DNA 5-hydroxymethylcytosine in pediatric central nervous system tumors may impact tumor classification and is a positive prognostic marker

Background: Nucleotide-specific 5-hydroxymethylcytosine (5hmC) remains understudied in pediatric central nervous system (CNS) tumors. 5hmC is abundant in the brain, and alterations to 5hmC in adult CNS tumors have been reported. However, traditional approaches to measure DNA methylation do not distinguish between 5-methylcytosine (5mC) and its oxidized counterpart 5hmC, including those used to build CNS tumor DNA methylation classification systems. We measured 5hmC and 5mC epigenome-wide at nucleotide resolution in glioma, ependymoma, and embryonal tumors from children, as well as control pediatric brain tissues using tandem bisulfite and oxidative bisulfite treatments followed by hybridization to the Illumina Methylation EPIC Array that interrogates over 860,000 CpG loci. Results: Linear mixed effects models adjusted for age and sex tested the CpG-specific differences in 5hmC between tumor and non-tumor samples, as well as between tumor subtypes. Results from model-based clustering of tumors was used to test the relation of cluster membership with patient survival through multivariable Cox proportional hazards regression. We also assessed the robustness of multiple epigenetic CNS tumor classification methods to 5mC-specific data in both pediatric and adult CNS tumors. Compared to non-tumor samples, tumors were hypohydroxymethylated across the epigenome and tumor 5hmC localized to regulatory elements crucial to cell identity, including transcription factor binding sites and super-enhancers. Differentially hydroxymethylated loci among tumor subtypes tended to be hypermethylated and disproportionally found in CTCF binding sites and genes related to posttranscriptional RNA regulation, such as DICER1. Model-based clustering results indicated that patients with low 5hmC patterns have poorer overall survival and increased risk of recurrence. Our results suggest 5mC-specific data from OxBS-treated samples impacts methylation-based tumor classification systems giving new opportunities for further refinement of classifiers for both pediatric and adult tumors. Conclusions: We identified that 5hmC localizes to super-enhancers, and genes commonly implicated in pediatric CNS tumors were differentially hypohydroxymethylated. We demonstrated that distinguishing methylation and hydroxymethylation is critical in identifying tumor-related epigenetic changes. These results have implications for patient prognostication, considerations of epigenetic therapy in CNS tumors, and for emerging molecular neuropathology classification approaches

A Fluctuation Analysis of the Bolocam 1.1mm Lockman Hole Survey

We perform a fluctuation analysis of the 1.1mm Bolocam Lockman Hole Survey, which covers 324 square arcmin to a very uniform point source-filtered RMS noise level of 1.4 mJy/beam. The fluctuation analysis has the significant advantage of utilizing all of the available data. We constrain the number counts in the 1-10 mJy range, and derive significantly tighter constraints than in previous work: the power-law index is 2.7 (+0.18, -0.15), while the amplitude is equal to 1595 (+85,-238) sources per mJy per square degree, or N(>1 mJy) = 940 (+50,-140) sources/square degree (95% confidence). Our results agree extremely well with those derived from the extracted source number counts by Laurent et al (2005). Our derived normalization is about 2.5 times smaller than determined by MAMBO at 1.2mm by Greve et al (2004). However, the uncertainty in the normalization for both data sets is dominated by the systematic (i.e., absolute flux calibration) rather than statistical errors; within these uncertainties, our results are in agreement. We estimate that about 7% of the 1.1mm background has been resolved at 1 mJy.Comment: To appear in the Astrophysical Journal; 22 pages, 9 figure

AsiFood and its output and prospects: An Erasmus+ project on capacity building in food safety and quality for South-East Asia

The Asifood project is a capacity building project in the field of higher education involving collaboration among thirteen partners from Cambodia, Thailand, Vietnam, Austria, Belgium, Italy and France. This project aimed to support the universities in Vietnam, Thailand and Cambodia in building their capacities and their link with professionals in food safety and food quality, in the context of ASEAN integration. Further, training for trainers around a key theme, ‘food safety and quality’ for partner countries was set up involving students and teachers, professional stakeholders, political decision-makers and association leaders. During the first year of the project, study and diagnostic phase were carried out to properly assess the training as per each university needs. In the second year, the training paths around three axes: courses, quality and laboratory analysis were conducted. Finally, a test phase was carried out with the partners by inserting the modules created in the bachelor's and master's degree courses offered by the universities as well as short term trainings on innovations in food safety and quali

CD1d-expressing Dendritic Cells but Not Thymic Epithelial Cells Can Mediate Negative Selection of NKT Cells

Natural killer T (NKT) cells are a unique immunoregulatory T cell population that is positively selected by CD1d-expressing thymocytes. Previous studies have shown that NKT cells exhibit autoreactivity, which raises the question of whether they are subject to negative selection. Here, we report that the addition of agonist glycolipid α-galactosylceramide (α-GalCer) to a fetal thymic organ culture (FTOC) induces a dose-dependent disappearance of NKT cells, suggesting that NKT cells are susceptible to negative selection. Overexpression of CD1d in transgenic (Tg) mice results in reduced numbers of NKT cells, and the residual NKT cells in CD1d-Tg mice exhibit both an altered Vβ usage and a reduced sensitivity to antigen. Furthermore, bone marrow (BM) chimeras between Tg and WT mice reveal that CD1d-expressing BM-derived dendritic cells, but not thymic epithelial cells, mediate the efficient negative selection of NKT cells. Thus, our data suggest that NKT cells developmentally undergo negative selection when engaged by high-avidity antigen or abundant self-antigen

Multifragmentation in Xe(50A MeV)+Sn Confrontation of theory and data

We compare in detail central collisions Xe(50A MeV) + Sn, recently measured by the INDRA collaboration, with the Quantum Molecular Dynamics (QMD) model in order to identify the reaction mechanism which leads to multifragmentation. We find that QMD describes the data quite well, in the projectile/target region as well as in the midrapidity zone where also statistical models can be and have been employed. The agreement between QMD and data allows to use this dynamical model to investigate the reaction in detail. We arrive at the following observations: a) the in medium nucleon nucleon cross section is not significantly different from the free cross section, b) even the most central collisions have a binary character, c) most of the fragments are produced in the central collisions and d) the simulations as well as the data show a strong attractive in-plane flow resembling deep inelastic collisions e) at midrapidity the results from QMD and those from statistical model calculations agree for almost all observables with the exception of ${d^2 \sigma \over dZdE}$. This renders it difficult to extract the reaction mechanism from midrapidity fragments only. According to the simulations the reaction shows a very early formation of fragments, even in central collisions, which pass through the reaction zone without being destroyed. The final transverse momentum of the fragments is very close to the initial one and due to the Fermi motion. A heating up of the systems is not observed and hence a thermal origin of the spectra cannot be confirmed.Comment: figures 1 and 2 changed (no more ps -errors

Optimal neighborhood indexing for protein similarity search

Background: Similarity inference, one of the main bioinformatics tasks, has to face an exponential growth of the biological data. A classical approach used to cope with this data flow involves heuristics with large seed indexes. In order to speed up this technique, the index can be enhanced by storing additional information to limit the number of random memory accesses. However, this improvement leads to a larger index that may become a bottleneck. In the case of protein similarity search, we propose to decrease the index size by reducing the amino acid alphabet.\ud \ud Results: The paper presents two main contributions. First, we show that an optimal neighborhood indexing combining an alphabet reduction and a longer neighborhood leads to a reduction of 35% of memory involved into the process, without sacrificing the quality of results nor the computational time. Second, our approach led us to develop a new kind of substitution score matrices and their associated e-value parameters. In contrast to usual matrices, these matrices are rectangular since they compare amino acid groups from different alphabets. We describe the method used for computing those matrices and we provide some typical examples that can be used in such comparisons. Supplementary data can be found on the website http://bioinfo.lifl.fr/reblosum.\ud \ud Conclusions: We propose a practical index size reduction of the neighborhood data, that does not negatively affect the performance of large-scale search in protein sequences. Such an index can be used in any study involving large protein data. Moreover, rectangular substitution score matrices and their associated statistical parameters can have applications in any study involving an alphabet reduction

Pancreatic β-cell imaging in humans: Fiction or option?

Diabetes mellitus is a growing worldwide epidemic disease, currently affecting 1 in 12 adults. Treatment of disease complications typically consumes ∼10% of healthcare budgets in developed societies. Whilst immune‐mediated destruction of insulin‐secreting pancreatic β cells is responsible for Type 1 diabetes, both the loss and dysfunction of these cells underly the more prevalent Type 2 diabetes. The establishment of robust drug development programmes aimed at β‐cell restoration is still hampered by the absence of means to measure β‐cell mass prospectively in vivo, an approach which would provide new opportunities for understanding disease mechanisms and ultimately assigning personalized treatments. In the present review, we describe the progress towards this goal achieved by the Innovative Medicines Initiative in Diabetes, a collaborative public–private consortium supported by the European Commission and by dedicated resources of pharmaceutical companies. We compare several of the available imaging methods and molecular targets and provide suggestions as to the likeliest to lead to tractable approaches. Furthermore, we discuss the simultaneous development of animal models that can be used to measure subtle changes in β‐cell mass, a prerequisite for validating the clinical potential of the different imaging tracers

Multifragmentation of a very heavy nuclear system (I): Selection of single-source events

A sample of `single-source' events, compatible with the multifragmentation of very heavy fused systems, are isolated among well-measured 155Gd+natU 36AMeV reactions by examining the evolution of the kinematics of fragments with Z>=5 as a function of the dissipated energy and loss of memory of the entrance channel. Single-source events are found to be the result of very central collisions. Such central collisions may also lead to multiple fragment emission due to the decay of excited projectile- and target-like nuclei and so-called `neck' emission, and for this reason the isolation of single-source events is very difficult. Event-selection criteria based on centrality of collisions, or on the isotropy of the emitted fragments in each event, are found to be inefficient to separate the two mechanisms, unless they take into account the redistribution of fragments' kinetic energies into directions perpendicular to the beam axis. The selected events are good candidates to look for bulk effects in the multifragmentation process.Comment: 39 pages including 15 figures; submitted to Nucl. Phys.

Multifragmentation of a very heavy nuclear system (II): bulk properties and spinodal decomposition

The properties of fragments and light charged particles emitted in multifragmentation of single sources formed in central 36AMeV Gd+U collisions are reviewed. Most of the products are isotropically distributed in the reaction c.m. Fragment kinetic energies reveal the onset of radial collective energy. A bulk effect is experimentally evidenced from the similarity of the charge distribution with that from the lighter 32AMeV Xe+Sn system. Spinodal decomposition of finite nuclear matter exhibits the same property in simulated central collisions for the two systems, and appears therefore as a possible mechanism at the origin of multifragmentation in this incident energy domain.Comment: 28 pages including 14 figures; submitted to Nucl. Phys.

Reliability and Validity of Nonverbal Thin Slices in Social Interactions

Four studies investigated the reliability and validity of thin slices of nonverbal behavior from social interactions including (a) how well individual slices of a given behavior predict other slices in the same interaction; (b) how well a slice of a given behavior represents the entirety of that behavior within an interaction; (c) how long a slice is necessary to sufficiently represent the entirety of a behavior within an interaction; (d) which slices best capture the entirety of behavior, across different behaviors; and (e) which behaviors (of six measured behaviors) are best captured by slices. Notable findings included strong reliability and validity for thin slices of gaze and nods, and that a 1.5-min slice from the start of an interaction may adequately represent some behaviors. Results provide useful information to researchers making decisions about slice measurement of behavior