High-resolution mapping of cancer cell networks using co-functional interactions.

Powerful new technologies for perturbing genetic elements have recently expanded the study of genetic interactions in model systems ranging from yeast to human cell lines. However, technical artifacts can confound signal across genetic screens and limit the immense potential of parallel screening approaches. To address this problem, we devised a novel PCA-based method for correcting genome-wide screening data, bolstering the sensitivity and specificity of detection for genetic interactions. Applying this strategy to a set of 436 whole genome CRISPR screens, we report more than 1.5 million pairs of correlated "co-functional" genes that provide finer-scale information about cell compartments, biological pathways, and protein complexes than traditional gene sets. Lastly, we employed a gene community detection approach to implicate core genes for cancer growth and compress signal from functionally related genes in the same community into a single score. This work establishes new algorithms for probing cancer cell networks and motivates the acquisition of further CRISPR screen data across diverse genotypes and cell types to further resolve complex cellular processes

Absolute differential cross sections for electron-impact excitation of CO near threshold: II. The Rydberg states of CO

Absolute differential cross sections for electron-impact excitation of Rydberg states of CO have been measured from threshold to 3.7 eV above threshold and for scattering angles between 20° and 140°. Measured excitation functions for the b 3Σ+, B 1Σ+ and E 1π states are compared with cross sections calculated by the Schwinger multichannel method. The behaviour of the excitation functions for these states and for the j 3Σ+ and C 1Σ+ states is analysed in terms of negative-ion states. One of these resonances has not been previously reported

Directional genetic differentiation and asymmetric migration

Understanding the population structure and patterns of gene flow within species is of fundamental importance to the study of evolution. In the fields of population and evolutionary genetics, measures of genetic differentiation are commonly used to gather this information. One potential caveat is that these measures assume gene flow to be symmetric. However, asymmetric gene flow is common in nature, especially in systems driven by physical processes such as wind or water currents. Since information about levels of asymmetric gene flow among populations is essential for the correct interpretation of the distribution of contemporary genetic diversity within species, this should not be overlooked. To obtain information on asymmetric migration patterns from genetic data, complex models based on maximum likelihood or Bayesian approaches generally need to be employed, often at great computational cost. Here, a new simpler and more efficient approach for understanding gene flow patterns is presented. This approach allows the estimation of directional components of genetic divergence between pairs of populations at low computational effort, using any of the classical or modern measures of genetic differentiation. These directional measures of genetic differentiation can further be used to calculate directional relative migration and to detect asymmetries in gene flow patterns. This can be done in a user-friendly web application called divMigrate-online introduced in this paper. Using simulated data sets with known gene flow regimes, we demonstrate that the method is capable of resolving complex migration patterns under a range of study designs.Comment: 25 pages, 8 (+3) figures, 1 tabl

Safety, the Preface Paradox and Possible Worlds Semantics

This paper contains an argument to the effect that possible worlds semantics renders semantic knowledge impossible, no matter what ontological interpretation is given to possible worlds. The essential contention made is that possible worlds semantic knowledge is unsafe and this is shown by a parallel with the preface paradox

Role of CD56 in Normal Kidney Development and Wilms Tumorigenesis

The cell-surface glycoprotein CD56 has three major isoforms that play important roles in cell adhesion and signaling, which may promote cell proliferation, differentiation, survival, or migration. It is an important molecule in normal kidney development and acts as a key marker in Wilms tumor stem and progenitor cells. Here, we review the structural and genetic features of the CD56 glycoprotein, and summarize its roles in the normal versus diseased metanephric blastema. We discuss areas of CD56-related research that may complement or improve existing Wilms tumor treatment strategies, including the antibody-drug conjugate lorvotuzumab mertansine that binds to CD56

A genome-wide investigation of the worldwide invader Sargassum muticum shows high success albeit (almost) no genetic diversity

Twenty years of genetic studies of marine invaders have shown that successful invaders are often characterized by native and introduced populations displaying similar levels of genetic diversity. This pattern is presumably due to high propagule pressure and repeated introductions. The opposite pattern is reported in this study of the brown seaweed, Sargassum muticum, an emblematic species for circumglobal invasions. Albeit demonstrating polymorphism in the native range, microsatellites failed to detect any genetic variation over 1,269 individuals sampled from 46 locations over the Pacific-Atlantic introduction range. Single-nucleotide polymorphisms (SNPs) obtained from ddRAD sequencing revealed some genetic variation, but confirmed severe founder events in both the Pacific and Atlantic introduction ranges. Our study thus exemplifies the need for extreme caution in interpreting neutral genetic diversity as a proxy for invasive potential. Our results confirm a previously hypothesized transoceanic secondary introduction from NE Pacific to Europe. However, the SNP panel unexpectedly revealed two additional distinct genetic origins of introductions. Also, conversely to scenarios based on historical records, southern rather than northern NE Pacific populations could have seeded most of the European populations. Finally, the most recently introduced populations showed the lowest selfing rates, suggesting higher levels of recombination might be beneficial at the early stage of the introduction process (i.e., facilitating evolutionary novelties), whereas uniparental reproduction might be favored later in sustainably established populations (i.e., sustaining local adaptation).Agence Nationale de la Recherche - ANR-10-BTBR-04; European Regional Development Fund; Fundacao para a Ciencia e a Tecnologia - SFRH/BPD/107878/2015, UID/Multi/04326/2016, UID/Multi/04326/2019; Brittany Region;info:eu-repo/semantics/publishedVersio

Museum DNA reveals the demographic history of the endangered Seychelles warbler

The importance of evolutionary conservation – how understanding evolutionary forces can help guide conservation decisions – is widely recognized. However, the historical demography of many endangered species is unknown, despite the fact that this can have important implications for contemporary ecological processes and for extinction risk. Here, we reconstruct the population history of the Seychelles warbler (Acrocephalus sechellensis) – an ecological model species. By the 1960s, this species was on the brink of extinction, but its previous history is unknown. We used DNA samples from contemporary and museum specimens spanning 140 years to reconstruct bottleneck history. We found a 25% reduction in genetic diversity between museum and contemporary populations, and strong genetic structure. Simulations indicate that the Seychelles warbler was bottlenecked from a large population, with an ancestral Ne of several thousands falling to <50 within the last century. Such a rapid decline, due to anthropogenic factors, has important implications for extinction risk in the Seychelles warbler, and our results will inform conservation practices. Reconstructing the population history of this species also allows us to better understand patterns of genetic diversity, inbreeding and promiscuity in the contemporary populations. Our approaches can be applied across species to test ecological hypotheses and inform conservation

Demonstration of a Quantum Gate using Electromagnetically Induced Transparency

We demonstrate a native $\mathrm{CNOT}$ gate between two individually addressed neutral atoms based on electromagnetically induced transparency (EIT). This protocol utilizes the strong long-range interactions of Rydberg states to enable conditional state transfer on the target qubit when operated in the blockade regime. An advantage of this scheme is it enables implementation of multi-qubit CNOT$^k$ gates using a pulse sequence independent of qubit number, and provides an simple gate for efficient implementation of quantum algorithms and error correction. We achieve a loss corrected gate fidelity of $\mathcal{F}_\mathrm{CNOT}^\mathrm{cor} = 0.82(6)$, and prepare an entangled Bell-state with $\mathcal{F}_\mathrm{Bell}^\mathrm{cor} = 0.66(5)$, limited at present by laser power. We present a number of technical improvements to advance this to a level required for fault-tolerant scaling.Comment: 6 pages, 5 figures plus Supplementary Materia