No abstract

Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1- and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer.

Total lipid levels, determined by the phosphosulphovanillin colorimetric method, declined significantly in ramose scleractinian corals and their xanthid crab symbionts during the 1983 El Nino warming event on the Pacific coast of Panama. This decline was observed in a controlled laboratory experiment, employing host corals (Pocillopora darnicornis) and obligate crab symbionts (Trapezia corallina and Trapezia ferruginea), concurrently with morbidity and mortality observed on coral reefs in the field. Lipid levels decreased from 0.59% (dry weight) to 0.34% in normal versus affected and dead corals, and from 4.54% (dry weight) to 1.20% in normal versus affected and dead crabs in a two-week period. Lipid depletion in corals accompanied the loss of zooxanthellae and increased morbidity and death; in crabs, a decrease in the number of egg-carrying females, a high emigration rate, a slight increase in mortality, and a decline in defensive behavior occurred. These findings suggest that symbiotic crabs were deprived of food from their coral hosts who initially lost zooxanthellae, an event correlated with the prolonged El Nino sea warming.

Over half of the world's population lives in urban areas with, according to the United Nations (UN), nearly 70% expected to live in cities by 2050 (United Nations, 2019). Our cities are built by and for humans, but are also complex, adaptive biological systems involving a diversity of other living species. The majority of these species are invisible and constitute the city's microbiome. Our design decisions for the built environment shape these invisible populations, and we interact with them on a constant basis. A growing body of evidence shows us that our health and well-being are dependent on these interactions. Indeed, multicellular organisms owe meaningful aspects of their development and phenotype to interactions with the microorganisms-bacteria or fungi-with which they live in continual exchange and symbiosis. While the processing and sequencing of samples can be high-throughput, gathering samples is still very expensive, labor intensive, and can require mobilizing large numbers of volunteers to get a snapshot of the microbial landscape of a city, such as City Sampling Day (metasub.org). Here we postulate that honeybees may be effective collaborators in the sampling process, as they daily forage within a 2-mile radius of their hive. We describe the results of a pilot study conducted with 3 rooftop beehives in Brooklyn, NY, where we evaluated the potential of was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which this version posted May 7, 2020. . https://doi.org/10.1101/2020.05.07.075093 doi: bioRxiv preprint various hive materials (beeswax, honey, debris, pollen, propolis) to reveal information as to the surrounding metagenomic landscape, and where we conclude that the bee debris are the richest substrate. Based on these results, we profiled 4 additional cities in this manner: Sydney, Melbourne, Venice and Tokyo. While the molecular and computational methods used here were based on DNA analysis, it is possible they could be used to monitor RNA-based viruses such as Sars-Cov-2. Here we present the results of this study, and discuss them in terms of architectural implications, as well as the potential of this method for epidemic surveillance.

Background Over half of the world’s population lives in urban areas with, according to the United Nations, nearly 70% expected to live in cities by 2050. Our cities are built by and for humans, but are also complex, adaptive biological systems involving a diversity of other living species. The majority of these species are invisible and constitute the city’s microbiome. Our design decisions for the built environment shape these invisible populations, and as inhabitants we interact with them on a constant basis. A growing body of evidence shows us that human health and well-being are dependent on these interactions. Indeed, multicellular organisms owe meaningful aspects of their development and phenotype to interactions with the microorganisms—bacteria or fungi—with which they live in continual exchange and symbiosis. Therefore, it is meaningful to establish microbial maps of the cities we inhabit. While the processing and sequencing of environmental microbiome samples can be high-throughput, gathering samples is still labor and time intensive, and can require mobilizing large numbers of volunteers to get a snapshot of the microbial landscape of a city. Results Here we postulate that honeybees may be effective collaborators in gathering samples of urban microbiota, as they forage daily within a 2-mile radius of their hive. We describe the results of a pilot study conducted with three rooftop beehives in Brooklyn, NY, where we evaluated the potential of various hive materials (honey, debris, hive swabs, bee bodies) to reveal information as to the surrounding metagenomic landscape, and where we conclude that the bee debris are the richest substrate. Based on these results, we profiled 4 additional cities through collected hive debris: Sydney, Melbourne, Venice and Tokyo. We show that each city displays a unique metagenomic profile as seen by honeybees. These profiles yield information relevant to hive health such as known bee symbionts and pathogens. Additionally, we show that this method can be used for human pathogen surveillance, with a proof-of-concept example in which we recover the majority of virulence factor genes for Rickettsia felis, a pathogen known to be responsible for “cat scratch fever”. Conclusions We show that this method yields information relevant to hive health and human health, providing a strategy to monitor environmental microbiomes on a city scale. Here we present the results of this study, and discuss them in terms of architectural implications, as well as the potential of this method for epidemic surveillance.