A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma.

Background: Sarcomas represent an extensive group of malignant diseases affecting mesodermal tissues. Among sarcomas, the clinical management of chondrosarcomas remains a complex challenge, as high-grade tumours do not respond to current therapies. Mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes are among the most common mutations detected in chondrosarcomas and may represent a therapeutic opportunity.

Breath-Body-Mind Core Techniques to Manage Medical Student Stress.

Objectives: This pilot study evaluated the feasibility of a live, interactive, synchronous, online, manualized intervention, Breath-Body-Mind Introductory Course (BBM-IC), for medical students. BBM-IC includes breathing, movement, and attention-focus techniques for stress management and better emotion regulation, energy, sleep, and mental focus.

Methods: Medical students attending a 2-h BBM demonstration were invited to participate in the 12-h BBM-IC and weekly 45-min 6-week group practice.

Uncovering the Cryptic Gene Cluster for 3-amino-4-hydroxybenzoate Derived Ahbamycins, by Searching SARP Regulator Encoding Genes in the Genome.

Genome mining using standard bioinformatics tools has allowed for the uncovering of hidden biosynthesis gene clusters for specialized metabolites in genomes. In this work, we have used an alternative approach consisting in seeking " Antibiotic Regulatory Proteins" (SARP) encoding genes and analyzing their surrounding DNA region to unearth cryptic gene clusters that cannot be identified using standard bioinformatics tools. This strategy has allowed the unveiling of the new cluster in , which had not been retrieved before using antiSMASH.

Combinatorial biosynthesis yields novel hybrid argimycin P alkaloids with diverse scaffolds in Streptomyces argillaceus.

Coelimycin P1 and argimycins P are two types of polyketide alkaloids produced by Streptomyces coelicolor and Streptomyces argillaceus, respectively. Their biosynthesis pathways share some early steps that render very similar aminated polyketide chains, diverging the pathways afterwards. By expressing the putative isomerase cpkE and/or the putative epoxidase/dehydrogenase cpkD from the coelimycin P1 gene cluster into S.

Instability after reverse total shoulder arthroplasty: risk factors and how to avoid them.

Instability after RTSA (4'7%) remains a complication with limited salvage options...

Roles of Low Temperature Sputtered Indium Tin Oxide for Solar Photovoltaic Technology.

Different functionalities of materials based on indium tin oxide and fabricated at soft conditions were investigated with the goal of being used in a next generation of solar photovoltaic devices. These thin films were fabricated in a commercial UNIVEX 450B magnetron sputtering. The first studied functionality consisted of an effective n-type doped layer in an n-p heterojunction based on p-type crystalline silicon.

AlInN on Si (100) Solar Cells (x = 0-0.56) Deposited by RF Sputtering.

We investigate the photovoltaic performance of solar cells based on n-AlInN (x = 0-0.56) on p-Si (100) hetero-junctions deposited by radio frequency sputtering. The AlInN layers own an optical bandgap absorption edge tuneable from 1.

Single GaAs nanowire based photodetector fabricated by dielectrophoresis.

Mechanical manipulation of nanowires (NWs) for their integration in electronics is still problematic because of their reduced dimensions, risking to produce mechanical damage to the NW structure and electronic properties during the assembly process. In this regard, contactless NW manipulation based methods using non-uniform electric fields, like dielectrophoresis (DEP) are usually much softer than mechanical methods, offering a less destructive alternative for integrating nanostructures in electronic devices. Here, we report a feasible and reproducible dielectrophoretic method to assemble single GaAs NWs (with radius 35-50 nm, and lengths 3-5 μm) on conductive electrodes layout with assembly yields above 90% per site, and alignment yields of 95%.

Long-Range Distributed Solar Irradiance Sensing Using Optical Fibers.

Until recently, the amount of solar irradiance reaching the Earth surface was considered to be a steady value over the years. However, there is increasing observational evidence showing that this quantity undergoes substantial variations over time, which need to be addressed in different scenarios ranging from climate change to solar energy applications. With the growing interest in developing solar energy technology with enhanced efficiency and optimized management, the monitoring of solar irradiance at the ground level is now considered to be a fundamental input in the pursuit of that goal.

New Chondrosarcoma Cell Lines with Preserved Stem Cell Properties to Study the Genomic Drift During In Vitro/In Vivo Growth.

For the cancer genomics era, there is a need for clinically annotated close-to-patient cell lines suitable to investigate altered pathways and serve as high-throughput drug-screening platforms. This is particularly important for drug-resistant tumors like chondrosarcoma which has few models available. Here we established and characterized new cell lines derived from two secondary (CDS06 and CDS11) and one dedifferentiated (CDS-17) chondrosarcomas as well as another line derived from a CDS-17-generated xenograft (T-CDS17).

Improving Pleasure and Motivation in Schizophrenia: A Randomized Controlled Clinical Trial.

Background: Negative symptoms are frequent in patients with schizophrenia and are associated with marked impairments in social functioning. The efficacy of drug-based treatments and psychological interventions on primary negative symptoms remains limited. The Positive Emotions Programme for Schizophrenia (PEPS) is designed to improve pleasure and motivation in schizophrenia patients by targeting emotion regulation and cognitive skills relevant to apathy and anhedonia.

Desertomycin G, a New Antibiotic with Activity against Mycobacterium tuberculosis and Human Breast Tumor Cell Lines Produced by Streptomyces althioticus MSM3, Isolated from the Cantabrian Sea Intertidal Macroalgae Ulva sp.

The isolation and structural elucidation of a structurally new desertomycin, designated as desertomycin G (), with strong antibiotic activity against several clinically relevant antibiotic resistant pathogens are described herein. This new natural product was obtained from cultures of the marine actinomycete MSM3, isolated from samples of the intertidal seaweed sp. collected in the Cantabrian Sea (Northeast Atlantic Ocean).

The multikinase inhibitor EC-70124 synergistically increased the antitumor activity of doxorubicin in sarcomas.

Cytotoxic drugs like doxorubicin remain as the most utilized agents in sarcoma treatment. However, advanced sarcomas are often resistant, thus stressing the need for new therapies aimed to overcome this resistance. Multikinase inhibitors provide an efficient way to target several pro-tumorigenic pathways using a single agent and may constitute a valuable strategy in the treatment of sarcomas, which frequently show an aberrant activation of pro-tumoral kinases.

Characterization of the Jomthonic Acids Biosynthesis Pathway and Isolation of Novel Analogues in GUA-06-05-006A.

Jomthonic acids (JAs) are a group of natural products (NPs) with adipogenic activity. Structurally, JAs are formed by a modified β-methylphenylalanine residue, whose biosynthesis involves a methyltransferase that in has been identified as MppJ. Up to date, three JA members (A⁻C) and a few other natural products containing β-methylphenylalanine have been discovered from soil-derived microorganisms.

Uncovering production of specialized metabolites by Streptomyces argillaceus: Activation of cryptic biosynthesis gene clusters using nutritional and genetic approaches.

Sequencing of Streptomyces genomes has revealed they harbor a high number of biosynthesis gene cluster (BGC), which uncovered their enormous potentiality to encode specialized metabolites. However, these metabolites are not usually produced under standard laboratory conditions. In this manuscript we report the activation of BGCs for antimycins, carotenoids, germicidins and desferrioxamine compounds in Streptomyces argillaceus, and the identification of the encoded compounds.

A Novel Growth Method To Improve the Quality of GaAs Nanowires Grown by Ga-Assisted Chemical Beam Epitaxy.

The successful synthesis of high crystalline quality and high aspect ratio GaAs nanowires (NWs) with a uniform diameter is needed to develop advanced applications beyond the limits established by thin film and bulk material properties. Vertically aligned GaAs NWs have been extensively grown by Ga-assisted vapor-liquid-solid (VLS) mechanism on Si(111) substrates, and they have been used as building blocks in photovoltaics, optoelectronics, electronics, and so forth. However, the nucleation of parasitic species such as traces and nanocrystals on the Si substrate surface during the NW growth could affect significantly the controlled nucleation of those NWs, and therefore the resulting performance of NW-based devices.

New Insights into the Biosynthesis Pathway of Polyketide Alkaloid Argimycins P in .

Argimycins P are a recently identified family of polyketide alkaloids encoded by the cryptic gene cluster of . These compounds contain either a piperideine ring, or a piperidine ring which may be fused to a five membered ring, and a polyene side chain, which is bound in some cases to an -acetylcysteine moiety. The cluster consists of 11 genes coding for structural proteins, two for regulatory proteins and one for a hypothetical protein.

Searching for Glycosylated Natural Products in Actinomycetes and Identification of Novel Macrolactams and Angucyclines.

Many bioactive natural products are glycosylated compounds in which the sugar components usually participate in interaction and molecular recognition of the cellular target. Therefore, the presence of sugar moieties is important, in some cases essential, for bioactivity. Searching for novel glycosylated bioactive compounds is an important aim in the field of the research for natural products from actinomycetes.

Paulomycin G, a New Natural Product with Cytotoxic Activity against Tumor Cell Lines Produced by Deep-Sea Sediment Derived Micromonospora matsumotoense M-412 from the Avilés Canyon in the Cantabrian Sea.

The present article describes a structurally novel natural product of the paulomycin family, designated as paulomycin G (), obtained from the marine strain M-412, isolated from Cantabrian Sea sediments collected at 2000 m depth during an oceanographic expedition to the submarine Avilés Canyon. Paulomycin G is structurally unique since-to our knowledge-it is the first member of the paulomycin family of antibiotics lacking the paulomycose moiety. It is also the smallest bioactive paulomycin reported.

Lobophorin K, a New Natural Product with Cytotoxic Activity Produced by Streptomyces sp. M-207 Associated with the Deep-Sea Coral Lophelia pertusa.

The present article describes the isolation of a new natural product of the lobophorin family, designated as lobophorin K (), from cultures of the marine actinobacteria sp. M-207, previously isolated from the cold-water coral collected at 1800 m depth during an expedition to the submarine Avilés Canyon. Its structure was determined using a combination of spectroscopic techniques, mainly ESI-TOF MS and 1D and 2D NMR.

Identification by Genome Mining of a Type I Polyketide Gene Cluster from Involved in the Biosynthesis of Pyridine and Piperidine Alkaloids Argimycins P.

Genome mining of the mithramycin producer ATCC 12956 revealed 31 gene clusters for the biosynthesis of secondary metabolites, and allowed to predict the encoded products for 11 of these clusters. Cluster 18 (renamed cluster ) corresponded to a type I polyketide gene cluster related to the previously described coelimycin P1 and streptazone gene clusters. The cluster consists of fourteen genes, including genes coding for putative regulatory proteins (a SARP-like transcriptional activator and a TetR-like transcriptional repressor), genes coding for structural proteins (three PKSs, one aminotransferase, two dehydrogenases, two cyclases, one imine reductase, a type II thioesterase, and a flavin reductase), and one gene coding for a hypothetical protein.

Branimycins B and C, Antibiotics Produced by the Abyssal Actinobacterium Pseudonocardia carboxydivorans M-227.

Two new antibiotics, branimycins B (2) and C (3), were produced by fermentation of the abyssal actinobacterium Pseudonocardia carboxydivorans M-227, isolated from deep seawater of the Avilés submarine Canyon. Their structures were elucidated by HRMS and NMR analyses. These compounds exhibit antibacterial activities against a panel of Gram-positive bacteria, including Corynebacterium urealyticum, Clostridium perfringens, and Micrococcus luteus, and against the Gram-negative bacterium Neisseria meningitidis.