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Compartmentalization of the endoplasmic reticulum in the early C. elegans embryos
(2016)The Journal of Cell BiologyThe one-cell Caenorhabditis elegans embryo is polarized to partition fate determinants between the cell lineages generated during its first division. Using fluorescence loss in photobleaching, we find that the endoplasmic reticulum (ER) of the C. elegans embryo is physically continuous throughout the cell, but its membrane is compartmentalized shortly before nuclear envelope breakdown into an anterior and a posterior domain, indicating ...Journal Article -
Standardized benchmarking in the quest for orthologs
(2016)Nature MethodsAchieving high accuracy in orthology inference is essential for many comparative, evolutionary and functional genomic analyses, yet the true evolutionary history of genes is generally unknown and orthologs are used for very different applications across phyla, requiring different precision–recall trade-offs. As a result, it is difficult to assess the performance of orthology inference methods. Here, we present a community effort to establish ...Journal Article -
Inferring causal molecular networks: empirical assessment through a community-based effort
(2016)Nature MethodsIt remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than ...Journal Article -
Abnormal Intermediate Filament Organization Alters Mitochondrial Motility in Giant Axonal Neuropathy Fibroblasts
(2016)Molecular Biology of the CellGiant axonal neuropathy (GAN) is a rare disease caused by mutations in the GAN gene, which encodes gigaxonin, an E3 ligase adapter that targets intermediate filament (IF) proteins for degradation in numerous cell types, including neurons and fibroblasts. The cellular hallmark of GAN pathology is the formation of large aggregates and bundles of IFs. In this study, we show that both the distribution and motility of mitochondria are altered ...Journal Article -
Global reorganization of budding yeast chromosome conformation in different physiological conditions
(2016)The Journal of Cell BiologyThe organization of the genome is nonrandom and important for correct function. Specifically, the nuclear envelope plays a critical role in gene regulation. It generally constitutes a repressive environment, but several genes, including the GAL locus in budding yeast, are recruited to the nuclear periphery on activation. Here, we combine imaging and computational modeling to ask how the association of a single gene locus with the nuclear ...Journal Article -
Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling
(2016)The Journal of Cell BiologyRho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal ...Journal Article -
Analysis of the Protein Kinase A-Regulated Proteome of Cryptococcus neoformans Identifies a Role for the Ubiquitin-Proteasome Pathway in Capsule Formation
(2016)mBioThe opportunistic fungal pathogenCryptococcus neoformanscauses life-threatening meningitis in immunocompro-mised individuals. The expression of virulence factors, including capsule and melanin, is in part regulated by the cyclic-AMP/protein kinase A (cAMP/PKA) signal transduction pathway. In this study, we investigated the influence of PKA on the composi-tion of the intracellular proteome to obtain a comprehensive understanding of the ...Journal Article -
The bee microbiome: Impact on bee health and model for evolution and ecology of host-microbe interactions
(2016)mBioAs pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the microbiome. The bee microbiome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly ...Journal Article -
Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer
(2016)Journal of Pathology InformaticsBackground: Intratumoral hypoxia plays an important role with regard to tumor biology and susceptibility to radio- and chemotherapy. For further investigation of hypoxia-related changes, areas of certain hypoxia must be reliably detected within cancer tissues. Pimonidazole, a 2-nitroimindazole, accumulates in hypoxic tissue and can be easily visualized using immunohistochemistry. Materials and Methods: To improve detection of highly hypoxic ...Journal Article -
In vivo single-particle imaging of nuclear mRNA export in budding yeast demonstrates an essential role for Mex67p
(2015)The Journal of Cell BiologyMany messenger RNA export proteins have been identified; yet the spatial and temporal activities of these proteins and how they determine directionality of messenger ribonucleoprotein (mRNP) complex export from the nucleus remain largely undefined. Here, the bacteriophage PP7 RNA-labeling system was used in Saccharomyces cerevisiae to follow single-particle mRNP export events with high spatial precision and temporal resolution. These data ...Journal Article