Role of SPI-1 Secreted Effectors in Acute Bovine Response to Salmonella enterica Serovar Typhimurium: A Systems Biology Analysis Approach

Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis with diarrhea and polymorphonuclear cell (PMN) influx into the intestinal mucosa in humans and calves. The Salmonella Type III Secretion System (T3SS) encoded at Pathogenicity Island I translocates Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into epithelial cells and is required for induction of diarrhea. These effector proteins act together to induce intestinal fluid secretion and transcription of C-X-C chemokines, recruiting PMNs to the infection site. While individual molecular interactions of the effectors with cultured host cells have been characterized, their combined role in intestinal fluid secretion and inflammation is less understood. We hypothesized that comparison of the bovine intestinal mucosal response to wild type Salmonella and a SipA, SopABDE2 effector mutant relative to uninfected bovine ileum would reveal heretofore unidentified diarrhea-associated host cellular pathways. To determine the coordinated effects of these virulence factors, a bovine ligated ileal loop model was used to measure responses to wild type S. Typhimurium (WT) and a ΔsipA, sopABDE2 mutant (MUT) across 12 hours of infection using a bovine microarray. Data were analyzed using standard microarray analysis and a dynamic Bayesian network modeling approach (DBN). Both analytical methods confirmed increased expression of immune response genes to Salmonella infection and novel gene expression. Gene expression changes mapped to 219 molecular interaction pathways and 1620 gene ontology groups. Bayesian network modeling identified effects of infection on several interrelated signaling pathways including MAPK, Phosphatidylinositol, mTOR, Calcium, Toll-like Receptor, CCR3, Wnt, TGF-β, and Regulation of Actin Cytoskeleton and Apoptosis that were used to model of host-pathogen interactions. Comparison of WT and MUT demonstrated significantly different patterns of host response at early time points of infection (15 minutes, 30 minutes and one hour) within phosphatidylinositol, CCR3, Wnt, and TGF-β signaling pathways and the regulation of actin cytoskeleton pathway

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Constraints on slow slip from landsliding and faulting

The discovery of slow-slip has radically changed the way we understand the relative movement of Earth’s tectonic plates and the accumulation of stress in fault zones that fail in large earthquakes. Prior to the discovery of slow-slip, faults were thought to relieve stress either through continuous aseismic sliding, as is the case for continental creeping faults, or in near instantaneous failure. Aseismic deformation reflects fault slip that is slow enough that both inertial forces and seismic radiation are negligible. The durations of observed aseismic slip events range from days to years, with displacements of up to tens of centimeters. These events are not unique to a specific depth range and occur on faults in a variety of tectonic settings. This aseismic slip can sometimes also trigger more rapid slip somewhere else on the fault, such as small embedded asperities. This is thought to be the mechanism generating observed Low Frequency Earthquakes (LFEs) and small repeating earthquakes.I have preformed a series of studies to better understanding the nature of tectonic faulting which are compiled here. The first is entitled “3D surface deformation derived from airborne interferometric UAVSAR: Application to the Slumgullion Landslide”, and was originally published in the Journal of Geophysical Research in 2016. In order to understand how landslides respond to environmental forcing, we quantify how the hydro-mechanical forces controlling the Slumgullion Landslide express themselves kinematically in response to the infiltration of seasonal snowmelt. The well-studied Slumgullion Landslide, which is 3.9 km long and moves persistently at rates up to ∼2 cm/day is an ideal natural laboratory due to its large spatial extent and rapid deformation rates. The lateral boundaries of the landslide consist of strike-slip fault features, which over time have built up large flank ridges.The second study compiled here is entitled “Temporal variation of intermediate-depth earthquakes around the time of the M9.0 Tohoku-oki earthquake” and was originally published in Geophysical Research Letters in 2017. The temporal evolution of intermediate depth seismicity before and after the 2011 M 9.0 Tohoku-oki earthquake reveals interactionsbetween plate interface slip and deformation in the subducting slab. I investigate seismicity rate changes in the upper and lower planes of the double seismic zone beneath northeast Japan. The average ratio of upper plane to lower plane activity and the mean deep aseismic slip rate both increased by factor of two. An increase of down-dip compression in the slab resulting from coseismic and postseismic deformation enhanced seismicity in the upper plane, which is dominated by events accommodating down-dip shortening from plate unbending.In the third and final study included here I use geodetic measurements to place a quantitative upper bound on the size of the slow slip accompanying large bursts of quasi-periodic tremors and LFEs on the Parkfield section of the SAF. We use a host of analysis methods to try to isolate the small signal due to the slow slip and characterize noise properties. We find that in addition to subduction zones, transform faults are also capable of producing ETSs. However, given the upper-bounds from our analysis, surface geodetic measurements of this slow slip is likely to remain highly challenging

Seismic Wave Speeds Derived from Nuclear Resonant Inelastic X-ray Scattering for Comparison with Seismological Observations

Nuclear resonant inelastic X-ray scattering (NRIXS) experiments have been applied to Earth materials, and the Debye speed is often related to the material’s seismic wave speeds. However, for anisotropic samples, the Debye speed extracted from NRIXS measurements is not equal to the Debye speed obtained using the material’s isotropic seismic wave speeds. The latter provides an upper bound for the Debye speed of the material. Consequently, the acoustic wave speeds estimated from the Debye speed extracted from NRIXS (Nuclear Resonant Inelastic X-ray Scattering) measurements are underestimated compared to the material’s true seismic wave speeds. To illustrate the differences, the effects of various assumptions used to estimate the Debye speed, as well as seismic wave speeds, are examined with iron alloys at Earth’s inner core conditions. For the case of pure iron, the variation of the crystal orientation relative to the incoming X-ray beam causes a 40 % variation in the measured Debye speed, and leads to 3% and 31% underestimation in the compressional and shear wave speeds, respectively. Based upon various iron alloys, the error in the inferred seismic shear wave speed strongly depends upon the strength of anisotropy that can be quantified. We can also derive Debye speeds based upon seismological observations such as the PREM (Preliminary Reference Earth Model) and inner core anisotropy model. We show that these seismically derived Debye speeds are upper bounds for Debye speeds obtained from NRIXS experiments and that interpretation of the Debye speeds from the NRIXS measurements in terms of seismic wave speeds should be done with utmost caution

Emergency medical services: clinical practice and systems oversight (1)

xix, 551 hlm. : ilus. ; tab. ; 28 cm

Emergency medical services: clinical practice and systems oversight (2)

xvii, 467 hlm. : ilus. tab. ; 28 cm

Simultaneous creation of a large vapor plume and pumice raft by the 2021 Fukutoku-Oka-no-Ba shallow submarine eruption

International audienceThe 12 August 2021 eruption of Fukutoku-Oka-no-Ba, a shallow submarine volcano in the Izu-Bonin arc of Japan, is one of few documented submarine eruptions to make a large aerial plume and floating pumice raft. Relative to past eruptions, this event was well-covered by multiple high resolution satellite remote sensors, raising the possibility of resolving important questions about the timing of raft and plume formation, and their relationship. Here we use satellite remote sensing to assess the eruption timeline, style, rates, and products. We use the Himawari-8 satellite to assess the plume volume flux and height through time. In addition, we use a combination of ultra-high resolution satellite imagery to assess the timing and mechanisms of raft formation. We find that the 16 km eruption plume was ice-rich and conclude that the 0.1 km3 raft and eruption plume were co-genetic. Finally, we suggest that pumice clasts were delivered to the raft by tephra jets, ballistics, and near-vent fallout from the plume. Together our observations reveal that the fallout of pumice lapilli from a water-rich eruption column generated a large pumice raft