Adolescent Cardiovascular Fitness Changes One Year Post Gastric-Band Surgery

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Adolescent Strength and Body Composition Changes One Year Post Gastric-Band Surgery

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Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective B therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (P<0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5’-azacytidine and decitabine in controlling disease progression in vivo

A new twist on sea silk : the peculiar protein ultrastructure of fan shell and pearl oyster byssus

11 pagesInternational audienceNumerous mussel species produce byssal threads - tough proteinaceous fibers, which anchor mussels in aquatic habitats. Byssal threads from Mytilus species, which are comprised of modified collagen proteins - have become a veritable archetype for bio-inspired polymers due to their self-healing properties. However, threads from different species are comparatively much less understood. In particular, the byssus of Pinna nobilis comprises thousands of fine fibers utilized by humans for millennia to fashion lightweight golden fabrics known as sea silk. P. nobilis is very different from Mytilus from an ecological, morphological and evolutionary point of view and it stands to reason that the structure-function relationships of its byssus are distinct. Here, we performed compositional analysis, X-ray diffraction (XRD) and transmission electron microscopy (TEM) to investigate byssal threads of P. nobilis, as well as a closely related bivalve species (Atrina pectinata) and a distantly related one (Pinctada fucata). This comparative investigation revealed that all three threads share a similar molecular superstructure comprised of globular proteins organized helically into nanofibrils, which is completely distinct from the Mytilus thread ultrastructure, and more akin to the supramolecular organization of bacterial pili and F-actin. This unexpected discovery hints at a possible divergence in byssus evolution in Pinnidae mussels, perhaps related to selective pressures in their respective ecological niches

The cuttlefish Sepia officinalis (Sepiidae, Cephalopoda) constructs cuttlebone from a liquid-crystal precursor

Cuttlebone, the sophisticated buoyancy device of cuttlefish, is made of extensive superposed chambers that have a complex internal arrangement of calcified pillars and organic membranes. It has not been clear how this structure is assembled. We find that the membranes result from a myriad of minor membranes initially filling the whole chamber, made of nanofibres evenly oriented within each membrane and slightly rotated with respect to those of adjacent membranes, producing a helical arrangement. We propose that the organism secretes a chitin-protein complex, which self-organizes layer-by-layer as a cholesteric liquid crystal, whereas the pillars are made by viscous fingering. The liquid crystallization mechanism permits us to homologize the elements of the cuttlebone with those of other coleoids and with the nacreous septa and the shells of nautiloids. These results challenge our view of this ultra-light natural material possessing desirable mechanical, structural and biological properties, suggesting that two self-organizing physical principles suffice to understand its formation.Spanish Ministerio de Ciencia e Innovacion [CGL2010-20748-CO2-01, CGL2013-48247-P, FIS2013-48444-C2-2-P]; Andalusian Consejeria de Innovacion Ciencia y Tecnologia [RNM6433]; (Sepiatech, PROMAR program) of the Portuguese Ministerio da Agricultura e do Mar, Portugal [31.03.05.FEP.002]; Junta de Andalucia [RNM363]; FP7 COST Action of the European Community. [TD0903]info:eu-repo/semantics/publishedVersio

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

Controlled Lactonization of o-Coumaric Esters Mediated by Supramolecular Gels

Fragrances are volatile organic compounds widely used in our daily life. Unfortunately, the high volatility required to reach human receptors reduces their persistency in the air. To contrast this effect, several strategies may be used. Among them, we present here the combination of two techniques: the microencapsulation in supramolecular gels and the use of profragrances. We report a study on the controlled lactonization of four esters derived from o-coumaric acid. The ester lactonization spontaneously occurs after exposure to solar light, releasing coumarin and the corresponding alcohol. To determine the rate of fragrance release, we compared the reaction in solution and in a supramolecular gel and we demonstrated that the lactonization reaction always occurs slower in the gel. We also studied the more suitable gel for this aim, by comparing the properties of two supramolecular gels obtained with the gelator Boc-L-DOPA(Bn)(2)-OH in a 1:1 ethanol/water mixture in different gelator concentration (0.2% and 1% w/v). The gel prepared with 1% w/v gelator concentration is stronger and less transparent than the other and was used for the profragrances encapsulation. In any case, we obtained a significative reduction of lactonization reaction in gel, compared with the same reaction in solution

A one-mutation mathematical model can explain the age incidence of acute myeloid leukemia with mutated nucleophosmin (NPM1)

Acute myeloid leukemia with mutated NPM1 gene and aberrant cytoplasmic expression of nucleophosmin (NPMc+acute myeloid leukemia) shows distinctive biological and clinical features. Experimental evidence of the oncogenic potential of the nucleophosmin mutant is, however, still lacking, and it is unclear whether other genetic lesion(s), e.g. FLT3 internal tandem duplication, cooperate with NPM1 mutations in acute myeloid leukemia development. An analysis of age-specific incidence, together with mathematical modeling of acute myeloid leukemia epidemiology, can help to uncover the number of genetic events needed to cause leukemia. We collected data on age at diagnosis of acute myeloid leukemia patients from five European Centers in Germany, The Netherlands and Italy, and determined the age-specific incidence of AML with mutated NPM1 (a total of 1,444 cases) for each country. Linear regression of the curves representing age-specific rates of diagnosis per year showed similar slopes of about 4 on a double logarithmic scale. We then adapted a previously designed mathematical model of hematopoietic tumorigenesis to analyze the age incidence of acute myeloid leukemia with mutated NPM1 and found that a one-mutation model can explain the incidence curve of this leukemia entity. This model fits with the hypothesis that NPMc+acute myeloid leukemia arises from an NPM1 mutation with haploinsufficiency of the wild-type NPM1 allele

Splines Parameterization of Planar Domains by Physics-Informed Neural Networks

The generation of structured grids on bounded domains is a crucial issue in the development of numerical models for solving differential problems. In particular, the representation of the given computational domain through a regular parameterization allows us to define a univalent mapping, which can be computed as the solution of an elliptic problem, equipped with suitable Dirichlet boundary conditions. In recent years, Physics-Informed Neural Networks (PINNs) have been proved to be a powerful tool to compute the solution of Partial Differential Equations (PDEs) replacing standard numerical models, based on Finite Element Methods and Finite Differences, with deep neural networks; PINNs can be used for predicting the values on simulation grids of different resolutions without the need to be retrained. In this work, we exploit the PINN model in order to solve the PDE associated to the differential problem of the parameterization on both convex and non-convex planar domains, for which the describing PDE is known. The final continuous model is then provided by applying a Hermite type quasi-interpolation operator, which can guarantee the desired smoothness of the sought parameterization. Finally, some numerical examples are presented, which show that the PINNs-based approach is robust. Indeed, the produced mapping does not exhibit folding or self-intersection at the interior of the domain and, also, for highly non convex shapes, despite few faulty points near the boundaries, has better shape-measures, e.g., lower values of the Winslow functional