What can the SEDs of first hydrostatic core candidates reveal about their nature?

The first hydrostatic core (FHSC) is the first stable object to form in simulations of star formation. This stage has yet to be observed definitively, although several candidate FHSCs have been reported. We have produced synthetic spectral energy distributions (SEDs) from 3D hydrodynamical simulations of pre-stellar cores undergoing gravitational collapse for a variety of initial conditions. Variations in the initial rotation rate, radius and mass lead to differences in the location of the SED peak and far-infrared flux. Secondly, we attempt to fit the SEDs of five FHSC candidates from the literature and five newly identified FHSC candidates located in the Serpens South molecular cloud with simulated SEDs. The most promising FHSC candidates are fitted by a limited number of model SEDs with consistent properties, which suggests the SED can be useful for placing constraints on the age and rotation rate of the source. The sources we consider most likely to be in FHSC phase are B1-bN, CB17-MMS, Aqu-MM1 and Serpens South candidate K242. We were unable to fit SerpS-MM22, Per-Bolo 58 and Chamaeleon-MMS1 with reasonable parameters, which indicates that they are likely to be more evolved.Comment: 26 pages, 28 figures. Accepted for publication in MNRA

Evaluating SPIO-labelled cell MR efficiency by three-dimensional quantitativeT2* MRI

An in vitro MR-assay for superparamagnetic iron oxide (SPIO) particle cell labelling assessment via three-dimensional quantitative T [math image] MR microscopy was proposed. On high-resolution images, and due to the high susceptibility difference between the particles and the surrounding medium, SPIO internalized in cells induces signal loss which may be counted and measured on T [math image] maps. The increase in both labelled cell percentage and the average perturbation volume with an added amount of iron in the incubation medium proved that intracellular iron uptake is dependent upon the initial concentration of incubation iron. It also proved that the observed increases in total cellular iron uptake measured by inductively coupled plasma optical emission spectroscopy are due to both an increase in the iron mass per cell and also an increase in labelled cell concentration. MR results were compared with Prussian blue staining histology. The sensitivity of the MR methodology was then used to distinguish labelling differences for two different types of particle coating. The MRI-assay we proposed is a compulsory tool to optimize labelling efficiency in order to improve in vivo cell detection. Key parameters for detection, such as the percentage of cell labelling, the effect on the image for a given amount of internalized iron and labelling distribution among a cell population, are easily obtained. The comparison of different contrast agents for labelling one cell type, the assessment of one type of contrast agent for labelling different cell types and/or the evaluation of labelling strategies, are possible without having recourse to classical methods, and provide improved accuracy, since the principle is based on intracellular relaxivity

A dedicated haem lyase is required for the maturation of a novel bacterial cytochrome c with unconventional covalent haem binding

In bacterial c-type cytochromes, the haem cofactor is covalently attached via two cysteine residues organized in a haem c-binding motif. Here, a novel octa-haem c protein, MccA, is described that contains only seven conventional haem c-binding motifs (CXXCH), in addition to several single cysteine residues and a conserved CH signature. Mass spectrometric analysis of purified MccA from Wolinella succinogenes suggests that two of the single cysteine residues are actually part of an unprecedented CX15CH sequence involved in haem c binding. Spectroscopic characterization of MccA identified an unusual high-potential haem c with a red-shifted absorption maximum, not unlike that of certain eukaryotic cytochromes c that exceptionally bind haem via only one thioether bridge. A haem lyase gene was found to be specifically required for the maturation of MccA in W. succinogenes. Equivalent haem lyase-encoding genes belonging to either the bacterial cytochrome c biogenesis system I or II are present in the vicinity of every known mccA gene suggesting a dedicated cytochrome c maturation pathway. The results necessitate reconsideration of computer-based prediction of putative haem c-binding motifs in bacterial proteomes

Dystrophin Gene Mutation Location and the Risk of Cognitive Impairment in Duchenne Muscular Dystrophy

Contains fulltext : 88828.pdf (publisher's version ) (Open Access)BACKGROUND: A significant component of the variation in cognitive disability that is observed in Duchenne muscular dystrophy (DMD) is known to be under genetic regulation. In this study we report correlations between standardised measures of intelligence and mutational class, mutation size, mutation location and the involvement of dystrophin isoforms. METHODS AND RESULTS: Sixty two male subjects were recruited as part of a study of the cognitive spectrum in boys with DMD conducted at the Sydney Children's Hospital (SCH). All 62 children received neuropsychological testing from a single clinical psychologist and had a defined dystrophin gene (DMD) mutation; including DMD gene deletions, duplications and DNA point mutations. Full Scale Intelligence Quotients (FSIQ) in unrelated subjects with the same mutation were found to be highly correlated (r = 0.83, p = 0.0008), in contrast to results in previous publications. In 58 cases (94%) it was possible to definitively assign a mutation as affecting one or more dystrophin isoforms. A strong association between the risk of cognitive disability and the involvement of groups of DMD isoforms was found. In particular, improvements in the correlation of FSIQ with mutation location were identified when a new classification system for mutations affecting the Dp140 isoform was implemented. SIGNIFICANCE: These data represent one of the largest studies of FSIQ and mutational data in DMD patients and is among the first to report on a DMD cohort which has had both comprehensive mutational analysis and FSIQ testing through a single referral centre. The correlation between FSIQ results with the location of the dystrophin gene mutation suggests that the risk of cognitive deficit is a result of the cumulative loss of central nervous system (CNS) expressed dystrophin isoforms, and that correct classification of isoform involvement results in improved estimates of risk

Mechanisms of innate immune activation by gluten peptide p31-43 in mice

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Innate immunity contributes to the pathogenesis of CD, but the mechanisms remain poorly understood. Although previous in vitro work suggests that gliadin peptide p31-43 acts as an innate immune trigger, the underlying pathways are unclear and have not been explored in vivo. Here we show that intraluminal delivery of p31-43 induces morphological changes in the small intestinal mucosa of normal mice consistent with those seen in CD, including increased cell death and expression of inflammatory mediators. The effects of p31-43 were dependent on MyD88 and type I IFNs, but not Toll-like receptor 4 (TLR4), and were enhanced by coadministration of the TLR3 agonist polyinosinic:polycytidylic acid. Together, these results indicate that gliadin peptide p31-43 activates the innate immune pathways in vivo, such as IFN-dependent inflammation, relevant to CD. Our findings also suggest a common mechanism for the potential interaction between dietary gluten and viral infections in the pathogenesis of CD.Instituto de Estudios Inmunológicos y Fisiopatológico

Mechanisms of innate immune activation by gluten peptide p31-43 in mice

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Innate immunity contributes to the pathogenesis of CD, but the mechanisms remain poorly understood. Although previous in vitro work suggests that gliadin peptide p31-43 acts as an innate immune trigger, the underlying pathways are unclear and have not been explored in vivo. Here we show that intraluminal delivery of p31-43 induces morphological changes in the small intestinal mucosa of normal mice consistent with those seen in CD, including increased cell death and expression of inflammatory mediators. The effects of p31-43 were dependent on MyD88 and type I IFNs, but not Toll-like receptor 4 (TLR4), and were enhanced by coadministration of the TLR3 agonist polyinosinic:polycytidylic acid. Together, these results indicate that gliadin peptide p31-43 activates the innate immune pathways in vivo, such as IFN-dependent inflammation, relevant to CD. Our findings also suggest a common mechanism for the potential interaction between dietary gluten and viral infections in the pathogenesis of CD

Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and vascular development

Molecular oxygen is essential for the development, growth and survival of multicellular organisms. Hypoxic microenvironments and oxygen gradients are generated physiologically during embryogenesis and organogenesis. In the eye, oxygen plays a crucial role in both physiological vascular development and common blinding diseases. The retinal pigment epithelium (RPE) is a monolayer of cells essential for normal ocular development and in the mature retina provides support for overlying photoreceptors and their vascular supply. Hypoxia at the level of the RPE is closely implicated in pathogenesis of age-related macular degeneration. Adaptive tissue responses to hypoxia are orchestrated by sophisticated oxygen sensing mechanisms. In particular, the von Hippel-Lindau tumour suppressor protein (pVhl) controls hypoxia-inducible transcription factor (HIF)-mediated adaptation. However, the role of Vhl/Hif1a in the RPE in the development of the eye and its vasculature is unknown. In this study we explored the function of Vhl and Hif1a in the developing RPE using a tissue-specific conditional-knockout approach. We found that deletion of Vhl in the RPE results in RPE apoptosis, aniridia and microphthalmia. Increased levels of Hif1a, Hif2a, Epo and Vegf are associated with a highly disorganised retinal vasculature, chorioretinal anastomoses and the persistence of embryonic vascular structures into adulthood. Additional inactivation of Hif1a in the RPE rescues the RPE morphology, aniridia, microphthalmia and anterior vasoproliferation, but does not rescue retinal vasoproliferation. These data demonstrate that Vhl-dependent regulation of Hif1a in the RPE is essential for normal RPE and iris development, ocular growth and vascular development in the anterior chamber, whereas Vhl-dependent regulation of other downstream pathways is crucial for normal development and maintenance of the retinal vasculature

Congenital hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Congenital hepatic fibrosis is an uncommon cause of portal hypertension. Despite the presence of portal hypertension, hepatocellular and renal function are usually well preserved. Congenital hepatic fibrosis is included in the group of congenital diseases of fibropolycystic disorders. These include a broad spectrum of clinical diseases which are usually accompanied by hepatic involvement.</p> <p>Case presentation</p> <p>We report the case of a 27-year-old Iranian woman with congenital hepatic fibrosis leading to cirrhosis and subsequently hepatocellular carcinoma.</p> <p>Conclusion</p> <p>Advanced cirrhosis was diagnosed and our patient was scheduled for liver transplantation. During preparation for transplant, a hepatic mass was discovered which was found to be hepatocellular carcinoma. Radiofrequency ablation was performed and our patient was referred for transplantation.</p

An evaluation of metal removal during wastewater treatment: The potential to achieve more stringent final effluent standards

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2011 Taylor & Francis.Metals are of particular importance in relation to water quality, and concern regarding the impact of these contaminants on biodiversity is being encapsulated within the latest water-related legislation such as the Water Framework Directive in Europe and criteria revisions to the Clean Water Act in the United States. This review undertakes an evaluation of the potential of 2-stage wastewater treatment consisting of primary sedimentation and biological treatment in the form of activated sludge processes, to meet more stringent discharge consents that are likely to be introduced as a consequence. The legislation, sources of metals, and mechanisms responsible for their removal are discussed, to elucidate possible pathways by which the performance of conventional processes may be optimized or enhanced. Improvements in effluent quality, achievable by reducing concentrations of suspended solids or biochemical oxygen demand, may also reduce metal concentrations although meeting possible requirements for the removal of copper my be challenging

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research