Determination of ubiquitin fitness landscapes under different chemical stresses in a classroom setting

Ubiquitin is essential for eukaryotic life and varies in only 3 amino acid positions between yeast and humans. However, recent deep sequencing studies indicate that ubiquitin is highly tolerant to single mutations. We hypothesized that this tolerance would be reduced by chemically induced physiologic perturbations. To test this hypothesis, a class of first year UCSF graduate students employed deep mutational scanning to determine the fitness landscape of all possible single residue mutations in the presence of five different small molecule perturbations. These perturbations uncover \u27shared sensitized positions\u27 localized to areas around the hydrophobic patch and the C-terminus. In addition, we identified perturbation specific effects such as a sensitization of His68 in HU and a tolerance to mutation at Lys63 in DTT. Our data show how chemical stresses can reduce buffering effects in the ubiquitin proteasome system. Finally, this study demonstrates the potential of lab-based interdisciplinary graduate curriculum

Assessing the speed and ease of extracting group and person information from faces

This research was supported by the Australian Research Council (FLFL110100199) and the Canadian Institute for Advanced Research (Social Interactions Identity and Well-Being Program).The human face is a key source of social information. In particular, it communicates a target's personal identity and some of their group memberships. Different models of social perception posit distinct stages at which this group-level and person-level information is extracted from the face, with divergent downstream consequences for cognition and behavior. This paper presents four experiments that explore the time-course of extracting group and person information from faces. In Experiments 1 and 2, we explore the effect of chunked versus unchunked processing on the speed of extracting group versus person information, as well as the impact of familiarity in Experiment 2. In Experiment 3, we examine the effect of the availability of a diagnostic cue on these same judgments. In Experiment 4, we explore the effect of both group-level and person-level prototypicality of face exemplars. Across all four experiments, we find no evidence for the perceptual primacy of either group or person information. Instead, we find that chunked processing, featural processing based on a single diagnostic cue, familiarity, and the prototypicality of face exemplars all result in a processing speed advantage for both group-level and person-level judgments equivalently. These results have important implications for influential models of impression formation and can inform, and be integrated with, an understanding of the process of social categorization more broadly.PostprintPeer reviewe

Sinistral shear during Middle Jurassic emplacement of the Matancilla Plutonic Complex in northern Chile (25.4\u3csup\u3e◦\u3c/sup\u3e S) as evidence of oblique plate convergence during the early Andean orogeny

Arc magmatism in a continental subduction zone facilitates rheological weakening of the rigid upper plate, and can accommodate the partitioned trench-parallel component of oblique subduction into an intra-arc shear zone. We document a shear zone at latitude 25.4◦ S near Taltal, Chile that was associated with intrusion of the Matancilla Plutonic Complex at ~169 Ma to evaluate intra-arc deformation and possible tectonic plate configurations during this time period. Polyphase folding of Paleozoic metasedimentary rocks is overprinted by mylonitic fabrics that are most extensive in a zone up to 1.4 km wide in the thermal aureole of the granodioritic Matancilla pluton, where contact metamorphic andalusite porphyroblasts are synkinematic with fabric development. Mylonite in metasedimentary rocks is overprinted by a ~130 Ma granodiorite (zircon U–Pb) and by ~133 Ma postkinematic monazite (U–Pb). Within the Jurassic Matancilla granodiorite, pervasive ductile shear occurs along the intrusive contact while centimeter-scale discrete high-strain zones throughout the pluton are associated with focused hydrothermal alteration and reaction weakening. Mylonitic foliation in the metasedimentary rocks and within the pluton strikes N- to NE and dips steeply, while stretching lineations are subhorizontal on average. Kinematic indicators record dominantly sinistral shear, though some dextral or symmetric indicators and S \u3e L fabrics suggest a component of coaxial strain and flattening. Sinistral strike-slip kinematics in the Matancilla shear zone may indicate that Middle Jurassic convergence had sinistral obliquity that was locally partitioned into the contemporaneous magmatic arc. Sinistral-oblique convergence would require the Phoenix- Farallon spreading center to be north of ~25◦ S in the Middle Jurassic, providing a constraint to plate reconstructions during the early Andean orogeny

Flow-topography interactions in the northern California Current System observed from geostationary satellite data

Data from Geostationary Operational Environmental Satellites are used to study the seasonal evolution of temperature fronts in the northern California Current System (CCS), focusing on the interactions with topographic features. Fronts first appear close to the coast in response to upwelling winds, moving offshore with the continuous input of energy to the system. Late in the upwelling season (after July), the upwelling front is persistently found over deeper waters south of Heceta Bank, Oregon, than north of it, suggesting that the equatorward jet separates from the shelf at Heceta Bank. Inshore of the upwelling front, weak gradients are found on the Bank. The interaction of the equatorward flow with Heceta Bank and Cape Blanco, Oregon, farther south, substantially increases the mesoscale activity and oceanic frontal habitat downstream to the south in the CCS, where fronts are persistently found greater than 100 km from the coast

Sea surface temperature fronts in the California Current System from geostationary satellite observations

Sea surface temperature (SST) fronts are determined for the 2001–2004 time period from Geostationary Operational Environmental Satellites (GOES) data in the California Current System (CCS). The probability of detecting a SST front at an individual pixel location in the CCS is presented as a bi-monthly climatology. Fronts clearly indicate the seasonal evolution of coastal upwelling, as well as meanders and filaments that are often linked with irregularities in coastline geometry. Winter is characterized by low frontal activity along the entire coast. Fronts first appear close to the coast during spring, particularly south of Cape Blanco, where upwelling favorable winds are already persistent. The area of high frontal activity continues to increase during summer, especially between Monterey Bay and Cape Blanco, extending more than 300 km from the coast. The region with high frontal activity widens at ~2.6 km day¯¹. Off northern Baja California, a band with persistent fronts is found close to the coast year-round, but there is no evidence of a seasonal widening of the area of higher activity. During fall, the weakening of upwelling favorable winds leads to a gradual decrease in frontal activity. An empirical orthogonal function (EOF) decomposition reveals the development of SST fronts associated with seasonal upwelling for locations north of Monterey Bay, with less summer intensification to the south. The first appearance of fronts close to the coast during spring and the occurrence of the fronts offshore later in the season are represented by additional statistically significant EOF modes.Copyrighted by American Geophysical Union

CandidaDB: a genome database for Candida albicans pathogenomics

CandidaDB is a database dedicated to the genome of the most prevalent systemic fungal pathogen of humans, Candida albicans. CandidaDB is based on an annotation of the Stanford Genome Technology Center C.albicans genome sequence data by the European Galar Fungail Consortium. CandidaDB Release 2.0 (June 2004) contains information pertaining to Assembly 19 of the genome of C.albicans strain SC5314. The current release contains 6244 annotated entries corresponding to 130 tRNA genes and 5917 protein-coding genes. For these, it provides tentative functional assignments along with numerous pre-run analyses that can assist the researcher in the evaluation of gene function for the purpose of specific or large-scale analysis. CandidaDB is based on GenoList, a generic relational data schema and a World Wide Web interface that has been adapted to the handling of eukaryotic genomes. The interface allows users to browse easily through genome data and retrieve information. CandidaDB also provides more elaborate tools, such as pattern searching, that are tightly connected to the overall browsing system. As the C.albicans genome is diploid and still incompletely assembled, CandidaDB provides tools to browse the genome by individual supercontigs and to examine information about allelic sequences obtained from complementary contigs. CandidaDB is accessible at http://genolist.pasteur.fr/CandidaDB

CandidaDB: A genome database for Candida albicans pathogenomics

CandidaDB is a database dedicated to the genome of the most prevalent systemic fungal pathogen of humans, Candida albicans. CandidaDB is based on an annotation of the Stanford Genome Technology Center C.albicans genome sequence data by the European Galar Fungail Consortium. CandidaDB Release 2.0 (June 2004) contains information pertaining to Assembly 19 of the genome of C.albicans strain SC5314. The current release contains 6244 annotated entries corresponding to 130 tRNA genes and 5917 protein-coding genes. For these, it provides tentative functional assignments along with numerous pre-run analyses that can assist the researcher in the evaluation of gene function for the purpose of specific or large-scale analysis. CandidaDB is based on GenoList, a generic relational data schema and a World Wide Web interface that has been adapted to the handling of eukaryotic genomes. The interface allows users to browse easily through genome data and retrieve information. CandidaDB also provides more elaborate tools, such as pattern searching, that are tightly connected to the overall browsing system. As the C.albicans genome is diploid and still incompletely assembled, CandidaDB provides tools to browse the genome by individual supercontigs and to examine information about allelic sequences obtained from complementary contigs. CandidaDB is accessible at http://genolist.pasteur.fr/CandidaDB.Sequence data from C.albicans were obtained from the Stanford Genome Technology Center (http://www.sequence. stanford.edu/group/candida). Sequencing of C.albicans was accomplished with the support of the NIDR and the Burroughs Wellcome Fund. This work was supported by grants from the European Commission (QLK2-2000-00795; MCRTN-CT-2003-504148; ‘Galar Fungail Consortium’) to A.J.P.B., C.E., A.D., J.E., C.G., B.H., F.M.K., J.P.M. and R.S. and the Ministere de la Recherche et de la Technologie (PRFMMIP ‘Re´seau Infections Fongiques’) to C.E. and C.G. F.T. was supported by the Institut Pasteur Strategic Horizontal Program on Anopheles gambiae. N.M. was supported by a fellowship of the Junta de Castilla y Leon and by grants DGCYT (PM-98-0317 and BIO 2002-02124) to A.D. R.S. was supported in part by grants from the Spanish Ministerio de Ciencia y Tecnologia (BMC2003- 01023) and Agencia Valenciana de Ciencia i Tecnologia de la Generalitat Valenciana (Grupos 03/187)

Genetic interaction mapping informs integrative structure determination of protein complexes

Determining structures of protein complexes is crucial for understanding cellular functions. Here, we describe an integrative structure determination approach that relies on in vivo measurements of genetic interactions. We construct phenotypic profiles for point mutations crossed against gene deletions or exposed to environmental perturbations, followed by converting similarities between two profiles into an upper bound on the distance between the mutated residues. We determine the structure of the yeast histone H3-H4 complex based on similar to 500,000 genetic interactions of 350 mutants. We then apply the method to subunits Rpb1-Rpb2 of yeast RNA polymerase II and subunits RpoB-RpoC of bacterial RNA polymerase. The accuracy is comparable to that based on chemical cross-links; using restraints from both genetic interactions and cross-links further improves model accuracy and precision. The approach provides an efficient means to augment integrative structure determination with in vivo observations