Requirement of Podocalyxin in TGF-Beta Induced Epithelial Mesenchymal Transition

Epithelial mesenchymal transition (EMT) is characterized by the development of mesenchymal properties such as a fibroblast-like morphology with altered cytoskeletal organization and enhanced migratory potential. We report that the expression of podocalyxin (PODXL), a member of the CD34 family, is markedly increased during TGF-β induced EMT. PODXL is enriched on the leading edges of migrating A549 cells. Silencing of podocalyxin expression reduced cell ruffle formation, spreading, migration and affected the expression patterns of several proteins that normally change during EMT (e.g., vimentin, E-cadherin). Cytoskeletion assembly in EMT was also found to be dependent on the production of podocalyin. Compositional analysis of podocalyxin containing immunoprecipitates revealed that collagen type 1 was consistently associated with these isolates. Collagen type 1 was also found to co-localize with podocalyxin on the leading edges of migrating cells. The interactions with collagen may be a critical aspect of podocalyxin function. Podocalyxin is an important regulator of the EMT like process as it regulates the loss of epithelial features and the acquisition of a motile phenotype

Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

BACKGROUND: Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF), was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. METHODS: We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF) were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. RESULTS: We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM) and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM) or nucleolin (on the cell surfaces) eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of laminin-binding integrins, nor can they be linked to expression of the known HGF receptor Met, as neither LNCaP nor clonally-derived C4-2 sub-line contain any detectable Met protein. Even in the absence of Met, small GTPases are activated, linking HGF stimulation to membrane protrusion and integrin activation. Membrane-localized nucelolin levels increase during cancer progression, as modeled by both the PC3 and LNCaP prostate cancer progression cell lines. CONCLUSION: We propose that cell surface localized nucleolin protein may function in these cells as a novel HGF receptor. Membrane localized nucleolin binds heparin-bound growth factors (including HGF) and appears upregulated during prostate cancer progression. Antibodies against nucleolin are able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. HGF-nucleolin interactions could be partially responsible for the complexity of HGF responses and met expression reported in the literature

Security and Privacy Service Level Agreement composition for Internet of Things systems on top of standard controls

The growing markets of Cloud services and IoT platforms have dramatically raised system flexibility and deployment options. However, increasing complexity and dependency on third-party providers make it difficult to assess the security and privacy levels that distributed systems can offer to their users. In the last years, machine-readable Service Level Agreements (SLAs) have been studied as an optimal method for copying with security and privacy policies. Still, the computation of the SLAs of applications distributed in diverse infrastructures remains a challenging task. This paper presents a methodology to compose security SLAs (SecSLAs) and privacy SLAs (PLAs) of Cloud-based IoT applications on top of standard controls. The composition considers individual components’ SLAs and the control delegation relationships between the components with respect to different types of controls (common, system-specific or hybrid controls). Furthermore, we propose a technique to calculate the Service Level Objectives (SLO) of the controls declared in the composite SLA based on the SLOs granted by individual components. Finally, the paper presents the validation of the methodology carried out to create the SecSLAs and PLAs of a real multiCloud-based IoT application in the eHealth domain

Moderating factors of the association between being sexually solicited by adults and active online sexual behaviors in adolescents

Online sexual solicitation involves receiving sexual solicitations from adults, which can be followed by active online sexual behaviors by the victims. This study examined the moderator role of some characteristics of adolescents (sex, age, and problematic Internet use) that could make them more vulnerable to react by engaging in active sexual behaviors when they are the recipients of sexual solicitations. The final sample was comprised of 1260 adolescents (55.6% girls, 12–17 years) who completed measures in two waves with an interval of one year. The measures included online sexual solicitation, active sexual interaction with an adult, and sexting to friends and/or one's partner in both waves of the study. Sexual solicitations by adults predicted an increase in sexualized interactions with adults and sending sexts to friends and/or one's partner. Moderation tests indicated that, although girls receive more sexual solicitations, they are actively involved to a lesser extent than boys in sexualized interactions with adults and in sending sexts. The youngest adolescents received fewer sexual solicitations, but those who did receive sexual solicitations sent more sexts to friends and/or one's partner. Problematic Internet use, although associated with all online sexual risks, did not moderate the dynamics between risks

Adaptive divergence despite low effective population size in a peripherally isolated population of the pygmy rabbit, Brachylagus idahoensis

Local adaptation can occur when spatially separated populations are subjected to contrasting environmental conditions. Historically, understanding the genetic basis of adaptation has been difficult, but increased availability of genome-wide markers facilitates studies of local adaptation in non-model organisms of conservation concern. The pygmy rabbit (Brachylagus idahoensis) is an imperiled lagomorph that relies on sagebrush for forage and cover. This reliance has led to widespread population declines following reductions in the distribution of sagebrush, leading to geographic separation between populations. In this study, we used \u3e20,000 single nucleotide polymorphisms, genotype-environment association methods, and demographic modeling to examine neutral genetic variation and local adaptation in the pygmy rabbit in Nevada and California. We identified 308 loci as outliers, many of which had functional annotations related to metabolism of plant secondary compounds. Likewise, patterns of spatial variation in outlier loci were correlated with landscape and climatic variables including proximity to streams, sagebrush cover, and precipitation. We found that populations in the Mono Basin of California probably diverged from other Great Basin populations during late Pleistocene climate oscillations, and that this region is adaptively differentiated from other regions in the southern Great Basin despite limited gene flow and low effective population size. Our results demonstrate that peripherally isolated populations can maintain adaptive divergence

Safety and Security Interference Analysis in the Design Stage

Safety and security engineering have been traditionally separated disciplines (e.g., different required knowledge and skills, terminology, standards and life-cycles) and operated in quasi-silos of knowledge and practices. However, the co-engineering of these two critical qualities of a system is being largely investigated as it promises the removal of redundant work and the detection of trade-offs in early stages of the product development life-cycle. In this work, we enrich an existing safety-security co-analysis method in the design stage providing capabilities for interference analysis. Reports on interference analyses are crucial to trigger co-engineering meetings leading to the trade-offs analyses and system refinements. We detail our automatic approach for this interference analysis, performed through fault trees generated from safety and security local analyses. We evaluate and discuss our approach from the perspective of two industrial case studies on the space and medical domains.The research leading to this paper has received funding from the AQUAS project (H2020-ECSEL grant agreement 737475). The ECSEL Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme