Formation of rings in galactic discs by infalling small companions

We use N-body simulations to study the formation of rings in a disc galaxy by the impact of a small spherical companion. Both barred and nonbarred target discs are considered. We discuss the effect of the properties of the target disc (distribution of mass in the disc, velocity dispersion, etc.) as well as of the mass and orbit of the companion on the properties of the rings, such as their amplitude, width, shape, expansion velocity and lifetime. In particular the amplitude, width, lifetime and expansion velocity of the first ring increase considerably with companion mass, and so does the expansion velocity of the particles in it and the total extent of the disc after the interaction. We also discuss the formation and evolution of spokes and show that they can be caused by companions of relatively small mass. In our three examples of oblique impacts on barred target galaxies we note important transient displacements of the bar, as well as changes of its pattern speed and size. An asymmetric pseudoring is formed in each case, and during the first stages of its evolution the bar forms part of it.Comment: 21 pages Latex, 22 figures, of which 7 as separate gif-files. Requires mn.sty, accepted for publication in MNRAS. High resolution version at http://www-obs.cnrs-mrs.fr/dynamique/pap/ring.htm

Going higher in the First-order Quantifier Alternation Hierarchy on Words

We investigate the quantifier alternation hierarchy in first-order logic on finite words. Levels in this hierarchy are defined by counting the number of quantifier alternations in formulas. We prove that one can decide membership of a regular language to the levels $\mathcal{B}\Sigma_2$ (boolean combination of formulas having only 1 alternation) and $\Sigma_3$ (formulas having only 2 alternations beginning with an existential block). Our proof works by considering a deeper problem, called separation, which, once solved for lower levels, allows us to solve membership for higher levels

Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease

Hydrolytic and enzymatic degradation of a poly(å-caprolactone) network

“NOTICE: this is the author’s version of a work that was accepted for publication in Polymer Degradation and Stability. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Polymer Degradation and Stability, [Volume 97, Issue 8, August 2012, Pages 1241–1248] DOI 10.1016/j.polymdegradstab.2012.05.038Long-term hydrolytic and enzymatic degradation profiles of poly(å-caprolactone) (PCL) networks were obtained. The hydrolytic degradation studies were performed in water and phosphate buffer solution (PBS) for 65 weeks. In this case, the degradation rate of PCL networks was faster than previous results in the literature on linear PCL, reaching a weight loss of around 20% in 60 weeks after immersing the samples either in water or in PBS conditions. The enzymatic degradation rate in Pseudomonas Lipase for 14 weeks was also studied, with the conclusion that the degradation profile of PCL networks is lower than for linear PCL, also reaching a 20% weight loss. The weight lost, degree of swelling, and calorimetric and mechanical properties were obtained as a function of degradation time. Furthermore, the morphological changes in the samples were studied carefully through electron microscopy and crystal size through X-ray diffraction. The changes in some properties over the degradation period such as crystallinity, crystal size and Young¿s modulus were smaller in the case of enzymatic studies, highlighting differences in the degradation mechanism in the two studies, hydrolytic and enzymatic.The authors would like to acknowledge the support of the Spanish Ministry of Science and Education through the DPI2010-20399-004-03 project. JM Meseguer-Duenas and A Vidaurre also would like to acknowledge the support of the CIBER-BBN, an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The translation of this paper was funded by the Universidad Politecnica de Valencia, SpainCastilla Cortázar, MIC.; Más Estellés, J.; Meseguer Dueñas, JM.; Escobar Ivirico, JL.; Marí Soucase, B.; Vidaurre, A. (2012). Hydrolytic and enzymatic degradation of a poly(å-caprolactone) network. Polymer Degradation and Stability. 97(8):1241-1248. https://doi.org/10.1016/j.polymdegradstab.2012.05.038S1241124897

Mitochondrial genome sequence analysis: A custom bioinformatics pipeline substantially improves Affymetrix MitoChip v2.0 call rate and accuracy

BACKGROUND: Mitochondrial genome sequence analysis is critical to the diagnostic evaluation of mitochondrial disease. Existing methodologies differ widely in throughput, complexity, cost efficiency, and sensitivity of heteroplasmy detection. Affymetrix MitoChip v2.0, which uses a sequencing-by-genotyping technology, allows potentially accurate and high-throughput sequencing of the entire human mitochondrial genome to be completed in a cost-effective fashion. However, the relatively low call rate achieved using existing software tools has limited the wide adoption of this platform for either clinical or research applications. Here, we report the design and development of a custom bioinformatics software pipeline that achieves a much improved call rate and accuracy for the Affymetrix MitoChip v2.0 platform. We used this custom pipeline to analyze MitoChip v2.0 data from 24 DNA samples representing a broad range of tissue types (18 whole blood, 3 skeletal muscle, 3 cell lines), mutations (a 5.8 kilobase pair deletion and 6 known heteroplasmic mutations), and haplogroup origins. All results were compared to those obtained by at least one other mitochondrial DNA sequence analysis method, including Sanger sequencing, denaturing HPLC-based heteroduplex analysis, and/or the Illumina Genome Analyzer II next generation sequencing platform. RESULTS: An average call rate of 99.75% was achieved across all samples with our custom pipeline. Comparison of calls for 15 samples characterized previously by Sanger sequencing revealed a total of 29 discordant calls, which translates to an estimated 0.012% for the base call error rate. We successfully identified 4 known heteroplasmic mutations and 24 other potential heteroplasmic mutations across 20 samples that passed quality control. CONCLUSIONS: Affymetrix MitoChip v2.0 analysis using our optimized MitoChip Filtering Protocol (MFP) bioinformatics pipeline now offers the high sensitivity and accuracy needed for reliable, high-throughput and cost-efficient whole mitochondrial genome sequencing. This approach provides a viable alternative of potential utility for both clinical diagnostic and research applications to traditional Sanger and other emerging sequencing technologies for whole mitochondrial genome analysis

A neuroepithelial wave of BMP signalling drives anteroposterior specification of the tuberal hypothalamus

The tuberal hypothalamus controls life-supporting homeostatic processes, but despite its fundamental role, the cells and signalling pathways that specify this unique region of the central nervous system in embryogenesis are poorly characterised. Here, we combine experimental and bioinformatic approaches in the embryonic chick to show that the tuberal hypothalamus is progressively generated from hypothalamic floor plate-like cells. Fate-mapping studies show that a stream of tuberal progenitors develops in the anterior-ventral neural tube as a wave of neuroepithelial-derived BMP signalling sweeps from anterior to posterior through the hypothalamic floor plate. As later-specified posterior tuberal progenitors are generated, early specified anterior tuberal progenitors become progressively more distant from these BMP signals and differentiate into tuberal neurogenic cells. Gain- and loss-of-function experiments in vivo and ex vivo show that BMP signalling initiates tuberal progenitor specification, but must be eliminated for these to progress to anterior neurogenic progenitors. scRNA-Seq profiling shows that tuberal progenitors that are specified after the major period of anterior tuberal specification begin to upregulate genes that characterise radial glial cells. This study provides an integrated account of the development of the tuberal hypothalamus

Single-cell analysis of early chick hypothalamic development reveals that hypothalamic cells are induced from prethalamic-like progenitors

The hypothalamus regulates many innate behaviors, but its development remains poorly understood. Here, we used single-cell RNA sequencing (RNA-seq) and hybridization chain reaction (HCR) to profile multiple stages of early hypothalamic development in the chick. Hypothalamic neuroepithelial cells are initially induced from prethalamic-like cells. Two distinct hypothalamic progenitor populations then emerge and give rise to tuberal and mammillary/paraventricular hypothalamic cells. At later stages, the regional organization of the chick and mouse hypothalamus is highly similar. We identify selective markers for major subdivisions of the developing chick hypothalamus and many previously uncharacterized candidate regulators of hypothalamic induction, regionalization, and neurogenesis. As proof of concept for the power of the dataset, we demonstrate that prethalamus-derived follistatin inhibits hypothalamic induction. This study clarifies the organization of the nascent hypothalamus and identifies molecular mechanisms that may control its induction and subsequent development

Socio-Emotional Competencies and School Performance in Adolescence: What Role for School Adjustment?

There is growing evidence in the literature of positive relationships between socio-emotional competencies and school performance. Several hypotheses have been used to explain how these variables may be related to school performance. In this paper, we explored the role of various school adjustment variables in the relationship between interpersonal socio-emotional competencies and school grades, using a weighted network approach. This network approach allowed us to analyze the structure of interrelations between each variable, pointing to both central and mediatory school and socio-emotional variables within the network. Self-reported data from around 3,400 French vocational high school students were examined. This data included a set of interpersonal socio-emotional competencies (cognitive and affective empathy, socio-emotional behaviors and collective orientation), school adjustment measures (adaptation to the institution, school anxiety, self-regulation at school, and self-perceived competence at school) as well as grades in mathematics and French language. The results showed that self-regulation at school weighted the most strongly on the whole network, and was the most important mediatory pathway. More specifically, self-regulation mediated the relationships between interpersonal socio-emotional competencies and school grades

Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD

Pathogenic variants in INPP5E cause Joubert syndrome (JBTS), a ciliopathy with retinal involvement. However, despite sporadic cases in large cohort sequencing studies, a clear association with non-syndromic inherited retinal degenerations (IRDs) has not been made. We validate this association by reporting 16 non-syndromic IRD patients from ten families with bi-allelic mutations in INPP5E. Additional two patients showed early onset IRD with limited JBTS features. Detailed phenotypic description for all probands is presented. We report 14 rare INPP5E variants, 12 of which have not been reported in previous studies. We present tertiary protein modeling and analyze all INPP5E variants for deleteriousness and phenotypic correlation. We observe that the combined impact of INPP5E variants in JBTS and non-syndromic IRD patients does not reveal a clear genotype–phenotype correlation, suggesting the involvement of genetic modifiers. Our study cements the wide phenotypic spectrum of INPP5E disease, adding proof that sequence defects in this gene can lead to early-onset non-syndromic IRD