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Scientists across disciplines must often work together to address pressing global issues facing our societies. For interdisciplinary projects to flourish, scientists must recognise the potential contribution of other disciplines in answering key research questions. Recent research suggested that social sciences may be appreciated less than hard sciences overall. Building on the extensive evidence of ingroup bias and ethnocentrism in intergroup relations, however, one could also expect scientists, especially those belonging to high status disciplines, to play down the contributions of other disciplines to important research questions. The focus of the present research was to investigate how hard and social scientists perceive one another and the impact of interdisciplinary collaborations on these perceptions. We surveyed 280 scientists at Wave 1 and with 129 of them followed up at Wave 2 to establish how ongoing interdisciplinary collaborations underpinned perceptions of other disciplines. Based on Wave 1 data, scientists who report having interdisciplinary experiences more frequently are also more likely to recognise the intellectual contribution of other disciplines and perceive more commonalities with them. However, in line with the intergroup bias literature, group membership in the more prestigious hard sciences is related to a stronger tendency to downplay the intellectual contribution of social science disciplines compared to other hard science disciplines. This bias was not present among social scientists who produced very similar evaluation of contribution of hard and social science disciplines. Finally, using both waves of the survey, the social network comparison of discipline pairs shows that asymmetries in the evaluation of other disciplines are only present among discipline pairs that do not have any experience of collaborating with one another. These results point to the need for policies that incentivise new collaborations between hard and social scientists and foster interdisciplinary contact.

ABSTRACTBackgroundIn the MEETINGDEM project, the Meeting Centers Support Program (MCSP) was adaptively implemented and evaluated in three European countries: Italy, Poland, and the United Kingdom. The aim of this study was to investigate overall and country-specific facilitators and barriers to the implementation of MCSP in these European countries. MethodsA qualitative multiple case study design was used. Based on the theoretical model of adaptive implementation, a checklist was composed of potential facilitators and barriers to the implementation of MCSP. This checklist was administered among stakeholders involved in the implementation of MCSP to trace the experienced facilitators and barriers. Twenty-eight checklists were completed. ResultsMain similarities between countries were related to the presence of suitable staff, management, and a project manager, and the fact that the MCSP is attuned to needs and wishes of people with dementia and informal caregivers. Main differences between countries were related to: communication with potential referrers, setting up an inter-organizational collaboration network, receiving support of national organizations, having clear discharge criteria for the MCSP and continuous PR in the region. ConclusionThe results of this study provide insight into generic and country specific factors that can influence the implementation of MCSP in different European countries. This study informs further implementation and dissemination of MCSP in Europe and may also serve as an example for the dissemination and implementation of other effective psychosocial support interventions for people with dementia and their informal caregivers across and beyond Europe.

Matrix metalloproteinases 2 and 9 (MMP2 and MMP9) are proteolytic enzymes involved with extracellular matrix degradation. They play a role in tumor invasion and metastases. Because of their ability to degrade signaling molecules presented in extracellular matrix, MMPs contribute to tumor proliferation and apoptosis. The aim of this study was to evaluate expression of MMP2 (latent and both active and latent forms) and MMP9 (active, latent, active and latent forms) in different subtypes of canine lymphomas and their relationship with proliferative (mitotic index and percentage of Ki67-positive cells) and apoptotic (apoptotic index) markers. Expression of MMPs was assessed immunohistochemically using an immunoreactive score system. Expression of both MMPs was found in all 20 examined lymphomas belonging to six subtypes. Most cases showed a moderate level of all analyzed forms of MMP2 and MMP9. High expression of MMPs was found in single cases. Except for a positive correlation between the active form of MMP9 and the mitotic index for all lymphoma cases, no other correlations between any remaining forms of MMPs and neither proliferative nor apoptotic markers were found, irrespective of whether the analysis encompassed all cases or the most numerous lymphoma subtypes i.e. centroblastic and Burkitt-like. Our results were not able to clearly confirm the influence of MMPs on the proliferation and apoptotic activity of canine lymphoma cells. However, further studies examining MMPs activity by zymography, expression of their inhibitors and other factors involved in activation of cell proliferation and apoptosis inhibition are needed to clarify the role of MMPs, especially the active form of MMP9, in the behavior of canine lymphoma cells.

Survivin regulates cell cycle and mitosis and has antiapoptotic properties. Because of its dual function survivin has been the subject of much research focusing on its role in tumorigenesis and the relationship between survivin expression and apoptotic and/or proliferative activity in many types of human tumor including non-Hodgkin's Lymphomas. Such studies have not been conducted in canine lymphomas. The aim of this study was to evaluate the expression of survivin in canine lymphomas of low (5/25) and high (20/25) grades in relation to apoptotic markers (apoptotic index and index of caspase-3). Survivin was found in all examined lymphomas. Most tumors (18/25) showed survivin expression in 10%-25% of positive cells. Only in single cases was lower (0-10% positive cells, 1/25) or higher (25%-50% and >50% positive cells, 5/25 and 1/25, respectively) survivin expression. No significant differences between mean values of either index of survivin or apoptotic index was found between low and high grade lymphomas. However, such a difference among lymphoma grades was shown regarding the caspase-3 index. No correlation between the survivin index and either the apoptotic index or caspase-3 index was found, irrespective of the method of quantification: in whole specimens or in areas of low and high survivin expression. Positive correlation was consistently noted only between both apoptotic markers. The results indicate that survivin is commonly expressed in canine lymphomas. It seems that survivin does not exhibit anti-apoptotic activity in canine lymphomas. Lack of correlation between survivin expression and apoptotic markers could indicate its potential role in cell cycle activation in lymphoma cells.

Combination chemiotherapy is the current standard of care for dogs with lymphoma. Multidrug resistance is one of the most important factors contributing to the efficacy of chemiotherapy. The major protein responsible for this phenomenon is P-glycoprotein. Little is known about P-glycoprotein expression in particular subtypes of lymphomas. The aim of the study was evaluation of P-glycoprotein expression in various subtypes of canine lymphomas. Positive reaction with P-glycoprotein was found in 12/25 cases of various morphological subtypes of lymphomas, however, in 3/11 lymphomas the percentage of positively weakly stained cells was < 10% and those tumors were also considered negative. Tumors with 10-50% P-glycoprotein positive cells were found in single cases of centroblastic and centroblastic-centrocytic tumors. In 5 lymphomas P-glycoprotein expression exceeded 50% of tumor cells. Those cases were found among centroblastic, centroblastic-centrocytic, lymphoblastic and Burkitt-like subtypes. Positive reaction was observed mainly in the cell cytoplasm, however, in some cases prominent perinuclear dot-like staining pattern was found. In 2 cases focal staining pattern comprised dominant type of immunolabelling. Among all lymphomas containing P-glycoprotein positive cells intensity of imunolabelling was assessed as weak (6/25), moderate (2/25) and strong (3/25). Our results indicate that P-glycoprotein expression is present in nearly one third of newly diagnosed canine lymphomas of different morphological subtypes including those most commonly occurring, such as cenroblastic lymphomas. Hence, determination of P-glycoprotein expression at the time of diagnosis could provide valuable information for the design of treatment protocols. Moreover, our results have shown that P-glycoprotein expression in canine tumors could be located in Golgi-zone.

Survivin is a member of apoptosis inhibiting proteins family. Apart from its antiapoptotic activity it plays a critical role in regulating the cell cycle and mitosis. It is overexpressed in most human malignancies. While the prognostic significance of survivin expression is widely investigated in human non-Hodgkin's lymphomas, little is known about its expression in canine lymphomas. The aim of the study was to evaluate the expression of survivin in canine lymphomas in relation to proliferation markers (mitotic index and percentage of Ki67-positive cells). Survivin was found in all examined lymphomas belonging to 6 different morphological subtypes with nuclear immunoreactivity. In most of lymphomas (18/25) survivin expression ranged 10%-25% of positive cells. Only single cases had lower (0-10% positive cells, 1/25) or higher (25-50% and > 50% positive cells, 5/25 and 1/25, respectively) index of survivin. Neither mitotic index nor proliferative index correlated with survivin expression when the values quantified randomly in whole specimens were compared. However, when survivin expression were quantified in selected tumor areas of low and high proliferation activity the high correlations between survivin expression and proliferation index were found. The results indicated that survivin is commonly expressed in canine lymphomas. Nuclear labelling together with the relation of its expression and proliferative activity in highly proliferative areas of neoplastic tissue suggest a potential role of survivin in cell cycle activation in canine lymphoma cells. However, further studies of the relation between expression of survivin and other proteins involved in cell cycle regulation are needed. Moreover, the results suggest that survivin may pose the therapeutic target in canine lymphomas.

The insulin-like growth factor-1 receptor (IGF-IR) and the human polyomavirus JCV protein, T-antigen cooperate in the transformation of neuronal precursors in the cerebellum, which may be a contributing factor in the development of brain tumors. Because it is not clear why T-antigen requires IGF-IR for transformation, we investigated this process in neural progenitors from IGF-IR knockout embryos (ko-IGF-IR) and from their wild-type nontransgenic littermates (wt-IGF-IR). In contrast to wt-IGF-IR, the brain and dorsal root ganglia of ko-IGF-IR embryos showed low levels of the antiapoptotic protein Survivin, accompanied by elevated numbers of apoptotic neurons and an earlier differentiation phenotype. In wt-IGF-IR neural progenitors in vitro , induction of T-antigen expression tripled the expression of Survivin and accelerated cell proliferation. In ko-IGF-IR progenitors induction of T-antigen failed to increase Survivin, resulting in massive apoptosis. Importantly, ectopic expression of Survivin protected ko-IGF-IR progenitor cells from apoptosis and siRNA inhibition of Survivin activated apoptosis in wt-IGF-IR progenitors expressing T-antigen. Our results indicate that reactivation of the antiapoptotic Survivin may be a critical step in JCV T-antigen-induced transformation, which in neural progenitors requires IGF-IR.

We have previously reported that insulin-like growth factor-I (IGF-I) supports growth and survival of mouse and human medulloblastoma cell lines, and that IGF-I receptor (IGF-IR) is constitutively phosphorylated in human medulloblastoma clinical samples. Here, we demonstrate that a specific inhibitor of insulin-like growth factor-I receptor (IGF-IR), NVP-AEW541, attenuated growth and survival of mouse (BsB8) and human (D384, Daoy) medulloblastoma cell lines. Cell cycle analysis demonstrated that G1 arrest and apoptosis contributed to the action of NVP-AEW54. Interestingly, very aggressive BsB8 cells, which derive from cerebellar tumors of transgenic mice expressing viral oncoprotein (large T-antigen from human polyomavirus JC) became much more sensitive to NVP-AEW541 when exposed to anchorage-independent culture conditions. This high sensitivity to NVP-AEW54 in suspension was accompanied by the loss of GSK-3 β constitutive phosphorylation and was independent from T-antigen-mediated cellular events ( Supplementary Materials ). BsB8 cells were partially rescued from NVP-AEW541 by GSK3 β inhibitor, lithium chloride and were sensitized by GSK3 β activator, sodium nitroprusside (SNP). Importantly, human medulloblastoma cells, D384, which demonstrated partial resistance to NVP-AEW541 in suspension cultures, become much more sensitive following SNP-mediated GSK3 β dephosphorylation (activation). Our results indicate that hypersensitivity of medulloblastoma cells in anchorage-independence is linked to GSK-3 β activity and suggest that pharmacological intervention against IGF-IR with simultaneous activation of GSK3 β could be highly effective against medulloblastomas, which have intrinsic ability of disseminating the CNS via cerebrospinal fluid.

The human immunodeficiency virus type 1 (HIV-1) viral protein R ( vpr ) gene is an evolutionarily conserved gene among the primate lentiviruses. Several functions are attributed to Vpr including the ability to cause cell death, cell cycle arrest, apoptosis and DNA damage. The Vpr domain responsible for DNA damage as well as the mechanism(s) through which Vpr induces this damage is unknown. Using site-directed mutagenesis, we identified the helical domain II within Vpr (aa 37–50) as the region responsible for causing DNA damage. Interestingly, Vpr Δ(37–50) failed to cause cell cycle arrest or apoptosis, to induce Ku70 or Ku80 and to suppress tumor growth, but maintained its capability to activate the HIV-1 LTR, to localize to the nucleus and to promote nonhomologous end-joining. In addition, our cytogenetic data indicated that helical domain II induced chromosomal aberrations, which mimicked those induced by cisplatin, an anticancer agent. This novel molecular mimicry function of Vpr might lead to its potential therapeutic use as a tumor suppressor.

Bronchial asthma is a common disease characterized by chronic inflammation of the airways. Paediatric asthma is still a current problem and children with exacerbation frequently are hospitalized. The aim of the study was to determine the prevalence of allergic and non-allergic asthma in children hospitalized at the Department of Paediatric Pulmonology and Rheumatology of the University Children’s Hospital in Lublin in 2016-2020, and to analyze the most common allergens associated with allergic asthma. The study group consisted of 667 patients, aged 6 to 215 months (average 64 months). The data collected for this retrospective study includes: gender, age, month, quarter of year, and year of hospitalization, type of asthma and type of allergens. We observed a decrease of hospitalization in the analyzed years: in 2016 – 160 children, and in 2020 – 74. Children with allergic asthma (375 children) were more frequently hospitalized than patients with non-allergic asthma, and we found correlations between age and type of asthma and between age and type of allergy. Non-allergic asthma was observed in the youngest children, while in older children, allergic-asthma dominated. We also observed significant differences in children’s hospitalization depending on the season of the year. The most frequent allergen causing asthma was house dust mites. The incidence of hospitalizations caused by asthma exacerbation is declining. Among the youngest population, exacerbations of asthma related to respiratory tract infection predominate, while in the older, allergy to inhalation allergens is the main cause.