Enhanced Symmetries in Multiparameter Flux Vacua

We give a construction of type IIB flux vacua with discrete R-symmetries and vanishing superpotential for hypersurfaces in weighted projective space with any number of moduli. We find that the existence of such vacua for a given space depends on properties of the modular group, and for Fermat models can be determined solely by the weights of the projective space. The periods of the geometry do not in general have arithmetic properties, but live in a vector space whose properties are vital to the construction.Comment: 32 pages, LaTeX. v2: references adde

Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses

In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum

Content and performance of the MiniMUGA genotyping array: A new tool to improve rigor and reproducibility in mouse research

The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost-effective, informative, and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole-genome sequencing. Here, we describe the content and performance of a new iteration of the Mouse Universal Genotyping Array (MUGA), MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: (1) chromosomal sex determination, (2) discrimination between substrains from multiple commercial vendors, (3) diagnostic SNPs for popular laboratory strains, (4) detection of constructs used in genetically engineered mice, and (5) an easy-to-interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA, we genotyped 6899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays, both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived, and recombinant inbred lines. Here, we also report the detection of a substantial number of XO and XXY individuals across a variety of sample types, new markers that expand the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. We provide preliminary evidence that the array can be used to identify both partial sex chromosome duplication and mosaicism, and that diagnostic SNPs can be used to determine how long inbred mice have been bred independently from the relevant main stock. We conclude that MiniMUGA is a valuable platform for genetic QC, and an important new tool to increase the rigor and reproducibility of mouse research

Cutthroat cooperation: the effects of team role decisions on adaptation to alternative reward structures

Structural Adaptation Theory proposes that it is more difficult for teams to change from competitive to cooperative reward conditions than it is for them to change in the opposite direction, and this has been labeled the cutthroat cooperation effect [Johnson, M. D., Hollenbeck, J. R., Ilgen, D. R., Humphrey, S. E., Meyer, C. J., & Jundt, D. K. (2006). Cutthroat cooperation: Asymmetrical adaptation of team reward structures. Academy of Management Journal, 49, 103-120]. The current study investigated whether team role discussion can neutralize this effect and promote successful adaptation from competitive to cooperative reward structures. Consistent with our predictions, in a study that involved 75 four-person teams performing a complex task under cooperative reward conditions, we found that teams with a history of competitive rewards performed worse than teams with a history of cooperative rewards in a control condition. However, this effect was neutralized when teams allocated their roles in a team role discussion. This neutralization effect was driven by behavioral coordination and unmet expectations regarding conflict

Lrp5 functions in bone to regulate bone mass

The human skeleton is affected by mutations in low-density lipoprotein receptor-related protein 5 (LRP5). To understand how LRP5 influences bone properties, we generated mice with osteocyte-specific expression of inducible Lrp5 mutations that cause high and low bone mass phenotypes in humans. We found that bone properties in these mice were comparable to bone properties in mice with inherited mutations. We also induced an Lrp5 mutation in cells that form the appendicular skeleton but not in cells that form the axial skeleton; we observed that bone properties were altered in the limb but not in the spine. These data indicate that Lrp5 signaling functions locally, and they suggest that increasing LRP5 signaling in mature bone cells may be a strategy for treating human disorders associated with low bone mass, such as osteoporosis