The “creatures” of the human cortical somatosensory system, bioRxiv, 2019-06-22
AbstractPenfield’s description of the “homunculus”, a “grotesque creature” with large lips and hands and small trunk and legs depicting the representation of body-parts within the primary somatosensory cortex (S1), is one of the most prominent contributions to the neurosciences. Since then, numerous studies have identified additional body-parts representations outside of S1. Nevertheless, it has been implicitly assumed that S1’s homunculus is representative of the entire somatosensory cortex. Therefore, the distribution of body-parts representations in other brain regions, the property that gave Penfield’s homunculus its famous “grotesque” appearance, has been overlooked. We used whole-body somatosensory stimulation, functional MRI and a new cortical parcellation to quantify the organization of the cortical somatosensory representation. Our analysis showed first, an extensive somatosensory response over the cortex; and second, that the proportional representation of body-parts differs substantially between major neuroanatomical regions and from S1, with, for instance, much larger trunk representation at higher brain regions, potentially in relation to the regions’ functional specialization. These results extend Penfield’s initial findings to the higher level of somatosensory processing and suggest a major role for somatosensation in human cognition.
biorxiv neuroscience 0-100-users 2019The genomic impact of European colonization of the Americas, bioRxiv, 2019-06-21
AbstractThe human genetic diversity of the Americas has been shaped by several events of gene flow that have continued since the Colonial Era and the Atlantic slave trade. Moreover, multiple waves of migration followed by local admixture occurred in the last two centuries, the impact of which has been largely unexplored.Here we compiled a genome-wide dataset of ∼12,000 individuals from twelve American countries and ∼6,000 individuals from worldwide populations and applied haplotype-based methods to investigate how historical movements from outside the New World affected i) the genetic structure, ii) the admixture profile, iii) the demographic history and iv) sex-biased gene-flow dynamics, of the Americas.We revealed a high degree of complexity underlying the genetic contribution of European and African populations in North and South America, from both geographic and temporal perspectives, identifying previously unreported sources related to Italy, the Middle East and to specific regions of Africa.
biorxiv genomics 100-200-users 2019A live-cell screen for altered Erk dynamics reveals principles of proliferative control, bioRxiv, 2019-06-20
Complex, time-varying responses have been observed widely in cell signaling, but how specific dynamics are generated or regulated is largely unknown. One major obstacle has been that high-throughput screens for identifying pathway components are typically incompatible with the live-cell assays used to monitor dynamics. Here, we address this challenge by performing a drug screen for altered Erk signaling dynamics in primary mouse keratinocytes. We screened a library of 429 kinase inhibitors, monitoring Erk activity over 5 h in more than 80,000 single live cells. The screen revealed both known and uncharacterized modulators of Erk dynamics, including inhibitors of non-EGFR receptor tyrosine kinases (RTKs) that increased Erk pulse frequency and overall activity. Using drug treatment and direct optogenetic control, we demonstrate that drug-induced changes to Erk dynamics alter the conditions under which cells proliferate. Our work opens the door to high-throughput screens using live-cell biosensors and reveals that cell proliferation integrates information from Erk dynamics as well as additional permissive cues.
biorxiv cell-biology 0-100-users 2019Aequorea victoria’s secrets, bioRxiv, 2019-06-20
Using mRNA-Seq and de novo transcriptome assembly, we identified, cloned and characterized nine previously undiscovered fluorescent protein (FP) homologs from Aequorea victoria and a related Aequorea species, with most sequences highly divergent from avGFP. Among these FPs are the brightest GFP homolog yet characterized and a reversibly photochromic FP that responds to UV and blue light. Beyond green emitters, Aequorea species express purple- and blue-pigmented chromoproteins (CPs) with absorbances ranging from green to far-red, including two that are photoconvertible. X-ray crystallography revealed that Aequorea CPs contain a chemically novel chromophore with an unexpected crosslink to the main polypeptide chain. Because of the unique attributes of several of these newly discovered FPs, we expect that Aequorea will, once again, give rise to an entirely new generation of useful probes for bioimaging and biosensing.
biorxiv biochemistry 500+-users 2019Higher fitness yeast genotypes are less robust to deleterious mutations, bioRxiv, 2019-06-20
AbstractNatural selection drives populations towards higher fitness, but second-order selection for adaptability and mutational robustness can also influence the dynamics of adaptation. In many microbial systems, diminishing returns epistasis contributes to a tendency for more-fit genotypes to be less adaptable, but no analogous patterns for robustness are known. To understand how robustness varies across genotypes, we measure the fitness effects of hundreds of individual insertion mutations in a panel of yeast strains. We find that more-fit strains are less robust they have distributions of fitness effects (DFEs) with lower mean and higher variance. These shifts in the DFE arise because many mutations have more strongly deleterious effects in faster-growing strains. This negative correlation between fitness and robustness implies that second-order selection for robustness will tend to conflict with first-order selection for fitness.
biorxiv evolutionary-biology 0-100-users 2019Motility induced fracture reveals a ductile to brittle crossover in the epithelial tissues of a simple animal, bioRxiv, 2019-06-20
ABSTRACTAnimals are characterized by their movement, and their tissues are continuously subjected to dynamic force loading while they crawl, walk, run or swim1. Tissue mechanics fundamentally determine the ecological niches that can be endured by a living organism2. While epithelial tissues provide an important barrier function in animals, they are subjected to extreme strains during day to day physiological activities, such as breathing1, feeding3, and defense response4. How-ever, failure or inability to withstand to these extreme strains can result in epithelial fractures5, 6 and associated diseases7, 8. From a materials science perspective, how properties of living cells and their interactions prescribe larger scale tissue rheology and adaptive response in dynamic force landscapes remains an important frontier9. Motivated by pushing tissues to the limits of their integrity, we carry out a multi-modal study of a simple yet highly dynamic organism, the Trichoplax Adhaerens10–12, across four orders of magnitude in length (1 µm to 10 mm), and six orders in time (0.1 sec to 10 hours). We report the discovery of abrupt, bulk epithelial tissue fractures (∼10 sec) induced by the organism’s own motility. Coupled with rapid healing (∼10 min), this discovery accounts for dramatic shape change and physiological asexual division in this early-divergent metazoan. We generalize our understanding of this phenomena by codifying it in a heuristic model, highlighting the fundamental questions underlying the debondingbonding criterion in a soft-active-living material by evoking the concept of an ‘epithelial alloy’. Using a suite of quantitative experimental and numerical techniques, we demonstrate a force-driven ductile to brittle material transition governing the morphodynamics of tissues pushed to the edge of rupture. This work contributes to an important discussion at the core of developmental biology13–17, with important applications to an emerging paradigm in materials and tissue engineering5, 18–20, wound healing and medicine8, 21, 22.
biorxiv biophysics 200-500-users 2019