Focus on collagen: in vitro systems to study fibrogenesis and antifibrosis _ state of the art

Fibrosis represents a major global disease burden, yet a potent antifibrotic compound is still not in sight. Part of the explanation for this situation is the difficulties that both academic laboratories and research and development departments in the pharmaceutical industry have been facing in re-enacting the fibrotic process in vitro for screening procedures prior to animal testing. Effective in vitro characterization of antifibrotic compounds has been hampered by cell culture settings that are lacking crucial cofactors or are not holistic representations of the biosynthetic and depositional pathway leading to the formation of an insoluble pericellular collagen matrix. In order to appreciate the task which in vitro screening of antifibrotics is up against, we will first review the fibrotic process by categorizing it into events that are upstream of collagen biosynthesis and the actual biosynthetic and depositional cascade of collagen I. We point out oversights such as the omission of vitamin C, a vital cofactor for the production of stable procollagen molecules, as well as the little known in vitro tardy procollagen processing by collagen C-proteinase/BMP-1, another reason for minimal collagen deposition in cell culture. We review current methods of cell culture and collagen quantitation vis-à-vis the high content options and requirements for normalization against cell number for meaningful data retrieval. Only when collagen has formed a fibrillar matrix that becomes cross-linked, invested with ligands, and can be remodelled and resorbed, the complete picture of fibrogenesis can be reflected in vitro. We show here how this can be achieved. A well thought-out in vitro fibrogenesis system represents the missing link between brute force chemical library screens and rational animal experimentation, thus providing both cost-effectiveness and streamlined procedures towards the development of better antifibrotic drugs

The mismeasure of ape social cognition

In his classic analysis, The Mismeasure of Man, Gould (1981) demolished the idea that intelligence was an inherent, genetic trait of different human groups by emphasizing, among other things, (a) its sensitivity to environmental input, (b) the incommensurate pre-test preparation of different human groups, and (c) the inadequacy of the testing contexts, in many cases. According to Gould, the root cause of these oversights was confirmation bias by psychometricians, an unwarranted commitment to the idea that intelligence was a fixed, immutable quality of people. By virtue of a similar, systemic interpretive bias, in the last two decades, numerous contemporary researchers in comparative psychology have claimed human superiority over apes in social intelligence, based on two-group comparisons between postindustrial, Western Europeans and captive apes, where the apes have been isolated from European styles of social interaction, and tested with radically different procedures. Moreover, direct comparisons of humans with apes suffer from pervasive lapses in argumentation: Research designs in wide contemporary use are inherently mute about the underlying psychological causes of overt behavior. Here we analyze these problems and offer a more fruitful approach to the comparative study of social intelligence, which focuses on specific individual learning histories in specific ecological circumstances

The cognitive implications of intentional communication: a multifaceted mirror

There is a central concern in contemporary cognitive science with the validity of the use of epistemic and intentional terms to interpret the communication patterns of non-human animals. Here I argue (a) that the human developmental transition to intentional communication is a well-described phenomenon, from an empirical standpoint; (b) that the behavioural patterns that characterise intentional communication in our own species are also well-described in the communication of our nearest living relatives, the great apes; (c) that the presence of the behavioural markers for intentional communication in non-human primates does not unambiguously implicate any particular one of a large number of often mutually contradictory hypothetical psychological process models; and (d) that intentional communication by young humans is also consistent with hypothetical process models that are, themselves, mutually contradictory. Intentional communication is a class of behaviour that is open to public, objective measurement. In contrast, the hypothetical cognitive processes supporting intentional communication in both human and non-human animals are not specified by the fact that intentional communication has occurred—they could not be, except when there is an unambiguous behavioural index of invisible psychological processes, which is a contradiction in terms. In this chapter, I will examine a number of contemporary scientific practices that purportedly reveal aspects of psychological processes underlying intentional communication and demonstrate the deficiencies of these protocols. In general, these methodological infelicities support a systematic, discipline-wide double standard of interpretation of the communication of animals and humans. I will conclude that there is no convincing evidence extant of different psychological processes in the intentional communication of apes and preverbal humans