Opioids: Pharmacology and Epidemiology

Los opioides desde hace muchos años son los analgésicos más utilizados y efectivos para el tratamiento del dolor. Este trabajo da a conocer la clasificación farmacológica, usos terapéuticos, riesgos a la salud y reacciones adversas de los opioides como fármacos, planteando el paradigma del usar este tipo de fármacos para el control del dolor, sin embargo se han convertido en un problema de salud en distintos países ya que en ciertas circunstancias tienen un alto potencial de causar adicción. Además de su uso contra el dolor, los opioides son utilizados como antidiarreicos, antitusivos y para el tratamiento de diversas sintomatologías. A pesar de los efectos adversos, el mal uso y abuso de los opioides; se consideran imprescindibles en la terapia contra el dolor. Actualmente las investigaciones farmacéuticas trabajan en la búsqueda constante de nuevos fármacos con efectos menos severos y con potencia analgésicaOpioids have been used for many years as the most effective analgesics for pain management. This work discloses the pharmacological classification, therapeutic uses, health risks and adverse reactions of opioids as medicines, setting out the paradigm of using this type of drug to control pain. However, they have become a health problem in distinct countries, as they have a high addictive potential under certain circumstances. In addition to their use against pain, opioids are also employed as antidiarrheal, antitussive and for the treatment of diverse symptomatology. Despite the adverse effects, misuse and abuse of opioids, they are still considered as indispensable in pain therapy. Currently pharmaceutical research is working on the constant development for new drugs with less severe effects and a high analgesic potency

Coordinated Destruction of Cellular Messages in Translation Complexes by the Gammaherpesvirus Host Shutoff Factor and the Mammalian Exonuclease Xrn1

Several viruses encode factors that promote host mRNA degradation to silence gene expression. It is unclear, however, whether cellular mRNA turnover pathways are engaged to assist in this process. In Kaposi's sarcoma-associated herpesvirus this phenotype is enacted by the host shutoff factor SOX. Here we show that SOX-induced mRNA turnover is a two-step process, in which mRNAs are first cleaved internally by SOX itself then degraded by the cellular exonuclease Xrn1. SOX therefore bypasses the regulatory steps of deadenylation and decapping normally required for Xrn1 activation. SOX is likely recruited to translating mRNAs, as it cosediments with translation initiation complexes and depletes polysomes. Cleaved mRNA intermediates accumulate in the 40S fraction, indicating that recognition occurs at an early stage of translation. This is the first example of a viral protein commandeering cellular mRNA turnover pathways to destroy host mRNAs, and suggests that Xrn1 is poised to deplete messages undergoing translation in mammalian cells

Soil Fungal Diversity of the Aguarongo Andean Forest (Ecuador)

Fungi represent an essential component of ecosystems, functioning as decomposers and biotrophs, and they are one of the most diverse groups of Eukarya. In the tropics, many species are unknown. In this work, high-throughput DNA sequencing was used to discover the biodiversity of soil fungi in the Aguarongo forest reserve, one of the richest biodiversity hotspots in Ecuador. The rDNA metabarcoding analysis revealed the presence of seven phyla: Ascomycota, Basidiomycota, Mortierellomycota, Mucoromycota, Glomeromycota, Chytridiomycota, and Monoblepharomycota. A total of 440 identified species were recorded. They mainly belonged to Ascomycota (263) and Basidiomycota (127). In Mortierellomycota, 12 species were recorded, among which Podila verticillata is extremely frequent and represents the dominant species in the entire mycobiota of Aguarongo. The present research provides the first account of the entire soil mycobiota in the Aguarongo forest, where many fungal species exist that have strong application potential in agriculture, bioremediation, chemical, and the food industry. The Aguarongo forest hides a huge number of unknown fungal species that could be assessed, and its protection is of the utmost importance

Host Shutoff Is a Conserved Phenotype of Gammaherpesvirus Infection and Is Orchestrated Exclusively from the Cytoplasm▿

Lytic infection with the two human gammaherpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), leads to significant depletion of the cellular transcriptome. This host shutoff phenotype is driven by the conserved herpesviral alkaline exonuclease, termed SOX in KSHV and BGLF5 in EBV, which in gammaherpesviruses has evolved the genetically separable ability to target cellular mRNA. We now show that host shutoff is also a prominent consequence of murine gammaherpesvirus 68 (MHV68) infection, which is widely used as a model system to study pathogenesis of these viruses in vivo. The effector of MHV68-induced host shutoff is its SOX homolog, here termed muSOX. There is remarkable functional conservation of muSOX host shutoff activities with those of KSHV SOX, including the recently described ability of SOX to induce mRNA hyperadenylation in the nucleus as well as cause nuclear relocalization of the poly(A) binding protein. SOX and muSOX localize to both the nucleus and cytoplasm of infected cells. Using spatially restricted variants of these proteins, we go on to demonstrate that all known host shutoff-related activities of SOX and muSOX are orchestrated exclusively from the cytoplasm. These results have important mechanistic implications for how SOX and muSOX target nascent cellular transcripts in the nucleus. Furthermore, our findings establish MHV68 as a new, genetically tractable model to study host shutoff

The PYHIN Protein p205 Regulates the Inflammasome by Controlling Asc Expression

Members of the IFN-inducible PYHIN protein family, such as absent in melanoma-2 and IFN-γ-inducible protein (IFI)16, bind dsDNA and form caspase-1-activating inflammasomes that are important in immunity to cytosolic bacteria, DNA viruses, or HIV. IFI16 has also been shown to regulate transcription of type I IFNs during HSV infection. The role of other members of the PYHIN protein family in the regulation of immune responses is much less clear. In this study, we identified an immune-regulatory function for a member of the murine PYHIN protein family, p205 (also called Ifi205). Examination of immune responses induced by dsDNA and other microbial ligands in bone marrow-derived macrophages lacking p205 revealed that inflammasome activation by dsDNA, as well as ligands that engage the NLRP3 inflammasome, was severely compromised in these cells. Further analysis revealed that p205-knockdown cells showed reduced expression of apoptosis-associated speck-like molecule containing CARD domain (Asc) at the protein and RNA levels. p205 knockdown resulted in reduced binding of actively transcribing RNA polymerase II to the endogenous Asc gene, resulting in decreased transcription and processing of Asc pre-mRNA. Deletion of p205 in B16 melanoma cells using CRISPR/Cas9 showed a similar loss of Asc expression. Ectopic expression of p205 induced expression of an Asc promoter-luciferase reporter gene. Together, these findings suggest that p205 controls expression of Asc mRNA to regulate inflammasome responses. These findings expand on our understanding of immune-regulatory roles for the PYHIN protein family

A Novel Partial Deletion of Exons 2–10 of the STS Gene in Recessive X-Linked Ichthyosis

X-linked ichthyosis is an inherited disease due to steroid sulfatase deficiency. Onset is at birth or early after birth with dark, regular, and adherent scales of skin. Approximately 85%-90% of X-linked ichthyosis patients have large deletions of the STS gene and flanking sequences. Three patients have been identified with partial deletions of the gene. Two deletions have been found at the 3′ extreme and the other one implicating exons 2–5. This study describes a novel partial deletion of the STS gene in an X-linked ichthyosis patient. The subject was classified through steroid sulfatase assay in leukocytes using 7-[3H]-dehydroepiandrosterone sulfate as a substrate. Exons 1, 2, 5, and 7–10, and 3′ flanking sequences DXS1131, DXS1133, DXS237, DXS1132, DXF22S1, and DXS278 of the STS gene were analyzed through polymerase chain reaction. The DNA analysis showed that exon 1 and 3′ flanking sequences from DXS237 to DXS278 were present. In this study we report the fourth partial deletion of the STS gene and the first spanning exons 2–10 in X-linked ichthyosis patients

Coordinated destruction of cellular messages in translation complexes by the gammaherpesvirus host shutoff factor and the mammalian exonuclease Xrn1.

Several viruses encode factors that promote host mRNA degradation to silence gene expression. It is unclear, however, whether cellular mRNA turnover pathways are engaged to assist in this process. In Kaposi's sarcoma-associated herpesvirus this phenotype is enacted by the host shutoff factor SOX. Here we show that SOX-induced mRNA turnover is a two-step process, in which mRNAs are first cleaved internally by SOX itself then degraded by the cellular exonuclease Xrn1. SOX therefore bypasses the regulatory steps of deadenylation and decapping normally required for Xrn1 activation. SOX is likely recruited to translating mRNAs, as it cosediments with translation initiation complexes and depletes polysomes. Cleaved mRNA intermediates accumulate in the 40S fraction, indicating that recognition occurs at an early stage of translation. This is the first example of a viral protein commandeering cellular mRNA turnover pathways to destroy host mRNAs, and suggests that Xrn1 is poised to deplete messages undergoing translation in mammalian cells

Bosques oligárquicos de Oecopetalum mexicanum enriquecidos con especies nativas de la Sierra de Misantla, México

Abstract The practice of enrichment of managed forests implies the insertion of species with cultural, economic and ecological value. It generally takes place in sites with some degree of anthropic impact, and also applies in sites known as oligarchic forests. They are historically modified and man-managed systems to favor a single species. Examples are the cachichinales woodlands typical of the Sierra de Misantla region, Veracruz, dominated by Oecopetalum mexicanum, a tree of edible seeds. In this study, two planting techniques were tested: translocation and nursery transplantation of three tree species highly valued in the region: Ocotea puberula, Beilschmiedia anay and Pseudolmedia glabrata. We used a paired model (Anova) to evaluate its physiological state, growth and survival. All three species showed marked stress in the early stages of their establishment; a survival rate greater than 50% was recorded after one year, regardless the technique used for either specie. Growth-wise, O. puberula was the most successful; although we found overall high survivals rates in all three species, which lead us to conclude it is feasible to introduce them into cachichinales.Resumen El enriquecimiento de los bosques manejados es una práctica que implica la inserción de especies de valor cultural, económico y ecológico. Son sistemas que han sido históricamente modificados y manejados por el hombre para favorecer una sola especie. Ejemplo de ello son los cachichinales, bosquecillos típicos de la región Sierra de Misantla, en el centro de Veracruz, dominados por Oecopetalum mexicanum, un árbol de semillas comestibles. En este estudio se probaron dos técnicas de plantación para su enriquecimiento: translocación y trasplante de vivero. Se utilizaron tres especies arbóreas altamente valoradas en la región: Ocotea puberula, Beilschmiedia anay y Pseudolmedia glabrata. Para evaluar el estado fisiológico, crecimiento y supervivencia de las plantas se utilizó un análisis de varianza. Las tres especies tuvieron un marcado estrés (estado de la planta) en las primeras etapas de establecimiento. Después de 12 meses se registró una supervivencia mayor a 50%, indistintamente entre las técnicas utilizadas para cada especie. El crecimiento de O. puberula fue mayor (promedio y probabilidad) en el ensayo de translocación, en comparación con las otras especies. Ambas técnicas de siembra tuvieron una alta supervivencia, por lo que es factible utilizarlas indistintamente en proyectos de introducción de especies nativas en bosques enriquecidos

Metabolic Footprints of Burkholderia Sensu Lato Rhizosphere Bacteria Active against Maize Fusarium Pathogens

Consistent with their reported abundance in soils, several Burkholderia sensu lato strains were isolated from the rhizosphere of maize plants cultivated at different sites in central México. Comparative analysis of their 16S rRNA gene sequences permitted their separation into three distinctive clades, which were further subdivided into six other clusters by their close resemblance to (1) Trinickia dinghuensis; (2) Paraburkholderia kirstenboschensis, P. graminis, P. dilworthii and P. rhynchosiae; (3) B. gladioli; (4) B. arboris; (5) B. contaminans, or (6) B. metallica representative species. Direct confrontation assays revealed that these strains inhibited the growth of pathogenic Fusarium oxysporum f. sp. radicis-lycopersici, and F. verticillioides within a roughly 3–55% inhibition range. The use of a DIESI-based non-targeted mass spectroscopy experimental strategy further indicated that this method is an option for rapid determination of the pathogen inhibitory capacity of Burkholderia sensu lato strains based solely on the analysis of their exometabolome. Furthermore, it showed that the highest anti-fungal activity observed in B. contaminans and B. arboris was associated with a distinctive abundance of certain m/z ions, some of which were identified as components of the ornbactin and pyochelin siderophores. These results highlight the chemical diversity of Burkholderia sensu lato bacteria and suggest that their capacity to inhibit the Fusarium-related infection of maize in suppressive soils is associated with siderophore synthesis

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ITESO, A.C