Intracellular killing of Streptococcus pneumoniae is complemented by induction of macrophage apoptosis. Here, we show that the toxin pneumolysin (PLY) contributes both to lysosomal/phagolysosomal membrane permeabilization (LMP), an upstream event programing susceptibility to apoptosis, and to apoptosis execution via a mitochondrial pathway, through distinct mechanisms. PLY is necessary but not sufficient for the maximal induction of LMP and apoptosis. PLY’s ability to induce both LMP and apoptosis is independent of its ability to form cytolytic pores and requires only the first three domains of PLY. LMP involves TLR (Toll-like receptor) but not NLRP3/ASC (nucleotide-binding oligomerization domain [Nod]-like receptor family, pyrin domain-containing protein 3/apoptosis-associated speck-like protein containing a caspase recruitment domain) signaling and is part of a PLY-dependent but phagocytosis-independent host response that includes the production of cytokines, including interleukin-1 beta (IL-1β). LMP involves progressive and selective permeability to 40-kDa but not to 250-kDa fluorescein isothiocyanate (FITC)-labeled dextran, as PLY accumulates in the cytoplasm. In contrast, the PLY-dependent execution of apoptosis requires phagocytosis and is part of a host response to intracellular bacteria that also includes NO generation. In cells challenged with PLY-deficient bacteria, reconstitution of LMP using the lysomotrophic detergent LeuLeuOMe favored cell necrosis whereas PLY reconstituted apoptosis. The results suggest that PLY contributes to macrophage activation and cytokine production but also engages LMP. Following bacterial phagocytosis, PLY triggers apoptosis and prevents macrophage necrosis as a component of a broad-based antimicrobial strategy. This illustrates how a key virulence factor can become the focus of a multilayered and coordinated innate response by macrophages, optimizing pathogen clearance and limiting inflammation.

Christianity, Faith at Work Scale, Judaism, psychometric, scale, vocation, workplace spirituality, workplace religion,

Religiosity can significantly impact human behavior yet little is known about how religious belief and practice integrate with work. Using the Faith at Work Scale, we surveyed Christian workers in the United States (n = 374) and found that work-faith integration was positively associated with faith maturity, church attendance, age and denominational strictness, and negatively associated with organizational size. Denominational groups varied in their degree of integration but displayed similar patterns across dimensions of integration. Work-faith integration was manifest most strongly in integration related to the self, and somewhat less so in areas related to others and in transcendent aspects of work. Respondents attributed spiritual disciplines and workplace mentors as salient influences of work-faith integration. Implications for workplace spirituality scholarship and management are explored.

This article analyses the core sources of evidence that were claimed to underpin the wide-ranging reforms of the criminal justice system under the Criminal Justice Act 2003. Drawing from Foucault’s governmentality thesis, it argues that the processes of evidence collection and deployment did not comply with the government’s theoretical and methodological dictates of ‘evidence-based-policy’ as a guiding principle in all public policymaking. On the contrary, the parameters of the exercise were framed in such a way that critical evidence that questioned the wisdom of many of the planned reforms on the grounds that they will cause miscarriages of justice was completely disregarded. It is, therefore, concluded that the Criminal Justice Act (2003) is not ‘non-ideological’ as claimed. Rather, it symbolizes a governmental technique (in the Foucauldian sense) to transform ideology into discourse, which then provides the legitimate authority to force through the intended reform agenda.

The impact of COVID‐19 has underlined the need for reliable information to guide clinical practice and policy. This urgency has to be balanced against disruption to journal handling capacity and the continued need to ensure scientific rigour. We examined the reporting quality of highly disseminated COVID‐19 research papers using a bibliometric analysis examining reporting quality and risk of bias (RoB) amongst 250 top scoring Altmetric Attention Score (AAS) COVID‐19 research papers between January and April 2020. Method‐specific RoB tools were used to assess quality. After exclusions, 84 studies from 44 journals were included. Forty‐three (51%) were case series/studies, and only one was an randomized controlled trial. Most authors were from institutions based in China ( n = 44, 52%). The median AAS and impact factor was 2015 (interquartile range [IQR] 1,105–4,051.5) and 12.8 (IQR 5–44.2) respectively. Nine studies (11%) utilized a formal reporting framework, 62 (74%) included a funding statement, and 41 (49%) were at high RoB. This review of the most widely disseminated COVID‐19 studies highlights a preponderance of low‐quality case series with few research papers adhering to good standards of reporting. It emphasizes the need for cautious interpretation of research and the increasingly vital responsibility that journals have in ensuring high‐quality publications.

Abstract:The paper examines the problematic understanding of “risk” in entrepreneurial literature that locates courage in either the loss or gain of having or in the difficulty and hardship of the doing. We argue in this paper that what is lost in this vernacular view of courage is a deeper notion of the subjective dimension of work and the social need of society. Grounded within the Catholic social and moral tradition, we find a richer notion of courage, which in part corrects and rounds out the insufficient description of the vernacular understanding of courage in entrepreneurship. What we also find in this account of the virtues and subjective dimension of work is greater explanatory power of what happens to the entrepreneur in the work that he or she does. The end result of this analysis is a more spiritual, ethical and social understanding of entrepreneurship.

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