Not That Kind of Adult Toy: A Post-Adolescent Predilection for Plastic Playthings

This project is an exploratory study of the practice of toy collecting by adults. It examines the way they conceptualize their use of toys, what attracts them to these objects, the organization of communities of toy collectors, how they use the toys, and ultimately, what the toys provide for them. Using first-hand accounts collected at two pop culture conventions, information gathered from fan websites, respondent accounts featured in several recent documentaries, and panel presentations at three separate conventions, this study seeks to complicate the expectations of who toy consumers are (they’re not just children), as well as demonstrate the way these fans combine both adult and childlike aspects of play into their activities. While the conception of the adult toy enthusiast is taking hold in popular culture, adult toy fans must still contest with a characterization of their hobby as odd and immature. To combat this tension and provide rationalization for their interest, toy enthusiasts employ a number of strategies involving the use of legitimizing language and activities. Ultimately, the following demonstrates that adult and child toy play do not encompass discrete categories, rather existing on a continuum of play throughout the life course

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Not That Kind of Adult Toy: A Post-Adolescent Predilection for Plastic Playthings

This project is an exploratory study of the practice of toy collecting by adults. It examines the way they conceptualize their use of toys, what attracts them to these objects, the organization of communities of toy collectors, how they use the toys, and ultimately, what the toys provide for them. Using first-hand accounts collected at two pop culture conventions, information gathered from fan websites, respondent accounts featured in several recent documentaries, and panel presentations at three separate conventions, this study seeks to complicate the expectations of who toy consumers are (they’re not just children), as well as demonstrate the way these fans combine both adult and childlike aspects of play into their activities. While the conception of the adult toy enthusiast is taking hold in popular culture, adult toy fans must still contest with a characterization of their hobby as odd and immature. To combat this tension and provide rationalization for their interest, toy enthusiasts employ a number of strategies involving the use of legitimizing language and activities. Ultimately, the following demonstrates that adult and child toy play do not encompass discrete categories, rather existing on a continuum of play throughout the life course

Standardized multi-omics of Earth’s microbiomes reveals microbial and metabolite diversity

Extended data is available for this paper at https://doi.org/10.1038/s41564-022-01266-x.Despite advances in sequencing, lack of standardization makes comparisons across studies challenging and hampers insights into the structure and function of microbial communities across multiple habitats on a planetary scale. Here we present a multi-omics analysis of a diverse set of 880 microbial community samples collected for the Earth Microbiome Project. We include amplicon (16S, 18S, ITS) and shotgun metagenomic sequence data, and untargeted metabolomics data (liquid chromatography-tandem mass spectrometry and gas chromatography mass spectrometry). We used standardized protocols and analytical methods to characterize microbial communities, focusing on relationships and co-occurrences of microbially related metabolites and microbial taxa across environments, thus allowing us to explore diversity at extraordinary scale. In addition to a reference database for metagenomic and metabolomic data, we provide a framework for incorporating additional studies, enabling the expansion of existing knowledge in the form of an evolving community resource. We demonstrate the utility of this database by testing the hypothesis that every microbe and metabolite is everywhere but the environment selects. Our results show that metabolite diversity exhibits turnover and nestedness related to both microbial communities and the environment, whereas the relative abundances of microbially related metabolites vary and co-occur with specific microbial consortia in a habitat-specific manner. We additionally show the power of certain chemistry, in particular terpenoids, in distinguishing Earth’s environments (for example, terrestrial plant surfaces and soils, freshwater and marine animal stool), as well as that of certain microbes including Conexibacter woesei (terrestrial soils), Haloquadratum walsbyi (marine deposits) and Pantoea dispersa (terrestrial plant detritus). This Resource provides insight into the taxa and metabolites within microbial communities from diverse habitats across Earth, informing both microbial and chemical ecology, and provides a foundation and methods for multi-omics microbiome studies of hosts and the environment.The Samuel Freeman Charitable Trust, US National Institute of Health (NIH), US Department of Agriculture – National Institute of Food and Agriculture, the US National Science Foundation (NSF) - Center for Aerosol Impacts on Chemistry of the Environment, Crohn’s & Colitis Foundation Award (CCFA), US Department of Energy - Office of Science - Office of Biological and Environmental Research - Environmental System Science Program, Semiconductor Research Corporation and Defence Advanced Research Projects Agency (SRC/DARPA), Department of Defense, the Office of Naval Research (ONR, the Emerald Foundation, IBM Research AI through the AI Horizons Network, and the Center for Microbiome Innovation, the NIH, the Danish Council for Independent Research (DFF) , the Research Foundation – Flanders, Deutsche Forschungsgemeinschaft, the Gordon and Betty Moore Foundation. Metabolomics analyses at Pacific Northwest National Laboratory (PNNL) were supported by the Laboratory Directed Research and Development program via the Microbiomes in Transition Initiative and performed in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the US Office of Biological and Environmental Research and located at PNNL.http://www.nature.com/nmicrobiolam2023GeneticsNon

Thousands of small, novel genes predicted in global phage genomes.

Small genes (&lt;150 nucleotides) have been systematically overlooked in phage genomes. We employ a large-scale comparative genomics approach to predict &gt;40,000 small-gene families in ∼2.3 million phage genome contigs. We find that small genes in phage genomes are approximately 3-fold more prevalent than in host prokaryotic genomes. Our approach enriches for small genes that are translated in microbiomes, suggesting the small genes identified are coding. More than 9,000 families encode potentially secreted or transmembrane proteins, more than 5,000 families encode predicted anti-CRISPR proteins, and more than 500 families encode predicted antimicrobial proteins. By combining homology and genomic-neighborhood analyses, we reveal substantial novelty and diversity within phage biology, including small phage genes found in multiple host phyla, small genes encoding proteins that play essential roles in host infection, and small genes that share genomic neighborhoods and whose encoded proteins may share related functions

Thousands of small, novel genes predicted in global phage genomes

Fremin BJ, Bhatt AS, Kyrpides NC, et al. Thousands of small, novel genes predicted in global phage genomes. Cell Reports. 2022;39(12): 110984

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu