Sustainable Development Aspects in Cross-Border Cooperation Programmes: The Case of Croatia and Montenegro

The cross-border area between Croatia and Montenegro has similar development preconditions: large potential for tourism development and rich natural and cultural heritage. Both have experience in EU funded cross-border cooperation (CBC) programmes. The importance of the sustainable development aspect and is formally included into various national strategic documents, but implementation of such vague strategic documents is often problematic and sustainability aspects need to be examined on programme and project level. The current Integrated Pre-accession Assistance (IPA) Cross-border Cooperation Programme Croatia-Montenegro 2007-2013 is the basis for our research and sustainability evaluation. As recognised in the Cross-border Cooperation (CBC) Programme, one of the main challenges of the cross-border area besides the impact of globalization on the regional economy and developing competitive economy based on knowledge etc., are also environmental challenges. The Programme’s strategic orientation to sustainable development encompasses economic development, human resources development, social justice and environmental protection. The overall objective focuses on the development of the cross-border region through cooperation and networks following the guidelines and regulations provided by the European Commission (EC) through the IPA Implementing Regulation. Specific objectives focus on development of SMEs, tourism, trade, environment, culture and sport. The long-term opportunities for the programming area are: competitive regional economies based on high quality service sector in tourism; efficient protection of the environment; natural and cultural heritage; and sustainable use of nature resources; as well as high quality public and social services necessary for community development. At project level, environmental issues were only to a very limited degree included and addressed in the application package through evaluation of financial, institutional, policy level and environmental sustainability aspects. Since the CBC Programme is implemented through projects, our questions are the following: What is the structural impact of the proposed actions and do they lead to improved legislation, codes of conduct, and methods? Is there an environmental impact? To which extent is guidance on sustainability issues provided and what is needed for improved implementation? How are participatory approaches during project planning and implementation used?

A tehetetlenség lehetséges okai a gyermekjóléti szolgáltatás területén

A gyermekjóléti szolgálatok helyzetével, szakmai tevékenységük és az ezzel összefüggő dilemmák lényegi összefoglalásával foglalkozik e tanulmány. Tíz éve annak, hogy a gyermekek védelméről és a gyámügyi igazgatásról szóló, 1997. évi XXXI. törvény megalkotta az új, intézményesült, gyermekvédelmi ellátás feladatkörét és működésének kereteit. A törvény a szociális munkát tekinti az ellátás fő eszközének. A tanulmány első része a szociális munka komplexitásának és interdiszciplináris természetének lényegét, és az ebből fakadó dilemmát próbálja felvázolni. Ezt követően bemutatja a szociális esetmunka keretét, tartalmát és határait. Kiemelten foglalkozik a szociális munka és a kontroll viszonyának kérdésével. Kiáll a szociális munka lélektani szempontjai, ezen belül a segítő kapcsolat minőségi feltételrendszerének a fontossága mellett, részletezve hatásának fontosságát a kliens változása szempontjából. A szerző többször is támaszkodik a konstruktív szociális munkának az elméletére, és az ezzel összefüggő külföldi szakirodalomra, valamint David Howe (1992; 1996) kutatásainak eredményeire. A tanulmány második részében részletesen bemutatja a családgondozás lépéseit, mint a gyermek veszélyeztetettségének megszüntetésre irányuló feladatotok rendszerét. Összeveti ezeket feltételeket a szociális munka belső természetével. Elemzése során kiemeli a szolgálat két az eltérő szerepéből fakadó, ellentmondásos működését, amely a segítő és hatósági szerep között húzódik meg. Ennek feloldására több lehetséges megoldási irányt is felvázol. Sürgetőnek érzi a szolgálat tevékenységének, szerepeinek tisztázását az ellátást igénybevevők, de a területen dolgozók érdekében is. A szolgálat kapcsán pedig ugyanúgy elengedhetetlen a szociális munka szakmai identitásának a tisztázása, főként a segítő kapcsolat és a külső kontroll feloldhatatlannak tűnő, ellentmondásos kapcsolata vonatkozásában

Concomitant deletion of Ptpn6 and Ptpn11 in T cells fails to improve anticancer responses

Anticancer T cells acquire a dysfunctional state characterized by poor effector function and expression of inhibitory receptors, such as PD-1. Blockade of PD-1 leads to T cell reinvigoration and is increasingly applied as an effective anticancer treatment. Recent work challenged the commonly held view that the phosphatase PTPN11 (known as SHP-2) is essential for PD-1 signaling in T cells, suggesting functional redundancy with the homologous phosphatase PTPN6 (SHP-1). Therefore, we investigated the effect of concomitant Ptpn6 and Ptpn11 deletion in T cells on their ability to mount antitumour responses. In vivo data show that neither sustained nor acute Ptpn6/11 deletion improves T cell-mediated tumor control. Sustained loss of Ptpn6/11 also impairs the therapeutic effects of anti-PD1 treatment. In vitro results show that Ptpn6/11-deleted CD8(+) T cells exhibit impaired expansion due to a survival defect and proteomics analyses reveal substantial alterations, including in apoptosis-related pathways. These data indicate that concomitant ablation of Ptpn6/11 in polyclonal T cells fails to improve their anticancer properties, implying that caution shall be taken when considering their inhibition for immunotherapeutic approaches

Tuning MPL signaling to influence hematopoietic stem cell differentiation and inhibit essential thrombocythemia progenitors

Thrombopoietin (TPO) and the TPO-receptor (TPO-R, or c-MPL) are essential for hematopoietic stem cell (HSC) maintenance and megakaryocyte differentiation. Agents that can modulate TPO-R signaling are highly desirable for both basic research and clinical utility. We developed a series of surrogate protein ligands for TPO-R, in the form of diabodies (DBs), that homodimerize TPO-R on the cell surface in geometries that are dictated by the DB receptor binding epitope, in effect "tuning" downstream signaling responses. These surrogate ligands exhibit diverse pharmacological properties, inducing graded signaling outputs, from full to partial TPO agonism, thus decoupling the dual functions of TPO/TPO-R. Using single-cell RNA sequencing and HSC self-renewal assays we find that partial agonistic diabodies preserved the stem-like properties of cultured HSCs, but also blocked oncogenic colony formation in essential thrombocythemia (ET) through inverse agonism. Our data suggest that dampening downstream TPO signaling is a powerful approach not only for HSC preservation in culture, but also for inhibiting oncogenic signaling through the TPO-R

Gelsolin dysfunction causes photoreceptor loss in induced pluripotent cell and animal retinitis pigmentosa models

Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause X-linked RP (XLRP), an untreatable, inherited retinal dystrophy that leads to premature blindness. RPGR localises to the photoreceptor connecting cilium where its function remains unknown. Here we show, using murine and human induced pluripotent stem cell models, that RPGR interacts with and activates the actin-severing protein gelsolin, and that gelsolin regulates actin disassembly in the connecting cilium, thus facilitating rhodopsin transport to photoreceptor outer segments. Disease-causing RPGR mutations perturb this RPGR-gelsolin interaction, compromising gelsolin activation. Both RPGR and Gelsolin knockout mice show abnormalities of actin polymerisation and mislocalisation of rhodopsin in photoreceptors. These findings reveal a clinically-significant role for RPGR in the activation of gelsolin, without which abnormalities in actin polymerisation in the photoreceptor connecting cilia cause rhodopsin mislocalisation and eventual retinal degeneration in XLRP.Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause retinal dystrophy, but how this arises at a molecular level is unclear. Here, the authors show in induced pluripotent stem cells and mouse knockouts that RPGR mediates actin dynamics in photoreceptors via the actin-severing protein, gelsolin

TYK2 Kinase Activity Is Required for Functional Type I Interferon Responses In Vivo

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family and is involved in cytokine signalling. In vitro analyses suggest that TYK2 also has kinase-independent, i.e., non-canonical, functions. We have generated gene-targeted mice harbouring a mutation in the ATP-binding pocket of the kinase domain. The Tyk2 kinase-inactive (Tyk2K923E) mice are viable and show no gross abnormalities. We show that kinase-active TYK2 is required for full-fledged type I interferon- (IFN) induced activation of the transcription factors STAT1-4 and for the in vivo antiviral defence against viruses primarily controlled through type I IFN actions. In addition, TYK2 kinase activity was found to be required for the protein’s stability. An inhibitory function was only observed upon over-expression of TYK2K923E in vitro. Tyk2K923E mice represent the first model for studying the kinase-independent function of a JAK in vivo and for assessing the consequences of side effects of JAK inhibitors

Bouncing back from psychological contract breach:how commitment recovers over time

The Post-Violation Model of the psychological contract (Tomprou, Rousseau, & Hansen, 2015) outlines four ways in which a psychological contract may be resolved after breach (i.e., psychological contract thriving, reactivation, impairment, and dissolution). To explore the implications of this model for post-breach restoration of organizational commitment, we recorded dynamic patterns of organizational commitment across a fine-grained longitudinal design in a sample of young academics who reported breach events while undergoing job changes (N = 109). By tracking organizational commitment up until 10 weeks after the first reported breach event, we ascertain that employees may indeed bounce back from a breach incidence, albeit that some employees do so more successfully than others. We further demonstrate that the emotional impact of the breach and post-breach perceived organizational support are related to the success of the breach resolution process. Additionally, we reveal a non-linear component in post-breach trajectories of commitment which suggests that processes determining breach resolution success are more complex than currently assumed

Caught in the Middle: How and When Psychological Contract Breach by Subordinates Relates to Weekly Emotional Exhaustion of Supervisors

In psychological contract research, the side of the supervisor is strongly underexposed. However, supervisors are responsible for maintaining relationships with both their subordinates and senior management and are likely to be influenced by events unfolding in these relationships. In this study, we state that supervisor well-being may be affected by subordinates who fail to meet their obligations. This study adds to psychological contract research by developing an understanding of how and when subordinate psychological contract break (PCB) is associated with supervisor emotional exhaustion. Through a weekly diary survey among 56 Dutch supervisors, we test hypotheses about the relationships between subordinate PCB and the emotional exhaustion of the supervisor, the mediating role of perceptions of performance pressure by the supervisor in this relationship, and the moderating role of i-deals between the supervisor and senior management. Multilevel analyses support the first two hypotheses, but contradictory to our expectations show that the positive association between subordinate PCB and the emotional exhaustion of the supervisor is strengthened when the supervisor has high levels of i-deals with senior management. We discuss the findings in relation to their contribution to psychological contract theory

Pleiotropic Effects of Sox2 during the Development of the Zebrafish Epithalamus

The zebrafish epithalamus is part of the diencephalon and encompasses three major components: the pineal, the parapineal and the habenular nuclei. Using sox2 knockdown, we show here that this key transcriptional regulator has pleiotropic effects during the development of these structures. Sox2 negatively regulates pineal neurogenesis. Also, Sox2 is identified as the unknown factor responsible for pineal photoreceptor prepatterning and performs this function independently of the BMP signaling. The correct levels of sox2 are critical for the functionally important asymmetrical positioning of the parapineal organ and for the migration of parapineal cells as a coherent structure. Deviations from this strict control result in defects associated with abnormal habenular laterality, which we have documented and quantified in sox2 morphants