Modeling the shortening history of a fault tip fold using structural and geomorphic records of deformation

We present a methodology to derive the growth history of a fault tip fold above a basal detachment. Our approach is based on modeling the stratigraphic and geomorphic records of deformation, as well as the finite structure of the fold constrained from seismic profiles. We parameterize the spatial deformation pattern using a simple formulation of the displacement field derived from sandbox experiments. Assuming a stationary spatial pattern of deformation, we simulate the gradual warping and uplift of stratigraphic and geomorphic markers, which provides an estimate of the cumulative amounts of shortening they have recorded. This approach allows modeling of isolated terraces or growth strata. We apply this method to the study of two fault tip folds in the Tien Shan, the Yakeng and Anjihai anticlines, documenting their deformation history over the past 6–7 Myr. We show that the modern shortening rates can be estimated from the width of the fold topography provided that the sedimentation rate is known, yielding respective rates of 2.15 and 1.12 mm/yr across Yakeng and Anjihai, consistent with the deformation recorded by fluvial and alluvial terraces. This study demonstrates that the shortening rates across both folds accelerated significantly since the onset of folding. It also illustrates the usefulness of a simple geometric folding model and highlights the importance of considering local interactions between tectonic deformation, sedimentation, and erosion

Mast Cells and Company

Classically, allergy depends on IgE antibodies and on high-affinity IgE receptors expressed by mast cells and basophils. This long accepted IgE/FcεRI/mast cell paradigm, on which the definition of immediate hypersensitivity was based in the Gell and Coomb’s classification, appears too reductionist. Recently accumulated evidence indeed requires that not only IgE but also IgG antibodies, that not only FcεRI but also FcγR of the different types, that not only mast cells and basophils but also neutrophils, monocytes, macrophages, eosinophils, and other myeloid cells be considered as important players in allergy. This view markedly changes our understanding of allergic diseases and, possibly, their treatment

Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus

Public health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of immune cell lines. These observations prompted us to investigate the molecular mechanisms and responses to antibody-mediated infection in human macrophages.published_or_final_versio

Antibody-dependent enhancement of SARS coronavirus infection and its role in the pathogenesis of SARS

1. Anti-SARS-CoV spike antibodies promote infection of primary human immune cells by SARS-CoV. 2. The antibody-dependent enhancement (ADE) infection pathway grants SARS-CoV an opportunity to infect primary human macrophages, but it does not sustain productive viral replication in the infected cells. 3. ADE of SARS-CoV infection does not alter pro-inflammatory gene expression profile of primary human macrophages. 4. Infectivity of SARS-CoV does not rely solely on the potency of target cells to bind — via Fcγ receptor II (CD32) — infectious immune complexes, but depends on the properties of the intracellular domain of the FcγRII. 5. Occurrence of ADE of SARS-CoV infection into human primary macrophages, without alteration to their pro-inflammatory properties, advocates cautious development of SARS-CoV vaccine in humans, and provides new ways of investigation to understand the pathogenesis of SARS.published_or_final_versio

The clumped isotope geothermometer in soil and paleosol carbonate

We studied both modern soils and buried paleosols in order to understand the relationship of temperature estimated from clumped isotopes in carbonates (T°C_(clumped)) to actual surface and burial temperatures. Carbonates from modern soils in a broad range of climates were sampled from Arizona, Nevada, Tibet, and India. T°C_(clumped) obtained from these soils shows that soil carbonate only forms in the very warmest months of the year, largely in the afternoon, and probably in response to intense soil dewatering. The highest T°C_(clumped) obtained from modern soil carbonate are <40°C On average, T°C_(clumped) significantly exceeds mean annual temperature by 10-15°C due to (1) summertime bias in soil carbonate formation, and (2) sensible heating of soil. Secondary controls on T°C_(clumped) are site aspect, but especially soil depth and shading

Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation

Mastocytosis is a rare neoplastic disease characterized by a pathologic accumulation of tissue mast cells (MCs). Mastocytosis is often associated with a somatic point mutation in the Kit protooncogene leading to an Asp/Val substitution at position 816 in the kinase domain of this receptor. The contribution of this mutation to mastocytosis development remains unclear. In addition, the clinical heterogeneity presented by mastocytosis patients carrying the same mutation is unexplained. We report that a disease with striking similarities to human mastocytosis develops spontaneously in transgenic mice expressing the human Asp816Val mutant Kit protooncogene specifically in MCs. This disease is characterized by clinical signs ranging from a localized and indolent MC hyperplasia to an invasive MC tumor. In addition, bone marrow–derived MCs from transgenic animals can be maintained in culture for >24 mo and acquire growth factor independency for proliferation. These results demonstrate a causal link in vivo between the Asp816Val Kit mutation and MC neoplasia and suggest a basis for the clinical heterogeneity of human mastocytosis

Displaying Fel d1 on virus-like particles prevents reactogenicity despite greatly enhanced immunogenicity: a novel therapy for cat allergy

Allergen-specific desensitization is the only disease-modifying therapy currently available for the treatment of allergies. These therapies require application of allergen over several years and some may induce life-threatening anaphylactic reactions. An ideal vaccine for desensitization should be highly immunogenic and should alleviate allergic symptoms upon few injections while being nonreactogenic. We describe such a vaccine for the treatment of cat allergy, consisting of the major cat allergen Fel d1 coupled to bacteriophage Qβ-derived virus-like particles (Qβ–Fel d1). Qβ–Fel d1 was highly immunogenic, and a single vaccination was sufficient to induce protection against type I allergic reactions. Allergen-specific immunoglobulin G antibodies were shown to be the critical effector molecules and alleviated symptoms by two distinct mechanisms. Although allergen-induced systemic basophil degranulation was inhibited in an FcγRIIb-dependent manner, inhibition of local mast cell degranulation in tissues occurred independently of FcγRIIb. In addition, treatment with Qβ–Fel d1 abolished IgE memory responses upon antigen recall. Despite high immunogenicity, the vaccine was essentially nonreactogenic and vaccination induced neither local nor systemic anaphylactic reactions in sensitized mice. Moreover, Qβ–Fel d1 did not induce degranulation of basophils derived from human volunteers with cat allergies. These data suggest that vaccination with Qβ–Fel d1 may be a safe and effective treatment for cat allergy

Kinematics of fault-related folding derived from a sandbox experiment

We analyze the kinematics of fault tip folding at the front of a fold-and-thrust wedge using a sandbox experiment. The analog model consists of sand layers intercalated with low-friction glass bead layers, deposited in a glass-sided experimental device and with a total thickness h = 4.8 cm. A computerized mobile backstop induces progressive horizontal shortening of the sand layers and therefore thrust fault propagation. Active deformation at the tip of the forward propagating basal décollement is monitored along the cross section with a high-resolution CCD camera, and the displacement field between pairs of images is measured from the optical flow technique. In the early stage, when cumulative shortening is less than about h/10, slip along the décollement tapers gradually to zero and the displacement gradient is absorbed by distributed deformation of the overlying medium. In this stage of detachment tip folding, horizontal displacements decrease linearly with distance toward the foreland. Vertical displacements reflect a nearly symmetrical mode of folding, with displacements varying linearly between relatively well defined axial surfaces. When the cumulative slip on the décollement exceeds about h/10, deformation tends to localize on a few discrete shear bands at the front of the system, until shortening exceeds h/8 and deformation gets fully localized on a single emergent frontal ramp. The fault geometry subsequently evolves to a sigmoid shape and the hanging wall deforms by simple shear as it overthrusts the flat ramp system. As long as strain localization is not fully established, the sand layers experience a combination of thickening and horizontal shortening, which induces gradual limb rotation. The observed kinematics can be reduced to simple analytical expressions that can be used to restore fault tip folds, relate finite deformation to incremental folding, and derive shortening rates from deformed geomorphic markers or growth strata

Mouse and human neutrophils induce anaphylaxis

International audienceAnaphylaxis is a life-threatening hyperacute immediate hypersensitivity reaction. Classically, it depends on IgE, FcεRI, mast cells, and histamine. However, anaphylaxis can also be induced by IgG antibodies, and an IgG1-induced passive type of systemic anaphylaxis has been reported to depend on basophils. In addition, it was found that neither mast cells nor basophils were required in mouse models of active systemic anaphylaxis. Therefore, we investigated what antibodies, receptors, and cells are involved in active systemic anaphylaxis in mice. We found that IgG antibodies, FcγRIIIA and FcγRIV, platelet-activating factor, neutrophils, and, to a lesser extent, basophils were involved. Neutrophil activation could be monitored in vivo during anaphylaxis. Neutrophil depletion inhibited active, and also passive, systemic anaphylaxis. Importantly, mouse and human neutrophils each restored anaphylaxis in anaphylaxis-resistant mice, demonstrating that neutrophils are sufficient to induce anaphylaxis in mice and suggesting that neutrophils can contribute to anaphylaxis in humans. Our results therefore reveal an unexpected role for IgG, IgG receptors, and neutrophils in anaphylaxis in mice. These molecules and cells could be potential new targets for the development of anaphylaxis therapeutics if the same mechanism is responsible for anaphylaxis in humans