bluuebunny/crossref_metadata_2025 huggingface dataset:
Killer immunoglobulin-like receptor locus polymorphisms in multiple sclerosis
Authors: Jelčić Ilijas , Hsu Katharine C , Kakalacheva Kristina , Breiden Petra , Dupont Bo , Uhrberg Markus , Martin Roland , Münz Christian , Lünemann Jan D
Published: December 2011

Objective:

The objective of this study was to analyze whether inhibitory and activating killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I alleles defined by their KIR binding motifs are associated with multiple sclerosis (MS) susceptibility or severity.

Method:

We performed a population-based case–control study in 321 patients with clinically isolated syndrome (CIS) and clinically definite MS (CDMS) and 156 healthy blood donors (HD). Inhibitory and activating KIRs and HLA class I alleles were genotyped using polymerase chain reaction (PCR) sequence-specific primers. Allelic frequencies were correlated with prevalence, age of onset, disability and disease duration of CIS and CDMS.

Results:

The frequency of the inhibitory KIR2DL3 gene was significantly reduced in patients with CIS and CDMS ( p = 3.1 × 10−5). KIR2DL3-dependent risk reduction remained significant after elimination of patients carrying MS-associated DRB1*15, DRB1*03, DRB1*01 alleles. In addition, individuals carrying two copies for KIR2DL2/KIR2DS2 but lacking KIR2DL3 were overrepresented in the CIS/CDMS cohort. However, both genes did not affect disease risk in presence of KIR2DL3. We did not detect any association between the presence or absence of KIR genes with clinical disease parameters.

Conclusion:

Absence of the inhibitory KIR2DL3 gene is associated with the development of CIS/CDMS. These findings, if confirmed in larger cohorts, suggest that KIR-mediated recognition of HLA class I molecules should be further explored as potential disease mechanism in MS.
The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude
Authors: Lechner-Scott J , Spencer B , de Malmanche T , Attia J , Fitzgerald M , Trojano M , Grand’Maison F , Gomez J Antonio C , Izquierdo G , Duquette P , Girard M , Grammond P , Oreja-Guevara C , Hupperts R , Bergamaschi R , Boz C , Giuliani G , van Pesch V , Iuliano G , Fiol M , Cristiano E , Verheul F , Saladino M Laura , Slee M , Barnett M , Deri N , Flechter S , Vella N , Shaw C , Herbert J , Moore F , Petkovska-Boskova T , Jokubaitis V , Butzkueven H
Published: December 2011

Background:

With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) statusfor the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power.

Methods:

In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome.

Results:

A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude ( p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change ( p < 0.001).

Conclusions:

The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.
Moral performance, inhuman and degrading treatment and prison pain
Authors: Liebling Alison
Published: December 2011

Empirical research on the moral quality of life in prison suggests that some prisons are more survivable than others. Prisoners describe stark differences in the moral and emotional climates of prisons serving similar functions. The ‘differences that matter’ concern interpersonal relationships and treatment, and the use of authority, which lead to stark differences in perceived fairness and safety and different outcomes for prisoners, including rates of suicide. These identifiable differences between prisons in one jurisdiction may provide the beginnings of a framework for addressing the broader question of standards being set by the European Court of Human Rights. Concepts like ‘dignity’ and ‘humanity’ are difficult to operationalize and practise. Prisoners are articulate about them, however, and know the difference between ‘feeling humiliated’ and ‘retaining an identity’. The worlds of ‘moral measurement’ and ‘human rights standards’ in penology should be brought closer together in a way that deepens the conversation about prison life and experience.
Doing the programme or doing me? The pains of youth imprisonment
Authors: Cox Alexandra
Published: December 2011

This article draws on research about young people's responses to being governed in secure residential facilities. It focuses on young people's expressions of agency as they ‘do programme’ in these facilities. It points to the ways that young people's language of choice and responsibility reflects their performances of ‘programme’ as they manage complicated emotions about change and growth. It is argued that there are various ‘splits’ that exist between official notions of programme compliance and those embodied and understood by young people. The article illuminates some of the more invisible pains experienced by young people in custody by revealing the intractability of the discourses of self-control in these young people's lives.
Mother–child interactions during shared literacy activities: Education in a fractured bilingual environment
Authors: Quiroz Blanca , Dixon L. Quentin
Published: December 2011

Research indicates that mothers scaffold the literacy skills of their children when jointly engaged in literacy-related activities in monolingual families (Tamis-LeMonda et al., 2001). Yet little is known about the linguistic environment of English language learners in the USA, a group at high risk for reading difficulties if they are only taught in English and the school is not mindful of their linguistic and cultural strengths (Snow et al., 1998). We studied mother–child language interactions in Spanish-speaking families in the USA during two literacy-related activities at home (book reading and a homework-like task). We employed language data analysis, discourse analysis, surveys and observations to study four cases of mother–child communication and its relation to the children’s literacy and language skills (letter-word identification, dictation, vocabulary). Mother–child proficiency in the same language (Spanish, English or bilingual similarities between mother and child) was necessary, but not sufficient, to facilitate their communication. Maternal language and literacy skills in this sample related to the quality of language input, but only in dyads with shared language did it relate to successful communication and the child’s skills. Continuity between home/school language and literacy showed compounded support for language that transferred to literacy skills across languages. This association was observed even in dyads with mothers who had scored low on receptive vocabulary or/and had only a few years of formal education. These findings suggest that maintaining a school language environment that preserves mother–child communication and its positive association with learning would yield the best educational outcomes for this particular population.
Investigation of stress distribution in upholstery of soft furniture
Authors: Jucienė Milda , Vobolis Jonas
Published: December 2011

In the process of use, upholstery of soft furniture undergoes continuous deformation. This results in puckering of upholstery, change of its initial shape, whereas longer usage of upholstery leads to deterioration thereof. For investigation, an original testing bench of soft furniture has been applied. After inducing transverse resonant oscillations in soft pieces of furniture, stress in upholstery of soft pieces of furniture and stress distribution over the plane have been assessed. Variation of the value of the load simulating the tensioning defect of upholstery allows determining an adequate change in stress of upholstery. Under the action of the load, the following uneven changes in stresses have been established irrespective of the initial condition of stresses in soft pieces: some places demonstrate decrease of stresses, whereas other ones show increase thereof up to a few times. It has been illustrated that variation of the position of the additional load in respect of the investigation point leads to ‘accentuation’ of stresses in the close area. The methodology and equipment presented may be employed to assess the assembling quality of soft furniture in the process of manufacture and use.
Sovereignty and Imperial Law
Authors: Joyce Richard
Published: December 2011

This commentary reflects on the imperial qualities of modern sovereignty and law, through the lens of Jacques Derrida’s notion of sovereign “autopositioning.” It argues that modern sovereignty is essentially imperial and yet carries an inextinguishable anti-imperial thrust. These characteristics highlight the self-grounded force of sovereign claims and at the same time expose the contingency of those claims. The commentary argues that this relationship between force and contingency creates a need for vigilant critique of and a space for resistance to, sovereign claims.
The Illocutions of Exile
Authors: Goodman Nan
Published: December 2011

This commentary argues that the typical representation of exiles and immigrants in literature be distinguished from their representation in the law, where they are often given not to descriptive and plaintive expressions of their plight, as is the case in so many literary texts, but to simple affirmations of their existence. As the commentary goes on to show, the expression of exilic presence often comes in the form of an illocution – statements that make things happen as opposed to merely describing them – which have the potential to alter our view of exiles and immigrants as outsiders who are powerless and bereft anywhere but in their country of origin.
Bob Sabiston in Conversation with Paul Ward
Authors: Sabiston Bob
Published: December 2011

Bob Sabiston has been working in animation since the 1980s, when he studied at the Media Lab at Massachusetts Institute of Technology. In this conversation with Paul Ward, he talks about his development of the software with which he is most associated, the digital rotoscoping program Rotoshop, as well as the artists and animators who have influenced him. Central to Sabiston’s work is an interest in the everyday and how animation can capture and creatively treat it. Any discussion of animation and realism, or animation and documentary, arguably has to engage with his work. Rotoshop’s often misunderstood status as a form of image filtering rather than a sophisticated form of digital mark-making means it also goes right to the heart of debates about how we define animation, what constitutes ‘proper’ animation (as opposed to some form of ‘short cut’) and how we view different kinds of animation labour. Although Sabiston is most associated with Rotoshop films, he is also active in the development of software for other platforms.
The interplay between collective memory and the erosion of nation states – the paradigmatic case of Belgium: Introduction to the special issue
Authors: Luminet Olivier , Licata Laurent , Klein Olivier , Rosoux Valérie , Heenen-Wolff Susann , van Ypersele Laurence , Stone Charles B.
Published: December 2011

The main goal of the special issue on ‘the interplay between collective memory and the erosion of nation states: The paradigmatic case of Belgium’ is to examine the erosion of the Belgian State as an exemplary illustration of the way memories of past events can influence current attitudes, emotions, representations and behaviours. We believe that the recent political crisis in Belgium, with no government for more than one year after the 2010 general elections, could be partly illuminated by the diverging and sometimes contradictory memories each linguistic group (Dutch- vs. French-speakers) in Belgium holds about the past. These issues will be examined through different disciplines from the social sciences and humanities: social psychology, history, psychoanalysis, political sciences, and literature.
Targeted therapies through microRNAs: pulp or fiction?
Authors: Langer Christian , Rücker Frank G. , Buske Christian , Döhner Hartmut , Kuchenbauer Florian
Published: December 2011

With the discovery of post-transcriptional silencing, the idea of targeted therapies became an approachable goal. The widespread involvement of microRNAs (miRNAs) was thought to be the magic bullet against multiple diseases. However, several hurdles, ranging from targeted delivery to side effects still have to be resolved. In this review, we discuss recent progress on delivery as well as current applications for miRNAs as therapeutic agents.
Authenticity Work
Authors: Scott Anne
Published: December 2011

Peer support is a relatively new form of funded mental health service provision, in which services are provided by current or former service users. It operates from recovery philosophies, aiming for deep, transformative relationships. This article asks how such “love labour” can be sustained through processes of paid work. It argues that authenticity is central to achieving this, created by a type of emotion work that focuses on clearing obstacles to the development of mutual, caring relationships. I call this authenticity work. Authenticity depends on what Bolton and Boyd call philanthropic emotional management, but requiring this as a part of paid employment creates tensions for peer support, which are addressed in debates around boundaries. This article looks at what peer supporters had to say about boundaries, authenticity, and the sustainability of their work; it is grounded in an interview-based study of 14 peer support services in Aotearoa New Zealand.
Fatal immune dysregulation due to a gain of glycosylation mutation in lymphocyte perforin
Authors: Chia Jenny , Thia Kevin , Brennan Amelia J. , Little Margaret , Williams Bronwyn , Lopez Jamie A. , Trapani Joseph A. , Voskoboinik Ilia
Published: December 2011

Mutations in the perforin gene (PRF1) are a common cause of the fatal immune dysregulation disorder, familial hemophagocytic lymphohistiocytosis (type 2 FHL, FHL2). Here we report a female infant born with biallelic PRF1 mutations: a novel substitution, D49N, and a previously identified in-frame deletion, K285del. We assessed the effects of each mutation on the cytotoxicity of human NK cells in which the expression of endogenous perforin was ablated with miR30-based short hairpin (sh) RNAs. Both mutations were detrimental for function, thereby explaining the clinically severe presentation and rapidly fatal outcome. We demonstrate that D49N exerts its deleterious effect by generating an additional (third) N-linked glycosylation site, resulting in protein misfolding and degradation in the killer cell. Our data provide a rationale for treating some cases of type 2 familial hemophagocytic lymphohistiocytosis, based on the pharmacologic inhibition or modification of glycosylation.
TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome
Authors: Rücker Frank G. , Schlenk Richard F. , Bullinger Lars , Kayser Sabine , Teleanu Veronica , Kett Helena , Habdank Marianne , Kugler Carla-Maria , Holzmann Karlheinz , Gaidzik Verena I. , Paschka Peter , Held Gerhard , von Lilienfeld-Toal Marie , Lübbert Michael , Fröhling Stefan , Zenz Thorsten , Krauter Jürgen , Schlegelberger Brigitte , Ganser Arnold , Lichter Peter , Döhner Konstanze , Döhner Hartmut
Published: December 2011

To assess the frequency of TP53 alterations and their correlation with other genetic changes and outcome in acute myeloid leukemia with complex karyotype (CK-AML), we performed integrative analysis using TP53 mutational screening and array-based genomic profiling in 234 CK-AMLs. TP53 mutations were found in 141 of 234 (60%) and TP53 losses were identified in 94 of 234 (40%) CK-AMLs; in total, 164 of 234 (70%) cases had TP53 alterations. TP53-altered CK-AML were characterized by a higher degree of genomic complexity (aberrations per case, 14.30 vs 6.16; P < .0001) and by a higher frequency of specific copy number alterations, such as −5/5q−, −7/7q−, −16/16q−, −18/18q−, +1/+1p, and +11/+11q/amp11q13∼25; among CK-AMLs, TP53-altered more frequently exhibited a monosomal karyotype (MK). Patients with TP53 alterations were older and had significantly lower complete remission rates, inferior event-free, relapse-free, and overall survival. In multivariable analysis for overall survival, TP53 alterations, white blood cell counts, and age were the only significant factors. In conclusion, TP53 is the most frequently known altered gene in CK-AML. TP53 alterations are associated with older age, genomic complexity, specific DNA copy number alterations, MK, and dismal outcome. In multivariable analysis, TP53 alteration is the most important prognostic factor in CK-AML, outweighing all other variables, including the MK category.
Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling
Authors: Hume David A. , MacDonald Kelli P. A.
Published: December 2011

Macrophage-colony stimulating factor (CSF-1) signaling through its receptor (CSF-1R) promotes the differentiation of myeloid progenitors into heterogeneous populations of monocytes, macrophages, dendritic cells, and bone-resorbing osteoclasts. In the periphery, CSF-1 regulates the migration, proliferation, function, and survival of macrophages, which function at multiple levels within the innate and adaptive immune systems. Macrophage populations elicited by CSF-1 are associated with, and exacerbate, a broad spectrum of pathologies, including cancer, inflammation, and bone disease. Conversely, macrophages can also contribute to immunosuppression, disease resolution, and tissue repair. Recombinant CSF-1, antibodies against the ligand and the receptor, and specific inhibitors of CSF-1R kinase activity have been each been tested in a range of animal models and in some cases, in patients. This review examines the potential clinical uses of modulators of the CSF-1/CSF-1R system. We conclude that CSF-1 promotes a resident-type macrophage phenotype. As a treatment, CSF-1 has therapeutic potential in tissue repair. Conversely, inhibition of CSF-1R is unlikely to be effective in inflammatory disease but may have utility in cancer.
Topical application of marine briarane-type diterpenes effectively inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and dermatitis in murine skin
Authors: Wei Wen-Chi , Lin Sheng-Yen , Chen Yi-Jyun , Wen Chih-Chun , Huang Chiung-Yao , Palanisamy Arulselvan , Yang Ning-Sun , Sheu Jyh-Horng
Published: December 2011

Background

Skin is the largest organ in the body, and is directly exposed to extrinsic assaults. As such, the skin plays a central role in host defense and the cutaneous immune system is able to elicit specific local inflammatory and systemic immune responses against harmful stimuli. 12-O-tetradecanoylphorbol-13-acetate (TPA) can stimulate acute and chronic inflammation and tumor promotion in skin. TPA-induced dermatitis is thus a useful in vivo pharmacological platform for drug discovery. In this study, the inhibitory effect of briarane-type diterpenes (BrDs) from marine coral Briareum excavatum on TPA-induced dermatitis and dendritic cell (DC) function was explored.

Methods

Evans blue dye exudation was used to determine vascular permeability. H&E-stained skin section was used to determine the formation of edema in mouse abdominal skin. We also used immunohistochemistry staining and western blot assays to evaluate the activation of specific inflammation makers and key mediators of signaling pathway in the mouse skin. Furthermore, mouse bone marrow DCs were used to determine the relationship between the chemical structure of BrDs and their regulation of DC function.

Results

BrD1 remarkably suppressed TPA-induced vascular permeability and edema in skin. At the biochemical level, BrD1 inhibited TPA-induced expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase-9, the key indicators of cutaneous inflammation. This inhibition was apparently mediated by interference with the Akt/NF-κB-mediated signaling network. BrD1 also inhibited TNF-α and IL-6 expression in LPS-stimulated BMDCs. The 8, 17-epoxide of BrDs played a crucial role in the inhibition of IL-6 expression, and replacement of the C-12 hydroxyl group with longer esters in BrDs gradually decreased this inhibitory activity.

Conclusions

Our results suggest that BrDs warrant further investigation as natural immunomodulatory agents for control of inflammatory skin diseases.
Generation of a reference transcriptome for evaluating rainbow trout responses to various stressors
Authors: Sánchez Cecilia C , Weber Gregory M , Gao Guangtu , Cleveland Beth M , Yao Jianbo , Rexroad Caird E
Published: December 2011

Background

Fish under intensive culture conditions are exposed to a variety of acute and chronic stressors, including high rearing densities, sub-optimal water quality, and severe thermal fluctuations. Such stressors are inherent in aquaculture production and can induce physiological responses with adverse effects on traits important to producers and consumers, including those associated with growth, nutrition, reproduction, immune response, and fillet quality. Understanding and monitoring the biological mechanisms underlying stress responses will facilitate alleviating their negative effects through selective breeding and changes in management practices, resulting in improved animal welfare and production efficiency.

Results

Physiological responses to five treatments associated with stress were characterized by measuring plasma lysozyme activity, glucose, lactate, chloride, and cortisol concentrations, in addition to stress-associated transcripts by quantitative PCR. Results indicate that the fish had significant stressor-specific changes in their physiological conditions. Sequencing of a pooled normalized transcriptome library created from gill, brain, liver, spleen, kidney and muscle RNA of control and stressed fish produced 3,160,306 expressed sequence tags which were assembled and annotated. SNP discovery resulted in identification of ~58,000 putative single nucleotide polymorphisms including 24,479 which were predicted to fall within exons. Of these, 4907 were predicted to occupy the first position of a codon and 4110 the second, increasing the probability to impact amino acid sequence variation and potentially gene function.

Conclusion

We have generated and characterized a reference transcriptome for rainbow trout that represents multiple tissues responding to multiple stressors common to aquaculture production environments. This resource compliments existing public transcriptome data and will facilitate approaches aiming to evaluate gene expression associated with stress in this species.
Shared component modelling as an alternative to assess geographical variations in medical practice: gender inequalities in hospital admissions for chronic diseases
Authors: Ibáñez-Beroiz Berta , Librero-López Julián , Peiró-Moreno Salvador , Bernal-Delgado Enrique
Published: December 2011

Background

Small area analysis is the most prevalent methodological approach in the study of unwarranted and systematic variation in medical practice at geographical level. Several of its limitations drive researchers to use disease mapping methods -deemed as a valuable alternative. This work aims at exploring these techniques using - as a case of study- the gender differences in rates of hospitalization in elderly patients with chronic diseases.

Methods

Design and study setting: An empirical study of 538,358 hospitalizations affecting individuals aged over 75, who were admitted due to a chronic condition in 2006, were used to compare Small Area Analysis (SAVA), the Besag-York-Mollie (BYM) modelling and the Shared Component Modelling (SCM). Main endpoint: Gender spatial variation was measured, as follows: SAVA estimated gender-specific utilization ratio; BYM estimated the fraction of variance attributable to spatial correlation in each gender; and, SCM estimated the fraction of variance shared by the two genders, and those specific for each one.

Results

Hospitalization rates due to chronic diseases in the elderly were higher in men (median per area 21.4 per 100 inhabitants, interquartile range: 17.6 to 25.0) than in women (median per area 13.7 per 100, interquartile range: 10.8 to 16.6). Whereas Utilization Ratios showed a similar geographical pattern of variation in both genders, BYM found a high fraction of variation attributable to spatial correlation in both men (71%, CI95%: 50 to 94) and women (62%, CI95%: 45 to 77). In turn, SCM showed that the geographical admission pattern was mainly shared, with just 6% (CI95%: 4 to 8) of variation specific to the women component.

Conclusions

Whereas SAVA and BYM focused on the magnitude of variation and on allocating where variability cannot be due to chance, SCM signalled discrepant areas where latent factors would differently affect men and women.
Novel sequences of subgroup J avian leukosis viruses associated with hemangioma in Chinese layer hens
Authors: Pan Wei , Gao Yulong , Sun Fenfen , Qin Litin , Liu Zaisi , Yun Bingling , Wang Yongqiang , Qi Xiaole , Gao Honglei , Wang Xiaomei
Published: December 2011

Background

Avian leukosis virus subgroup J (ALV-J) preferentially induces myeloid leukosis (ML) in meat-type birds. Since 2008, many clinical cases of hemangioma rather than ML have frequently been reported in association with ALV-J infection in Chinese layer flocks.

Results

Three ALV-J strains associated with hemangioma were isolated and their proviral genomic sequences were determined. The three isolates, JL093-1, SD09DP03 and HLJ09MDJ-1, were 7,670, 7,670, and 7,633 nt in length. Their gag and pol genes were well conserved, with identities of 94.5-98.6% and 97.1-99.5%, respectively, with other ALV-J strains at the amino acid level (aa), while the env genes of the three isolates shared a higher aa identity with the env genes of other hemangioma strains than with those of ML strains. Interestingly, two novel 19-bp insertions in the U3 region in the LTR and 5' UTR, most likely derived from other retroviruses, were found in all the three isolates, thereby separately introducing one E2BP binding site in the U3 region in the LTR and RNA polymerase II transcription factor IIB and core promoter motif ten elements in the 5' UTR. Meanwhile, two binding sites in the U3 LTRs of the three isolates for NFAP-1 and AIB REP1 were lost, and a 1-base deletion in the E element of the 3' UTR of JL093-1 and SD09DP03 introduced a binding site for c-Ets-1. In addition to the changes listed above, the rTM of the 3' UTR was deleted in each of the three isolates.

Conclusion

Our study is the first to discovery the coexistence of two novel insertions in the U3 region in the LTR and the 5' UTR of ALV-J associated with hemangioma symptoms, and the transcriptional regulatory elements introduced should be taken into consideration in the occurrence of hemangioma.
Recombinant human erythropoietin promotes the acquisition of a malignant phenotype in head and neck squamous cell carcinoma cell lines in vitro
Authors: Abhold Eric , Rahimy Elham , Wang-Rodriguez Jessica , Blair Katherine J , Yu Michael A , Brumund Kevin T , Weisman Robert A , Ongkeko Weg M
Published: December 2011

Background

Recent studies indicate an increase in tumor progression and recurrence in head and neck squamous cell carcinomas (HNSCC) of cancer patients taking recombinant human erythropoietin (rhEpo) for anemia. This study was undertaken to investigate the potential role of rhEpo in invasion, proliferation, and cisplatin-induced cell death in HNSCC cell lines.

Methods

The following experiments were performed with two HNSCC cell lines, UMSCC-10B and UMSCC-22B. Presence of EpoR in both cell lines was determined by western blot and quantitative PCR. Colorimetric MTS assays and clonogenic assays were used to study the effect of rhEpo at pharmacologically relevant doses on cell proliferation. Matrigel invasion assays were performed in order to determine effects of exogenous rhEpo on invasive abilities. Clonogenic assays were also used to study potential cytoprotective effects of rhEpo against cisplatin. Immunoblotting was done to analyze the effect of rhEpo on Akt phosphorylation. Finally, MTS and TUNEL assays were performed to test our hypothesis that Akt activation by PI3K was involved in rhEpo-mediated cisplatin resistance.

Results

HNSCC cell lines were shown to express Epo receptor (EpoR). RhEpo increased invasion 1.8-fold in UMSCC-10B and 2.6-fold in UMSCC-22B compared to control. RhEpo at 10 U/ml increased cell proliferation by 41% and 53% in UMSCC-10B and UMSCC-22B, respectively, and colony formation by 1.5-fold and 1.8-fold. UMSCC-10B treated with cisplatin and exposed to rhEpo at 1 and 10 U/ml resulted in a 1.7-fold and 3.0-fold increase in colony number compared to control, respectively. UMSCC-22B treated with cisplatin and rhEpo at 1 or 10 U/ml resulted in ~2.5-fold increase in colony number. A TUNEL assay demonstrated a 30.5% and 76.5% increase in survival in UMSCC-10B and UMSCC-22B cells, respectively, in cisplatin and rhEpo-treated cells compared to cisplatin alone. MTS assay showed similar cytoprotective effects. Western blot revealed increased phosphorylation of Akt upon exposure of HNSCC cell lines to rhEpo. MTS assay and TUNEL analyses implicate Akt as a likely contributor to regulation of rhEpo-mediated cytoprotection.

Conclusions

The results demonstrate that, in HNSCC cells expressing functional EpoR, rhEpo promotes invasion, cell proliferation, and induces resistance to cisplatin, which may contribute to tumor progression.
Methoxyflavone derivatives modulate the effect of TRAIL-induced apoptosis in human leukemic cell lines
Authors: Wudtiwai Benjawan , Sripanidkulchai Bungorn , Kongtawelert Prachya , Banjerdpongchai Ratana
Published: December 2011

Background

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells, but does not affect normal cells or human leukemic cells, such as MOLT-4 and U937 cells, which are relatively resistant to TRAIL. Three flavonoids extracted from the rhizome of K. parviflora were 5,7-dimethoxyflavone (DMF), 5,7,4'-trimethoxyflavone (TMF) and 3,5,7,3',4'-pentamethoxyflavone (PMF), and synthetic flavonoids including 5-methoxyflavone (5-MF) and 2'-methoxyflavone (2"-MF) were chosen for testing in this study. The aims of this study were to examine whether the treatment of TRAIL-resistant leukemia MOLT-4 and U937 cells, with methoxyflavone derivatives could enhance the apoptotic response and to identify the mechanism involved.

Methods

The cytotoxic effect of methoxyflavone (MF) derivatives in MOLT-4, U937 and peripheral blood mononuclear cells (PBMCs) was analyzed by the MTT assay. The induction of apoptosis and the reduction of mitochondrial transmembrane potential (ΔΨm) after staining with annexin V FITC and propidium iodide (PI), and 3,3'-dihexyloxacarbocyanine iodide (DiOC6), respectively, were performed using flow cytometry. ROS production was determined by staining with 2',7'-dichlorofluorescin diacetate and processed with a flow cytometer. DR4, DR5, cFLIP, Mcl-1, BAX and Bid expression were demonstrated by immunoblotting. Caspase-8 and -3 activities were determined by using IETD-AFC and DEVD-AFC substrates and the fluorescence intensity was measured.

Results

All methoxyflavone derivatives were cytotoxic to MOLT-4, U937 cells and PBMCs, except DMF, TMF and PMF were not toxic to PBMCs. All MF derivatives induced human leukemic MOLT-4 cell apoptosis, but not in U937 cells. Percentage of MOLT-4 cells with (ΔΨm) was increased when treated with DMF, TMF, PMF, 5-MF and 2'-MF in the presence of TRAIL. 5-MF and 2'-MF enhanced TRAIL-induced apoptosis through the up-regulation of both DRs and the down-regulation of cFLIP and Mcl-1. Bid was cleaved and BAX was up-regulated, followed by the activation of caspase-8 and -3. Oxidative stress was also increased. 2'-MF gave the same result compared with 5-MF but with a less effect.

Conclusion

Methoxyflavone derivatives enhanced TRAIL-induced apoptosis in human leukemic MOLT-4 cells through the death receptors and mitochondrial pathways.
Difference in symptom severity between early and late grass pollen season in patients with seasonal allergic rhinitis
Authors: de Weger Letty A , Beerthuizen Thijs , Gast‐Strookman Jeannette M , van der Plas Dirk T , Terreehorst Ingrid , Hiemstra Pieter S , Sont Jacob K
Published: December 2011

Background

For the development of forecasts for seasonal allergic rhinitis symptoms, it is essential to understand the relationship between grass pollen concentrations and the symptoms of grass pollen allergic patients.

Objective

The aim of this study was to delineate this relationship between seasonal allergic rhinitis symptoms and grass pollen concentrations in the Netherlands.

Methods

Grass pollen allergic patients (n = 80 [2007] ‐ 84 [2008]) were enrolled into the study. They were asked to enter their seasonal allergic rhinitis symptoms (runny nose, sneezing, blocked nose, post nasal drip, and eye symptoms) daily on a scale from 0 to 3 to the study centre either by short message service (SMS) or by internet from May‐July 2007 and April‐July 2008. Daily pollen counts were used to define the early and the late grass pollen season as the period ‘before and during’ respectively ‘after’ the first grass pollen peak (more than 150 pollen/m3).

Results

At similar grass pollen concentrations, the daily mean of the individual maximum symptom scores reported in the early season were higher as compared to that reported in the late season [differences of ‐0.41 (2007) and ‐0.30 (2008)]. This difference could not be explained by medication use by the patients nor by co‐sensitization to birch.

Conclusions

We conclude that seasonal allergic rhinitis symptoms at similar grass pollen concentrations are more severe in the early flowering season as compared to those in the late flowering season. This finding is not only relevant for development of forecasts for seasonal allergic rhinitis symptoms but also for understanding symptom development and planning and analysis of clinical studies.
Curcumin Down-Regulates Visfatin Expression and Inhibits Breast Cancer Cell Invasion
Authors: Kim Su-Ryun , Park Hyun-Joo , Bae Yun-Hee , Ahn Soon-Cheol , Wee Hee-Jun , Yun Il , Jang Hye-Ock , Bae Moon-Kyoung , Bae Soo-Kyung
Published: December 2011

Obesity is frequently associated with breast cancer. Such associations are possibly mediated by adipokines. Visfatin, an adipokine, has recently been shown to be related to the development and progression of breast cancer. Therefore, the down-regulation of visfatin may be a novel strategy for breast cancer therapy. Curcumin has anticancer activities by modulating multiple signaling pathways and genes. The purpose of this study was to investigate whether visfatin gene expression is affected by curcumin in human breast cancer cells and to characterize the functional role of visfatin in breast cancer. We found that the mRNA and protein levels of visfatin were down-regulated by curcumin in MDA-MB-231, MDA-MB-468, and MCF-7 breast cancer cells, along with decreased activity of constitutive nuclear factor (NF)-κB. We confirmed the repressive effect of curcumin on visfatin transcription by performing a visfatin promoter-driven reporter assay and identified two putative NF-κB-binding sites on visfatin promoter that are important for this effect. EMSA and chromatin immunoprecipitation analysis indicated the binding of p65 to the visfatin promoter, which was effectively blocked by curcumin. Enforced expression of p65 protein increased visfatin promoter activity, whereas blocking NF-κB signaling suppressed visfatin gene expression. Visfatin could enhance the invasion of MDA-MB-231 cells and also attenuate curcumin-induced inhibition of cell invasion; on the other hand, visfatin knockdown by small interfering RNA led to the reduction of cell invasion. Our data demonstrate, for the first time, that curcumin down-regulates visfatin gene expression in human breast cancer cells by a mechanism that is, at least in part, NF-κB dependent and suggest that visfatin may contribute to breast cancer cell invasion and link obesity to breast cancer development and progression.
Performance and three-dimensional kinematics of bipedal lizards during obstacle negotiation
Authors: Olberding Jeffrey P. , McBrayer Lance D. , Higham Timothy E.
Published: December 2011

Bipedal running is common among lizard species, but although the kinematics and performance of this gait have been well characterized, the advantages in biologically relevant situations are still unclear. Obstacle negotiation is a task that is ecologically relevant to many animals while moving at high speeds, such as during bipedal running, yet little is known about how obstacles impact locomotion and performance. We examined the effects of obstacle negotiation on the kinematics and performance of lizards during bipedal locomotion. We quantified three-dimensional kinematics from high-speed video (500 Hz) of six-lined racerunners (Aspidoscelis sexlineata) running on a 3 m racetrack both with and without an obstacle spanning the width of the track. The lizards did not alter their kinematics prior to contacting the obstacle. Although contact with the obstacle caused changes to the hindlimb kinematics, mean forward speed did not differ between treatments. The deviation of the vertical position of the body center of mass did not differ between treatments, suggesting that in the absence of a cost to overall performance, lizards forgo maintaining normal kinematics while negotiating obstacles in favor of a steady body center of mass height to avoid destabilizing locomotion.
Endogenous aldosterone is involved in vascular calcification in rat
Authors: Wu Sheng-Ying , Yu Yan-Rong , Cai Yan , Jia Li-Xin , Wang Xiong , Xiao Chuan-Shi , Tang Chao-Shu , Qi Yong-Fen
Published: December 2011

Aldosterone (Aldo) is an important active hormone in the renin–angiotensin–aldosterone system and plays a vital role in the development of hypertension, heart failure and other cardiovascular diseases. We aimed to explore the role of endogenous Aldo in aortic calcification in rats. We induced arterial calcification in rats by intramuscular administration of vitamin D3 plus oral nicotine (VDN) and determined calcium content, 45Ca2+ accumulation and activity of alkaline phosphatase (ALP). The mRNA level of osteopontin (OPN) was measured by semi-quantitative reverse transcriptase polymerase chain reaction. Deposition of collagen in the aorta wall was measured by Sirius red staining. The content of angiotensin II (Ang II) and Aldo in plasma and myocardial and vascular tissue was determined by radioimmunoassay. In rats with VDN treatment, von Kossa staining showed calcification in vascular smooth muscle cells and extracellular matrix, and the content of calcium in calcified arteries was 5.8-fold of that in control arteries ( P < 0.01). The accumulation of 45Ca2+ and activity of ALP in calcified aortic tissue was three- and 2.5-fold, respectively, that in control tissue ( P < 0.01). The mRNA expression of OPN was significantly higher, by 58%, in calcified than control tissue ( P < 0.01). Vascular fibrosis was greater in rats with calcified tissue than in control rats. The level of Ang II and Aldo was 58% and 80% higher, respectively, in calcified than control tissue (both P < 0.01). The changes could be significantly improved by treatment with captopril, an angiotensin-converting enzyme inhibitor, and the Aldo receptor antagonist spironolactone. These results suggest that Aldo is an endogenous bioactive factor involved in vascular calcification.
Ad Gist: Ad Communication in a Single Eye Fixation
Authors: Pieters Rik , Wedel Michel
Published: December 2011

Most ads in practice receive no more than a single eye fixation. This study investigates the limits of what ads can communicate under such adverse exposure conditions. We find that consumers already know at maximum levels of accuracy and with high degree of certainty whether something is an ad or is editorial material after an exposure of less than 100 milliseconds and—if the ad is typical—which product is being advertised. Even after an extremely coarse visual presentation of 100 milliseconds, the product and brand in typical ads are identified well above chance levels, with atypical ads doing slightly better at the brand level. We propose a new metric that quantifies how effectively individual ads communicate their gist in adverse exposure conditions and that predicts the immediate interest that ads draw. Bayesian mediation analyses show that because of their better gist performance, typical ads rather than atypical ones raise immediate interest after very brief exposures. These findings challenge some of the received knowledge in advertising theory and practice, and they reveal the immediate communication benefits of typical ads.
Whose evidence base? The dynamic effects of ownership, receptivity and values on collaborative evidence-informed policy making
Authors: Shine Kasey Treadwell , Bartley Brendan
Published: December 2011

This paper explores questions of ownership of and receptivity to research-based evidence and, in combination with often competing values, their effect on collaborative evidence-informed policy making (EIPM). We propose that these issues generate a ‘dynamo’ of push–pull factors for policy makers, researchers and research managers. Through the process of producing and managing new knowledge in collaborative EIPM efforts, these factors shape different ‘realities’. We argue that these help to prevent, break, distort or facilitate the conceptual cycle of EIPM. The paper sets out ideas for mapping ownership, receptivity and values and their dynamic effects, drawn from actor network theory, complexity theory and the Competing Values Framework. In conclusion, it suggests that engagement with and development of policy making as a form of emergent ordering may provide ways for more effective EIPM.
Echinocandin Use in the Neonatal Intensive Care Unit
Authors: Caudle Kelly E , Inger Amanda G , Butler Dawn R , Rogers P David
Published: December 2011

OBJECTIVE:

To evaluate the literature regarding the use of echinocandins to treat invasive fungal infections caused by Candida spp. in patients in the neonatal intensive care unit.

DATA SOURCES:

Literature retrieval was accessed through MEDLINE (Jan 2000-September 2011) using the search terms echinocandin, caspofungin, micafungin, anidulafungin, and neonate with limits for age group (ie, birth to 1 month). Reference citations from identified articles were also reviewed.

STUDY SELECTION AND DATA EXTRACTION:

Relevant information on the pharmacokinetics, efficacy, and safety of echinocandins in neonates was selected. Prospective studies, retrospective studies, and case series in English identified from MEDLINE were evaluated.

DATA SYNTHESIS:

Neonates, especially preterm neonates, have many risk factors that predispose them for invasive fungal infections caused by Candida spp. To date, the only antifungals recommended for use in neonates for treatment of candidiasis are amphotericin B (deoxycholate or a lipid formulation) and fluconazole; however, the toxicities associated with amphotericin B and resistance of certain Candida spp. to fluconazole limit their use in neonates. There is a need for a broad-spectrum antifungal agent with limited toxicity for use in this patient population. The echinocandins may represent such a class of antifungals. To date, micafungin is the most studied echinocandin in the neonatal population, followed by caspofungin; however, studies evaluating their efficacy and pharmacokinetic parameters in neonates are few.

CONCLUSIONS:

Although studies suggest that the echinocandins may have a favorable safety profile, the lack of pharmacokinetic data and standardized study designs limit current recommendations of use of echinocandins as first-line agents in neonates in the treatment of fungal infections. However, if an echinocandin is to be used in this population, the data presented in this review suggest the use of micafungin over the other echinocandins, and higher doses of micafungin (10-15 mg/kg/day) should be used when central nervous system involvement is suspected.
Not your parents' marching bands: The history of HONK!, pedagogy and music education
Authors: GAROFALO REEBEE
Published: December 2011

The HONK! Festival of Activist Street Bands (honkfest.org) is an independent, grassroots, non-commercial weekend festival held each autumn in Somerville, Massachusetts. It is a moving spectacle of colourful marching bands, gigantic puppets, creative bikers, jugglers, hoopers, flag twirlers
and stilt walkers, interspersed with unions, activist organizations and community groups. The deep history of HONK! derives from the role of military brass and drums in colonial conquest and religious conversion. As empires crumbled, these military and religious ensembles gave rise to community-based
civilian bands that incorporated local popular musics to create new transcultural hybrids. HONK! represents one visible tip of a substantial underground of alternative street bands that encompasses large parts of the globe. The processes by which these bands operate provide an alternative
model (or complement) to traditional music education. This research represents an embryonic attempt to articulate the values and techniques that comprise what I call HONK! pedagogy.
For their musical uplift: Emma Azalia Hackley and voice culture in African American communities
Authors: KARPF JUANITA
Published: December 2011

The noted African American soprano Emma Azalia Hackley (1867-1922) abandoned her concert career in the early twentieth century and began travelling throughout the United States, organizing community choruses and promoting community music making. She spent the remainder of her life engaged
in what she called 'musical social uplift', which entailed teaching voice culture to hundreds of thousands of African Americans. To accomplish her goals, she formulated a unique pedagogy especially suited to black citizens in times of racism and segregation. Because of her commitment to music
education and community activism, she became famous as the 'National Vocal Teacher' of African Americans.
In memorial: Christopher Small, with gratitude
Authors: COHEN MARY L.
Published: December 2011

Christopher Small's (1927-2011) concept of musicking provides community music researchers and practitioners a theoretical framework that directly supports our work. With ideas based in Gregory Bateson's writings, Small argues that music is an activity, all people are capable of music-making,
both individual and social components are key parts of his concept, and both sonic and social relationships occur in musical performances. This brief memorial about Small's writing highlights key themes in his concept of musicking.