Direct imaging of RecA nucleation and growth on single molecules of SSB-coated ssDNA.

Escherichia coli RecA is the defining member of a ubiquitous class of DNA strand-exchange proteins that are essential for homologous recombination, a pathway that maintains genomic integrity by repairing broken DNA. To function, filaments of RecA must nucleate and grow on single-stranded DNA (ssDNA) in direct competition with ssDNA-binding protein (SSB), which rapidly binds and continuously sequesters ssDNA, kinetically blocking RecA assembly. This dynamic self-assembly on a DNA lattice, in competition with another protein, is unique for the RecA family compared to other filament-forming proteins such as actin and tubulin. The complexity of this process has hindered our understanding of RecA filament assembly because ensemble measurements cannot reliably distinguish between the nucleation and growth phases, despite extensive and diverse attempts. Previous single-molecule assays have measured the nucleation and growth of RecA--and its eukaryotic homologue RAD51--on naked double-stranded DNA and ssDNA; however, the template for RecA self-assembly in vivo is SSB-coated ssDNA. Using single-molecule microscopy, here we directly visualize RecA filament assembly on single molecules of SSB-coated ssDNA, simultaneously measuring nucleation and growth. We establish that a dimer of RecA is required for nucleation, followed by growth of the filament through monomer addition, consistent with the finding that nucleation, but not growth, is modulated by nucleotide and magnesium ion cofactors. Filament growth is bidirectional, albeit faster in the 5'→3' direction. Both nucleation and growth are repressed at physiological conditions, highlighting the essential role of recombination mediators in potentiating assembly in vivo. We define a two-step kinetic mechanism in which RecA nucleates on transiently exposed ssDNA during SSB sliding and/or partial dissociation (DNA unwrapping) and then the RecA filament grows. We further demonstrate that the recombination mediator protein pair, RecOR (RecO and RecR), accelerates both RecA nucleation and filament growth, and that the introduction of RecF further stimulates RecA nucleation

What is the Hidden Depolarization Mechanism in Low Luminosity AGN?

Millimeter wavelength polarimetry of accreting black hole systems can provide a tomographic probe of the accretion flow on a wide range of linear scales. We searched for linear polarization in two low luminosity active galactic nuclei (LLAGN), M81 and M84, using the Combined Array for Millimeter Astronomy (CARMA) and the Submillimeter Array (SMA). We find upper limits of $\sim 1 - 2\%$ averaging over the full bandwidth and with a rotation measure (RM) synthesis technique. These low polarization fractions, along with similar low values for LLAGN M87 and 3C84, suggest that LLAGN have qualitatively different polarization properties than radio-loud sources and Sgr A*. If the sources are intrinsically polarized and then depolarized by Faraday rotation then we place lower limits on the RM of a few times $10^7\, {\rm rad\, m^{-2}}$ for the full bandwidth case and $\sim 10^9\, {\rm rad\, m^{-2}}$ for the RM synthesis analysis. These limits are inconsistent with or marginally consistent with expected accretion flow properties. Alternatively, the sources may be depolarized by cold electrons within a few Schwarzschild radii from the black hole, as suggested by numerical models.Comment: Accepted for publication in ApJ

Keys to academic success for under-represented minority young investigators: recommendations from the Research in Academic Pediatrics Initiative on Diversity (RAPID) National Advisory Committee.

BackgroundAlthough Latinos, African-Americans, and American Indians/Alaska Natives comprise 34% of Americans, these under-represented minorities (URMs) account for only 7% of US medical-school faculty. Even when URMs become faculty, they face many substantial challenges to success. Little has been published, however, on keys to academic success for URM young faculty investigators.MethodsThe Research in Academic Pediatrics Initiative on Diversity (RAPID) goal is to enhance the professional advancement of URM junior faculty pursuing research careers in general academic pediatrics. One important RAPID component is the annual mentoring/career-development conference, which targets URM residents, fellows, and junior faculty, and has included 62 URM participants since its 2013 inception. A conference highlight is the panel discussion on keys to academic success for URM young investigators, conducted by the RAPID National Advisory Committee, a diverse group of leading senior researchers. The article aim was to provide a guide to academic success for URM young investigators using the 2018 RAPID Conference panel discussion. A modified Delphi technique was used to provide a systematic approach to obtaining answers to six key questions using an expert panel: the single most important key to success for URM young investigators; ensuring optimal mentorship; how to respond when patients/families say, "I don't want you to see my child because you are ____"; best strategies for maximizing funding success; how to balance serving on time-consuming committees with enough time to advance research/career objectives; and the single thing you wish someone had told you which would have substantially enhanced your success early on.Results/conclusionsThis is the first published practical guide on keys to academic success for URM young investigators. Identified keys to success included having multiple mentors, writing prolifically, being tenaciously persistent, having mentors who are invested in you, dealing with families who do not want you to care for their child because of your race/ethnicity by seeking to understand the reasons and debriefing with colleagues, seeking non-traditional funding streams, balancing committee work with having enough time to advance one's research and career by using these opportunities to generate scholarly products, and asking for all needed resources when negotiating for new jobs

Cross-Hedging Distillers Dried Grains Using Corn and Soybean Meal Futures Contracts

Ethanol mandates have led to an increase in the production of distillers dried grains (DDGs), a co-product of ethanol production that is incorporated into livestock rations. As with most competitive industries, there is some level of price risk in handling DDGs, and there is no DDG futures contract available for managing price risk. Commonly, DDGs are hedged using only corn futures. Our results suggest that cross-hedge risk may be reduced by including soybean meal futures in an encompassing cross-hedge strategy. Further, we also conclude soybean meal futures currently may be slightly more effective at reducing risk than in the past.cross-hedge, distillers dried grains, ethanol, price risk, Agribusiness, Demand and Price Analysis,

Adaptation without natural selection

Document is itself an extended abstract

The Occurrence and Distribution of Heterandria formosa (Teleostei, Poeciliidae) in Lowndes County, Georgia

Heretofore in the literature, Heterandria formosa had not been reported from Lowndes County, Georgia. Based on a survey of Lowndes County; we discovered eight localities from the southeast­ern portion of the county that collectively produced 30 specimens of H. formosa. The southeastern portion of the county is primarily flatwoods with numerous wetlands and low gradient streams compared to the remainder of the county, which is typified by a more upland habitat with greater relief and greater stream gradients. It is postulated that the greater stream gradients inhibited the migration of H. formosa into the southwestern and northern portions of the county

A tale of two niches: methods, concepts, and evolution

Being snapshots in time, species ranges may fall short of representing all of the geographic or environmental space that they are able to occupy. This has important implications for niche studies yet most comparative studies overlook the transient nature of species distributions and assume that they are at equilibrium. We review the methods most widely used for niche comparisons today and suggest a modified framework to describe and compare niches based on snapshot species range data. First, we introduce a new environmental space-based Niche Equivalence Statistic to test niche similarity between two species, which explicitly incorporates the spatial distribution of environments and their availability into statistical tests. We also introduce a new Background Statistic to measure the ability of this Niche Equivalence Statistic to detect differences based on the available environmental-space. These metrics enable fair comparisons between different geographies when the ranges of species are out of equilibrium. Based on distinct parameterizations of the new Equivalence and Background statistics, we then propose a Niche Divergence Test and a Niche Overlap Test, which allow assessment of whether differences between species emerge from true niche divergences. These methods are implemented in a new R package, ‘humboldt’ and applied to simulated species with pre-defined niches. The new methods improve accuracy of niche similarity and associated tests – consistently outperforming other tests. We show that the quantification of niche similarity should be performed only in environmental space, which is less sensitive than geographic space to the spatial abundance of key environmental variables. Further, our methods characterize the relationships between non-analogous and analogous climates in the species’ distributions, something not available previously. These improvements allow assessment of whether the different environmental spaces occupied by two taxa emerge from true niche evolution, as opposed to differences in life history and biological interactors, or differences in the variety and configuration of environments accessible to them

Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms.

BackgroundAlthough differences in brain anatomy in autism have been difficult to replicate using manual tracing methods, automated whole brain analyses have begun to find consistent differences in regions of the brain associated with the social cognitive processes that are often impaired in autism. We attempted to replicate these whole brain studies and to correlate regional volume changes with several autism symptom measures.MethodsWe performed MRI scans on 24 individuals diagnosed with DSM-IV autistic disorder and compared those to scans from 23 healthy comparison subjects matched on age. All participants were male. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM).ResultsControlling for age and total gray matter volume, the volumes of the medial frontal gyri, left pre-central gyrus, right post-central gyrus, right fusiform gyrus, caudate nuclei and the left hippocampus were larger in the autism group relative to controls. Regions exhibiting smaller volumes in the autism group were observed exclusively in the cerebellum. Significant partial correlations were found between the volumes of the caudate nuclei, multiple frontal and temporal regions, the cerebellum and a measure of repetitive behaviors, controlling for total gray matter volume. Social and communication deficits in autism were also associated with caudate, cerebellar, and precuneus volumes, as well as with frontal and temporal lobe regional volumes.ConclusionGray matter enlargement was observed in areas that have been functionally identified as important in social-cognitive processes, such as the medial frontal gyri, sensorimotor cortex and middle temporal gyrus. Additionally, we have shown that VBM is sensitive to associations between social and repetitive behaviors and regional brain volumes in autism

If you can't be with the one you love, love the one you're with: How individual habituation of agent interactions improves global utility

Simple distributed strategies that modify the behaviour of selfish individuals in a manner that enhances cooperation or global efficiency have proved difficult to identify. We consider a network of selfish agents who each optimise their individual utilities by coordinating (or anti-coordinating) with their neighbours, to maximise the pay-offs from randomly weighted pair-wise games. In general, agents will opt for the behaviour that is the best compromise (for them) of the many conflicting constraints created by their neighbours, but the attractors of the system as a whole will not maximise total utility. We then consider agents that act as 'creatures of habit' by increasing their preference to coordinate (anti-coordinate) with whichever neighbours they are coordinated (anti-coordinated) with at the present moment. These preferences change slowly while the system is repeatedly perturbed such that it settles to many different local attractors. We find that under these conditions, with each perturbation there is a progressively higher chance of the system settling to a configuration with high total utility. Eventually, only one attractor remains, and that attractor is very likely to maximise (or almost maximise) global utility. This counterintutitve result can be understood using theory from computational neuroscience; we show that this simple form of habituation is equivalent to Hebbian learning, and the improved optimisation of global utility that is observed results from wellknown generalisation capabilities of associative memory acting at the network scale. This causes the system of selfish agents, each acting individually but habitually, to collectively identify configurations that maximise total utility