 13,619 RC patients (combined mean ± SD age: 77.2 ± 7.0 years; 55% female; 87% white). In recent years, more CC patients were diagnosed at Stage I and fewer at Stages II and IV, and more RC patients were diagnosed at Stage I and fewer at Stages II and III. CC and RC patients diagnosed in later years were slightly older with somewhat better Charlson scores and were more likely to be female, from the Northeast, and from areas with higher average education levels. Surgery alone was more common in later years for CC patients while combined surgery, chemotherapy, and radiotherapy was more common for RC patients. Between 1992 and 2000, 5-year observed survival improved from 43.0% to 46.3% for CC patients and from 39.4% to 42.2% for RC patients. Multivariate logistic regressions indicate that patients diagnosed in 2000 had significantly greater odds of 5-year survival than those diagnosed in 1992 (OR: 1.35 for CC, 1.38 for RC). Our decomposition suggests that early detection had little impact on survival; rather, technological improvements (e.g., new medical technologies or more effective use of existing technologies) and changing demographics were responsible for the largest share of the change in 5-year survival in CC and RC between 1992 and 2000.

Conclusion

Technological advances and changes in patient demographics had the largest impact on improved colorectal cancer survival during the study period.
Differences in regulation of tight junctions and cell morphology between VHL mutations from disease subtypes
Authors: Bangiyeva Valentina , Rosenbloom Ava , Alexander Ashlynn E , Isanova Bella , Popko Timothy , Schoenfeld Alan R
Published: July 2009

Background

In von Hippel-Lindau (VHL) disease, germline mutations in the VHL tumor suppressor gene cause clear cell renal carcinomas, hemangioblastomas, and pheochromocytomas. The VHL gene product is part of an ubiquitin E3 ligase complex and hypoxia-inducible factor alpha (HIF-α) is a key substrate, although additional VHL functions have been described. A genotype-phenotype relationship exists in VHL disease such that specific VHL mutations elicit certain subsets of these tumors. Here, we examine VHL genotype-phenotype correlations at the cellular level, focusing on the regulation of tight junctions and cell morphology.

Methods

Wild-type and various mutant VHL proteins representing VHL disease subtypes were stably expressed in 3 VHL-negative renal carcinoma cell lines. Using these cell lines, the roles of various VHL-associated cellular functions in regulation of cell morphology were investigated.

Results

As a whole, type 1 mutants varied greatly from type 2 mutants, demonstrating high levels of HIF-2α, cyclin D1 and α5 integrin, lower p27 levels, and a spindly, fibroblastic cellular appearance. Type 2 mutations demonstrated an epithelial morphology similar to wild-type VHL in the majority of the renal cell lines used. Knockdown of p27 in cells with wild-type VHL led to perturbations of both epithelial morphology and ZO-1 localization to tight junctions. ZO-1 localization correlated well with VHL disease subtypes, with greater mislocalization observed for genotypes associated with a higher risk of renal carcinoma. HIF-2α knockdown in 786-O partially restored ZO-1 localization, but did not restore an epithelial morphology.

Conclusion

VHL has both HIF-α dependent and HIF-α independent functions in regulating tight junctions and cell morphology that likely impact the clinical phenotypes seen in VHL disease.
Early effect of a single intravenous injection of ethanol on hepatic sinusoidal endothelial fenestrae in rabbits
Authors: Jacobs Frank , Wisse Eddie , De Geest Bart
Published: July 2009

Background

It has been postulated that ethanol affects hepatic sinusoidal and perisinusoidal cells. In the current experimental study, we investigated the early effect of a single intravenous dose of ethanol on the diameter of liver sinusoidal endothelial fenestrae in New Zealand White rabbits. The diameter of fenestrae in these rabbits is similar to the diameter found in humans with healthy livers. The effect of ethanol on the size of fenestrae was studied using transmission electron microscopy, because plastic embedding provides true measures for the diameter of fenestrae.

Results

After intravenous administration of a single dose of 0.75 g/kg, ethanol concentration peaked at 1.1 ± 0.10 g/l at ten minutes after injection. Compared to control rabbits (103 ± 1.1 nm; n = 8), the average diameter of fenestrae in ethanol-injected rabbits determined at 10 minutes after injection was significantly (p < 0.01) smaller (96 ± 2.2 nm; n = 5). Detailed analysis of distribution histograms of the diameters of fenestrae showed that the effect of ethanol was highly homogeneous.

Conclusion

A decrease of the diameter of fenestrae 10 minutes after ethanol administration is likely the earliest morphological alteration induced by ethanol in the liver and underscores the potential role of liver sinusoidal endothelial cells in alcoholic liver injury.
Tetraspanins regulate cell-to-cell transmission of HIV-1
Authors: Krementsov Dimitry N , Weng Jia , Lambelé Marie , Roy Nathan H , Thali Markus
Published: July 2009

Background

The presence of the tetraspanins CD9, CD63, CD81 and CD82 at HIV-1 budding sites, at the virological synapse (VS), and their enrichment in HIV-1 virions has been well-documented, but it remained unclear if these proteins play a role in the late phase of the viral replication cycle. Here we used overexpression and knockdown approaches to address this question.

Results

Neither ablation of CD9, CD63 and/or CD81, nor overexpression of these tetraspanins was found to affect the efficiency of virus release. However, confirming recently reported data, tetraspanin overexpression in virus-producing cells resulted in the release of virions with substantially reduced infectivity. We also investigated the roles of these tetraspanins in cell-to-cell transmission of HIV-1. Overexpression of CD9 and CD63 led to reduced cell-to-cell transmission of this virus. Interestingly, in knockdown experiments we found that ablation of CD63, CD9 and/or CD81 had no effect on cell-free infectivity. However, knockdown of CD81, but not CD9 and CD63, enhanced productive particle transmission to target cells, suggesting additional roles for tetraspanins in the transmission process. Finally, tetraspanins were found to be downregulated in HIV-1-infected T lymphocytes, suggesting that HIV-1 modulates the levels of these proteins in order to maximize the efficiency of its transmission within the host.

Conclusion

Altogether, these results establish an active role of tetraspanins in HIV-1 producer cells.
Temporal and geographic evidence for evolution of Sin Nombre virus using molecular analyses of viral RNA from Colorado, New Mexico and Montana
Authors: Black William C , Doty Jeffrey B , Hughes Mark T , Beaty Barry J , Calisher Charles H
Published: July 2009

Background

All viruses in the family Bunyaviridae possess a tripartite genome, consisting of a small, a medium, and a large RNA segment. Bunyaviruses therefore possess considerable evolutionary potential, attributable to both intramolecular changes and to genome segment reassortment. Hantaviruses (family Bunyaviridae, genus Hantavirus) are known to cause human hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome. The primary reservoir host of Sin Nombre virus is the deer mouse (Peromyscus maniculatus), which is widely distributed in North America. We investigated the prevalence of intramolecular changes and of genomic reassortment among Sin Nombre viruses detected in deer mice in three western states.

Methods

Portions of the Sin Nombre virus small (S) and medium (M) RNA segments were amplified by RT-PCR from kidney, lung, liver and spleen of seropositive peromyscine rodents, principally deer mice, collected in Colorado, New Mexico and Montana from 1995 to 2007. Both a 142 nucleotide (nt) amplicon of the M segment, encoding a portion of the G2 transmembrane glycoprotein, and a 751 nt amplicon of the S segment, encoding part of the nucleocapsid protein, were cloned and sequenced from 19 deer mice and from one brush mouse (P. boylii), S RNA but not M RNA from one deer mouse, and M RNA but not S RNA from another deer mouse.

Results

Two of 20 viruses were found to be reassortants. Within virus sequences from different rodents, the average rate of synonymous substitutions among all pair-wise comparisons (πs) was 0.378 in the M segment and 0.312 in the S segment sequences. The replacement substitution rate (πa) was 7.0 × 10-4 in the M segment and 17.3 × 10-4 in the S segment sequences. The low πa relative to πs suggests strong purifying selection and this was confirmed by a Fu and Li analysis. The absolute rate of molecular evolution of the M segment was 6.76 × 10-3 substitutions/site/year. The absolute age of the M segment tree was estimated to be 37 years. In the S segment the rate of molecular evolution was 1.93 × 10-3 substitutions/site/year and the absolute age of the tree was 106 years. Assuming that mice were infected with a single Sin Nombre virus genotype, phylogenetic analyses revealed that 10% (2/20) of viruses were reassortants, similar to the 14% (6/43) found in a previous report.

Conclusion

Age estimates from both segments suggest that Sin Nombre virus has evolved within the past 37–106 years. The rates of evolutionary changes reported here suggest that Sin Nombre virus M and S segment reassortment occurs frequently in nature.
Suppressive response of confections containing the extractive from leaves of Morus Alba on postprandial blood glucose and insulin in healthy human subjects
Authors: Nakamura Mariko , Nakamura Sadako , Oku Tsuneyuki
Published: July 2009

Background

The first aim of this study was to clarify the effective ratio of extractive from leaves of Morus Alba (ELM) to sucrose so as to apply this knowledge to the preparation of confections that could effectively suppress the elevation of postprandial blood glucose and insulin. The second aim was to identify the efficacy of confections prepared with the optimally effective ratio determined from the first study, using healthy human subjects.

Methods

Ten healthy females (22.3 years, BMI 21.4 kg/m2) participated in this within-subject, repeated measures study. For the first aim of this study, the test solutions containing 30 g of sucrose and 1.2 or 3.0 g of ELM were repeatedly and randomly given to each subject. To identify the practically suppressive effects on postprandial blood glucose and insulin, some confections with added ELM were prepared as follows: Mizu-yokan, 30 g of sucrose with the addition of 1.5 or 3.0 g ELM; Daifuku-mochi, 9.0 g of starch in addition to 30 g of sucrose and 1.5 or 3.0 g ELM; Chiffon-cake, 24 g of sucrose, starch, and 3.0 or 6.0 g of ELM, and were ingested by each subject. Blood and end-expiration were collected at selected periods after test food ingestion.

Results

When 30 g of sucrose with 1.2 or 3.0 g of ELM were ingested by subjects, the elevations of postprandial blood glucose and insulin were effectively suppressed (p < 0.01), and the most effective ratio of ELM to sucrose was evaluated to be 1:10. AUC (area under the curve) of breath hydrogen excretion for 6 h after the ingestion of an added 3 g of ELM significantly increased (p < 0.01). When AUCs-3h of incremental blood glucose of confections without ELM was 100, that of Mizu-yokan and Daifuku-mochi with the ratio (1:10) of ELM to sucrose was decreased to 53.4 and 58.2, respectively. Chiffon-cake added one-fourth ELM was 29.0.

Conclusion

ELM-containing confections for which the ratio of ELM and sucrose is one-tenth effectively suppress the postprandial blood glucose and insulin by inhibiting the intestinal sucrase, thus creating a prebiotic effect. The development of confections with ELM can therefore contribute to the prevention and the quality of life for prediabetic and diabetic patients.
IS711-based real-time PCR assay as a tool for detection of Brucellaspp. in wild boars and comparison with bacterial isolation and serology
Authors: Hinić Vladimira , Brodard Isabelle , Thomann Andreas , Holub Milena , Miserez Raymond , Abril Carlos
Published: July 2009

Background

Control of brucellosis in livestock, wildlife and humans depends on the reliability of the methods used for detection and identification of bacteria. In the present study, we describe the evaluation of the recently established real-time PCR assay based on the Brucella-specific insertion sequence IS711 with blood samples from 199 wild boars (first group of animals) and tissue samples from 53 wild boars (second group of animals) collected in Switzerland. Results from IS711 real-time PCR were compared to those obtained by bacterial isolation, Rose Bengal Test (RBT), competitive ELISA (c-ELISA) and indirect ELISA (i-ELISA).

Results

In the first group of animals, IS711 real-time PCR detected infection in 11.1% (16/144) of wild boars that were serologically negative. Serological tests showed different sensitivities [RBT 15.6%, c-ELISA 7.5% and i-ELISA 5.5%] and only 2% of blood samples were positive with all three tests, which makes interpretation of the serological results very difficult. Regarding the second group of animals, the IS711 real-time PCR detected infection in 26% of animals, while Brucella spp. could be isolated from tissues of only 9.4% of the animals.

Conclusion

The results presented here indicate that IS711 real-time PCR assay is a specific and sensitive tool for detection of Brucella spp. infections in wild boars. For this reason, we propose the employment of IS711 real-time PCR as a complementary tool in brucellosis screening programs and for confirmation of diagnosis in doubtful cases.
Chick Lrrn2, a novel downstream effector of Hoxb1 and Shh, functions in the selective targeting of rhombomere 4 motor neurons
Authors: Andreae Laura C , Lumsden Andrew , Gilthorpe Jonathan D
Published: July 2009

Background

Capricious is a Drosophila adhesion molecule that regulates specific targeting of a subset of motor neurons to their muscle target. We set out to identify whether one of its vertebrate homologues, Lrrn2, might play an analogous role in the chick.

Results

We have shown that Lrrn2 is expressed from early development in the prospective rhombomere 4 (r4) of the chick hindbrain. Subsequently, its expression in the hindbrain becomes restricted to a specific group of motor neurons, the branchiomotor neurons of r4, and their pre-muscle target, the second branchial arch (BA2), along with other sites outside the hindbrain. Misexpression of the signalling molecule Sonic hedgehog (Shh) via in ovo electroporation results in upregulation of Lrrn2 exclusively in r4, while the combined expression of Hoxb1 and Shh is sufficient to induce ectopic Lrrn2 in r1/2. Misexpression of Lrrn2 in r2/3 results in axonal rerouting from the r2 exit point to the r4 exit point and BA2, suggesting a direct role in motor axon guidance.

Conclusion

Lrrn2 acts downstream of Hoxb1 and plays a role in the selective targeting of r4 motor neurons to BA2.
The interactome of the amyloid β precursor protein family members is shaped by phosphorylation of their intracellular domains
Authors: Tamayev Robert , Zhou Dawang , D'Adamio Luciano
Published: July 2009

Background

Brain tissue from patients with Alzheimer's disease has shown an increase of phosphorylation of Tyr-682, located on the conserved Y682ENPTY motif, and Thr-668 residues, both in the intracellular domain (AID) of amyloid β precursor protein (APP), although the role of these two residues is not yet known.

Results

Here, we report that the phosphorylation status of Tyr-682, and in some cases Thr-668, shapes the APP interactome. It creates a docking site for SH2-domain containing proteins, such as ShcA, ShcB, ShcC, Grb7, Grb2, as well as adapter proteins, such as Crk and Nck, that regulate important biological processes, cytosolic tyrosine kinases, such as Abl, Lyn and Src, which regulate signal transduction pathways, and enzymes that control phosphatidylinositols levels and signaling, such as PLC-γ. At the same time, it either reduces (like for JIP1, NUMB, NUMBL and ARH) or abolishes (like for Fe65, Fe65L1 and Fe65L2) binding of other APP interactors. Phosphorylation of Thr-668, unlike Tyr-682, does not seem to affect APP's ability to interact with the various proteins, with Pin1 and X11 being the exclusions. We also found that there are some differences between the interactions to AID and to ALID1 and ALID2, its two homologues.

Conclusion

Our data indicates that APP can regulate diverse cellular processes and that, vice versa, a network of signaling events can impact APP processing. Our results also suggest that phosphorylation of the APP Intracellular Domain will dramatically shape the APP interactome and, consequently, will regulate APP processing, APP transport and APP/AID-mediated functions.
RIZ1 is potential CML tumor suppressor that is down-regulated during disease progression
Authors: Lakshmikuttyamma Ashakumary , Takahashi Naoto , Pastural Elodie , Torlakovic Emina , Amin Hesham M , Garcia-Manero Guillermo , Voralia Michael , Czader Magdalena , DeCoteau John F , Geyer C Ronald
Published: July 2009

Background

RIZ1 expression and activity are reduced in many cancers. In AML cell lines and patient material, RIZ1 expression is reduced relative to normal bone marrow. In chronic myelogenous leukemia (CML), blastic transformation is associated with loss of heterozygosity in the region where RIZ1 is located. RIZ1 is a PR domain methyltransferase that methylates histone H3 lysine 9, a modification important for transcriptional repression. In CML blast crisis cell lines RIZ1 represses insulin-like growth factor-1 expression and autocrine signaling. Together these observations suggest that RIZ1 may have a role in the chronic phase to blast crisis transition in CML.

Results

In CML patient material, we observed that RIZ1 expression was decreased during progression from chronic phase to blast crisis. RIZ1 was expressed in mature myeloid and CD34+ cells demonstrating that decreased RIZ1 expression in blast crisis is not due to an increased immature cell population. Expression of RIZ1 CML blast crisis cell lines decreased proliferation, increased apoptosis, and enhanced differentiation.

Conclusion

RIZ1 is a candidate tumor suppressor gene whose expression is decreased in blast crisis. Loss of RIZ1 activity results in decreased apoptosis and differentiation and enhanced proliferation. Together these results suggest that loss of RIZ1 expression will lead to an increase in myeloid blast cell population resulting in CML progression.
Head & neck optical diagnostics: vision of the future of surgery
Authors: Upile Tahwinder , Jerjes Waseem , Sterenborg Henricus JCM , El-Naggar Adel K , Sandison Ann , Witjes Max JH , Biel Merrill A , Bigio Irving , Wong Brian JF , Gillenwater Ann , MacRobert Alexander J , Robinson Dominic J , Betz Christian S , Stepp Herbert , Bolotine Lina , McKenzie Gordon , Mosse Charles Alexander , Barr Hugh , Chen Zhongping , Berg Kristian , D'Cruz Anil K , Stone Nicholas , Kendall Catherine , Fisher Sheila , Leunig Andreas , Olivo Malini , Richards-Kortum Rebecca , Soo Khee Chee , Bagnato Vanderlei , Choo-Smith Lin-Ping , Svanberg Katarina , Tan I Bing , Wilson Brian C , Wolfsen Herbert , Yodh Arjun G , Hopper Colin
Published: July 2009

Review paper and Proceedings of the Inaugural Meeting of the Head and Neck Optical Diagnostics Society (HNODS) on March 14th 2009 at University College London.

The aim of our research must be to provide breakthrough translational research which can be applied clinically in the immediate rather than the near future. We are fortunate that this is indeed a possibility and may fundamentally change current clinical and surgical practice to improve our patients' lives.