A kinematic study of planetary nebulae in the dwarf irregular galaxy IC10

We present positions, kinematics, and the planetary nebula luminosity function (PNLF) for 35 planetary nebulae (PNe) in the nearest starburst galaxy IC10 extending out to 3kpc from the galaxy's centre. We take advantage of the deep imaging and spectroscopic capabilities provided by the spectrograph FOCAS on the 8.2m Subaru telescope. The PN velocities were measured through the slitless-spectroscopy technique, which allows us to explore the kinematics of IC10 with high precision. Using these velocities, we conclude that there is a kinematic connection between the HI envelope located around IC10 and the galaxy's PN population. By assuming that the PNe in the central regions and in the outskirts have similar ages, our results put strong observational constraints on the past tidal interactions in the Local Group. This is so because by dating the PN central stars, we, therefore, infer the epoch of a major episode of star formation likely linked to the first encounter of the HI extended envelope with the galaxy. Our deep [OIII] images also allow us to use the PNLF to estimate a distance modulus of 24.1+/-0.25, which is in agreement with recent results in the literature based on other techniques.Comment: 10 pages, 9 figures, 2 tables. Accepted for publication in MNRA

The fundamental group and Betti numbers of toric origami manifolds

Toric origami manifolds are characterized by origami templates, which are combinatorial models built by gluing polytopes together along facets. In this paper, we examine the topology of orientable toric oigami manifolds with coorientable folding hypersurface. We determine the fundamental group. In our previous paper [HP], we studied the ordinary and equivariant cohomology rings of simply connected toric origami manifolds. We conclude this paper by computing some Betti numbers in the non-simply connected case.Comment: 21 pages, 4 figures, 1 table. Background in Section 1 draws heavily from the background section of our previous paper arXiv:1211.643

IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species

Improvements on colony morphology identification towards bacterial profiling

Colony morphology may be an indicator of phenotypic variation, this being an important adaptive process adopted by bacteria to overcome environmental stressors. Furthermore, alterations in colony traits may reflect increased virulence and antimicrobial resistance. Despite the potential relevance of using colony morphological traits, the influence of experimental conditions on colony morphogenesis has been scarcely studied in detail. This study aims to clear and systematically at demonstrating the impact of some variables, such as colony growth time, plate colony density, culture medium, planktonic or biofilm mode of growth and strains genetic background, on bacterial colony morphology features using two P. aeruginosa strains. Results, based on 5-replicate experiments, demonstrated that all variables influenced colony morphogenesis and 18 different morphotypes were identified, showing different sizes, forms, colours, textures and margins. Colony growth time and composition of the medium were the variables that caused the highest impact on colony differentiation both derived from planktonic and biofilm cultures. Colony morphology characterization before 45 h of incubation was considered inadequate and TSA, a non-selective medium, provided more colony diversity in contrast to P. aeruginosa selective media. In conclusion, data obtained emphasized the need to perform comparisons between colony morphologies in equivalent experimental conditions to avoid misinterpretation of microbial diagnostics and biomedical studies. Since colony morphotyping showed to be a reliable method to evaluate phenotypic switching and also to infer about bacterial diversity in biofilms, these unambiguous comparisons between morphotypes may offer a quite valuable input to clinical diagnosis, aiding the decision-making towards the selection of the most suitable antibiotic and supportive treatments

Replication of Associations of Genetic Loci Outside the HLA Region With Susceptibility to Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis

OBJECTIVE: Genetic polymorphisms within the HLA region explain only a modest proportion of anti-cyclic citrullinated peptide (anti-CCP)-negative rheumatoid arthritis (RA) heritability. However, few non-HLA markers have been identified so far. This study was undertaken to replicate the associations of anti-CCP-negative RA with non-HLA genetic polymorphisms demonstrated in a previous study. METHODS: The Rheumatoid Arthritis Consortium International densely genotyped 186 autoimmune-related regions in 3,339 anti-CCP-negative RA patients and 15,870 controls across 6 different populations using the Illumina ImmunoChip array. We performed a case-control replication study of the anti-CCP-negative markers with the strongest associations in that discovery study, in an independent cohort of anti-CCP-negative UK RA patients. Individuals from the arcOGEN Consortium and Wellcome Trust Case Control Consortium were used as controls. Genotyping in cases was performed using Sequenom MassArray technology. Genome-wide data from controls were imputed using the 1000 Genomes Phase I integrated variant call set release version 3 as a reference panel. RESULTS: After genotyping and imputation quality control procedures, data were available for 15 non-HLA single-nucleotide polymorphisms in 1,024 cases and 6,348 controls. We confirmed the known markers ANKRD55 (meta-analysis odds ratio [OR] 0.80; P = 2.8 × 10(-13) ) and BLK (OR 1.13; P = 7.0 × 10(-6) ) and identified new and specific markers of anti-CCP-negative RA (prolactin [PRL] [OR 1.13; P = 2.1 × 10(-6) ] and NFIA [OR 0.85; P = 2.5 × 10(-6) ]). Neither of these loci is associated with other common, complex autoimmune diseases. CONCLUSION: Anti-CCP-negative RA and anti-CCP-positive RA are genetically different disease subsets that only partially share susceptibility factors. Genetic polymorphisms located near the PRL and NFIA genes represent examples of genetic susceptibility factors specific for anti-CCP-negative RA

Exogenous Liposomal ceramide-c6 ammeliorates lipidomic profile, energy homeostasis and anti-oxidant systems in NASH

In non-alcoholic steatohepatitis (NASH), many lines of investigation have reported a dysregulation in lipid homeostasis, leading to intrahepatic lipid accumulation. Recently, the role of dysfunctional sphingolipid metabolism has also been proposed. Human and animal models of NASH have been associated with elevated levels of long chain ceramides and pro-apoptotic sphingolipid metabolites, implicated in regulating fatty acid oxidation and inflammation. Importantly, inhibition of de novo ceramide biosynthesis or knock-down of ceramide synthases reverse some of the pathology of NASH. In contrast, cell permeable, short chain ceramides have shown anti-inflammatory actions in multiple models of inflammatory disease. Here, we investigated non-apoptotic doses of a liposome containing short chain C6-Ceramide (Lip-C6) administered to human hepatic stellate cells (hHSC), a key effector of hepatic fibrogenesis, and an animal model characterized by inflammation and elevated liver fat content. On the basis of the results from unbiased liver transcriptomic studies from non-alcoholic fatty liver disease patients, we chose to focus on adenosine monophosphate activated kinase (AMPK) and nuclear factor-erythroid 2-related factor (Nrf2) signaling pathways, which showed an abnormal profile. Lip-C6 administration inhibited hHSC proliferation while improving anti-oxidant protection and energy homeostasis, as indicated by upregulation of Nrf2, activation of AMPK and an increase in ATP. To confirm these in vitro data, we investigated the effect of a single tail-vein injection of Lip-C6 in the methionine-choline deficient (MCD) diet mouse model. Lip-C6, but not control liposomes, upregulated phospho-AMPK, without inducing liver toxicity, apoptosis, or exacerbating inflammatory signaling pathways. Alluding to mechanism, mass spectrometry lipidomics showed that Lip-C6-treatment reversed the imbalance in hepatic phosphatidylcholines and diacylglycerides species induced by the MCD-fed diet. These results reveal that short-term Lip-C6 administration reverses energy/metabolic depletion and increases protective anti-oxidant signaling pathways, possibly by restoring homeostatic lipid function in a model of liver inflammation with fat accumulation

Pilot-WINGS: An extended MUSE view of the structure of Abell 370

We investigate the strong-lensing cluster Abell 370 (A370) using a wide Integral Field Unit (IFU) spectroscopic mosaic from the Multi-Unit Spectroscopic Explorer (MUSE). IFU spectroscopy provides significant insight into the structure and mass content of galaxy clusters, yet IFU-based cluster studies focus almost exclusively on the central Einstein-radius region. Covering over 14 arcmin2, the new MUSE mosaic extends significantly beyond the A370 Einstein radius, providing, for the first time, a detailed look at the cluster outskirts. Combining these data with wide-field, multi-band Hubble Space Telescope (HST) imaging from the BUFFALO project, we analyse the distribution of objects within the cluster and along the line of sight. Identifying 416 cluster galaxies, we use kinematics to trace the radial mass profile of the halo, providing a mass estimate independent from the lens model. We also measure radially averaged properties of the cluster members, tracking their evolution as a function of infall. Thanks to the high spatial resolution of our data, we identify six cluster members acting as galaxy–galaxy lenses, which constrain localized mass distributions beyond the Einstein radius. Finally, taking advantage of MUSE’s 3D capabilities, we detect and analyse multiple spatially extended overdensities outside of the cluster that influence lensing-derived halo mass estimates. We stress that much of this work is only possible thanks to the robust, extended IFU coverage, highlighting its importance even in less optically dense cluster regions. Overall, this work showcases the power of combining HST + MUSE, and serves as the initial step towards a larger and wider program targeting several clusters

MorphoCol: an ontology-based knowledgebase for the characterisation of clinically significant bacterial colony morphologies

Background One of the major concerns of the biomedical community is the increasing prevalence of antimicrobial resistant microorganisms. Recent findings show that the diversification of colony morphology may be indicative of the expression of virulence factors and increased resistance to antibiotic therapeutics. To transform these findings, and upcoming results, into a valuable clinical decision making tool, colony morphology characterisation should be standardised. Notably, it is important to establish the minimum experimental information necessary to contextualise the environment that originated the colony morphology, and describe the main morphological features associated unambiguously. Results This paper presents MorphoCol, a new ontology-based tool for the standardised, consistent and machine-interpretable description of the morphology of colonies formed by human pathogenic bacteria. The Colony Morphology Ontology (CMO) is the first controlled vocabulary addressing the specificities of the morphology of clinically significant bacteria, whereas the MorphoCol publicly Web-accessible knowledgebase is an end-user means to search and compare CMO annotated colony morphotypes. Its ultimate aim is to help correlate the morphological alterations manifested by colony-forming bacteria during infection with their response to the antimicrobial treatments administered. Conclusions MorphoCol is the first tool to address bacterial colony morphotyping systematically and deliver a free of charge resource to the community. Hopefully, it may introduce interesting features of analysis on pathogenic behaviour and play a significant role in clinical decision making.The authors thank the project PTDC/SAU-ESA/646091/2006/FCOMP-01-0124-FEDER-007480FCT, the Strategic Project PEst-OE/EQB/LA0023/2013, the Project "BioHealth - Biotechnology and Bioengineering approaches to improve health quality", Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER, the project "RECI/BBB-EBI/0179/2012 - Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB", Ref. FCOMP-01-0124-FEDER-027462, FEDER, and the Agrupamento INBIOMED from DXPCTSUG-FEDER unha maneira de facer Europa (2012/273). The research leading to these results has received funding from the European Union's Seventh Framework Programme FP7/REGPOT-2012-2013.1 under grant agreement no 316265, BIOCAPS. This document reflects only the author's views and the European Union is not liable for any use that may be made of the information contained herein. The authors also acknowledge PhD Grant of Ana Margarida Sousa SFRH/BD/72551/2010

The role of salt abuse on risk for hypercalciuria

<p>Abstract</p> <p>Background</p> <p>Elevated sodium excretion in urine resulting from excessive sodium intake can lead to hypercalciuria and contribute to the formation of urinary stones. The aim of this study was to evaluate salt intake in patients with urinary lithiasis and idiopathic hypercalciuria (IH).</p> <p>Methods</p> <p>Between August 2007 and June 2008, 105 lithiasic patients were distributed into 2 groups: Group 1 (n = 55): patients with IH (urinary calcium excretion > 250 mg in women and 300 mg in men with normal serum calcium); Group 2 (n = 50): normocalciuric patients (NC). Inclusion criteria were: age over 18 years, normal renal function (creatinine clearance ≥ 60 ml/min), absent proteinuria and negative urinary culture. Pregnant women, patients with intestinal pathologies, chronic diarrhea or using corticoids were excluded. The protocol of metabolic investigation was based on non-consecutive collection of two 24-hour samples for dosages of: calcium, sodium, uric acid, citrate, oxalate, magnesium and urinary volume. Food intake was evaluated by the three-day dietary record quantitative method, and the Body Mass Index (BMI) was calculated and classified according to the World Health Organization (WHO). Sodium intake was evaluated based on 24-hour urinary sodium excretion.</p> <p>Results</p> <p>The distribution in both groups as regards mean age (42.11 ± 10.61 vs. 46.14 ± 11.52), weight (77.14 ± 16.03 vs. 75.99 ± 15.80), height (1.64 ± 0.10 vs. 1.64 <b>± plusorminus </b>0.08) and BMI (28.78 ± 5.81 vs. 28.07 ± 5.27) was homogeneous. Urinary excretion of calcium (433.33 ± 141.92 vs. 188.93 ± 53.09), sodium (280.08 ± 100.94 vs. 200.44.93 ± 65.81), uric acid (880.63 ± 281.50 vs. 646.74 ± 182.76) and magnesium (88.78 ± 37.53 vs. 64.34 ± 31.84) was significantly higher in the IH group (p < 0.05). There was no statistical difference in calcium intake between the groups, and there was significantly higher salt intake in patients with IH than in NC.</p> <p>Conclusions</p> <p>This study showed that salt intake was higher in patients with IH as compared to NC.</p

Autophagy fights disease through cellular self-digestion

Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing. Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62766/1/nature06639.pd