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The underlying mechanisms of appendage regeneration remain largely unknown and uncovering these mechanisms in capable organisms has far-reaching implications for potential treatments in humans. Recent studies implicate a requirement for metabolic reprogramming reminiscent of the Warburg effect during successful appendage and organ regeneration. As changes are thus predicted to be highly dynamic, methods permitting direct, real-time visualization of metabolites at the tissue and organismal level, would offer a significant advance in defining the influence of metabolism on regeneration and healing. We sought to examine whether glycolytic activity was altered during larval fin regeneration, utilising the genetically encoded biosensor, Laconic, enabling the spatiotemporal assessment of lactate levels in living zebrafish. We present evidence for a rapid increase in lactate levels within minutes following injury, with a role of aerobic glycolysis in actomyosin contraction and wound closure. We also find a second wave of lactate production, associated with overall larval tail regeneration. Chemical inhibition of glycolysis attenuates both contraction of the wound and regrowth of tissue following tail amputation, suggesting aerobic glycolysis is necessary at two distinct stages of regeneration.

The development of paired appendages was a key innovation during evolution and facilitated the aquatic to terrestrial transition of vertebrates. Largely derived from the lateral plate mesoderm (LPM), one hypothesis for the evolution of paired fins invokes derivation from unpaired median fins via a pair of lateral fin folds located between pectoral and pelvic fin territories1. Whilst unpaired and paired fins exhibit similar structural and molecular characteristics, no definitive evidence exists for paired lateral fin folds in larvae or adults of any extant or extinct species. As unpaired fin core components are regarded as exclusively derived from paraxial mesoderm, any transition presumes both co-option of a fin developmental programme to the LPM and bilateral duplication2. Here, we identify that the larval zebrafish unpaired pre-anal fin fold (PAFF) is derived from the LPM and thus may represent a developmental intermediate between median and paired fins. We trace the contribution of LPM to the PAFF in both cyclostomes and gnathostomes, supporting the notion that this is an ancient trait of vertebrates. Finally, we observe that the PAFF can be bifurcated by increasing bone morphogenetic protein signalling, generating LPM-derived paired fin folds. Our work provides evidence that lateral fin folds may have existed as embryonic anlage for elaboration to paired fins. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Published version This work was funded by the Industry Aligned Fund (IAF) Agency for Science, Technology and Research (grant to T.J.C. and K.-W.T.); Ministry of Education (MoE) Tier 3 (grant 2016-T3-1-005 to T.J.C., C.W. and H.M.); Ministry of Education (MoE) Tier 1 (grant 2016-T1-001-055 to T.J.C. and C.Z.); Ministry of Education (MoE) Tier 2 (grant MOE-T2EP30221-0008 to C.W.); the Company of Biologists (travelling fellowship to M.J.T.); the National Science Foundation (grants IOS-1853949 to M.C.D. and 2203311 to C.M.); the Swiss National Science Foundation Sinergia (grant CRSII5_180345 to C.M.); the Swiss Bridge Foundation (C.M.); Additional Ventures Single Ventricle Research Fund (SVRF) (grant 1048003 to C.M.); the University of Colorado School of Medicine Anschutz Medical Campus and the Children’s Hospital Colorado Foundation (C.M.); the National Institutes of Health (NIH), National Institute of General Medical Sciences (grants 1T32GM141742-01 to H.R.M. and 3T32GM121742-02S1 to H.R.M.); Australian Research Council (discovery grant DP200103219 to F.J.T. and P.D.C); National Health and Medical Research Council (senior principal research fellow APP1136567 to P.D.C.); and the NIH (grant R35NS111564 to J.S. and M.E.B.).

Mesenchymal stem cells (MSCs) are multipotent adult stem cells with great potential in regenerative medicine. One method for stimulating proliferation and differentiation of MSCs is via electrical stimulation (ES). A valuable approach for evaluating the response of MSCs to ES is to assess changes in gene expression, relative to one or more reference genes. In a survey of 25 publications that used ES on cells, 70% selected GAPDH as the reference gene. We conducted a study to assess the suitability of six potential reference genes on an immortalized human MSC line following direct current ES at seeding densities of 5000 and 10,000 cells/cm2 . We employed three methods to validate the most stable reference genes from qRT-PCR data. Our findings show that GAPDH and ACTB exhibit reduced stability when seeded at 5000 cell/cm2 . In contrast, we found that the most stable genes across both plating densities and stimulation regimes were PPIA and YWHAZ. Thus, in ES gene expression studies in MSCs, we support the use of PPIA and YWHAZ as an optimal reference gene pair, and discourage the use of ACTB and GAPDH at lower seeding densities. However, it is strongly recommended that similar verification studies are carried out based on cell type and different ES conditions.

Biological systems achieve precise control over ambient fluids through the self-organization of active protein structures including flagella, cilia, and cytoskeletal networks. In active structures individual proteins consume chemical energy to generate force and motion at molecular length scales. Self-organization of protein components enables the control and modulation of fluid flow fields on micron scales. The physical principles underlying the organization and control of active-matter driven fluid flows are poorly understood. Here, we apply an optically-controlled active-matter system composed of microtubule filaments and light-switchable kinesin motor proteins to analyze the emergence of persistent flow fields in a model active matter system. Using light, we form contractile microtubule networks of varying shape. We analyze the fluid flow fields generated by a wide range of microtubule network geometries and explain the resulting flow fields within a unified theoretical framework. We specifically demonstrate that the geometry of microtubule flux at the boundary of contracting microtubule networks predicts the steady-state fluid flow fields across polygonal network geometries through finite-element simulations. Our work provides a foundation for programming microscopic fluid-flows with controllable active matter and could enable the engineering of versatile and dynamic microfluidic devices.

Sustained elevated levels of reactive oxygen species (ROS) have been shown to be essential for whole body, appendage and organ regeneration in various organisms, including planarians, Hydra, zebrafish, axolotl, Xenopus, geckos and mice. In the majority of cases these roles have been shown via the use of NADPH oxidase pharmacological inhibitors, which generally target all NAPDH oxidases (NOXes). To identify the specific NOX or NOXes essential for ROS production during adult fin regeneration in zebrafish, we generated nox mutants for duox, nox5 and cyba (a key subunit of NOXes 1-4). We also crossed these mutant lines to a transgenic line ubiquitously expressing HyPer, which permits the measurement of ROS levels in adult zebrafish fins. Using this approach, we found that homozygous duox mutants have significantly attenuated ROS levels following fin amputation, and this correlated with a significantly diminished rate of fin regeneration. While the other nox homozygous mutants (nox5 and cyba) showed less of an effect on ROS levels or adult fin regeneration, duox/cyba double mutants showed a more diminished rate of fin regeneration than duox mutants alone, suggesting that Nox1-4 do play a role during regeneration, but one that is secondary to that of Duox. This work also serendipitously found that ROS levels in amputated adult zebrafish fins oscillate during the day with a circadian rhythm.

Introduction: Migraine is a polygenic multifactorial disorder with a neuronal initiation of a cascade of neurochemical processes leading to incapacitating headaches. Headaches are generally unilateral, throbbing, 4–72 h in duration, and associated with nausea, vomiting, photophobia, and sonophobia. Chronic migraine (CM) is the presence of a headache at least 15 days per month for ≥3 months and has a high global impact on health and economy, and therapeutic guidelines are lacking. Methods: Using the Grading of Recommendations, Assessment, Development, and Evaluations system, we conducted a search in MEDLINE and Cochrane to investigate the current evidence and generate recommendations of clinical practice on the identification of risk factors and treatment of CM in adults. Results: We recommend avoiding overmedication of non-steroidal anti-inflammatory drugs (NSAIDs); ergotamine; caffeine; opioids; barbiturates; and initiating individualized prophylactic treatment with topiramate eptinezumab, galcanezumab, erenumab, fremanezumab, or botulinum toxin. We highlight the necessity of managing comorbidities initially. In the acute management, we recommend NSAIDs, triptans, lasmiditan, and gepants alone or with metoclopramide if nausea or vomiting. Non-pharmacological measures include neurostimulation. Conclusions: We have identified the risk factors and treatments available for the management of CM based on a grading system, which facilitates selection for individualized management.

Epithelial tissues are primed to respond to insults by activating epithelial cell motility and rapid inflammation. Such responses are also elicited upon overexpression of the membrane-bound protease, Matriptase, or mutation of its inhibitor, Hai1. Unrestricted Matriptase activity also predisposes to carcinoma. How Matriptase leads to these cellular outcomes is unknown. We demonstrate that zebrafish hai1a mutants show increased H2O2, NfκB signalling, and IP3R -mediated calcium flashes, and that these promote inflammation, but do not generate epithelial cell motility. In contrast, inhibition of the Gq subunit in hai1a mutants rescues both the inflammation and epithelial phenotypes, with the latter recapitulated by the DAG analogue, PMA. We demonstrate that hai1a has elevated MAPK pathway activity, inhibition of which rescues the epidermal defects. Finally, we identify RSK kinases as MAPK targets disrupting adherens junctions in hai1a mutants. Our work maps novel signalling cascades mediating the potent effects of Matriptase on epithelia, with implications for tissue damage response and carcinoma progression., eLife digest Cancer occurs when normal processes in the cell become corrupted or unregulated. Many proteins can contribute, including one enzyme called Matriptase that cuts other proteins at specific sites. Matriptase activity is tightly controlled by a protein called Hai1. In mice and zebrafish, when Hai1 cannot adequately control Matriptase activity, invasive cancers with severe inflammation develop. However, it is unclear how unregulated Matriptase leads to both inflammation and cancer invasion. One outcome of Matriptase activity is removal of proteins called Cadherins from the cell surface. These proteins have a role in cell adhesion: they act like glue to stick cells together. Without them, cells can dissociate from a tissue and move away, a critical step in cancer cells invading other organs. However, it is unknown exactly how Matriptase triggers the removal of Cadherins from the cell surface to promote invasion. Previous work has shown that Matriptase switches on a receptor called Proteinase-activated receptor 2, or Par2 for short, which is known to activate many enzymes, including one called phospholipase C. When activated, this enzyme releases two signals into the cell: a sugar called inositol triphosphate, IP3; and a lipid or fat called diacylglycerol, DAG. It is possible that these two signals have a role to play in how Matriptase removes Cadherins from the cell surface. To find out, Ma et al. mapped the effects of Matriptase in zebrafish lacking the Hai1 protein. This revealed that Matriptase increases IP3 and DAG levels, which initiate both inflammation and invasion. IP3 promotes inflammation by switching on pro-inflammatory signals inside the cell such as the chemical hydrogen peroxide. At the same time, DAG promotes cell invasion by activating a well-known cancer signalling pathway called MAPK. This pathway activates a protein called RSK. Ma et al. show that this protein is required to remove Cadherins from the surface of cells, thus connecting Matriptase’s activation of phospholipase C with its role in disrupting cell adhesion. An increase in the ratio of Matriptase to HAI-1 (the human equivalent of Hai1) is present in many cancers. For this reason, the signal cascades described by Ma et al. may be of interest in developing treatments for these cancers. Understanding how these signals work together could lead to more direct targeted anti-cancer approaches in the future.

The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds pro-vide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac4GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac4GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole or-ganisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems.

Contains fulltext : 235683.pdf (Publisher’s version ) (Open Access) The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds provide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac(4)GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac(4)GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole organisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems.

The underlying mechanisms of appendage regeneration remain largely unknown, and uncovering these mechanisms in capable organisms have far-reaching implications for potential treatments in humans. Recent studies implicate a requirement for metabolic reprogramming reminiscent of the Warburg effect during successful appendage and organ regeneration. Changes are thus predicted to be highly dynamic, methods permitting direct visualization of metabolites at the tissue and organismal level, in real time, would offer a significant advance in defining the influence of metabolism on regeneration and healing. We sought to examine whether glycolytic activity was altered during larval fin regeneration, utilising the genetically encoded biosensor, Laconic, enabling the spatiotemporal assessment of lactate levels in living zebrafish. We present evidence for a rapid increase in lactate levels within minutes following injury, with a role of aerobic glycolysis in actomyosin contraction and wound closure. We also find a second wave of lactate production, associated with overall larval tail regeneration. Chemical inhibition of glycolysis attenuates both contraction of the wound and regrowth of tissue following tail amputation, suggesting aerobic glycolysis is necessary at two distinct stages of regeneration. SUMMARY STATEMENT By combining a genetically encoded lactate FRET sensor with chemical inhibitors, we demonstrate a critical role for the Warburg effect and metabolic reprogramming during zebrafish wound closure and tail regeneration.

Tissues respond to damage by increasing inflammation and epithelial cell motility. How damage detection and responses are orchestrated is unclear. Overexpression of the membrane bound protease, Matriptase, or mutation of its inhibitor, Hai1, results in inflamed epithelia, in which cells have increased motility and are prone to carcinoma. How Matriptase leads to these cellular outcomes is unknown. We demonstrate that zebrafishhai1amutants show increased H2O2, NfκB signalling, and IP3R-mediated calcium flashes, and that these promote inflammation, but do not generate epithelial cell motility. In contrast, inhibition of the Gq subunit rescues both thehai1ainflammation and epithelial phenotypes, with the latter recapitulated by the DAG analogue, PMA. We demonstrate thathai1ahas elevated pERK, inhibition of which rescues the epidermal defects. Finally, we identify RSK kinases as pERK targets disrupting adherens junctions inhai1amutants. Our work maps novel signalling cascades mediating the potent effects of Matriptase on epithelia, with implications for tissue damage response and carcinoma progression.

In humans, myocardial infarction (MI) is associated with irreversible damage to heart tissue, resulting in increased morbidity and mortality in patients. By comparison, the zebrafish (Danio rerio) is capable of repairing damaged and injured hearts by activating a full regenerative response. By studying model organisms that can regenerate loss heart tissue following injury, such as the zebrafish, a greater insight will be gained into the molecular pathways that can induce and sustain a regenerative response following injury. There is hope that such information may lead to new treatments or therapies aimed at stimulating a better regenerative response in humans that have suffered heart attacks. Recent findings in zebrafish have highlighted an important role for sustained elevated levels of Reactive Oxygen Species (ROS), including hydrogen peroxide (H2O2) in the promotion of a regenerative response. Given that elevated levels of H2O2 can be harmful, simply elevating ROS levels directly may not be easy or practical to translate clinically. An alternative approach would be to identify the critical downstream targets of ROS in the promotion of heart regeneration, and then target these clinically using drugs. One such family of potential downstream targets of ROS during heart regeneration are the family of protein tyrosine phosphatases (PTPs), which are known to be exquisitely sensitive to redox regulation and whose inhibition have been linked to the promotion of heart regeneration in zebrafish. In this review, we present an overview of the zebrafish as a model organism for studying cardiac regeneration, including the molecular mechanisms by which cardiac regeneration occurs in response to injury. We then present recent findings linking elevated ROS levels to heart regeneration and their potential downstream targets, the PTPs, including protein tyrosine phosphatase 1B (PTP1B) and the dual specificity phosphatase 6 (DUSP6) in the promotion of heart regeneration.

Historically, in the city of Tunja there has been a phenomenon of occupation of the natural channels of rainwater, altering the hydrology of the natural basins. Currently, the city is experiencing considerable and accelerated urban development towards the Northeast, which has resulted in overflows in the drainage system and floods that have affected residents. The current drainage system is not capable of registering the flow of water that leaves the urban sector due to a lack of instrumentation. In this study, precipitation and water flow equipment was installed in the northeastern district of the city, also known as Barrio Santa Ines. The basin was separated into 56 different sub-basins with physical and drainage parameters calculated for each sub-basin. The associated parameters were calibrated to the initial hydrological losses and roughness. A validated and calibrated urban drainage model was created in the program SWMM 5.1, allowing for the temporal hydrodynamic modelling of the system to be obtained. The model reproduces the real evolution of the system and was used in order to make predictions according to a maximum precipitation design event. This model resulted in the detection of two areas that are vulnerable to flooding. The identification of different sub-basins and the desegregation of the hydrodynamic model resulted in a reduction in the uncertainty of the evolution of water flow in the system.

In

To determine the association of Borrelia burgdorferi infection with Alzheimer’s disease or mild cognitive impairment (MCI) in older adults. Case–control study. Patients older than 60 years, both sexes, were included. Three groups were created: with probable Alzheimer’s disease cases with NINCDS–ADRDA criteria, MCI cases in those not meeting NINCDS–ADRDA criteria for dementia, but who had an abnormal cognitive evaluation and independence in instrumental activities of daily living (IADL), cognitively healthy controls were diagnosed with normal cognitive evaluation and independence in IADL were identified in the community. Western blot IgG against B. burgdorferi in serum was done in all the participants. Non-conditional logistic regression was applied to estimate the association of Alzheimer’s disease or MCI and seropositive to B. burgdorferi. Thirty-eight patients with Alzheimer’s disease, mean age of 75.6 ± 3.4 years, 69% were females, education 8.3 ± 4.8 years. 39 patients with MCI, mean age of 72.2 ± 6.8 years, 85% were females, education 11.2 ± 4.2 years. A total of 11/38 (29%) were positive to B. burgdorferi with Alzheimer’s disease, 9/39 (23%) with MCI, and 11/108 (10%) of controls. In patients with Alzheimer’s disease, an adjusted odds ratio (aOR) = 3.65 (95% CI 1.2–11.1) adjusted for education and a history of cerebrovascular disease (CVD) was estimated, and in patients with MCI an aOR = 3.2 (95% CI 1.1–9.1) for a history of diabetes mellitus and CVD was estimated. In our study, there was an increased risk of Alzheimer’s disease and MCI in seropositive IgG patients to B. burgdorferi. Establish if Borrelia burgdorferi infection is associated with Alzheimer's disease and/or mild cognitive impairment (MCI) in older adults. In patients with Borrelia burgdorferi infection and Alzheimer's disease, an adjusted Odds Ratio (AOR) = 3.65 (95% CI = 1.2−11.1) was estimated, which was similar to that of patients with Borrelia burgdorferi infection and MCI with an AOR = 3.2 (95% CI = 1.1−9.1). In our study, there was an increased risk of Alzheimer's disease and MCI in seropositive IgG patients to B. burgdorferi.

Understanding how to promote organ and appendage regeneration is a key goal of regenerative medicine. The frog

Understanding how to promote organ and appendage regeneration is a key goal of regenerative medicine. The frog, Xenopus, can achieve both scar-free healing and tissue regeneration during its larval stages, although it predominantly loses these abilities during metamorphosis and adulthood. This transient regenerative capacity, alongside their close evolutionary relationship with humans, makes Xenopus an attractive model to uncover the mechanisms underlying functional regeneration. Here, we present an overview of Xenopus as a key model organism for regeneration research and highlight how studies of Xenopus have led to new insights into the mechanisms governing regeneration.

Summary While it is appreciated that reactive oxygen species (ROS) can act as second messengers in both homeostastic and stress response signaling pathways, potential roles for ROS during early vertebrate development have remained largely unexplored. Here, we show that fertilization in Xenopus embryos triggers a rapid increase in ROS levels, which oscillate with each cell division. Furthermore, we show that the fertilization-induced Ca2+ wave is necessary and sufficient to induce ROS production in activated or fertilized eggs. Using chemical inhibitors, we identified mitochondria as the major source of fertilization-induced ROS production. Inhibition of mitochondrial ROS production in early embryos results in cell-cycle arrest, in part, via ROS-dependent regulation of Cdc25C activity. This study reveals a role for oscillating ROS levels in early cell cycle regulation in Xenopus embryos., Graphical Abstract, Highlights • ROS, including hydrogen peroxide, are produced after fertilization in Xenopus • Ca2+ signaling after fertilization induces ROS production in mitochondria • Mitochondria are the major source of oscillating ROS levels • ROS regulate Cdc25C activity and the early cell cycle, Han et al. show that the fertilization-triggered calcium wave induces reactive oxygen species production from mitochondria, which oscillate with each cell division in Xenopus embryos. Moreover, they demonstrate that inhibition of mitochondrial ROS production disrupts cell cycle progression.

The significant role of the immune system in cancer treatment has given rise to an emerging field of study within oncology, and one that is attracting increasing attention from researchers. Immunotherapy has demonstrated that the immune system is crucial in the fight against cancer. This challenge has led researchers to analyze whether the immune influencing capacity of immunonutrition may aid in improving immune status, modulate the acquired immune response, decrease the treatment toxicity and improve patient outcomes. Immunonutrition, new developed formulas has been demonstrated to improve outcome in surgical patients. This improvement is related to the modulation of the inflammatory response in the peri-operative period. The aim of this review is to analyze current evidence on the benefit of immunonutrition in patients undergoing pro-inflammatory processes in cancer, such as receiving chemotherapy or radiation treatment. With this aim, authors have analyzed the problem studying different aspects: the role of the immune system in cancer treatment, current evidence regarding immunonutrition in perioperative period, current evidence regarding immunonutrition in cancer patients and the relation between immunity and radiotherapy. The conclusions of this review confirm that immunonutrition formulas could modulate inflammatory and immune response in cancer patients. This effect decreases acute toxicity, although the pathways and the measure of this immune response are unclear. Immunonutrition is an emerging field in oncology, and further research is needed.

El objetivo de este trabajo es acercarse a las vías de “retiro” de pandilleros en el país, a fin de mostrar el panorama general de las opciones existentes y describir sus características esenciales. La metodología se basa en la aplicación de dos técnicas de investigación: la revisión documental y las entrevistas en profundidad. Se exponen categorías de análisis importantes con respecto a los expandilleros, como por ejemplo las de “calmado”, “retirado” y “peseta”, cada una de las cuales plantea escenarios y prospectivas diferentes. Además, se explora el papel del Gobierno, el rol de la sociedad civil (incluyendo las iglesias católica y evangélica; en especial, las pentecostales), la participación del sector privado y ciertos mecanismos de las pandillas mismas. En definitiva, a todo el estudio le subyace una reflexión de carácter “identitario”, por cuanto concierne a la construcción, deconstrucción y eventual reconstrucción de la identidad, a nivel personal y grupal, de los miembros y exmiembros de maras o pandillas.

El presente libro es resultado del proyecto de investigacion denominado “Las relaciones y fenomenos del redimensionamiento de las FARC y su posicionamiento estrategico en la Comunidad Internacional”, del grupo de investigacion “Masa Critica” de la Escuela Superior de Guerra “General Rafael Reyes Prieto”. En este documento se desarrolla un analisis amplio sobre los aspectos estrategicos de la transicion politico-militar que se ha implementado en Colombia. Este proceso involucra a la guerrilla mas antigua del mundo, y del contexto colombiano, en el paso de la vida armada a la vida politica. En una primera instancia, se analiza el inicio y nacimiento de la FARC como guerrilla y su paso historico de adaptacion a las circunstancias nacionales e internacionales, con el fin de mantenerse en el escenario politico-militar como un movimiento armado para alcanzar el Poder. En segunda instancia, se analiza el cambio de la estrategia de este grupo armado en cuanto al aspecto militar y las capacidades politicas que iba implementando en su objetivo, desde el proceso de la gestacion de la Union Patriotica y su fortalecimiento militar; el nuevo contexto de adaptacion por la caida y desaparicion de la Union Sovietica y la complejidad del Sistema Internacional a partir de la decada 1990. En tercera instancia, el analisis continua en el marco de tiempo comprendido entre el 2002 y el 2016, periodo enmarcado en el proceso de aumento del conflicto armado abierto y la implementacion de la politica de “Seguridad Democratica” del presidente Alvaro Uribe Velez, catalogando a las FARC como un grupo terrorista y, de paso, se logra el debilitamiento militar del grupo armado y el escenario perfecto para las negociaciones de paz en La Habana, liderados por el senor presidente Juan Manuel Santos Calderon. Al finalizar el analisis, se centra en las estrategias de las FARC en el marco de movimiento politico civil y el animo de propagacion de sus ideales y mensajes politicos.

Thyroid dyshormonogenesis is a leading cause of congenital hypothyroidism, a highly prevalent but treatable condition. Thyroid hormone (TH) synthesis is dependent on the formation of reactive oxygen species (ROS). In humans, the primary sources for ROS production during thyroid hormone synthesis are the NADPH oxidases DUOX1 and DUOX2. Indeed, mutations in DUOX1 and DUOX2 have been linked with congenital hypothyroidism. Unlike humans, zebrafish has a single orthologue for DUOX1 and DUOX2. In this study, we investigated the phenotypes associated with two nonsense mutant alleles, sa9892 and sa13017, of the single duox gene in zebrafish. Both alleles gave rise to readily observable phenotypes reminiscent of congenital hypothyroidism, from the larval stages through to adulthood. By using various methods to examine external and internal phenotypes, we discovered a strong correlation between TH synthesis and duox function, beginning from an early larval stage, when T4 levels are already noticeably absent in the mutants. Loss of T4 production resulted in growth retardation, pigmentation defects, ragged fins, thyroid hyperplasia/external goiter and infertility. Remarkably, all of these defects associated with chronic congenital hypothyroidism could be rescued with T4 treatment, even when initiated when the fish had already reached adulthood. Our work suggests that these zebrafish duox mutants may provide a powerful model to understand the aetiology of untreated and treated congenital hypothyroidism even in advanced stages of development. This article has an associated First Person interview with the first author of the paper., Summary: Zebrafish harbouring two loss-of-function alleles of the single duox gene exhibit various adult phenotypes reminiscent of human congenital hypothyroidism.

Este artículo constituye un modesto aporte al décimo número de la revista “Policía y Seguridad Pública”, y tiene como objetivo general hacer un breve análisis, muy preliminar y genérico, del estado actual del clima organizacional en la PNC a partir de dos momentos elementales de referencia: su fundación y su situación presente.La metodología empleada incluyó la aplicación de las técnicas de revisión documental, entrevistas en profundidad y encuesta. Casi la totalidad de los datos analizados fueron recabados en un acotado período de tiempo; y, asimismo, el conjunto de informantes que se consultaron estuvo delimitado por un cierto perfil preestablecido. Por ello, los hallazgos y los resultados globales deben ser adecuadamente localizados, dimensionados y tomados con cautela, así como las conclusiones y las recomendaciones que se derivan de aquéllos.

Survival of any living organism critically depends on its ability to repair and regenerate damaged tissues and/or organs during its lifetime following injury, disease, or aging. Various animal models from invertebrates to vertebrates have been used to investigate the molecular and cellular mechanisms of wound healing and tissue regeneration. It is hoped that such studies will form the framework for identifying novel clinical treatments that will improve the healing and regenerative capacity of humans. Amongst these models, Xenopus stands out as a particularly versatile and powerful system. This review summarizes recent findings using this model, which have provided fundamental knowledge of the mechanisms responsible for efficient and perfect tissue repair and regeneration.

Thyroid dyshormonogenesis is a leading cause of congenital hypothyroidism, a highly prevalent but treatable condition. Thyroid hormone synthesis is dependent on the formation of reactive oxygen species (ROS). In humans, the primary sources for ROS production during thyroid hormone synthesis are the NADPH oxidase, DUOX1 and DUOX2. Indeed mutations inDUOX1andDUOX2have been linked with congenital hypothyroidism. Unlike humans, zebrafish has a single orthologue forDUOX1andDUOX2. In this study, we investigated the phenotypes associated with two nonsense mutant alleles of the singleduoxgene in zebrafish,sa9892andsa13017. Both alleles gave rise to readily observable phenotypes reminiscent of congenital hypothyroidism, from the larval stages through to adulthood. By using various methods to examine the external and internal phenotypes, we discovered a strong correlation between TH synthesis andduoxfunction, beginning from the early larval stage, when T4levels are already noticeably absent in the mutants. Loss of T4production resulted in growth retardation, pigmentation defects, ragged fins, thyroid hyperplasia / external goiter, and infertility. Remarkably all of these defects associated with chronic congenital hypothyroidism could be rescued with T4treatment, even when initiated when the fish had already reached adulthood. Our work suggests that these zebrafishduoxmutants may provide a powerful model to understand the aetiology of untreated and treated congenital hypothyroidism even in advance stages of development.

To determine the association of Borrelia burgdorferi infection with Alzheimer's disease or mild cognitive impairment (MCI) in older adults.Case-control study. Patients older than 60 years, both sexes, were included. Three groups were created: with probable Alzheimer's disease cases with NINCDS-ADRDA criteria, MCI cases in those not meeting NINCDS-ADRDA criteria for dementia, but who had an abnormal cognitive evaluation and independence in instrumental activities of daily living (IADL), cognitively healthy controls were diagnosed with normal cognitive evaluation and independence in IADL were identified in the community. Western blot IgG against B. burgdorferi in serum was done in all the participants. Non-conditional logistic regression was applied to estimate the association of Alzheimer's disease or MCI and seropositive to B. burgdorferi.Thirty-eight patients with Alzheimer's disease, mean age of 75.6 ± 3.4 years, 69% were females, education 8.3 ± 4.8 years. 39 patients with MCI, mean age of 72.2 ± 6.8 years, 85% were females, education 11.2 ± 4.2 years. A total of 11/38 (29%) were positive to B. burgdorferi with Alzheimer's disease, 9/39 (23%) with MCI, and 11/108 (10%) of controls. In patients with Alzheimer's disease, an adjusted odds ratio (aOR) = 3.65 (95% CI 1.2-11.1) adjusted for education and a history of cerebrovascular disease (CVD) was estimated, and in patients with MCI an aOR = 3.2 (95% CI 1.1-9.1) for a history of diabetes mellitus and CVD was estimated.In our study, there was an increased risk of Alzheimer's disease and MCI in seropositive IgG patients to B. burgdorferi.

The African clawed frog

Guillain-Barré Syndrome (GBS) is an acute polyneuropathy characterized by symmetrical weakness of the limbs with hyporeflexia or areflexia with a maximum progression within four weeks and can impair respiratory function and implies disability at a long. The aim of this paper was to describe the clinical, epidemiological and neurophysiological features of patients with GBS at the Hospital de Especialidades del Centro Medico Nacional Siglo XXI (HECMNSXXI)An observational, retrospective cross-sectional study, data were collected form clinical records of adults with GBS hospitalized in HECMNSXXI from March 2012 to March 2016. The recorded variables were demographics, previous infection, clinical presentation, disability scores, prognosis scores and neurophysiological subtypes.Clinical records of 94 patients were analysed with a mean age of 53 years, 61% male, with previous infection in 80%. Albumin cytologic dissociation was present in 50%. Medical Research Council (MRC) sum scores mean was 32, the SGB disability score at admittance with a mean of 3.63. The axonal subtype was in 68%, and demyelinating in 29%, not conclusive in 3%.In this study the demographic and clinical features are similar to other previous reports, we documented a greater proportion of axonal subtype, which are related with important disability and worse prognosis.El síndrome de Guillain-Barré (SGB) es una polirradiculoneuropatía aguda caracterizada por debilidad simétrica progresiva de las extremidades con hipo o arreflexia, que progresa en un máximo de 4 semanas y que puede llevar a la falla respiratoria y a discapacidad a largo plazo. El objetivo de este trabajo fue describir las características clínicas, epidemiológicas y neurofisiológicas de pacientes con SGB del Hospital de Especialidades del Centro Médico Nacional Siglo XXI (HECMNSXXI).Se realizó un estudio observacional de tipo transversal retrolectivo. Se obtuvieron datos de expedientes clínicos de adultos con diagnóstico de SGB hospitalizados en el HECMNSXXI en el periodo de marzo de 2012 a marzo de 2016. Se registraron variables demográficas, clínicas y neurofisiológicas.Se incluyeron 94 pacientes con un promedio de edad de 53 años, en su mayoría hombres, con infección previa en 80%. La fuerza muscular medida con la escala del Medical Research Council (MRC) fue en promedio de 32, la escala de discapacidad del SGB (Hughes) al ingreso tuvo un promedio de 3.63. La variedad axonal se encontró en 68%, la desmielinizante en 29% y en 3% no concluyente.Se documentan en esta muestra características demográficas y clínicas similares a lo reportado en la literatura, así como la mayor proporción de variedades axonales, las cuales tienen mayor severidad en la presentación clínica así como mal pronóstico.

Este artículo tiene por objetivo general examinar y analizar preliminarmente, el proceso a través del cual se dividió la pandilla Barrio 18 en “los Sureños” y “los Revolucionarios”. La metodología empleada se ha basado en la aplicación de las técnicas de revisión documental y entrevistas en profundidad. Este trabajo arranca de un esfuerzo previo, en el que, con una visión holística, se entiende a las maras o pandillas apartir de cuatro criterios: 1) Su forma organizacional; 2) Su composición; 3) La naturaleza de sus acciones; y 4) Su conjunto de valores y normas socioculturales. La definición de pandilla como categoría en clave de identidad resulta esencial. La necesidad de construir una definición holística de pandilla tiene el objetivo de evitar “suavizar” el accionar delictivo de los pandilleros, así como “sobre-criminalizar”a las pandillas.Revista Policía y Seguridad Pública 5(1) 2015: 149-178

This article’s general objective is to provide a prelimary examination and analysis of the process through which Barrio 18 split into “los Sureños” and “los Revolucionarios”.The methodology this study was based on, used specialized techniques such as documentreview and in-depth interviews. This work starts from a previous effort, in which, through a holistic vision, gangs or maras are understood from four different perspectives: 1) Their organizational structure; 2) Their composition; 3) The nature of their actions; and 4)Their set of values and socio-cultural norms. The definition of gang as a key category as far as their identity is essential. The need to build a holistic definition of gang is meant to “tone down” gang member’s criminal activities, as well as to “over-criminalize” gangs.Revista Policía y Seguridad Pública 5(1) 2015: 149-178

Fertilisation triggers embryonic development culminating with the activation of a number of highly co-ordinated and evolutionarily conserved signalling pathways, which induce and pattern the mesoderm of the developing embryo. Previous studies in invertebrates have shown that hydrogen peroxide (H2O2), a reactive oxygen species (ROS), can act as a signalling molecule for axis specification during early development. Using a HyPer transgenicXenopus laevisline that expresses a H2O2-sensitive fluorescent protein sensor maternally, we recently found that fertilisation triggers a rapid increase in ROS production. Here we show that this increase in ROS levels is sustained throughout early embryogenesis, lasting until the tailbud stages. In addition we show that lowering ROS levels from the blastula stage through the gastrula stages via antioxidant treatments disrupts mesoderm formation. Furthermore, we show that attenuating ROS levels during the blastula / gastrula stages affects some, but not all, growth factor signalling pathways involved in mesoderm induction and patterning, including the PI3K/Akt, TGF-β/Nodal, and Wnt/β-catenin signalling pathways. These data suggest that sustained elevated ROS levels during the blastula and gastrula stages are essential for early vertebrate embryonic development, at least partly, through their roles in promoting growth factor signalling.

For the past 50 years, the Xenopus amphibian model has been a cornerstone of biomedical research. Studies using this model have lead to many groundbreaking discoveries in areas as diverse as vertebrate embryology, cell and molecular biology, physiology, neurobiology, and endocrinology. These insights have paved the way for important applications across modern medicine. The tremendous impact of Xenopus in the research arena is afforded by a combination of its unique advantages, including large, robust, abundant eggs and embryos, its cost effectiveness, and its close evolutionary relationship to mammals, including humans. Looking forward, Xenopus will continue to be a powerful model system in biomedical research, as many of the latest state-of-the-art techniques are perfectly suited to the system. This chapter is intended to provide an overview for the clinician embarking on research using Xenopus. It is geared toward demonstrating its strengths as an adaptable, multifunctional model for studying human disease mechanisms.