bluuebunny/crossref_metadata_2025 huggingface dataset:
Capitalizing Disease
Authors: Prasad Amit
Published: August 2009

Recent success of Indian engineers, businessmen, as well as other technically qualified professionals has created an obsession with knowledge and creativity. Documents like India as a Knowledge Superpower have proliferated and we continually hear the mantra of investing in and harnessing of human capital. There are, however, several strands of human capital in India and not all of them harness knowledge and creativity. People on whom drugs are being tested represent one such human capital, which, even though it is being energetically mobilized to provide India with a strategic advantage in the world market, also highlights the contradictions within India’s shifting imaginary, economy and politics. Drug trials in India, in the context of neoliberal globalization, not only challenge and complicate, but also operate within a constellation of divisions — labor/capital, west/non-west, colonial/sovereign, national/global and so on. In this article I analyze how the people on whom drug testing is being done in India are being ‘harnessed’ as human capital, which leads to politicization of ‘bare life’ through ‘inclusive-exclusion’.
Hesperidin attenuates benzo[α] pyrene-induced testicular toxicity in rats via regulation of oxidant/antioxidant balance
Authors: Arafa HMM , Aly HAA , Abd-Ellah MF , El-Refaey HM
Published: August 2009

Benzo[α]pyrene (BaP) is one of the polycyclic aromatic hydrocarbons, which has shown carcinogenic, teratogenic, and mutagenic potentials. The reproductive toxicity of BaP in male was not well investigated. Thereby, we have addressed in the current study the testicular toxicity of BaP and the postulate whether or not the citrus flavonoid, hesperidin (HDN), could ameliorate such toxicity in male Swiss albino rats. In this sense, animals were challenged with BaP (50 mg/kg/day, orally) for 10 consecutive days. HDN (200 mg/kg/day, orally) was administered ahead of BaP challenge for 10 consecutive days. BaP induced testicular toxicity that was well characterized histologically and biochemically. It decreased the relative testis weight and induced pyknosis and necrobiotic changes as well as chromatolysis in the nuclei of the spermatocytes in the seminiferous tubules. It also markedly deteriorated epididymal function as shown by decreased sperm count, motility, and daily sperm production. The polyaromatic hydrocarbon also reduced the testicular activities of lactate dehydrogenase (LDH-X), superoxide dismutase (SOD), and glutathione-S-transferase (GST). Besides, it decreased the testicular reduced glutathione (GSH) but increased malondialdehyde (MDA) contents. Prior administration of HDN ahead of BaP challenge ameliorated all the histological and biochemical alterations induced by BaP. It improved the epididymal function and mitigated the injurious effects of BaP on the seminiferous tubules. In conclusion, HDN has proven protective effects in BaP-induced testicular toxicity paradigm, and this protection resides, at least in part, on its antioxidant properties.
A Cross-Sector Comparison of Motivation-Related Concepts in For-Profit and Not-For-Profit Service Organizations
Authors: De Cooman Rein , De Gieter Sara , Pepermans Roland , Jegers Marc
Published: August 2009

This contribution examines differences in four motivation-related concepts between employees in not-for-profit and for-profit sector service organizations. Using regression analyses, 630 knowledge workers, employed in either the not-for-profit or the for-profit sector, were compared. The majority of the hypotheses were supported by the data. Even after the impact of gender, age, seniority, contract type, and task characteristics were controlled for, employees from both sectors differed significantly. Not-for-profit workers valued more social service, perceived a better person—organization fit, and were more motivated by identified and integrated regulation. Their for-profit counterparts valued more advancement and were more motivated by external regulation. These conclusions account for a broad range of activities within the service industry because a wide variety of organizations were included in the study.
Incorporated but Not IRS-Registered: Exploring the (Dark) Grey Fringes of the Nonprofit Universe
Authors: Grønbjerg Kirsten A. , Liu Helen K. , Pollak Thomas H.
Published: August 2009

Listings of Internal Revenue Service (IRS)-registered and state-incorporated nonprofits for the same region may differ for a variety of reasons. Using Indiana as a case study, we first describe the distribution of nonprofits across these two listings. We then present findings from a small telephone survey of incorporated nonprofits that are not registered with the IRS for Indiana to explore whether they are excluded from the IRS-listing for statutory, technical, or compliance reasons. We consider several aspects of state incorporation status: date of incorporation and whether active status has been maintained or not. We conclude that researchers need to pay careful attention to the limitations of the IRS registration system when wishing to examine the dimensions of the nonprofit sector at local, state, or regional levels. Our finding, that some nonprofits fail to maintain active incorporation status, points to significant problems of nonprofit capacity.
Networking in Europe for special centres of excellence for autoimmune diseases
Authors: Vasconcelos C , Cervera R
Published: August 2009

The studies developed by the European Working Party on Systemic Lupus Erythematosus and the European Forum on Antiphospholipid Antibodies stress the importance of the creation of international networks devoted to the study of autoimmune diseases and the need for centres of excellence in the management of these conditions. This article analyses the importance of such centres and networks in Europe.
European attempts for the standardisation of the antiphospholipid antibodies
Authors: Tincani A , Filippini M , Scarsi M , Galli M , Meroni PL
Published: August 2009

According to the Sydney criteria, antiphospholipid syndrome (APS) diagnosis is closely related to the demonstration of antiphospholipid antibodies (aPL) in patients sera. For this purpose, three different assays are conventionally accepted: lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2 glycoprotein I (β2GPI) antibodies. LA, described in the 1950s is a coagulation-based functional assay, which indirectly detects the presence of aPL. The aCL ELISA was developed in 1985; the identification of β2GPI as a major target of aPL, allowed the introduction of anti-β2GPI ELISA. Even if the diagnostic criteria for APS have been well defined, the laboratory detection of aPL is not always reproducible for many reasons. To achieve a univocal diagnostic definition of APS, efforts were made to reduce the inter- and/or intra-laboratory variability of the diagnostic tests. In this article, we analyse the studies performed to standardise aPL assays that were developed within the European Forum on Antiphospholipid Antibodies.
Intravenous immunoglobulins in systemic lupus erythematosus: from the bench to the bedside
Authors: Zandman-Goddard G , Blank M , Shoenfeld Y
Published: August 2009

This article is an update on the clinical and research data available on systemic lupus erythematosus (SLE) and intravenous immunoglobulin (IVIg) therapy that includes some studies performed under the umbrella of the European Working Party on SLE. Various mechanisms of IVIg may play a role, some synergistically, in the modulation of SLE. Recently it has been suggested that IVIg also suppresses the expansion of autoreactive B lymphocytes through signalling of the FcgRIIB, idiotype-mediated inhibition of B cell receptors and neutralisation of cytokines such as the B cell survival factors (B cell activation factor (BAFF and APRIL). In case reports and in open trials, high-dose IVIg (2 g/kg over a 5-day period) has consistently been shown to be a beneficial and safe adjunct therapeutic agent for over 20 manifestations in patients with SLE. It can be given as a first choice of therapy in some cases, for example, in neurological involvement and in those patients who refuse certain immunosuppressive agents such as cyclophosphamide, or in patients who have concomitant infections. Furthermore, IVIg may have a steroid-sparing effect although this characteristic needs further investigation. Specific IVIg (an anti-idiotype to anti-DNA, phosphorylcholine and antiphospholipids) has been shown to be effective in experimental murine models. Hence, extractable IVIg that is directed to the specific pathogenic immunoglobulins will enable the more specific therapy for patients with lupus.
Ethical Analysis of Non-Medical Fetal Ultrasound
Authors: Leung John Lai Yin , Pang Samantha Mei Che
Published: August 2009

Obstetric ultrasound is the well-recognized prenatal test used to visualize and determine the condition of a pregnant woman and her fetus. Apart from the clinical application, some businesses have started promoting the use of fetal ultrasound machines for nonmedical reasons. Non-medical fetal ultrasound (also known as ‘keepsake’ ultrasound) is defined as using ultrasound to view, take a picture, or determine the sex of a fetus without a medical indication. Notwithstanding the guidelines and warnings regarding ultrasound safety issued by governments and professional bodies, the absence of scientifically proven physical harm to fetuses from this procedure seems to provide these businesses with grounds for rapid expansion. However, this argument is too simplistic because current epidemiological evidence is not synchronous with advancing ultrasound technology. As non-medical fetal ultrasound has aroused very significant public attention, a thorough ethical analysis of this topic is essential. Using a multifaceted approach, we analyse the ethical perspective of non-medical fetal ultrasound in terms of the expectant mother, the fetus and health professionals. After applying four major theories of ethics and principles (the precautionary principle; theories of consequentialism and impartiality; duty-based theory; and rights-based theories), we conclude that obstetric ultrasound practice is ethically justifiable only if the indication for its use is based on medical evidence. Non-medical fetal ultrasound can be considered ethically unjustifiable. Nevertheless, the ethical analysis of this issue is time dependent owing to rapid advancements in ultrasound technology and the safety issue. The role of health professionals in ensuring that obstetric ultrasound is an ethically justifiable practice is also discussed.
Management of a Request for Physician-Assisted Suicide
Authors: Rodriguez Davila Sandra L. , Vidal Elizabeth , Stewart Jonathan T. , Caserta Maria T.
Published: August 2009

With the legalization of physician-assisted suicide (PAS) in several states, it remains controversial whether present guidelines take into account the complexity of identifying treatable sources of suffering, including underlying depression and other psychiatric disorders, in this high risk population. We present a case in which a patient with end-stage prostate cancer requested PAS; this request was in a state where PAS is not a legal option. He was evaluated psychiatrically and was not found to be depressed, but ample opportunities were found to improve his quality of life. With appropriate treatment, he lost interest in PAS as an option. We discuss the need for a comprehensive evaluation to properly assess and manage the untreated physical and emotional suffering that may influence a patient’s decision to hasten death.
Hodgkin’s Lymphoma Presenting as Dominant Gastric Lesion in Immunocompetent Patients: Report of 5 Cases With EBV Analysis
Authors: Gualco Gabriela , Ortega Virginia , Chioato Lucimara , Musto Maria L. , Bacchi Livia M. , Weiss Lawrence M. , Bacchi Carlos E.
Published: August 2009

Primary Hodgkin’s lymphoma (HL) of the stomach is an extremely rare entity. Most cases of gastric involvement by HL are observed in the setting of disseminated disease. The nonspecific nature of the symptoms and endoscopic findings, which include a large malignant-looking ulcer and mass or wall thickening, together with the considerable histological overlap between HLs and some non-HLs or undifferentiated carcinoma, make the surgical resection diagnosis extremely difficult. An accurate diagnosis is important as treatment and outcome differ significantly for these neoplasms. In small endoscopic gastric biopsies and even in postoperative specimens, the precise histological diagnosis of HL is particularly challenging. Here, the authors report 5 cases of 2 women and 3 men aged 22 to 68, with gastric involvement by classic HLs—3 primary gastric HLs and 2 as part of widespread disease. All 5 patients presented with digestive symptoms. At endoscopy, the lesions presented as ulcerated and elevated lesions, with or without mucosal thickening. Four patients were misdiagnosed in the preoperative biopsy or in the gastrectomy specimen. Association with Epstein-Barr virus (EBV) was detected in 4 cases, with a predominance of subtype A EBV. These cases illustrate the significant difficulties, both clinical and pathological, in achieving the diagnosis of HL involving the stomach in immunocompetent patients.
Cognitive decline in multiple sclerosis: impact of topographic lesion distribution on differential cognitive deficit patterns
Authors: Tiemann L. , Penner IK , Haupts M. , Schlegel U. , Calabrese P.
Published: August 2009

Background: Multiple sclerosis (MS) is often accompanied by cognitive dysfunction. A negative correlation between cerebral lesion load and atrophy and cognitive performance has been pointed out almost consistently. Further, the distribution of lesions might be critical for the emergence of specific patterns of cognitive deficits.

Objective: The current study evaluated the significance of total lesion area (TLA) and central atrophy for the prediction of general cognitive dysfunction and tested for a correspondence between lesion topography and specific cognitive deficit patterns.

Methods: Thirty-seven patients with MS underwent neuropsychological assessment and magnetic resonance imaging. Lesion burden and central atrophy were quantified. Patients were classified into three groups by means of individual lesion topography (punctiform lesions/periventricular lesions/confluencing lesions in both periventricular and extra-periventricular regions).

Results: TLA was significantly related to 7 cognitive variables, whereas third ventricle width was significantly associated with 20 cognitive parameters. The three groups differed significantly in their performances on tasks concerning alertness, mental speed, and memory function.

Conclusion: Third ventricle width as a straight-forward measure of central atrophy proved to be of substantial predictive value for cognitive dysfunction, whereas total lesion load played only a minor role. Periventricular located lesions were significantly related to decreased psychomotor speed, whereas equally distributed cerebral lesion load did not. These findings support the idea that periventricular lesions have a determinant impact on cognition in patients with MS.
The Subjective Health Complaints Inventory: A useful instrument to identify various aspects of health and ability to cope in older people?
Authors: Thygesen Elin , Lindstrom Torill Christine , Saevareid Hans Inge , Engedal Knut
Published: August 2009

Aims: The aims were to investigate the factor structure of the Subjective Health Complaints Inventory (SHC) in a population of 75 years and above and to identify whether somatic, psychosocial, and coping factors were associated with the SHC factors. Methods: Data from 242 elderly persons were analyzed. The measures were: the SHC Inventory, Sense of Coherence, Social Provision Scale, Self-Rated Health, General Health Questionnaire, Clinical Dementia Rating, Reported Illness, Barthel ADL Index, sex, age, and education. Results: The factor analysis resulted in four subgroups: musculoskeletal pain (15% of variance), gastrointestinal problems (12% of variance), respiratory/allergy complaints (11% of variance), and pseudoneurology (11% of variance). The occurrence of complaints was 76% for musculoskeletal complaints, 51% for gastrointestinal complaints, 30% for flu, 43% for allergy, and 93% for pseudoneurology. Self-rated health and reported illness were significantly associated with musculoskeletal complaints (15% of variance), impairment in activities of daily living (ADL) with gastrointestinal complaints (3% of variance), and finally sense of coherence, self-rated health, and psychological distress were associated with pseudoneurology (32% of variance). No variables were associated with respiratory/allergy complaints. Conclusions: This study supports the stability of the SHC’s factor structure. The low occurrence of health complaints could possibly be due to survival effects, or that old people to a greater extent than younger people compare themselves with aged peers. The subscales focusing on somatic symptoms were explained by reported illnesses and functional impairments to a limited degree only. The pseudoneurology subscale score was associated with psychological measures, particularly ability to cope.
What is an island? Concepts, meanings and polysemies of insulartopoiin Greek sources
Authors: Kopaka Katerina
Published: August 2009

This article proposes an alternative way to explore a series of definitions, concepts, meanings and, sometimes, polysemies of island worlds, by using mainly ancient Greek literary sources, diachronic island names, and their etymologies, epithets, and other systems of labelling and describing them. It argues that such evidence literally and metaphorically involves mirrors and maps, and transcribes important parameters of an eloquent cognitive geography, forged from long-established knowledge and empirical wisdom, and relevant to modern scientific insights, including archaeological ones. If systematically investigated and thoroughly deciphered, this may disclose numerous meaningful elements of the insulartopoiwe study; and thus enrich significantly our efforts to conceive them as ‘total’ natural and cultural geographies – or ‘insularities’ – through time. Here, a limited number of cited examples illustrate a few, and mainly physical, aspects of their morphological, geological, topographic and other environmental traits – only tentatively touching upon their human-made landscapes. All the same, the information this provides may be also relevant, even if indirectly, to the islands' cultural environments. Furthermore, this approach can certainly be expanded to cover various other general and specific insular properties – including their inhabitants and diachronic monuments.
Estimating Attendance at Major League Baseball Games for the 2007 Season
Authors: Lemke Robert J. , Leonard Matthew , Tlhokwane Kelebogile
Published: August 2009

Using games from Major League Baseball’s 2007 season, individual game attendance is estimated using censored normal regression with home-team fixed-effects. Included in the model are several factors affecting attendance, such as divisional and interleague rivalries, that to date have been omitted from the literature. The relationship between attendance and game characteristics is shown to be fundamentally different between small market and large market teams. Attendance is also shown to steadily increase as the probability that the home team will win the game increases, which stands in contrast to the uncertainty of outcome hypothesis that predicts that attendance will eventually decrease if the home team’s chance of winning the game gets too large.
Women Who Fight
Authors: Abel Ernest L
Published: August 2009

AbstractAlthough only recently legalized in many countries, women's boxing is gaining increasing worldwide popularity. However, participation of women in this hypermasculinized sport is inconsistent with long-standing cultural expectations of femininity. This survey catalogs the nicknames given to women boxers, obtained from two online data bases (Women's Boxing Archive Network; Boxing Encyclopedia) and contends that many of these nicknames are intended to reassure the boxing audience, and often the boxers themselves, that despite their aggressiveness, these women are still inherently female.
Regulation of JAK2 by miR-135a: prognostic impact in classic Hodgkin lymphoma
Authors: Navarro Alfons , Diaz Tania , Martinez Antonio , Gaya Anna , Pons Aina , Gel Bernat , Codony Carles , Ferrer Gerardo , Martinez Carmen , Montserrat Emili , Monzo Mariano
Published: August 2009

The behavior of classic Hodgkin lymphoma (cHL) is determined by both the intrinsic features of the tumor cells and the characteristics of the microenvironment, making the analysis of entire lymph nodes an effective approach to understanding the disease. We examined the influence of our previously reported 25-microRNA signature for cHL on clinical outcome in 89 homogeneously treated cHL patients with a median follow-up of 80 months. Patients with low miR-135a expression had a higher probability of relapse (P = .04) and a shorter disease-free survival (P = .02). Functional analysis of cHL cell lines showed that mature miR-135a levels increased after pre–miR-135a transfection, causing apoptosis and decreased cell growth. Target analysis showed a direct regulation by miR-135a of JAK2, a cytoplasmic tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. miR-135a–mediated JAK2 down-regulation led to decreased mRNA and protein levels of the antiapoptotic gene Bcl-xL, suggesting a role for Bcl-xL in miR-135a/JAK2–mediated apoptosis. Our findings confirm the critical role of miR-135a in the survival of cHL cells and in the prognosis of cHL patients, indicating that novel treatment approaches targeting miR-135a may potentially benefit these patients.
The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model
Authors: Cheng Ke , Sportoletti Paolo , Ito Keisuke , Clohessy John G. , Teruya-Feldstein Julie , Kutok Jeffery L. , Pandolfi Pier Paolo
Published: August 2009

Although NPM1 gene mutations leading to aberrant cytoplasmic expression of nucleophosmin (NPMc+) are the most frequent genetic lesions in acute myeloid leukemia, there is yet no experimental model demonstrating their oncogenicity in vivo. We report the generation and characterization of a transgenic mouse model expressing the most frequent human NPMc+ mutation driven by the myeloid-specific human MRP8 promoter (hMRP8-NPMc+). In parallel, we generated a similar wild-type NPM trans-genic model (hMRP8-NPM). Interestingly, hMRP8-NPMc+ transgenic mice developed myeloproliferation in bone marrow and spleen, whereas nontransgenic littermates and hMRP8-NPM transgenic mice remained disease free. These findings provide the first in vivo evidence indicating that NPMc+ confers a proliferative advantage in the myeloid lineage. No spontaneous acute myeloid leukemia was found in hMPR8-NPMc+ or hMRP8-NPM mice. This model will also aid in the development of therapeutic regimens that specifically target NPMc+.
AML at older age: age-related gene expression profiles reveal a paradoxical down-regulation of p16INK4A mRNA with prognostic significance
Authors: de Jonge Hendrik J. M. , de Bont Eveline S. J. M. , Valk Peter J. M. , Schuringa Jan Jacob , Kies Marcel , Woolthuis Carolien M. , Delwel Ruud , Veeger Nic J. G. M. , Vellenga Edo , Löwenberg Bob , Huls Gerwin
Published: August 2009

Acute myeloid leukemia (AML) has a different clinical and biologic behavior in patients at older age. To gain further insight into the molecular differences, we examined a cohort of 525 adults to compare gene expression profiles of the one-third of youngest cases (n = 175; median age 31 years) with the one-third of oldest cases (n = 175; median age 59 years). This analysis revealed that 477 probe sets were up-regulated and 492 probe sets were down-regulated with increasing age at the significance level of P < .00001. After validation with 2 independent AML cohorts, the 969 differentially regulated probe sets on aging could be pointed to 41 probe sets, including the tumor-suppressor gene CDKN2A (encoding p16INK4A). In contrast to the induced p16INK4A expression that is associated with physiologic aging, p16INK4A is down-regulated in AML samples of patients with increasing age. However, this was only noticed in the intermediate- and unfavorable-risk group and not in the favorable-risk group and the molecularly defined subset “NPM1 mutant without FLT3-ITD.” Multivariate analysis revealed p16INK4A, besides cytogenetic risk groups, as an independent prognostic parameter for overall survival in older patients. We conclude that, in addition to altered clinical and biologic characteristics, AML presenting at older age shows different gene expression profiles.
Safety and efficacy of hematopoietic stem cell collection from mobilized peripheral blood in unrelated volunteers: 12 years of single-center experience in 3928 donors
Authors: Hölig Kristina , Kramer Michael , Kroschinsky Frank , Bornhäuser Martin , Mengling Thilo , Schmidt Alexander H. , Rutt Claudia , Ehninger Gerhard
Published: August 2009

We present results of peripheral blood stem cell (PBSC) mobilization, collection, and follow-up from 3928 consecutive unrelated stem cell donors. Assessments were performed prospectively at baseline, leukapheresis, 1 month, 6 months, and annually after PBSC donation. During follow-up, side effects were recorded by return post questionnaires. The median CD34+ cell counts on day 5 were 67.5/μL in male and 51/μL in female donors. Bone pain and headache were the most common side effects of recombinant human granulocyte-colony stimulating factor. Central venous access was required for 23 donations (0.6%). Throughout the follow-up, the absolute neutrophil counts were slightly below the initial baseline values but remained within the normal range. The majority of the donors reported good or very good health. Malignancies occurred in 12 donors (0.3%), among whom were 1 case of acute myeloid leukemia, 1 case of chronic lymphatic leukemia, and 2 cases of Hodgkin disease. Only the incidence of Hodgkin lymphoma differed significantly from an age-adjusted population. In conclusion, 7.5 μg/kg per day lenograstim proved to be safe and effective for mobilizing hematopoietic stem cells for allogeneic transplantation. Long-term monitoring of healthy PBSC donors remains important to guarantee the safety standards of PBSC mobilization and collection.
Dynamic behavior of NK cells during activation in lymph nodes
Authors: Beuneu Hélène , Deguine Jacques , Breart Béatrice , Mandelboim Ofer , Di Santo James P. , Bousso Philippe
Published: August 2009

During infection, Toll-like receptor agonists induce natural killer (NK)–cell activation by stimulating dendritic cells (DCs) to produce cytokines and transpresent IL-15 to NK cells. Yet the cellular dynamics underlying NK-cell activation by DCs in secondary lymphoid organs are largely unknown. Here, we have visualized NK-cell activation using mice in which NK cells and DCs express different fluorescent proteins. In response to polyI:C or lipopolysaccharide, NK cells maintained a vigorous migratory behavior, establishing multiple short contacts with maturing DCs. Furthermore, mature antigen-loaded DCs that made long-lived interactions with T cells formed short-lived contacts with NK cells. The different behaviors of T cells and NK cells during activation was correlated with distinct calcium responses upon interaction with DCs. That NK cells become activated while remaining motile may constitute an efficient strategy for sampling local concentrations of cytokines around DCs in secondary lymphoid tissues.
A fungal phylogeny based on 82 complete genomes using the composition vector method
Authors: Wang Hao , Xu Zhao , Gao Lei , Hao Bailin
Published: August 2009

Background

Molecular phylogenetics and phylogenomics have greatly revised and enriched the fungal systematics in the last two decades. Most of the analyses have been performed by comparing single or multiple orthologous gene regions. Sequence alignment has always been an essential element in tree construction. These alignment-based methods (to be called the standard methods hereafter) need independent verification in order to put the fungal Tree of Life (TOL) on a secure footing. The ever-increasing number of sequenced fungal genomes and the recent success of our newly proposed alignment-free composition vector tree (CVTree, see Methods) approach have made the verification feasible.

Results

In all, 82 fungal genomes covering 5 phyla were obtained from the relevant genome sequencing centers. An unscaled phylogenetic tree with 3 outgroup species was constructed by using the CVTree method. Overall, the resultant phylogeny infers all major groups in accordance with standard methods. Furthermore, the CVTree provides information on the placement of several currently unsettled groups. Within the sub-phylum Pezizomycotina, our phylogeny places the Dothideomycetes and Eurotiomycetes as sister taxa. Within the Sordariomycetes, it infers that Magnaporthe grisea and the Plectosphaerellaceae are closely related to the Sordariales and Hypocreales, respectively. Within the Eurotiales, it supports that Aspergillus nidulans is the early-branching species among the 8 aspergilli. Within the Onygenales, it groups Histoplasma and Paracoccidioides together, supporting that the Ajellomycetaceae is a distinct clade from Onygenaceae. Within the sub-phylum Saccharomycotina, the CVTree clearly resolves two clades: (1) species that translate CTG as serine instead of leucine (the CTG clade) and (2) species that have undergone whole-genome duplication (the WGD clade). It places Candida glabrata at the base of the WGD clade.

Conclusion

Using different input data and methodology, the CVTree approach is a good complement to the standard methods. The remarkable consistency between them has brought about more confidence to the current understanding of the fungal branch of TOL.
A physical map of the papaya genome with integrated genetic map and genome sequence
Authors: Yu Qingyi , Tong Eric , Skelton Rachel L , Bowers John E , Jones Meghan R , Murray Jan E , Hou Shaobin , Guan Peizhu , Acob Ricelle A , Luo Ming-Cheng , Moore Paul H , Alam Maqsudul , Paterson Andrew H , Ming Ray
Published: August 2009

Background

Papaya is a major fruit crop in tropical and subtropical regions worldwide and has primitive sex chromosomes controlling sex determination in this trioecious species. The papaya genome was recently sequenced because of its agricultural importance, unique biological features, and successful application of transgenic papaya for resistance to papaya ringspot virus. As a part of the genome sequencing project, we constructed a BAC-based physical map using a high information-content fingerprinting approach to assist whole genome shotgun sequence assembly.

Results

The physical map consists of 963 contigs, representing 9.4× genome equivalents, and was integrated with the genetic map and genome sequence using BAC end sequences and a sequence-tagged high-density genetic map. The estimated genome coverage of the physical map is about 95.8%, while 72.4% of the genome was aligned to the genetic map. A total of 1,181 high quality overgo (overlapping oligonucleotide) probes representing conserved sequences in Arabidopsis and genetically mapped loci in Brassica were anchored on the physical map, which provides a foundation for comparative genomics in the Brassicales. The integrated genetic and physical map aligned with the genome sequence revealed recombination hotspots as well as regions suppressed for recombination across the genome, particularly on the recently evolved sex chromosomes. Suppression of recombination spread to the adjacent region of the male specific region of the Y chromosome (MSY), and recombination rates were recovered gradually and then exceeded the genome average. Recombination hotspots were observed at about 10 Mb away on both sides of the MSY, showing 7-fold increase compared with the genome wide average, demonstrating the dynamics of recombination of the sex chromosomes.

Conclusion

A BAC-based physical map of papaya was constructed and integrated with the genetic map and genome sequence. The integrated map facilitated the draft genome assembly, and is a valuable resource for comparative genomics and map-based cloning of agronomically and economically important genes and for sex chromosome research.
Computational identification of hepatitis C virus associated microRNA-mRNA regulatory modules in human livers
Authors: Peng Xinxia , Li Yu , Walters Kathie-Anne , Rosenzweig Elizabeth R , Lederer Sharon L , Aicher Lauri D , Proll Sean , Katze Michael G
Published: August 2009

Background

Hepatitis C virus (HCV) is a major cause of chronic liver disease by infecting over 170 million people worldwide. Recent studies have shown that microRNAs (miRNAs), a class of small non-coding regulatory RNAs, are involved in the regulation of HCV infection, but their functions have not been systematically studied. We propose an integrative strategy for identifying the miRNA-mRNA regulatory modules that are associated with HCV infection. This strategy combines paired expression profiles of miRNAs and mRNAs and computational target predictions. A miRNA-mRNA regulatory module consists of a set of miRNAs and their targets, in which the miRNAs are predicted to coordinately regulate the level of the target mRNA.

Results

We simultaneously profiled the expression of cellular miRNAs and mRNAs across 30 HCV positive or negative human liver biopsy samples using microarray technology. We constructed a miRNA-mRNA regulatory network, and using a graph theoretical approach, identified 38 miRNA-mRNA regulatory modules in the network that were associated with HCV infection. We evaluated the direct miRNA regulation of the mRNA levels of targets in regulatory modules using previously published miRNA transfection data. We analyzed the functional roles of individual modules at the systems level by integrating a large-scale protein interaction network. We found that various biological processes, including some HCV infection related canonical pathways, were regulated at the miRNA level during HCV infection.

Conclusion

Our regulatory modules provide a framework for future experimental analyses. This report demonstrates the utility of our approach to obtain new insights into post-transcriptional gene regulation at the miRNA level in complex human diseases.
Modulations of cell cycle checkpoints during HCV associated disease
Authors: Sarfraz Saira , Hamid Saeed , Ali Syed , Jafri Wasim , Siddiqui Anwar A
Published: August 2009

Background

Impaired proliferation of hepatocytes has been reported in chronic Hepatitis C virus infection. Considering the fundamental role played by cell cycle proteins in controlling cell proliferation, altered regulation of these proteins could significantly contribute to HCV disease progression and subsequent hepatocellular carcinoma (HCC). This study aimed to identify the alterations in cell cycle genes expression with respect to early and advanced disease of chronic HCV infection.

Methods

Using freshly frozen liver biopsies, mRNA levels of 84 cell cycle genes in pooled RNA samples from patients with early or advanced fibrosis of chronic HCV infection were studied. To associate mRNA levels with respective protein levels, four genes (p27, p15, KNTC1 and MAD2L1) with significant changes in mRNA levels (> 2-fold, p-value < 0.05) were selected, and their protein expressions were examined in the liver biopsies of 38 chronic hepatitis C patients.

Results

In the early fibrosis group, increased mRNA levels of cell proliferation genes as well as cell cycle inhibitor genes were observed. In the advanced fibrosis group, DNA damage response genes were up-regulated while those associated with chromosomal stability were down-regulated. Increased expression of CDK inhibitor protein p27 was consistent with its mRNA level detected in early group while the same was found to be negatively associated with liver fibrosis. CDK inhibitor protein p15 was highly expressed in both early and advanced group, but showed no correlation with fibrosis. Among the mitotic checkpoint regulators, expression of KNTC1 was significantly reduced in advanced group while MAD2L1 showed a non-significant decrease.

Conclusion

Collectively these results are suggestive of a disrupted cell cycle regulation in HCV-infected liver. The information presented here highlights the potential of identified proteins as predictive factors to identify patients with high risk of cell transformation and HCC development.
Down-regulation of the pro-apoptotic XIAP associated factor-1 (XAF1) during progression of clear-cell renal cancer
Authors: Kempkensteffen Carsten , Fritzsche Florian Rudolf , Johannsen Manfred , Weikert Steffen , Hinz Stefan , Dietel Manfred , Riener Marc-Oliver , Moch Holger , Jung Klaus , Krause Hans , Miller Kurt , Kristiansen Glen
Published: August 2009

Background

Decreased expression of the interferon-stimulated, putative tumour suppressor gene XAF1 has been shown to play a role during the onset, progression and treatment failure in various malignancies. However, little is yet known about its potential implication in the tumour biology of clear-cell renal cell cancer (ccRCC).

Methods

This study assessed the expression of XAF1 protein in tumour tissue obtained from 291 ccRCC patients and 68 normal renal tissue samples, utilizing immunohistochemistry on a tissue-micro-array. XAF1 expression was correlated to clinico-pathological tumour features and prognosis.

Results

Nuclear XAF1 expression was commonly detected in normal renal- (94.1%) and ccRCC (91.8%) samples, without significant differences of expression levels. Low XAF1 expression in ccRCC tissue, however, was associated with progression of tumour stage (p = 0.040) and grade (p < 0.001). Low XAF1 tumour levels were also prognostic of significantly shortened overall survival times in univariate analysis (p = 0.018), but did not provide independent prognostic information.

Conclusion

These data suggest down-regulation of XAF1 expression to be implicated in ccRCC progression and implies that its re-induction may provide a therapeutic approach. Although the prognostic value of XAF1 in ccRCC appears to be limited, its predictive value remains to be determined, especially in patients with metastatic disease undergoing novel combination therapies of targeted agents with Interferon-alpha.
Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells
Authors: Ailan He , Xiangwen Xiao , Daolong Ren , Lu Gan , Xiaofeng Ding , Xi Qiao , Xingwang Hu , Rushi Liu , Jian Zhang , Shuanglin Xiang
Published: August 2009

Background

Activator protein 2 gamma (AP-2γ) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2γ has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis.

Methods

To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2γ binding sites on genomic DNA from human breast cancer cell line MDA-MB-453.

Results

20 novel DNA fragments proximal to potential AP-2γ targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2γ target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2γ. Decreased expression and overexpression of AP-2γ in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2γ directly regulates them.

Conclusion

This suggested that AP-2γ can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future.
Short-term effects of implemented high intensity shoulder elevation during computer work
Authors: Larsen Mette K , Samani Afshin , Madeleine Pascal , Olsen Henrik B , Søgaard Karen , Holtermann Andreas
Published: August 2009

Background

Work-site strength training sessions are shown effective to prevent and reduce neck-shoulder pain in computer workers, but difficult to integrate in normal working routines. A solution for avoiding neck-shoulder pain during computer work may be to implement high intensity voluntary contractions during the computer work. However, it is unknown how this may influence productivity, rate of perceived exertion (RPE) as well as activity and rest of neck-shoulder muscles during computer work. The aim of this study was to investigate short-term effects of a high intensity contraction on productivity, RPE and upper trapezius activity and rest during computer work and a subsequent pause from computer work.

Methods

18 female computer workers performed 2 sessions of 15 min standardized computer mouse work preceded by 1 min pause with and without prior high intensity contraction of shoulder elevation. RPE was reported, productivity (drawings per min) measured, and bipolar surface electromyography (EMG) recorded from the dominant upper trapezius during pauses and sessions of computer work. Repeated measure ANOVA with Bonferroni corrected post-hoc tests was applied for the statistical analyses.

Results

The main findings were that a high intensity shoulder elevation did not modify RPE, productivity or EMG activity of the upper trapezius during the subsequent pause and computer work. However, the high intensity contraction reduced the relative rest time of the uppermost (clavicular) trapezius part during the subsequent pause from computer work (p < 0.04).

Conclusion

Since a preceding high intensity shoulder elevation did not impose a negative impact on perceived effort, productivity or upper trapezius activity during computer work, implementation of high intensity contraction during computer work to prevent neck-shoulder pain may be possible without affecting the working routines. However, the unexpected reduction in clavicular trapezius rest during a pause with preceding high intensity contraction requires further investigation before high intensity shoulder elevations can be recommended as an integrated part of computer work.
Identifying the needs of penile cancer sufferers: A systematic review of the quality of life, psychosexual and psychosocial literature in penile cancer
Authors: Maddineni Satish B , Lau Maurice M , Sangar Vijay K
Published: August 2009

Background

Penile cancer is an uncommon malignancy with an incidence of 1 per 100,000. Conservative and radical treatments can be disfiguring and may have an impact on sexual function, quality of life (QOL), social interactions, self-image and self-esteem. Knowledge of how this disease affects patients is paramount to developing a global, multi-disciplinary approach to treatment.

Methods

A Medline/PubMed literature search was conducted using the terms "sexual function penis cancer"; "quality of life penis cancer" and "psychological effects penis cancer" from 1985 to 2008. Articles containing quantitative data on QOL, sexual function or psychological well-being were included.

Results

128 patients from 6 studies were included. 5 studies contained retrospective data whilst 1 study collected prospective data on erectile function. In the 6 studies 13 different quantitative tools were used to assess psychological well-being, QOL and sexual function. The General Health Questionnaire (GHQ) showed impaired well-being in up to 40% in 2 studies. Patients undergoing more mutilating treatments were more likely to have impaired well-being. The Hospital Anxiety and Depression Score (HADS) demonstrated pathological anxiety up to 31% in 2 studies. 1 study used the Diagnostic and Statistical Manual of Mental Disorders of psychiatric illness (DSM III-R) with 53% exhibiting mental illness, 25% avoidance behaviour and 40% impaired well-being. 12/30 suffered from post-traumatic stress disorder. The IIEF-15 was the commonest tool used to assess sexual function. The results varied from 36% in 1 study with no sexual function to 67% in another reporting reduced sexual satisfaction to 78% in another reporting high confidence with erections.

Conclusion

The treatment of penile cancer results in negative effects on well-being in up to 40% with psychiatric symptoms in approximately 50%. Up to two-thirds of patients report a reduction in sexual function. This study demonstrates that penile cancer sufferers can exhibit significant psychological dysfunction, yet no standardised tools or interventional pathways are available. Therefore, there is a need to identify and assess adequate tools to measure psychological and sexual dysfunction in this group of patients.
Use of placebo interventions among Swiss primary care providers
Authors: Fässler Margrit , Gnädinger Markus , Rosemann Thomas , Biller-Andorno Nikola
Published: August 2009

Background

Placebo interventions can have meaningful effects for patients. However, little is known about the circumstances of their use in clinical practice. We aimed to investigate to what extent and in which way Swiss primary care providers use placebo interventions. Furthermore we explored their ideas about the ethical and legal issues involved.

Methods

599 questionnaires were sent to general practitioners (GPs) and paediatricians in private practice in the Canton of Zurich in Switzerland. To allow for subgroup analysis GPs in urban, suburban, and rural areas as well as paediatricians were selected in an even ratio.

Results

233 questionnaires were completed (response rate 47%). 28% of participants reported that they never used placebo interventions. More participants used impure placebos therapeutically than pure placebos (57% versus 17%, McNemar's χ2 = 78, p < 0.001). There is not one clear main reason for placebo prescription. Placebo use was communicated to patients mostly as being "a drug or a therapy" (64%). The most frequently chosen ethical premise was that they "can be used as long as the physician and the patient work together in partnership" (60% for pure and 75% for impure placebos, McNemar's χ2 = 12, p < 0.001). A considerable number of participants (11–38%) were indecisive about statements regarding the ethical and legal legitimacy of using placebos.

Conclusion

The data obtained from Swiss primary care providers reflect a broad variety of views about placebo interventions as well as a widespread uncertainty regarding their legitimacy. Primary care providers seem to preferentially use impure as compared to pure placebos in their daily practice. An intense debate is required on appropriate standards regarding the clinical use of placebo interventions among medical professionals.