Nuclear DNA damage and ligation of plasma-membrane death receptors have long been recognized as initial triggers of apoptosis that induce mitochondrial membrane permeabilization (MMP) and/or the ...direct activation of caspases. Accumulating evidence suggests that other organelles, including the endoplasmic reticulum (ER), lysosomes and the Golgi apparatus, are also major points of integration of pro-apoptotic signalling or damage sensing. Each organelle possesses sensors that detect specific alterations, locally activates signal transduction pathways and emits signals that ensure inter-organellar cross-talk. The ER senses local stress through chaperones, Ca2+-binding proteins and Ca2+ release channels, which might transmit ER Ca2+ responses to mitochondria. The ER also contains several Bcl-2-binding proteins, and Bcl-2 has been reported to exert part of its cytoprotective effect within the ER. Upon membrane destabilization, lysosomes release cathepsins that are endowed with the capacity of triggering MMP. The Golgi apparatus constitutes a privileged site for the generation of the pro-apoptotic mediator ganglioside GD3, facilitates local caspase-2 activation and might serve as a storage organelle for latent death receptors. Intriguingly, most organelle-specific death responses finally lead to either MMP or caspase activation, both of which might function as central integrators of the death pathway, thereby streamlining lysosome-, Golgi- or ER-elicited responses into a common pathway.
The determination of rock friction at seismic slip rates (about 1 m s(-1)) is of paramount importance in earthquake mechanics, as fault friction controls the stress drop, the mechanical work and the ...frictional heat generated during slip. Given the difficulty in determining friction by seismological methods, elucidating constraints are derived from experimental studies. Here we review a large set of published and unpublished experiments (∼300) performed in rotary shear apparatus at slip rates of 0.1-2.6 m s(-1). The experiments indicate a significant decrease in friction (of up to one order of magnitude), which we term fault lubrication, both for cohesive (silicate-built, quartz-built and carbonate-built) rocks and non-cohesive rocks (clay-rich, anhydrite, gypsum and dolomite gouges) typical of crustal seismogenic sources. The available mechanical work and the associated temperature rise in the slipping zone trigger a number of physicochemical processes (gelification, decarbonation and dehydration reactions, melting and so on) whose products are responsible for fault lubrication. The similarity between (1) experimental and natural fault products and (2) mechanical work measures resulting from these laboratory experiments and seismological estimates suggests that it is reasonable to extrapolate experimental data to conditions typical of earthquake nucleation depths (7-15 km). It seems that faults are lubricated during earthquakes, irrespective of the fault rock composition and of the specific weakening mechanism involved.
For the Ice Giants, atmospheric entry probes provide critical measurements not attainable via remote observations. Including the 2013–2022 NASA Planetary Decadal Survey, there have been at least five ...comprehensive atmospheric probe engineering design studies performed in recent years by NASA and ESA. International science definition teams have assessed the science requirements, and each recommended similar measurements and payloads to meet science goals with current instrument technology. The probe system concept has matured and converged on general design parameters that indicate the probe would include a 1-meter class aeroshell and have a mass around 350 to 400-kg. Probe battery sizes vary, depending on the duration of a post-release coast phase, and assumptions about heaters and instrument power needs. The various mission concepts demonstrate the need for advanced power and thermal protection system development. The many completed studies show an Ice Giant mission with an
in situ
probe is feasible and would be welcomed by the international science community.
Host-adapted Gram-negative bacterial pathogens from the Pasteurellaceae, Neisseriaceae, and Moraxellaceae families normally reside in the upper respiratory or genitourinary tracts of their hosts and ...rely on utilizing iron from host transferrin (Tf) for growth and survival. The surface receptor proteins that mediate this critical iron acquisition pathway have been proposed as ideal vaccine targets due to the critical role that they play in survival and disease pathogenesis in vivo. In particular, the surface lipoprotein component of the receptor, Tf binding protein B (TbpB), had received considerable attention as a potential antigen for vaccines in humans and food production animals but this has not translated into the series of successful vaccine products originally envisioned. Preliminary immunization experiments suggesting that host Tf could interfere with development of the immune response prompted us to directly address this question with site-directed mutant proteins defective in binding Tf. Site-directed mutants with dramatically reduced binding of porcine transferrin and nearly identical structure to the native proteins were prepared. A mutant Haemophilus parasuis TbpB was shown to induce an enhanced B-cell and T-cell response in pigs relative to native TbpB and provide superior protection from infection than the native TbpB or a commercial vaccine product. The results indicate that binding of host transferrin modulates the development of the immune response against TbpBs and that strategies designed to reduce or eliminate binding can be used to generate superior antigens for vaccines.
Introduction
A primary disruption of the bodily self is considered a core feature of schizophrenia patients (SCZ). The “disembodied” self would be underpinned by an inefficient body-related ...multisensory integration mechanism occurring in the Peripersonal Space (PPS). PPS is a plastic sector of space surrounding our body, whose extent is altered in SCZ. Although PPS represents a malleable interface marking the perceptual border between self and others, no study has investigated the potential alteration of its plasticity in SCZ.
Objectives
We investigated the PPS extension and its plasticity in SCZ and their potential correlations with the clinical scales.
Methods
Thirty SCZ and thirty healthy controls (HC) underwent a multisensory task to estimate PPS boundary before and after a motor training. Patients were also administered the Positive And Negative Syndrome Scale (PANSS) and the Examination of Anomalous Self-Experience (EASE).
Results
Data confirm a narrower PPS extent in SCZ than in HC, whereas no differences in PPS expansion was found in the two groups after the motor training (Figure 1). Positive symptoms were associated directly with PPS extent and inversely with PPS plasticity. No associations were found between PPS and EASE domains. Figure1: Graphical representation of PPS expansion in SCZ and HC. Both panels show individual normalized sigmoid fits
Conclusions
The present study suggests a narrower PPS extent and a preserved PPS plasticity in SCZ with respect to HC. Both PPS extent and plasticity are related to the severity of positive symptoms. These results highlight the potential role of rehabilitation interventions in order to improve patients’ weakened body boundary.
Disclosure
No significant relationships.
Descent probes afford the opportunity to make essential atmospheric measurements that are beyond the reach of remote sensing, including the atmospheric abundances of noble gases and key isotopes, and ...the structure of the atmosphere beneath the cloud tops. Measurements are defined as Tier 1, representing threshold science required to justify the probe mission, and Tier 2 representing valuable science that significantly complement and enhance the threshold measurements, but of themselves are not sufficient to justify the mission. Tier 1 measurements comprise atmospheric noble gas abundances including helium, key noble gas isotope ratios, and the thermal structure of the atmosphere. Instrumentation required to achieve the Tier 1 measurements include a mass spectrometer, a helium abundance detector, and an atmospheric structure instrument comprising both sensors for pressure, temperature, and atmospheric acoustic properties (speed of sound). Tier 1 science can be achieved with a probe making measurements near one to several bars. Tier 2 science includes measurements of key isotopic ratios, the abundances of atmospheric condensables and disequilibrium species, atmospheric dynamics, the net radiative flux transfer profile of the atmosphere, and the location, composition, properties, and structure of the clouds. To achieve all the Tier 2 science objectives requires a probe descending through at least ten bars carrying the full Tier 1 suite of instruments as well as a nephelometer, net flux radiometer, and an ultrastable oscillator to enable Doppler wind tracking of the probe throughout descent.
Abstract
It is crucial to control the tuning and improve the emission of a quantum emitter at the nanoscale. We report multiple Fano resonances in metallic nanostructures on an Er
3+
-doped tellurite ...glass. Periodic nanoslits were fabricated with a focused gallium ion beam on a gold thin film deposited on the tellurite glass. Is proposed a coupling function with Fano line-shape form, and the asymmetric parameter
q
for each resonance wavelength in the 515 to 535 nm region was calculated. This asymmetric resonance effect is a consequence of the quantum interaction between the continuum state, generated in the nanostructure, and the Stark splits of the
$$^2$$
2
H
$$_{11/2}$$
11
/
2
state.
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