We have identified EMS-induced mutations in Drosophila Miro (dMiro), an atypical mitochondrial GTPase that is orthologous to human Miro (hMiro). Mutant dmiro animals exhibit defects in locomotion and die prematurely. Mitochondria in dmiro mutant muscles and neurons are abnormally distributed. Instead of being transported into axons and dendrites, mitochondria accumulate in parallel rows in neuronal somata. Mutant neuromuscular junctions (NMJs) lack presynaptic mitochondria, but neurotransmitter release and acute Ca2+ buffering is only impaired during prolonged stimulation. Neuronal, but not muscular, expression of dMiro in dmiro mutants restored viability, transport of mitochondria to NMJs, the structure of synaptic boutons, the organization of presynaptic microtubules, and the size of postsynaptic muscles. In addition, gain of dMiro function causes an abnormal accumulation of mitochondria in distal synaptic boutons of NMJs. Together, our findings suggest that dMiro is required for controlling anterograde transport of mitochondria and their proper distribution within nerve terminals.

In this paper, I begin by defending permissivism: the claim that, sometimes, there is more than one way to rationally respond to a given body of evidence. Then I argue that, if we accept permissivism, certain worries that arise as a result of learning that our beliefs were caused by the communities we grew up in, the schools we went to, or other irrelevant influences dissipate. The basic strategy is as follows: First, I try to pinpoint what makes irrelevant influences worrying and I come up with two candidate principles. I then argue that one principle should be rejected because it is inconsistent with permissivism. The principle we should accept implies that it is sometimes rational to maintain our beliefs, even upon learning that they were caused by irrelevant influences.

The aim of this paper is to apply the accuracy based approach to epistemology to the case of higher order evidence: evidence that bears on the rationality of one's beliefs. I proceed in two stages. First, I show that the accuracy based framework that is standardly used to motivate rational requirements supports steadfastness—a position according to which higher order evidence should have no impact on one's doxastic attitudes towards first order propositions. The argument for this will require a generalization of an important result by Greaves and Wallace for the claim that conditionalization maximizes expected accuracy. The generalization I provide will, among other things, allow us to apply the result to cases of self‐locating evidence. In the second stage, I develop an alternative framework. Very roughly, what distinguishes the traditional approach from the alternative one is that, on the traditional picture, we're interested in evaluating the expected accuracy of conforming to an update procedure. On the alternative picture that I develop, instead of considering how good an update procedure is as a plan to conform to, we consider how good it is as a plan to make. I show how, given the use of strictly proper scoring rules, the alternative picture vindicates calibrationism: a view according to which higher order evidence should have a significant impact on our beliefs. I conclude with some thoughts about why higher order evidence poses a serious challenge for standard ways of thinking about rationality.

No abstract