We demonstrate both experimentally and theoretically that a colloidal sphere trapped in a static optical tweezer does not come to equilibrium, but rather reaches a steady state in which its probability flux traces out a toroidal vortex. This non-equilibrium behavior can be ascribed to a subtle bias of thermal fluctuations by non-conservative optical forces. The circulating sphere therefore acts as a Brownian motor. We briefly discuss ramifications of this effect for studies in which optical tweezers have been treated as potential energy wells.Most discussions of the dynamics of optically trapped particles assume at least implicitly that the forces exerted by an optical tweezer [1] are path-independent and therefore conserve mechanical energy. Optical forces due to gradients in the intensity are manifestly conservative in this sense [2]. Radiation pressure, by contrast, is not [2,3]. The experimental studies described in this Letter demonstrate that the non-conservative component of the optical force has measurable consequences for the dynamics of optically trapped colloidal spheres. In particular, the probability density for a sphere trapped in a static optical tweezer exhibits steady-state toroidal currents, a phenomenon we call a fountain of probability. We use the Fokker-Planck formalism to explain how nonconservative forces bias random thermal fluctuations to induce circulating probability currents. Figure 1 schematically represents the deceptively simple system. A single colloidal sphere is drawn to the focus of a converging laser beam by forces arising from gradients in the beam's intensity [1,2]. These intensitygradient forces establish a three-dimensional potential energy well, V (r), determined by the local intensity, I(r). A particle trapped in this well also experiences radiation pressure that drives it downstream with a force proportional to I(r). In the absence of thermal fluctuations, a trapped particle would come to rest at a stable mechanical equilibrium downstream of the focus.Treating the displaced equilibrium point as the origin of an effective potential energy well is tempting but misleading. To appreciate the problem, consider a thermally driven trajectory such as the example shown schematically in Fig. 1. Were the system in thermodynamic equilibrium, forward and reverse trajectories around this loop would have equal probability. Because the light is more intense near the optical axis, however, radiation pressure biases the random walk in the forward direction. This departure from detailed balance should induce irreversible circulation in the particle's otherwise random fluctuations [4].We demonstrate this effect by observing the motions of colloidal silica spheres 2.2 µm in diameter (Bangs Lab-

Joubert syndrome (JBTS) is a recessive ciliopathy in which a subset of affected individuals also have the skeletal dysplasia Jeune asphyxiating thoracic dystrophy (JATD). Here, we have identified biallelic truncating CSPP1 (centrosome and spindle pole associated protein 1) mutations in 19 JBTS-affected individuals, four of whom also have features of JATD. CSPP1 mutations explain ∼5% of JBTS in our cohort, and despite truncating mutations in all affected individuals, the range of phenotypic severity is broad. Morpholino knockdown of cspp1 in zebrafish caused phenotypes reported in other zebrafish models of JBTS (curved body shape, pronephric cysts, and cerebellar abnormalities) and reduced ciliary localization of Arl13b, further supporting loss of CSPP1 function as a cause of JBTS. Fibroblasts from affected individuals with CSPP1 mutations showed reduced numbers of primary cilia and/or short primary cilia, as well as reduced axonemal localization of ciliary proteins ARL13B and adenylyl cyclase III. In summary, CSPP1 mutations are a major cause of the Joubert-Jeune phenotype in humans; however, the mechanism by which these mutations lead to both JBTS and JATD remains unknown.

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