A Retinotopic Basis for the Division of High-Level Scene Processing between Lateral and Ventral Human Occipitotemporal Cortex

In humans, there is a repeated category-selective organization across the lateral and ventral surfaces of the occipitotemporal cortex. This apparent redundancy is often explained as a feedforward hierarchy, with processing within lateral areas preceding the processing within ventral areas. Here, we tested the alternative hypothesis that this structure better reflects distinct high-level representations of the upper (ventral surface) and lower (lateral surface) contralateral quadrants of the visual field, consistent with anatomical projections from early visual areas to these surfaces in monkey. Using complex natural scenes, we provide converging evidence from three independent functional imaging and behavioral studies. First, population receptive field mapping revealed strong biases for the contralateral upper and lower quadrant within the ventral and lateral scene-selective regions, respectively. Second, these same biases were observed in the position information available both in the magnitude and multivoxel response across these areas. Third, behavioral judgments of a scene property strongly represented within the ventral scene-selective area (open/closed), but not another equally salient property (manmade/natural), were more accurate in the upper than the lower field. Such differential representation of visual space poses a substantial challenge to the idea of a strictly hierarchical organization between lateral and ventral scene-selective regions. Moreover, such retinotopic biases seem to extend beyond these regions throughout both surfaces. Thus, the large-scale organization of high-level extrastriate cortex likely reflects the need for both specialized representations of particular categories and constraints from the structure of early vision. SIGNIFICANCE STATEMENT One of the most striking findings in fMRI has been the presence of matched category-selective regions on the lateral and ventral surfaces of human occipitotemporal cortex. Here, we focus on scene-selective regions and provide converging evidence for a retinotopic explanation of this organization. Specifically, we demonstrate that scene-selective regions exhibit strong biases for different portions of the visual field, with the lateral region representing the contralateral lower visual field and the ventral region the contralateral upper visual field. These biases are consistent with the retinotopy found in the early visual areas that lie directly antecedent to category-selective areas on both surfaces. Furthermore, these biases extend beyond scene-selective cortex and provide a retinotopic basis for the large-scale organization of occipitotemporal cortex

Operational Performance of MOSFIRE with Its Cryogenic Configurable Slitmask Unit at the W. M. Keck Observatory

The Multi-Object Spectrograph for Infrared Exploration (MOSFIRE) achieved first light on the W. M. Keck Observatory’s Keck I telescope on 4 April 2012 and quickly became the most popular Keck I instrument. One of the primary reasons for the instrument’s popularity is that it uses a configurable slitmask unit developed by the Centre Suisse d’Electronique et Microtechnique (CSEM SA) to isolate the light from up to 46 objects simultaneously. In collaboration with the instrument development team and CSEM engineers, the Keck observatory staff present how MOSFIRE is successfully used, and we identify what contributed to routine and trouble free nighttime operations

Innovations and advances in instrumentation at the W. M. Keck Observatory

Since the start of operations in 1993, the twin 10 meter W. M. Keck Observatory telescopes have continued to maximize their scientific impact and to produce transformative discoveries that keep the observing community on the frontiers of astronomical research. Upgraded capabilities and new instrumentation are provided though collaborative partnerships with Caltech and UC instrument development teams. The observatory adapts and responds to the observers’ evolving needs as defined in the observatory’s strategic plan, periodically refreshed in collaboration with the science community. This paper summarizes the performance of recently commissioned infrastructure projects, technology upgrades, and new additions to the suite of instrumentation at the observatory. We will also provide a status of projects currently in the design or development phase, and since we need to keep our eye on the future, we mention projects in exploratory phases that originate from our strategic plan. Recently commissioned projects include telescope control system upgrades, OSIRIS spectrometer and imager upgrades, and deployments of the Keck Cosmic Web Imager (KCWI), the Near-Infrared Echellette Spectrometer (NIRES), and the Keck I Deployable Tertiary Mirror (KIDM3). Under development are upgrades to the NIRSPEC instrument and adaptive optics (AO) system. Major instrumentation in design phases include the Keck Cosmic Reionization Mapper and the Keck Planet Finder. Future instrumentation studies and proposals underway include a Ground Layer Adaptive Optics system, NIRC2 upgrades, the energy sensitive instrument KRAKENS, an integral field spectrograph LIGER, and a laser tomography AO upgrade. Last, we briefly discuss recovering MOSFIRE and its return to science operations

Global investigation of protein–protein interactions in yeast Saccharomyces cerevisiae using re-occurring short polypeptide sequences

Protein–protein interaction (PPI) maps provide insight into cellular biology and have received considerable attention in the post-genomic era. While large-scale experimental approaches have generated large collections of experimentally determined PPIs, technical limitations preclude certain PPIs from detection. Recently, we demonstrated that yeast PPIs can be computationally predicted using re-occurring short polypeptide sequences between known interacting protein pairs. However, the computational requirements and low specificity made this method unsuitable for large-scale investigations. Here, we report an improved approach, which exhibits a specificity of ∼99.95% and executes 16 000 times faster. Importantly, we report the first all-to-all sequence-based computational screen of PPIs in yeast, Saccharomyces cerevisiae in which we identify 29 589 high confidence interactions of ∼2 × 107 possible pairs. Of these, 14 438 PPIs have not been previously reported and may represent novel interactions. In particular, these results reveal a richer set of membrane protein interactions, not readily amenable to experimental investigations. From the novel PPIs, a novel putative protein complex comprised largely of membrane proteins was revealed. In addition, two novel gene functions were predicted and experimentally confirmed to affect the efficiency of non-homologous end-joining, providing further support for the usefulness of the identified PPIs in biological investigations

Operational Performance of MOSFIRE with Its Cryogenic Configurable Slitmask Unit at the W. M. Keck Observatory

The Multi-Object Spectrograph for Infrared Exploration (MOSFIRE) achieved first light on the W. M. Keck Observatory’s Keck I telescope on 4 April 2012 and quickly became the most popular Keck I instrument. One of the primary reasons for the instrument’s popularity is that it uses a configurable slitmask unit developed by the Centre Suisse d’Electronique et Microtechnique (CSEM SA) to isolate the light from up to 46 objects simultaneously. In collaboration with the instrument development team and CSEM engineers, the Keck observatory staff present how MOSFIRE is successfully used, and we identify what contributed to routine and trouble free nighttime operations

Saccharomyces Genome Database: the genomics resource of budding yeast

The Saccharomyces Genome Database (SGD, http://www.yeastgenome.org) is the community resource for the budding yeast Saccharomyces cerevisiae. The SGD project provides the highest-quality manually curated information from peer-reviewed literature. The experimental results reported in the literature are extracted and integrated within a well-developed database. These data are combined with quality high-throughput results and provided through Locus Summary pages, a powerful query engine and rich genome browser. The acquisition, integration and retrieval of these data allow SGD to facilitate experimental design and analysis by providing an encyclopedia of the yeast genome, its chromosomal features, their functions and interactions. Public access to these data is provided to researchers and educators via web pages designed for optimal ease of use

Apoptosis Signal-Regulating Kinase 1 Mediates MPTP Toxicity and Regulates Glial Activation

Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase 3 family, is activated by oxidative stress. The death-signaling pathway mediated by ASK1 is inhibited by DJ-1, which is linked to recessively inherited Parkinson's disease (PD). Considering that DJ-1 deficiency exacerbates the toxicity of the mitochondrial complex I inhibitor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we sought to investigate the direct role and mechanism of ASK1 in MPTP-induced dopamine neuron toxicity. In the present study, we found that MPTP administration to wild-type mice activates ASK1 in the midbrain. In ASK1 null mice, MPTP-induced motor impairment was less profound, and striatal dopamine content and nigral dopamine neuron counts were relatively preserved compared to wild-type littermates. Further, microglia and astrocyte activation seen in wild-type mice challenged with MPTP was markedly attenuated in ASK1−/− mice. These data suggest that ASK1 is a key player in MPTP-induced glial activation linking oxidative stress with neuroinflammation, two well recognized pathogenetic factors in PD. These findings demonstrate that ASK1 is an important effector of MPTP-induced toxicity and suggest that inhibiting this kinase is a plausible therapeutic strategy for protecting dopamine neurons in PD

Collaborative care for depression and anxiety problems

This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2012, Issue 10. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.Common mental health problems, such as depression and anxiety, are estimated to affect up to 15% of the UK population at any one time, and health care systems worldwide need to implement interventions to reduce the impact and burden of these conditions. Collaborative care is a complex intervention based on chronic disease management models that may be effective in the management of these common mental health problems

Integrated genomic study of quadruple-WT GIST (KIT/PDGFRA/SDH/RAS pathway wild-type GIST)

BACKGROUND: About 10-15% of adult gastrointestinal stromal tumors (GIST) and the vast majority of pediatric GIST do not harbour KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutations (J Clin Oncol 22:3813-3825, 2004; Hematol Oncol Clin North Am 23:15-34, 2009). The molecular biology of these GIST, originally defined as KIT/PDGFRA wild-type (WT), is complex due to the existence of different subgroups with distinct molecular hallmarks, including defects in the succinate dehydrogenase (SDH) complex and mutations of neurofibromatosis type 1 (NF1), BRAF, or KRAS genes (RAS-pathway or RAS-P).In this extremely heterogeneous landscape, the clinical profile and molecular abnormalities of the small subgroup of WT GIST suitably referred to as quadruple wild-type GIST (quadrupleWT or KITWT/PDGFRAWT/SDHWT/RAS-PWT) remains undefined. The aim of this study is to investigate the genomic profile of KITWT/PDGFRAWT/SDHWT/RAS-PWT GIST, by using a massively parallel sequencing and microarray approach, and compare it with the genomic profile of other GIST subtypes. METHODS: We performed a whole genome analysis using a massively parallel sequencing approach on a total of 16 GIST cases (2 KITWT/PDGFRAWT/SDHWT and SDHBIHC+/SDHAIHC+, 2 KITWT/PDGFRAWT/SDHAmut and SDHBIHC-/SDHAIHC- and 12 cases of KITmut or PDGFRAmut GIST). To confirm and extend the results, whole-genome gene expression analysis by microarray was performed on 9 out 16 patients analyzed by RNAseq and an additional 20 GIST patients (1 KITWT/PDGFRAWTSDHAmut GIST and 19 KITmut or PDGFRAmut GIST). The most impressive data were validated by quantitave PCR and Western Blot analysis. RESULTS: We found that both cases of quadrupleWT GIST had a genomic profile profoundly different from both either KIT/PDGFRA mutated or SDHA-mutated GIST. In particular, the quadrupleWT GIST tumors are characterized by the overexpression of molecular markers (CALCRL and COL22A1) and of specific oncogenes including tyrosine and cyclin- dependent kinases (NTRK2 and CDK6) and one member of the ETS-transcription factor family (ERG). CONCLUSION: We report for the first time an integrated genomic picture of KITWT/PDGFRAWT/SDHWT/RAS-PWT GIST, using massively parallel sequencing and gene expression analyses, and found that quadrupleWT GIST have an expression signature that is distinct from SDH-mutant GIST as well as GIST harbouring mutations in KIT or PDGFRA. Our findings suggest that quadrupleWT GIST represent another unique group within the family of gastrointestintal stromal tumors

Gene Ontology annotations and resources.

The Gene Ontology (GO) Consortium (GOC, http://www.geneontology.org) is a community-based bioinformatics resource that classifies gene product function through the use of structured, controlled vocabularies. Over the past year, the GOC has implemented several processes to increase the quantity, quality and specificity of GO annotations. First, the number of manual, literature-based annotations has grown at an increasing rate. Second, as a result of a new 'phylogenetic annotation' process, manually reviewed, homology-based annotations are becoming available for a broad range of species. Third, the quality of GO annotations has been improved through a streamlined process for, and automated quality checks of, GO annotations deposited by different annotation groups. Fourth, the consistency and correctness of the ontology itself has increased by using automated reasoning tools. Finally, the GO has been expanded not only to cover new areas of biology through focused interaction with experts, but also to capture greater specificity in all areas of the ontology using tools for adding new combinatorial terms. The GOC works closely with other ontology developers to support integrated use of terminologies. The GOC supports its user community through the use of e-mail lists, social media and web-based resources