Protease activated receptors (PAR)-1 and -2 mediate cellular effects of factor VII activating protease (FSAP).

Factor VII activating protease (FSAP) is a circulating serine protease implicated in thrombosis, atherosclerosis, stroke, and cancer. Using an overexpression strategy, we have systematically investigated the role of protease activated receptors (PAR)-1, -2, -3, and -4 on FSAP-mediated signaling in HEK293T and A549 cells. Cleavage of PAR-reporter constructs and MAPK phosphorylation was used to monitor receptor activation. FSAP cleaved PAR-2 and to a lesser degree PAR-1, but not PAR-3 or PAR-4 in both cell types. Robust MAPK activation in response to FSAP was observed after PAR-2, but not PAR-1 overexpression in HEK293T. Recombinant serine protease domain of wild type FSAP, but not the Marburg I isoform of FSAP, could reproduce the effects of plasma purified FSAP. Canonical cleavage of both PARs was suggested by mass spectrometric analysis of synthetic peptide substrates from the N-terminus of PARs and site directed mutagenesis studies. Surprisingly, knockdown of endogenous PAR-1, but not PAR-2, prevented the apoptosis-inhibitory effect of FSAP, suggesting that PAR1 is nevertheless a direct or indirect target in some cell types. This molecular characterization of PAR-1 and -2 as cellular receptors of FSAP will help to define the actions of FSAP in the context of cancer and vascular biology.

Role of nanowire length on the performance of a self-driven NIR photodetector based on mono/bi-layer graphene (camphor)/Si-nanowire Schottky junction.

In this article, we have demonstrated a solid carbon source such as camphor as a natural precursor to synthesize a large area mono/bi-layer graphene (MLG) sheet to fabricate a nanowire junction-based near infrared photodetectors (NIRPDs). In order to increase the surface-to-volume ratio, we have developed Si-nanowire arrays (SiNWAs) of varying lengths by etching planar Si. Then, the camphor-based MLG/Si and MLG/SiNWAs Schottky junction photodetectors have been fabricated to achieve an efficient response with self-driven properties in the near infrared (NIR) regime. Due to a balance between light absorption capability and surface recombination centers, devices having SiNWAs obtained by etching for 30 min shows a better photoresponse, sensitivity and detectivity. Fabricated NIRPDs can also be functioned as self-driven devices which are highly responsive and very stable at low optical power signals up to 2 V with a fast rise and decay time of 34/13 ms. A tremendous enhancement has been witnessed from 36 µA W-1 to 22 mA W-1 in the responsivity at 0 V for MLG/30 min SiNWAs than planar MLG/Si PDs indicating an important development of self-driven NIRPDs based on camphor-based MLG for future optoelectronic devices.

Structural modeling defines transmembrane residues in ADAM17 that are crucial for Rhbdf2-ADAM17-dependent proteolysis.

A disintegrin and metalloproteinase 17 (ADAM17) controls the release of the pro-inflammatory cytokine tumor necrosis factor α (TNFα, also known as TNF) and is crucial for protecting the skin and intestinal barrier by proteolytic activation of epidermal growth factor receptor (EGFR) ligands. The seven-membrane-spanning protein called inactive rhomboid 2 (Rhbdf2; also known as iRhom2) is required for ADAM17-dependent TNFα shedding and crosstalk with the EGFR, and a point mutation (known as sinecure, sin) in the first transmembrane domain (TMD) of Rhbdf2 (Rhbdf2sin) blocks TNFα shedding, yet little is known about the underlying mechanism. Here, we used a structure-function analysis informed by structural modeling to evaluate the interaction between the TMD of ADAM17 and the first TMD of Rhbdf2, and the role of this interaction in Rhbdf2-ADAM17-dependent shedding. Moreover, we show that double mutant mice that are homozygous for Rhbdf2sin/sin and lack Rhbdf1 closely resemble Rhbdf1/2-/- double knockout mice, highlighting the severe functional impact of the Rhbdf2sin/sin mutation on ADAM17 during mouse development. Taken together, these findings provide new mechanistic and conceptual insights into the critical role of the TMDs of ADAM17 and Rhbdf2 in the regulation of the ADAM17 and EGFR, and ADAM17 and TNFα signaling pathways.

Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

Platelet and Erythrocyte Sources of S1P Are Redundant for Vascular Development and Homeostasis, but Both Rendered Essential After Plasma S1P Depletion in Anaphylactic Shock.

RATIONALE: Sphingosine-1-phosphate (S1P) signaling is essential for vascular development and postnatal vascular homeostasis. The relative importance of S1P sources sustaining these processes remains unclear. OBJECTIVE: To address the level of redundancy in bioactive S1P provision to the developing and mature vasculature. METHODS AND RESULTS: S1P production was selectively impaired in mouse platelets, erythrocytes, endothelium, or smooth muscle cells by targeted deletion of genes encoding sphingosine kinases -1 and -2. S1P deficiency impaired aggregation and spreading of washed platelets and profoundly reduced their capacity to promote endothelial barrier function ex vivo. However, and in contrast to recent reports, neither platelets nor any other source of S1P was essential for vascular development, vascular integrity, or hemostasis/thrombosis. Yet rapid and profound depletion of plasma S1P during systemic anaphylaxis rendered both platelet- and erythrocyte-derived S1P essential for survival, with a contribution from blood endothelium observed only in the absence of circulating sources. Recovery was sensitive to aspirin in mice with but not without platelet S1P, suggesting that platelet activation and stimulus-response coupling is needed. S1P deficiency aggravated vasoplegia in this model, arguing a vital role for S1P in maintaining vascular resistance during recovery from circulatory shock. Accordingly, the S1P2 receptor mediated most of the survival benefit of S1P, whereas the endothelial S1P1 receptor was dispensable for survival despite its importance for maintaining vascular integrity. CONCLUSIONS: Although source redundancy normally secures essential S1P signaling in developing and mature blood vessels, profound depletion of plasma S1P renders both erythrocyte and platelet S1P pools necessary for recovery and high basal plasma S1P levels protective during anaphylactic shock.

Optoelectrical modeling of solar cells based on c-Si/a-Si:H nanowire array: focus on the electrical transport in between the nanowires.

By coupling optical and electrical modeling, we have investigated the photovoltaic performances of p-i-n radial nanowires array based on crystalline p-type silicon (c-Si) core/hydrogenated amorphous silicon (a-Si:H) shell. By varying either the doping concentration of the c-Si core, or back contact work function we can separate and highlight the contribution to the cell's performance of the nanowires themselves (the radial cell) from the interspace between the nanowires (the planar cell). We show that the build-in potential (V bi) in the radial and planar cells strongly depends on the doping of c-Si core and the work function of the back contact respectively. Consequently, the solar cell's performance is degraded if either the doping concentration of the c-Si core, or/and the work function of the back contact is too low. By inserting a thin (p) a-Si:H layer between both core/absorber and back contact/absorber, the performance of the solar cell can be improved by partly fixing the V bi at both interfaces due to strong electrostatic screening effect. Depositing such a buffer layer playing the role of an electrostatic screen for charge carriers is a suggested way of enhancing the performance of solar cells based on radial p-i-n or n-i-p nanowire array.

Matriptase zymogen supports epithelial development, homeostasis and regeneration.

BACKGROUND: Matriptase is a membrane serine protease essential for epithelial development, homeostasis, and regeneration, as well as a central orchestrator of pathogenic pericellular signaling in the context of inflammatory and proliferative diseases. Matriptase is an unusual protease in that its zymogen displays measurable enzymatic activity. RESULTS: Here, we used gain and loss of function genetics to investigate the possible biological functions of zymogen matriptase. Unexpectedly, transgenic mice mis-expressing a zymogen-locked version of matriptase in the epidermis displayed pathologies previously reported for transgenic mice mis-expressing wildtype epidermal matriptase. Equally surprising, mice engineered to express only zymogen-locked endogenous matriptase, unlike matriptase null mice, were viable, developed epithelial barrier function, and regenerated the injured epithelium. Compatible with these observations, wildtype and zymogen-locked matriptase were equipotent activators of PAR-2 inflammatory signaling. CONCLUSION: The study demonstrates that the matriptase zymogen is biologically active and is capable of executing developmental and homeostatic functions of the protease.

The cytoplasmic domain of a disintegrin and metalloproteinase 10 (ADAM10) regulates its constitutive activity but is dispensable for stimulated ADAM10-dependent shedding.

The membrane-anchored metalloproteinase a disintegrin and metalloprotease 10 (ADAM10) is required for shedding of membrane proteins such as EGF, betacellulin, the amyloid precursor protein, and CD23 from cells. ADAM10 is constitutively active and can be rapidly and post-translationally enhanced by several stimuli, yet little is known about the underlying mechanism. Here, we use ADAM10-deficient cells transfected with wild type or mutant ADAM10 to address the role of its cytoplasmic and transmembrane domain in regulating ADAM10-dependent protein ectodomain shedding. We report that the cytoplasmic domain of ADAM10 negatively regulates its constitutive activity through an ER retention motif but is dispensable for its stimulated activity. However, chimeras with the extracellular domain of ADAM10 and the transmembrane domain of ADAM17 with or without the cytoplasmic domain of ADAM17 show reduced stimulated shedding of the ADAM10 substrate betacellulin, whereas the ionomycin-stimulated shedding of the ADAM17 substrates CD62-L and TGFα is not affected. Moreover, we show that influx of extracellular calcium activates ADAM10 but is not essential for its activation by APMA and BzATP. Finally, the rapid stimulation of ADAM10 is not significantly affected by incubation with proprotein convertase inhibitors for up to 8 h, arguing against a major role of increased prodomain removal in the rapid stimulation of ADAM10. Thus, the cytoplasmic domain of ADAM10 negatively influences constitutive shedding through an ER retention motif, whereas the cytoplasmic domain and prodomain processing are not required for the rapid activation of ADAM10-dependent shedding events.

MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands.

Toll-like receptors (TLRs) trigger intestinal inflammation when the epithelial barrier is breached by physical trauma or pathogenic microbes. Although it has been shown that TLR-mediated signals are ultimately protective in models of acute intestinal inflammation [such as dextran sulfate sodium (DSS)-induced colitis], it is less clear which cells mediate protection. Here we demonstrate that TLR signaling in the nonhematopoietic compartment confers protection in acute DSS-induced colitis. Epithelial cells of MyD88/Trif-deficient mice express diminished levels of the epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG), and systemic lipopolysaccharide administration induces their expression in the colon. N-ethyl-N-nitrosourea (ENU)-induced mutations in Adam17 (which is required for AREG and EREG processing) and in Egfr both produce a strong DSS colitis phenotype, and the Adam17 mutation exerts its deleterious effect in the nonhematopoietic compartment. The effect of abrogation of TLR signaling is mitigated by systemic administration of AREG. A TLR→MyD88→AREG/EREG→EGFR signaling pathway is represented in nonhematopoietic cells of the intestinal tract, responds to microbial stimuli once barriers are breached, and mediates protection against DSS-induced colitis.

ADAM17 is regulated by a rapid and reversible mechanism that controls access to its catalytic site.

Protein ectodomain shedding is crucial for cell-cell interactions because it controls the bioavailability of soluble tumor necrosis factor-α (TNFα) and ligands of the epidermal growth factor (EGF) receptor, and the release of many other membrane proteins. Various stimuli can rapidly trigger ectodomain shedding, yet much remains to be learned about the identity of the enzymes that respond to these stimuli and the mechanisms underlying their activation. Here, we demonstrate that the membrane-anchored metalloproteinase ADAM17, but not ADAM10, is the sheddase that rapidly responds to the physiological signaling pathways stimulated by thrombin, EGF, lysophosphatidic acid and TNFα. Stimulation of ADAM17 is swift and quickly reversible, and does not depend on removal of its inhibitory pro-domain by pro-protein convertases, or on dissociation of an endogenous inhibitor, TIMP3. Moreover, activation of ADAM17 by physiological stimuli requires its transmembrane domain, but not its cytoplasmic domain, arguing against inside-out signaling via cytoplasmic phosphorylation as the underlying mechanism. Finally, experiments with the tight binding hydroxamate inhibitor DPC333, used here to probe the accessibility of the active site of ADAM17, demonstrate that this inhibitor can quickly bind to ADAM17 in stimulated, but not quiescent cells. These findings support the concept that activation of ADAM17 involves a rapid and reversible exposure of its catalytic site.

Pathological neovascularization is reduced by inactivation of ADAM17 in endothelial cells but not in pericytes.

RATIONALE: Pathological neovascularization is a critical component of diseases such as proliferative retinopathies, cancer and rheumatoid arthritis, yet much remains to be learned about the underlying causes. Previous studies showed that vascular endothelial growth factor (VEGF)-A activates the membrane-anchored metalloproteinase ADAM17 (a disintegrin and metalloproteinase 17) in endothelial cells, thereby stimulating crosstalk between VEGF receptor 2 and extracellular signal-regulated kinase. These findings raised interesting questions about the role of ADAM17 in angiogenesis and neovascularization in vivo. OBJECTIVE: The objective of this study was to inactivate ADAM17 in endothelial cells or in pericytes to determine how this affects developmental angiogenesis, pathological retinal neovascularization and heterotopic tumor growth. METHODS AND RESULTS: We generated animals in which floxed ADAM17 was removed by Tie2-Cre in endothelial cells, or by smooth muscle (sm) Cre in smooth muscle cells and pericytes. There were no evident developmental defects in either conditional knockout strain, but pathological retinal neovascularization and growth of heterotopically injected tumor cells was reduced in Adam17flox/flox/Tie2-Cre mice, although not in Adam17flox/flox/sm-Cre mice. Moreover, lack of ADAM17 in endothelial cells decreased ex vivo chord formation, and this could be largely restored by addition of the ADAM17 substrate HB-EGF (heparin-binding epidermal growth factor-like growth factor). Finally we found that ADAM17 is important for the VEGF receptor 2 stimulated processing of several receptors with known functions in endothelial cell biology. CONCLUSIONS: These results provide the first evidence for a role for ADAM17 in pathological neovascularization in vivo. Because ADAM17 does not appear to be required for normal developmental angiogenesis or vascular homeostasis, it could emerge as a good target for treatment of pathological neovascularization.

Custom plating of nanoscale semiconductor/catalyst junctions for photoelectrochemical water splitting.

Photoelectrochemical water splitting under harsh chemical conditions can be promoted by dispersed transition metal nanoparticles electrodeposited on n-Si surfaces, without the need for classical protection layers. Although this method is simple, it only allows for poor control of metal morphology and geometry on the photoanode surface. Herein, we introduce templated nanoscale electrodeposition on photoactive n-Si for the customization of nanoscale inhomogeneous Schottky junctions and demonstrate their use as stable photoanodes. The photoelectrochemical properties of the so-manufactured photoanodes exhibit a strong dependence on the photoanodes' geometrical features, and the obtained experimental trends are rationalized using simulation.

Substrate selectivity of epidermal growth factor-receptor ligand sheddases and their regulation by phorbol esters and calcium influx.

Signaling via the epidermal growth factor receptor (EGFR), which has critical roles in development and diseases such as cancer, is regulated by proteolytic shedding of its membrane-tethered ligands. Sheddases for EGFR-ligands are therefore key signaling switches in the EGFR pathway. Here, we determined which ADAMs (a disintegrin and metalloprotease) can shed various EGFR-ligands, and we analyzed the regulation of EGFR-ligand shedding by two commonly used stimuli, phorbol esters and calcium influx. Phorbol esters predominantly activate ADAM17, thereby triggering a burst of shedding of EGFR-ligands from a late secretory pathway compartment. Calcium influx stimulates ADAM10, requiring its cytoplasmic domain. However, calcium influx-stimulated shedding of transforming growth factor alpha and amphiregulin does not require ADAM17, even though ADAM17 is essential for phorbol ester-stimulated shedding of these EGFR-ligands. This study provides new insight into the machinery responsible for EGFR-ligand release and thus EGFR signaling and demonstrates that dysregulated EGFR-ligand shedding may be caused by increased expression of constitutively active sheddases or activation of different sheddases by distinct stimuli.

Mesopore Formation and Silicon Surface Nanostructuration by Metal-Assisted Chemical Etching With Silver Nanoparticles.

This article presents a study on Metal-Assisted Chemical Etching (MACE) of silicon in HF-H2O2 using silver nanoparticles as catalysts. Our aim is a better understanding of the process to elaborate new 3D submicrometric surface structures useful for light management. We investigated MACE over the whole range of silicon doping, i.e., p++, p+, p, p-, n, n+, and n++. We discovered that, instead of the well-defined and straight mesopores obtained in p and n-type silicon, in p++ and n++ silicon MACE leads to the formation of cone-shaped macropores filled with porous silicon. We account for the transition between these two pore-formation regimes (straight and cone-shaped pores) by modeling (at equilibrium and under polarization) the Ag/Si/electrolyte (HF) system. The model simulates the system as two nanodiodes in series. We show that delocalized MACE is explained by a large tunnel current contribution for the p-Si/Ag and n-Si/HF diodes under reverse polarization, which increases with the doping level and when the size of the nanocontacts (Ag, HF) decreases. By analogy with the results obtained on heavily doped silicon, we finally present a method to form size-controlled cone-shaped macropores in p silicon with silver nanoparticles. This shape, instead of the usual straight mesopores, is obtained by applying an external anodic polarization during MACE. Two methods are shown to be effective for the control of the macropore cone angle: one by adjusting the potential applied during MACE, the other by changing the H2O2 concentration. Under appropriate etching conditions, the obtained macropores exhibit optical properties (reflectivity ~3 %) similar to that of black silicon.

Local VOC Measurements by Kelvin Probe Force Microscopy Applied on P-I-N Radial Junction Si Nanowires.

This work focuses on the extraction of the open circuit voltage (VOC) on photovoltaic nanowires by surface photovoltage (SPV) based on Kelvin probe force microscopy (KPFM) measurements. In a first approach, P-I-N radial junction (RJ) silicon nanowire (SiNW) devices were investigated under illumination by KPFM and current-voltage (I-V) analysis. Within 5%, the extracted SPV correlates well with the VOC. In a second approach, local SPV measurements were applied on single isolated radial junction SiNWs pointing out shadowing effects from the AFM tip that can strongly impact the SPV assessment. Several strategies in terms of AFM tip shape and illumination orientation have been put in place to minimize this effect. Local SPV measurements on isolated radial junction SiNWs increase logarithmically with the illumination power and demonstrate a linear behavior with the VOC. The results show notably that contactless measurements of the VOC become feasible at the scale of single photovoltaic SiNW devices.

A low Schottky barrier height and transport mechanism in gold-graphene-silicon (001) heterojunctions.

The interface resistance at metal/semiconductor junctions has been a key issue for decades. The control of this resistance is dependent on the possibility to tune the Schottky barrier height. However, Fermi level pinning in these systems forbids a total control over interface resistance. The introduction of 2D crystals between semiconductor surfaces and metals may be an interesting route towards this goal. In this work, we study the influence of the introduction of a graphene monolayer between a metal and silicon on the Schottky barrier height. We used X-ray photoemission spectroscopy to rule out the presence of oxides at the interface, the absence of pinning of the Fermi level and the strong reduction of the Schottky barrier height. We then performed a multiscale transport analysis to determine the transport mechanism. The consistency in the measured barrier height at different scales confirms the good quality of our junctions and the role of graphene in the drastic reduction of the barrier height.

3D Patterning of Si by Contact Etching With Nanoporous Metals.

Nanoporous gold and platinum electrodes are used to pattern n-type silicon by contact etching at the macroscopic scale. This type of electrode has the advantage of forming nanocontacts between silicon, the metal and the electrolyte as in classical metal assisted chemical etching while ensuring electrolyte transport to and from the interface through the electrode. Nanoporous gold electrodes with two types of nanostructures, fine and coarse (average ligament widths of ~30 and 100 nm, respectively) have been elaborated and tested. Patterns consisting in networks of square-based pyramids (10 × 10 µm2 base × 7 µm height) and U-shaped lines (2, 5, and 10 µm width × 10 µm height × 4 µm interspacing) are imprinted by both electrochemical and chemical (HF-H2O2) contact etching. A complete pattern transfer of pyramids is achieved with coarse nanoporous gold in both contact etching modes, at a rate of ~0.35 µm min-1. Under the same etching conditions, U-shaped line were only partially imprinted. The surface state after imprinting presents various defects such as craters, pores or porous silicon. Small walls are sometimes obtained due to imprinting of the details of the coarse gold nanostructure. We establish that np-Au electrodes can be turned into "np-Pt" electrodes by simply sputtering a thin platinum layer (5 nm) on the etching (catalytic) side of the electrode. Imprinting with np Au/Pt slightly improves the pattern transfer resolution. 2D numerical simulations of the valence band modulation at the Au/Si/electrolyte interfaces are carried out to explain the localized aspect of contact etching of n-type silicon with gold and platinum and the different surface state obtained after patterning. They show that n-type silicon in contact with gold or platinum is in inversion regime, with holes under the metal (within 3 nm). Etching under moderate anodic polarization corresponds to a quasi 2D hole transfer over a few nanometers in the inversion layer between adjacent metal and electrolyte contacts and is therefore very localized around metal contacts.

Variations in Cellular Responses of Mouse T Cells to Adenosine-5'-Triphosphate Stimulation Do Not Depend on P2X7 Receptor Expression Levels but on Their Activation and Differentiation Stage.

A previous report has shown that regulatory T cells (Treg) were markedly more sensitive to adenosine-5'-triphosphate (ATP) than conventional T cells (Tconv). Another one has shown that Tregs and CD45RBlow Tconvs, but not CD45RBhigh Tconvs, displayed similar high sensitivity to ATP. We have previously reported that CD45RBlow Tconvs expressing B220/CD45RABC molecules in a pre-apoptotic stage are resistant to ATP stimulation due to the loss of P2X7 receptor (P2X7R) membrane expression. To gain a clearer picture on T-cell sensitivity to ATP, we have quantified four different cellular activities triggered by ATP in mouse T cells at different stages of activation/differentiation, in correlation with levels of P2X7R membrane expression. P2X7R expression significantly increases on Tconvs during differentiation from naive CD45RBhighCD44low to effector/memory CD45RBlowCD44high stage. Maximum levels of upregulation are reached on recently activated CD69+ naive and memory Tconvs. Ectonucleotidases CD39 and CD73 expression levels increase in parallel with those of P2X7R. Recently activated CD69+ CD45RBhighCD44low Tconvs, although expressing high levels of P2X7R, fail to cleave homing receptor CD62L after ATP treatment, but efficiently form pores and externalize phosphatidylserine (PS). In contrast, naive CD45RBhighCD44low Tconvs cleave CD62L with high efficiency although they express a lower level of P2X7, thus suggesting that P2X7R levels are not a limiting factor for signaling ATP-induced cellular responses. Contrary to common assumption, P2X7R-mediated cellular activities in mouse Tconvs are not triggered in an all-or-none manner, but depend on their stage of activation/differentiation. Compared to CD45RBlow Tconvs, CD45RBlowFoxp3+ Tregs show significantly higher levels of P2X7R membrane expression and of sensitivity to ATP as evidenced by their high levels of CD62L shedding, pore formation and PS externalization observed after ATP treatment. In summary, the different abilities of ATP-treated Tconvs to form pore or cleave CD62L depending on their activation and differentiation state suggests that P2X7R signaling varies according to the physiological role of T convs during antigen activation in secondary lymphoid organs or trafficking to inflammatory sites.

Tunable Surface Structuration of Silicon by Metal Assisted Chemical Etching with Pt Nanoparticles under Electrochemical Bias.

An in-depth study of metal assisted chemical etching (MACE) of p-type c-Si in HF/H2O2 aqueous solutions using Pt nanoparticles as catalysts is presented. Combination of cyclic voltammetry, open circuit measurements, chronoamperometry, impedance spectroscopy, and 2D band bending modeling of the metal/semiconductor/electrolyte interfaces at the nanoscale and under different etching conditions allows gaining physical insights into this system. Additionally, in an attempt to mimic the etching conditions, the modeling has been performed with a positively biased nanoparticle buried in the Si substrate. Following these findings, the application of an external polarization during etching is introduced as a novel efficient approach for achieving straightforward control of the pore morphology by acting upon the band bending at the Si/electrolyte junction. In this way, nanostructures ranging from straight mesopores to cone-shaped macropores are obtained as the Si sample is biased from negative to positive potentials. Remarkably, macroscopic cone-shaped pores in the 1-5 µm size range with a high aspect ratio (L/W ∼ 1.6) are obtained by this method. This morphology leads to a reduction of the surface reflectance below 5% over the entire VIS-NIR domain, which outperforms macrostructures made by state of the art texturization techniques for Si solar cells.

Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction.

Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit-independent MC-deficient (Cpa3(Cre/+)) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca(2+) desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force-Ca(2+) interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators.