Glossaire illustré sur les formes d’altération de la pierre

The ICOMOS International Scientific Committee for Stone (ISCS) is providing a forum for the interchange of experience, ideas, and knowledge in the field of stone conservation. ISCS aims at facilitating the publication, dissemination and presentation of state of the art reviews on pre-identified issues. Simplification and demystification of scientific information for practitioners are also part of the main goals of the group. In studies on stone deterioration and conservation, terminological confusions lead to major communication problems between scientists, conservators and practitioners. In this context, it is of primary importance to set up a common language; if degradation patterns can be shown, named and described, then they can be recognised and compared with similar ones in a more accurate way in further investigations. The ISCS glossary constitutes an important tool for scientific discussions on decay phenomena and processes. It is also an excellent basis for tutorials on stone deterioration. It is based on the careful examination of pre-existing glossaries of English terms. It does not aim at replacing these glossaries, often set up originally in a language other than English, and for most of them done to a high standard. As President of ICOMOS I would like to congratulate the International Scientific Committee for Stone and its President Véronique Verges-Belmin for the results of years of research presented in this publication. Stone conservation is a crucial topic in monument conservation and many of our National Committees all over the world hope for advice and help from the specialists familiar with traditional and modern methods of conservation. The Illustrated Glossary on Stone Deterioration Patterns offers a wide range of suggestions and practical advice. Probably, after the English-French version becomes available the Glossary will also be translated into other languages. In view of the accelerating decay of our stone monuments worldwide this is an exemplary contribution which will promote the international cooperation so important in this field.peer-reviewe

Spine-to-Dendrite Calcium Modeling Discloses Relevance for Precise Positioning of Ryanodine Receptor-Containing Spine Endoplasmic Reticulum

Abstract The endoplasmic reticulum (ER) forms a complex endomembrane network that reaches into the cellular compartments of a neuron, including dendritic spines. Recent work discloses that the spine ER is a dynamic structure that enters and leaves spines. While evidence exists that ER Ca2+ release is involved in synaptic plasticity, the role of spine ER morphology remains unknown. Combining a new 3D spine generator with 3D Ca2+ modeling, we addressed the relevance of ER positioning on spine-to-dendrite Ca2+ signaling. Our simulations, which account for Ca2+ exchange on the plasma membrane and ER, show that spine ER needs to be present in distinct morphological conformations in order to overcome a barrier between the spine and dendritic shaft. We demonstrate that RyR-carrying spine ER promotes spine-to-dendrite Ca2+ signals in a position-dependent manner. Our simulations indicate that RyR-carrying ER can initiate time-delayed Ca2+ reverberation, depending on the precise position of the spine ER. Upon spine growth, structural reorganization of the ER restores spine-to-dendrite Ca2+ communication, while maintaining aspects of Ca2+ homeostasis in the spine head. Our work emphasizes the relevance of precise positioning of RyR-containing spine ER in regulating the strength and timing of spine Ca2+ signaling, which could play an important role in tuning spine-to-dendrite Ca2+ communication and homeostasis

Spine-to-dendrite calcium modeling discloses relevance for precise positioning of ryanodine receptor-containing spine endoplasmic reticulum

The endoplasmic reticulum (ER) forms a complex endomembrane network that reaches into the cellular compartments of a neuron, including dendritic spines. Recent work discloses that the spine ER is a dynamic structure that enters and leaves spines. While evidence exists that ER Ca2+ release is involved in synaptic plasticity, the role of spine ER morphology remains unknown. Combining a new 3D spine generator with 3D Ca2+ modeling, we addressed the relevance of ER positioning on spine-to-dendrite Ca2+ signaling. Our simulations, which account for Ca2+ exchange on the plasma membrane and ER, show that spine ER needs to be present in distinct morphological conformations in order to overcome a barrier between the spine and dendritic shaft. We demonstrate that RyR-carrying spine ER promotes spine-to-dendrite Ca2+ signals in a position-dependent manner. Our simulations indicate that RyR-carrying ER can initiate time-delayed Ca2+ reverberation, depending on the precise position of the spine ER. Upon spine growth, structural reorganization of the ER restores spine-to-dendrite Ca2+ communication, while maintaining aspects of Ca2+ homeostasis in the spine head. Our work emphasizes the relevance of precise positioning of RyR-containing spine ER in regulating the strength and timing of spine Ca2+ signaling, which could play an important role in tuning spine-to-dendrite Ca2+ communication and homeostasis

Calcium modeling of spine apparatus-containing human dendritic spines demonstrates an "all-or-nothing" communication switch between the spine head and dendrite.

Dendritic spines are highly dynamic neuronal compartments that control the synaptic transmission between neurons. Spines form ultrastructural units, coupling synaptic contact sites to the dendritic shaft and often harbor a spine apparatus organelle, composed of smooth endoplasmic reticulum, which is responsible for calcium sequestration and release into the spine head and neck. The spine apparatus has recently been linked to synaptic plasticity in adult human cortical neurons. While the morphological heterogeneity of spines and their intracellular organization has been extensively demonstrated in animal models, the influence of spine apparatus organelles on critical signaling pathways, such as calcium-mediated dynamics, is less well known in human dendritic spines. In this study we used serial transmission electron microscopy to anatomically reconstruct nine human cortical spines in detail as a basis for modeling and simulation of the calcium dynamics between spine and dendrite. The anatomical study of reconstructed human dendritic spines revealed that the size of the postsynaptic density correlates with spine head volume and that the spine apparatus volume is proportional to the spine volume. Using a newly developed simulation pipeline, we have linked these findings to spine-to-dendrite calcium communication. While the absence of a spine apparatus, or the presence of a purely passive spine apparatus did not enable any of the reconstructed spines to relay a calcium signal to the dendritic shaft, the calcium-induced calcium release from this intracellular organelle allowed for finely tuned "all-or-nothing" spine-to-dendrite calcium coupling; controlled by spine morphology, neck plasticity, and ryanodine receptors. Our results suggest that spine apparatus organelles are strategically positioned in the neck of human dendritic spines and demonstrate their potential relevance to the maintenance and regulation of spine-to-dendrite calcium communication

Implication of the Receptor Tyrosine Kinase AXL in Head and Neck Cancer Progression

Head and neck squamous cell carcinoma (HNSCC) remains a clinical challenge and identification of novel therapeutic targets is necessary. The receptor tyrosine kinase AXL has been implicated in several tumor entities and a selective AXL small molecule inhibitor (BGB324) is currently being tested in clinical trials for patients suffering from non-small cell lung cancer or acute myeloid leukemia. Our study investigates AXL expression during HNSCC progression and its use as a potential therapeutic target in HNSCC. AXL protein expression was determined in a HNSCC cohort (n = 364) using immunohistochemical staining. For functional validation, AXL was either overexpressed or inhibited with BGB324 in HNSCC cell lines to assess proliferation, migration and invasion. We found AXL protein expression increasing during tumor progression with highest expression levels in recurrent tumors. In HNSCC cell lines in vitro, AXL overexpression increased migration as well as invasion. Both properties could be reduced through treatment with BGB324. In contrast, proliferation was neither affected by AXL overexpression nor by inhibition with BGB324. Our patient-derived data and in vitro results show that, in HNSCC, AXL is important for the progression to more advanced tumor stages. Moreover, they suggest that AXL could be a target for precision medicine approaches in this dismal tumor entity

Targeting DDR2 in head and neck squamous cell carcinoma with dasatinib

Squamous cell carcinoma of the head and neck (HNSCC) is the tenth most common tumor entity in men worldwide. Nevertheless therapeutic options are mostly limited to surgery and radio-chemotherapy resulting in 5-year survival rates of around 50%. Therefore new therapeutic options are urgently needed. During the last years, targeting of receptor tyrosine kinases has emerged as a promising strategy that can complement standard therapeutical approaches. Here, we aimed at investigating if the receptor tyrosine kinase DDR2 is a targetable structure in HNSCC. DDR2 expression was assessed on a large HNSCC cohort (554 patients) including primary tumors, lymph node metastases and recurrences and normal mucosa as control. Subsequently, DDR2 was stably overexpressed in two different cell lines (FaDu and HSC-3) using lentiviral technology. Different tumorigenic properties such as proliferation, migration, invasion, adhesion and anchorage independent growth were assessed with and without dasatinib treatment using in-vitro cell models and in-vivo zebrafish xenografts. DDR2 was overexpressed in all tumor tissues when compared to normal mucosa. DDR2 overexpression led to increased migration, invasion, adhesion and anchorage independent growth whereas proliferation remained unaltered. Upon dasatinib treatment migration, invasion and adhesion could be inhibited in-vitro and in-vivo whereas proliferation was unchanged. Our data suggest treatment with dasatinib as a promising new therapeutic option for patients suffering from DDR2 overexpressing HNSCC. Since dasatinib is already FDA-approved we propose to test this drug in clinical trials so that patients could directly benefit from this new treatment option

Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia

Early allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as primary treatment modality for patients with chronic myeloid leukemia (CML). This concept has been challenged by transplantation mortality and improved drug therapy. In a randomized study, primary HSCT and best available drug treatment (IFN based) were compared in newly diagnosed chronic phase CML patients. Assignment to treatment strategy was by genetic randomization according to availability of a matched related donor. Evaluation followed the intention-to-treat principle. Six hundred and twenty one patients with chronic phase CML were stratified for eligibility for HSCT. Three hundred and fifty four patients (62% male; median age, 40 years; range, 11-59 years) were eligible and randomized. One hundred and thirty five patients (38%) had a matched related donor, of whom 123 (91%) received a transplant within a median of 10 months (range, 2-106 months) from diagnosis. Two hundred and nineteen patients (62%) had no related donor and received best available drug treatment. With an observation time up to 11.2 years (median, 8.9 years), survival was superior for patients with drug treatment (P = .049), superiority being most pronounced in low-risk patients (P = .032). The general recommendation of HSCT as first-line treatment option in chronic phase CML can no longer be maintained. It should be replaced by a trial with modern drug treatment first