Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations

Mfn2, an oligomeric mitochondrial protein important for mitochondrial fusion, is mutated in Charcot-Marie-Tooth disease (CMT) type 2A, a peripheral neuropathy characterized by axonal degeneration. In addition to homooligomeric complexes, Mfn2 also associates with Mfn1, but the functional significance of such heterooligomeric complexes is unknown. Also unknown is why Mfn2 mutations in CMT2A lead to cell type–specific defects given the widespread expression of Mfn2. In this study, we show that homooligomeric complexes formed by many Mfn2 disease mutants are nonfunctional for mitochondrial fusion. However, wild-type Mfn1 complements mutant Mfn2 through the formation of heterooligomeric complexes, including complexes that form in trans between mitochondria. Wild-type Mfn2 cannot complement the disease alleles. Our results highlight the functional importance of Mfn1–Mfn2 heterooligomeric complexes and the close interplay between the two mitofusins in the control of mitochondrial fusion. Furthermore, they suggest that tissues with low Mfn1 expression are vulnerable in CMT2A and that methods to increase Mfn1 expression in the peripheral nervous system would benefit CMT2A patients

Virtual HR Departments: Getting Out of the Middle

In this chapter, we explore the notion of virtual HR departments: a network-based organization built on partnerships and mediated by information technologies in order to be simultaneously strategic, flexible, cost-efficient, and service-oriented. We draw on experiences and initiatives at Merck Pharmaceuticals in order to show how information technology in establishing an infrastructure for virtual HR. Then, we present a model for mapping the architecture of HR activities that includes both internal and external sourcing options. We conclude by offering some recommendations for management practice as well as future research

Fluctuation Induced Instabilities in Front Propagation up a Co-Moving Reaction Gradient in Two Dimensions

We study 2D fronts propagating up a co-moving reaction rate gradient in finite number reaction-diffusion systems. We show that in a 2D rectangular channel, planar solutions to the deterministic mean-field equation are stable with respect to deviations from planarity. We argue that planar fronts in the corresponding stochastic system, on the other hand, are unstable if the channel width exceeds a critical value. Furthermore, the velocity of the stochastic fronts is shown to depend on the channel width in a simple and interesting way, in contrast to fronts in the deterministic MFE. Thus, fluctuations alter the behavior of these fronts in an essential way. These affects are shown to be partially captured by introducing a density cutoff in the reaction rate. Some of the predictions of the cutoff mean-field approach are shown to be in quantitative accord with the stochastic results