Regional equivalent water thickness modeling from remote sensing across a tree cover/lai gradient in mediterranean forests of northern Tunisia

The performance of vegetation indexes derived from moderate resolution imaging spectroradiometer (MODIS) sensors is explored for drought monitoring in the forests of Northern Tunisia; representing a transition zone between the Mediterranean Sea and the Sahara Desert. We investigated the suitability of biomass and moisture vegetation indexes for vegetation water content expressed by the equivalent water thickness (EWT) in a Mediterranean forest ecosystem with contrasted water budgets and desiccation rates. We proposed a revised EWT at canopy level (EWTCAN) based on weekly field measurements of fuel moisture in seven species during the 2010 dry period, considering the mixture of plant functional types for water use (trees, shrubs and herbaceous layers) and a varying vegetation cover. MODIS vegetation indexes computed and smoothed over the dry season were highly correlated with the EWTCAN. The performances of moisture indexes Normalized Difference Infrared Index (NDII6 and NDII7) and Global Moisture Vegetation Index (GVMI6 and GVMI7) were comparable, whereas for biomass vegetation indexes, Normalized Difference Vegetation Index (NDVI), Modified Soil Adjusted Vegetation Index (MSAVI) and Adjusted Normalized Difference Vegetation Index (ANDVI) performed better than Enhanced Vegetation Index (EVI) and Soil Adjusted Vegetation Index (SAVI). We also identified the effect of Leaf Area Index (LAI) on EWTCAN monitoring at the regional scale under the tree cover/LAI gradient of the region from relatively dense to open forest. Statistical analysis revealed a significant decreasing linear relationship; indicating that for LAI less than two, the greater the LAI, the less responsive are the vegetation indexes to changes in EWTCAN; whereas for higher LAI, its influence becomes less significant and was not considered in the inversion models based on vegetation indexes. The EWTCAN time-course from LAI-adapted inversion models based on significantly-related vegetation indexes to EWTCAN showed close profiles resulting from the inversion models using NDVI, ANDVI, MSAVI and NDII6 applied during the dry season. The developed EWTCAN model from MODIS vegetation indexes for the study region was finally tested for its ability to capture the topo-climatic effects on the seasonal and the spatial patterns of desiccation/rewetting for keystone periods of Mediterranean vegetation functioning. Implications for further use in scientific developments or management are discussed

Self-assembly of diblock molecular polymer brushes in the spherical confinement of nanoemulsion droplets

Understanding the self-assembly behavior of polymers of various topologies is key to a reliable design of functional polymer materials. Self-assembly under confinement conditions emerges as a versatile avenue to design polymer particles with complex internal morphologies while simultaneously facilitating scale-up. However, only linear block copolymers have been studied to date, despite the increasing control over macromolecule composition and architecture available. This study extends the investigation of polymer self-assembly in confinement from regular diblock copolymers to diblock molecular polymer brushes (MPBs). Block-type MPBs with polystyrene (PS) and polylactide (PLA) compartments of different sizes are incorporated into surfactant-stabilised oil-in-water (chloroform/water) emulsions. The increasing confinement in the nanoemulsion droplets during solvent evaporation directs the MPBs to form solid nano/microparticles. Microscopy studies reveal an intricate internal particle structure, including interpenetrating networks and axially-stacked lamellae of PS and PLA, depending on the PS/PLA ratio of the brushes.Australian Research Council. Grant Number: DE180100007 endowed professorship. Grant Number: 2016‐2022 German Research Foundation (DFG). Grant Numbers: 2017‐2022, 37692067

Computational Design To Reduce Conformational Flexibility and Aggregation Rates of an Antibody Fab Fragment

Computationally-guided semi-rational design has significant potential for improving the aggregation kinetics of protein biopharmaceuticals. While improvement in the global conformational stability can stabilise proteins to aggregation under some conditions, previous studies suggest that such an approach is limited because thermal transition temperatures (Tm) and the fraction of protein unfolded (fT) tend to only correlate with aggregation kinetics where the protein is incubated at temperatures approaching the Tm. This is because under these conditions, aggregation from globally unfolded protein becomes dominant. However, under native conditions, the aggregation kinetics are presumed to be dependent on local structural fluctuations or partial unfolding of the native state, that reveal regions of high propensity to form protein-protein interactions that lead to aggregation. In this work, we have targeted the design of stabilising mutations to regions of the A33 Fab surface structure, that were predicted to be more flexible. This Fab already has high global stability, and global unfolding is not the main cause of aggregation under most conditions. Therefore, the aim was to reduce the conformational flexibility and entropy of the native protein at various locations, and thus identify which of those regions has the greatest influence on the aggregation kinetics. Highly dynamic regions of structure were identified through both molecular dynamics simulation, and B-factor analysis of related X-ray crystal structures. The most flexible residues were mutated into more stable variants, as predicted by Rosetta, which evaluates the ΔΔGND for each potential point mutation. Additional destabilising variants were prepared as controls to evaluate the prediction accuracy, and also to assess the general influence of conformational stability on aggregation kinetics. The thermal conformational stability, and aggregation rates of eighteen variants at 65 °C, were each examined at pH 4, 200 mM ionic strength, under which conditions the initial wild-type protein was <5% unfolded. Variants with decreased Tm values led to more rapid aggregation due to an increase in the fraction of protein unfolded under the conditions studied. As expected, no significant improvements were observed in the global conformational stability as measured by Tm. However, six of the twelve stable variants led to an increase in the cooperativity of unfolding, consistent with lower conformational flexibility and entropy in the native ensemble. Three of these had 5-11% lower aggregation rates, and their structural clustering indicated that the local dynamics of the C-terminus of the heavy chain had a role in influencing the aggregation rate

Case Report: Giant cystic schwannoma of the middle mediastinum with cervical extension

Schwannomas (neurilemmomas) are benign tumors arising from the Schwann cells of the neural sheath. They are typically, well-encapsulated lesions which rarely adhere to the adjacent structures. In the chest, schwannomas are often seen within the posterior mediastinum and commonly originating along intercostal nerves. Several operative approaches have previously been described for the resection of these tumors, including thoracoscopic techniques and posterolateral thoracotomy. We report in this case a giant cystic mediastinal schwannoma of the left recurrent laryngeal nerve with cervical extension, unresectable by the usual described approaches, which was completely removed through a cervical approach.Keywords: mediastinal tumor; schwannoma; thoracotomy; cervicotom

Comparison of the pH- and thermally-induced fluctuations of a therapeutic antibody Fab fragment by molecular dynamics simulation

Successful development of protein therapeutics depends critically on achieving stability under a range of conditions. A deeper understanding of the drivers of instability across different stress conditions, will enable the engineering of more robust protein scaffolds. We compared the impacts of low pH and high temperature stresses on the structure of a humanized antibody fragment (Fab) A33, using atomistic molecular dynamics simulations, using a recent 2.5 Å crystal structure. This revealed that low-pH induced the loss of native contacts in the domain CL. By contrast, thermal stress led to 5–7% loss of native contacts in all four domains, and simultaneous loss of >30% of native contacts in the VL-VH and CL-CH interfaces. This revealed divergent destabilising pathways under the two different stresses. The underlying cause of instability was probed using FoldX and Rosetta mutation analysis, and packing density calculations. These agreed that mutations in the CL domain, and CL-CH1 interface have the greatest potential for stabilisation of Fab A33. Several key salt bridge losses underpinned the conformational change in CL at low pH, whereas at high temperature, salt bridges became more dynamic, thus contributing to an overall destabilization. Lastly, the unfolding events at the two stress conditions exposed different predicted aggregation-prone regions (APR) to solvent, which would potentially lead to different aggregation mechanisms. Overall, our results identified the early stages of unfolding and stability-limiting regions of Fab A33, and the VH and CL domains as interesting future targets for engineering stability to both pH- and thermal-stresses simultaneously

Localisation nasosinusienne des tumeurs plasmocytaires

Introduction : Les tumeurs plasmocytaires représentent 3 à 4% des tumeurs des cavités naso-sinusiennes. Elles nécessitent un bilan diagnostique spécifique et une prise en charge adéquate. Nous nous proposons d’étudier les particularités diagnostiques et thérapeutiques des plasmocytomes naso-sinusiens. Matériel et méthodes : Notre étude est rétrospective comportant 5 cas de plasmocytomes naso-sinusiens confirmés histologiquement.Résultats : Il s’agit de 3 hommes et 2 femmes âgés de 32 à 77 ans. Le plasmocytome avait une localisation sphénoïdale dans un cas, nasale dans 2 cas, ethmoïdo-nasale dans un cas et naso-maxillaire dans le cas restant. Il s’agissait d’un myélome multiple dans un cas. Trois patients ont eu une radiothérapie. Celle-ci était associée à une chimiothérapie dans le cas du myélome multiple et à une exérèse chirurgicale dans les 2 autres cas La chirurgie a été seule dans un cas. La chimiothérapie exclusive a été proposée dans un cas de plasmocytome localement avancé mais le patient a été perdu de vue. Pour les patients suivis, une seule récidive a été notée à 18 mois.Conclusion : La présentation clinique des plasmocytomes nasosinusiens est aspécifique. Le diagnostic est confirmé par l’histologie. Le pronostic est dominé par la présence ou non d’un myélome multiple et par la taille tumorale. Un suivi prolongé est nécessaire.Mots clés : plasmocytome extramédullaire ; cavités naso-sinusiennes ; radiothérapie ; chirurgie.Introduction: Plasmocytomas represent 3-4% of tumors naso-sinus cavities. Their diagnosis requires a specific investigations and adequate management. We report 5 cases of naso-sinus plasmacytoma and we propose to study their diagnostic and therapeutic characteristics.Materials and methods: Our study is retrospective including 5 cases of naso-sinus plasmacytoma confirmed histologically.Results: There were 3 men and 2 women aged 32 to 77 years. The plasmacytoma had a sphenoidal location in one case, nasal in 2 cases, ethmoid-nasal in one case and naso-maxillary in the remaining case. Multiple myeloma was found in one case. Three patients underwent radiotherapy. This was associated with chemotherapy in multiple myeloma case and surgical resection in 2 cases. Surgery alone was performed in one case. Exclusive chemotherapy was proposed in a case of plasmacytoma locally advanced but the patient was lost sight of. For followed patients, only one recurrence was noted at 18 months.Conclusion: The clinical presentation of sinonasal plasmacytomas is aspecific. The diagnosis is confirmed by histology. The prognosis is dominated by the presence or absence of multiple myeloma and tumor size. Prolonged follow-up is necessary.Keywords : extramedullary plasmacytoma, naso-sinus cavities, radiotherapy ; surgery

Confinement Assembly of ABC Triblock Terpolymers for the High-Yield Synthesis of Janus Nanorings

Block copolymers are versatile building blocks for the self-assembly of functional nanostructures in bulk and solution. While spheres, cylinders, and bilayer sheets are thermodynamically preferred shapes and frequently observed, ring-shaped nanoparticles are more challenging to realize due to energetic penalties that originate from their anisotropic curvature. Today, a handful of concepts exist that produce core-shell nanorings, while more complex (e.g. patchy) nanorings are currently out of reach and have only been predicted theoretically. Here, we demonstrate that confinement assembly of properly designed ABC triblock terpolymers is a general route to synthesize Janus nanorings in high purity. The triblock terpolymer self-assembles in the spherical confinement of nanoemulsion droplets into prolate ellipsoidal microparticles with an axially-stacked lamellar-ring (lr)-morphology. We clarified and visualized this complex, yet well-ordered, morphology with transmission electron tomography (ET). Blocks A and C formed stacks of lamellae with the B microdomain sandwiched in-between as nanorings. Cross-linking of the B-rings allows disassembly of the microparticles into Janus nanorings (JNRs) carrying two strictly separated polymer brushes of A and C on top and bottom. Decreasing the B volume leads to Janus spheres and rods, while an increase of B results in perforated and filled Janus disks. The confinement assembly of ABC triblock terpolymers is a general process that can be extended to other block chemistries and will allow to synthesize a large variety of complex micro- and nanoparticles that inspire studies in self-assembly, interfacial stabilization, colloidal packing, and nanomedicine

Quel bilan d’extension faut-il faire pour les carcinomes indifferencies du nasopharynx ?

Introduction: Nasopharyngeal carcinoma prognosis is often correlated with its local extension but especially lymphatic node and metastatic.The aimof our work was to study sensitivity and the specificity of clinical and paraclinic explorations in the initial assessmentPatients and methods : It .s about a retrospective study of 366 patients having nasopharyngeal carcinoma, diagnosed over eleven years period between 1993 and 2003 in Sfax hospital. Into pretherapeutic, all the patients had a complementary assessment including:- Nasopharyngeal tomodensitometry (TDM), in all the cases, extended to the cervical area in 112 cases and a magnetic resonnance Imagery (MRI) of the nasopharynx and cerebral in 18 cases.- Metastatic assessment: comprising systematically a chest radiography, an abdominal ultrasonography and an osseous scintiscanning. The statistical study comprised a descriptive study and an analytical study.Results : The metastasis diagnosis was retained in 39 cases (10,7%): osseous in 82%, hepatic in 23% and pulmonary in 12,8% of the cases. The tumour was associated to lymph node N3 in 25 cases (64%). At univariate study, we retained the presence of significant difference between the groups of the metastatic and lack metastatic patients for : the male sex, reason for consultation (cervical node, rhinologic signs and otologic signs) and cervical node at the examination.The multivariate analysis for all the factors was without interest. We choose the parameters according to the result of the univariate study, the literature and parameters' found among all patients with discovered CNP. It comes out from this study that the following elements are providers of metastases: age between 40 and 45years, male sex and cervical node N3a stage.Discussion : The assessment of extension is not standardized for all the authors. Indeed, for the study of the pulmonary extension (AJCC)/ (UICC) recommends the systematic practice of the chest radiography. For (NCCN), the practice of chest radiography is only for patients classified at the stage 2 and 3 in WHO classification. For KUMAR, LEUNG and our results, it is recommended systematically to practice the chest radiography . This radiography would be supplemented by a thoracic tomodensitometry with the least suspect lesion. For the hepatic assessment, some recommend the systematic practice of abdominal echography for the advanced nodestages (N3). For others, it will be indicated only for the symptomatic patients. For (AJCC)/ (UICC) abdominal echography is systematic.For the osseous assessment, KRAIPHIBUL recommends the practice of the osseous scintiscanning only for patients having signs of osseous call but LEUNG and SHAM recommend the practice of the osseous scintiscanning only for the patients having cervical node N3.Key words: Nasopharyngeal carcinoma/ extension assessment/ metastasis

Formes histologiques particulieres du cancer du nasopharynx

Le carcinome épidermoïde du nasopharynx est la forme histopathologique la plus fréquente. Cependant, d'autres formeshistologiques, bien qu’exceptionnelles peuvent se voir. Le but de notre travail est d'étudier le profil thérapeutique et évolutif de ces entités. Nous rapportons trois observations particulières de cancer du cavum. Il s'agissait de 3 patientes âgées respectivement de 15, 36 et 33 ans. La première patiente, atteinte d'un mélanome malin du cavum (T2aN2Mo) (UICCC 97), a bénéficié d'un évidement ganglionnaire cervical radical droit suivi d'une chimiothérapie. La patiente est décédée un mois et demi plus tard. La deuxième patiente, atteinte d'un carcinome mucoépidermoïde du cavum (T4NoMo) (UICCC 97) a bénéficié d'uneradio-chimiothérapie concomitante avec rémission complète à 17 mois de recul. La troisième patiente, présente un carcinome adénoïde kystique du cavum (T2bNoMo) (UICCC 97), a bénéficié d'une exérèse tumorale large avec évidement ganglionnaire cervical homolatéral suivie d'une radiothérapie post opératoire. Elle a présenté des métastases pulmonaires 12 mois après, traitées par chimiothérapie avec une réponse partielle. Actuellement, elle est à 18 mois de recul après la chimiothérapie. Ces formes histopathologiques du cancer du cavum sont exceptionnelles (< 1 % des tumeurs malignes du cavum). Il n'existe aucune particularité clinique ou radiologique et le diagnostic reste histopathologique. Ces tumeurs posent un problème de prise en charge puisqu’il n’existe pas de traitement codifié pour ces formes rares. Le pronostic dépend du stade de la maladie et du type histologique.Mots clés : nasopharynx, cancer, mélanome, carcinome mucoépidermoïde, carcinome adénoïde kystique, chirurgie, radiothérapie, chimiothérapie

GPI-anchor signal sequence influences PrPC sorting, shedding and signalling, and impacts on different pathomechanistic aspects of prion disease in mice

The cellular prion protein (PrPC) is a cell surface glycoprotein attached to the membrane by a glycosylphosphatidylinositol (GPI)-anchor and plays a critical role in transmissible, neurodegenerative and fatal prion diseases. Alterations in membrane attachment influence PrPC-associated signaling, and the development of prion disease, yet our knowledge of the role of the GPI-anchor in localization, processing, and function of PrPC in vivo is limited We exchanged the PrPC GPI-anchor signal sequence of for that of Thy-1 (PrPCGPIThy-1) in cells and mice. We show that this modifies the GPI-anchor composition, which then lacks sialic acid, and that PrPCGPIThy-1 is preferentially localized in axons and is less prone to proteolytic shedding when compared to PrPC. Interestingly, after prion infection, mice expressing PrPCGPIThy-1 show a significant delay to terminal disease, a decrease of microglia/astrocyte activation, and altered MAPK signaling when compared to wild-type mice. Our results are the first to demonstrate in vivo, that the GPI-anchor signal sequence plays a fundamental role in the GPI-anchor composition, dictating the subcellular localization of a given protein and, in the case of PrPC, influencing the development of prion disease