Role of beta-1 integrin in tumor growth and dissemination

SUMMARY Cancer is one of the leading causes of disease-related mortality. In most cases, death is due to the spread of cells from the primary tumor to distant sites causing formation of metastases. To become tumorigenic, cells should acquire ability, including self-sufficiency in growth signals, insensitivity to anti-growth signals, resistance to apoptosis, sustained angiogenesis, limitless replicative potential and tissue invasion and metastasis. Tumor progression depends, in part on the relationship between tumor cells and host tissue stroma, characterized by changes of tumor cell adhesion to their microenvironment and activation of a variety of extracellular proteases that play a role in ECM degradation. integrins are adhesion proteins implicated in tumorigenesis. Their main function is to mediate cell adhesion to the ECM or to other cells and to create a link between the ECM and the cytoskeleton. Tumor cells like normal cells use integrins to attach to ECM, migrate into surrounding tissues and derive survival and growth signals. Integrin-dependent adhesion and migration are thought to play an important role in tumor dissemination. A strategy was designed to address the role of β1 integrin tumor growth and dissemination. Murine mammary carcinoma (TA3) cells were stably transfected with a soluble β1 integrin construct, which is anticipated to play a dominant negative role, being able to associate with different α-subunits expressed on the cell surface but unable to transduce signals to the nucleus. Results from studies based on soluble β1 integrin TA3 transfectants showed that 1) the integrin expression pattern at the cell surface changed with an induction of α2β1 and α5β1 heterodimers; 2) adhesion to collagens, especially collagen I was increased; 3) tumor dissemination after intrape-ritoneal injection in syngeneic mice was abolished and 4) local growth after orthotopic injection was maintained but delayed. Taken together, the data presented here suggest that β1 integrin plays a potentially important role in the regulation of tumor behavior. RESUME Le cancer est une des principales causes de mortalité suite à une maladie. Dans la plupart des cas, la mort est la conséquence de la dissémination de cellules, provenant de la tumeur primaire, dans des endroits distants et causant la formation de métastases. Afin de devenir cancéreuse, une cellule doit acquérir certaines capacités, telles qu'une auto-suffisance en facteurs de croissance, une insensibilité aux facteurs empêchant la croissance cellulaire, une résistance à l'apoptose, une angiogénèse soutenue, un potentiel de réplication illimité et une capacité à pénétrer dans les tissus et à former des colonies métastatiques. La progression d'une tumeur dépend, en partie, de la relation entre les cellules tumorales et les cellules tissulaires de l'hôte. Cette relation est caractérisée par des modifications des cellules tumorales quant à leur adhésion au microenvironnement et à l'activation de protéases qui permettent de dégrader la matrice extracellulaire. Les intégrines sont des protéines impliquées dans le développement tumoral. Leur fonction principale est de réguler l'adhésion des cellules à la matrice extracellulaire, ou à d'autres cellules, et de créer un lien entre cette matrice extracellulaire et le cytosquelette. Les cellules tumorales utilisent également les intégrines pour se lier à la matrice extracellulaire, pour migrer dans les tissus adjacents et pour induire des signaux de croissance et de survie. Ces événements d'adhésion et de migration, qui dépendent des intégrines, jouent un rôle primordial dans la dissémination des cellules cancéreuses. Une stratégie a été élaborée afin de définir le rôle de l'intégrine β1 durant la croissance et la dissémination des cellules tumorales. Des cellules provenant d'un carcinome de la glande mammaire (TA3) ont été transfectées de manière stable avec un vecteur contenant la séquence codante de la partie extracellulaire de l'intégrine β1. L'intégrine tronquée doit être capable de se lier aux sous-unités α exprimées à la surface de la cellule, mais doit être incapable de transmettre un signal à l'intérieur de la cellule. Les résultats obtenus avec les cellules TA3 transfectées contenant l'intégrine β1 soluble montrent que I) le répertoire d'expression des intégrines à la surface de la cellule a changé en faveur des hétérodimères α2β1 et α5β1; 2) l'adhésion aux collagènes, particulièrement au collagène de type I a augmenté; 3) la dissémination des cellules tumorales après une injection intrapéritonéale est empêchée; 4) la croissance tumorale après une injection orthotopique est conservée mais retardée. Ces résultats montrent que l'intégrine β1 joue un rôle primordial dans la régulation du comportement tumoral.

The importance of relative performance feedback information: Evidence from a natural experiment using high school students

We study the effect of providing relative performance feedback information onperformance, when individuals are rewarded according to their absolute performance. Anatural experiment that took place in a high school offers an unusual opportunity to testthis effect in a real-effort setting. For one year only, students received information thatallowed them to know whether they were performing above (below) the class average aswell as the distance from this average. We exploit a rich panel data set and find that theprovision of this information led to an increase of 5% in students grades. Moreover, theeffect was significant for the whole distribution. However, once the information wasremoved, the effect disappeared. To rule out the concern that the effect may beartificially driven by teachers within the school, we verify our results using nationallevel exams (externally graded) for the same students, and the effect remains.

Demographic and behavioral factors associated with adolescent pregnancy in Switzerland.

Switzerland has the lowest adolescent fertility rate in Western Europe. According to data collected in 1993 as part of the Swiss Multicentre Adolescent Survey on Health, 5% of 1,726 sexually active adolescents in a group of 3,993 15-20-year-old women enrolled in academic or vocational classes had ever been pregnant; most of these women (80%) had terminated their pregnancy. Adolescents who had ever been pregnant did not differ significantly from those who had not by demographic characteristics. Multiple logistic regression analysis identified seven factors associated with pregnancy: having had four or more sexual partners; not having used contraceptives at first intercourse; ever use of less-effective contraceptive methods; having used illicit drugs during the last 30 days; living apart from one's parents; recently experiencing stress; and perceiving a lack of future prospects.

Autoreactive T cells that bypass negative selection are not tolerant and respond to self-antigen stimulation during infection

Le répertoire cellulaire Τ a pour but d'être tolérant aux antigènes du soi afin d'éviter l'induction de maladies autoimmunes. C'est pourquoi les lymphocytes Τ autoréactifs sont éliminés dans le thymus lors de leur développement par le processus de sélection négative. La plupart des recherches étudient les lymphocytes Τ de haute avidité. Ces lymphocytes Τ de haute avidité sont très sensibles et réagissent fortement à un antigène du soi. En conséquence, ces cellules induisent le développement de maladies autoimmunes lorsqu'elles ciblent des organes exprimant l'antigène du soi. Plusieurs études ont montré que les lymphocytes Τ qui réagissent faiblement aux antigènes spécifiques à un tissu, nommé lymphocytes Τ de faible avidité, peuvent contourner les mécanismes de tolérance centrale et périphérique. J'ai utilisé des souris Rip-mOva qui expriment l'Ovalbumine comme antigène du soi spécifique à un tissu. Dans ces souris transgéniques Rip-mOva, les lymphocytes Τ de faible avidité survivent à la sélection négative. Une fois stimulés à la périphérie, ces lymphocytes Τ CD8+ de faible avidité ont la capacité d'infiltrer les organes qui expriment l'antigène du soi chez les souris Rip-mOva et peuvent induire une destruction tissulaire. L'objectif principal de mon projet de thèse était de comprendre les caractéristiques phénotypiques et fonctionnelles de ces lymphocytes Τ dans un état d'équilibre et dans un contexte infectieux. Pour étudier ces cellules dans un modèle murin bien défini, nous avons généré des souris exprimant un récepteur de cellule Τ transgénique appelé OT-3. Ces souris transgéniques OT-3 ont des lymphocytes Τ CD8+ de faible avidité spécifiques à l'épitope SIINFEKL de l'antigène Ovalbumine. Nous avons démontré qu'un grand nombre de lymphocytes Τ CD8+ OT-3 ne sont pas éliminés lors de la sélection négative dans le thymus après avoir rencontré l'antigène du soi. Par conséquent, les lymphocytes Τ OT-3 de faible avidité sont présents dans une fenêtre de sélection comprise entre la sélection positive et négative. Cette limite se définie comme le seuil d'affinité et est impliquée dans l'échappement de certains lymphocytes Τ OT- 3 autoréactifs. A la périphérie, ces cellules sont capables d'induire une autoimmunité après stimulation au cours d'une infection, ce qui nous permet de les définir comme étant non tolérante et non dans un état anergique à la périphérie. Nous avons également étudié le seuil d'activation des lymphocytes Τ OT-3 à faible avidité à la périphérie et avons constaté que des ligands peptidiques plus faibles que l'épitope natif SIINFEKL sont capables de les activer au cours d'une infection ainsi que de les différencier en lymphocytes Τ effecteurs et mémoires. Les données illustrent une déficience lors de la sélection négative dans le thymus de lymphocytes Τ CD8+ autoréactifs de faible avidité contre un antigène du soi spécifique à tissu et montrent que ces cellules sont entièrement compétentes lors d'une infection. - The diverse Τ cell repertoire needs to be tolerant to self-antigen to avoid the induction of autoimmunity. This is why autoreactive developing Τ cells are deleted in the thymus. The deletion of self-reactive Τ cells occurs through the process of negative selection. Most studies investigated high avidity Τ cells. These high avidity Τ cells are very sensitive and strongly react to a self-antigen. As a consequence, these cells induce the development of autoimmunity when they target organs which express the self-antigen. High avidity autoreactive CD8+ Τ cells are deleted in the thymus. However, several studies have shown Τ cells that weakly respond to tissue-restricted antigen, referred to as low avidity Τ cells, can bypass central and peripheral tolerance mechanisms. I used Rip-mOva mice that expressed Ovalbumin as a neo self-antigen in a tissue-restricted fashion. In these transgenic Rip-mOva mice low avidity CD8+ Τ cells survive negative selection. Upon stimulation in the periphery, these low avidity CD8+ Τ cells have the ability to infiltrate organs that express the self-antigen in the Rip-mOva mice and can also induce the destruction of the tissue. The major aim of my PhD project was to understand the phenotypic and functionality characteristics of these Τ cells in a steady-state condition and in a context of an infection. To study these cells in a well-defined mouse model, we generated OT-3 Τ cell receptor transgenic mice that express low avidity CD8+ Τ cells that are specific for the SIINFEKL epitope of the Ovalbumin antigen. We have been able to demonstrate that a large number of OT-3 CD8+ Τ cells survive negative selection in the thymus after encountering the self-antigen. Thus, low avidity OT-3 Τ cells are present in a window of selection comprised between positive and negative selection. This boundary defined as the affinity threshold is involved in the escape of some autoreactive low avidity OT-3 Τ cells. Once they circulate in the periphery, they are able to induce autoimmunity after stimulation during an infection, allowing us to allocate these cells as being non-tolerant and not in an anergic state in the periphery. We have also looked at the threshold of activation of low avidity OT-3 CD8+ Τ cells in the periphery and found that peptide ligands that are weaker than the native SIINFEKL epitope are able to activate OT-3 Τ cells during an infection and to differentiate them into effector and memory Τ cells. The data illustrate the impairment of negatively selecting low avidity autoreactive CD8+ Τ cells against a tissue-restricted antigen in the thymus and shows that these cells are fully competent upon an infection.

Adolescent(e)s migrant(e)s et sexualité [Migrant adolescents and sexuality].

Besides its emotional, hormonal and physical components, sexuality has also an important social function. Analyzing these interactions in immigrant adolescents who are challenged at the same time by developmental changes and modified cultural and social rules--especially if they differ from the rules assimilated during childhood--might help professionals to access better comprehension. Personal experience, individual and external resources, whether they are family oriented or professional, are prone to influence on behavior, perception and outcome related to sexual health. The subject is discussed on the base of scientific literature and medical practice.

Estratègies de cura i presa de decisions en persones grans amb dependència ingressades en una unitat geriàtrica d'atenció intermèdia : estudi descriptiu

Aquest estudi té com objectiu observar les relacions entre les estratègies de cura (formal, informal, mixta) que fan servir els cuidadors de persones grans dependents, la seva situació social i les seves motivacions per la decisió respecte a com fan la cura. L’estat del tema destaca el predomini de les cures informals sobre les formals en els models de benestar mediterranis i la rellevància de la interacció entre factors personals socioculturals i les polítiques socials en la presa de decisions individuals sobre la cura de la dependència. La llei de la dependència, de recent implementació a l’Estat espanyol, ha universalitzat l’accés als recursos formals, creant un nou paradigma d’interacció cuidadors-recursos. Es tracta d’un estudi observacional, transversal, descriptiu de tipus mixt quantitatiu/qualitatiu realitzat a partir d’entrevistes individuals als cuidadors de dependents ingressats en una unitat geriàtrica d’atenció intermèdia. Es recullen dades sobre el context sociofamiliar, l’estratègia de cura, l’autopercepció i les motivacions. Els resultats mostren que els cuidadors combinen prestacions econòmiques i serveis (públics i privats) per adaptar al màxim l’estratègia a les condicions del dependent i a les seves pròpies. Tenen la convicció generalitzada que l’atenció cal fer-la al domicili per motius de reciprocitat i respecte a la persona cuidada. El pas a l’atenció residencial és una decisió molt difícil pels cuidadors. La implantació de la llei de la dependència ha normalitzat la relació entre cuidadors i recursos formals, però la burocratització i la insuficiència de l’oferta de serveis no afavoreixen canvis substancials en la provisió de l’ajut, que continua essent majoritàriament informal. La millora en la percepció de continuïtat d’atenció entre el domicili i la residència, i també en la gestió i l’oferta de serveis formals públics es presenten com a reptes de treball importants al nostre país.

(K)over-bar* mesons in dense matter

We study the properties of (K) over bar* mesons in nuclear matter using a unitary approach in coupled channels within the framework of the local hidden gauge formalism and incorporating the (K) over bar pi decay channel in matter. The in-medium (K) over bar *N interaction accounts for Pauli blocking effects and incorporates the (K) over bar* self-energy in a self-consistent manner. We also obtain the (K) over bar* (off-shell) spectral function and analyze its behavior at finite density and momentum. At a normal nuclear matter density, the (K) over bar* meson feels a moderately attractive potential, while the (K) over bar* width becomes five times larger than in free space. We estimate the transparency ratio of the gamma A -> K+K*(-) A` reaction, which we propose as a feasible scenario at the present facilities to detect changes in the properties of the (K) over bar* meson in nuclear medium.

Alpha-band suppression in the visual word form area as a functional bottleneck to consciousness.

The current state of empirical investigations refers to consciousness as an all-or-none phenomenon. However, a recent theoretical account opens up this perspective by proposing a partial level (between nil and full) of conscious perception. In the well-studied case of single-word reading, short-lived exposure can trigger incomplete word-form recognition wherein letters fall short of forming a whole word in one's conscious perception thereby hindering word-meaning access and report. Hence, the processing from incomplete to complete word-form recognition straightforwardly mirrors a transition from partial to full-blown consciousness. We therefore hypothesized that this putative functional bottleneck to consciousness (i.e. the perceptual boundary between partial and full conscious perception) would emerge at a major key hub region for word-form recognition during reading, namely the left occipito-temporal junction. We applied a real-time staircase procedure and titrated subjective reports at the threshold between partial (letters) and full (whole word) conscious perception. This experimental approach allowed us to collect trials with identical physical stimulation, yet reflecting distinct perceptual experience levels. Oscillatory brain activity was monitored with magnetoencephalography and revealed that the transition from partial-to-full word-form perception was accompanied by alpha-band (7-11 Hz) power suppression in the posterior left occipito-temporal cortex. This modulation of rhythmic activity extended anteriorly towards the visual word form area (VWFA), a region whose selectivity for word-forms in perception is highly debated. The current findings provide electrophysiological evidence for a functional bottleneck to consciousness thereby empirically instantiating a recently proposed partial perspective on consciousness. Moreover, the findings provide an entirely new outlook on the functioning of the VWFA as a late bottleneck to full-blown conscious word-form perception.

Dreaming without REM sleep.

To test whether mental activities collected from non-REM sleep are influenced by REM sleep, we suppressed REM sleep using clomipramine 50mg (an antidepressant) or placebo in the evening, in a double blind cross-over design, in 11 healthy young men. Subjects were awakened every hour and asked about their mental activity. The marked (81%, range 39-98%) REM-sleep suppression induced by clomipramine did not substantially affect any aspects of dream recall (report length, complexity, bizarreness, pleasantness and self-perception of dream or thought-like mentation). Since long, complex and bizarre dreams persist even after suppressing REM sleep either partially or totally, it suggests that the generation of mental activity during sleep is independent of sleep stage.

Self-selection and risk selection on the Swiss health insurance market

Abstract This thesis presents three empirical studies in the field of health insurance in Switzerland. First we investigate the link between health insurance coverage and health care expenditures. We use claims data for over 60 000 adult individuals covered by a major Swiss Health Insurance Fund, followed for four years; the data show a strong positive correlation between coverage and expenditures. Two methods are developed and estimated in order to separate selection effects (due to individual choice of coverage) and incentive effects ("ex post moral hazard"). The first method uses the comparison between inpatient and outpatient expenditures to identify both effects and we conclude that both selection and incentive effects are significantly present in our data. The second method is based on a structural model of joint demand of health care and health insurance and makes the most of the change in the marginal cost of health care to identify selection and incentive effects. We conclude that the correlation between insurance coverage and health care expenditures may be decomposed into the two effects: 75% may be attributed to selection, and 25 % to incentive effects. Moreover, we estimate that a decrease in the coinsurance rate from 100% to 10% increases the marginal demand for health care by about 90% and from 100% to 0% by about 150%. Secondly, having shown that selection and incentive effects exist in the Swiss health insurance market, we present the consequence of this result in the context of risk adjustment. We show that if individuals choose their insurance coverage in function of their health status (selection effect), the optimal compensations should be function of the se- lection and incentive effects. Therefore, a risk adjustment mechanism which ignores these effects, as it is the case presently in Switzerland, will miss his main goal to eliminate incentives for sickness funds to select risks. Using a simplified model, we show that the optimal compensations have to take into account the distribution of risks through the insurance plans in case of self-selection in order to avoid incentives to select risks.Then, we apply our propositions to Swiss data and propose a simple econometric procedure to control for self-selection in the estimation of the risk adjustment formula in order to compute the optimal compensations.

Risk perception by healthcare professionals related to drug use during pregnancy: a Swiss survey.

PRINCIPLE: Healthcare professionals' (HCPs') perception of risk associated with drug use in pregnancy may have an impact on the pharmacological treatment of some women. The aim of this study was to examine this risk perception in a sample of Swiss HCPs with a special focus on their knowledge and use of available specialised information sources. METHOD: An online, French and German, questionnaire was e-mailed to 7,136 members of four Swiss professional societies (gynaecologists, paediatricians, midwives and pharmacists). The questionnaire was designed (a) to collect demographic characteristics, (b) to evaluate the frequency of use of several specialised sources of information on drugs in pregnancy in their daily practice, and (c) to examine the perception of risk associated with drug use during pregnancy. RESULTS: A total of 1,310 questionnaires were collected (response rate of 18.4%). More than 80% of the respondent HCPs use the Swiss Drug Reference Book (Compendium) to assess the risk associated with drugs during pregnancy and are not aware of available specialised information sources (books, websites or information centres). Despite some disparities between HPCs, the risk related to drug intake was overall highly misperceived. Blinded reading of three product monographs in the Compendium was associated with an overestimated perception of risk (e.g., after reading the "paracetamol" monograph, 38% of the participants stated they would probably not advise the use of this drug to a pregnant patient). CONCLUSION: Overall, an overestimation of the risk associated with drug use during pregnancy has been observed in our sample of HCPs, which might be related to the underuse of specialised information source among other factors. These findings evidenced the need for increased training for HCPs in order to optimise medication use during pregnancy. Further studies are needed to confirm these results and identify causes.

Who eats healthily? A population-based study among young Swiss residents.

OBJECTIVE: To assess whether Swiss residents aged 15-24 years follow current nutritional guidelines and whether differences exist according to gender and weight status. DESIGN: Cross-sectional national survey. SETTING: Switzerland. SUBJECTS: The 1786 participants (48·4 % women) were divided into overweight, normal weight and underweight. We used traditional BMI cut-offs for people ≥18 years of age (underweight = BMI < 18·5 kg/m2, normal weight = BMI ≥ 18·5 kg/m2 and <25 kg/m2, overweight = BMI ≥ 25 kg/m2) and age- and gender-appropriate tables for people aged <18 years, with BMI calculated from self-reported weight and height. We performed bivariate analyses by gender, and then bivariate and multivariate analyses comparing overweight to normal weight people (excluding underweight, n 129, 71·6 % women) regarding adherence to recommendations for fruit, vegetables, meat, fish and dairy products; physical activity; attitude towards body weight; depression, smoking and alcohol consumption. RESULTS: Overall, adherence to nutritional guidelines was low, particularly for vegetables and dairy products. Women had a higher adherence than men except for fish and dairy products. In the multivariate analyses, overweight women had a lower vegetable intake, were less satisfied with body weight and had more often been on a diet, whereas overweight men were less satisfied with body weight and wanted to lose weight more often than their normal weight peers. There were no significant differences for physical activity. CONCLUSIONS: Overweight prevention programmes should target youth specifically by gender and promote an appropriate self-perception. Overweight women should be encouraged to eat more vegetables and men to be more sensitised on healthy food. Further research is needed to assess how to make nutritional guidelines more adaptable to young people's daily life.

Psychometric evaluation of the IWQOL-Lite (Spanish version) when applied to a sample of obese patients awaiting bariatric surgery

Background Obesity may have an impact on key aspects of health-related quality of life (HRQOL). In this context, the Impact of Weight Quality of Life (IWQOL) questionnaire was the first scale designed to assess HRQOL. The aim of the present study was twofold: to assess HRQOL in a sample of Spanish patients awaiting bariatric surgery and to determine the psychometric properties of the IWQOL-Lite and its sensitivity to detect differences in HRQOL across groups. Methods Participants were 109 obese adult patients (BMI¿ 35 kg/m2) from Barcelona, to whom the following measurement instruments were applied: IWQOL-Lite, Depression Anxiety Stress Scales, Brief Symptom Inventory, and self-perception items. Results Descriptive data regarding the IWQOL-Lite scores obtained by these patients are reported. Principal components analysis revealed a five-factor model accounting for 72.05% of the total variance, with factor loadings being adequate for all items. Corrected itemtotal correlations were acceptable for all items. Cronbach"s alpha coefficients were excellent both for the subscales (0.880.93) and the total scale (0.95). The relationship between the IWQOLLite and other variables supports the construct validity of the scale. Finally, sensitivity analysis revealed large effect sizes when comparing scores obtained by extreme BMI groups. Conclusions This is the first study to report the application of the IWQOL-Lite to a sample of Spanish patients awaiting bariatric surgery and to confirm that the Spanish version of the instrument has adequate psychometric properties.

Assessment of emotional reactivity produced by exposure to virtual environments in patients with eating disorders

The aim of this study was to assess the usefulness of virtual environments representing situations that are emotionally significant to subjects with eating disorders (ED). These environments may be applied with both evaluative and therapeutic aims and in simulation procedures to carry out a range of experimental studies. This paper is part of a wider research project analyzing the influence of the situation to which subjects are exposed on their performance on body image estimation tasks. Thirty female patients with eating disorders were exposed to six virtual environments: a living-room (neutral situation), a kitchen with highcalorie food, a kitchen with low-calorie food, a restaurant with high-calorie food, a restaurant with low-calorie food, and a swimming-pool. After exposure to each environment the STAI-S (a measurement of state anxiety) and the CDB (a measurement of depression) were administered to all subjects. The results show that virtual reality instruments are particularly useful for simulating everyday situations that may provoke emotional reactions such as anxiety and depression, in patients with ED. Virtual environments in which subjects are obliged to ingest high-calorie food provoke the highest levels of state anxiety and depression.

Tissue-specific FLAGELLIN-SENSING 2 (FLS2) expression in roots restores immune responses in Arabidopsis fls2 mutants.

The flagellin receptor of Arabidopsis, At-FLAGELLIN SENSING 2 (FLS2), has become a model for mechanistic and functional studies on plant immune receptors. Responses to flagellin or its active epitope flagellin 22 (flg22) have been extensively studied in Arabidopsis leaves. However, the perception of microbe-associated molecular patterns (MAMPs) and the immune responses in roots are poorly understood. Here, we show that isolated root tissue is able to induce pattern-triggered immunity (PTI) responses upon flg22 perception, in contrast to elf18 (the active epitope of elongation factor thermo unstable (EF-Tu)). Making use of fls2 mutant plants and tissue-specific promoters, we generated transgenic Arabidopsis lines expressing FLS2 only in certain root tissues. This allowed us to study the spatial requirements for flg22 responses in the root. Remarkably, the intensity of the immune responses did not always correlate with the expression level of the FLS2 receptor, but depended on the expressing tissue, supporting the idea that MAMP perception and sensitivity in different tissues contribute to a proper balance of defense responses according to the expected exposure to elicitors. In summary, we conclude that each investigated root tissue is able to perceive flg22 if FLS2 is present and that tissue identity is a major element of MAMP perception in roots.