Cellular and ultrastructural location of angiotensinogen in rat and sheep kidney

Cellular and ultrastructural location of angiotensinogen in rat and sheep kidney. Recent evidence suggests the involvement of a local renin-angiotensin system in some renal actions of angiotensin II (Ang II). In this study the renal distribution of the precursor to angiotensin formation, angiotensinogen, was investigated in rats and sheep using immunohistochemistry, immunoelectron microscopy and non-isotopic hybridization histochemistry. Immunostaining for angiotensinogen was seen in proximal tubules (PCT) of both rat and sheep kidneys. In the rat the strongest immunostaining was found in the kidneys of neonatal (1 day old) rats. Staining declined after birth. Non-isotopic hybridization histochemistry using oligodeoxynucleotide probes labeled with biotin confirmed the presence of angiotensinogen mRNA expression in PCT of the rat renal cortex. Electron microscopic immunohistochemistry using antibodies raised against rat angiotensinogen showed weak staining in the adult of granule-like structures close to the apical membrane of PCT cells. In the neonatal rat kidney, angiotensinogen immunostaining was found throughout the PCT cells and was markedly stronger than that seen in adult rat kidney. In sheep, angiotensinogen immunostaining with an antibody raised against purified ovine angiotensinogen showed staining of PCT in fetal, newborn and adult sheep kidney. The strongest immunostaining seen was in fetal sheep kidney with a decline seen after birth. Reverse transcription polymerase chain reaction (RT-PCR) showed that angiotensinogen mRNA was expressed in the sheep kidney at all ages studied. Angiotensinogen expression was higher in fetal sheep kidneys (77 day and 141 day gestation) than in adult sheep kidney. In conclusion, angiotensinogen mRNA expression was detected in both rat and sheep kidneys. Immunostaining showed angiotensinogen protein in PCT cells of the renal cortex. Angiotensinogen staining and mRNA expression is highest during development and declines in the adult

Cardiovascular magnetic resonance-guided right heart catheterization in a conventional CMR environment - predictors of procedure success and duration in pulmonary artery hypertension

Background Cardiovascular magnetic resonance imaging (CMR) is valuable for the investigation and management of pulmonary artery hypertension (PAH), but the direct measurement of pulmonary hemodynamics by right heart catheterization is still necessary. CMR-guided right heart catheterization (CMR-RHC) combines the benefits of CMR and invasive cardiac catheterization, but its feasibility in patients with acquired PAH has not been established. The aims of this study are to: (1) demonstrate the feasibility of CMR-RHC in patients being assessed for PAH in a conventional diagnostic CMR scanner room; (2) determine the predictors of (i) procedure duration, and (ii) procedural failure or technical difficulty as determined by the adjunctive need for a guidewire. Methods Fifty patients investigated for suspected or known PH underwent CMR-RHC. Durations of separate procedural components were recorded, including time taken to pass the catheter from the femoral vein to a stable wedge position (procedure time) and total time the patient spent in the CMR department (department time). Associations between procedural failure/guidewire usage and hemodynamic/CMR measures were assessed using logistic regression. Relationships between procedure times and hemodynamic/CMR measures were evaluated using Spearman’s correlation coefficient. Results A full CMR-RHC study was successfully completed in 47 (94%) patients. CMR-conditional guidewires were used in 6 (12%) patients. Metrics associated with guidewire use/procedural failure were higher mean pulmonary artery (PA) pressures (mPAP: OR = 1.125, p = 0.018), right heart dilatation (right ventricular (RV) end-systolic volume (RVESV): OR = 1.028, p = 0.018), RV hypertrophy (OR = 1.050, p = 0.0067) and RV ejection fraction (EF) (OR = 0.914, p = 0.014). Median catheter and department times were 3.6 (2.0–7.7) minutes and 60.0 (54.0–68.5) minutes, respectively. All procedure times became significantly shorter with increasing procedural experience (p < 0.05). Catheterization time was also associated with PH severity (RV systolic pressure: rho = 0.46, p = 0.0013) and increasing RV end-systolic volume (RVESV: rho = 0.41, p = 0.0043), hypertrophy (rho = 0.43, p = 0.0025) and dysfunction (RVEF: rho = − 0.32, p = 0.031). Conclusions This study demonstrates that CMR-RHC using standard technology can be incorporated into routine clinical practice for the investigation of PAH. Procedural failure was rare but more likely in patients with severe PAH. Procedure time is clinically acceptable and increases with worsening PAH severity

Marine environmental DNA biomonitoring reveals seasonal patterns in biodiversity and identifies ecosystem responses to anomalous climatic events

Marine ecosystems are changing rapidly as the oceans warm and become more acidic. The physical factors and the changes to ocean chemistry that they drive can all be measured with great precision. Changes in the biological composition of communities in different ocean regions are far more challenging to measure because most biological monitoring methods focus on a limited taxonomic or size range. Environmental DNA (eDNA) analysis has the potential to solve this problem in biological oceanography, as it is capable of identifying a huge phylogenetic range of organisms to species level. Here we develop and apply a novel multi-gene molecular toolkit to eDNA isolated from bulk plankton samples collected over a five-year period from a single site. This temporal scale and level of detail is unprecedented in eDNA studies. We identified consistent seasonal assemblages of zooplankton species, which demonstrates the ability of our toolkit to audit community composition. We were also able to detect clear departures from the regular seasonal patterns that occurred during an extreme marine heatwave. The integration of eDNA analyses with existing biotic and abiotic surveys delivers a powerful new long-term approach to monitoring the health of our world's oceans in the context of a rapidly changing climate

Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

On the statistical mechanics of prion diseases

We simulate a two-dimensional, lattice based, protein-level statistical mechanical model for prion diseases (e.g., Mad Cow disease) with concommitant prion protein misfolding and aggregation. Our simulations lead us to the hypothesis that the observed broad incubation time distribution in epidemiological data reflect fluctuation dominated growth seeded by a few nanometer scale aggregates, while much narrower incubation time distributions for innoculated lab animals arise from statistical self averaging. We model `species barriers' to prion infection and assess a related treatment protocol.Comment: 5 Pages, 3 eps figures (submitted to Physical Review Letters

Two-dimensional knowledge-based volumetric reconstruction of the right ventricle documents short-term improvement in pulmonary hypertension

BACKGROUND: Data are scarce about short-term right ventricular changes in pulmonary hypertension. Two-dimensional knowledge-based reconstruction of the right ventricle with 2D echocardiography (2DKBR) has been shown to be a valid alternative to Cardiac MRI. PATIENTS AND METHODS: In this longitudinal study 25 pulmonary hypertension patients underwent 2DKBR of the right ventricle, assessment of NT-proBNP levels and functional class at baseline and after a mean follow-up of 6.1 months. Patients were followed up clinically for a further mean of 8.2 months. The majority of patients had connective tissue disease (CTD) associated pulmonary arterial hypertension (n=15) or chronic thromboembolic pulmonary hypertension (CTEPH; n=6). A total of 15 patients underwent an intervention, either new targeted therapy, escalation of targeted therapy or pulmonary endarterectomy. A total of 10 clinically stable patients were routinely followed up without any change in therapy. RESULTS: There were significant improvements in the right ventricular end-diastolic volume index (111±29 mL/m² vs 100±36 mL/m²; P=.038), end-systolic volume index (72±23 mL/m² vs 61±25 mL/m²; P=.001), and ejection fraction (35±10% vs 40±9%; P=.030). Changes in NT-proBNP levels correlated strongest with changes in end-systolic volume index (r=-.77; P=<.0001). Four patients experienced clinical worsening during extended follow-up, dilatation of the right ventricle was associated with clinical worsening. CONCLUSION: In a CTD and CTEPH dominated patient population significant reverse remodeling and improvement of ejection fraction occurred despite a short follow-up and was paralleled by significant changes in NT-proBNP levels. Further right ventricular dilatation was associated with worse clinical outcome. 2DKBR is a feasible substitute for Cardiac MRI to follow-up right ventricular indices in pulmonary hypertension

Management Approach : The Virtuous Corporation as a Moral Agent for Sustainable Development

This chapter examines the corporation as a moral agent for sustainable development. While sustainable development in business organizations can be argued from utility-and duty-based ethical theories, it is suggested that virtue-based ethics is needed to develop a moral agency for sustainable development, as it focuses on the organizational character. In addition, it is proposed that the biosphere (the global sum of all ecosystems) is accepted as the ultimate principal for all planetary agents to avoid an anthropocentric and only inward-looking position typical for ethical theories. Thus, a business organization can work as a nexus for virtue and develop a moral agency that contributes to the well-being of the biosphere and all of its members.Peer reviewe

A qualitative study of primary health care access, barriers and satisfaction among people with mental illness

Research has found that a substantial proportion of individuals with mental illness have high morbidity and mortality rates, and high under-diagnosis of major physical illnesses. Furthermore, people with a mental illness tend not to seek out or utilise health care services. The reasons for the negative attitudes and behaviour towards health care services among this population have not been investigated. This paper presents findings from a study that investigated the health care service needs of people with mental illness (n = 20), and views from health care providers (n = 16) regarding access to these services by people with a mental illness. Results indicated that psychiatric patients identified a range of barriers to their health care usage and low levels of health care satisfaction. These views were shared with health care professionals. Reasons for these findings and strategies to address these problems so that there is better access to health care services for people with mental illness are discussed. <br /

Studying Sun-Planet Connections Using the Heliophysics Integrated Observatory (HELIO)

The Heliophysics Integrated Observatory (HELIO) is a software infrastructure involving a collection of web services, heliospheric data sources (e.g., solar, planetary, etc.), and event catalogues – all of which are accessible through a unified front end. In this paper we use the HELIO infrastructure to perform three case studies based on solar events that propagate through the heliosphere. These include a coronal mass ejection that intersects both Earth and Mars, a solar energetic particle event that crosses the orbit of Earth, and a high-speed solar wind stream, produced by a coronal hole, that is observed in situ at Earth (L1). A ballistic propagation model is run as one of the HELIO services and used to model these events, predicting if they will interact with a spacecraft or planet and determining the associated time of arrival. The HELIO infrastructure streamlines the method used to perform these kinds of case study by centralising the process of searching for and visualising data, indicating interesting features on the solar disk, and finally connecting remotely observed solar features with those detected by in situ solar wind and energetic particle instruments. HELIO represents an important leap forward in European heliophysics infrastructure by bridging the boundaries of traditional scientific domains

Methods and strategies for gene structure curation in WormBase

The Caenorhabditis elegans genome sequence was published over a decade ago; this was the first published genome of a multi-cellular organism and now the WormBase project has had a decade of experience in curating this genome's sequence and gene structures. In one of its roles as a central repository for nematode biology, WormBase continues to refine the gene structure annotations using sequence similarity and other computational methods, as well as information from the literature- and community-submitted annotations. We describe the various methods of gene structure curation that have been tried by WormBase and the problems associated with each of them. We also describe the current strategy for gene structure curation, and introduce the WormBase ‘curation tool’, which integrates different data sources in order to identify new and correct gene structures