Phylogeographical inferences, applied in a comparative framework across multiple species at a regional scale, provide the means for detecting regional and landscape-level patterns of biodiversity, which are important for understanding macroecology and evolution in a geographical mosaic against a backdrop broadly impacted by geological events. Although information on Patagonian phylogeographical patterns has accumulated for both aquatic and terrestrial organisms in recent years, no attempt has been made to compare patterns across major organismal groups. In this review, we compiled studies on the phylogeography of co-distributed plants and terrestrial vertebrates from Patagonia. From each study, we extracted information on levels of genetic diversity, and inferred demographic processes and phylogeographical breaks, as well as on putative refugia, to produce the first summary of emerging phylogeographical patterns for this region. This review reveals some congruent phylogeographical patterns within and among plants and terrestrial vertebrates, and suggests that PreQuaternary as well as Quaternary geological events would have been important driving forces in the evolutionary history of Patagonian lineages. Different processes and directional range shifts suggest a mosaic of phylogeographical patterns, far more complex than the several north-south common patterns traditionally proposed.Las inferencias filogeográficas, dentro de un marco comparativo cuando incluyen varias especies a escala regional, permiten detectar patrones de biodiversidad regional y de paisaje (fisonómicos), importantes para entender tanto la macroecología como el impacto a gran escala de los eventos geológicos. En los últimos años, el conocimiento filogeográfico de Patagonia se ha acumulado para organismos acuáticos y terrestres, y aunque se han propuesto pocos patrones demográficos o espaciales cualitativamente concordantes, no se ha hecho ningún intento de revisar comparativamente algunos de esos patrones considerando grandes grupos de organismos. En esta revisión compilamos el conocimiento publicado sobre la filogeografía de plantas vasculares y vertebrados terrestres de Patagonia con el propósito de comparar niveles de diversidad genética, procesos demográficos, quiebres filogeográ-ficos y localización de posibles refugios, para producir el primer resumen de patrones filogeográficos emergentes

In addition to being key elements in hemostasis and thrombosis, platelets amplify neutrophil function. We aimed to gain further insight into the stimuli, mediators, molecular pathways, and regulation of neutrophil extracellular trap formation mediated by human platelets. Platelets stimulated by lipopolysaccharide, a wall component of gram-negative bacteria, Pam3-cysteine-serine-lysine 4, a mimetic of lipopeptide from gram-positive bacteria, Escherichia coli, Staphylococcus aureus, or physiologic platelet agonists promoting neutrophil extracellular trap formation and myeloperoxidase-associated DNA activity under static and flow conditions. Although P-selectin or glycoprotein IIb/IIIa were not involved, platelet glycoprotein Ib, neutrophil cluster of differentiation 18, and the release of von Willebrand factor and platelet factor 4 seemed to be critical for the formation of neutrophil extracellular traps. The secretion of these molecules depended on thromboxane A(2) production triggered by lipopolysaccharide or Pam3-cysteine-serine-lysine 4 but not on high concentrations of thrombin. Accordingly, aspirin selectively inhibited platelet-mediated neutrophil extracellular trap generation. Signaling through extracellular signal-regulated kinase, phosphatidylinositol 3-kinase, and Src kinases, but not p38 or reduced nicotinamide adenine dinucleotide phosphate oxidase, was involved in platelet-triggered neutrophil extracellular trap release. Platelet-mediated neutrophil extracellular trap formation was inhibited by prostacyclin. Our results support a role for stimulated platelets in promoting neutrophil extracellular trap formation, reveal that an endothelium-derived molecule contributes to limiting neutrophil extracellular trap formation, and highlight platelet inhibition as a potential target for controlling neutrophil extracellular trap cell death.

The formation of neutrophil extracellular traps (NETs) is a newly described phenomenon that increases the bacteria-killing ability and the inflammatory response of neutrophils. Because NET generation occurs in an inflammatory microenvironment, we examined its regulation by anti-inflammatory drugs. Treatment of neutrophils with dexamethasone had no effect, but acetylsalicylic acid (ASA) treatment prevented NET formation. NETosis was also abrogated by the presence of BAY 11-7082 [(E)-3-[4-methylphenylsulfonyl]-2-propenenitrile] and Ro 106-9920 [6-(phenylsulfinyl)tetrazolo [1,5-b]pyridazine], two structurally unrelated nuclear factor-kB (NF-kB) inhibitors. The decrease in NET formation mediated by ASA, BAY-11-7082, and Ro 106-9920 was correlated with a significant reduction in the phosphorylation of NF-kB p65 subunit, indicating that the activation of this transcription factor is a relevant signaling pathway involved in the generation of DNA traps. The inhibitory effect of these drugs was also observed when NET generation was induced under acidic or hyperthermic conditions, two stress signals of the inflammatory microenvironment. In a mouse peritonitis model, while pretreatment of animals with ASA or BAY 11-7082 resulted in a marked suppression of NET formation along with increased bacteremia, dexamethasone had no effect. Our results show that NETs have an important role in the local control of infection and that ASA and NF-kB blockade could be useful therapies to avoid undesired effect of persistent neutrophil activation.

Sepsis is the leading cause of death in critically ill patients in intensive care units. Early recognition of sepsis and proper therapy are essential to reduce patient mortality. Moreover, treatment options for this deleterious inflammatory response to infection are limited. Neutrophils play an essential role in the innate immune response, providing the first line of host defense. It has recently been shown that these cells can trap and kill microorganisms by releasing neutrophil extracellular traps (NETs) composed of chromatin and antimicrobial proteins. Although the beneficial role of NETs during infections has been demonstrated, there is increasing evidence that NETs and their components contribute to the pathogenesis of several diseases, including sepsis. The aim of this review was to summarize the current evidence implicating NETs, as well as their components, in the development of sepsis and to discuss their potential use as novel therapeutic targets and as prognostic markers in septic patients.

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