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Growth hormone (GH) acts via JAK2 and LYN to regulate growth, metabolism, and neural function. However, the relationship between these tyrosine kinases remains enigmatic. Through an interdisciplinary approach combining cell biology, structural biology, computation, and single-particle tracking on live cells, we find overlapping LYN and JAK2 Box1-Box2-binding regions in GH receptor (GHR). Our data implicate direct competition between JAK2 and LYN for GHR binding and imply divergent signaling profiles. We show that GHR exhibits distinct mobility states within the cell membrane and that activation of LYN by GH mediates GHR immobilization, thereby initiating its nanoclustering in the membrane. Importantly, we observe that LYN mediates cytokine receptor degradation, thereby controlling receptor turnover and activity, and this applies to related cytokine receptors. Our study offers insight into the molecular interactions of LYN with GHR and highlights important functions for LYN in regulating GHR nanoclustering, signaling, and degradation, traits broadly relevant to many cytokine receptors. [Display omitted] • LYN and JAK2 compete for binding to the Box1-Box2 region of the growth hormone receptor (GHR) • Competition results in divergent signaling cascades • LYN/ERK1/2 pathway activation promotes cytokine receptor degradation • Nanoclustering of GHRs at the membrane is regulated by kinases Chhabra et al. establish a functionally relevant competition between two tyrosine kinases (JAK2/LYN) for the growth hormone receptor at overlapping sites within its intracellular domain. Their findings show that differential kinase binding leads to differential signaling cascades, receptor stabilities, and nanoclustering at the plasma membrane. [ABSTRACT FROM AUTHOR]

The cortical actin network is a tight array of filaments located beneath the plasma membrane. In neurosecretory cells, secretory vesicles are recruited on this network via a small insert isoform of myosin VI in a Ca 2+ -dependent manner. Upon secretagogue stimulation, myosin II mediates a relaxation of the actin network leading to synchronous translocation of bound or caged vesicles to the plasma membrane where they undergo exocytosis. F-actin is also recruited to secretory sites, where structural changes are detected immediately preceding and following exocytic events. Here we examine the mechanism underpinning the astonishing multifunctionality of this network in the various stages of vesicular exocytosis and compensatory bulk endocytosis. We propose a theoretical framework incorporating critical roles of the actin network in coupling these processes. [ABSTRACT FROM AUTHOR]

Chemical communication is underpinned by the fusion of neurotransmitter-containing synaptic vesicles with the plasma membrane at active zones. With the advent of super-resolution microscopy, the door is now opened to unravel the dynamic remodeling of synapses underpinning learning and memory. Imaging proteins with conventional light microscopy cannot provide submicron information vital to determining the nanoscale organization of the synapse. We will first review the current super-resolution microscopy techniques available to investigate the localization and movement of synaptic proteins and how they have been applied to visualize the synapse. We discuss the new techniques and analytical approaches have provided comprehensive insights into synaptic organization in various model systems. Finally, this review provides a brief update on how these super-resolution techniques and analyses have opened the way to a much greater understanding of the synapse, the fusion and compensatory endocytosis machinery. • Super-resolution microscopy approaches are key to uncovering the dynamic organization of the synapse. • Single-particle tracking has allowed us to uncover a more detailed mechanism of synaptic plasticity. • Advanced analytical approaches have provided insights into the transient nanoclustering of the remodelling synapse. [ABSTRACT FROM AUTHOR]

Abstract: We show how to prove combinatorially the Splitting Necklace Theorem by Alon for any number of thieves. Such a proof requires developing a combinatorial theory for abstract simplotopal complexes and simplotopal maps, which generalizes the theory of abstract simplicial complexes and abstract simplicial maps. Notions like orientation, subdivision, and chain maps are defined combinatorially, without using geometric embeddings or homology. This combinatorial proof requires also a -simplotopal version of Tucker’s Lemma. [Copyright &y& Elsevier]

Abstract: Cars have to be painted in two colors in a sequence where each car occurs twice; assign the two colors to the two occurrences of each car so as to minimize the number of color changes. This problem is denoted by . This version and a more general version—with an arbitrary multiset of colors for each car—were proposed and studied for the first time in 2004 by Epping, Hochstättler and Oertel. Since then, other results have been obtained: for instance, Meunier and Sebő have found a class of instances for which the greedy algorithm is optimal. In the present paper, we focus on and find a larger class of instances for which the greedy algorithm is still optimal. Moreover, we show that when one draws uniformly at random an instance w of , the greedy algorithm needs at most 1/3 of the length of w color changes. We conjecture that asymptotically the true factor is not 1/3 but 1/4. Other open questions are emphasized. [Copyright &y& Elsevier]

Abstract: The following problem has been presented in [T. Epping, W. Hochstättler, P. Oertel, Complexity results on a paint shop problem, Discrete Applied Mathematics 136 (2004) 217–226] by Epping, Hochstättler and Oertel: cars have to be painted in two colors in a sequence where each car occurs twice; assign the two colors to the two occurrences of each car so as to minimize the number of color changes. More generally, the “paint shop scheduling problem” is defined with an arbitrary multiset of colors given for each car, where this multiset has the same size as the number of occurrences of the car; the mentioned article states two conjectures about the general problem and proves its NP-hardness. In a subsequent paper in [P. Bonsma, Th. Epping, W. Hochstättler, Complexity results for restricted instances of a paint shop problem for words, Discrete Applied Mathematics 154 (2006) 1335–1343], Bonsma, Epping and Hochstättler proved its APX-hardness and noticed the applicability of some classical results in special cases. We first identify the problem concerning two colors as a minimum odd circuit cover problem in particular graphs, exactly situating the problem. A resulting two-way reduction to a special minimum uncut problem leads to polynomial algorithms for subproblems, to observing APX-hardness through MAX CUT in 3-regular graphs, and to a solution with at most 3/4th of all possible remaining color changes (when all obliged color changes have been made). For the general problem concerning an arbitrary number of colors, we realize that the two aforementioned conjectures are corollaries of the celebrated “necklace splitting” theorem of Alon, Goldberg and West. [Copyright &y& Elsevier]

Résumé Depuis les travaux de Monahan, les auteurs s’accordent sur la pertinence de l’utilisation des outils d’évaluation standardisés du risque chez les auteurs de violence sexuelle, y compris par les experts dans le domaine médico-légal. Plusieurs instruments spécifiques ont été développés et validés, parmi lesquels, les outils de jugement clinique structurés HCR-20 et RSVP dont la capacité prédictive s’améliore avec la confrontation de plusieurs évaluations cliniques. La plateforme référentielle auteurs de violences sexuelles du Rhône accueille, autour d’une évaluation complète, infirmière, psychiatrique, psychologique et criminologique clinique, les patients en ambulatoire, afin de proposer un projet adapté et personnalisé incluant des soins spécifiques. Au terme de l’évaluation, une réunion de concertation pluriprofessionnelle est organisée avec les différents évaluateurs et les soignants ayant adressé le patient. Une cotation collective des outils de jugement clinique structuré RSVP et HCR20 est effectuée. Ces outils permettent de déterminer, en équipe, les points les plus pertinents de la prise en charge des auteurs, et d’en dégager un programme de soins individualisé proposé au patient à l’issue. L’analyse des résultats obtenus aux échelles RSVP et HCR20 de dix patients pris en charge dans la plateforme montre une variation des scores similaires pour les deux outils. Les scores obtenus à la RSVP ne semblent pas liés avec le type de passage à l’acte. Malgré des contenus d’apparence proche, il existe une complémentarité des deux outils dans l’évaluation et la prise en charge des patients. L’utilisation systématique de la RSVP et de la HCR20 est précieuse pour l’animation des réunions cliniques ; elle permet de dégager les axes de prise en charge les plus pertinents pour le patient, tout en fournissant aux professionnels une évaluation objective du niveau de risque présenté afin de proposer des interventions en conséquence. Objectives It has been well established that standardised evaluation tools better predict violence or sexual recidivism risk than general clinical examination only (Monahan, 1984 ; Pham and Réveillère, 2015). Several specific scales have been validated, but their use is not widespread in France despite their clinical interest. In particular, clinical structured judgment tools such as HCR-20 (Webster et al., 1997) and RSVP (Hart et al., 2003) are easy to implement in clinical settings, especially since their predictive power is enhanced by a multiprofessionnal scoring (Ducro, 2009). Patients or materials and methods Our ambulatory reference center specifically receives sexual offenders for a complete evaluation in order to propose a personalized care and treatment program. Patients are referred to the facility by a health professional. They first begin a nurse evaluation, then psychiatric and psychological interviews including the MMPI2-RF, the semi-structured dynamic interview QICPASS, as well as actuarial tools if needed. At the end of these separate evaluations, a multidisciplinary consultation meeting is organised with the evaluators and the health professionals who had addressed the patient to the center. RSVP and HCR-20 are coded by all the clinical team, which allows to point the most salient objectives of the patient's care, and to propose him a personalized program of care and treatment. Results The results of RSVP and HCR-20 scorings concerning 10 patients, show a similar scores variation at RSVP and HCR-20. RSVP scorings do not seem to be linked to the type of sexual offence. Even if their contents seem similar, HCR-20 and RSVP are complementary tools for sexual offenders’ evaluation. Conclusions Systematic evaluation of RSVP and HCR-20 is useful for clinical staffs: first, it allows a systematic evaluation; then, salient problems are underlined and specific care and treatment are proposed; with these tools, professional evaluation of recidivism and violence risk is enhanced and specific interventions are proposed. [ABSTRACT FROM AUTHOR]