The cyclic GMP‐AMP synthase–stimulator of interferon genes (cGAS‐STING) pathway is central for the initiation of anti‐tumoural immune responses. Enormous effort has been made to optimise the design and administration of STING agonists to stimulate tumour immunogenicity. However, in certain contexts the cGAS‐STING axis fuels tumourigenesis. Here, we review recent findings on the regulation of cGAS expression and activity. We particularly focus our attention on the DNA‐dependent protein kinase (DNA‐PK) complex, that recently emerged as an activator of inflammatory (...) responses in tumour cells. We propose that stratification analyses on cGAS and DNA‐PK expression/activation status should be carried out to predict treatment efficacy. We herein also provide insights into non‐canonical functions borne by cGAS and cGAMP, highlighting how they may influence tumourigenesis. All these parameters should be taken into consideration concertedly to choose strategies aiming to effectively boost tumour immunogenicity. (shrink)

HIV‐1 infects dendritic cells (DCs) without triggering an effective innate antiviral immune response. As a consequence, the induction of adaptive immune responses controlling virus spread is limited. In a recent issue of Immunity, Lahaye and colleagues show that intricate interactions of HIV capsid with the cellular cofactor cyclophilin A (CypA) control infection and innate immune activation in DCs. Manipulation of HIV‐1 capsid to increase its affinity for CypA results in reduced virus infectivity and facilitates access of the cytosolic DNA sensor (...) cGAS to reverse transcribed DNA. This in turn induces a strong host response. Here, we discuss these findings in the context of recent developments in innate immunity and consider the implications for disease control and vaccine design. (shrink)

Ligation is a form of chemical self-assembly that involves dynamic formation of strong covalent bonds in the presence of weak associative forces. We study an extremely simple form of ligation by means of a dissipative particle dynamics (DPD) model extended to include the dynamic making and breaking of strong bonds, which we term dynamically bonding dissipative particle dynamics (DDPD). Then we use a chemical genetic algorithm (CGA) to optimize the model’s parameters to achieve a limited form of ligation of trimers—a (...) proof of principle for the evolutionary design of self-assembling chemical systems. (shrink)

Companions in guilt arguments respond to moral error theory by pointing out that its philosophical rationale mandates the rejection of all categorical normative reasons, including epistemic reasons. A number of philosophers have recently been engaging in a dialogue about the strength of this argumentative strategy and the significance of the criticisms that has been raised against it. In this paper, I identify a specific argument, which I dub the ‘bullet-biting response’ as a crucial element in some recent attacks on the (...) CGA. I assess five objections to the bullet-biting response and conclude that only the fifth poses a significant problem. Specifically, I argue that the proponent of the bullet-biting response is at a dialectical disadvantage in this particular debate. While this disadvantage is not decisive, it has two implications that raise serious concerns for the bullet-biting response. (shrink)

Arguably, no psychological variable has received more attention from behavioral geneticists than what has been called “general cognitive ability” (as well as “general intelligence” or “g”), and for good reason. GCA has a rich correlational network, implying that it may play an important role in multiple domains of functioning. GCA is highly correlated with various indicators of educational attainment, yet its predictive utility is not limited to academic achievement. It is also correlated with work performance, navigating the complexities of everyday (...) life, the absence of various social pathologies (such as criminal convictions), and even health and mortality. Although the causal basis for these associations is not always known, it is nonetheless the case that research on GCA has the potential to provide insights into the origins of a wide range of important social outcomes. In this essay, our discussion of why GCA is considered a fundamentally important dimension of behavior on which humans differ is followed by a look at behavioral genetics research on CGA. We summarize behavioral genetics research that has sought to identify and quantify the total contributions of genetic and environmental factors to individual differences in GCA as well as molecular genetic research that has sought to identify genetic variants that underlie inherited effects. (shrink)

This intervention study explored the effects of a newly developed intergenerational encounter program on cross-generational age stereotyping. Based on a biographical-narrative approach, participants were invited to share ideas about existential questions of life. Therefore, the dyadic Life Story Interview had been translated into a group format, consisting of 10 90-min sessions. Analyses verified that LSEP participants of both generations showed more favorable CGAS immediately after, but also 3 months after the program end. Such change in CGAS was absent (...) in a control group. The LSEP-driven short- and long-term effects on CGAS could be partially explained by two program benefits, the feeling of comfort with and the experience of learning from the other generation. (shrink)

Based on the texts of ‘Management Discussion and Analysis on Financial Status and Business’ collected from 118 American corporate annual reports, this study investigated how the professional discourse is realized from the dimensions of text, genre, professional practice and professional culture, according to the framework of the Critical Genre Analysis theory. It was found that In the text dimension, lexicon features regarding vocabulary volume, vocabulary highlighting, readability and sentiment are unique to MD&As; the genre of MD&As corresponds to a rhetorical (...) structure of 3 moves and 10 steps; the professional practice of MD&As is represented by three types of interdiscursivity, that is, shifting, mixing and embedding; the professional culture of MD&As is embodied through identity enculturation, human-oriented value, cooperation awareness and self-serving manner. The results of this study help to better understand the realization of professional discourse and expand the application of CGA in professional practice. The findings presented herein are expected to enhance interdisciplinary research that relates language with corporate performance. (shrink)

This article is concerned with the interconnection between three arguments: the Moral Explanatory Dispensability Argument, the Epistemic Explanatory Dispensability Argument, and the Companions in Guilt Argument. Silvan Wittwer has recently argued that the Epistemic EDA is self-effacing, whereas the Moral EDA is not. This difference between them is then leveraged by Wittwer to establish that there is a significant disparity between these arguments and that this disparity undermines attempts to use the CGA as a means of refuting the Moral EDA. (...) After explaining the connections between these arguments, I provide three different responses to Wittwer’s analysis. First, I develop a plausible case in favor of the conclusion that the Moral EDA is also self-effacing. Second, I defend the Epistemic EDA from the charge of self-effacement and respond to Wittwer’s assertion that my preferred method of escaping his argument is dialectically inappropriate. Finally, I explain how some arguments recently articulated by Richard Rowland and Ramon Das support my objections to Wittwer’s self-effacement argument. (shrink)