Interfering Waves of Adaptation Promote Spatial Mixing

A fundamental problem of asexual adaptation is that beneficial substitutions are not efficiently accumulated in large populations: Beneficial mutations often go extinct because they compete with one another in going to fixation. It has been argued that such clonal interference may have led to the evolution of sex and recombination in well-mixed populations. Here, we study clonal interference, and mechanisms of its mitigation, in an evolutionary model of spatially structured populations with uniform selection pressure. Clonal interference is much more prevalent with spatial structure than without, due to the slow wave-like spread of beneficial mutations through space. We find that the adaptation speed of asexuals saturates when the linear habitat size exceeds a characteristic interference length, which becomes shorter with smaller migration and larger mutation rate. The limiting speed is proportional to μ1/2 and μ1/3 in linear and planar habitats, respectively, where the mutational supply μ is the product of mutation rate and local population density. This scaling and the existence of a speed limit should be amenable to experimental tests as they fall far below predicted adaptation speeds for well-mixed populations (that scale as the logarithm of population size). Finally, we show that not only recombination, but also long-range migration is a highly efficient mechanism of relaxing clonal competition in structured populations. Our conservative estimates of the interference length predict prevalent clonal interference in microbial colonies and biofilms, so clonal competition should be a strong driver of both genetic and spatial mixing in those contexts

New targets for overactive bladder-ICI-RS 2109

Aim: To review evidence for novel drug targets that can manage overactive bladder (OAB) symptoms. Methods: A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterize their use to treat OAB. Results: Five classes of agents or cellular pathways were considered. (a) Cyclic nucleotide–dependent (cyclic adenosine monophosphate and cyclic guanosine monophosphate) pathways that modulate adenosine triphosphate release from motor nerves and urothelium. (b) Novel targets for β3 agonists, including the bladder wall vasculature and muscularis mucosa. (c) Several TRP channels (TRPV1, TRPV4, TRPA1, and TRPM4) and their modulators in affecting detrusor overactivity. (d) Small conductance Ca2+-activated K+ channels and their influence on spontaneous contractions. (e) Antifibrosis agents that act to modulate directly or indirectly the TGF-β pathway—the canonical fibrosis pathway. Conclusions: The specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above mentioned potential agents are distributed among most organ systems. The tasks are to determine more detail of the pathological changes that occur in the OAB and how the specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor

Soil respiration in a northeastern US temperate forest: a 22‐year synthesis

To better understand how forest management, phenology, vegetation type, and actual and simulated climatic change affect seasonal and inter‐annual variations in soil respiration (Rs), we analyzed more than 100,000 individual measurements of soil respiration from 23 studies conducted over 22 years at the Harvard Forest in Petersham, Massachusetts, USA. We also used 24 site‐years of eddy‐covariance measurements from two Harvard Forest sites to examine the relationship between soil and ecosystem respiration (Re). Rs was highly variable at all spatial (respiration collar to forest stand) and temporal (minutes to years) scales of measurement. The response of Rs to experimental manipulations mimicking aspects of global change or aimed at partitioning Rs into component fluxes ranged from −70% to +52%. The response appears to arise from variations in substrate availability induced by changes in the size of soil C pools and of belowground C fluxes or in environmental conditions. In some cases (e.g., logging, warming), the effect of experimental manipulations on Rs was transient, but in other cases the time series were not long enough to rule out long‐term changes in respiration rates. Inter‐annual variations in weather and phenology induced variation among annual Rs estimates of a magnitude similar to that of other drivers of global change (i.e., invasive insects, forest management practices, N deposition). At both eddy‐covariance sites, aboveground respiration dominated Re early in the growing season, whereas belowground respiration dominated later. Unusual aboveground respiration patterns—high apparent rates of respiration during winter and very low rates in mid‐to‐late summer—at the Environmental Measurement Site suggest either bias in Rs and Re estimates caused by differences in the spatial scale of processes influencing fluxes, or that additional research on the hard‐to‐measure fluxes (e.g., wintertime Rs, unaccounted losses of CO2 from eddy covariance sites), daytime and nighttime canopy respiration and its impacts on estimates of Re, and independent measurements of flux partitioning (e.g., aboveground plant respiration, isotopic partitioning) may yield insight into the unusually high and low fluxes. Overall, however, this data‐rich analysis identifies important seasonal and experimental variations in Rs and Re and in the partitioning of Re above‐ vs. belowground

Soil respiration in a northeastern US temperate forest: a 22‐year synthesis

To better understand how forest management, phenology, vegetation type, and actual and simulated climatic change affect seasonal and inter‐annual variations in soil respiration (Rs), we analyzed more than 100,000 individual measurements of soil respiration from 23 studies conducted over 22 years at the Harvard Forest in Petersham, Massachusetts, USA. We also used 24 site‐years of eddy‐covariance measurements from two Harvard Forest sites to examine the relationship between soil and ecosystem respiration (Re). Rs was highly variable at all spatial (respiration collar to forest stand) and temporal (minutes to years) scales of measurement. The response of Rs to experimental manipulations mimicking aspects of global change or aimed at partitioning Rs into component fluxes ranged from −70% to +52%. The response appears to arise from variations in substrate availability induced by changes in the size of soil C pools and of belowground C fluxes or in environmental conditions. In some cases (e.g., logging, warming), the effect of experimental manipulations on Rs was transient, but in other cases the time series were not long enough to rule out long‐term changes in respiration rates. Inter‐annual variations in weather and phenology induced variation among annual Rs estimates of a magnitude similar to that of other drivers of global change (i.e., invasive insects, forest management practices, N deposition). At both eddy‐covariance sites, aboveground respiration dominated Re early in the growing season, whereas belowground respiration dominated later. Unusual aboveground respiration patterns—high apparent rates of respiration during winter and very low rates in mid‐to‐late summer—at the Environmental Measurement Site suggest either bias in Rs and Re estimates caused by differences in the spatial scale of processes influencing fluxes, or that additional research on the hard‐to‐measure fluxes (e.g., wintertime Rs, unaccounted losses of CO2 from eddy covariance sites), daytime and nighttime canopy respiration and its impacts on estimates of Re, and independent measurements of flux partitioning (e.g., aboveground plant respiration, isotopic partitioning) may yield insight into the unusually high and low fluxes. Overall, however, this data‐rich analysis identifies important seasonal and experimental variations in Rs and Re and in the partitioning of Re above‐ vs. belowground

Dynamics and Formation of the Near-Resonant K2-24 System: Insights from Transit-Timing Variations and Radial Velocities

While planets between the size of Uranus and Saturn are absent within the Solar System, the star K2-24 hosts two such planets, K2-24b and c, with radii equal to $5.4~R_E$ and $7.5~R_E$, respectively. The two planets have orbital periods of 20.9 days and 42.4 days, residing only 1% outside the nominal 2:1 mean-motion resonance. In this work, we present results from a coordinated observing campaign to measure planet masses and eccentricities that combines radial velocity (RV) measurements from Keck/HIRES and transit-timing measurements from K2 and Spitzer. K2-24b and c have low, but non-zero, eccentricities of $e_1 \sim e_2 \sim 0.08$. The low observed eccentricities provide clues regarding the formation and dynamical evolution of K2-24b and K2-24c, suggesting that they could be the result of stochastic gravitational interactions with a turbulent protoplanetary disk, among other mechanisms. K2-24b and c are $19\pm2~M_E$ and $15\pm2~M_E$, respectively; K2-24c is 20% less massive than K2-24b, despite being 40% larger. Their large sizes and low masses imply large envelope fractions, which we estimate at $26^{+3}_{-3}\%$ and $52^{+5}_{-3}\%$. In particular, K2-24c's large envelope presents an intriguing challenge to the standard model of core nucleated accretion that predicts the onset of runaway accretion when $f_{env} \approx 50\%$.Comment: 14 pages, 9 figures, 2 tables, accepted to A

Natural Sciences at Parkland College - Fall 2017

The Parkland College Natural Sciences Department Newsletter for Fall 2017 -- this issue features an article on IR cameras, use of display case, engaging students outside the classroom with the Astronomy Club and the Parkland Science Club, the solar eclipse, updates from the professional development subcommittee for faculty, summaries from events and meetings, a report on Phenotypic Pasticity Research Experience for Community College Students (PRECS) first summer, and a special feature from former professor Rich Blazier, with a special feature on the history of the Natural Sciences Department

Rapidly fatal advanced EGFR -mutated lung cancers and the need for rapid tumor genotyping in clinical practice

Use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is associated with dramatic, durable, and tolerable responses and side effect profiles, respectively, when applied for palliation of advanced EGFR-mutated non-small-cell lung cancers (NSCLCs). Expert guidelines recommend that EGFR mutation testing results should be available within 10 working days of receipt of tumor specimen by the testing laboratory; in circumstances where the tumor specimen needs to be sent to an external laboratory for testing, the sample should be sent within 3 working days of receiving the request for testing. We report here 2 cases, out of 109 EGFR-mutated (exon 19 deletion or L858R) NSCLCs seen at our institution, experiencing rapid clinical deterioration and death within the window of time prescribed by consensus testing guidelines. We hypothesize that a faster turn-around time may have changed the clinical outcome. Improving rapid turnaround times for tumor genotyping may afford more optimal palliation vis-à-vis early initiation of oral targeted therapy in patients with advanced EGFR-mutated NSCLC