The interaction map of yeast: terra incognita?

A systematic curation of the literature on Saccharomyces cerevisiae has yielded a comprehensive collection of experimentally observed interactions. This new resource augments current views of the topological structure of yeast's physical and genetic networks, but also reveals that existing studies cover only a fraction of the cell

Neural Architecture Search without Training

The time and effort involved in hand-designing deep neural networks is immense. This has prompted the development of Neural Architecture Search (NAS) techniques to automate this design. However, NAS algorithms tend to be slow and expensive; they need to train vast numbers of candidate networks to inform the search process. This could be alleviated if we could partially predict a network's trained accuracy from its initial state. In this work, we examine the overlap of activations between datapoints in untrained networks and motivate how this can give a measure which is usefully indicative of a network's trained performance. We incorporate this measure into a simple algorithm that allows us to search for powerful networks without any training in a matter of seconds on a single GPU, and verify its effectiveness on NAS-Bench-101, NAS-Bench-201, NATS-Bench, and Network Design Spaces. Our approach can be readily combined with more expensive search methods; we examine a simple adaptation of regularised evolutionary search. Code for reproducing our experiments is available at https://github.com/BayesWatch/nas-without-training.Comment: Accepted at ICML 2021 for a long presentatio

VisANT: data-integrating visual framework for biological networks and modules

VisANT is a web-based software framework for visualizing and analyzing many types of networks of biological interactions and associations. Networks are a useful computational tool for representing many types of biological data, such as biomolecular interactions, cellular pathways and functional modules. Given user-defined sets of interactions or groupings between genes or proteins, VisANT provides: (i) a visual interface for combining and annotating network data, (ii) supporting function and annotation data for different genomes from the Gene Ontology and KEGG databases and (iii) the statistical and analytical tools needed for extracting topological properties of the user-defined networks. Users can customize, modify, save and share network views with other users, and import basic network data representations from their own data sources, and from standard exchange formats such as PSI-MI and BioPAX. The software framework we employ also supports the development of more sophisticated visualization and analysis functions through its open API for Java-based plug-ins. VisANT is distributed freely via the web at and can also be downloaded for individual use

VisANT: data-integrating visual framework for biological networks and modules

VisANT is a web-based software framework for visualizing and analyzing many types of networks of biological interactions and associations. Networks are a useful computational tool for representing many types of biological data, such as biomolecular interactions, cellular pathways and functional modules. Given user-defined sets of interactions or groupings between genes or proteins, VisANT provides: (i) a visual interface for combining and annotating network data, (ii) supporting function and annotation data for different genomes from the Gene Ontology and KEGG databases and (iii) the statistical and analytical tools needed for extracting topological properties of the user-defined networks. Users can customize, modify, save and share network views with other users, and import basic network data representations from their own data sources, and from standard exchange formats such as PSI-MI and BioPAX. The software framework we employ also supports the development of more sophisticated visualization and analysis functions through its open API for Java-based plug-ins. VisANT is distributed freely via the web at and can also be downloaded for individual use

Cyclic-AMP Increases Nuclear Actin Monomer Which Promotes Proteasomal Degradation of RelA/p65 Leading to Anti-Inflammatory Effects

The second messenger, cAMP has potent immunosuppressive and anti-inflammatory actions. These have been attributed, in part, to the ability of cAMP-induced signals to interfere with the function of the proinflammatory transcription factor Nuclear Factor-kappa B (NF-κB). However, the mechanisms underlying the modulation of NF-κB activity by cAMP remain unclear. Here we demonstrate an important role for cAMP-mediated increase in nuclear actin monomer levels in inhibiting NF-κB activity. Elevated cAMP or forced expression of a nuclear localised polymerisation defective actin mutant (NLS-Actin(R62D)) inhibited basal and TNFα induced mRNA levels of NF-κB-dependent genes and NF-κB-dependent reporter gene activity. Elevated cAMP or NLS-Actin(R62D) did not affect NF-κB nuclear translocation but did reduce total cellular and nuclear RelA/p65 levels. Preventing the cAMP-induced increase in nuclear actin monomer, either by expressing a nuclear localised active mutant of the actin polymerising protein mDIA, silencing components of the nuclear actin import complex IPO9 and CFL1 or overexpressing the nuclear export complex XPO6, rescued RelA/p65 levels and NF-κB reporter gene activity in forskolin-stimulated cells. Elevated cAMP or NLS-Actin(R62D) reduced the half-life of RelA/p65, which was reversed by the proteasome inhibitor MG132. Accordingly, forskolin stimulated association of RelA/p65 with ubiquitin affinity beads, indicating increased ubiquitination of RelA/p65 or associated proteins. Taken together, our data demonstrate a novel mechanism underlying the anti-inflammatory effects of cAMP and highlight the important role played by nuclear actin in the regulation of inflammation

VisANT 3.0: new modules for pathway visualization, editing, prediction and construction

With the integration of the KEGG and Predictome databases as well as two search engines for coexpressed genes/proteins using data sets obtained from the Stanford Microarray Database (SMD) and Gene Expression Omnibus (GEO) database, VisANT 3.0 supports exploratory pathway analysis, which includes multi-scale visualization of multiple pathways, editing and annotating pathways using a KEGG compatible visual notation and visualization of expression data in the context of pathways. Expression levels are represented either by color intensity or by nodes with an embedded expression profile. Multiple experiments can be navigated or animated. Known KEGG pathways can be enriched by querying either coexpressed components of known pathway members or proteins with known physical interactions. Predicted pathways for genes/proteins with unknown functions can be inferred from coexpression or physical interaction data. Pathways produced in VisANT can be saved as computer-readable XML format (VisML), graphic images or high-resolution Scalable Vector Graphics (SVG). Pathways in the format of VisML can be securely shared within an interested group or published online using a simple Web link. VisANT is freely available at http://visant.bu.edu

VisANT 3.0: new modules for pathway visualization, editing, prediction and construction

With the integration of the KEGG and Predictome databases as well as two search engines for coexpressed genes/proteins using data sets obtained from the Stanford Microarray Database (SMD) and Gene Expression Omnibus (GEO) database, VisANT 3.0 supports exploratory pathway analysis, which includes multi-scale visualization of multiple pathways, editing and annotating pathways using a KEGG compatible visual notation and visualization of expression data in the context of pathways. Expression levels are represented either by color intensity or by nodes with an embedded expression profile. Multiple experiments can be navigated or animated. Known KEGG pathways can be enriched by querying either coexpressed components of known pathway members or proteins with known physical interactions. Predicted pathways for genes/proteins with unknown functions can be inferred from coexpression or physical interaction data. Pathways produced in VisANT can be saved as computer-readable XML format (VisML), graphic images or high-resolution Scalable Vector Graphics (SVG). Pathways in the format of VisML can be securely shared within an interested group or published online using a simple Web link. VisANT is freely available at http://visant.bu.edu

Clinical Study Neutrophil Gelatinase-Associated Lipocalin: Its Response to Hypoxia and Association with Acute Mountain Sickness

Acute Mountain Sickness (AMS) is a common clinical challenge at high altitude (HA). A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL) rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort ( = 22) undertaking 6 hours exercise at near sea-level (SL); a cohort ( = 14) during 3 hours of normobaric hypoxia (FiO2 11.6%) and on two trekking expeditions ( = 52) to over 5000 m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean ± sd, range) rose significantly ( < 0.001) from 68 ± 14 (60-102) at 1300 m to 183 ± 107 (65-519); 143 ± 66 (60-315) and 150 ± 71 (60-357) at 3400 m, 4270 m and 5150 m respectively. At 5150 m there was a significant difference in NGAL between those with severe AMS ( = 7), mild AMS ( = 16) or no AMS ( = 23): 201 ± 34 versus 171 ± 19 versus 124 ± 12 respectively ( = 0.009 for severe versus no AMS; = 0.026 for mild versus no AMS). In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS