PrPs: Proteins with a purpose: Lessons from the zebrafish

The best-known attribute of the prion protein (PrP) is its tendency to misfold into a rogue isoform. Much less understood is how this misfolded isoform causes deadly brain illnesses. Neurodegeneration in prion disease is often seen as a consequence of abnormal PrP function yet, amazingly little is known about the normal, physiological role of PrP. In particular, the absence of obvious phenotypes in PrP knockout mice has prevented scientists from answering this important question. Using knockdown approaches, we previously produced clear PrP loss-of-function phenotypes in zebrafish embryos. Analysis of these phenotypes revealed that PrP can modulate E-cadherin-based cell-cell adhesion, thereby controlling essential morphogenetic cell movements in the early gastrula. Our data also showed that PrP itself can elicit homophilic cell-cell adhesion and trigger intracellular signaling via Src-related kinases. Importantly, these molecular functions of PrP are conserved from fish to mammals. Here we discuss the use of the zebrafish in prion biology and how it may advance our understanding of the roles of PrP in health and disease.Key words: PrP, zebrafish, development, cell adhesion, signaling     

Function without purpose

Philosophers of evolutionary biology favor the so-called etiological concept of function according to which the function of a trait is its evolutionary purpose, defined as the effect for which that trait was favored by natural selection. We term this the selected effect (SE) analysis of function. An alternative account of function was introduced by Robert Cummins in a non-evolutionary and non-purposive context. Cummins's account has received attention but little support from philosophers of biology. This paper will show that a similar non-purposive concept of function, which we term causal role (CR) function, is crucial to certain research programs in evolutionary biology, and that philosophical criticisms of Cummins's concept are ineffective in this scientific context. Specifically, we demonstrate that CR functions are a vital and ineliminable part of research in comparative and functional anatomy, and that biological categories used by anatomists are not defined by the application of SE functional analysis. Causal role functions are non-historically defined, but may themselves be used in an historical analysis. Furthermore, we show that a philosophical insistence on the primary of SE functions places practicing biologists in an untenable position, as such functions can rarely be demonstrated (in contrast to CR functions). Biologists who study the form and function of organismal design recognize that it is virtually impossible to identify the past action of selection on any particular structure retrospectively, a requirement for recognizing SE functions.     

Larval source reduction with a purpose: Designing and evaluating a household- and school-based intervention in coastal Kenya

BackgroundSince Aedes aegypti mosquitoes preferentially breed in domestic containers, control efforts focus on larval source reduction. Our objectives were to design and test the effectiveness of a source reduction intervention to improve caregiver knowledge and behaviors in coastal Kenya.Methodology/Principal findingsWe conducted a cluster-randomized controlled trial with 261 households from 5 control villages and 259 households from 5 intervention villages. From each household, one child (10–16 years old) and his or her primary caregiver participated in the intervention. We assessed caregiver knowledge and behavior at baseline, as well as 3 and 12 months after the intervention. We assessed household entomological indices at baseline and 12 months after the intervention to avoid seasonal interference. We conducted qualitative interviews with 34 caregivers to understand barriers and facilitators to change. We counted and weighed containers collected by children and parents during a community container clean-up and recycling event. After 12 months, caregiver knowledge about and self-reported behavior related to at least one source reduction technique was more than 50 percentage points higher in the intervention compared to control arm (adjusted risk differences for knowledge: 0.69, 95% CI [0.56 to 0.82], and behavior: 0.58 [0.43 to 0.73]). Respondents stated that other family members’ actions were the primary barriers to proper container management. The number of containers at households did not differ significantly across arms even though children and parents collected 17,200 containers (1 ton of plastics) which were used to planted 4,000 native trees as part of the community event.Conclusions/SignificanceOur study demonstrates that source reduction interventions can be effective if designed with an understanding of the social and entomological context. Further, source reduction is not an individual issue, but rather a social/communal issue, requiring the participation of other household and community members to be sustained.     

Hegel's notion of natural purpose

This paper argues that the notion of natural purpose developed by Hegel can only be thoroughly grasped by considering its intimate connection with the idea of contradiction and, particularly, with what Hegel in his philosophy of nature called the 'activity of deficiency'. This expression is used by Hegel to denote the ontological situation of every living being, which is embodied most authentically in the concepts of need and drive. For Hegel, life itself is imbued with contradiction because it is inextricably bound up with what it lacks: its identity is at one with its negation. This paper defends the thesis that Hegel's philosophy-and not just his philosophy of nature-can be characterized as an 'ontology of life' (to use the same expression that Martin Heidegger applied to Aristotle's De Anima), or more precisely, as an ontology of living individuality.     

Always talking to some purpose

Distinguished molecular biologist, Sydney Brenner, has said he won't write an autobiography. Mark Ptashne reviews the next best thing.     

Model synthesis of nucleoside boranophosphoramidate with amino acid for prodrug purpose

A model synthesis of a nucleoside boranophosphoramidate prodrug with (L)-tryptophan methyl ester was accomplished in a one-pot reaction via an H-phosphonate approach. This new type of compound is expected to possess the potent antiviral and anticancer advantages conferred by boranophosphates and normal nucleoside amino acid phosphoramidate.