The Right-Based View of the Cathedral: Liability Rules and Corrective Justice

In their celebrated paper, Calabresi and Melamed offered a framework, often referred to as the ‘‘Cathedral’’ analysis, which explains when and why entitlements should be protected using two main sets of rules—property rules and liability rules. This framework is now widely used to explain some private law doctrines. However, cases that are easily explained as applications of liability rules are usually difficult to explain under the private law theory of correlative corrective justice. This is because the basic idea underlying corrective justice conflicts with the notion of rules that allow the nonconsensual property appropriation subject to compensation. In this Article, we attempt to reconcile liability rules under both Cathedral analysis and corrective justice. To do so, we discuss three positive examples of pure liability rules and analyze them under a new model that we believe is consistent with corrective justice. We then discuss the model’s further implications

Isolation of the first toxin from the scorpion Buthus occitanus israelis showing preference for Shaker potassium channels

AbstractWe have purified BoiTx1, the first toxin from the venom of the Israeli scorpion, Buthus occitanus israelis, and studied its activity and genomic organization. BoiTx1 is a 37 amino acid-long peptide contained six conserved cysteines, and is classified as an α-KTx3.10 toxin. The pharmacological effects of BoiTx1 were studied on various cloned K+ channels expressed in Xenopus laevis oocytes. BoiTx1 inhibited currents through Drosophila Shaker channels with an IC50 value of 3.5±0.5nM, yet had much lesser effect on its mammalian orthologs. Thus, BoiTx1 is the first member of the α-KTx3 family that preferentially affects insect potassium channels

Does team psychological capital predict team outcomes at work?

This study is situated in the paradigms of positive organizational scholarship (POS) and positive organizational behaviour (POB). It draws upon the theoretical mechanisms of social learning and emotional contagion to suggest that psychological capital may spread through work teams to impact team outcomes such as performance, innovation, and organizational citizenship behavior (OCB). The degree to which team psychological capital (TPsyCap) mediated the relationship between leader psychological capital (LPsyCap) and team outcomes was also tested (n = 94 teams; n = 94 leaders; n = 550 employees). Using structural equation modelling, LPsyCap and TPsyCap were both related to team-level organizational citizenship behavior, team performance, and team innovation. However, the relationship between LPsyCap and TPsyCap was not significant. These findings support the positioning of psychological capital as an important resource for optimal team functioning but also suggest that workplaces cannot expect that leaders, through their own psychological capital alone, can create team-level psychological capital. Instead, the current research suggests that other organizational initiatives and experiences are needed to enhance LPsyCap. The results contribute to a better understanding of POS and POB in general and, specifically, to the recently emerging construct of team psychological capital

Changes in Routine Pediatric Practice in Light of Coronavirus 2019 (COVID-19)

The outbreak of severe acute respiratory syndrome coronavirus or coronavirus 2019 (COVID-19)1 in the city of Wuhan, China, in December 2019 has rapidly emerged into a pandemic affecting national communities throughout the world.2 As of May 17, 2020, more than 4.5 million people have been infected globally at a pace of 100 000/d, and 307 395 have died.3 We will briefly discuss the effects of COVID-19 on routine pediatric practice that have surfaced during the months after the onset of the pandemic and the implications for children’s health. Our aim is to raise awareness about the likely need to remodel routine pediatric practice, both in hospital and ambulatory services, in light of COVID-19, and in the event of future similar infectious emergencies

The Effect of Gentamicin-Induced Readthrough on a Novel Premature Termination Codon of CD18 Leukocyte Adhesion Deficiency Patients

Leukocyte adhesion deficiency 1 (LAD1) is an inherited disorder of neutrophil function. Nonsense mutations in the affected CD18 (ITB2) gene have rarely been described. In other genes containing such mutations, treatments with aminoglycoside types of antibiotics (e.g., gentamicin) were reported to partially correct the premature protein termination, by induction of readthrough mechanism.Genetic analysis was performed on 2 LAD1 patients. Expression, functional and immunofluorescence assays of CD18 in the patients were used to determine the in-vivo and in-vitro effects of gentamicin-induced readthrough. A theoretical modeling of the corrected CD18 protein was developed to predict the protein function.We found a novel premature termination codon, C562T (R188X), in exon 6 of the CD18 gene that caused a severe LAD1 phenotype in two unrelated Palestinian children. In-vivo studies on these patients' cells after gentamicin treatment showed abnormal adhesion and chemotactic functions, while in-vitro studies showed mislocalization of the corrected protein to the cytoplasm and not to the cell surface. A theoretical modeling of the corrected CD18 protein suggested that the replacement of the wild type arginine by gentamicin induced tryptophan at the position of the nonsense mutation, although enabled the expression of the entire CD18 protein, this was not sufficient to stabilize the CD18/11 heterodimer at the cell surface.A novel nonsense mutation in the CD18 gene causing a complete absence of CD18 protein and severe LAD1 clinical phenotype is reported. Both in vivo and in vitro treatments with gentamicin resulted in the expression of a corrected full-length dysfunctional or mislocalized CD18 protein. However, while the use of gentamicin increased the expression of CD18, it did not improve leukocyte adhesion and chemotaxis. Moreover, the integrity of the CD18/CD11 complex at the cell surface was impaired, due to abnormal CD18 protein and possibly lack of CD11a expression

Group creativity

Many creative endeavors take place in groups or teams. Because groups can build on more diverse resources than individuals, they have considerable creative potential. However, this potential often remains unfulfilled: Productivity loss and suboptimal decision-making threaten all aspects of the creative process. This article summarizes findings on group creativity including the pitfalls that threaten groups, and some basic principles of effective group design for creativity.</p

Proteome analysis of human neutrophil granulocytes from patients with monogenic disease using data-independent acquisition

Neutrophil granulocytes are critical mediators of innate immunity and tissue regeneration. Rare diseases of neutrophil granulocytes may affect their differentiation and/or functions. However, there are very few validated diagnostic tests assessing the functions of neutrophil granulocytes in these diseases. Here, we set out to probe omics analysis as a novel diagnostic platform for patients with defective differentiation and function of neutrophil granulocytes. We analyzed highly purified neutrophil granulocytes from 68 healthy individuals and 16 patients with rare monogenic diseases. Cells were isolated from fresh venous blood (purity >99%) and used to create a spectral library covering almost 8000 proteins using strong cation exchange fractionation. Patient neutrophil samples were then analyzed by data-independent acquisition proteomics, quantifying 4154 proteins in each sample. Neutrophils with mutations in the neutrophil elastase gene ELANE showed large proteome changes that suggest these mutations may affect maturation of neutrophil granulocytes and initiate misfolded protein response and cellular stress mechanisms. In contrast, only few proteins changed in patients with leukocyte adhesion deficiency (LAD) and chronic granulomatous disease (CGD). Strikingly, neutrophil transcriptome analysis showed no correlation with its proteome. In case of two patients with undetermined genetic causes, proteome analysis guided the targeted genetic diagnostics and uncovered the underlying genomic mutations. Data-independent acquisition proteomics may help to define novel pathomechanisms in neutrophil diseases and provide a clinically useful diagnostic dimension

Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects.

BACKGROUND: Profound combined immunodeficiency can present with normal numbers of T and B cells, and therefore the functional defect of the cellular and humoral immune response is often not recognized until the first severe clinical manifestation. Here we report a patient of consanguineous descent presenting at 13 months of age with hypogammaglobulinemia, Pneumocystis jirovecii pneumonia, and a suggestive family history. OBJECTIVE: We sought to identify the genetic alteration in a patient with combined immunodeficiency and characterize human caspase recruitment domain family, member 11 (CARD11), deficiency. METHODS: Molecular, immunologic, and functional assays were performed. RESULTS: The immunologic characterization revealed only subtle changes in the T-cell and natural killer cell compartment, whereas B-cell differentiation, although normal in number, was distinctively blocked at the transitional stage. Genetic evaluation revealed a homozygous deletion of exon 21 in CARD11 as the underlying defect. This deletion abrogated protein expression and activation of the canonical nuclear factor κB (NF-κB) pathway in lymphocytes after antigen receptor or phorbol 12-myristate 13-acetate stimulation, whereas CD40 signaling in B cells was preserved. The abrogated activation of the canonical NF-κB pathway was associated with severely impaired upregulation of inducible T-cell costimulator, OX40, cytokine production, proliferation of T cells, and B cell-activating factor receptor expression on B cells. CONCLUSION: Thus in patients with CARD11 deficiency, the combination of impaired activation and especially upregulation of inducible T-cell costimulator on T cells, together with severely disturbed peripheral B-cell differentiation, apparently leads to a defective T-cell/B-cell cooperation and probably germinal center formation and clinically results in severe immunodeficiency. This report discloses the crucial and nonredundant role of canonical NF-κB activation and specifically CARD11 in the antigen-specific immune response in human subjects

The relationship between the perception of distributed leadership in secondary schools and teachers' and teacher leaders' job satisfaction and organizational commitment

This study investigates the relation between distributed leadership, the cohesion of the leadership team, participative decision-making, context variables, and the organizational commitment and job satisfaction of teachers and teacher leaders. A questionnaire was administered to teachers and teacher leaders (n=1770) from 46 large secondary schools. Multiple regression analyses and path analyses revealed that the study variables explained significant variance in organizational commitment. The degree of explained variance for job satisfaction was considerably lower compared to organizational commitment. Most striking was that the cohesion of the leadership team and the amount of leadership support was strongly related to organizational commitment, and indirectly to job satisfaction. Decentralization of leadership functions was weakly related to organizational commitment and job satisfaction