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El presente artículo tuvo como objetivo establecer las capacidades logísticas necesarias para la internacionalización de las pequeñas y medianas empresas (pymes), lo anterior, con el propósito de fortalecer la capacidad competitiva de estas. La metodología empleada fue de tipo cualitativa, centrada en una revisión sistemática (RS); además, se analizaron investigaciones científicas en el período 2011 a 2021. Como fuente de información se utilizaron bases de datos como: Scielo, Dialnet, Redalyc, Google Académico, Web of Science y Scopus. Los resultados de la investigación adelantada permitieron concluir que existen factores de gran relevancia inherentes al desarrollo de capacidades logísticas dentro de la organización como: aprovisionamiento, almacenamiento, distribución, infraestructura, optimización de costes, tecnología e innovación, adaptación al cambio y gestión del riesgo, que fortalecen las habilidades de las Pymes para el logro de objetivos como la expansión comercial, así mismo, la permanente actualización de estas, contribuye a la adopción y diseño de medidas y estrategias corporativas para incrementar la participación en los mercados externos, generando ventajas competitivas para la internacionalización de las Pymes.

El objetivo de la investigación fue describir como interviene el uso de los dispositivos móviles en la comunicación terapéutica enfermera-paciente durante su estancia hospitalaria en un hospital público de tercer nivel de atención en ciudad Obregón, Sonora. Para el análisis del estudio, se utilizaron referencias teóricas sobre la comunicación y la relación terapéutica que establecen teóricas como Peplau y Watson. El abordaje metodológico fue el cualitativo realizando entrevistas a profundidad y realizando el análisis de contenido a través del enfoque del interaccionismo simbólico surgiendo los significados de tres categorías teóricas: Categoría 1.- Comunicación enfermera-paciente, Categoría 2.- Comunicación emocional, y Categoría 3.- Dispositivo móvil y praxis de enfermería.

AMPylation, the post-translational modification with adenosine monophosphate (AMP), is catalyzed by effector proteins from a variety of pathogens. Legionella pneumophila is thus far the only known pathogen that, in addition to encoding an AMPylase (SidM/DrrA), also encodes a deAMPylase, called SidD, that reverses SidM-mediated AMPylation of the vesicle transport GTPase Rab1. DeAMPylation is catalyzed by the N-terminal phosphatase-like domain of SidD. Here, we determined the crystal structure of full length SidD including the uncharacterized C-terminal domain (CTD). A flexible loop rich in aromatic residues within the CTD was required to target SidD to model membranes in vitro and to the Golgi apparatus within mammalian cells. Deletion of the loop (Δloop) or substitution of its aromatic phenylalanine residues rendered SidD cytosolic, showing that the hydrophobic loop is the primary membrane-targeting determinant of SidD. Notably, deletion of the two terminal alpha helices resulted in a CTD variant incapable of discriminating between membranes of different composition. Moreover, a L. pneumophila strain producing SidDΔloop phenocopied a L. pneumophila ΔsidD strain during growth in mouse macrophages and displayed prolonged co-localization of AMPylated Rab1 with LCVs, thus revealing that membrane targeting of SidD via its CTD is a critical prerequisite for its ability to catalyze Rab1 deAMPylation during L. pneumophila infection. ; This work was funded by the Intramural Research Program of the National Institutes of Health, USA (https://irp.nih.gov/) (Project Number: 1ZIAHD008893-07) to M.P.M. This work was also funded by the Spanish Ministry of Economy and Competitiveness (https://www.povertyactionlab.org/partners/government-spain-ministry-economy-industry-and-competition)[BFU2017-88766-R], the Basque Government (http://www.stemcoalition.eu/members/basque-government)[KK-2017/00067; KK- 2018/00050], Fundación BBVA (https://www.fbbva.es/en/) [IN17_BBM_BAS_0054], and the Severo Ochoa Excellence Program (http://www.ciencia.gob.es/portal/site/MICINN/excellentinstitutions)[SEV-2016-0644] to A.H.

The eukaryotic ubiquitylation machinery catalyzes the covalent attachment of the small protein modifier ubiquitin to cellular target proteins in order to alter their fate. Microbial pathogens exploit this post-translational modification process by encoding molecular mimics of E3 ubiquitin ligases, eukaryotic enzymes that catalyze the final step in the ubiquitylation cascade. Here, we show that the Legionella pneumophila effector protein RavN belongs to a growing class of bacterial proteins that mimic host cell E3 ligases to exploit the ubiquitylation pathway. The E3 ligase activity of RavN was located within its N-terminal region and was dependent upon interaction with a defined subset of E2 ubiquitin-conjugating enzymes. The crystal structure of the N-terminal region of RavN revealed a U-box-like motif that was only remotely similar to other U-box domains, indicating that RavN is an E3 ligase relic that has undergone significant evolutionary alteration. Substitution of residues within the predicted E2 binding interface rendered RavN inactive, indicating that, despite significant structural changes, the mode of E2 recognition has remained conserved. Using hidden Markov model-based secondary structure analyses, we identified and experimentally validated four additional L. pneumophila effectors that were not previously recognized to possess E3 ligase activity, including Lpg2452/SdcB, a new paralog of SidC. Our study provides strong evidence that L. pneumophila is dedicating a considerable fraction of its effector arsenal to the manipulation of the host ubiquitylation pathway. ; This work was funded by the Intramural Research Program of the National Institutes of Health (to MPM)(Project Number: 1ZIAHD008893-07) and by the Spanish Ministry of Economy and Competitiveness Grant (to AH)(BFU2014-59759-R) and the Severo Ochoa Excellence Accreditation (to AH)(SEV-2016-0644). This study made use of the Diamond Light Source beamline I04 (Oxfordshire, UK) and ALBA synchrotron beamline BL13-XALOC, funded in part by the Horizon 2020 programme of the European Union, iNEXT (H2020 Grant # 653706).

The eukaryotic ubiquitylation machinery catalyzes the covalent attachment of the small protein modifier ubiquitin to cellular target proteins in order to alter their fate. Microbial pathogens exploit this post-translational modification process by encoding molecular mimics of E3 ubiquitin ligases, eukaryotic enzymes that catalyze the final step in the ubiquitylation cascade. Here, we show that the Legionella pneumophila effector protein RavN belongs to a growing class of bacterial proteins that mimic host cell E3 ligases to exploit the ubiquitylation pathway. The E3 ligase activity of RavN was located within its N-terminal region and was dependent upon interaction with a defined subset of E2 ubiquitin-conjugating enzymes. The crystal structure of the N-terminal region of RavN revealed a U-box-like motif that was only remotely similar to other U-box domains, indicating that RavN is an E3 ligase relic that has undergone significant evolutionary alteration. Substitution of residues within the predicted E2 binding interface rendered RavN inactive, indicating that, despite significant structural changes, the mode of E2 recognition has remained conserved. Using hidden Markov model-based secondary structure analyses, we identified and experimentally validated four additional L. pneumophila effectors that were not previously recognized to possess E3 ligase activity, including Lpg2452/SdcB, a new paralog of SidC. Our study provides strong evidence that L. pneumophila is dedicating a considerable fraction of its effector arsenal to the manipulation of the host ubiquitylation pathway. ; Funding: This work was funded by the Intramural Research Program of the National Institutes of Health (to MPM)(Project Number: 1ZIAHD008893-07) and by the Spanish Ministry of Economy and Competitiveness Grant (to AH)(BFU2014-59759-R) and the Severo Ochoa Excellence Accreditation (to AH)(SEV-2016-0644). This study made use of the Diamond Light Source beamline I04 (Oxfordshire, UK) and ALBA synchrotron beamline BL13-XALOC, funded in part by the Horizon 2020 programme of the European Union, iNEXT (H2020 Grant # 653706). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Microbial pathogens employ sophisticated virulence strategies to cause infections in humans. The intracellular pathogen Legionella pneumophila encodes RidL to hijack the host scaffold protein VPS29, a component of retromer and retriever complexes critical for endosomal cargo recycling. Here, we determined the crystal structure of L. pneumophila RidL in complex with the human VPS29?VPS35 retromer subcomplex. A hairpin loop protruding from RidL inserts into a conserved pocket on VPS29 that is also used by cellular ligands, such as Tre-2/Bub2/Cdc16 domain family member 5 (TBC1D5) and VPS9-ankyrin repeat protein for VPS29 binding. Consistent with the idea of molecular mimicry in protein interactions, RidL outcompeted TBC1D5 for binding to VPS29. Furthermore, the interaction of RidL with retromer did not interfere with retromer dimerization but was essential for association of RidL with retromer-coated vacuolar and tubular endosomes. Our work thus provides structural and mechanistic evidence into how RidL is targeted to endosomal membranes. ; ACKNOWLEDGMENTS: We thank Ander Vidaurrazaga (Centro de Investigación Cooperativa en Biociencias) for technical assistance and Devanand Bondage (National Institute of Child Health and Human Development) for proliferation assays of Legionella pneumophila. This study made use of the Diamond Light Source (Oxfordshire, United Kingdom), the European Synchrotron Radiation Facility (Grenoble, France), and the ALBA synchrotron beamline BL13-XALOC, funded in part by the Horizon 2020 programme of the European Union, iNEXT (H2020 Grant 653706). We thank all the staff from these facilities for technical and human support. This work was supported by the Spanish Ministry of Economy and Competitiveness Grant BFU2014-59759-R (to A.H.); the Severo Ochoa Excellence Accreditation SEV-2016-0644; and the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human development (Projects ZIA HD001607 and ZIA HD008893). M.R.-M. is supported by a pre-doctoral fellowship from the Basque Government (PRE_2016_2_0249).

Salp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in the inhibition of early signaling events and the production of the autocrine growth factor, interleukin-2. The fate of the CD4 T cells activated in the presence of Salp15 or its long-term effects are, however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished cross-antigenic antibody production even after interruption of the treatment with the protein. Transcriptionally, the salivary protein provokes an acute effect that includes known activation markers, such as Il2 or Cd44, and that fades over time. The long-term effects exerted by Salp15 do not involve the induction of either anergy traits nor increased populations of regulatory T cells. Similarly, the treatment with Salp15 does not result in B cell anergy or the generation of myeloid suppressor cells. However, Salp15 induces the increased expression of the ectoenzyme, CD73, in regulatory T cells and increased production of adenosine. Our study provides a profound characterization of the immunomodulatory activity of Salp15 and suggests that its long-term effects are due to the specific regulation of CD73. Introduction ; Supported by grants from the Department of Education of the Basque Government (PI2013-49 to JA and PI2012-42 to RB). JA is funded by the European Union (Grant Agreement number 602272). AMA and JLL's work was supported by the Basque Department of Industry, Tourism and Trade (Etortek and Elkartek Programs), the Innovation Technology Department of Bizkaia and the CIBERehd Network. The work of AC is supported by a Ramón y Cajal award, the Basque Department of Industry, Tourism and Trade (Etortek), ISCIII (PI13/00031), FERO VIII Fellowship, the BBVA foundation, MINECO (SAF2016-79381-R) and the European Research Council Starting Grant (336343). CIBERonc was co-funded with FEDER funds. AC-M was funded by a Juan de la Cierva program award and the European Union MSCA program (CIG 660191). RB was funded by MINECO grants BFU2011-25986 and BFU2014-52282-P and the Consolider Program (BFU2014-57703-REDC). FJB was funded by a MINECO grant (CTQ2014-56966-R). D.B. is funded by a MINECO FPI fellowship. We thank the MINECO for the Severo Ochoa Excellence accreditation (SEV-2016-0644). ; Peer reviewed