Biology subjects

Buchanan, B.

Publications and source records attributed to Buchanan, B..

3 recordsLinked to original sources

bioRxiv2021

Ribosome changes elicit non-canonical translation for chemosurvival in G0 leukemic cells

Quiescent leukemic cells survive chemotherapy, with translation changes. Our data reveal that FXR1, a protein amplified in several aggressive cancers, increases in quiescent and chemo- treated leukemic cells, and promotes chemosurvival. This suggests undiscovered roles for this RNA- and ribosome-associated protein in chemosurvival. FXR1 depletion decreases translation and ribosome subunits, with altered rRNAs, snoRNAs, and ribosomal proteins (RPs). We find that FXR1 binds factors that promote ribosome gene transcription and bind snoRNAs. Ribosome changes increased in FXR1-overexpressing cells, including increased snoRNAs and RPLP0/uL10, activate eIF2 kinases. Accordingly, phospho-eIF2 increases, enabling non- canonical translation of survival and immune regulators in FXR1-overexpressing cells. Overriding these with inhibitors reduces chemosurvival. Thus, increased FXR1 in quiescent or chemo-treated leukemic cells, alters ribosomes that trigger stress signals to re-direct translation for chemosurvival. One Sentence SummaryFXR1 alters ribosomes in G0, which induce stress signals to elicit noncanonical translation for AML drug and immune survival.

molecular biology↗

bioRxiv2021

Reconstructing hunter-gatherer planet Earthusing machine-learning

Estimating the total human population size (i.e., abundance) of the preagricultural planet is important for setting the baseline expectations for human-environment interactions if all energy and material requirements to support growth, maintenance, and well-being were foraged from local environments. However, demographic parameters and biogeographic distributions do not preserve directly in the archaeological record. Rather than attempting to estimate human abundance at some specific time in the past, a principled approach to making inferences at this scale is to ask what the human demography and biogeography of a hypothetical planet Earth would look like if populated by ethnographic hunter-gatherer societies. Given ethnographic hunter-gatherer societies likely include the largest, densest, and most complex foraging societies to have existed, we suggest population inferences drawn from this sample provide an upper bound to demographic estimates in prehistory. Our goal in this paper is to produce principled estimates of hunter-gatherer abundance, diversity, and biogeography. To do this we trained an extreme gradient boosting algorithm (XGBoost) to learn ethnographic hunter-gatherer population densities from a large matrix of climatic, environmental, and geographic data. We used the predictions generated by this model to reconstruct the hunter-gatherer biogeography of the rest of the planet. We find the human abundance of this world to be 6.1{+/-}2 million with an ethnolinguistic diversity of 8,330{+/-}2,770 populations, most of whom would have lived near coasts and in the tropics. Significance StatementUnderstanding the abundance of humans on planet Earth prior to the development of agriculture and the industrialized world is essential to understanding human population growth. However, the problem is that these features of human populations in the past are unknown and so must be estimated from data. We developed a machine learning approach that uses ethnographic and environmental data to reconstruct the demography and biogeography of planet Earth if populated by hunter-gatherers. Such a world would house about 6 million people divided into about 8,330 populations with a particular concentration in the tropics and along coasts.

ecology↗

bioRxiv2020

Evolution of transmissible spongiform encephalopathy and the prion protein gene (PRNP) in mammals

Wildlife managers are concerned with transmissible spongiform encephalopathies (TSEs) as they are currently incurable, always fatal, and have the potential to cross species boundaries. Although a wide range of mammals exhibit TSEs, it is currently unclear whether they are evolutionarily clustered or if TSE+ species are randomly distributed phylogenetically. We tested whether mammalian species with TSEs are phylogenetically underdispersed on a tree derived from 102 PRNP sequences obtained from the Orthologous Mammalian Markers database. We determined that the PRNP tree was topologically congruent with a species tree for these same 102 taxa constructed from 20 aligned gene sequences, excluding the PRNP sequence. Searches in Google Scholar were done to determine whether a species is known to have expressed a TSE. TSEs were present in a variety of orders excluding Chiroptera, Eulipotyphyla, and Lagomorpha and no marine mammals (Artiodactyla) were recorded to have a TSE. We calculated the phylogenetic signal of binary traits (D-Value) to infer if the phylogenetic distribution of TSEs are conserved or dispersed. The occurrence of TSEs in both trees is non-random (Species tree D-value = 0.291; PRNP tree D-value = 0.273), and appears to have arisen independently in the recent history of different mammalian groups. Our findings suggest that the evolution of TSEs develops in groups of species irrespective of PRNP genotype. The evolution of TSEs merits continued exploration at a more in-depth phylogenetic level, as well as the search for genetic combinations that might underlie TSE diseases.

evolutionary biology↗