A preliminary study of the metabolic stability of a series of benzoxazinone derivatives as potent neuropeptide Y5 antagonists

The metabolic stability of benzoxazinone derivatives, a potent series of NPY Y5 antagonists, has been investigated. This study resulted in the identification of the structural moieties prone to metabolic transformations and which strongly influenced the in vitro half-life. This provides opportunities to optimize the structure of this new class of NPY Y5 antagonists.     

Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems

Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology), we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis.     

Characterization of the 2012 Highly Pathogenic Avian Influenza H7N3 Virus Isolated from Poultry in an Outbreak in Mexico: Pathobiology and Vaccine Protection

In June of 2012, an H7N3 highly pathogenic avian influenza (HPAI) virus was identified as the cause of a severe disease outbreak in commercial laying chicken farms in Mexico. The purpose of this study was to characterize the Mexican 2012 H7N3 HPAI virus (A/chicken/Jalisco/CPA1/2012) and determine the protection against the virus conferred by different H7 inactivated vaccines in chickens. Both adult and young chickens intranasally inoculated with the virus became infected and died at between 2 and 4 days postinoculation (p.i.). High virus titers and viral replication in many tissues were demonstrated at 2 days p.i. in infected birds. The virus from Jalisco, Mexico, had high sequence similarity of greater than 97% to the sequences of wild bird viruses from North America in all eight gene segments. The hemagglutinin gene of the virus contained a 24-nucleotide insert at the hemagglutinin cleavage site which had 100% sequence identity to chicken 28S rRNA, suggesting that the insert was the result of nonhomologous recombination with the host genome. For vaccine protection studies, both U.S. H7 low-pathogenic avian influenza (LPAI) viruses and a 2006 Mexican H7 LPAI virus were tested as antigens in experimental oil emulsion vaccines and injected into chickens 3 weeks prior to challenge. All H7 vaccines tested provided ≥90% protection against clinical disease after challenge and decreased the number of birds shedding virus and the titers of virus shed. This study demonstrates the pathological consequences of the infection of chickens with the 2012 Mexican lineage H7N3 HPAI virus and provides support for effective programs of vaccination against this virus in poultry.     

Mise en Évidence d'une Induction de Résistance chez le Piment et la tomate Après Absorption par les Racines d'une Fraction Élicitrice Hydrosoluble

Resistance induction on pepper and tomato after dipping roots into watersoluble elicitor Fractions issued from Phytophthora casici culture filtrate are generally tested for the elicitor activity on detached cotyledons, Another technic is proposed: young plants (pepper or tomato) are uprooted and their roots dipped into elicitor; after detaching the foliar organs, resistance induction is controlled against Phytophthora capsici or Phytophthora infestans. With pepper, dipping time optimum is about 48 hours; the leaves are better protected than the cotyledons. After elicitation and transplanting, resistance induction remains at the level of the leaves during about one month (50% protection) and decreases progressively beyond. Systemicity of induction is discussed and several hypothesis proposed.     

Regulation of Androgen Receptor Activity by Transient Interactions of Its Transactivation Domain with General Transcription Regulators

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Barcelona conference on epigenetics and cancer 2015: Coding and non-coding functions of the genome

The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled “Coding and Non-Coding functions of the Genome” took place October 29–30, 2015 in Barcelona. The 2015 BCEC was the third edition of a series of annual conferences jointly organized by 5 leading research centers in Barcelona together with B-Debate, an initiative of BioCat. Luciano Di Croce from the Center for Genomic Regulation and Marcus Buschbeck from the Josep Carreras Leukemia Research Institute put together the scientific program with a particular focus on the role of non-coding RNAs in enhancer regulation, epigenetic control by Polycomb complexes, histone variants, and nuclear organization. In one and a half days, 22 talks and 56 posters were presented to an audience of 215 participants.     

High-throughput assessment of CpG site methylation for distinguishing between HCV-cirrhosis and HCV-associated hepatocellular carcinoma

Methylation of promoter CpG islands has been associated with gene silencing and demonstrated to lead to chromosomal instability. Therefore, some postulate that aberrantly methylated CpG regions may be important biomarkers indicative of cancer development. In this study we used the Illumina GoldenGate Methylation BeadArray Cancer Panel I for simultaneously profiling methylation of 1,505 CpG sites in order to identify methylation differences in 76 liver tissues ranging from normal to pre-neoplastic and neoplastic states. CpG sites for ESR1, GSTM2, and MME were significantly differentially methylated when comparing the pre-neoplastic tissues from patients with concomitant hepatocellular carcinoma (HCC) to the pre-neoplastic tissues from patients without HCC. When comparing paired HCC tissues to their corresponding pre-neoplastic non-tumorous tissues, eight CpG sites, including one CpG site that was hypermethylated (APC) and seven (NOTCH4, EMR3, HDAC9, DCL1, HLA-DOA, HLA-DPA1, and ERN1) that were hypomethylated in HCC, were identified. Our study demonstrates that high-throughput methylation technologies may be used to identify differentially methylated CpG sites that may prove to be important molecular events involved in carcinogenesis.