MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.

Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p < 0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients.

Modeling growth and yield of loblolly pinestands under intensive management

Abstract:The objective of this work was to develop and validate a prognosis system for volume yield and basal area of intensively managed loblolly pine (Pinus taeda) stands, using stand and diameter class models compatible in basal area estimates. The data used in the study were obtained from plantations located in northern Uruguay. For model validation without data loss, a three-phase validation scheme was applied: first, the equations were fitted without the validation database; then, model validation was carried out; and, finally, the database was regrouped to recalibrate the parameter values. After the validation and final parameterization of the models, a simulation of the first commercial thinning was carried out. The developed prognosis system was precise and accurate in estimating basal area production per hectare or per diameter classes. There was compatibility in basal area estimates between diameter class and whole stand models, with a mean difference of -0.01 m2ha-1. The validation scheme applied is logic and consistent, since information on the accuracy and precision of the models is obtained without the loss of any information in the estimation of the models' parameters.

Sparse image reconstruction on the sphere: implications of a new sampling theorem.

We study the impact of sampling theorems on the fidelity of sparse image reconstruction on the sphere. We discuss how a reduction in the number of samples required to represent all information content of a band-limited signal acts to improve the fidelity of sparse image reconstruction, through both the dimensionality and sparsity of signals. To demonstrate this result, we consider a simple inpainting problem on the sphere and consider images sparse in the magnitude of their gradient. We develop a framework for total variation inpainting on the sphere, including fast methods to render the inpainting problem computationally feasible at high resolution. Recently a new sampling theorem on the sphere was developed, reducing the required number of samples by a factor of two for equiangular sampling schemes. Through numerical simulations, we verify the enhanced fidelity of sparse image reconstruction due to the more efficient sampling of the sphere provided by the new sampling theorem.

Cluster-based active learning for compact image classification

In this paper, we consider active sampling to label pixels grouped with hierarchical clustering. The objective of the method is to match the data relationships discovered by the clustering algorithm with the user's desired class semantics. The first is represented as a complete tree to be pruned and the second is iteratively provided by the user. The active learning algorithm proposed searches the pruning of the tree that best matches the labels of the sampled points. By choosing the part of the tree to sample from according to current pruning's uncertainty, sampling is focused on most uncertain clusters. This way, large clusters for which the class membership is already fixed are no longer queried and sampling is focused on division of clusters showing mixed labels. The model is tested on a VHR image in a multiclass classification setting. The method clearly outperforms random sampling in a transductive setting, but cannot generalize to unseen data, since it aims at optimizing the classification of a given cluster structure.

Molecular tracking of coagulase-negative staphylococcal isolates from catheter-related infections

Three molecular typing methods (pulsed-field electrophoresis, localization of the mecA gene, and probing the vicinity of mec) have been used for the characterization of 40 catheter-related isolates of coagulase-negative staphylococci (CNS) in 14 patients admitted to the same hospital. The 40 isolates yielded 14 different SmaI banding patterns and corresponding unique localizations of mecA, each associated with a unique ClaI mecA polymorph. In 6 of the 14 patients the contaminated skin at the catheter entry site was the source of 4 local infections and 2 cases of bacteremia. A contaminated hub was the origin of 2 local infections and 4 cases of bacteremia in 6 more patients. The remaining 2 patients had positive cultures from both skin and catheter hub. In each bacteremic patient, the CNS recovered from catheter-related sites (tip, skin, and/or hub) and the CNS recovered from blood were identical, but each of these matching isolates was unique to the particular patient, indicating a low rate of cross-infection from patient to patient. Although classical methods for typing CNS (e.g., biotype and antibiotype) are readily available for most hospital laboratories, they have limitations concerning reproducibility and discriminatory power. Molecular epidemiologic techniques can provide powerful support to traditional techniques in determining the etiologic role of CNS in the disease process

Polarized cell growth in Arabidopsis requires endosomal recycling mediated by GBF1-related ARF exchange factors.

Polarized tip growth is a fundamental cellular process in many eukaryotic organisms, mediating growth of neuronal axons and dendrites or fungal hyphae. In plants, pollen and root hairs are cellular model systems for analysing tip growth. Cell growth depends on membrane traffic. The regulation of this membrane traffic is largely unknown for tip-growing cells, in contrast to cells exhibiting intercalary growth. Here we show that in Arabidopsis, GBF1-related exchange factors for the ARF GTPases (ARF GEFs) GNOM and GNL2 play essential roles in polar tip growth of root hairs and pollen, respectively. When expressed from the same promoter, GNL2 (in contrast to the early-secretory ARF GEF GNL1) is able to replace GNOM in polar recycling of the auxin efflux regulator PIN1 from endosomes to the basal plasma membrane in non-tip growing cells. Thus, polar recycling facilitates polar tip growth, and GNL2 seems to have evolved to meet the specific requirement of fast-growing pollen in higher plants.

Study of biomacromolecule conformational changes by Scanning Force Microscopy

L?objectif de ce travail de thèse est l?étude des changements conformationels des biomacromolecules à l?échelle d?une molécule unique. Pour cela on a utilisé la Microscopie à Force Atomique (AFM) appliqué à l?étude des protéines et des acides nucléiques déposés sur une surface. Dans ce type de microscopie, une pointe très fine attachée à l?extrémité d?un levier est balayée au dessus d?une surface. L?interaction de la pointe avec la surface de l?échantillon induit la déflection du levier et ce phénomène permet de reconstruire la topographie de l?échantillon. Très importante dans cette technique est la possibilité de travailler en liquide. Cela permet de étudier les biomolécules en conditions quasi-physiologiques sans qu?elles perdent leur activité. On a étudié GroEL, la chaperonin de E.coli, qui est un homo oligomère avec une structure à double anneau qui joue un rôle très important dans le repliement des protéines dénaturées et celles qui viennent d?être synthétisées. En particulier on a focalisé notre attention sur la stabilité mécanique et sur les changements conformationels qui ont lieu pendant l?activité de GroEL. Une analyse détaillée des changements dans la stabilité mécanique et des effets produits par la liaison et l?hydrolyse de l?ATP est présentée dans ce travail. On a montré que le point le plus faible dans la structure de GroEL est l?interface entre les deux anneaux et que l?étape critique dans l?affaiblissement de la structure est l?hydrolyse de l?ATP. En ce qui concerne le changement conformationel, le passage d?une surface hydrophobe à hydrophile, induit par l?hydrolyse de l?ATP, a été montré. Ensuite on a étudié le changement dans la conformation et dans la topologie de l?ADN résultant de l?interaction avec des molécules spécifiques et en réponse à l?exposition des cellules de E.coli à des conditions de stress. Le niveau de surenroulement est un paramètre très sensible, de façon variée, à tous ces facteurs. Les cellules qui ont crus à de températures plus élevées que leur température optimale ont la tendance à diminuer le nombre de surenroulements négatif pour augmenter la stabilité thermique de leur plasmides. L?interaction avec des agents intercalant induit une transition d?un surenroulement négatif à un surenroulement positif d?une façon dépendante de la température. Finalement, l?effet de l?interaction de l?ADN avec des surfaces différentes a été étudié et une application pratique sur les noeuds d?ADN est présentée.<br/><br/>The aim of the present thesis work is to study the conformational changes of biomacromolecules at the single molecule level. To that end, Atomic Force Microcopy (AFM) imaging was performed on proteins and nucleic acids adsorbed onto a surface. In this microcopy technique a very sharp tip attached at the end of a soft cantilever is scanned over a surface, the interaction of the tip with the sample?s surface will induce the deflection of the cantilever and thus it will make possible to reconstruct the topography. A very important feature of AFM is the possibility to operate in liquid, it means with the sample immersed in a buffer solution. This allows one to study biomolecules in quasi-physiological conditions without loosing their activity. We have studied GroEL, the chaperonin of E.coli, which is a double-ring homooligomer which pays a very important role in the refolding of unfolded and newly synthetized polypeptides. In particular we focus our attention on its mechanical stability and on the conformational change that it undergoes during its activity cycle. A detailed analysis of the change in mechanical stability and how it is affected by the binding and hydrolysis of nucleotides is presented. It has been shown that the weak point of the chaperonin complex is the interface between the two rings and that the critical step to weaken the structure is the hydrolysis of ATP. Concerning the conformational change we have directly measured, with a nanometer scale resolution, the switching from a hydrophobic surface to a hydrophilic one taking place inside its cavity induced by the ATP hydrolysis. We have further studied the change in the DNA conformation and topology as a consequence of the interaction with specific DNA-binding molecules and the exposition of the E.coli cells to stress conditions. The level of supercoiling has been shown to be a very sensitive parameter, even if at different extents, to all these factors. Cells grown at temperatures higher than their optimum one tend to decrease the number of the negative superhelical turns in their plasmids in order to increase their thermal stability. The interaction with intercalating molecules induced a transition from positive to negative supercoiling in a temperature dependent way. The effect of the interaction of the DNA with different surfaces has been investigated and a practical application to DNA complex knots is reported.<br/><br/>Observer les objets biologiques en le touchant Schématiquement le Microscope a Force Atomique (AFM) consiste en une pointe très fine fixée a l?extrémité d?un levier Lors de l?imagerie, la pointe de l?AFM gratte la surface de l?échantillon, la topographie de celui-ci induit des déflections du levier qui sont enregistrées au moyen d?un rayon laser réfléchi par le levier. Ces donnés sont ensuit utilisés par un ordinateur pour reconstituer en 3D la surface de l?échantillon. La résolution de l?instrument est fonction entre autre de la dureté, de la rugosité de l?échantillon et de la forme de la pointe. Selon l?échantillon et la pointe utilisée la résolution de l?AFM peut aller de 0.1 A (sur des cristaux) a quelque dizaine de nanomètres (sur des cellules). Cet instrument est particulierment intéressant en biologie en raison de sa capacité à imager des échantillons immergés dans un liquide, c?est à dire dans des conditions quasiphysiologiques. Dans le cadre de ce travail nous avons étudié les changements conformationels de molécules biologiques soumises à des stimulations externes. Nous avons essentielment concentré notre attention sur des complexes protéiques nommé Chaperons Moléculaires et sur des molécules d?ADN circulaire (plasmides). Les Chaperons sont impliqués entre autre dans la résistance des organismes vivants aux stress thermiques et osmotiques. Leur activité consiste essentielment à aider les autres protéines à être bien pliés dans leur conformation finale et, en conséquence, à eviter que ils soient dénaturées et que ils puissent s?agréger. L?ADN, quant à lui est la molécule qui conserve, dans sa séquence, l?information génétique de tous les organismes vivants. Ce travail a spécifiquement concerné l?étude des changements conformationels des chaperonins suit a leur activation par l?ATP. Ces travaux ont montrés a l?échelle de molécule unique la capacité de ces protéines de changer leur surface de hydrophobique a hydrophilique. Nous avons également utilisé l?AFM pour étudier le changement du nombre des surenroulements des molécules d?ADN circulaire lors d?une exposition à un changement de température et de force ionique. Ces travaux ont permis de montrer comment la cellule regle le nombre de surenroulements dans ces molécules pour répondre et contrôler l?expression génétique même dans de conditions extrêmes. Pour les deux molécules en général, c?était très important d?avoir la possibilité de observer leur transitions d?une conformation a l?autre directement a l?échelle d?une seul molécule et, surtout, avec une résolution largement au dessous des la longueur d?onde de la lumière visible que représente le limite pour l?imagerie optique.

Computational Analysis and Optimization of Real Gas Flow In Small Centrifugal Compressors

Small centrifugal compressors are more and more widely used in many industrialsystems because of their higher efficiency and better off-design performance comparing to piston and scroll compressors as while as higher work coefficient perstage than in axial compressors. Higher efficiency is always the aim of the designer of compressors. In the present work, the influence of four partsof a small centrifugal compressor that compresses heavy molecular weight real gas has been investigated in order to achieve higher efficiency. Two parts concern the impeller: tip clearance and the circumferential position of the splitter blade. The other two parts concern the diffuser: the pinch shape and vane shape. Computational fluid dynamics is applied in this study. The Reynolds averaged Navier-Stokes flow solver Finflo is used. The quasi-steady approach is utilized. Chien's k-e turbulence model is used to model the turbulence. A new practical real gas model is presented in this study. The real gas model is easily generated, accuracy controllable and fairly fast. The numerical results and measurements show good agreement. The influence of tip clearance on the performance of a small compressor is obvious. The pressure ratio and efficiency are decreased as the size of tip clearance is increased, while the total enthalpy rise keeps almost constant. The decrement of the pressure ratio and efficiency is larger at higher mass flow rates and smaller at lower mass flow rates. The flow angles at the inlet and outlet of the impeller are increased as the size of tip clearance is increased. The results of the detailed flow field show that leakingflow is the main reason for the performance drop. The secondary flow region becomes larger as the size of tip clearance is increased and the area of the main flow is compressed. The flow uniformity is then decreased. A detailed study shows that the leaking flow rate is higher near the exit of the impeller than that near the inlet of the impeller. Based on this phenomenon, a new partiallyshrouded impeller is used. The impeller is shrouded near the exit of the impeller. The results show that the flow field near the exit of the impeller is greatly changed by the partially shrouded impeller, and better performance is achievedthan with the unshrouded impeller. The loading distribution on the impeller blade and the flow fields in the impeller is changed by moving the splitter of the impeller in circumferential direction. Moving the splitter slightly to the suction side of the long blade can improve the performance of the compressor. The total enthalpy rise is reduced if only the leading edge of the splitter ismoved to the suction side of the long blade. The performance of the compressor is decreased if the blade is bended from the radius direction at the leading edge of the splitter. The total pressure rise and the enthalpy rise of thecompressor are increased if pinch is used at the diffuser inlet. Among the fivedifferent pinch shape configurations, at design and lower mass flow rates the efficiency of a straight line pinch is the highest, while at higher mass flow rate, the efficiency of a concave pinch is the highest. The sharp corner of the pinch is the main reason for the decrease of efficiency and should be avoided. The variation of the flow angles entering the diffuser in spanwise direction is decreased if pinch is applied. A three-dimensional low solidity twisted vaned diffuser is designed to match the flow angles entering the diffuser. The numerical results show that the pressure recovery in the twisted diffuser is higher than in a conventional low solidity vaned diffuser, which also leads to higher efficiency of the twisted diffuser. Investigation of the detailed flow fields shows that the separation at lower mass flow rate in the twisted diffuser is later than in the conventional low solidity vaned diffuser, which leads to a possible wider flow range of the twisted diffuser.

Effect of Mechanical and Geometric Mismatching on Fatigue and Damage of Welded Joints

The future of high technology welded constructions will be characterised by higher strength materials and improved weld quality with respect to fatigue resistance. The expected implementation of high quality high strength steel welds will require that more attention be given to the issues of crack initiation and mechanical mismatching. Experiments and finite element analyses were performed within the framework of continuum damage mechanics to investigate the effect of mismatching of welded joints on void nucleation and coalescence during monotonic loading. It was found that the damage of undermatched joints mainly occurred in the sandwich layer and the damageresistance of the joints decreases with the decrease of the sandwich layer width. The damage of over-matched joints mainly occurred in the base metal adjacent to the sandwich layer and the damage resistance of the joints increases with thedecrease of the sandwich layer width. The mechanisms of the initiation of the micro voids/cracks were found to be cracking of the inclusions or the embrittled second phase, and the debonding of the inclusions from the matrix. Experimental fatigue crack growth rate testing showed that the fatigue life of under-matched central crack panel specimens is longer than that of over-matched and even-matched specimens. Further investigation by the elastic-plastic finite element analysis indicated that fatigue crack closure, which originated from the inhomogeneousyielding adjacent to the crack tip, played an important role in the fatigue crack propagation. The applicability of the J integral concept to the mismatched specimens with crack extension under cyclic loading was assessed. The concept of fatigue class used by the International Institute of Welding was introduced in the parametric numerical analysis of several welded joints. The effect of weld geometry and load condition on fatigue strength of ferrite-pearlite steel joints was systematically evaluated based on linear elastic fracture mechanics. Joint types included lap joints, angle joints and butt joints. Various combinations of the tensile and bending loads were considered during the evaluation with the emphasis focused on the existence of both root and toe cracks. For a lap joint with asmall lack-of-penetration, a reasonably large weld leg and smaller flank angle were recommended for engineering practice in order to achieve higher fatigue strength. It was found that the fatigue strength of the angle joint depended strongly on the location and orientation of the preexisting crack-like welding defects, even if the joint was welded with full penetration. It is commonly believed that the double sided butt welds can have significantly higher fatigue strength than that of a single sided welds, but fatigue crack initiation and propagation can originate from the weld root if the welding procedure results in a partial penetration. It is clearly shown that the fatigue strength of the butt joint could be improved remarkably by ensuring full penetration. Nevertheless, increasing the fatigue strength of a butt joint by increasing the size of the weld is an uneconomical alternative.

Un modelo de educación trilingüe. El sistema educativo del Valle de Áran. Descripción, actitudes y perspectivas

La comarca del Valle de Arán se encuentra situada en el extremo noroccidental de la provincia de Lleida, en plenos Pirineos. En las últimas décadas, este territorio se encuentra inmerso en un proceso de transformación cultural. La situación viene marcada por varios aspectos: a) un fuerte incremento de población, proveniente principalmente de la inmigración; b) la coexistecia en el territorio de tres lenguas oficiales: el occitano-aranés, como lengua propia de la comarca, el catalán y el castellano, y c) una situación de contacto entre lenguas y culturas bastante diferenciadas. El artículo presenta el proceso de transformación que ha sufrido el sistema educativo en el Valle de Arán en los últimos 20 años, caracterizado principalmente por el paso de un modelo de educación monolingüe a un modelo de educación trilingüe.

Assessment on nutrient levels in the aerial biomass of irrigated guava in São Francisco Valley, Brazil

In perennial crops, fertilizers are applied to restore the amount of nutrient removed from the plant by harvesting. Nevertheless, the immobilized nutrient inside the whole plant should be considered. Based on it, the nutrient concentrations in the guava leaf and fruit and the nutrient contents removed by fruits and post-harvest pruning were evaluated in an irrigated orchard, in Petrolina, State of Pernambuco, Brazil. The greatest contents removed by fruits were N and K among the macronutrients, while Fe, Zn and Mn presented higher levels among the micronutrients. More than 60% of the total content of N, P, K, Mg, Fe, and B removed by pruning were immobilized in the leaf and non-marketable fruit.

Percutaneous Endovascular Salvage Techniques for Implanted Venous Access Device Dysfunction.

PURPOSE: Implanted venous access devices (IVADs) are often used in patients who require long-term intravenous drug administration. The most common causes of device dysfunction include occlusion by fibrin sheath and/or catheter adherence to the vessel wall. We present percutaneous endovascular salvage techniques to restore function in occluded catheters. The aim of this study was to evaluate the feasibility, safety, and efficacy of these techniques. METHODS AND MATERIALS: Through a femoral or brachial venous access, a snare is used to remove fibrin sheath around the IVAD catheter tip. If device dysfunction is caused by catheter adherences to the vessel wall, a new "mechanical adhesiolysis" maneuver was performed. IVAD salvage procedures performed between 2005 and 2013 were analyzed. Data included clinical background, catheter tip position, success rate, recurrence, and rate of complication. RESULTS: Eighty-eight salvage procedures were performed in 80 patients, mostly women (52.5 %), with a mean age of 54 years. Only a minority (17.5 %) of evaluated catheters were located at an optimal position (i.e., cavoatrial junction ±1 cm). Mechanical adhesiolysis or other additional maneuvers were used in 21 cases (24 %). Overall technical success rate was 93.2 %. Malposition and/or vessel wall adherences were the main cause of technical failure. No complications were noted. CONCLUSION: These IVAD salvage techniques are safe and efficient. When a catheter is adherent to the vessel wall, mechanical adhesiolysis maneuvers allow catheter mobilization and a greater success rate with no additional risk. In patients who still require long-term use of their IVAD, these procedures can be performed safely to avoid catheter replacement.

Advances in apple culture worldwide

Over the last 60 years, planting densities for apple have increased as improved management systems have been developed. Dwarfing rootstocks have been the key to the dramatic changes in tree size, spacing and early production. The Malling series of dwarfing rootstocks (M.9 and M.26) have been the most important dwarfing rootstocks in the world but are poorly adapted in some areas of the world and they are susceptible to the bacterial disease fire blight and the soil disease complex, apple replant disease which limits their uses in some areas. Rootstock breeding programs in several parts of the world are developing improved rootstocks with resistance to fire blight, and replant disease, and improved cold hardiness and yield efficiency. A second important trend has been the increasing importance of new cultivars. New cultivars have provided opportunities for higher prices until they are over-produced. A new trend is the "variety club" in which variety owners manage the production and marketing of a new unique cultivar to bring higher prices to the growers and variety owners. This has led to many fruit growers being unable to plant or grow some new cultivars. Important rootstock and cultivar genes have been mapped and can be used in marker assisted selection of future rootstock and cultivar selections. Other important improvements in apple culture include the development of pre-formed trees, the development of minimal pruning strategies and limb angle bending which have also contributed to the dramatic changes in early production in the 2nd-5th years after planting. Studies on light interception and distribution have led to improved tree forms with better fruit quality. Simple pruning strategies and labor positioning platform machines have resulted in partial mechanization of pruning which has reduced management costs. Improved plant growth regulators for thinning and the development of a thinning prediction model based on tree carbohydrate balance have improved the ability to produce the optimum fruit size and crop load. Other new plant growth regulators have also allowed control of shoot growth, control of preharvest fruit drop and control of fruit softening in storage after harvest. As we look to the future, there will be continued incremental improvement in our understanding of plant physiology that will lead to continued incremental improvements in orchard management but there is likely to be dramatic changes in orchard production systems through genomics research and genetic engineering. A greater understanding of the genetic control of dwarfing, precocity, rooting, vegetative growth, flowering, fruit growth and disease resistance which will lead to new varieties and rootstocks which are less expensive to grow and manage.

Worldwide Population Structure, Long-Term Demography, and Local Adaptation of Helicobacter pylori.

Helicobacter pylori is an important human pathogen associated with serious gastric diseases. Owing to its medical importance and close relationship with its human host, understanding genomic patterns of global and local adaptation in H. pylori may be of particular significance for both clinical and evolutionary studies. Here we present the first such whole genome analysis of 60 globally distributed strains, from which we inferred worldwide population structure and demographic history and shed light on interesting global and local events of positive selection, with particular emphasis on the evolution of San-associated lineages. Our results indicate a more ancient origin for the association of humans and H. pylori than previously thought. We identify several important perspectives for future clinical research on candidate selected regions that include both previously characterized genes (e.g., transcription elongation factor NusA and tumor necrosis factor alpha-inducing protein Tipα) and hitherto unknown functional genes.

Integrin-Specific Mechanoresponses to Compression and Extension Probed by Cylindrical Flat-Ended AFM Tips in Lung Cells

Cells from lung and other tissues are subjected to forces of opposing directions that are largely transmitted through integrin-mediated adhesions. How cells respond to force bidirectionality remains ill defined. To address this question, we nanofabricated flat-ended cylindrical Atomic Force Microscopy (AFM) tips with ~1 µm2 cross-section area. Tips were uncoated or coated with either integrin-specific (RGD) or non-specific (RGE/BSA) molecules, brought into contact with lung epithelial cells or fibroblasts for 30 s to form focal adhesion precursors, and used to probe cell resistance to deformation in compression and extension. We found that cell resistance to compression was globally higher than to extension regardless of the tip coating. In contrast, both tip-cell adhesion strength and resistance to compression and extension were the highest when probed at integrin-specific adhesions. These integrin-specific mechanoresponses required an intact actin cytoskeleton, and were dependent on tyrosine phosphatases and Ca2+ signaling. Cell asymmetric mechanoresponse to compression and extension remained after 5 minutes of tip-cell adhesion, revealing that asymmetric resistance to force directionality is an intrinsic property of lung cells, as in most soft tissues. Our findings provide new insights on how lung cells probe the mechanochemical properties of the microenvironment, an important process for migration, repair and tissue homeostasis.