Molecular genetics of naringenin biosynthesis, a typical plant secondary metabolite produced by Streptomyces clavuligerus

Background: Some types of flavonoid intermediates seemed to be restricted to plants. Naringenin is a typical plant metabolite, that has never been reported to be produced in prokariotes. Naringenin is formed by the action of a chal cone synthase using as starter 4-coumaroyl-CoA, which in dicotyledonous plants derives from phenylalanine by the action of a phenylalanine ammonia lyase. Results: A compound produced by Streptomyces clavuligerus has been identified by LC–MS and NMR as naringenin and coelutes in HPLC with a naringenin standard. Genome mining of S. clavuligerus revealed the presence of a gene for a chalcone synthase (ncs), side by side to a gene encoding a P450 cytochrome (ncyP) and separated from a gene encoding a Pal/Tal ammonia lyase (tal). Deletion of any of these genes results in naringenin non producer mutants. Complementation with the deleted gene restores naringenin production in the transformants. Furthermore, narin genin production increases in cultures supplemented with phenylalanine or tyrosine. Conclusion: This is the first time that naringenin is reported to be produced naturally in a prokariote. Interestingly three non-clustered genes are involved in naringenin production, which is unusual for secondary metabolites. A ten tative pathway for naringenin biosynthesis has been proposed

The Drosophila FMRP and LARK RNA-binding proteins function together to regulate eye development and circadian behavior

Fragile X syndrome (FXS) is the most common form of hereditary mental retardation. FXS patients have a deficit for the fragile X mental retardation protein (FMRP) that results in abnormal neuronal dendritic spine morphology and behavioral phenotypes, including sleep abnormalities. In a Drosophila model of FXS, flies lacking the dfmr1 protein (dFMRP) have abnormal circadian rhythms apparently as a result of altered clock output. In this study, we present biochemical and genetic evidence that dFMRP interacts with a known clock output component, the LARK RNA-binding protein. Our studies demonstrate physical interactions between dFMRP and LARK, that the two proteins are present in a complex in vivo, and that LARK promotes the stability of dFMRP. Furthermore, we show genetic interactions between the corresponding genes indicating that dFMRP and LARK function together to regulate eye development and circadian behavior

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

T1b Glottic Tumor and Anterior Commissure Involvement: Is the Transoral CO2 Laser Microsurgery a Safe Option?

[Abstract] Objectives: Transoral CO2 laser therapy represents the treatment of choice for early-stage laryngeal tumors. The anterior commissure involvement (ACI) is related to a worse local control and a lower rates of organ preservation. The objective of this study is to analyze the differences in survival, local control, and organ preservation in T1b glottic patients according to the presence of ACI. Methods: Observational prospective study in pT1b treated with transoral CO2 laser between 2009 and 2014. Results: Forty patients (37 male and 3 female) with a mean age of 66.43 ± 8.16 years were recruited. Anterior commissure involvement was present in 70% of the patients. The 5-year specific cause survival was 91.66%, with 32.50% of local recurrences. Laryngeal preservation was 80%, being lower in the group with local recurrence (P < .000). The involvement of the anterior commissure does not influence the organ preservation (P = .548), the appearance of local recurrences (P = .391), or the survival (P = .33). Conclusions: Transoral CO2 laser therapy is an effective and reproducible treatment for early-stage laryngeal tumors. The results obtained are similar to previous studies, although they present discrepancies in relation to the role of the ACI. Prospective randomized trials are required focusing also on the patients’ quality of life and functional outcome in order to clarify the role of the ACI and the need to implement changes in its evaluation, staging, and evolution

Robotics and augmented reality for elderly assistance

This article presents a tele-assistance system based on augmented reality for elderly people that is integrated in a mobile platform. We propose the use of augmented reality for simplifying interaction with its users. The first prototype has been designed to help in medication control for ederly people. In this paper, both hardware and software architectures are described.The robotic platform is a slightly modified version of the Turtlebot platform. The software is based on ROS for the platform control, and in ArUco for the augmented reality interface. It also integrates other related systems in teleassistance such as VoIP, friendly user interface, etc

Interplay of Linker Functionalization and Hydrogen Adsorption in the Metal–Organic Framework MIL-101

Functionalization of metal–organic frameworks results in higher hydrogen uptakes owing to stronger hydrogen–host interactions. However, it has not been studied whether a given functional group acts on existing adsorption sites (linker or metal) or introduces new ones. In this work, the effect of two types of functional groups on MIL-101 (Cr) is analyzed. Thermal-desorption spectroscopy reveals that the −Br ligand increases the secondary building unit’s hydrogen affinity, while the −NH2 functional group introduces new hydrogen adsorption sites. In addition, a subsequent introduction of −Br and −NH2 ligands on the linker results in the highest hydrogen-store interaction energy on the cationic nodes. The latter is attributed to a push-and-pull effect of the linkers

Realidad aumentada para la teleasistencia en ancianos

[ES] En las últimas décadas las mejoras en campos como la alimentación o la medicina ha permitido mejorar el día a día de los mayores y alargar su esperanza de vida lo que ha significado un aumento de la población mayor. Ahora bien, ante estas nuevas circunstancias debemos abordar las necesidades específicas sobre este grupo de población. Creemos que, aprovechando las ventajas que las nuevas tecnologías pueden ofrecernos, podemos desarrollar nuevos sistemas tecnológicos adaptados a los ancianos que les permitirán aprovechar las nueva etapas que tienen ante ellos

ArgR of Streptomyces coelicolor is a versatile regulator

[EN] ArgR is the regulator of arginine biosynthesis genes in Streptomyces species. Transcriptomic comparison by microarrays has been made between Streptomyces coelicolor M145 and its mutant S. coelicolor ΔargR under control, unsupplemented conditions, and in the presence of arginine. Expression of 459 genes was different in transcriptomic assays, but only 27 genes were affected by arginine supplementation. Arginine and pyrimidine biosynthesis genes were derepressed by the lack of ArgR, while no strong effect on expression resulted on arginine supplementation. Several nitrogen metabolism genes expression as glnK, glnA and glnII, were downregulated in S. coelicolor ΔargR. In addition, downregulation of genes for the yellow type I polyketide CPK antibiotic and for the antibiotic regulatory genes afsS and scbR was observed. The transcriptomic data were validated by either reverse transcription-PCR, expression of the gene-promoter coupled to the luciferase gene, proteomic or by electrophoresis mobility shift assay (EMSA) using pure Strep-tagged ArgR. Two ARG-boxes in the arginine operon genes suggest that these genes are more tightly controlled. Other genes, including genes encoding regulatory proteins, possess a DNA sequence formed by a single ARG-box which responds to ArgR, as validated by EMSASIThis work was supported by Grants from the Spanish Comisión Interministerial de Ciencia y Tecnología GEN2003-20245, BIO2009-09820, and by the European Project LSHM-CT-2004-005224. AB received a fellowship from the Ministry of Science and Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Hemotin, a regulator of phagocytosis encoded by a small ORF and xonserved across metazoans

Translation of hundreds of small ORFs (smORFs) of less than 100 amino acids has recently been revealed in vertebrates and Drosophila. Some of these peptides have essential and conserved cellular functions. In Drosophila, we have predicted a particular smORF class encoding ~80 aa hydrophobic peptides, which may function in membranes and cell organelles. Here, we characterise hemotin, a gene encoding an 88aa transmembrane smORF peptide localised to early endosomes in Drosophila macrophages. hemotin regulates endosomal maturation during phagocytosis by repressing the cooperation of 14-3-3ζ with specific phosphatidylinositol (PI) enzymes. hemotin mutants accumulate undigested phagocytic material inside enlarged endo-lysosomes and as a result, hemotin mutants have reduced ability to fight bacteria, and hence, have severely reduced life span and resistance to infections. We identify Stannin, a peptide involved in organometallic toxicity, as the Hemotin functional homologue in vertebrates, showing that this novel regulator of phagocytic processing is widely conserved, emphasizing the significance of smORF peptides in cell biology and disease

Spa-Stocsy: An Automated Tool for Identifying Annotated and Non-annotated Metabolites in High-Throughput NMR Spectra

MOTIVATION: Nuclear magnetic resonance spectroscopy (NMR) is widely used to analyze metabolites in biological samples, but the analysis requires specific expertise, it is time-consuming, and can be inaccurate. Here, we present a powerful automate tool, SPatial clustering Algorithm-Statistical TOtal Correlation SpectroscopY (SPA-STOCSY), which overcomes challenges faced when analyzing NMR data and identifies metabolites in a sample with high accuracy. RESULTS: As a data-driven method, SPA-STOCSY estimates all parameters from the input dataset. It first investigates the covariance pattern among datapoints and then calculates the optimal threshold with which to cluster datapoints belonging to the same structural unit, i.e. the metabolite. Generated clusters are then automatically linked to a metabolite library to identify candidates. To assess SPA-STOCSY\u27s efficiency and accuracy, we applied it to synthesized spectra and spectra acquired on Drosophila melanogaster tissue and human embryonic stem cells. In the synthesized spectra, SPA outperformed Statistical Recoupling of Variables (SRV), an existing method for clustering spectral peaks, by capturing a higher percentage of the signal regions and the close-to-zero noise regions. In the biological data, SPA-STOCSY performed comparably to the operator-based Chenomx analysis while avoiding operator bias, and it requiredOverall, SPA-STOCSY is a fast, accurate, and unbiased tool for untargeted analysis of metabolites in the NMR spectra. It may thus accelerate the use of NMR for scientific discoveries, medical diagnostics, and patient-specific decision making