UAP1 is overexpressed in prostate cancer and is protective against inhibitors of N-linked glycosylation

Prostate cancer is the second most common cause of cancer-associated deaths in men, and signaling via a transcription factor called androgen receptor (AR) is an important driver of the disease. Consequently, AR target genes are prominent candidates to be specific for prostate cancer and also important for the survival of the cancer cells. Here we assess the levels of all hexosamine biosynthetic pathway (HBP) enzymes in 15 separate clinical gene expression data sets and identify the last enzyme in the pathway, UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), to be highly overexpressed in prostate cancer. We analyzed 3261 prostate cancers on a tissue microarray and found that UAP1 staining correlates negatively with Gleason score (P=0.0039) and positively with high AR expression (P<0.0001). Cells with high UAP1 expression have 10-fold increased levels of the HBP end-product, UDP-N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is essential for N-linked glycosylation occurring in the endoplasmic reticulum (ER) and high UAP1 expression associates with resistance against inhibitors of N-linked glycosylation (tunicamycin and 2-deoxyglucose) but not with a general ER stress-inducing agent, the calcium ionophore A23187. Knockdown of UAP1 expression re-sensitized cells towards inhibitors of N-linked glycosylation, as measured by proliferation and activation of ER stress markers. Taken together, we have identified an enzyme, UAP1, which is highly overexpressed in prostate cancer and protects cancer cells from ER stress conferring a growth advantage.

Biosensor analysis of dynamics of interleukin 5 receptor subunit beta(c) interaction with IL5:IL5R(alpha) complexes

To gain insight into IL5 receptor subunit recruitment mechanism, and in particular the experimentally elusive pathway for assembly of signaling subunit beta(c), we constructed a soluble beta(c) ectodomain (s(beta)(c)) and developed an optical biosensor assay to measure its binding kinetics. Functionally active s(beta)(c) was anchored via a C-terminal His tag to immobilized anti-His monoclonal antibodies on the sensor surface. Using this surface, we quantitated for the first time direct binding of s(beta)(c) to IL5R(alpha) complexed to either wild-type or single-chain IL5. Binding was much weaker if at all with either R(alpha) or IL5 alone. Kinetic evaluation revealed a moderate affinity (0.2-1 microM) and relatively fast off rate for the s(beta)(c) interaction with IL5:R(alpha) complexes. The data support a model in which beta(c) recruitment occurs with preformed IL5:R(alpha) complex. Dissociation kinetics analysis suggests that the IL5-alpha-beta(c) complex is relatively short-lived. Overall, this study solidifies a model of sequential recruitment of receptor subunits by IL5, provides a novel biosensor binding assay of beta(c) recruitment dynamics, and sets the stage for more advanced characterization of the roles of structural elements within R(alpha), beta(c), and cytokines of the IL5/IL3/GM-CSF family in receptor recruitment and activation.

The influence of area level social deprivation on preoperative disease severity and postoperative outcomes following unicompartmental knee joint replacement

BACKGROUND: This study investigated the effect of socioeconomic deprivation on preoperative disease and outcome following unicompartmental knee replacement (UKR).

METHODS: 307 Oxford UKRs implanted between 2008 and 2013 under the care of one surgeon using the same surgical technique were analysed. Deprivation was quantified using the Northern Ireland Multiple Deprivation Measure. Preoperative disease severity and postoperative outcome were measured using the Oxford Knee Score (OKS).

RESULTS: There was no difference in preoperative OKS between deprivation groups. Preoperative knee range of motion (ROM) was significantly reduced in more deprived patients with 10° less ROM than least deprived patients. Postoperatively there was no difference in OKS improvement between deprivation groups (p=0.46), with improvements of 19.5 and 21.0 units in the most and least deprived groups respectively. There was no significant association between deprivation and OKS improvement on unadjusted or adjusted analysis. Preoperative OKS, Short Form 12 mental component score and length of stay were significant independent predictors of OKS improvement. A significantly lower proportion of the most deprived group (15%) reported being able to walk an unlimited distance compared to the least deprived group (41%) one year postoperatively.

CONCLUSION: More deprived patients can achieve similar improvements in OKS to less deprived patients following UKR.

LEVEL OF EVIDENCE: 2b - retrospective cohort study of prognosis.

Nuclear cataract shows significant familial aggregation in an older population after adjustment for possible shared environmental factors.

PURPOSE: To quantify the association between siblings in age-related nuclear cataract, after adjusting for known environmental and personal risk factors. METHODS: All participants (probands) in the Salisbury Eye Evaluation (SEE) project and their locally resident siblings underwent digital slit lamp photography and were administered a questionnaire to assess risk factors for cataract including: age, gender, lifetime sun exposure, smoking and diabetes history, and use of alcohol and medications such as estrogens and steroids. In addition, blood pressure, body mass index, and serum antioxidants were measured in all participants. Lens photographs were graded by trained observers masked to the subjects' identity, using the Wilmer Cataract Grading System. The odds ratio for siblings for affectedness with nuclear cataract and the sibling correlation of nuclear cataract grade, after adjusting for covariates, were estimated with generalized estimating equations. RESULTS: Among 307 probands (mean age, 77.6 +/- 4.5 years) and 434 full siblings (mean age, 72.4 +/- 7.4 years), the average sibship size was 2.7 per family. After adjustment for covariates, the probability of development of nuclear cataract was significantly increased (odds ratio [OR] = 2.07, 95% confidence interval [CI], 1.30-3.30) among individuals with a sibling with nuclear cataract (nuclear grade > or = 3.0). The final fitted model indicated a magnitude of heritability for nuclear cataract of 35.6% (95% CI: 21.0%-50.3%) after adjustment for the covariates. CONCLUSIONS: Findings in this study are consistent with a genetic effect for age-related nuclear cataract, a common and clinically significant form of lens opacity.

Root caries development in older adults- a prospective cohort study

Objectives: To identify factors associated with root caries development during a two year period in a population of independently living older adults. Methods: A prospective cohort study was carried out with 334 independently living volunteers aged 65 and older. At baseline (t0), each participant completed a questionnaire which recorded age, gender, medical history, fluoride exposure, oral and denture hygiene practices, smoking and alcohol consumption, diet information, and socio economic information. Clinical examinations were performed and stimulated saliva samples were collected. Patients were reviewed 12(t1) and 24(t2) months later to determine the root caries increment. Results: 307 adults were assessed at t1 and 280 were assessed at t2 with 83.8% of participants examined at 24 months. Incidence of root caries in this cohort was 17.4% at t1 and 21.6% at t2. The mean root caries increment was 0.43 (SD 1.45) surfaces at t1 and 0.70 (SD 1.86) surfaces at t2. Age >70 years, completing education at primary level, poor oral hygiene, xerostomia, coronal decay at baseline, higher root caries index at baseline and number of exposed root surfaces showed a statistically significant association (P < 0.05) with root caries development. Conclusion: Root caries is a substantive dental health problem for our older population. Root caries prevention strategies should be targeted at older adults who have poor plaque control and high levels of caries experience. In particular patients with xerostomia should be targeted with preventive measures.

Effective collision strengths for forbidden transitions among the 3s23p3 fine-structure levels of Cl III

Effective collision strengths for the 10 astrophysically important fine-structure forbidden transitions among the ⁴S^o, ²D^o and ²P^o levels in the 3s²3p³ configuration of Cl III are presented. The calculation employs the multichannel R-matrix method to compute the electron-impact excitation collision strengths in a close-coupling expansion, which incorporates the lowest 23 LS target eigenstates of Cl III. These states are formed from the 3s²3p³, 3s3p⁴, 3s²3p²3d and 3s²3p²4s configurations. The Maxwellian-averaged effective collision strengths are presented graphically for all 10 fine-structure transitions over a wide range of electron temperatures appropriate for astrophysical applications [log T(K) = 3.3 - log T(K) = 5.9]. Comparisons are made with the earlier seven-state close-coupling calculation of Butler & Zeippen, and in general excellent agreement is found in the low-temperature region where a comparison is possible [log T(K) = 3.3 - log T(K) = 4.7]. However, discrepancies of up to 30 per cent are found to occur for the forbidden transitions which involve the ⁴S^o ground state level, particularly for the lowest temperatures considered. At the higher temperatures, the present data are the only reliable results currently available.

The Portuguese continental shelf soft-bottom benthic habitats

As comunidades de macrofauna bentónica são ecológica e economicamente relevantes, sendo fonte de diversos bens e serviços. A sua identificação, caracterização e mapeamento são importantes para identificar áreas marinhas protegidas e para uma melhor utilização do ambiente marinho. Este trabalho apresenta um estudo holístico da diversidade e distribuição espacial das comunidades de macrofauna bentónica ao longo da plataforma continental Portuguesa. Cerca de 145 locais posicionados ao longo da plataforma ocidental e setentrional foram amostrados com uma draga Smith-McIntyre de área 0,1 m2, a profundidades que variaram entre os 13 e 195 metros. Os sedimentos foram caracterizados em termos de granulometria, de matéria orgânica e geoquímica. São propostos seis habitats bentónicos principais para a plataforma continental Portuguesa, analisada a relação entre os dados biológicos e ambientais e discutidas questões biogeográficas relacionadas com a distribuição espacial de espécies e das comunidades. A distribuição da granulometria e assinatura geoquímica dos sedimentos da plataforma continental revelou-se bastante complexa, refletindo importantes diferenças nas fontes (naturais e antropogénicas), origem fluvial, geomorfologia da plataforma, hidrodinamismo e atividade biológica. Relativamente à macrofauna, entre os mais de 30 mil indivíduos recolhidos, foram identificados cerca de 737 taxa, dos quais quatro são novas espécies e aproximadamente 40 correspondem a primeiras ocorrências para a costa Portuguesa. As espécies mais frequentes foram a Ampharete finmarchica, Ampelisca sp. e Lumbrineris lusitanica sp. nov. enquanto as mais abundantes foram Mediomastus fragilis, Polygordius appendiculatus e Ampharete finmarchica. A abundância por local de amostragem variou entre 7 e 1.307 espécimens e a diversidade alfa atingiu um máximo de 96 taxa. Os sedimentos mais grosseiros apresentaram maior diversidade e abundância comparativamente com os sedimentos envasados. Foram identificados seis habitats bentónicos na plataforma continental Portuguesa: (a) sedimentos grosseiros com Protodorvillea kefersteini, Pisione remota, Angulus pygmaeus e várias espécies intersticiais; (b) areias finas hidrodinamicamente expostas e próximas da linha de costa com Magelona johnstoni, Urothoe pulchella e Angulus fabula; (c) comunidade de Abra alba em areia envasadas da plataforma profunda do noroeste; (d) Galathowenia oculata, Lumbrinerides amoureuxi e outros poliquetas escavadores e tubícolas em areais envasadas muito profundas na plataforma sudoeste; (e) Euchone rubrocincta, Nematonereis unicornis e várias espécies setentrionais nas areias envasadas da plataforma sul; (f) vasas com Sternaspis scutata, Heteromastus filiformis e Psammogammarus caecus. A granulometria do sedimento (particularmente teor em finos), matéria orgânica, profundidade e hidrodinamismo foram as variáveis ambientais com a maior relação com os padrões de distribuição da macrofauna. As espécies cosmopolitas e de latitudes superiores (clima Boreal ou Temperado Frio) dominaram o setor noroeste, sendo substituídas por espécies mais quentes na área de transição entre os canhões da Nazaré e S. Vicente, que dominaram por conseguinte a plataforma sul. O presente estudo evidenciou a abundância e diversidade da macrofauna bentónica ao longo da área costeira de Portugal, na qual coexistem faunas das províncias biogeográficas do norte da Europa, bem como subtropicais. Integrado com outro estudos, este poderá ser a base para uma melhor gestão da plataforma continental Portuguesa.

HIV positive men as fathers: Accounts of displacement, ir/responsibility and paternal emergence

It is now apparent that socio-cultural constructions of masculinity variously impact men’s experiences of their HIV positive status, yet how being a father can feature in this mix remains under-researched. This study employed in-depth semi-structured interviews and Foucauldian-informed discourse analysis to explore the accounts of six self-identifying heterosexual fathers (four black African migrants, two white European) who had been living with HIV from five to 24 years. While the HIV-related literature calls for the need to subvert ‘traditional’ expressions of masculinity as a means of promoting HIV prevention and HIV health, we argue that the lived experience for HIV positive men as fathers is more socially, discursively and thus more psychologically nuanced. We illustrate this by highlighting ways in which HIV positive men as fathers are not simply making sense of themselves as a HIV positive man for whom the modern (new) man and father positions are useful strategies for adapting to HIV and combating associated stigma. Discourses of modern and patriarchal fatherhoods, a gender-specific discourse of irresponsibility, and the neoliberal conflation of heath and self-responsibility are also at work in the sense making frames that HIV positive men, who are also fathers, can variously deploy. Our analysis shows how this discursive mix can underpin possibilities of often conflicted meaning and identity when living as a man and father with HIV in the UK, and specifically how discourses of fatherhood and HIV ‘positive’ health can complicate these men’s expressions and inhabitations of masculinity.

Composition, temporal and spatial patterns of very-nearshore larval fish assemblages at the Arrábida marine park

Tese dout., Ciências do Mar, Universidade do Algarve, 2006

Ecological tools for the management of cyanobacteria blooms in the Guadiana River watershed, Southwest Iberia

Strong water demand for irrigation, energy and drinking water production is responsible for an increasingly regulation of freshwater flow patterns and watersheds. In this context, the construction of dams allows water storage but seriously restricts freshwater flow downstream. Due to scarcity of freshwater resources, reservoir water management often promotes high hydraulic residence. This may cause strong impacts on biological components of aquatic ecosystems, influencing the development of cyanobacteria blooms and aggravating their harmful impacts.

For host factors weddings and a Koch’s bacillus funeral: actin, lipids, phagosome maturation and inflammasome activation

The chapter describes the 10 years research of Anes Laboratory on the interactions of M. tuberculosis with macrophages namely with the actin. modulation by lipids, phagosome maturation and inflammasome activation

'Incorrigibly Plural’: New Histories of Ulster and Northern Ireland’

Review article of Carson’s Army: The Ulster Volunteer Force, 1910–22. By Timothy Bowman. Manchester University Press, Manchester, 2007. 256 pp. ISBN 0719073715, £55. A History of the Northern Ireland Labour Party: Democratic Socialism and Sectarianism. By Aaron Edwards. Manchester University Press, Manchester, 2009. xiii + 240 pp. ISBN 0719078741, £60. Catholic Belfast and Nationalist Ireland in the Era of Joe Devlin 1871–1934. By A.C. Hepburn. Oxford University Press, Oxford, 2008. xix +307 pp. ISBN 019929884X, £55. The Big House in the North of Ireland: Land, Power and Social Elites, 1878–1960. By Olwen Purdue. University College Dublin Press, Dublin, 2009. xv + 297 pp. ISBN 978-1-906359-25-6, £24.

Social Capital in Inter-Organizational Partnership Research

This chapter focuses on the use of social capital as a construct to examine and explain the formation and operation of inter-organizational partnerships. In particular it shows how social capital contributes to the sustainability of a public sector partnership. In this research context social capital is defined as the networks, trust, norms and values that enable individuals and organizations to achieve mutual goals through collaboration. This definition draws upon the author’s empirical research on partnerships and partnership working in the field of post-compulsory education and her practical experience of establishing, managing and leading international partnerships for teaching and research in teacher education. The emphasis is on the practical application of social capital to qualitative data and on identifying sources of evidence, including research literature from different disciplines in the social sciences to interpret and theorize primary data. The first section of the chapter considers the complexities of defining social capital in the context of rival theoretical and political perspectives and leads to a discussion of the dimensions of social capital that are found in effective and sustained partnerships.

Increasing the speed of parallel decoding of turbo codes

Turbo codes experience a significant decoding delay because of the iterative nature of the decoding algorithms, the high number of metric computations and the complexity added by the (de)interleaver. The extrinsic information is exchanged sequentially between two Soft-Input Soft-Output (SISO) decoders. Instead of this sequential process, a received frame can be divided into smaller windows to be processed in parallel. In this paper, a novel parallel processing methodology is proposed based on the previous parallel decoding techniques. A novel Contention-Free (CF) interleaver is proposed as part of the decoding architecture which allows using extrinsic Log-Likelihood Ratios (LLRs) immediately as a-priori LLRs to start the second half of the iterative turbo decoding. The simulation case studies performed in this paper show that our parallel decoding method can provide %80 time saving compared to the standard decoding and %30 time saving compared to the previous parallel decoding methods at the expense of 0.3 dB Bit Error Rate (BER) performance degradation.