p21-activated kinase (PAK) regulates cytoskeletal reorganization and directional migration in human neutrophils

Neutrophils serve as a first line of defense in innate immunity owing in part to their ability to rapidly migrate towards chemotactic factors derived from invading pathogens. As a migratory function, neutrophil chemotaxis is regulated by the Rho family of small GTPases. However, the mechanisms by which Rho GTPases orchestrate cytoskeletal dynamics in migrating neutrophils remain ill-defined. In this study, we characterized the role of p21-activated kinase (PAK) downstream of Rho GTPases in cytoskeletal remodeling and chemotactic processes of human neutrophils. We found that PAK activation occurred upon stimulation of neutrophils with f-Met-Leu-Phe (fMLP), and PAK accumulated at the actin-rich leading edge of stimulated neutrophils, suggesting a role for PAK in Rac-dependent actin remodeling. Treatment with the pharmacological PAK inhibitor, PF3758309, abrogated the integrity of RhoA-mediated actomyosin contractility and surface adhesion. Moreover, inhibition of PAK activity impaired neutrophil morphological polarization and directional migration under a gradient of fMLP, and was associated with dysregulated Ca2+ signaling. These results suggest that PAK serves as an important effector of Rho-family GTPases in neutrophil cytoskeletal reorganization, and plays a key role in driving efficient directional migration of human neutrophils

Search for CPCP violation in the phase space of D0→π+π−π+π−D^0\rightarrow\pi^+\pi^-\pi^+\pi^- decays

A search for time-integrated $CP$ violation in the Cabibbo-suppressed decay \mbox{D^0\rightarrow\pi^+\pi^-\pi^+\pi^-} is performed using an unbinned, model-independent technique known as the energy test. This is the first application of the energy test in four-body decays. The search is performed for $P$-even $CP$ asymmetries and, for the first time, is extended to probe the $P$-odd case. Using proton-proton collision data corresponding to an integrated luminosity of 3.0 fb$^{-1}$ collected by the LHCb detector at centre-of-mass energies of $\sqrt{s}=$7 TeV and 8 TeV, the world's best sensitivity to $CP$ violation in this decay is obtained. The data are found to be consistent with the hypothesis of $CP$ symmetry with a $p$-value of $(4.6\pm0.5)\%$ in the $P$-even case, and marginally consistent with a $p$-value of $(0.6\pm0.2)\%$ in the $P$-odd case, corresponding to a significance for $CP$ non-conservation of 2.7 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-044.htm

Endocranial morphology of the piciformes (Aves, Coraciimorphae): Functional and ecological implications

We used three-dimensional digital models to investigate the brain and endosseous labyrinth morphology of selected Neotropical Piciformes (Picidae, Ramphastidae, Galbulidae and Bucconidae). Remarkably, the brain morphology of Galbulidae clearly separates from species of other families. The eminentiae sagittales of Galbulidae and Bucconidae (insectivorous with high aerial maneuverability abilities) are smaller than those of the toucans (scansorial frugivores). Galbula showed the proportionally largest cerebellum, and Ramphastidae showed the least foliated one. Optic lobes ratio relative to the telencephalic hemispheres showed a strong phylogenetic signal. Three hypotheses were tested: (a) insectivorous taxa that need precise and fast movements to catch their prey, have well developed eminentiae sagittales compared to fruit eaters, (b) species that require high beak control would show larger cerebellum compared to other brain regions and higher number of visible folia and (c) there are marked differences between the brain shape of the four families studied here that bring valuable information of this interesting bird group. Hypotheses H1 and H2 are rejected, meanwhile H3 is accepted.Fil: Demmel Ferreira, María Manuela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Degrange, Federico Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Tirao, German Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Tambussi, Claudia Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; Argentin