bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Prediction of Cardiovascular Disease Based on a Panel of Single Nucleotide Polymorphisms Identified Through Genome-Wide Association Studies
Authors: Davies Robert W. , Dandona Sonny , Stewart Alexandre F.R. , Chen Li , Ellis Stephan G. , Wilson Tang W.H. , Hazen Stanley L. , Roberts Robert , McPherson Ruth , Wells George A.
Published: August 2010

Background—

Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) at multiple loci that are significantly associated with coronary artery disease (CAD) risk. In this study, we sought to determine and compare the predictive capabilities of 9p21.3 alone and a panel of SNPs identified and replicated through GWAS for CAD.

Methods and Results—

We used the Ottawa Heart Genomics Study (OHGS) (3323 cases, 2319 control subjects) and the Wellcome Trust Case Control Consortium (WTCCC) (1926 cases, 2938 control subjects) data sets. We compared the ability of allele counting, logistic regression, and support vector machines. Two sets of SNPs, 9p21.3 alone and a set of 12 SNPs identified by GWAS and through a model-fitting procedure, were considered. Performance was assessed by measuring area under the curve (AUC) for OHGS using 10-fold cross-validation and WTCCC as a replication set. AUC for logistic regression using OHGS increased significantly from 0.555 to 0.608 (
P
=3.59×10
−14
) for 9p21.3 versus the 12 SNPs, respectively. This difference remained when traditional risk factors were considered in a subgroup of OHGS (1388 cases, 2038 control subjects), with AUC increasing from 0.804 to 0.809 (
P
=0.037). The added predictive value over and above the traditional risk factors was not significant for 9p21.3 (AUC 0.801 versus 0.804,
P
=0.097) but was for the 12 SNPs (AUC 0.801 versus 0.809,
P
=0.0073). Performance was similar between OHGS and WTCCC. Logistic regression outperformed both support vector machines and allele counting.

Conclusions—

Using the collective of 12 SNPs confers significantly greater predictive capabilities for CAD than 9p21.3, whether traditional risks are or are not considered. More accurate models probably will evolve as additional CAD-associated SNPs are identified.
Apolipoprotein E Polymorphisms and Postprandial Triglyceridemia Before and After Fenofibrate Treatment in the Genetics of Lipid Lowering and Diet Network (GOLDN) Study
Authors: Irvin Marguerite R. , Kabagambe Edmond K. , Tiwari Hemant K. , Parnell Laurence D. , Straka Robert J. , Tsai Michael , Ordovas Jose M. , Arnett Donna K.
Published: August 2010

Background—

Although much is known about the effect of Apolipoprotein E (
APOE
) alleles on fasting lipid concentrations, less is known about the effect of
APOE
alleles on postprandial triglyceridemia or the triglyceride response to fenofibrate.

Methods and Results—

We evaluated the effects of the
APOE
locus on fasting and postprandial triglyceride concentrations as part of the Genetics of Lipid Lowering and Diet Network (GOLDN) study. Participants were evaluated after a high-fat meal challenge before (n=1072) and after 3 weeks of daily treatment with 160 mg of fenofibrate (n=738). Mixed models adjusted for sex, age, waist circumference, and family relationship were used to examine the association of the ε4 carrier and ε2 carrier status versus ε3 homozygotes with fasting triglycerides and the area under the curve (AUC) for triglycerides during the high-fat meal challenge. Compared with the ε3/ε3 genotype, ε2 carriers had on average higher fasting triglyceride concentrations (130.5 mg/dL versus 109.3 mg/dL,
P
<0.001). After fenofibrate treatment, the
APOE
genotype differences persisted in the fasting state (ε2 carriers: 85.1 mg/dL versus ε3/ε3: 75.9 mg/dL,
P
<0.05). Carriers of the ε4 allele had significantly higher fasting triglyceride concentrations only prefenofibrate (120.9 mg/dL versus 109.3 mg/dL,
P
=0.008).
APOE
alleles did not have an effect on response to fenofibrate. Postprandial triglycerides were significantly higher for ε2 carriers versus ε3 homozygotes (but not ε4 carriers) both before and after fenofibrate treatment (
P
=0.01 and
P
=0.005, respectively).

Conclusions—

APOE
polymorphisms are important determinants of triglyceride concentrations, especially in the fasting state.
Acquired von Willebrand Syndrome in Patients With an Axial Flow Left Ventricular Assist Device
Authors: Meyer Anna L. , Malehsa Doris , Bara Christoph , Budde Ulrich , Slaughter Mark S. , Haverich Axel , Strueber Martin
Published: August 2010

Background—

Rotary blood pumps used as left ventricular assist devices (LVADs) allow for long-term support and may become suitable alternatives to heart transplantation. Effects of this technology on the coagulation system are not completely understood, leading to controversial anticoagulation protocols. Thus, we investigated the primary hemostasis in patients with chronic LVAD therapy.

Methods and Results—

Twenty-six outpatients received axial flow LVAD (HeartMate II; Thoratec) for a median support time of 4.5 months. In a cross-sectional protocol, platelet aggregation in response to ADP and epinephrine, von Willebrand antigen (vWF:AG), and collagen-binding capacity (vWF:CB) were obtained. Von Willebrand factor (vWF) multimer analyses were performed, and patients were screened for bleeding events. This analysis was repeated after removal of the device for transplantation or recovery (n=12) and after a median of 15.5 months in ongoing patients (n=11). In all patients on devices, severe impairment of platelet aggregation as well as a loss of large vWF multimers were found. In 10 patients, a decreased vWF:CB/vWF:AG ratio was observed. Bleeding episodes occurred with an incidence of 0.17 per patient-year. After removal of the device, normal patterns of platelet aggregation, multimer analysis, and vWF:CB/vWF:AG ratio were recorded. In the second analysis of ongoing patients, impairment of platelet aggregation and loss of large vWF multimers were verified.

Conclusions—

A diagnosis of von Willebrand syndrome type 2 was established in all patients after LVAD implantation, and bleeding events confirmed this finding. Reversibility of this condition was found after removal of the device.
Towards a borderless social work: Reconsidering notions of international social work
Authors: Hugman Richard , Moosa-Mitha Mehmoona , Moyo Otrude
Published: August 2010

This article explores varied ideas describing the concept of international social work. Looking at international social work from the idea of glocalization, we explore how international social work is figuratively embodied in migrations. How we see ourselves in international social work not only forms a dialogue that problematizes power relations in the international social arena but also provides an instructive venture into considerations of borderless social work.
Processing and Water Absorption Behavior of Foamed Potato Starch
Authors: Sjöqvist Mia , Boldizar Antal , Rigdahl Mikael
Published: August 2010

Starch foams were prepared from four types of potato starch using two-step extrusion with an intermediate conditioning step at 53% relative humidity in order to control the moisture content. The moisture content was the driving force for the expansion during the second extrusion. The second extrusion was performed with two different dies in order to achieve differences in porosity of the materials. Glycerol in combination with water was used as plasticizer for the starches. The rheological properties of the melts and the moisture content of the starch materials prior to the expansion were determined. The porosity of the expanded structures was characterized using environmental scanning electron microscopy imaging and density measurements. The absorption capability of the starch-based foams was investigated using aqueous NaCl solutions, and the water uptake of thin starch-based films from humid air was also evaluated. Foams prepared from amylopectin potato starch were found to exhibit the highest porosity, the lowest density, and the greatest absorption capability, both from water and from humid air. Not only the density but also the absorption capability was influenced by the porosity level.
Characterization of Progenitor Cells in Pulps of Murine Incisors
Authors: Balic A. , Mina M.
Published: August 2010

The continuous growth of rodent incisors requires the presence of stem cells capable of generating ameloblasts and odontoblasts. While epithelial stem cells giving rise to ameloblasts have been well-characterized, cells giving rise to the odontoblasts in incisors have not been fully characterized. The goal of this study was to gain insight into the potential population in dental pulps of unerupted and erupted incisors that give rise to odontoblasts. We show that pulps from unerupted incisors contain a significant mesenchymal-stem-cell (MSC)-like population (cells expressing CD90+/CD45-, CD117+/CD45-, Sca-1+/CD45-) and few CD45+ cells. Our in vitro studies showed that these cells displayed extensive osteo-dentinogenic potential, but were unable to differentiate into chondrocytes and adipocytes. Dental pulps from erupted incisors displayed increased percentages of CD45+ and decreased percentages of cells expressing markers of an MSC-like population. Despite these differences, pulps from erupted incisors also displayed extensive osteo-dentinogenic potential and inability to differentiate into chondrocytes and adipocytes. These results provide evidence that continuous generation of odontoblasts and dentin on the labial and lingual sides of unerupted and erupted incisors is supported by a progenitor population and not multipotent MSCs in the dental pulp.
Neuron-immune Interactions in the Sensitized Thalamus Induced by Mustard Oil Application to Rat Molar Pulp
Authors: Kawamura J. , Kaneko T. , Kaneko M. , Sunakawa M. , Kaneko R. , Chokechanachaisakul U. , Okiji T. , Suda H.
Published: August 2010

We have reported that mustard oil application to the rat dental pulp induces neuronal activation in the thalamus. To address the mechanisms involved in the thalamic changes, we performed neuronal responsiveness recording, immunohistochemistry, and molecular biological analysis. After mustard oil application, neuronal responsiveness was increased in the mediodorsal nucleus. When MK801 (an N-methyl- D-aspartate receptor antagonist) was applied to the mediodorsal nucleus, the enhanced responsiveness was decreased. N-methyl- D-aspartate receptor 2D, glial fibrillary acidic protein, and antigen-presenting cell-related gene mRNAs in the contralateral thalamus were up-regulated at 10 minutes after mustard oil application, but were down-regulated within 10 minutes after the antagonist application. OX6-expressing microglia and glial fibrillary acidic protein-expressing astrocytes did not increase until 60 minutes after mustard oil application. These results suggested that the thalamic neurons play some roles in regulating the glial cell activation in the mediodorsal nucleus via N-methyl- D-aspartate receptor 2D during pulp inflammation-induced central sensitization.
Dental Development in Hemifacial Microsomia
Authors: Ongkosuwito E.M. , de Gijt P. , Wattel E. , Carels C.E.L. , Kuijpers-Jagtman A.M.
Published: August 2010

Hemifacial microsomia (HFM) is a congenital disorder marked by facial asymmetry. Whether facial asymmetry accounts for asymmetrical dental development is unknown. There are few data on dental development relative to mandibular development or severity of HFM, or on development over time. We hypothesized that when mandibular development was severely disturbed, local dental development was also affected. We compared dental development scores between affected and non-affected mandibular sides in patients with HFM (n = 84) and compared these data with those collected from Dutch control children (n = 451). Logistic functions were constructed for dental age over time for all four Pruzansky/Kaban types. The results showed a tendency toward delayed dental development in Pruzansky/Kaban types IIb and III at younger ages. The temporary delay of tooth formation in patients with severe forms of HFM and the distribution of agenic teeth suggest an interaction between mandibular and dental development.
Machining fantasy: Spinoza, Hume and the miracle in a politics of desire
Authors: McGee Kyle
Published: August 2010

Philosophy has long been fascinated by miracles, and with good reason. Where, however, the problem of the miracle once offered unparalleled insight into the inner workings of natural laws and of human knowledge, today, the attention commanded by it is essentially political. The sovereign’s miraculous suspension is the most well studied of these political dimensions, but this formulation is, in fact, ill-suited to the complexities inherent in the concept of the miracle. Political theology understands the miracle poorly, for it captures only the inaugural movement of exception; it knows nothing of the social and political conditions it inspires. A key claim defended in this article is that the miracle possesses continuing interest for philosophy precisely because it lies in the heart of contemporary political formations, instituting a bond that tethers a collective to its present. It is thus more interesting as a figure of inception than of exception. The miraculous is uniformly distinguished as the unengendered, the neutral point of equilibrium against which any distribution of beings is measured. This is the meaning given the miraculous in the thought of Gilles Deleuze and Félix Guattari, and this article frames the political aspect of that theme by developing their concept of miraculation, which foregrounds the movement of inception. The article works out a conceptual genealogy, tracing the descent of the miracle back from Deleuze and Guattari to Baruch Spinoza and David Hume. Each contributes an element essential for the constitution of miraculation. It is argued that the miracle has always bound ‘desire and the social’, though in diverse ways.
Racism: A barrier to entry? Experiences of small ethnic minority retail businesses
Authors: Ishaq Mohammed , Hussain Asifa , Whittam Geoff
Published: August 2010

The participation of ethnic minorities in self-employment has been a phenomenon of the British labour market for many decades. One area in which there has been a preponderance of ethnic minority groups, especially those of South Asian origin, has been the independent retail sector, where many set up what became commonly known as ‘corner shops’. This sector has experienced radical change in the last decade, which has posed a real threat to the livelihood of business owners, leading to a decline in the number and profitability of shops. Many of those which have survived have to face one of society’s social ills, racism. This study, based on semi-structured interviews, attempts to establish the degree of racial discrimination experienced by owners of small retail businesses in Glasgow, with a working hypothesis that racism in all its forms will not be conducive to encouraging potential entrepreneurs from ethnic minority backgrounds to establish new businesses, and hence racism is a barrier to entry.
Senior Centers
Authors: Pardasani Manoj , Thompson Peter
Published: August 2010

Nationally, 11,000 senior centers play a vital role in supporting community-dwelling older adults by offering a diverse array of recreational, nutritional, health, and social service programs. The purpose of this study was to identify innovative models of senior centers nationwide and evaluate their impact on the communities they serve. Applying a multiple-case study approach to a national survey sample, six innovative models were identified by members of the New Models Taskforce (NMTF), a project sponsored by the National Institute of Senior Centers (NISC). The NMTF hoped to document the innovative efforts of senior centers to reimagine and reposition themselves within the aging services field. This article will highlight the defining characteristics of each model and discuss their implications for the field. The potential impact of each model on the senior center field will be illustrated.
Social Performance and Secret Ritual: Battling Against Obsessive-Compulsive Disorder
Authors: Brooks Catherine Francis
Published: August 2010

This autoethnography offers an account of my experience with mental illness and provides an analysis of the performative aspects of obsessive-compulsive disorder (OCD). OCD is a genetic disorder triggered by environmental stressors involving a chemical imbalance in the brain. The resulting biologically altered state leaves individuals to steer themselves among and between “appropriate” performance and secret rituals. Analyzing my own communication practices through a performance lens highlights the importance of image management for people struggling with disability. In telling my own story, this article provides readers an in-depth look at OCD as a traumatic brain disorder whose sufferers rely on communicative performance to maintain their public and private identities, and as a disease that impedes social life for its sufferers. Implications of this account for those struggling with mental disability and for practitioners aiming to help them are discussed.
Evaluation of the symbol digit modalities test (SDMT) and MS neuropsychological screening questionnaire (MSNQ) in natalizumab-treated MS patients over 48 weeks
Authors: Morrow SA , O'Connor PW , Polman CH , Goodman AD , Kappos L , Lublin FD , Rudick RA , Jurgensen S , Paes D , Forrestal F , Benedict RHB
Published: August 2010

Background and Objectives: Brief cognitive tests to monitor cognitive impairment in patients with multiple sclerosis (MS) are needed.

Methods: Performance on monthly administrations of the Symbol Digit Modalities Test (SDMT) and the MS Neuropsychological Questionnaire (MSNQ) was assessed in 660 patients with MS in 21 countries (109 sites) for 48 weeks in an open-label, safety-extension study of natalizumab.

Results: At baseline, the cohort’s mean age was 40.1 years, 67.6% were female and the median Expanded Disability Status Scale score was 2.5. Test—retest correlations were high for both SDMT (range 0.89 for weeks 0—4 to 0.96 for weeks 44—48) and MSNQ (0.82 for weeks 0—4 to 0.93 for weeks 44—48). There were no statistically significant effects of geographic region. While SDMT scores improved by 15 points over 48 weeks ( p < 0.0001), incremental monthly changes were small (effect size d < 0.3). Similar results were obtained on the MSNQ except that scores moved downward, suggesting fewer cognitive complaints over 48 weeks ( p < 0.0001), but again the incremental monthly changes were small ( d <-0.2).

Conclusions: These results replicate earlier work in a smaller cohort treated with conventional disease-modifying therapy, and support the reliability of the SDMT and MSNQ as potential screening for monitoring tools for cognition over time.
Immunomodulatory effects of vitamin D on monocyte-derived dendritic cells in multiple sclerosis
Authors: Bartosik-Psujek Halina , Tabarkiewicz Jacek , Pocinska Krystyna , Stelmasiak Zbigniew , Rolinski Jacek
Published: August 2010

In order to evaluate the effects of vitamin D3 on monocyte-derived dendritic cells (DCs) of relapsing—remitting multiple sclerosis patients, DCs differentiation and maturation were evaluated in vitro based on surface phenotypic changes. The expression of CD14, CD83, CD1a, CD80, CD86, CD206 and C209 was analysed by fluorescence-activated cell sorting. The results reveal that vitamin D3 inhibits both the differentiation and maturation of DCs. Moreover, inhibits the secretion of IL 23/12p40 and increases the secretion of CCL2. The data suggest that one of the mechanisms of the beneficial action of vitamin D3 in multiple sclerosis may be associated with its influence on DCs.
Influence of the context of learning a language on the strategic competence of children
Authors: Le Pichon Emmanuelle , de Swart Henriette , Vorstman Jacob , van den Bergh Huub
Published: August 2010

The present study was set up to evaluate the extent to which the context in which a foreign language is learned can influence the strategic competence of children. To assess this we conducted a series of think aloud protocols with 101 children. We compared children who have learned an additional language in a formal context (abbreviated LLE, i.e. Language Learning Experience) to those who have acquired two languages in a non-formal context and before the age of 4 (i.e. ‘simultaneous bilingual’ children, abbreviated nLLE, i.e. without a Language Learning Experience). The primary outcome measure consisted of the children’s reactions to situations of communication where they could not understand the language. We hypothesized that LLE children would outperform nLLE children in their awareness of and willingness to use communicative strategies. We found that LLE children accessed more strategies and diversified their strategies more often. These findings are in line with our previous findings and indicate that LLE is a highly relevant factor when studying the strategic competence of children.
Mechanical reproduction in the age of the artwork? Faience and 5000 moulds from 14th-century BC Egypt
Authors: Quirke Stephen , Tajeddin Zahed
Published: August 2010

The excavations in the ancient city of Akhetaten at Tell El-Amarna in Egypt produced countless artefacts and fragments of brightly coloured material, known in Egyptology as ‘faience’, in addition to thousands of terracotta moulds for their production. These moulds provide direct evidence for technologies of mechanical reproduction in visual arts of the Late Bronze Age. The experimental recreation of moulds, as well as faience objects created from them, offers a significant advance in understanding perhaps the most crucial issue in faience production: the archetype behind the prototype. Despite the huge number of surviving moulds and faience products, there is no archaeological evidence that shows which material was used for the ‘master’ — the archetype required for the making of a mould. This article discusses faience production and its potential for reconsidering the specific trajectories of archetype to prototype and the distribution of the prototype.
Spirituality and faith in dementia
Authors: Jolley David , Benbow Susan Mary , Grizzell Moni , Willmott Sasi , Bawn Sadie , Kingston Paul
Published: August 2010

This study used a standardized instrument, the Royal Free Interview for Religious and Spiritual Beliefs, to investigate the spirituality of a population of people with dementia who scored 12 or more on the Mini Mental State Examination and their carers, who were attending a West Midlands Memory Clinic. Study patients were more likely to be well preserved cognitively, be female, and to be living with their spouse at home, than the clinic population as a whole. The population was predominantly white British and Christian. Both patients and carers found the Royal Free Interview acceptable: they rated their beliefs as strong and considered practices associated with their beliefs to be very important. Both groups described spirituality as evident in everyday experiences and as supportive in relation to life stresses. Service providers should integrate questions about spirituality and faith into routine assessments and structure care plans to accommodate identified spiritual needs.
Coping with dementia and older families of adults with Down syndrome
Authors: Janicki Matthew P. , Zendell Anna , DeHaven Kathleen
Published: August 2010

The authors studied a group of older carers of aging adults with Down syndrome (DS) to ascertain what effects such caregiving may have on them given the presence or possibility of age-associated decline or dementia. The study also examined the comparative levels of care provided, key signs noted when decline was beginning, the subjective burden experienced, and what were the key associated health factors when carers faced a changed level of care. The authors found that this group was made up of long-term, committed carers who have decided early on to look after their relative with DS over their lifetime. When faced with the onset and ongoing progression of dementia, their commitment was still evident as evidenced by adopting physical accommodations and finding ways to continue to provide care at home, while also seeking help from outside sources. Most saw a family or group home environment as the place of choice for their relative with DS when they decided they could no longer offer care. The study did not ascertain any burn-out or significant health related problems associated with their continued caregiving save for their concerns about day-to-day strain and what will happen in the future.
Sexual Practice Among Thai HIV-Infected Patients: Prevalence and Risk Factors for Unprotected Sex
Authors: Chaiyamahapurk Sakchai , Pannarunothai Supasit , Nopkesorn Tawesak
Published: August 2010

Positive prevention which focuses on prevention of HIV transmission from those already infected to those uninfected is an important issue for HIV prevention. A self-administered questionnaire on sexual practice survey of HIV-infected patients attending HIV clinics was undertaken. Of the 1160 patients, 53% knew their HIV status after being ill and 59% believed that they got infection from their regular sexual partner. In 3 months prior to the survey, 18% reported unprotected sex. Unprotected sex significantly decreased in people having adequate condoms but increased in those who believed that their sexual partners were already infected. Effect of disclosure of HIV status on unprotected sex depended on whether patients were men or women. Non-disclosure HIV-positive men claimed to have less unprotected sex than their counterpart, HIV-positive women. Factors related to unprotected sex should be addressed and sexual health must be integrated and promoted in HIV health care.
Low Prevalence of Primary HIV Resistance in Western Massachusetts
Authors: Iarikov Dmitri E. , Irizarry-Acosta Melina , Martorell Claudia , Hoffman Robert P. , Skiest Daniel J.
Published: August 2010

Most studies of primary antiretroviral (ARV) resistance have been conducted in large metropolitan areas with reported rates of 8% to 25%. We collected data on 99 HIV-1-infected antiretroviral-naive patients from several sites in Springfield, MA, who underwent genotypic resistance assay between 2004 and 2008. Only major resistance mutations per International AIDS Society-USA (IAS-USA) drug resistance mutations list were considered. The prevalence of resistance was 5% (5 of 99). Three patients had one nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation: 103N, 103N, and 190A, 1 patient had a protease inhibitor (PI) mutation: 90M; and 1 patient had 3-class resistance with NNRTI: 181C, 190A, PI: 90M, and nucleoside analogue reverse transcriptase inhibitor (NRTI): 41L, 210W. Mean time from HIV diagnosis to resistance testing was shorter in patients with resistance versus those without: 9 (range 0.3-42 months) versus 27 (range 0.1-418 months), P = .11. There was a trend to lower mean CD4 count in those with resistance, 170 versus 318 cells/mm3, P = .06. No differences were noted in gender, age, HIV risk category, or HIV RNA level. The low prevalence of primary resistance may be explained by differences in demographic and risk factors or may reflect the time from infection to resistance testing. Our findings emphasize the importance of continued resistance surveillance.
Impact of Heavy Polypropylene Mesh and Composite Light Polypropylene and Polyglactin 910 on the Inflammatory Response
Authors: Di Vita Gaetano , Patti Rosalia , Barrera Tommaso , Arcoleo Francesco , Ferlazzo Viviana , Cillari Enrico
Published: August 2010

The aim of the study was to analyze the acute inflammatory response after implantation of a heavyweight mesh of polypropylene (PP) compared with a composite mesh of light PP and polyglactin 910 (PG) in patients undergoing inguinal hernioplasty. A total of 30 male patients with inguinal hernia were included in the study and divided into 2 groups (PP and PP-PG) according to the mesh used. Changes of leukocytes, cytokines, growth factors, and acute phase proteins were evaluated in the sera. Leukocytes and acute phase proteins were significantly increased postoperatively in both groups, and the values were slightly higher in the PP group. Cytokine levels were significantly increased postoperatively in both groups; a slight increase was observed in the PP-PG group, especially for the proinflammatory cytokine. Growth factors decreased significantly in both groups immediately after surgery. The authors found that the use of the mesh is a stimulator of inflammatory response, and the 2 types of mesh induce a similar inflammatory response.
Role of c-Maf in Chondrocyte Differentiation
Authors: Hong Eunmee , Di Cesare Paul E. , Haudenschild Dominik R.
Published: August 2010

Chondrocyte differentiation in the growth plate is an important process for the longitudinal growth of endochondral bones. Sox9 and Runx2 are the most often-studied transcriptional regulators of the chondrocyte differentiation process, but the importance of additional factors is also becoming apparent. Mafs are a subfamily of the basic ZIP (bZIP) transcription factor superfamily, which act as key regulators of tissue-specific gene expression and terminal differentiation in many tissues. There is increasing evidence that c-Maf and its splicing variant Lc-Maf play a role in chondrocyte differentiation in a temporal-spatial manner. This review summarizes the functions of c-Maf in chondrocyte differentiation and discusses the possible role of c-Maf in osteoarthritis progression.
The Scope-Severity Paradox
Authors: Nordgren Loran F. , McDonnell Mary-Hunter Morris
Published: August 2010

Punishment should be sensitive to the severity of the crime. Yet in three studies the authors found that increasing the number of people victimized by a crime actually decreases the perceived severity of that crime and leads people to recommend less punishment for crimes that victimize more people. The authors further demonstrate the process behind the scope-severity paradox—the victim identifiability effect—and test a strategy for overcoming this bias. Although Studies 1 and 2 document this phenomenon in the lab, in Study 3 the authors used archival data to demonstrate that the scope-severity paradox is a robust, real-world effect. They collected archival data of actual jury verdicts spanning a 10-year period and found that juries required defendants to pay higher punitive damages when their negligent behavior harmed fewer people.
Survivin gene silencing sensitizes prostate cancer cells to selenium growth inhibition
Authors: Liu Xichun , Gao Ruijuan , Dong Yan , Gao Lifang , Zhao Yanying , Zhao Lijuan , Zhao Xuejian , Zhang Haitao
Published: August 2010

Background

Prostate cancer is a leading cause of cancer-related death in men worldwide. Survivin is a member of the inhibitor of apoptosis (IAP) protein family that is expressed in the majority of human tumors including prostate cancer, but is barely detectable in terminally differentiated normal cells. Downregulation of survivin could sensitize prostate cancer cells to chemotherapeutic agents in vitro and in vivo. Selenium is an essential trace element. Several studies have shown that selenium compounds inhibit the growth of prostate cancer cells. The objective of this study is to investigate whether survivin gene silencing in conjunction with selenium treatment could enhance the therapeutic efficacy for prostate cancer and to elucidate the underlying mechanisms.

Methods

Expression of survivin was analyzed in a collection of normal and malignant prostatic tissues by immunohistochemical staining. In vitro studies were conducted in PC-3M, C4-2B, and 22Rv1 prostate cancer cells. The effect of selenium on survivin expression was analyzed by Western blotting and semi-quantitative RT-PCR. Survivin gene knockdown was carried out by transfecting cells with a short hairpin RNA (shRNA) designed against survivin. Cell proliferation was quantitated by the 3-(4,5-Dimethylthiazol-2-yl)- 2,5-Diphenyltetrazolium Bromide (MTT) assay and apoptosis by propidium iodide staining followed by flow cytometry analysis. Finally, in vivo tumor growth assay was performed by establishing PC-3M xenograft in nude mice and monitoring tumor growth following transfection and treatment.

Results

We found that survivin was undetectable in normal prostatic tissues but was highly expressed in prostate cancers. Survivin knockdown or selenium treatment inhibited the growth of prostate cancer cells, but the selenium effect was modest. In contrast to what have been observed in other cell lines, selenium treatment had little or no effect on survivin expression in several androgen-independent prostate cancer cell lines. Survivin knockdown sensitized these cells to selenium growth inhibition and apoptosis induction. In nude mice bearing PC-3M xenografts, survivin knockdown synergizes with selenium in inhibiting tumor growth.

Conclusions

Selenium could inhibit the growth of hormone-refractory prostate cancer cells both in vitro and in vivo, but the effects were modest. The growth inhibition was not mediated by downregulating survivin expression. Survivin silencing greatly enhanced the growth inhibitory effects of selenium.
Surface EMG pattern recognition for real-time control of a wrist exoskeleton
Authors: Khokhar Zeeshan O , Xiao Zhen G , Menon Carlo
Published: August 2010

Background

Surface electromyography (sEMG) signals have been used in numerous studies for the classification of hand gestures and movements and successfully implemented in the position control of different prosthetic hands for amputees. sEMG could also potentially be used for controlling wearable devices which could assist persons with reduced muscle mass, such as those suffering from sarcopenia. While using sEMG for position control, estimation of the intended torque of the user could also provide sufficient information for an effective force control of the hand prosthesis or assistive device. This paper presents the use of pattern recognition to estimate the torque applied by a human wrist and its real-time implementation to control a novel two degree of freedom wrist exoskeleton prototype (WEP), which was specifically developed for this work.

Methods

Both sEMG data from four muscles of the forearm and wrist torque were collected from eight volunteers by using a custom-made testing rig. The features that were extracted from the sEMG signals included root mean square (rms) EMG amplitude, autoregressive (AR) model coefficients and waveform length. Support Vector Machines (SVM) was employed to extract classes of different force intensity from the sEMG signals. After assessing the off-line performance of the used classification technique, the WEP was used to validate in real-time the proposed classification scheme.

Results

The data gathered from the volunteers were divided into two sets, one with nineteen classes and the second with thirteen classes. Each set of data was further divided into training and testing data. It was observed that the average testing accuracy in the case of nineteen classes was about 88% whereas the average accuracy in the case of thirteen classes reached about 96%. Classification and control algorithm implemented in the WEP was executed in less than 125 ms.

Conclusions

The results of this study showed that classification of EMG signals by separating different levels of torque is possible for wrist motion and the use of only four EMG channels is suitable. The study also showed that SVM classification technique is suitable for real-time classification of sEMG signals and can be effectively implemented for controlling an exoskeleton device for assisting the wrist.
A mixed community of actinomycetes produce multiple antibiotics for the fungus farming ant Acromyrmex octospinosus
Authors: Barke Jörg , Seipke Ryan F , Grüschow Sabine , Heavens Darren , Drou Nizar , Bibb Mervyn J , Goss Rebecca JM , Yu Douglas W , Hutchings Matthew I
Published: August 2010

Background

Attine ants live in an intensely studied tripartite mutualism with the fungus Leucoagaricus gongylophorus, which provides food to the ants, and with antibiotic-producing actinomycete bacteria. One hypothesis suggests that bacteria from the genus Pseudonocardia are the sole, co-evolved mutualists of attine ants and are transmitted vertically by the queens. A recent study identified a Pseudonocardia-produced antifungal, named dentigerumycin, associated with the lower attine Apterostigma dentigerum consistent with the idea that co-evolved Pseudonocardia make novel antibiotics. An alternative possibility is that attine ants sample actinomycete bacteria from the soil, selecting and maintaining those species that make useful antibiotics. Consistent with this idea, a Streptomyces species associated with the higher attine Acromyrmex octospinosus was recently shown to produce the well-known antifungal candicidin. Candicidin production is widespread in environmental isolates of Streptomyces, so this could either be an environmental contaminant or evidence of recruitment of useful actinomycetes from the environment. It should be noted that the two possibilities for actinomycete acquisition are not necessarily mutually exclusive.

Results

In order to test these possibilities we isolated bacteria from a geographically distinct population of A. octospinosus and identified a candicidin-producing Streptomyces species, which suggests that they are common mutualists of attine ants, most probably recruited from the environment. We also identified a Pseudonocardia species in the same ant colony that produces an unusual polyene antifungal, providing evidence for co-evolution of Pseudonocardia with A. octospinosus.

Conclusions

Our results show that a combination of co-evolution and environmental sampling results in the diversity of actinomycete symbionts and antibiotics associated with attine ants.
Germ cell specification and ovary structure in the rotifer Brachionus plicatilis
Authors: Smith James M , Cridge Andrew G , Dearden Peter K
Published: August 2010

Background

The segregation of the germline from somatic tissues is an essential process in the development of all animals. Specification of the primordial germ cells (PGCs) takes place via different strategies across animal phyla; either specified early in embryogenesis by the inheritance of maternal determinants in the cytoplasm of the oocyte ('preformation') or selected later in embryonic development from undifferentiated precursors by a localized inductive signal ('epigenesis'). Here we investigate the specification and development of the germ cells in the rotiferBrachionus plicatilis, a member of the poorly-characterized superphyla Lophotrochozoa, by isolating theBrachionushomologues of the conserved germ cell markersvasaandnanos, and examining their expression usingin situhybridization.

Results

BpvasaandBpnosRNA expression have very similar distributions in theBrachionusovary, showing ubiquitous expression in the vitellarium, with higher levels in the putative germ cell cluster.BpvasRNA expression is present in freshly laid eggs, remaining ubiquitous in embryos until at least the 96 cell stage after which expression narrows to a small cluster of cells at the putative posterior of the embryo, consistent with the developing ovary.BpnosRNA expression is also present in just-laid eggs but expression is much reduced by the four-cell stage and absent by the 16-cell stage. Shortly before hatching of the juvenile rotifer from the egg,BpnosRNA expression is re-activated, located in a subset of posterior cells similar to those expressingBpvasat the same stage.

Conclusions

The observed expression ofvasaandnanosin the developingB. plicatilisembryo implies an epigenetic origin of primordial germ cells in Rotifer.
Progesterone Treatment Inhibits and Dihydrotestosterone (DHT) Treatment Potentiates Voltage-Gated Calcium Currents in Gonadotropin-Releasing Hormone (GnRH) Neurons
Authors: Sun Jianli , Moenter Suzanne M.
Published: August 2010

GnRH neurons are central regulators of fertility, and their activity is modulated by steroid feedback. In normal females, GnRH secretion is regulated by estradiol and progesterone (P). Excess androgens present in hyperandrogenemic fertility disorders may disrupt communication of negative feedback signals from P and/or independently stimulate GnRH release. Voltage-gated calcium channels (VGCCs) are important in regulating excitability and hormone release. Estradiol alters VGCCs in a time-of-day-dependent manner. To further elucidate ovarian steroid modulation of GnRH neuron VGCCs, we studied the effects of dihydrotestosterone (DHT) and P. Adult mice were ovariectomized (OVX) or OVX and treated with implants containing DHT (OVXD), estradiol (OVXE), estradiol and DHT (OVXED), estradiol and P (OVXEP), or estradiol, DHT, and P (OVXEDP). Macroscopic calcium current (ICa) was recorded in the morning or afternoon 8–12 d after surgery using whole-cell voltage-clamp. ICa was increased in afternoon vs. morning in GnRH neurons from OVXE mice but this increase was abolished in cells from OVXEP mice. ICa in cells from OVXD mice was increased regardless of time of day; there was no additional effect in OVXED mice. P reduced N-type and DHT potentiated N- and R-type VGCCs; P blocked the DHT potentiation of N-type-mediated current. These data suggest P and DHT have opposing actions on VGCCs in GnRH neurons, but in the presence of both steroids, P dominates. VGCCs are targets of ovarian steroid feedback modulation of GnRH neuron activity and, more specifically, a potential mechanism whereby androgens could activate GnRH neuronal function.
GADD45γ: a New Vitamin D-Regulated Gene that Is Antiproliferative in Prostate Cancer Cells
Authors: Flores Omar , Burnstein Kerry L.
Published: August 2010

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibits proliferation of normal and malignant prostate epithelial cells at least in part through inhibition of G1 to S phase cell cycle progression. The mechanisms of the antiproliferative effects of 1,25-(OH)2D3 have yet to be fully elucidated but are known to require the vitamin D receptor. We previously developed a 1,25-(OH)2D3-resistant derivative of the human prostate cancer cell line, LNCaP, which retains active vitamin D receptors but is not growth inhibited by 1,25-(OH)2D3. Gene expression profiling revealed two novel 1,25-(OH)2D3-inducible genes, growth arrest and DNA damage-inducible gene gamma (GADD45γ) and mitogen induced gene 6 (MIG6), in LNCaP but not in 1,25-(OH)2D3-resistant cells. GADD45γ up-regulation was associated with growth inhibition by 1,25-(OH)2D3 in human prostate cancer cells. Ectopic expression of GADD45γ in either LNCaP or ALVA31 cells resulted in G1 accumulation and inhibition of proliferation equal to or greater than that caused by 1,25-(OH)2D3 treatment. In contrast, ectopic expression of MIG6 had only minimal effects on cell cycle distribution and proliferation. Whereas GADD45γ has been shown to be induced by androgens in prostate cancer cells, up-regulation of GADD45γ by 1,25-(OH)2D3 was not dependent on androgen receptor signaling, further refuting a requirement for androgens/androgen receptor in vitamin D-mediated growth inhibition. These data introduce two novel 1,25-(OH)2D3-regulated genes and establish GADD45γ as a growth-inhibitory protein in prostate cancer. Furthermore, the induction of GADD45γ gene expression by 1,25-(OH)2D3 may mark therapeutic response in prostate cancer.
Targeting β-Cell Function Early in the Course of Therapy for Type 2 Diabetes Mellitus
Authors: Leahy Jack L. , Hirsch Irl B. , Peterson Kevin A. , Schneider Doron
Published: August 2010

Objective: This report examines current perspectives regarding likely mechanisms of β-cell failure in type 2 diabetes and their clinical implications for protecting or sparing β-cells early in the disease progression. In addition, it considers translation strategies to incorporate relevant scientific findings into educational initiatives targeting clinical practice behavior.

Participants: On January 10, 2009, a working group of basic researchers, clinical endocrinologists, and primary care physicians met to consider whether current knowledge regarding pancreatic β-cell defects justifies retargeting and retiming treatment for clinical practice. Based on this meeting, a writing group comprised of four meeting participants subsequently prepared this consensus statement. The conference was convened by The Endocrine Society and funded by an unrestricted educational grant from Novo Nordisk.

Evidence: Participants reviewed and discussed published literature, plus their own unpublished data.

Consensus Process: The summary and recommendations were supported unanimously by the writing group as representing the consensus opinions of the working group.

Conclusions: Workshop participants strongly advocated developing new systems to address common barriers to glycemic control and recommended several initial steps toward this goal. These recommendations included further studies to establish the clinical value of pharmacological therapies, continuing basic research to elucidate the nature and mechanisms of β-cell failure in type 2 diabetes mellitus, and exploring new educational approaches to promote pathophysiology-based clinical practices. The Endocrine Society has launched a new website to continue the discussion between endocrinologists and primary care physicians on β-cell pathophysiology in type 2 diabetes and its clinical implications. Join the conversation at http://www.betacellsindiabetes.org
DHT Selectively Reverses Smad3-Mediated/TGF-β-Induced Responses through Transcriptional Down-Regulation of Smad3 in Prostate Epithelial Cells
Authors: Song Kyung , Wang Hui , Krebs Tracy L. , Wang Bingcheng , Kelley Thomas J. , Danielpour David
Published: August 2010

Androgens suppress TGF-β responses in the prostate through mechanisms that are not fully explored. We have recently reported that 5α-dihydrotestosterone (DHT) suppresses the ability of TGF-β to inhibit proliferation and induce apoptosis of prostatic epithelial cells and provided evidence that such suppression was fueled by transcriptional down-regulation of TGF-β receptor II (ΤβRII). We now show that androgen receptor (AR) activated by DHT suppresses the TGF-β-induced phosphorylation of Sma- and Mad-related protein (Smad)3 in LNCaP cells overexpressing TβRII under the control of a cytomegalovirus promoter, which is not regulated by DHT, suggesting that transcriptional repression of TβRII alone does not fully account for the impact of DHT on TGF-β responses. Instead, we demonstrate that such suppression occurs through loss of total Smad3, resulting from transcriptional suppression of Smad3. We provide evidence that DHT down-regulates the promoter activity of Smad3 in various prostate cancer cell lines, including NRP-154+AR, DU145+AR, LNCaP, and VCaP, at least partly through androgen-dependent inactivation of Sp1. Moreover, we show that overexpression of Smad3 reverses the ability of DHT to protect against TGF-β-induced apoptosis in NRP-154+AR, supporting our model that loss of Smad3 by DHT is involved in the protection against TGF-β-induced apoptosis. Together, these findings suggest that deregulated/enhanced expression and activation of AR in prostate carcinomas may intercept the tumor suppressor function of TGF-β through transcriptional suppression of Smad3, thereby providing new mechanistic insight into the development of castration-resistant prostate cancer.
New Briarane-Related Diterpenoids from the Sea Whip Gorgonian Coral Junceella fragilis (Ellisellidae)
Authors: Sung Ping-Jyun , Wang Su-Hui , Chang Yu-Chia , Chen Yung-Husan , Lin Mei-Ru , Huang I-Chu , Chen Jih-Jung , Li Jan-Jung , Kung Ting-Hsuan , Fang Lee-Shing , Wang Wei-Hsien , Weng Ching-Feng
Published: August 2010

Two new briarane-type diterpenoids, fragilides H (1) and I (2), along with a known metabolite, (+)-11β,20β-epoxyjunceellolide D (3), were isolated from the sea whip gorgonian coral Junceella fragilis. The structures of briaranes 1–3 were elucidated by spectroscopic methods and by comparison with the spectral data from other known metabolites featuring a briarane carbon skeleton.