Foveal input is not required for perception of crowd facial expression.

The visual system extracts average features from groups of objects (Ariely, 2001; Dakin & Watt, 1997; Watamaniuk & Sekuler, 1992), including high-level stimuli such as faces (Haberman & Whitney, 2007, 2009). This phenomenon, known as ensemble perception, implies a covert process, which would not require fixation of individual stimulus elements. However, some evidence suggests that ensemble perception may instead be a process of averaging foveal input across sequential fixations (Ji, Chen, & Fu, 2013; Jung, Bulthoff, Thornton, Lee, & Armann, 2013). To test directly whether foveating objects is necessary, we measured observers' sensitivity to average facial emotion in the absence of foveal input. Subjects viewed arrays of 24 faces, either in the presence or absence of a gaze-contingent foveal occluder, and adjusted a test face to match the average expression of the array. We found no difference in accuracy between the occluded and non-occluded conditions, demonstrating that foveal input is not required for ensemble perception. Unsurprisingly, without foveal input, subjects spent significantly less time directly fixating faces, but this did not translate into any difference in sensitivity to ensemble expression. Next, we varied the number of faces visible from the set to test whether subjects average multiple faces from the crowd. In both conditions, subjects' performance improved as more faces were presented, indicating that subjects integrated information from multiple faces in the display regardless of whether they had access to foveal information. Our results demonstrate that ensemble perception can be a covert process, not requiring access to direct foveal information.

Saccadic remapping of object-selective information.

Saccadic remapping, a presaccadic increase in neural activity when a saccade is about to bring an object into a neuron's receptive field, may be crucial for our perception of a stable world. Studies of perception and saccadic remapping, like ours, focus on the presaccadic acquisition of information from the saccade target, with no direct reference to underlying physiology. While information is known to be acquired prior to a saccade, it is unclear whether object-selective or feature-specific information is remapped. To test this, we performed a series of psychophysical experiments in which we presented a peripheral, nonfoveated face as a presaccadic target. The target face disappeared at saccade onset. After making a saccade to the location of the peripheral target face (which was no longer visible), subjects misperceived the expression of a subsequent, foveally presented neutral face as being repelled away from the peripheral presaccadic face target. This effect was similar to a sequential shape contrast or negative aftereffect but required a saccade, because covert attention was not sufficient to generate the illusion. Additional experiments further revealed that inverting the faces disrupted the illusion, suggesting that presaccadic remapping is object-selective and not based on low-level features. Our results demonstrate that saccadic remapping can be an object-selective process, spatially tuned to the target of the saccade and distinct from covert attention in the absence of a saccade.

Visual motion shifts saccade targets.

Saccades are made thousands of times a day and are the principal means of localizing objects in our environment. However, the saccade system faces the challenge of accurately localizing objects as they are constantly moving relative to the eye and head. Any delays in processing could cause errors in saccadic localization. To compensate for these delays, the saccade system might use one or more sources of information to predict future target locations, including changes in position of the object over time, or its motion. Another possibility is that motion influences the represented position of the object for saccadic targeting, without requiring an actual change in target position. We tested whether the saccade system can use motion-induced position shifts to update the represented spatial location of a saccade target, by using static drifting Gabor patches with either a soft or a hard aperture as saccade targets. In both conditions, the aperture always remained at a fixed retinal location. The soft aperture Gabor patch resulted in an illusory position shift, whereas the hard aperture stimulus maintained the motion signals but resulted in a smaller illusory position shift. Thus, motion energy and target location were equated, but a position shift was generated in only one condition. We measured saccadic localization of these targets and found that saccades were indeed shifted, but only with a soft-aperture Gabor patch. Our results suggest that motion shifts the programmed locations of saccade targets, and this remapped location guides saccadic localization.

Facilitating recognition of crowded faces with presaccadic attention.

In daily life, we make several saccades per second to objects we cannot normally recognize in the periphery due to visual crowding. While we are aware of the presence of these objects, we cannot identify them and may, at best, only know that an object is present at a particular location. The process of planning a saccade involves a presaccadic attentional component known to be critical for saccadic accuracy, but whether this or other presaccadic processes facilitate object identification as opposed to object detection-especially with high level natural objects like faces-is less clear. In the following experiments, we show that presaccadic information about a crowded face reduces the deleterious effect of crowding, facilitating discrimination of two emotional faces, even when the target face is never foveated. While accurate identification of crowded objects is possible in the absence of a saccade, accurate identification of a crowded object is considerably facilitated by presaccadic attention. Our results provide converging evidence for a selective increase in available information about high level objects, such as faces, at a presaccadic stage.

Multiscale pattern analysis of orientation-selective activity in the primary visual cortex.

Although orientation columns are less than a millimeter in width, recent neuroimaging studies indicate that viewed orientations can be decoded from cortical activity patterns sampled at relatively coarse resolutions of several millimeters. One proposal is that these differential signals arise from random spatial irregularities in the columnar map. However, direct support for this hypothesis has yet to be obtained. Here, we used high-field, high-resolution functional magnetic resonance imaging (fMRI) and multivariate pattern analysis to determine the spatial scales at which orientation-selective information can be found in the primary visual cortex (V1) of cats and humans. We applied a multiscale pattern analysis approach in which fine- and coarse-scale signals were first removed by ideal spatial lowpass and highpass filters, and the residual activity patterns then analyzed by linear classifiers. Cat visual cortex, imaged at 0.3125 mm resolution, showed a strong orientation signal at the scale of individual columns. Nonetheless, reliable orientation bias could still be found at spatial scales of several millimeters. In the human visual cortex, imaged at 1 mm resolution, a majority of orientation information was found on scales of millimeters, with small contributions from global spatial biases exceeding approximately 1 cm. Our high-resolution imaging results demonstrate a reliable millimeters-scale orientation signal, likely emerging from irregular spatial arrangements of orientation columns and their supporting vasculature. fMRI pattern analysis methods are thus likely to be sensitive to signals originating from other irregular columnar structures elsewhere in the brain.

Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF complex to initiate cleavage furrow formation.

To complete cell division with high fidelity, cytokinesis must be coordinated with chromosome segregation. Mammalian Polo-like kinase 1, Plk1, may function as a critical link because it is required for chromosome segregation and establishment of the cleavage plane following anaphase onset. A central spindle-localized pool of the RhoGEF Ect2 promotes activation of the small GTPase RhoA, which drives contractile ring assembly at the equatorial cortex. Here, we have investigated how Plk1 promotes the central spindle recruitment of Ect2. Plk1 phosphorylates the noncatalytic N terminus of the RhoGAP HsCyk-4 at the central spindle, creating a phospho-epitope recognized by the BRCA1 C-terminal (BRCT) repeats of Ect2. Failure to phosphorylate HsCyk-4 blocks Ect2 recruitment to the central spindle and the subsequent induction of furrowing. Microtubules, as well as the microtubule-associated protein (MAP) Prc1, facilitate Plk1 phosphorylation of HsCyk-4. Characterization of a phosphomimetic version of HsCyk-4 indicates that Plk1 promotes Ect2 recruitment through multiple targets. Collectively, our data reveal that formation of the HsCyk-4-Ect2 complex is subject to multiple layers of regulation to ensure that RhoA activation occurs between the segregated sister chromatids during anaphase.

Single cells (put a ring on it).

Proper spatial and temporal regulation of the small GTPase RhoA at the equatorial cortex represents a critical step in the specification of the division plane in eukaryotes. Despite increased understanding of the mechanisms whereby RhoA becomes active following chromosome segregation, far less is known about how RhoA is spatially regulated so that it concentrates precisely at the division site. In the April 1, 2009, issue of Genes & Development, Yoshida and colleagues (pp. 810-823) uncovered two genetically separable mechanisms whereby Rho1 is recruited to the bud neck in the budding yeast Saccharomyces cerevisiae to facilitate cytokinesis.

The OpenMRS Implementers Network.

OBJECTIVE: OpenMRS (www.openmrs.org) is a configurable open source electronic medical record application developed and maintained by a large network of open source developers coordinated by the Regenstrief Institute and Partners in Health and mainly used for HIV patient and treatment information management in Africa. Our objective is to develop an open Implementers Network for OpenMRS to provide regional support for the growing number of OpenMRS implementations in Africa and to include African developers and implementers in the future growth of OpenMRS. METHODS: We have developed the OpenMRS Implementers Network using a dedicated Wiki site and e-mail server. We have also organized annual meetings in South Africa and regional training courses at African locations where OpenMRS is being implemented. An OpenMRS Internship program has been initiated and we have started collaborating with similar networks and projects working in Africa. To evaluate its potential, OpenMRS was implemented initially at one site in South Africa by a single implementer using a downloadable OpenMRS application and only the OpenMRS Implementers Network for support. RESULTS: The OpenMRS Implementers Network Wiki and list server have grown into effective means of providing implementation support and forums for exchange of implementation experiences. The annual OpenMRS Implementers meeting has been held in South Africa for the past three years and is attracting successively larger numbers of participants with almost 200 implementers and developers attending the 2008 meeting in Durban, South Africa. Six African developers are presently registered on the first intake of the OpenMRS Internship program. Successful collaborations have been started with several African developer groups and projects initiated to develop interoperability between OpenMRS and various applications. The South African OpenMRS Implementer group successfully configured, installed and maintained an integrated HIV/TB OpenMRS application without significant programming support. Since then, this model has been replicated in several other African sites. The OpenMRS Implementers Network has contributed substantially to the growth and sustainability of OpenMRS in Africa and has become a useful way of including Africans in the development and implementation of OpenMRS in developing countries. The Network provides valuable support and enables a basic OpenMRS application to be implemented in the absence of onsite programmers.

The role of Cdc14 phosphatases in the control of cell division.

The periodicity of CDKs (cyclin-dependent kinases) regulates most cell cycle transitions including cytokinesis. High Cdk1 activity promotes cytoskeletal rearrangements necessary for cell division while at the same time ensuring that cytokinesis does not begin before the separation of sister chromatids during anaphase. The conserved Cdc14 (cell division cycle 14)-family of phosphatases reverses Cdk phosphorylation events and therefore Cdc14 phosphatases promote the process of cytokinesis. Here, we review the elucidated roles of Cdc14 phosphatases in cytokinesis and the current outstanding questions regarding their function in this process.

The Clp1/Cdc14 phosphatase contributes to the robustness of cytokinesis by association with anillin-related Mid1.

Cdc14 phosphatases antagonize cyclin-dependent kinase-directed phosphorylation events and are involved in several facets of cell cycle control. We investigate the role of the fission yeast Cdc14 homologue Clp1/Flp1 in cytokinesis. We find that Clp1/Flp1 is tethered at the contractile ring (CR) through its association with anillin-related Mid1. Fluorescent recovery after photobleaching analyses indicate that Mid1, unlike other tested CR components, is anchored at the cell midzone, and this physical property is likely to account for its scaffolding role. By generating a mutation in mid1 that selectively disrupts Clp1/Flp1 tethering, we reveal the specific functional consequences of Clp1/Flp1 activity at the CR, including dephosphorylation of the essential CR component Cdc15, reductions in CR protein mobility, and CR resistance to mild perturbation. Our evidence indicates that Clp1/Flp1 must interact with the Mid1 scaffold to ensure the fidelity of Schizosaccharomyces pombe cytokinesis.

Phospho-regulation of the Cdc14/Clp1 phosphatase delays late mitotic events in S. pombe.

In eukaryotes, exit from mitosis occurs through the inactivation of the Cdk1-cyclin B kinase complex and the reversal of its phosphorylation events. These late mitotic events are tightly regulated to occur only after the onset of anaphase and prior to cytokinesis. Central to this regulation is the conserved Cdc14 family of protein phosphatases, whose activity reverses Cdk-dependent phosphorylation events. S. cerevisiae Cdc14 activity is restrained from dephosphorylating Cdk substrates and inactivating Cdk1 through its nucleolar sequestration prior to anaphase. Here, we describe a unique mode of Cdc14 regulation that operates prior to anaphase in fission yeast. Cdk1 phosphorylates and inhibits the catalytic activity of the Cdc14 family member, Clp1/Flp1. As Cdk1 activity declines during anaphase progression, Clp1/Flp1 autocatalytically reverses these phosphorylation events to stimulate its own activity. These findings point to a simple regulatory circuit that couples Cdk1 activation with its inactivation mediated through phosphorylation-dependent regulation of Clp1/Flp1 phosphatase activity.

The OpenMRS system: collaborating toward an open source EMR for developing countries.

OpenMRS is an open source infrastructure for the creation of medical record systems in developing countries. Produced and maintained collaboratively across multiple institutions, this framework consists of an open source data model, a set of core application functions, and a default implementation. The goal of this implementation is to provide the beginnings of an EMR that is suitable for all groups involved with healthcare in developing countries.

Split decisions: coordinating cytokinesis in yeast.

Cytokinesis in eukaryotes involves the regulated assembly and contraction of a ring comprising filamentous (F)-actin and myosin II. Assembly of the contractile ring occurs through the accumulation of cortical cues at the specified division plane, followed by recruitment of F-actin, myosin II and accessory proteins involved in generating the mature ring. Ring contraction is temporally regulated to occur only after chromosome segregation and, in yeast, it is controlled by a conserved signaling cascade that becomes active only after Cdk1-Cyclin-B inactivation. In this article (which is part of the Cytokinesis series), we discuss recent studies that have begun to clarify both the spatial and the temporal order of ring assembly and that have illuminated the signals that trigger ring contraction in yeast. These studies add to the growing knowledge of the processes that control eukaryotic cell division.

Inactivating Cdc25, mitotic style.

Mitotic entry and exit require activation and inactivation of the Cdk1-cyclin B kinase complex, respectively. The Cdc25 protein phosphatase family activates Cdk1-cyclin B at the G2/M transition by removing inhibitory phosphate groups. Cdc25 family members, held inactive during interphase, are activated during mitotic progression in an amplification loop involving Cdk1-cyclin B. While Cdc25 activation at the G2/M transition is required for the timely initiation of mitosis, recent evidence suggests that the inactivation of Cdc25 in late mitosis may play a role in supporting Cdk1-cyclin B inactivation. Here, we discuss the mechanisms of Cdc25 regulation and how they pertain to both mitotic entry and exit.

Fission yeast Clp1p phosphatase affects G2/M transition and mitotic exit through Cdc25p inactivation.

The Cdc14 family of phosphatases specifically reverses proline-directed phosphorylation events. In Saccharomyces cerevisiae, Cdc14p promotes Cdk1p inactivation at mitotic exit by reversing Cdk1p-dependent phosphorylations. Cdk1p is a proline-directed kinase whose activity is required in all eukaryotes for the transit into mitosis. At mitotic commitment, Cdk1p participates in its own regulation by activating the mitotic inducing phosphatase, Cdc25p, and inhibiting the opposing kinase, Wee1p. We have investigated the ability of Schizosaccharomyces pombe Clp1p, a Cdc14p homolog, to disrupt this auto-amplification loop. We show here that Clp1p is required to dephosphorylate, destabilize, and inactivate Cdc25p at the end of mitosis. Clp1p promotes recognition of Cdc25p by the anaphase-promoting complex/cyclosome, an E3 ubiquitin ligase. Failure to inactivate and destabilize Cdc25p in late mitosis delays progression through anaphase, interferes with septation initiation network signaling, and additionally advances the commitment to mitotic entry in the next cycle. This may be a widely conserved mechanism whereby Cdc14 proteins contribute to Cdk1p inactivation.

Proteomics analysis identifies new components of the fission and budding yeast anaphase-promoting complexes.

The anaphase-promoting complex (APC) is a conserved multisubunit ubiquitin ligase required for the degradation of key cell cycle regulators. Components of the APC have been identified through genetic screens in both Schizosaccharomyces pombe and Saccharomyces cerevisiae as well as through biochemical purification coupled with mass spectrometric protein identification. With these approaches, 11 subunits of the core S. cerevisiae APC have been identified. Here, we have applied a tandem affinity purification approach coupled with direct analysis of the purified complexes by mass spectrometry (DALPC) to reveal additional subunits of both the S. pombe and S. cerevisiae APCs. Our data increase the total number of identified APC subunits to 13 in both yeasts and indicate that previous approaches were biased against the identification of small subunits. These results underscore the power of direct analysis of protein complexes by mass spectrometry and set the foundation for further functional and structural studies of the APC.