Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance.

Calpain 3 is a member of the calpain family of calcium-dependent intracellular proteases. Thirteen years ago it was discovered that mutations in calpain 3 (CAPN3) result in an autosomal recessive and progressive form of limb girdle muscular dystrophy called limb girdle muscular dystrophy type 2A. While calpain 3 mRNA is expressed at high levels in muscle and appears to have some role in developmental processes, muscles of patients and mice lacking calpain 3 still form apparently normal muscle during prenatal development; thus, a functional calpain 3 protease is not mandatory for muscle to form in vivo but it is a pre-requisite for muscle to remain healthy. Despite intensive research in this field, the physiological substrates of the calpain 3 protein (hereafter referred to as CAPN3) and its alternatively spliced isoforms remain elusive. The existence of these multiple isoforms complicates the search for the physiological functions of CAPN3 and its pathophysiological role. In this review, we summarize the genetic and biochemical evidence that point to loss of function of the full-length isoform of CAPN3, also known as p94, as the pathogenic isoform. We also argue that its natural substrates must reside in its proximity within the sarcomere where it is stored in an inactive state anchored to titin. We further propose that CAPN3 has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance. Loss of these CAPN3-mediated activities can explain the "progressive" development of muscular dystrophy.

Climate Change, Neutrality and the Harm Principle

This paper aims at evaluating the compatibility of coercive climate policies with liberal neutrality. More precisely, it focuses on the doctrine of state neutrality as associated with the "harm principle". It argues that given the difficulty of attributing causal responsibilities for climate harms to individuals, the harm principle doesn't work in this case, at least if one endorses a liberal atomistic ontology. Furthermore, the definition of what constitutes climate harms implies making moral assumptions, which makes it impossible to justify climate policies in a neutral way. Finally, the paper shows another consequence of applying neutrality to the case of climate change, that is the risk of a shift from political forms of decision-making to technocracy. Focusing too much on liberty of choice may (paradoxically) be to the detriment of political freedom. The paper concludes that climate change is an intrinsically moral issue and that it should be the occasion of a political debate about our current values and lifestyles. It should not be reduced to a mere question of carbon metric.

Effects of selection and drift on G matrix evolution in a heterogeneous environment: a multivariate Qst-Fst Test with the freshwater snail Galba truncatula.

Unraveling the effect of selection vs. drift on the evolution of quantitative traits is commonly achieved by one of two methods. Either one contrasts population differentiation estimates for genetic markers and quantitative traits (the Q(st)-F(st) contrast) or multivariate methods are used to study the covariance between sets of traits. In particular, many studies have focused on the genetic variance-covariance matrix (the G matrix). However, both drift and selection can cause changes in G. To understand their joint effects, we recently combined the two methods into a single test (accompanying article by Martin et al.), which we apply here to a network of 16 natural populations of the freshwater snail Galba truncatula. Using this new neutrality test, extended to hierarchical population structures, we studied the multivariate equivalent of the Q(st)-F(st) contrast for several life-history traits of G. truncatula. We found strong evidence of selection acting on multivariate phenotypes. Selection was homogeneous among populations within each habitat and heterogeneous between habitats. We found that the G matrices were relatively stable within each habitat, with proportionality between the among-populations (D) and the within-populations (G) covariance matrices. The effect of habitat heterogeneity is to break this proportionality because of selection for habitat-dependent optima. Individual-based simulations mimicking our empirical system confirmed that these patterns are expected under the selective regime inferred. We show that homogenizing selection can mimic some effect of drift on the G matrix (G and D almost proportional), but that incorporating information from molecular markers (multivariate Q(st)-F(st)) allows disentangling the two effects.

Sympatric speciation in palms on an oceanic island.

The origin of species diversity has challenged biologists for over two centuries. Allopatric speciation, the divergence of species resulting from geographical isolation, is well documented. However, sympatric speciation, divergence without geographical isolation, is highly controversial. Claims of sympatric speciation must demonstrate species sympatry, sister relationships, reproductive isolation, and that an earlier allopatric phase is highly unlikely. Here we provide clear support for sympatric speciation in a case study of two species of palm (Arecaceae) on an oceanic island. A large dated phylogenetic tree shows that the two species of Howea, endemic to the remote Lord Howe Island, are sister taxa and diverged from each other well after the island was formed 6.9 million years ago. During fieldwork, we found a substantial disjunction in flowering time that is correlated with soil preference. In addition, a genome scan indicates that few genetic loci are more divergent between the two species than expected under neutrality, a finding consistent with models of sympatric speciation involving disruptive/divergent selection. This case study of sympatric speciation in plants provides an opportunity for refining theoretical models on the origin of species, and new impetus for exploring putative plant and animal examples on oceanic islands.

Business research, self-fulfilling prophecy, and the inherent responsibility of scholars.

Business research and teaching institutions play an important role in shaping the way businesses perceive their relations to the broader society and its moral expectations. Hence, as ethical scandals recently arose in the business world, questions related to the civic responsibilities of business scholars and to the role business schools play in society have gained wider interest. In this article, I argue that these ethical shortcomings are at least partly resulting from the mainstream business model with its taken-for granted basic assumptions such as specialization or the value-neutrality of business research. Redefining the roles and civic responsibilities of business scholars for business practice implies therefore a thorough analysis of these assumptions if not their redefinition. The takenforgrantedness of the mainstream business model is questioned by the transformation of the societal context in which business activities are embedded. Its value-neutrality in turn is challenged by self-fulfilling prophecy effects, which highlight the normative influence of business schools. In order to critically discuss some basic assumptions of mainstream business theory, I propose to draw parallels with the corporate citizenship concept and the stakeholder theory. Their integrated approach of the relation between business practice and the broader society provides interesting insights for the social reembedding of business research and teaching.