Search

Many perennial plants show mast seeding, characterized by synchronous and highly variable reproduction across years. We propose a general model of masting, integrating proximate factors (environmental variation, weather cues, and resource budgets) with ultimate drivers (predator satiation and pollination efficiency). This general model shows how the relationships between masting and weather shape the diverse responses of species to climate warming, ranging from no change to lower interannual variation or reproductive failure. The role of environmental prediction as a masting driver is being reassessed; future studies need to estimate prediction accuracy and the benefits acquired. Since reproduction is central to plant adaptation to climate change, understanding how masting adapts to shifting environmental conditions is now a central question., Competing Interests: Declaration of interests No competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Major histocompatibility complex (MHC)-bound peptides that originate from tumor-specific genetic alterations, known as neoantigens, are an important class of anticancer therapeutic targets. Accurately predicting peptide presentation by MHC complexes is a key aspect of discovering therapeutically relevant neoantigens. Technological improvements in mass spectrometry-based immunopeptidomics and advanced modeling techniques have vastly improved MHC presentation prediction over the past 2 decades. However, improvement in the accuracy of prediction algorithms is needed for clinical applications like the development of personalized cancer vaccines, the discovery of biomarkers for response to immunotherapies, and the quantification of autoimmune risk in gene therapies. Toward this end, we generated allele-specific immunopeptidomics data using 25 monoallelic cell lines and created Systematic Human Leukocyte Antigen (HLA) Epitope Ranking Pan Algorithm (SHERPA), a pan-allelic MHC-peptide algorithm for predicting MHC-peptide binding and presentation. In contrast to previously published large-scale monoallelic data, we used an HLA-null K562 parental cell line and a stable transfection of HLA allele to better emulate native presentation. Our dataset includes five previously unprofiled alleles that expand MHC diversity in the training data and extend allelic coverage in underprofiled populations. To improve generalizability, SHERPA systematically integrates 128 monoallelic and 384 multiallelic samples with publicly available immunoproteomics data and binding assay data. Using this dataset, we developed two features that empirically estimate the propensities of genes and specific regions within gene bodies to engender immunopeptides to represent antigen processing. Using a composite model constructed with gradient boosting decision trees, multiallelic deconvolution, and 2.15 million peptides encompassing 167 alleles, we achieved a 1.44-fold improvement of positive predictive value compared with existing tools when evaluated on independent monoallelic datasets and a 1.17-fold improvement when evaluating on tumor samples. With a high degree of accuracy, SHERPA has the potential to enable precision neoantigen discovery for future clinical applications., Competing Interests: Conflict of interest R. M. P., D. M., Steven Dea, C. A., S. V. Z., N. A. P., J. H., G. B., Sejal Desai, R. M., J. W., R. C., and S. M. B. are full-time employees of Personalis. M. P. S. cofounded Personalis. Personalis Inc provided the funding for this project., (Copyright © 2023. Published by Elsevier Inc.)

Seasonal life history events are often interdependent, but we know relatively little about how the relationship between different events is influenced by the abiotic and biotic environment. Such knowledge is important for predicting the immediate and evolutionary phenological response of populations to changing conditions. We manipulated germination timing and shade in a multi-factorial experiment to investigate the relationship between spring and autumn phenology in seedlings of the pedunculate oak, Quercus robur, and whether this relationship was mediated by natural colonization of leaves by specialist fungal pathogens (i.e., the oak powdery mildew complex). Each week delay in germination corresponded to about 2 days delay in autumn leaf senescence, and heavily shaded seedlings senesced 5-8 days later than seedlings in light shade or full sun. Within seedlings, leaves on primary-growth shoots senesced later than those on secondary-growth shoots in some treatments. Path analyses demonstrated that germination timing and shade affected autumn phenology both directly and indirectly via pathogen load, though the specific pattern differed among and within seedlings. Pathogen load increased with later germination and greater shade. Greater pathogen load was in turn associated with later senescence for seedlings, but with earlier senescence for individual leaves. Our findings show that relationships between seasonal events can be partly mediated by the biotic environment and suggest that these relationships may differ between the plant and leaf level. The influence of biotic interactions on phenological correlations across scales has implications for understanding phenotypic variation in phenology and for predicting how populations will respond to climatic perturbation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: While immune checkpoint blockade (ICB) has become a pillar of cancer treatment, biomarkers that consistently predict patient response remain elusive due to the complex mechanisms driving immune response to tumors. We hypothesized that a multi-dimensional approach modeling both tumor and immune-related molecular mechanisms would better predict ICB response than simpler mutation-focused biomarkers, such as tumor mutational burden (TMB)., Experimental Design: Tumors from a cohort of patients with late-stage melanoma ( n = 51) were profiled using an immune-enhanced exome and transcriptome platform. We demonstrate increasing predictive power with deeper modeling of neoantigens and immune-related resistance mechanisms to ICB., Results: Our neoantigen burden score, which integrates both exome and transcriptome features, more significantly stratified responders and nonresponders ( P = 0.016) than TMB alone ( P = 0.049). Extension of this model to include immune-related resistance mechanisms affecting the antigen presentation machinery, such as HLA allele-specific LOH, resulted in a composite neoantigen presentation score (NEOPS) that demonstrated further increased association with therapy response ( P = 0.002)., Conclusions: NEOPS proved the statistically strongest biomarker compared with all single-gene biomarkers, expression signatures, and TMB biomarkers evaluated in this cohort. Subsequent confirmation of these findings in an independent cohort of patients ( n = 110) suggests that NEOPS is a robust, novel biomarker of ICB response in melanoma., (©2021 The Authors; Published by the American Association for Cancer Research.)

This article has been withdrawn by the authors. A publication of the manuscript with the correct figures and tables has been approved and the authors state the conclusions of the manuscript remain unaffected. Specifically, errors are in Figure 6A, Supplementary Figure 10B, Supplementary Figure 10C, and Supplementary Table 5. The details of the errors are as follows: the HLA types for one sample were incorrectly assigned because of a tumor/normal mislabeling from the biobank vendor. Due to the differing HLA types between the tumor and normal sample, the sequence analysis established that the HLA alleles for this patient had been deleted (HLA LOH). The authors conclude that this was an artifact caused by the normal sample mislabeling. The corrected version can be accessed (Pyke, R.M., Mellacheruvu, D., Dea, S., Abbott, C.W., Zhang, S.V., Philips, N.A., Harris, J., Bartha, G., Desai, S., McClory, R., West, J., Snyder, M,P., Chen, R., Boyle, S.M. (2022) Precision Neoantigen Discovery Using Large-Scale Immunopeptidomics and Composite Modeling of MHC Peptide Presentation. Mol. Cell. Proteomics 22, 100506, Competing Interests: Conflict of interest R. M. P., D. M., S. D., C. W. A., S. V. Z., N. P., J. H., G. B., Sejal Desai, R. M., J. W., R. C., and S. M. B are full- time employees of Personalis and owners of Personalis stock. M. P. S. co-founded Personalis and owns Personalis stock., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Four experiments found that the colors people choose as corresponding to the odors of fine fragrances are influenced by the perceived masculinity/femininity of those fragrances. Experiment 1 examined the colors chosen for 3 male and 3 female fragrances. The pattern of colors chosen for female fragrances differed from that for male fragrances. Experiments 2 and 3 found that colors assigned to 2 unisex fragrances depend on whether subjects thought that the fragrances were male or female fragrances. Experiment 4, by labeling unisex fragrances as male or female, showed that this difference in color selection was the result of subjects' thinking that a fragrance is a male or female fragrance. Thinking of the masculinity/femininity of a fragrance influences the selection of colors that corresponds to these odors.

The genome of canine adenovirus type 1 (CAV-1) has been cloned and restriction maps compiled. These maps are compared with those of canine adenovirus type 2 (CAV-2). The left ends of both genomes were further characterised by DNA sequence analysis. Several features of the DNA sequence and predicted polypeptide sequence are similar to those of the human adenoviruses. The level of homology observed across the E1 regions appears to be of the same order as the overall DNA similarity between CAV-1 and CAV-2 (75%). Transfection experiments using the presumptive E1a containing region of CAV-2 suggests that it encodes a transactivating function typical of the human adenovirus E1a genes.