bluuebunny/crossref_metadata_2025 huggingface dataset:
PIN1 gene variants in Alzheimer's disease
Authors: Maruszak Aleksandra , Safranow Krzysztof , Gustaw Katarzyna , Kijanowska-Haładyna Beata , Jakubowska Katarzyna , Olszewska Maria , Styczyńska Maria , Berdyński Mariusz , Tysarowski Andrzej , Chlubek Dariusz , Siedlecki Janusz , Barcikowska Maria , Żekanowski Cezary
Published: November 2009

Background

Peptidyl-prolyl isomerase, NIMA-interacting 1 (PIN1) plays a significant role in the brain and is implicated in numerous cellular processes related to Alzheimer's disease (AD) and other neurodegenerative conditions. There are confounding results concerning PIN1 activity in AD brains. Also PIN1 genetic variation was inconsistently associated with AD risk.

Methods

We performed analysis of coding and promoter regions of PIN1 in early- and late-onset AD and frontotemporal dementia (FTD) patients in comparison with healthy controls.

Results

Analysis of eighteen PIN1 common polymorphisms and their haplotypes in EOAD, LOAD and FTD individuals in comparison with the control group did not reveal their contribution to disease risk.

In six unrelated familial AD patients four novel PIN1 sequence variants were detected. c.58+64C>T substitution that was identified in three patients, was located in an alternative exon. In silico analysis suggested that this variant highly increases a potential affinity for a splicing factor and introduces two intronic splicing enhancers. In the peripheral leukocytes of one living patient carrying the variant, a 2.82 fold decrease in PIN1 expression was observed.

Conclusion

Our data does not support the role of PIN1 common polymorphisms as AD risk factor. However, we suggest that the identified rare sequence variants could be directly connected with AD pathology, influencing PIN1 splicing and/or expression.
Evidence for genetic association of RORB with bipolar disorder
Authors: McGrath Casey L , Glatt Stephen J , Sklar Pamela , Le-Niculescu Helen , Kuczenski Ronald , Doyle Alysa E , Biederman Joseph , Mick Eric , Faraone Stephen V , Niculescu Alexander B , Tsuang Ming T
Published: November 2009

Background

Bipolar disorder, particularly in children, is characterized by rapid cycling and switching, making circadian clock genes plausible molecular underpinnings for bipolar disorder. We previously reported work establishing mice lacking the clock gene D-box binding protein (DBP) as a stress-reactive genetic animal model of bipolar disorder. Microarray studies revealed that expression of two closely related clock genes, RAR-related orphan receptors alpha (RORA) and beta (RORB), was altered in these mice. These retinoid-related receptors are involved in a number of pathways including neurogenesis, stress response, and modulation of circadian rhythms. Here we report association studies between bipolar disorder and single-nucleotide polymorphisms (SNPs) in RORA and RORB.

Methods

We genotyped 355 RORA and RORB SNPs in a pediatric cohort consisting of a family-based sample of 153 trios and an independent, non-overlapping case-control sample of 152 cases and 140 controls. Bipolar disorder in children and adolescents is characterized by increased stress reactivity and frequent episodes of shorter duration; thus our cohort provides a potentially enriched sample for identifying genes involved in cycling and switching.

Results

We report that four intronic RORB SNPs showed positive associations with the pediatric bipolar phenotype that survived Bonferroni correction for multiple comparisons in the case-control sample. Three RORB haplotype blocks implicating an additional 11 SNPs were also associated with the disease in the case-control sample. However, these significant associations were not replicated in the sample of trios. There was no evidence for association between pediatric bipolar disorder and any RORA SNPs or haplotype blocks after multiple-test correction. In addition, we found no strong evidence for association between the age-at-onset of bipolar disorder with any RORA or RORB SNPs.

Conclusion

Our findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder.
Re-organisation of oesophago-gastric cancer care in England: progress and remaining challenges
Authors: Palser Thomas R , Cromwell David A , Hardwick Richard H , Riley Stuart A , Greenaway Kimberley , Allum William , van der Meulen Jan HP
Published: November 2009

Background

Oesophago-gastric cancer services in England have been extensively reorganised since 2001 to deliver a centralised, specialist-led service. Our aim was to assess how well the National Health Service (NHS) in England met organisational standards for oesophago-gastric cancer care.

Methods

Questionnaires that asked about the provision of staging investigations, curative and palliative treatments and key personnel were sent in September 2007 to the lead clinician for oesophago-gastric cancer at all 30 cancer networks and 156 NHS acute trusts in England.

Results

Responses were received from all networks and 81% of NHS trusts. All networks provided essential staging investigations and a range of endoscopic palliative therapies. Only 16 of the 30 cancer networks discussed all patients at the specialist multi-disciplinary team meeting and 11 networks had not fully centralised curative surgery. There was also variation between NHS trusts in the integration of the palliative care team, the availability of nurse specialists and the use of dieticians to provide nutritional support.

Conclusion

There has been considerable progress in reforming oesophago-gastric cancer services but the process of reorganisation is still incomplete and regional differences in service provision exist that may lead to variation in patient outcomes.
A genome-wide synthetic dosage lethality screen reveals multiple pathways that require the functioning of ubiquitin-binding proteins Rad23 and Dsk2
Authors: Liu Chang , van Dyk Dewald , Li Yue , Andrews Brenda , Rao Hai
Published: November 2009

Background

Ubiquitin regulates a myriad of important cellular processes through covalent attachment to its substrates. A classic role for ubiquitin is to flag proteins for destruction by the proteasome. Recent studies indicate that ubiquitin-binding proteins (e.g. Rad23, Dsk2, Rpn10) play a pivotal role in transferring ubiquitylated proteins to the proteasome. However, the specific role of these ubiquitin receptors remains poorly defined. A key to unraveling the functions of these ubiquitin receptors is to identify their cellular substrates and biological circuits they are involved in. Although many strategies have been developed for substrate isolation, the identification of physiological targets of proteolytic pathways has proven to be quite challenging.

Results

Using a genome-wide functional screen, we have identified 11 yeast genes that cause slower growth upon their overexpression in cells lacking two ubiquitin-binding proteins Rad23 and Dsk2. Our results suggest that proper functioning of Rad23 and Dsk2 is required for efficient pheromone response, transcription, amino acid metabolism, and DNA damage response. Two proteins identified by the screen are shown to be proteolytic substrates of Dsk2, validating the large scale synthetic dosage lethality screen as a new strategy for identifying substrates of a specific degradation pathway.

Conclusion

In conclusion, as proof-of-concept, we show that a synthetic dosage lethality screen, which is based on the toxicity induced by gene overexpression, offers an effective, complementary method to elucidating biological functions of proteolytic pathways.
Evaluation of the psychometric properties of a modified version of the Social Phobia Screening Questionnaire for use in adolescents
Authors: Gren-Landell Malin , Björklind Andreas , Tillfors Maria , Furmark Tomas , Svedin Carl Göran , Andersson Gerhard
Published: November 2009

Background

Social phobia (social anxiety disorder - SAD) is a rather common but often undetected and undertreated psychiatric condition in youths. Screening of SAD in young individuals in community samples is thus important in preventing negative outcomes. The present study is the first report on the psychometric properties of the Social Phobia Screening Questionnaire for Children and adolescents (SPSQ-C).

Methods

The SPSQ-C was administered to a community sample of high-school students. Test-retest reliability over three weeks was evaluated (n = 127) and internal consistency was calculated for items measuring level of fear in eight social situations. To measure concurrent validity, subjects who reported SAD on at least one occasion and randomly selected non-cases were blindly interviewed with the Structured Clinical Interview for DSM-IV Axis-I disorders (SCID-I), as gold standard (n = 51).

Results

A moderate test-retest reliability, r = .60 (P < .01), and a satisfactory alpha coefficient of .78 was found. Values of sensitivity and specificity were 71% and 86% respectively, and area under the curve (AUC) was .79. Positive likelihood ratio (LR+) showed that a positive screening result was five times more likely to be correct than to reflect a non-case. Negative likelihood ratio (LR -) was .34. In addition, positive predictive value was 45% and negative predictive value was 95%. The prevalence of self-reported SAD was found to be 7.2% at the first assessment.

Conclusion

The SPSQ-C is a short and psychometrically sound questionnaire for screening of SAD in adolescents, with the advantage of being based on the DSM-IV criteria.
The occurrence and management of fluid retention associated with TKI therapy in CML, with a focus on dasatinib
Authors: Masiello David , Gorospe Gerry , Yang Allen S
Published: November 2009

Tyrosine kinase inhibitors (TKIs) like dasatinib and nilotinib are indicated as second-line treatment for chronic myeloid leukemia resistant or intolerant to the current first-line TKI imatinib. These are agents are well tolerated, but potent and as such should be monitored for potentially serious side-effects like fluid retention and pleural effusions. Here we present key clinical trial data and safety considerations for all FDA approved TKIs in context for effective management of fluid retention and pleural effusions. Altering the dasatinib regimen from 70 mg twice daily to 100 mg daily reduces the risk of pleural effusion for patients taking dasatinib. Should pleural effusion develop, dasatinib should be interrupted until the condition resolves. Patients with a history of pleural effusion risk factors should be monitored closely while taking dasatinib. Patients receiving imatinib and nilotinib are not without risk of fluid retention. All patients should also be educated to recognize and report key symptoms of fluid retention or pleural effusion. Pleural effusions are generally managed by dose interruption/reduction and other supportive measures in patients with chronic myeloid leukemia receiving dasatinib therapy.
Pelvic mass in von Recklinghausen's neurofibromatosis: diagnostic issues: a case report
Authors: Kluger Nicolas , Perrochia Hélène , Guillot Bernard
Published: November 2009

Background

Leiomyomas are benign smooth muscle cell tumours. They are the most common uterine neoplasms, although they may also occur elsewhere, such as in the gastrointestinal and urinary tracts. Leiomyomas are uncommon in von Recklinghausen's neurofibromatosis (NF1). However, the literature suggests that the association of NF1 and leiomyomas or leiomyosarcoma is not entirely coincidental.

Case Report

We report here the unusual case of a 47-year-old woman with NF1 who presented menorrhagias and a hard, tender pelvic mass composed of uterine leiomyomas. Positron emission tomography/computed tomography disclosed an area of increased 18-fluorodeoxyglucose (FDG) uptake in the upper right part of the mass that raised the suspicion of malignancy. Magnetic resonance imaging revealed numerous intramural leiomyomas ranging from 1 to 6 cm, including a 6-cm submucosal leiomyoma that had abundant cellularity, matching FDG uptake. Abdominal hysterectomy was performed and microscopic examination confirmed the diagnosis of multiple benign smooth muscle tumours (uterine leiomyomatosis).

Conclusion

Our case illustrates several diagnostic issues that arose while exploring this pelvic mass. Moreover, the association of uterine leiomyoma and NF1 may not be fortuitous.
Rapid and sustained improvements in health-related quality of life, fatigue, and other patient-reported outcomes in rheumatoid arthritis patients treated with certolizumab pegol plus methotrexate over 1 year: results from the RAPID 1 randomized controlled trial
Authors: Strand Vibeke , Mease Philip , Burmester Gerd R , Nikaï Enkeleida , Coteur Geoffroy , van Vollenhoven Ronald , Combe Bernard , Keystone Edward C , Kavanaugh Arthur
Published: November 2009

Introduction

The objective of this study was to assess the impact of certolizumab pegol (CZP) treatment on health-related quality of life (HRQoL), fatigue and other patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA).

Methods

Patients with active RA (N = 982) were randomized 2:2:1 to subcutaneous CZP (400 mg at weeks 0, 2 and 4; followed by CZP 200 mg or 400 mg) plus methotrexate (MTX) every other week, or placebo (PBO) plus MTX. PRO assessments included HRQoL, fatigue, physical function, arthritis pain and disease activity. Adjusted mean changes from baseline in all PROs were obtained using analysis of covariance (ANCOVA) applying last observation carried forward (LOCF) imputation. The proportion of patients achieving clinically meaningful improvements in each PRO was obtained using logistic regression and by applying non-responder imputation to missing values after rescue medication or withdrawal. The correlations between PRO responses and clinical responses were also assessed by tetrachoric correlation using non-responder imputation.

Results

Patients treated with CZP plus MTX reported significant (P < 0.001), clinically meaningful improvements in HRQoL at the first assessment (week 12); reductions in fatigue, disease activity and pain and improvements in physical function were reported at week 1. In particular, CZP-treated patients reported improvements in mental health. Mean changes from baseline in the SF-36 Mental Component Summary (MCS) at week 52 for CZP 200 mg and 400 mg plus MTX, and PBO plus MTX were 6.4, 6.4 and 2.1, respectively (P < 0.001). In addition, mental health and vitality scores in CZP-treated patients approached age- and gender-adjusted US population norms. Improvements in all PROs were sustained. Similar benefits were reported with both CZP doses. Changes in SF-36 MCS scores had the lowest correlation with disease activity scores (DAS28) and American College of Rheumatology 20% improvement (ACR20) response rates, while improvements in pain showed the highest correlation.

Conclusions

Treatment with CZP plus MTX resulted in rapid and sustained improvements in all PROs, indicating that the benefits of CZP extend beyond clinical efficacy endpoints into areas that are more relevant and meaningful for patients on a daily basis.

Trial Registration

ClinicalTrials.gov NCT00152386.
Lysophosphatidic Acid Up-Regulates Expression of Growth-Regulated Oncogene-α, Interleukin-8, and Monocyte Chemoattractant Protein-1 in Human First-Trimester Trophoblasts: Possible Roles in Angiogenesis and Immune Regulation
Authors: Chen Shee-Uan , Chou Chia-Hung , Chao Kuang-Han , Lee Hsinyu , Lin Chung-Wu , Lu Hsin-Fen , Yang Yu-Shih
Published: November 2009

The serum lysophospholipase D activity and production of lysophosphatidic acid (LPA) increase in women with pregnancy. The effects of LPA on human placenta tissue remained unclear. We investigate the expression of LPA receptors and function of LPA in human first-trimester trophoblasts. Normal villous trophoblasts were obtained from termination of first-trimester gestation. We examined the expression of LPA receptors in primary culture of trophoblasts and the tissue. The effects of LPA on the expressions of chemokines of trophoblasts were examined using RT-PCR and enzyme immunoassay. We delineate signal pathways of LPA-inducing relevant chemokines in trophoblasts. The secretory chemokines were tested for angiogenic function using human endometrial microvascular endothelial cells and for immunological chemotaxis using decidual natural killer cells and THP-1 monocytes. The results revealed the expression of LPA1 receptors in trophoblast cells. LPA enhanced growth-regulated oncogene (GRO)-α, IL-8 and monocyte chemoattractant protein (MCP)-1 expressions in a time- and dose-dependent manner. Mechanistic dissection disclosed that LPA functioned mainly via the LPA1 receptor, Gi protein, various signal mediators of ERK, protein kinase C, p38, Akt, and c-Jun N-terminal kinase, and nuclear factor-κB pathways to secrete these chemokines. LPA-induced IL-8 protein secretion of trophoblasts enhanced permeability, migration, proliferation, and capillary tube formation of human endometrial microvascular endothelial cells. LPA-induced GRO-α and MCP-1 incited chemotaxis of natural killer cells and monocytes. We demonstrate that LPA mediates trophoblast cells to produce GRO-α, IL-8, and MCP-1 via LPA1 receptors and nuclear factor-κB-dependent signal pathways. Through LPA-induced chemokine production, human first-trimester trophoblast cells may regulate angiogenesis and innate immune system in early pregnancy.
In the Realm of the Indigenous: Local, National, and Global Articulations in Fishing Luck
Authors: Chang Anita Wen-Shin
Published: November 2009

Marking a notable achievement in Taiwanese cinema, Fishing Luck (Deng dai fei yu), the first feature narrative film set on Taiwan's Orchid Island, home to the Tao Aborigines, premiered in 2005 at the Twelfth Women Make Waves film festival in Taipei. It was also the first feature film directed by award-winning Taiwanese woman director Tseng Wen-Chen. While contributing to the slowly growing canon of Taiwanese cinema, an industry historically dwarfed by the Hollywood machine, this essay examines how the film perpetuates notions of primitivism in cinema in its effort to build bridges of communication between Taiwanese Han and Aborigines. What is needed instead is a sincere commitment to supporting the expression of a multiplicity of evolving voices and experiences, which must include Taiwan's indigenous peoples. This essay calls for a sustainable training and funding infrastructure to nurture Aborigine talent in Taiwan's film industry, however vulnerable the industry may be.
Memory and Music in Okinawa: The Cultural Politics of War and Peace
Authors: Roberson James E.
Published: November 2009

This paper maps Okinawan songs from both pre- and postwar periods that have narrated Okinawan experiences of war and prayers for peace, arguing that these songs may be heard as sites of memory that trace Okinawa's conflicted positions within the Japanese empire and state, and between the United States and Japan. Especially in the long postwar period, these songs have invoked memories of the past and dreams for the future in making politically significant present-day claims.
Effete-mediated degradation of Cyclin A is essential for the maintenance of germline stem cells in Drosophila
Authors: Chen Dongsheng , Wang Qi , Huang Haidong , Xia Laixin , Jiang Xiaoyong , Kan Lijuan , Sun Qinmiao , Chen Dahua
Published: November 2009

Increasing evidence supports the idea that the regulation of stem cells requires both extrinsic and intrinsic mechanisms. However, much less is known about how intrinsic signals regulate the fate of stem cells. Studies on germline stem cells (GSCs) in the Drosophila ovary have provided novel insights into the regulatory mechanisms of stem cell maintenance. In this study, we demonstrate that a ubiquitin-dependent pathway mediated by the Drosophila eff gene, which encodes the E2 ubiquitin-conjugating enzyme Effete (Eff), plays an essential role in GSC maintenance. We show that Eff both physically and genetically interacts with dAPC2, a key component of the anaphase-promoting complex (APC), which acts as a multisubunit E3 ligase and plays an essential role in targeting mitotic regulators for degradation during exit from mitosis. This interaction indicates that Eff regulates the APC/C-mediated proteolysis pathway in GSCs. Moreover, we show that expression of a stable form of Cyclin A, but not full-length Cyclin A, results in GSC loss. Finally we show that, in common with APC2, Eff is required for the ubiquitylation of Cyclin A, and overexpression of full-length Cyclin A accelerates the loss of GSCs in the eff mutant background. Collectively, our data support the idea that Effete/APC-mediated degradation of Cyclin A is essential for the maintenance of germline stem cells in Drosophila. Given that the regulation of mitotic Cyclins is evolutionarily conserved between flies and mammals, our study also implies that a similar mechanism may be conserved in mammals.
The cadherin Fat2 is required for planar cell polarity in theDrosophilaovary
Authors: Viktorinová Ivana , König Tina , Schlichting Karin , Dahmann Christian
Published: November 2009

Planar cell polarity is an important characteristic of many epithelia. In the Drosophila wing, eye and abdomen, establishment of planar cell polarity requires the core planar cell polarity genes and two cadherins, Fat and Dachsous. Drosophila Fat2 is a cadherin related to Fat; however, its role during planar cell polarity has not been studied. Here, we have generated mutations in fat2 and show that Fat2 is required for the planar polarity of actin filament orientation at the basal side of ovarian follicle cells. Defects in actin filament orientation correlate with a failure of egg chambers to elongate during oogenesis. Using a functional fosmid-based fat2-GFP transgene, we show that the distribution of Fat2 protein in follicle cells is planar polarized and that Fat2 localizes where basal actin filaments terminate. Mosaic analysis demonstrates that Fat2 acts non-autonomously in follicle cells, indicating that Fat2 is required for the transmission of polarity information. Our results suggest a principal role for Fat-like cadherins during the establishment of planar cell polarity.
Sanpodo: a context-dependent activator and inhibitor of Notch signaling during asymmetric divisions
Authors: Babaoglan A. Burcu , O'Connor-Giles Kate M. , Mistry Hemlata , Schickedanz Adam , Wilson Beth A. , Skeath James B.
Published: November 2009

Asymmetric cell divisions generate sibling cells of distinct fates (‘A’, ‘B’) and constitute a fundamental mechanism that creates cell-type diversity in multicellular organisms. Antagonistic interactions between the Notch pathway and the intrinsic cell-fate determinant Numb appear to regulate asymmetric divisions in flies and vertebrates. During these divisions, productive Notch signaling requires sanpodo, which encodes a novel transmembrane protein. Here, we demonstrate that Drosophila sanpodo plays a dual role to regulate Notch signaling during asymmetric divisions — amplifying Notch signaling in the absence of Numb in the ‘A’ daughter cell and inhibiting Notch signaling in the presence of Numb in the ‘B’ daughter cell. In so doing, sanpodo ensures the asymmetry in Notch signaling levels necessary for the acquisition of distinct fates by the two daughter cells. These findings answer long-standing questions about the restricted ability of Numb and Sanpodo to inhibit and to promote, respectively, Notch signaling during asymmetric divisions.
Patched regulates Smoothened trafficking using lipoprotein-derived lipids
Authors: Khaliullina Helena , Panáková Daniela , Eugster Christina , Riedel Falko , Carvalho Maria , Eaton Suzanne
Published: November 2009

Hedgehog (Hh) is a lipoprotein-borne ligand that regulates both patterning and proliferation in a wide variety of vertebrate and invertebrate tissues. When Hh is absent, its receptor Patched (Ptc) represses Smoothened (Smo) signaling by an unknown catalytic mechanism that correlates with reduced Smo levels on the basolateral membrane. Ptc contains a sterol-sensing domain and is similar to the Niemann-Pick type C-1 protein, suggesting that Ptc might regulate lipid trafficking to repress Smo. However, no endogenous lipid regulators of Smo have yet been identified, nor has it ever been shown that Ptc actually controls lipid trafficking. Here, we show that Drosophila Ptc recruits internalized lipoproteins to Ptc-positive endosomes and that its sterol-sensing domain regulates trafficking of both lipids and Smo from this compartment. Ptc utilizes lipids derived from lipoproteins to destabilize Smo on the basolateral membrane. We propose that Ptc normally regulates Smo degradation by changing the lipid composition of endosomes through which Smo passes, and that the presence of Hh on lipoproteins inhibits utilization of their lipids by Ptc.
Cdx2 regulation of posterior development through non-Hox targets
Authors: Savory Joanne G. A. , Bouchard Nathalie , Pierre Vicki , Rijli Filippo M. , De Repentigny Yves , Kothary Rashmi , Lohnes David
Published: November 2009

The homeodomain transcription factors Cdx1, Cdx2 and Cdx4 play essential roles in anteroposterior vertebral patterning through regulation of Hox gene expression. Cdx2 is also expressed in the trophectoderm commencing at E3.5 and plays an essential role in implantation, thus precluding assessment of the cognate-null phenotype at later stages. Cdx2 homozygous null embryos generated by tetraploid aggregation exhibit an axial truncation indicative of a role for Cdx2 in elaborating the posterior embryo through unknown mechanisms. To better understand such roles, we developed a conditional Cdx2 floxed allele in mice and effected temporal inactivation at post-implantation stages using a tamoxifen-inducible Cre. This approach yielded embryos that were devoid of detectable Cdx2 protein and exhibited the axial truncation phenotype predicted from previous studies. This phenotype was associated with attenuated expression of genes encoding several key players in axial elongation, including Fgf8, T, Wnt3a and Cyp26a1, and we present data suggesting that T, Wnt3a and Cyp26a1 are direct Cdx2 targets. We propose a model wherein Cdx2 functions as an integrator of caudalizing information by coordinating axial elongation and somite patterning through Hox-independent and -dependent pathways, respectively.
Tumor-suppression functions of merlin are independent of its role as an organizer of the actin cytoskeleton in Schwann cells
Authors: Lallemand Dominique , Saint-Amaux Aurelie Lampin , Giovannini Marco
Published: November 2009

Merlin is the product of the Nf2 tumor-suppressor gene, and inactivation of Nf2 leads to the development of neural tumors such as schwannomas and meningiomas in humans and mice. Merlin is a member of the ERM (ezrin, radixin and moesin) family of proteins that function as organizers of the actin cytoskeleton. Merlin structure is thought to be similar to that of the ERM proteins, and is held in a closed clamp conformation via intramolecular interactions of its N-terminal FERM (four-point-one, ERM) domain with an α-helical C-terminal domain. Like ERMs, merlin can remodel actin-rich cortical structures, yet merlin uniquely inhibits the proliferation of many different cell types. Here, we report that the F2 subdomain of the FERM domain and a domain close to the C-terminus that is defined by residues 532-579 are essential for merlin-mediated inhibition of primary Schwann cell proliferation. Furthermore, we demonstrate that the F1 subdomain of the merlin FERM domain is required for actin colocalization, proper regulation of merlin C-terminal phosphorylation and for remodeling the cytoskeleton, yet is not required for the inhibition of Schwann cell proliferation. Thus, tumor suppression by merlin is independent of its role as an organizer of the actin cytoskeleton in Schwann cells.
Telomeric armor: the layers of end protection
Authors: Oganesian Liana , Karlseder Jan
Published: November 2009

The linear nature of eukaryotic chromosomes necessitates protection of their physical ends, the telomeres, because the DNA-repair machinery can misconstrue the ends as double-stranded DNA breaks. Thus, protection is crucial for avoiding an unwarranted DNA-damage response that could have catastrophic ramifications for the integrity and stability of the linear genome. In this Commentary, we attempt to define what is currently understood by the term `telomere protection'. Delineating the defining boundaries of chromosome-end protection is important now more than ever, as it is becoming increasingly evident that, although unwanted DNA repair at telomeres must be avoided at all costs, the molecular players involved in recognition, signaling and repair of DNA damage might also serve to protect telomeres.
Matric Suction Measurement in Stress Path Cyclic Triaxial Testing of Unbound Granular Base Materials
Authors: Craciun Ovidiu , Lo Sik-Cheung Robert
Published: November 2009

Unbound granular base (UGB) materials are commonly placed as part of pavement foundations. These materials are generally designed to be in an unsaturated state in order to resist the dominantly cyclic loading. Therefore, the response of UGB materials under cyclic loading needs to be studied using the framework of unsaturated soil mechanics. This requires the measurement of matric suction evolution during cyclic loading, which is a major experimental challenge to be resolved. This paper presents the development of a cyclic triaxial testing system and associated experimental techniques that meet the challenges of testing UGB materials as unsaturated soils. The testing system enables the initializing of matric suction of a specimen and facilitates direct measurement of its evolution during cyclic loading. Two types of cyclic loading could be imposed: with constant cell pressure and with cyclic cell pressure. Selected test results of both types of cyclic loading were presented to demonstrate satisfactory performance of the proposed methodology. Furthermore, a detailed analysis of these selected test results was also undertaken to show the importance of matric suction for understanding the behavior of UGB materials under cyclic loading.
Selective Review of Weathering Tests for Sealants and Thoughts on the Development of Novel Test Concept Based on Simultaneous Weathering and Movement
Authors: Klosowski Jerome M. , Gorman Patrick D.
Published: November 2009

This paper reviews sealant weathering test methods developed during the past 40 years and highlights the fact that repeated movement cycles were shown to be important to reproduce some of the damage seen on real buildings. The studies reviewed further demonstrate that water, sunlight (especially the UV portion), and heat are important degradation factors that act on real buildings.
Metformin decreases IGF1-induced cell proliferation and protein synthesis through AMP-activated protein kinase in cultured bovine granulosa cells
Authors: Tosca Lucie , Ramé Christelle , Chabrolle Christine , Tesseraud Sophie , Dupont Joëlle
Published: November 2009

Although its mechanism of action is still unclear, metformin is an anti-diabetic drug effective to restore cyclicity and spontaneous ovulation in women with polycystic ovary syndrome. It may also reduce the risk of cancer. We have recently shown that metformin treatment decreases steroidogenesis through AMP-activated kinase (AMPK) in granulosa cells of various species. Here, we investigated the effects and the molecular mechanisms of metformin in IGF1-induced proliferation and protein synthesis in cultured bovine granulosa cells. Treatment with metformin (10 mM) for 24 h reduced cell proliferation and the levels of cyclin D2 and E, and increased the associations cyclin D2/p21 and cyclin D2/p27 without affecting cell viability in response to IGF1 (10−8 M). It also decreased IGF1-induced protein synthesis and phosphorylation of P70S6 kinase and ribosomal S6 protein. Interestingly, metformin treatment for 1 h decreased MAPK3/1 (ERK1/2) and P90RSK phosphorylation without affecting AKT phosphorylation in response to IGF1. Adenovirus-mediated expression of dominant-negative AMPK totally abolished the effects of metformin on cell proliferation and phosphorylation of P70S6K in response to IGF1. It also eliminated the inhibitory effects of metformin on MAPK3/1 and P90RSK phosphorylation. Taken together, our results strongly suggest that metformin reduces cell growth, protein synthesis, MAPK3/1, and P90RSK phosphorylation in response to IGF1 through an AMPK-dependent mechanism in cultured bovine granulosa cells.
Investigational Use of Metomidate Hydrochloride as a Shipping Additive for Two Ornamental Fishes
Authors: Kilgore Kathy Heym , Hill Jeffrey E. , Powell James F. F. , Watson Craig A. , Yanong Roy P. E.
Published: November 2009

During shipping, ornamental fish can be stressed due to handling, high stocking densities, and deteriorating water quality. Adding sedatives, such as metomidate hydrochloride, to shipping water may improve fish survival rates and the percentage of fish in saleable condition. Although the effects of metomidate hydrochloride on the stress response in fish have been studied, its application as a shipping additive has not been well investigated, particularly for tropical ornamental fishes shipped under industry conditions. Convict cichlids Cichlasoma nigrofasciatum and black mollies Poecilia sphenops were evaluated for 7 d after a 24-h period of exposure (including ground and air transport) to one of four metomidate hydrochloride concentrations: 0.0, 0.2, 0.5, and 1.0 mg/L. Immediate posttransport and cumulative mortality data, as well as 12-h and 7-d posttransport appearance and behavior scores, were generated. In convict cichlids, the highest dose of metomidate hydrochloride (1.0 mg/L) reduced mortality (0% compared with cumulative means of 5.5–9.2% in other groups) and increased the percentage of saleable fish (91.7% were immediately saleable compared with 12.5–50% in other groups). No effect was detected in black mollies at any concentration tested. Metomidate hydrochloride showed promise as a shipping additive for convict cichlids, but further studies are warranted to evaluate species-specific responses in other ornamental species.
Studies on the Possibility of Vertical Transmission of Norwegian Salmonid Alphavirus in Production of Atlantic Salmon in Norway
Authors: Bratland André , Nylund Are
Published: November 2009

Disease associated with salmonid Alphavirus (SAV) infection is a significant problem for farm production of salmonids in Europe. The SAV subtype 3 (SAV3) is a Norwegian subtype present exclusively in production systems for Atlantic salmon Salmo salar and rainbow trout Oncorhynchus mykiss in western Norway. It has been suggested that SAV3 is transmitted through smolt transport from the main area for SAV disease in western Norway to as far as northern Norway. One explanation for this type of spread is that SAV is present at freshwater production sites for Atlantic salmon smolts. The present study confirms this, showing that SAV3 is present at smolt production sites in Norway. At two sites in northern Norway that had received eggs from broodfish companies in Hordaland County, western Norway, 2–4-g fry were positive for SAV3. Hence, it cannot be excluded that vertical transmission could have contributed to the presence of SAV3 in northern Norway. In the present study, we followed the normal production cycle for Atlantic salmon in a fish farming company in Hordaland County. Twelve of 353 broodfish in study 1 and 28 of 31 broodfish in study 2 were found to be carriers of SAV3. In the same two studies, SAV was also detected in eggs (1 of 220), eyed eggs (3 of 270), and fry (6 of 600). The SAV was not detected in parr, smolts, or postsmolts, but after a year at sea the fish developed SAV disease. Given the difficulties in tracing the virus through the production cycle until development of SAV disease in the marine farm, we cannot draw any firm conclusions about whether vertical transmission occurs in Norwegian salmon production, and we cannot exclude the possibility that the development of SAV after 1 year at sea was caused by horizontal transmission rather than vertical transmission.
Attenuation of the Fish Pathogen Francisella sp. by Mutation of the iglC* Gene
Authors: Soto Esteban , Fernandez Denise , Hawke John P.
Published: November 2009

Fish francisellosis is an emergent disease caused by gram-negative facultative intracellular bacteria of the genus Francisella. Different strains of the bacterium have caused high mortalities in warmwater and coldwater fish species. Francisella sp. isolates from fish have been found to share more than 97% identity to the human pathogen Francisella tularensis upon 16S ribosomal RNA sequence comparison. Homologue genes of the F. tularensis intracellular growth locus (iglA*, iglB*, iglC*, and iglD*) were identified from LADL 07-285A, a clinical isolate obtained from diseased Nile tilapia Oreochromis niloticus. The iglABCD operon DNA sequence comparison revealed that Francisella LADL 07-285A had 94% identity with F. philomiragia subsp. philomiragia and 83% identity with F. tularensis subsp. novicida U112. The functions of the conserved proteins corresponding to the genes are elusive but appear to be essential for the ability of Francisella sp. to survive within macrophages and cause disease. An insertion mutation was made in the iglC* gene of LADL 07-285A by allelic exchange, and the iglC* mutant was found to be attenuated after intraperitoneal and immersion challenges in Nile tilapia. Laboratory challenge methods for inducing francisellosis in Nile tilapia were evaluated by intraperitoneal injection and immersion with serial dilutions of Francisella LADL 07-285A. The dose lethal to 50% of test fish at 40 d postchallenge was 10−5.3 (about 1.2 × 103 colony-forming units/fish) by intraperitoneal injection and was 10−1 (2.3 × 107 colony-forming units/mL of tank water) by immersion.
Occurrence of Glugea pimephales in Planktonic Larvae of Fathead Minnow in Algonquin Park, Ontario
Authors: Forest Jonathon J. H. , King Stanley D. , Cone David K.
Published: November 2009

The microsporidian Glugea pimephales was found parasitizing larval fathead minnow Pimephales promelas in Scott Lake, Algonquin Park, Ontario. These fish were estimated to be 2–3 weeks posthatch and, given the development time of the parasite, must have acquired infection soon after commencement of exogenous feeding. Histological sections revealed that the parasite typically developed in loose connective tissue between the peritoneum and the dermis of the abdominal cavity, with protruding xenomas of up to 2.6 mm in diameter forming near the vent. Prevalence was estimated at 1% by divers performing snorkel surveys along the lake shoreline. Divers following schools of fathead minnow consistently reported that larvae with the obvious cysts wobbled during swimming and that infected fish were typically located at the back of the dispersing school. This case history joins a growing list of studies suggesting that fish can become infected with parasites soon after hatch, the potential importance of which has not been critically studied.
Identification of Vibrio harveyi Isolated from Diseased Asian Seabass Lates calcarifer by Use of 16S Ribosomal DNA Sequencing
Authors: Ransangan Julian , Mustafa Saleem
Published: November 2009

The grow out of Asian seabass Lates calcarifer in marine net-cages is a popular aquaculture activity in Malaysia. Production of this species is greatly affected by the occurrence of vibriosis, which causes heavy mortality. Generally, young fish are more susceptible; they exhibit anorexia and skin darkening, followed by heavy mortality. The acutely affected older fish may also exhibit bloody lesions around the anus and the base of the fins. Twenty-one bacterial isolates obtained from internal organs (kidney, heart, spleen and liver) of the affected specimens were subjected to phenotypic characterization, testing for antibiotic susceptibility, and 16S ribosomal DNA sequencing. The sequencing result showed that all of the bacterial isolates belonged to Vibrio harveyi. The phenotypic characterization, however, identified 4 of the bacterial isolates as V. harveyi, 16 as V. parahaemolyticus, and 1 as V. alginolyticus. These findings suggest that biochemical features alone cannot be reliably used to identify bacterial pathogens, including V. harveyi, in aquaculture. Antibiotic susceptibility assays showed that some antibiotics, including oxytetracycline, nitrofurantoin, furazolidone, streptomycin, sulfamethoxazole, chloramphenicol, nalidixic acid, and oxolinic acid were effective against V. harveyi. Considering the side effects of these antibiotics, however, their use is not recommended in the aquaculture of Asian seabass.
Expanded Range and New Host Species of Mycobacterium shottsii and M. pseudoshottsii
Authors: Stine Cynthia B. , Jacobs John M. , Rhodes Matt R. , Overton Anthony , Fast Mark , Baya Ana M.
Published: November 2009

Mycobacterium shottsii and M. pseudoshottsii are recently described mycobacteria commonly isolated from Chesapeake Bay striped bass Morone saxatilis. However, their distribution in striped bass outside of the Chesapeake region and their ability to infect alternative hosts have not been described. Mycobacteria identified as M. shottsii (based on fatty acid methyl ester analysis and multigene sequencing) were isolated from striped bass collected in Albemarle Sound, North Carolina, and white perch Morone americana in the Rhode River, Maryland, and detected in striped bass from the New York Bight off Long Island, New York. Mycobacterium pseudoshottsii were isolated from white perch in the Rhode and Corsica rivers, Maryland, and detected in striped bass in the New York Bight. This work demonstrates that these mycobacteria can be found outside of the Chesapeake Bay as well as in hosts other than striped bass.
Eficiência de fungos micorrízicos arbusculares isolados de solos sob diferentes sistemas de uso na região do Alto Solimões na Amazônia
Authors: Silva Gláucia Alves e , Siqueira José Oswaldo , Stürmer Sidney Luiz
Published: November 2009

Os fungos micorrízicos arbusculares (FMAs) são importantes componentes dos ecossistemas terrestres onde acredita-se desempenharem papel fundamental para a sustentabilidade destes. Estes fungos sofrem influência de diversos fatores antrópicos como o uso da terra, que modificam a estrutura e diversidade das comunidades podendo comprometer suas funções ecológicas. No presente estudo avaliou-se o comportamento de FMAs isolados de solos sob diferentes sistemas de uso (SUT). Fungos isolados de amostras de solo sob diferentes SUT foram testados em caupi [Vigna unguiculata (L.) Walp] em condições controladas. Verificou-se que todos os cinqüenta e um fungos avaliados colonizaram o caupi, porém de modo muito diferenciado, tal como ocorreu para os efeitos destes na absorção de fósforo e crescimento da planta. A colonização variou de 1 a 68%, e os efeitos positivos no crescimento variaram de 33 a 148%, sendo mais comuns nos fungos isolados de pastagem e roça. O aumento nos teores de fósforo foi generalizado (95% dos fungos testados), no entanto, nem todos foram capazes de promover o crescimento do Caupi. Apenas 39% dos fungos foram considerados eficientes, sendo estes isolados de quase todos os SUT. Os tratamentos fúngicos de mais alta eficiência continham as espécies: A. foveata, Glomus sp.1, Acaulospora sp.1 e mistura dos dois primeiros mais E. infrequens e A. bireticulata-like. Os resultados indicam ampla diversidade de eficiência dos FMAs do Alto Solimões. Embora a eficiência não tenha relação direta com o SUT, a proporção de isolados eficientes variou com a origem de isolamento.
Efetividade de rizóbios e caracterização fenotípica dos isolados que nodulam feijão-caupi em solos da Amazônia Central
Authors: Chagas Junior Aloísio Freitas , Oliveira Luiz Antonio de , Oliveira Arlem Nascimento de , Willerding André Luiz
Published: November 2009

O feijão-caupi (Vigna unguiculata) é uma cultura importante na Amazônia Central, mas os rizóbios associados a essa leguminosa são poucos estudados. O objetivo deste estudo foi avaliar a efetividade e caracterizar fenotipicamente os isolados de rizóbio que nodulam feijão-caupi na região. As populações de rizóbio de Novo Ayrão proporcionaram as maiores produções de matéria seca da parte aérea e total, raiz, número de nódulos e peso dos nódulos secos nas plantas de feijão-caupi; porém, não diferiram do tratamento testemunha com N. Com base nos critérios fenotípicos avaliados, foi possível identificar uma ampla diversidade de populações de rizóbios contidos nos solos da Amazônia.
Oryctini (Coleoptera: Scarabaeidae: Dynastinae) da coleção de invertebrados do Instituto Nacional de Pesquisas da Amazônia (INPA), Manaus, Amazonas, Brasil
Authors: Gasca Hector Jaime , Fonseca Claudio Ruy Vasconselos da
Published: November 2009

A Coleção de Invertebrados do Instituto Nacional de Pesquisas da Amazônia (INPA) possui 554 espécimes de Oryctini (Coleoptera: Scarabaeidae: Dynastinae), pertencentes a 7 gêneros, 16 espécies e 2 subespécies. As distribuições geográficas das espécies são fornecidas, sendo que 97% do material examinado procedem de coletas feitas em diferentes locais da Amazônia brasileira.
Avaliação das pesquisas e inovações tecnológicas ocorridas na silvicultura e na produção industrial de celulose no Brasil
Authors: Montebello Adriana Estela Sanjuan , Bacha Carlos José Caetano
Published: November 2009

O objetivo deste trabalho é analisar a evolução das pesquisas e inovações tecnológicas ocorridas na silvicultura e na produção industrial de celulose no Brasil, dando ênfase aos seus impactos sobre a expansão dessa indústria. Para tanto, são utilizados dados primários e secundários como forma de avaliar os principais tipos de pesquisas e inovações tecnológicas e a importância dessas inovações para a expansão da indústria de celulose no Brasil e sua maior inserção no comércio mundial desse produto. Constata-se que as inovações tecnológicas nas áreas florestal e industrial trouxeram expressivos aumentos de produtividade na silvicultura e na produção industrial de celulose e foram geradas a partir de um intenso processo de interação entre empresas, universidades e governo e implicaram redução no custo de produção da celulose. Esta última elevou a rentabilidade da indústria, causando sua expansão. O trabalho encerra-se analisando os desafios futuros que a indústria de celulose no Brasil terá quanto a pesquisas e inovações visando mantê-la competitiva no cenário internacional.
All Sexed Up: a resposta de mulheres lésbicas negras jovens ao sexo (mais) seguro em Johannesburg, África do Sul
Authors: Matebeni Zethu , Camargo Thais Medina Coeli Rochel de , Camargo Jr Kenneth Rochel de , Dias Laércio Fidelis
Published: November 2009

A saúde sexual de mulheres lésbicas não é um tema frequentemente discutido em nossas sociedades. As questões de saúde da mulher são classificadas sob uma única categoria abrangente e excluem algumas das preocupações específicas de mulheres lésbicas, que, em geral, não têm o mesmo comportamento em relação à saúde que as mulheres heterossexuais. Esta tendência se deve a uma série de razões, entre as quais: falta de conhecimento sobre saúde e risco sexuais lésbicos, medo de estigmatização pelos prestadores de serviço e o processo de "se assumir" (coming out) para esses profissionais, que além de desconhecido, é, algumas vezes, hostil. Além disso, a pouca pesquisa sobre lésbicas e saúde lésbica na África do Sul torna difícil para as mulheres que assim se autoclassificam saberem que questões de saúde sexual as afetam especificamente, bem como onde e de que forma lidar com certos problemas. Existe uma percepção equivocada e generalizada de que questões de sexo seguro não afetam mulheres lésbicas tanto quanto mulheres heterossexuais. O artigo apresenta as visões de um grupo de mulheres de 18 a 35 anos que se autoidentificam como lésbicas na África de Sul. Por meio de questionários autoaplicados e discussões, essas mulheres partilham suas experiências e pensamentos sobre sexo lésbico (seguro) e como elas têm-se relacionado e continuam a se relacionar sexualmente com outras mulheres no momento de HIV e Aids.