On the alignment of debris discs and their host stars' rotation axis - implications for spin-orbit misalignment in exoplanetary systems

It has been widely thought that measuring the misalignment angle between the orbital plane of a transiting exoplanet and the spin of its host star was a good discriminator between different migration processes for hot-Jupiters. Specifically, well-aligned hot-Jupiter systems (as measured by the Rossiter-McLaughlin effect) were thought to have formed via migration through interaction with a viscous disc, while misaligned systems were thought to have undergone a more violent dynamical history. These conclusions were based on the assumption that the planet-forming disc was well-aligned with the host star. Recent work by a number of authors has challenged this assumption by proposing mechanisms that act to drive the star-disc interaction out of alignment during the pre-main-sequence phase. We have estimated the stellar rotation axis of a sample of stars which host spatially resolved debris discs. Comparison of our derived stellar rotation axis inclination angles with the geometrically measured debris-disc inclinations shows no evidence for a misalignment between the two.

Characterisation and modelling of the thermorheological properties of pharmaceutical polymers and their blends using capillary rheometry: Implications for hot melt processing of dosage forms.

Given the growing interest in thermal processing methods, this study describes the use of an advanced rheological technique, capillary rheometry, to accurately determine the thermorheological properties of two pharmaceutical polymers, Eudragit E100 (E100) and hydroxypropylcellulose JF (HPC) and their blends, both in the presence and absence of a model therapeutic agent (quinine, as the base and hydrochloride salt). Furthermore, the glass transition temperatures (Tg) of the cooled extrudates produced using capillary rheometry were characterised using Dynamic Mechanical Thermal Analysis (DMTA) thereby enabling correlations to be drawn between the information derived from capillary rheometry and the glass transition properties of the extrudates. The shear viscosities of E100 and HPC (and their blends) decreased as functions of increasing temperature and shear rates, with the shear viscosity of E100 being significantly greater than that of HPC at all temperatures and shear rates. All platforms were readily processed at shear rates relevant to extrusion (approximately 200–300 s−1) and injection moulding (approximately 900 s−1). Quinine base was observed to lower the shear viscosities of E100 and E100/HPC blends during processing and the Tg of extrudates, indicative of plasticisation at processing temperatures and when cooled (i.e. in the solid state). Quinine hydrochloride (20% w/w) increased the shear viscosities of E100 and HPC and their blends during processing and did not affect the Tg of the parent polymer. However, the shear viscosities of these systems were not prohibitive to processing at shear rates relevant to extrusion and injection moulding. As the ratio of E100:HPC increased within the polymer blends the effects of quinine base on the lowering of both shear viscosity and Tg of the polymer blends increased, reflecting the greater solubility of quinine within E100. In conclusion, this study has highlighted the importance of capillary rheometry in identifying processing conditions, polymer miscibility and plasticisation phenomena.

In vitro bioassay investigations of the endocrine disrupting potential of steviol glycosides and their metabolite steviol, components of the natural sweetener Stevia

The food industry is moving towards the use of natural sweeteners such as those produced by Stevia rebaudiana due to the number of health and safety concerns surrounding artificial sweeteners. Despite the fact that these sweeteners are natural; they cannot be assumed safe. Steviol glycosides have a steroidal structure and therefore may have the potential to act as an endocrine disruptor in the body. Reporter gene assays (RGAs), H295R steroidogenesis assay and Ca(2+) fluorimetry based assays using human sperm cells have been used to assess the endocrine disrupting potential of two steviol glycosides: stevioside and rebaudioside A, and their metabolite steviol. A decrease in transcriptional activity of the progestagen receptor was seen following treatment with 25,000 ng/ml steviol in the presence of progesterone (157 ng/ml) resulting in a 31% decrease in progestagen response (p=<0.01). At the level of steroidogenesis, the metabolite steviol (500-25,000 ng/ml) increased progesterone production significantly by 2.3 fold when exposed to 10,000 ng/ml (p=<0.05) and 5 fold when exposed to 25,000 ng/ml (p=<0.001). Additionally, steviol was found to induce an agonistic response on CatSper, a progesterone receptor of sperm, causing a rapid influx of Ca(2+). The response was fully inhibited using a specific CatSper inhibitor. These findings highlight the potential for steviol to act as a potential endocrine disruptor.

Co-localization of GnRH ligands and their receptors in the European sea bass, Dicentrarchus labrax

The migration of the hypophysiotropic GnRH (GnRH-I) neurons during early development is a crucial step in establishing a normally functioning reproductive system in all vertebrates. These neurons derive from progenitor cells in the olfactory placode and subsequently migrate to their final position in the ventral forebrain, where they mediate hypophysiotropic control over Lh. We use zebrafish as a model to investigate the path and the factors that mediate the migration of the GnRH-I neurons during early development. A transgenic line of zebrafish, in which GnRH- I neurons specifically express a reporter gene (GFP) has been developed in our lab. This was achieved by integrating a GnRH-I promoter/GFP reporter transgene into the zebrafish genome. The resulting transgenic line allows us to track the route of the GnRH-I neuronal migration in real time and in vivo. We have used this line to conduct time lapse imaging to ascertain the exact migrational path and the final position in the ventral forebrain of the GnRH-I neurons.

Reliability of nasal auscultation and their relation to middle ear condition – a clinical interest to pediatrics respiratory physiotherapy

Background: Acute respiratory infections are usual in children under three years old occurring in upper respiratory tract, having an impact on child and caregiver’s quality of life predisposing to otitis media or bronchiolitis. There are few valid and reliable measures to determine the child’s respiratory condition and to guide the physiotherapy intervention. Aim: To assess the intra and inter rater reliability of nasal auscultation, to analyze the relation between sounds’ classification and middle ear’s pressure and compliance as well as with the Clinical Severity Score. Methods: A cross-sectional observational study was composed by 125 nursery children aged up to three years old. Tympanometry, pulmonary and nasal auscultation and application of Clinical Severity Score were performed to each child. Nasal auscultation sounds’ were recorded and sent to 3 blinded experts, that classified, as “obstructed” and “unobstructed”, with a 48 hours interval, in order to analyze inter and intra rater reliability. Results: Nasal auscultation revealed a substantial inter and intra rater reliability (=0,749 and evaluator A - K= 0,691; evaluator B - K= 0,605 and evaluator C - K= 0,724, respectively). Both ears’ pressure was significantly lower in children with an "unobstructed" nasal sound when compared with an “obstructed” nasal sound (t=-3,599, p<0,001 in left ear; t=-2,258, p=0,026 in right ear). Compliance in both ears was significantly lower in children with an "obstructed" nasal sound when compared with “unobstructed” nasal sound (t=-2,728, p=0,007 in left ear; t=-3,830, p<0,001 in right ear). There was a statistically significant association between sounds’ classification and tympanograms types in both ear’s (=11,437, p=0,003 in left ear; =13,535, p=0,001 in right ear). There was a trend to children with an "unobstructed" nasal sound that had a lower clinical severity score when compared with “obstructed” children. Conclusion: It was observed a good intra and substantial inter reliability for nasal auscultation. Nasal auscultation sounds’ classification was related to middle ears’ pressure and compliance.

Solid contact PVC membrane electrodes based on neutral or charged carriers for the selective reading of anionic sulfamethoxazole and their application to the analysis of aquaculture water

Sulfamethoxazole (SMX) is among the antibiotics employed in aquaculture for prophylactic and therapeutic reasons. Environmental and food spread may be prevented by controlling its levels in several stages of fish farming. The present work proposes for this purpose new SMX selective electrodes for the potentiometric determination of this sulphonamide in water. The selective membranes were made of polyvinyl chloride (PVC) with tetraphenylporphyrin manganese (III) chloride or cyclodextrin-based acting as ionophores. 2-nitrophenyl octyl ether was employed as plasticizer and tetraoctylammonium, dimethyldioctadecylammonium bromide or potassium tetrakis (4-chlorophenyl) borate was used as anionic or cationic additive. The best analytical performance was reported for ISEs of tetraphenylporphyrin manganese (III) chloride with 50% mol of potassium tetrakis (4-chlorophenyl) borate compared to ionophore. Nersntian behaviour was observed from 4.0 × 10−5 to 1.0 × 10−2 mol/L (10.0 to 2500 µg/mL), and the limit of detection was 1.2 × 10−5 mol/L (3.0 µg/mL). In general, the electrodes displayed steady potentials in the pH range of 6 to 9. Emf equilibrium was reached before 15 s in all concentration levels. The electrodes revealed good discriminating ability in environmental samples. The analytical application to contaminated waters showed recoveries from 96 to 106%.

Ankylosing spondylitis: genomic and functional characterization of candidate genes and their repercussion in clinical practice

RESUMO: Introdução: A espondilite anquilosante (EA) é uma doença inflamatória crónica caracterizada pela inflamação das articulações sacroilíacas e da coluna. A anquilose progressiva motiva uma deterioração gradual da função física e da qualidade de vida. O diagnóstico e o tratamento precoces podem contribuir para um melhor prognóstico. Neste contexto, a identificação de biomarcadores, assume-se como sendo muito útil para a prática clínica e representa hoje um grande desafio para a comunidade científica. Objetivos: Este estudo teve como objetivos: 1 - caracterizar a EA em Portugal; 2 - investigar possíveis associações entre genes, MHC e não-MHC, com a suscetibilidade e as características fenotípicas da EA; 3 - identificar genes candidatos associados a EA através da tecnologia de microarray. Material e Métodos: Foram recrutados doentes com EA, de acordo com os critérios modificados de Nova Iorque, nas consultas de Reumatologia dos diferentes hospitais participantes. Colecionaram-se dados demográficos, clínicos e radiológicos e colhidas amostras de sangue periférico. Selecionaram-se de forma aleatória, doentes HLA-B27 positivos, os quais foram tipados em termos de HLA classe I e II por PCR-rSSOP. Os haplótipos HLA estendidos foram estimados pelo algoritmo Expectation Maximization com recurso ao software Arlequin v3.11. As variantes alélicas dos genes IL23R, ERAP1 e ANKH foram estudadas através de ensaios de discriminação alélica TaqMan. A análise de associação foi realizada utilizando testes da Cochrane-Armitage e de regressão linear, tal como implementado pelo PLINK, para variáveis qualitativas e quantitativas, respetivamente. O estudo de expressão génica foi realizado por Illumina HT-12 Whole-Genome Expression BeadChips. Os genes candidatos foram validados usando qPCR-based TaqMan Low Density Arrays (TLDAs). Resultados: Foram incluídos 369 doentes (62,3% do sexo masculino, com idade média de 45,4 ± 13,2 anos, duração média da doença de 11,4 ± 10,5 anos). No momento da avaliação, 49,9% tinham doença axial, 2,4% periférica, 40,9% mista e 7,1% entesopática. A uveíte anterior aguda (33,6%) foi a manifestação extra-articular mais comum. Foram positivos para o HLA-B27, 80,3% dos doentes. Os haplótipo A*02/B*27/Cw*02/DRB1*01/DQB1*05 parece conferir suscetibilidade para a EA, e o A*02/B*27/Cw*01/DRB1*08/DQB1*04 parece conferir proteção em termos de atividade, repercussão funcional e radiológica da doença. Três variantes (2 para IL23R e 1 para ERAP1) mostraram significativa associação com a doença, confirmando a associação destes genes com a EA na população Portuguesa. O mesmo não se verificou com as variantes estudadas do ANKH. Não se verificou associação entre as variantes génicas não-MHC e as manifestações clínicas da EA. Foi identificado um perfil de expressão génica para a EA, tendo sido validados catorze genes - alguns têm um papel bem documentado em termos de inflamação, outros no metabolismo da cartilagem e do osso. Conclusões: Foi estabelecido um perfil demográfico e clínico dos doentes com EA em Portugal. A identificação de variantes génicas e de um perfil de expressão contribuem para uma melhor compreensão da sua fisiopatologia e podem ser úteis para estabelecer modelos com relevância em termos de diagnóstico, prognóstico e orientação terapêutica dos doentes. -----------ABSTRACT: Background: Ankylosing Spondylitis (AS) is a chronic inflammatory disorder characterized by inflammation in the spine and sacroiliac joints leading to progressive joint ankylosis and in progressive deterioration of physical function and quality of life. An early diagnosis and early therapy may contribute to a better prognosis. The identification of biomarkers would be helpful and represents a great challenge for the scientific community. Objectives: The present study had the following aims: 1- to characterize the pattern of AS in Portuguese patients; 2- to investigate MHC and non-MHC gene associations with susceptibility and phenotypic features of AS and; 3- to identify candidate genes associated with AS by means of whole-genome microarray. Material and Methods: AS was defined in accordance to the modified New York criteria and AS cases were recruited from hospital outcares patient clinics. Demographic and clinical data were recorded and blood samples collected. A random group of HLA-B27 positive patients and controls were selected and typed for HLA class I and II by PCR-rSSOP. The extended HLA haplotypes were estimated by Expectation Maximization Algorithm using Arlequin v3.11 software. Genotyping of IL23R, ERAP1 and ANKH allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests as implemented in PLINK, for dichotomous and quantitative variables, respectively. Gene expression profile was carried out using Illumina HT-12 Whole-Genome Expression BeadChips and candidate genes were validated using qPCR-based TaqMan Low Density Arrays (TLDAs). Results: A total of 369 patients (62.3% male; mean age 45.4±13.2 years; mean disease duration 11.4±10.5 years), were included. Regarding clinical disease pattern, at the time of assessment, 49.9% had axial disease, 2.4% peripheral disease, 40.9% mixed disease and 7.1% isolated enthesopathic disease. Acute anterior uveitis (33.6%) was the most common extra-articular manifestation. 80.3% of AS patients were HLA-B27 positive. The haplotype A*02/B*27/Cw*02/DRB1*01/DQB1*05 seems to confer susceptibility to AS, whereas A*02/B*27/Cw*01/DRB1*08/DQB1*04 seems to provide protection in terms of disease activity, functional and radiological repercussion. Three markers (two for IL23R and one for ERAP1) showed significant single-locus disease associations. Association of these genes with AS in the Portuguese population was confirmed, whereas ANKH markers studied did not show an association with AS. No association was seen between non-MHC genes and clinical manifestations of AS. A gene expression signature for AS was established; among the fourteen validated genes, a number of them have a well-documented inflammatory role or in modulation of cartilage and bone metabolism. Conclusions: A demographic and clinical profile of patients with AS in Portugal was established. Identification of genetic variants of target genes as well as gene expression signatures could provide a better understanding of AS pathophysiology and could be useful to establish models with relevance in terms of susceptibility, prognosis, and potential therapeutic guidance.

A Souvenir of the Niagara Falls, showing Summer and Winter views of Niagara Falls and their surroundings. --

Cover title: Niagara Falls illustrated, Summer and Winter.

Bacteriophages of Erwinia amylovora and their potential use in biological control

Forty-four bacteriophage isolates of Erwinia amy/ovora, the causal agent of fire blight, were collected from sites in and around the Niagara Region of Southern Ontario in the summer of 1998. Phages were isolated only from sites where fire blight was present. Thirty-seven of these phages were isolated from the soil surrounding infected trees, with the remainder isolated from aerial plant tissue samples. A mixture of six E. amy/ovora bacterial host strains was used to enrich field samples in order to avoid the selection bias of a single-host system. Molecular characterization of the phages with a combination of peR and restriction endonuclease digestions showed that six distinct phage types were isolated. Ten phage isolates related to the previously characterized E. amy/ovora phage PEa1 were isolated, with some divergence of molecular markers between phages isolated from different sites. The host ranges of the phages revealed that certain types were unable to efficiently lyse some E. amy/ovora strains, and that some types were able to lyse the epiphytic bacterium Pantoea agg/omerans. Biological control of E. amy/ovora by the bacteriophages was assessed in a bioassay using discs of immature pear fruit. Twenty-three phage isolates were able to significantly suppress the incidence of bacterial exudate on the pear disc surface. Quantification of the bacterial population remaining on the disc surface indicated that population reductions of up to 97% were obtainable by phage treatment, but that elimination of bacteria from the surface was not possible with this model system.