פרסומים

In the past decade, the identification of susceptibility genes for psychiatric disorders has become routine, but understanding the biology underlying these discoveries has proven extremely difficult. The large number of potential risk genes and the genetic overlap between disorders are major obstacles for studying the etiology of these conditions. Systems biology approaches relying on gene ontologies, gene coexpression, and protein-protein interactions are used to identify convergence of the genes in relation to biological processes, cell types, brain areas, and developmental stages. Across psychiatric disorders, there is a clear enrichment for genes expressed in the brain and especially in the cortex, but a higher resolution is vastly dependent on sample size and statistical power. There is indication that susceptibility genes tend to be expressed in the brain during periods preceding the typical onset of the disorders. Thus, the role of genes in prenatal brain development is more pronounced for childhood-onset disorders, such as autism spectrum disorder and attention-deficit/hyperactivity disorder, but is much less so for bipolar disorder and depression. One of the most consistent findings across multiple disorders and classes of genetic variants is the role of genes intolerant to mutations in psychiatric disorders, yet this association is more pronounced for disorders with a clear neurodevelopmental component. Notwithstanding, a detailed understanding of the neurobiology of psychiatric disorders is still lacking. It is possible that it will only be revealed by studying the risk genes at the level of the development and function of neuronal networks and circuits.

We show a Gromov-Hausdorff approximation to the product of the standard spheres for Riemannian manifolds with positive Ricci curvature under some pinching condition on the eigenvalues of the Laplacian acting on functions and forms.

Following a rise in the life expectancy of cystic fibrosis (CF) patients, many adults with CF form couple relationships. Yet, dyadic coping has not been previously examined in people with CF. This study examined how adults with CF and their partners cope as a couple with the illness, and what meanings each partner and the couple as a unit attribute to the experience. Seventeen adult CF patients and their partners participated in separate semi-structured in-depth interviews. Two main patterns of dyadic coping with CF were identified as follows: cooperation and tension. For couples in cooperation, the marital relationship served as a resource for adaptive coping. These couples were characterized by similarities in their perception of the place of CF in their lives and of their roles in the marital relationship. Couples in tension described the couple relationship as strained by difficulty of accepting the disease, proliferation of negative emotions, and a sense of burden and loneliness in the process of coping. Findings point to the importance of mutual empathy, clear and accepted division of roles between the partners, and open communication for facilitating coping as a couple.

The value is a solution concept for n-person strategic games, developed by Nash,Shapley, and Harsanyi. The value of a game is an a priori evaluation of the economicworth of the position of each player, reflecting the players’ strategic possibilities,including their ability to make threats against one another. Applications of the value in economics have been rare, at least in part because the existing definition (for games with more than two players) consists of an ad hoc scheme that does not easily lend itself to computation. This paper makes three contributions: We provide an axiomatic foundation for the value; exhibit a simple formula for its computation; and extend the value—its definition, axiomatic characterization, and computational formula—to Bayesian games. We then apply the value in simple models of corruption, oligopolistic competition, and information sharing.

Morphogenesis and differentiation are important stages in organ development and shape determination. However, how they are balanced and tuned during development is not fully understood. In the compound leaved tomato, an extended morphogenesis phase allows for the initiation of leaflets, resulting in the compound form. Maintaining a prolonged morphogenetic phase in early stages of compound-leaf development in tomato is dependent on delayed activity of several factors that promote differentiation, including the CIN-TCP transcription factor (TF) LA, the MYB TF CLAU and the plant hormone Gibberellin (GA), as well as on the morphogenesis-promoting activity of the plant hormone cytokinin (CK). Here, we investigated the genetic regulation of the morphogenesis-differentiation balance by studying the relationship between LA, CLAU, TKN2, CK and GA. Our genetic and molecular examination suggest that LA is expressed earlier and more broadly than CLAU and determines the developmental context of CLAU activity. Genetic interaction analysis indicates that LA and CLAU likely promote differentiation in parallel genetic pathways. These pathways converge downstream on tuning the balance between CK and GA. Comprehensive transcriptomic analyses support the genetic data and provide insights into the broader molecular basis of differentiation and morphogenesis processes in plants.

The variability in leaf form in nature is immense. Leaf patterning occurs by differential growth, taking place during a limited window of morphogenetic activity at the leaf marginal meristem. While many regulators have been implicated in the designation of the morphogenetic window and in leaf patterning, how these effectors interact to generate a particular form is still not well understood. We investigated the interaction among different effectors of tomato (Solanum lycopersicum) compound-leaf development, using genetic and molecular analyses. Mutations in the tomato auxin response factor SlARF5/SlMP, which normally promotes leaflet formation, suppressed the increased leaf complexity of mutants with extended morphogenetic window. Impaired activity of the NAC/CUC transcription factor GOBLET (GOB), which specifies leaflet boundaries, also reduced leaf complexity in these backgrounds. Analysis of genetic interactions showed that the patterning factors SlMP, GOB and the MYB transcription factor LYRATE (LYR) coordinately regulate leaf patterning by modulating in parallel different aspects of leaflet formation and shaping. This work places an array of developmental regulators in a morphogenetic context. It reveals how organ-level differentiation rate and local growth are coordinated to sculpture an organ. These concepts are applicable to the coordination of pattering and differentiation in other species and developmental processes.

The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq. Ensembl gene IDs with the nearest transcriptional start site to ChIP-seq peaks were explored as potential targets, and represented 846 protein coding genes common to UNDIFF and DIFF cells and 2773 unique to DIFF samples. Genes with overlapping peaks between samples (1343) enriched cell-cell adhesion, membrane transporters and lipid metabolism categories. To functionally verify targets, an HC11 line with Bmal1 gene knocked out (BMAL1-KO) using CRISPR-CAS was created. BMAL1-KO cultures had lower cell densities over an eight-day growth curve, which was associated with increased (p<0.05) levels of reactive oxygen species and lower expression of superoxide dismutase 3 (Sod3). RT-qPCR analysis also found lower expression of the putative targets, prolactin receptor (Prlr), Ppara, and beta-casein (Csn2). Findings support our hypothesis and highlight potential importance of clock in mammary development and substrate transport.

The coronavirus disease 2019 (COVID-19) pandemic stimulated both the scientific community and healthcare companies to undertake an unprecedented effort with the aim of understanding the molecular mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and developing effective therapeutic solutions. The peculiar immune response triggered by this virus, which seems to last only few months, led to a search for alternatives such as passive immunization in addition to conventional vaccinations. Convalescent sera, monoclonal antibodies selected from the most potent neutralizing binders induced by the virus infection, recombinant human single-domain antibodies, and binders of variable scaffold and different origin have been tested alone or in combination exploiting monovalent, multivalent and multispecific formats. In this review, we analyse the state of the research in this field and present a summary of the ongoing projects finalized to identify suitable molecules for therapies based on passive immunization.

The coronavirus disease 2019 (COVID-19) pandemic stimulated both the scientific community and healthcare companies to undertake an unprecedented effort with the aim of understanding the molecular mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and developing effective therapeutic solutions. The peculiar immune response triggered by this virus, which seems to last only few months, led to a search for alternatives such as passive immunization in addition to conventional vaccinations. Convalescent sera, monoclonal antibodies selected from the most potent neutralizing binders induced by the virus infection, recombinant human single-domain antibodies, and binders of variable scaffold and different origin have been tested alone or in combination exploiting monovalent, multivalent and multispecific formats. In this review, we analyse the state of the research in this field and present a summary of the ongoing projects finalized to identify suitable molecules for therapies based on passive immunization.

Journal of Experimental Botany, Volume 71, Issue 21, 2 December 2020, Pages 6830–6843, https://doi.org/10.1093/jxb/eraa258In the original publication of this article, in the penultimate sentence of the legend to Fig 3, there were errors in identifying coloured lines. These should read: “Direct polarization (blue line) samples all the Si atoms in the sample, while 1H-cross-polarization (black line) samples Si atoms in proximity to protons.” instead of “: “Direct polarization (black line) samples all the Si atoms in the sample, while 1H-cross-polarization (blue line) samples Si atoms in proximity to protons.” This error has now been corrected online.

Aging is an established risk factor for vascular diseases, but vascular aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that vascular endothelial growth factor (VEGF) signaling insufficiency, which is caused by increased production of decoy receptors, may drive physiological aging across multiple organ systems. Increasing VEGF signaling prevented age-associated capillary loss, improved organ perfusion and function, and extended life span. Healthier aging was evidenced by favorable metabolism and body composition and amelioration of aging-associated pathologies including hepatic steatosis, sarcopenia, osteoporosis, "inflammaging" (age-related multiorgan chronic inflammation), and increased tumor burden. These results indicate that VEGF signaling insufficiency affects organ aging in mice and suggest that modulating this pathway may result in increased mammalian life span and improved overall health.

Aging is an established risk factor for vascular diseases, but vascular aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that vascular endothelial growth factor (VEGF) signaling insufficiency, which is caused by increased production of decoy receptors, may drive physiological aging across multiple organ systems. Increasing VEGF signaling prevented age-associated capillary loss, improved organ perfusion and function, and extended life span. Healthier aging was evidenced by favorable metabolism and body composition and amelioration of aging-associated pathologies including hepatic steatosis, sarcopenia, osteoporosis, "inflammaging" (age-related multiorgan chronic inflammation), and increased tumor burden. These results indicate that VEGF signaling insufficiency affects organ aging in mice and suggest that modulating this pathway may result in increased mammalian life span and improved overall health.

Countertransference may reflect the patients’ diagnosis and can be used to better understand patients’ inner worlds and core conflictual relationship themes (CCRTs). Thus, the changing emotions of therapists can serve as a marker of treatment processes. This exploratory study aims to identify how the interaction between patients’ CCRT patterns and their respective therapists’ emotions associate with working alliance postsession and patient symptoms. The data analysis is based on 17 subjects who received supportive−expressive therapy. Therapists’ emotional reactions were assessed using the Feeling Word Checklist. The Working Alliance Inventory—Short Revised and the Outcome Questionnaire were completed at each session. The relationship between the patients’ CCRTs and (a) the therapists’ emotional profile, (b) therapists’ rated working alliance, and (c) patient symptoms was analyzed using mixed models. Results show that patients’ CCRT moderated the correlation between therapists’ feeling engaged and time. In addition, patients’ CCRTs and therapists’ emotions together was associated with therapists’ rated working alliance and patient symptoms. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Countertransference may reflect the patients’ diagnosis and can be used to better understand patients’ inner worlds and core conflictual relationship themes (CCRTs). Thus, the changing emotions of therapists can serve as a marker of treatment processes. This exploratory study aims to identify how the interaction between patients’ CCRT patterns and their respective therapists’ emotions associate with working alliance postsession and patient symptoms. The data analysis is based on 17 subjects who received supportive−expressive therapy. Therapists’ emotional reactions were assessed using the Feeling Word Checklist. The Working Alliance Inventory—Short Revised and the Outcome Questionnaire were completed at each session. The relationship between the patients’ CCRTs and (a) the therapists’ emotional profile, (b) therapists’ rated working alliance, and (c) patient symptoms was analyzed using mixed models. Results show that patients’ CCRT moderated the correlation between therapists’ feeling engaged and time. In addition, patients’ CCRTs and therapists’ emotions together was associated with therapists’ rated working alliance and patient symptoms. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

The actor?partner interdependence model (APIM) was employed in this study to investigate the mediating effect self-differentiation and spousal caregiving have on the relationship between recollection of parental care and acceptance and couple satisfaction. One hundred and forty-four non-clinical couples (N = 288) in enduring relationships were recruited. Results for actor effects revealed two mediating paths whereby, among both partners, recollection of maternal (but not paternal) acceptance was associated with their self-differentiation and responsive spousal caregiving, which, in turn, were linked to their spousal relationship satisfaction. Partner effects revealed three mediating paths: for both partners, recollection of childhood maternal acceptance was associated with responsive caregiving, which, in turn, was linked with their partner?s relationship satisfaction. Interestingly, the husbands? recollection of maternal acceptance was associated with their partners? responsive spousal caregiving, which was linked to both spouses? relationship satisfaction. Our results may support the theoretical assumptions regarding intergenerational continuity from perceptions of childhood via self-differentiation effecting couple caregiving to couple relationship, but only on the mother?s part.