Towards pathway-centric cancer therapies via pharmacogenomic profiling analysis of ERK signalling pathway

Background: Genomic heterogeneity in human cancers complicates gene-centric personalized medicine. Malignant tumors often share a core group of pathways that are perturbed by diverse genetic mutations. Therefore, one possible solution to overcome the heterogeneity challenge is a shift from gene-centric to pathway-centric therapies. Pathway-centric perspectives, which underscore the need to understand key pathways and their critical properties, could address the complexity of cancer heterogeneity better than gene-centric approaches to aid cancer drug discovery and therapy. Methods: We used large-scale pharmacogenomic profiling data provided by the Cancer Genome Project of the Wellcome Trust Sanger Institute and the Cancer Cell Line Encyclopedia. In a systematic in silico investigation of ERK signalling pathway components and topological structures determines their influences on pathway activity and targeted therapies. Mann–Whitney U test was used to identify gene alterations associated with drug sensitivity with p values and Benjamini–Hochberg correction for multiple hypotheses testing. Results: The analysis demonstrated that genetic alterations were crucial to activation of effector pathway and subsequent tumorigenesis, however drug sensitivity suffered from both drug effector and non-effector pathways, which were determined by not only underlying genomic alterations, but also interplay and topological relationship of components in pathway, suggesting that the combinatorial targets of key nodes in perturbed pathways may yield better treatment outcome. Furthermore, we proposed a model to provide a more comprehensive insight and understanding of pathway-centric cancer therapies. Conclusions: Our study provides a holistic view of factors influencing drug sensitivity and sheds light on pathway-centric cancer therapies. Electronic supplementary material The online version of this article (doi:10.1186/s40169-015-0066-1) contains supplementary material, which is available to authorized users

ATOMS: ALMA Three-millimeter Observations of Massive Star-forming regions – V. Hierarchical fragmentation and gas dynamics in IRDC G034.43+00.24

We present new 3-mm continuum and molecular lines observations from the ATOMS survey towards the massive protostellar clump, MM1, located in the filamentary infrared dark cloud (IRDC), G034.43+00.24 (G34). The lines observed are the tracers of either dense gas (e.g. HCO+/(HCO+)-C-13 J= 1-0) or outflows (e.g. CS J = 2-1). The most complete picture to date of seven cores in MM1 is revealed by dust continuum emission. These cores are found to be gravitationally bound, with virial parameter, alpha(vir) < 2. At least four outflows are identified in MM1 with a total outflowing mass of similar to 45 M-circle dot, and a total energy of 1 x 10(47) erg, typical of outflows from a B0-type star. Evidence of hierarchical fragmentation, where turbulence dominates over thermal pressure, is observed at both the cloud and the clump scales. This could be linked to the scale-dependent, dynamical mass inflow/accretion on clump and core scales. We therefore suggest that the G34 cloud could be undergoing a dynamical mass inflow/accretion process linked to the multiscale fragmentation, which leads to the sequential formation of fragments of the initial cloud, clumps, and ultimately dense cores, the sites of star formation.Peer reviewe

ATOMS : ALMA three-millimeter observations of massive star-forming regions - III. Catalogues of candidate hot molecular cores and hyper/ultra compact H II regions

A correction has been published: Monthly Notices of the Royal Astronomical Society, Volume 511, Issue 1, March 2022, Pages 501–505, https://doi.org/10.1093/mnras/stac039We have identified 453 compact dense cores in 3mm continuum emission maps in the ALMA Three-millimetre Observations of Massive Star-forming regions survey, and compiled three catalogues of high-mass star-forming cores. One catalogue, referred to as hyper/ultra compact (H/UC)-HII catalogue, includes 89 cores that enshroud H/UC HII regions as characterized by associated compact H40 alpha emission. A second catalogue, referred to as pure s-cHMC, includes 32 candidate hot molecular cores (HMCs) showing rich spectra (N >= 20 lines) of complex organic molecules (COMs) and not associated with H/UC-HII regions. The third catalogue, referred to as pure w-cHMC, includes 58 candidate HMCs with relatively low levels of COM richness and not associated with H/UC-Hii regions. These three catalogues of dense cores provide an important foundation for future studies of the early stages of high-mass star formation across the Milky Way. We also find that nearly half of H/UC-HII cores are candidate HMCs. From the number counts of COM-containing and H/UC-HII cores, we suggest that the duration of high-mass protostellar cores showing chemically rich features is at least comparable to the lifetime of H/UC-HII regions. For cores in the H/UC-HII catalogue, the width of the H40 alpha line increases as the core size decreases, suggesting that the non-thermal dynamical and/or pressure line-broadening mechanisms dominate on the smaller scales of the H/UC-HII cores.Peer reviewe

New lanthanide-based coordination polymers with 2,5-dihydroxyterephthalate

International audienceCrystal growths in gel medium of lanthanide-based coordination polymers with 2,5-dihydroxyterephthalate (dhbdc2−) as ligand lead to two different crystal structures depending on the lanthanide ion. Lanthanide-based coordination polymers that crystallize in these two structural type have respective chemical formulas [Ln2(dhbdc)3(H2O)12·6H2O]∞ with Ln = La-Nd, and [Ln2(dhbdc)3(H2O)8·6H2O]∞ with Ln = Sm-Yb plus Y. Only the Nd-based and the Yb-based coordination polymers exhibit luminescence properties in the near-infrared region

A new family of lanthanide-based coordination polymers with azoxybenzene-3,3′,5,5′-tetracarboxylic acid as ligand

International audienceReactions by solvothermal methods of lanthanide nitrates and azoxybenzene-3,3′,5,5′-tetracarboxylic acid (H4aobtc) lead to a family of isostructural lanthanide-based coordination polymers with general chemical formula [Ln(Haobtc)(H2O)2·2H2O]∞ with Ln = Nd − Er plus Y. The crystal structure has been solved on the basis of the Y3+-derivative. It crystallizes in the triclinic system, space group P-1 (n°2) with the following cell parameters: a = 6.6890(18) Å, b = 10.052(3) Å, c = 13.879(4) Å,α = 75.756(9)°, β = 77.551(9)°, γ = 83.964(9)° and Z = 2. The crystal structure is two-dimensional (2D). Thermal properties and luminescent properties of the Nd3+-containing compound have been studied

Enhanced Muscle Fibers of Epinephelus coioides by Myostatin Autologous Nucleic Acid Vaccine

Epinephelus coioides is a fish species with high economic value due to its delicious meat, high protein content, and rich fatty acid nutrition. It has become a high-economic fish in southern parts of China and some other Southeast Asian countries. In this study, the myostatin nucleic acid vaccine was constructed and used to immunize E. coioides. The results from body length and weight measurements indicated the myostatin nucleic acid vaccine promoted E. coioides growth performance by increasing muscle fiber size. The results from RT-qPCR analysis showed that myostatin nucleic acid vaccine upregulated the expression of myod, myog and p21 mRNA, downregulated the expression of smad3 and mrf4 mRNA. This preliminary study is the first report that explored the role of myostatin in E. coioides and showed positive effects of autologous nucleic acid vaccine on the muscle growth of E. coioides. Further experiments with increased numbers of animals and different doses are needed for its application to E. coiodes aquaculture production

mTORC1 Mediates Lysine-Induced Satellite Cell Activation to Promote Skeletal Muscle Growth

As the first limiting amino acid, lysine (Lys) has been thought to promote muscle fiber hypertrophy by increasing protein synthesis. However, the functions of Lys seem far more complex than that. Despite the fact that satellite cells (SCs) play an important role in skeletal muscle growth, the communication between Lys and SCs remains unclear. In this study, we investigated whether SCs participate directly in Lys-induced skeletal muscle growth and whether the mammalian target of rapamycin complex 1 (mTORC1) pathway was activated both in vivo and in vitro to mediate SC functions in response to Lys supplementation. Subsequently, the skeletal muscle growth of piglets was controlled by dietary Lys supplementation. Isobaric tag for relative and absolute quantitation (iTRAQ) analysis showed activated SCs were required for longissimus dorsi muscle growth, and this effect was accompanied by mTORC1 pathway upregulation. Furthermore, SC proliferation was governed by medium Lys concentrations, and the mTORC1 pathway was significantly enhanced in vitro. After verifying that rapamycin inhibits the mTORC1 pathway and suppresses SC proliferation, we conclude that Lys is not only a molecular building block for protein synthesis but also a signal that activates SCs to manipulate muscle growth via the mTORC1 pathway

Multi-Emissive Lanthanide-Based Coordination Polymers for Potential Application as Luminescent Bar-Codes

International audienc

Characterization of the Complete Mitochondrial Genome Sequences of Three Croakers (Perciformes, Sciaenidae) and Novel Insights into the Phylogenetics

The three croakers (Nibea coibor, Protonibea diacanthus and Argyrosomus amoyensis, Perciformes, Sciaenidae) are important commercial species inhabiting the Eastern Indian Ocean and Western Pacific. Molecular data employed in previous research on phylogenetic reconstruction have not been adequate and complete, and systematic and comprehensive phylogenetic relationships for these fish are unresolved. We sequenced the complete mitochondrial genomes of the three croakers using next-generation sequencing for the first time. We analyzed the composition and phylogenies between 19 species in the family Sciaenidae using the mitochondrial protein coding sequences of 204 species in the Series Eupercaria. We present the characterization of the complete mitochondrial genome sequences of the three croakers. Gene arrangement and distribution of the three croakers are canonically identical and consistent with other vertebrates. We found that the family Sciaenidae is an independent branch that is isolated from the order Perciformes and does not belong to any extant classification. Therefore, this family is expected to belong to a new classification at the order level and needs further analysis. The evolution of Sciaenidae has lagged far behind the Perciformes differentiation. This study presents a novel insight into the phylogenetics of the family Sciaenidae from the order Perciformes and facilitates additional studies on the evolution and phylogeny of Series Eupercaria