We investigate a large geodetic data set of interferometric synthetic aperture radar (InSAR) and GPS measurements to determine the source parameters for the three main shocks of the 2016 Central Italy earthquake sequence on 24 August and 26 and 30 October (Mw 6.1, 5.9, and 6.5, respectively). Our preferred model is consistent with the activation of four main coseismic asperities belonging to the SW dipping normal fault system associated with the Mount Gorzano‐Mount Vettore‐Mount Bove alignment. Additional slip, equivalent to a Mw ~ 6.1–6.2 earthquake, on a secondary (1) NE dipping antithetic fault and/or (2) on a WNW dipping low‐angle fault in the hanging wall of the main system is required to better reproduce the complex deformation pattern associated with the greatest seismic event (the Mw 6.5 earthquake). The recognition of ancillary faults involved in the sequence suggests a complex interaction in the activated crustal volume between the main normal faults and the secondary structures and a partitioning of strain release.

Hematopoietic and endothelial cell lineages share common progenitors. Accordingly, cytokines formerly thought to be specific for the hematopoietic system have been shown to affect several functions in endothelial cells, including angiogenesis. In this study, we investigated the angiogenic potential of erythropoietin (Epo), the main hormone regulating proliferation, differentiation, and survival of erythroid cells. Epo receptors (EpoRs) have been identified in the human EA.hy926 endothelial cell line by Western blot analysis. Also, recombinant human Epo (rHuEpo) stimulates Janus Kinase-2 (JAK-2) phosphorylation, cell proliferation, and matrix metalloproteinase-2 (MMP-2) production in EA.hy926 cells and significantly enhances their differentiation into vascular structures when seeded on Matrigel. In vivo, rHuEpo induces a potent angiogenic response in the chick embryo chorioallantoic membrane (CAM). Accordingly, endothelial cells of the CAM vasculature express EpoRs, as shown by immunostaining with an anti-EpoR antibody. The angiogenic response of CAM blood vessels to rHuEpo was comparable to that elicited by the prototypic angiogenic cytokine basic fibroblast growth factor (FGF2), it occurred in the absence of a significant mononuclear cell infiltrate, and it was not mimicked by endothelin-1 (ET-1) treatment. Taken together, these data demonstrate the ability of Epo to interact directly with endothelial cells and to elicit an angiogenic response in vitro and in vivo and thus act as a bona fide direct angiogenic factor.

S U M M A R YHere we report the preliminary results of GPS data inversions for coseismic and initial afterslip distributions of the M w 6.3 2009 April 6 L'Aquila earthquake. Coseismic displacements of continuous and survey-style GPS sites, show that the earthquake ruptured a planar SW-dipping normal fault with ∼0.6 m average slip and an estimated moment of 3.9 × 10 18 Nm. Geodetic data agree with the seismological and geological information pointing out the Paganica fault, as the causative structure of the main shock. The position of the hypocentre relative to the coseismic slip distribution supports the seismological evidence of southeastward rupture directivity. These results also point out that the main coseismic asperity probably ended downdip of the Paganica village at a depth of few kilometres in agreement with the small (1-10 cm) observed surface breaks. Time-dependent post-seismic displacements have been modelled with an exponential function. The average value of the estimated characteristic times for near-field sites in the hanging-wall of the fault is 23.9 ± 5.4 d. The comparison between coseismic slip and post-seismic displacements for the first 60 d after the main shock, shows that afterslip occurred at the edges of the main coseismic asperity with a maximum estimated slip of ∼25 cm and an equivalent seismic moment of 6.5 × 10 17 Nm. The activation of the Paganica fault, spatially intermediate between the previously recognized main active fault systems, suggests that strain accumulation in the central Apennines may be simultaneously active on distinct parallel fault systems.

14 C-PNU 145156E binds immobilized GST-Tat with a dissociation constant 5 times higher than heparin and is unable to bind GST-Tat R49/52/53/55/56/57A . Although heparin was an antagonist more potent than suramin, modifications of the backbone structure in selected suramin derivatives originated Tat antagonists whose potency was close to that shown by heparin.In conclusion, suramin derivatives bind the basic domain of Tat, prevent Tat/heparin and Tat/cell surface interactions, and inhibit the biological activity of extracellular Tat. Our data demonstrate that tailored polysulfonated compounds represent potent extracellular Tat inhibitors of possible therapeutic value.

Aquila destructive earthquake was successfully recorded by closely spaced 10 Hz and 1 Hz recording GPS receivers and strong motion accelerometers located above or close to the 50°dipping activated fault. We retrieved both static and dynamic displacements from very high rate GPS (VHRGPS) recordings by using Precise Point Positioning kinematic analysis. We compared the GPS positions' time series with the closest displacement time series obtained by doubly integrating strong motion data, first, to assess the GPS capability to detect the first seismic arrivals (P waves) and, second, to evaluate the accelerometers' capability to detect coseismic offsets up to ∼45 s after the earthquake occurrence. By comparing seismic and VHRGPS frequency contents, we inferred that GPS sampling rates greater than 2.5 Hz (i.e., 5 or 10 Hz) are required in the near field of moderate-magnitude events to provide "alias-free" solutions of coseismic dynamic displacements. Finally, we assessed the consistency of the dynamic VHRGPS results as a constraint on the kinematic rupture history of the main shock. These results suggested that the high-rate sampling GPS sites in the near field can be as useful as strong motion stations for earthquake source studies.

[1] The inversion of multitemporal DInSAR and GPS measurements unravels the coseismic and postseismic (afterslip) slip distributions associated with the 2009 M W 6.3 L'Aquila earthquake and provides insights into the rheological properties and long-term behavior of the responsible structure, the Paganica fault. Well-resolved patches of high postseismic slip (10-20 cm) appear to surround the main coseismic patch (maximum slip ≈1 m) through the entire seismogenic layer above the hypocenter without any obvious depth-dependent control. Time series of postseismic displacement are well reproduced by an exponential function with best-fit decay constants in the range of 20-40 days. A sudden discontinuity in the evolution of released postseismic moment at ≈130 days after the main shock does not correlate with independent seismological and geodetic data and is attributed to residual noise in the InSAR time series. The data are unable to resolve migration of afterslip along the fault probably because of the time interval (six days) between the main shock and the first radar acquisition. Surface fractures observed along the Paganica fault follow the steepest gradients of postseismic line-of-sight satellite displacements and are consistent with a sudden and delayed failure of the shallow layer in response to upward tapering of slip. The occurrence of afterslip at various levels through the entire seismogenic layer argues against exclusive depth-dependent variations of frictional properties on the fault, supporting the hypothesis of significant horizontal frictional heterogeneities and/or geometrical complexities. We support the hypothesis that such heterogeneities and complexities may be at the origin of the long-term variable behavior suggested by the paleoseismological studies. Rupture of fault patches with dimensions similar to that activated in 2009 appears to have a ≈500 year recurrence time interval documented by paleoseismic and historical studies. In addition to that, paleoseismological evidence of large (>0.5 m) coseismic offsets seems to require seismic events, recurring every 1000-2000 years, characterized by (1) multisegment linkage, (2) surface ruptures larger than in 2009, and (3) complete failure of the 2009 coseismic and postseismic patches.

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Pantothenate Kinase Associated Neurodegeneration (PKAN) is an autosomal recessive disorder with mutations in the pantothenate kinase 2 gene (PANK2), encoding an essential enzyme for Coenzyme A (CoA) biosynthesis. The molecular connection between defects in this enzyme and the neurodegenerative phenotype observed in PKAN patients is still poorly understood. We exploited the zebrafish model to study the role played by the pank2 gene during embryonic development and get new insight into PKAN pathogenesis. The zebrafish orthologue of hPANK2 lies on chromosome 13, is a maternal gene expressed in all development stages and, in adult animals, is highly abundant in CNS, dorsal aorta and caudal vein. The injection of a splice-inhibiting morpholino induced a clear phenotype with perturbed brain morphology and hydrocephalus; edema was present in the heart region and caudal plexus, where hemorrhages with reduction of blood circulation velocity were detected. We characterized the CNS phenotype by studying the expression pattern of wnt1 and neurog1 neural markers and by use of the Tg(neurod:EGFP/sox10:dsRed) transgenic line. The results evidenced that downregulation of pank2 severely impairs neuronal development, particularly in the anterior part of CNS (telencephalon). Whole-mount in situ hybridization analysis of the endothelial markers cadherin-5 and fli1a, and use of Tg(fli1a:EGFP/gata1a:dsRed) transgenic line, confirmed the essential role of pank2 in the formation of the vascular system. The specificity of the morpholino-induced phenotype was proved by the restoration of a normal development in a high percentage of embryos co-injected with pank2 mRNA. Also, addition of pantethine or CoA, but not of vitamin B5, to pank2 morpholino-injected embryos rescued the phenotype with high efficiency. The zebrafish model indicates the relevance of pank2 activity and CoA homeostasis for normal neuronal development and functioning and provides evidence of an unsuspected role for this enzyme and its product in vascular development.