Evolution of size-dependent flowering in a variable environment: construction and analysis of a stochastic integral projection model

Understanding why individuals delay reproduction is a classic problem in evolutionary biology. In plants, the study of reproductive delays is complicated because growth and survival can be size and age dependent, individuals of the same size can grow by different amounts and there is temporal variation in the environment. We extend the recently developed integral projection approach to include size- and age-dependent demography and temporal variation. The technique is then applied to a long-term individually structured dataset for Carlina vulgaris, a monocarpic thistle. The parameterized model has excellent descriptive properties in terms of both the population size and the distributions of sizes within each age class. In Carlina, the probability of flowering depends on both plant size and age. We use the parameterized model to predict this relationship, using the evolutionarily stable strategy approach. Considering each year separately, we show that both the direction and the magnitude of selection on the flowering strategy vary from year to year. Provided the flowering strategy is constrained, so it cannot be a step function, the model accurately predicts the average size at flowering. Elasticity analysis is used to partition the size- and age-specific contributions to the stochastic growth rate, λs. We use λs to construct fitness landscapes and show how different forms of stochasticity influence its topography. We prove the existence of a unique stochastic growth rate, λs, which is independent of the initial population vector, and show that Tuljapurkar's perturbation analysis for log(λs) can be used to calculate elasticities

Differential Requirement for the Cell Wall Integrity Sensor Wsc1p in Diploids Versus Haploids.

The primary role of the Cell Wall Integrity Pathway (CWI) in Saccharomyces cerevisiae is monitoring the state of the cell wall in response to general life cycle stresses (growth and mating) and imposed stresses (temperature changes and chemicals). Of the five mechanosensor proteins monitoring cell wall stress, Wsc1p and Mid2p are the most important. We find that WSC1 has a stringent requirement in zygotes and diploids, unlike haploids, and differing from MID2's role in shmoos. Diploids lacking WSC1 die frequently, independent of mating type. Death is due to loss of cell wall and plasma membrane integrity, which is suppressed by osmotic support. Overexpression of several CWI pathway components suppress wsc1∆ zygotic death, including WSC2, WSC3, and BEM2, as well as the Rho-GAPS, BEM3 and RGD2. Microscopic observations and suppression by BEM2 and BEM3 suggest that wsc1∆ zygotes die during bud emergence. Downstream in the CWI pathway, overexpression of a hyperactive protein kinase C (Pkc1p-R398P) causes growth arrest, and blocks the pheromone response. With moderate levels of Pkc1p-R398P, cells form zygotes and the wsc1∆ defect is suppressed. This work highlights functional differences in the requirement for Wsc1p in diploids Versus haploids and between Mid2p and Wsc1p during mating

A Case Study of Tire Crumb Use on Playgrounds: Risk Analysis and Communication When Major Clinical Knowledge Gaps Exist

Physicians and public health professionals working with the U.S. Environmental Protection Agency’s Region 8 Pediatric Environmental Health Specialty Unit (PEHSU) received several telephone calls requesting information regarding the safety of recycled tire crumb as a playground surface constituent placed below children’s play structures. There were no reported symptoms or adverse health effects in exposed children. The literature available on the safety and risk of exposure to crumb rubber constituents was limited and revealed no information quantifying exposures associated with product use. Callers were informed by the PEHSU that no evidence existed suggesting harm from intended use of the product, but gaps in knowledge about the product were identified and communicated. Here the case of crumb rubber on playgrounds is used as a model to present an approach to similar environmental medicine questions. From defining the question, to surveying traditional and nontraditional resources for information, synthesis of findings, and risk communication, the case provides a model to approach similar questions

Applications of discrete element method in modeling of grain postharvest operations

Grain kernels are finite and discrete materials. Although flowing grain can behave like a continuum fluid at times, the discontinuous behavior exhibited by grain kernels cannot be simulated solely with conventional continuum-based computer modeling such as finite-element or finite-difference methods. The discrete element method (DEM) is a proven numerical method that can model discrete particles like grain kernels by tracking the motion of individual particles. DEM has been used extensively in the field of rock mechanics. Its application is gaining popularity in grain postharvest operations, but it has not been applied widely. This paper reviews existing applications of DEM in grain postharvest operations. Published literature that uses DEM to simulate postharvest processing is reviewed, as are applications in handling and processing of grain such as soybean, corn, wheat, rice, rapeseed, and the grain coproduct distillers dried grains with solubles (DDGS). Simulations of grain drying that involve particles in both free-flowing and confined-flow conditions are also included. Review of existing literature indicates that DEM is a promising approach in the study of the behavior of deformable soft particulates such as grain and coproducts and it could benefit from the development of improved particle models for these complex-shaped particles

Photoionized plasma calculations using laboratory and astrophysical models

We present numerical simulations from the code GALAXY, frequently employed to model the distribution of excitation and ionization, and the spectral emission from laboratory plasma experiments. In particular, preliminary calculations relevant to the Lawrence Livermore National Laboratory photoionization collaboration are presented, along with results which compare GALAXY with results from the astrophysical code CLOUDY

Fatal Outcome of Disseminated Strongyloidiasis despite Detectable Plasma and Cerebrospinal Levels of Orally Administered Ivermectin

Strongyloides stercoralis affects over 100 million people worldwide. Those people most susceptible to infection are those with an immunocompromising condition, such as cancer or human immunodeficiency virus (HIV). Local disease may spread throughout the body of the host, causing a condition termed disseminated strongyloidiasis. Standard treatment for Strongyloides stercoralis infection is oral ivermectin. We describe a patient with chronic lymphocytic leukemia diagnosed with disseminated strongyloidiasis two weeks after initial presentation. After repeated dosing of oral ivermectin with no clinical response, serum and cerebral spinal fluid (CSF) concentrations of ivermectin were measured to assess absorption. The peak serum concentration of 49.3 ng/mL correlated with a CSF concentration of 0.14 ng/mL. Despite these concentrations, the patient eventually succumbed to multi-system organ failure. We discuss the reasons for treatment failure and explore the utility of measuring ivermectin concentrations

Functional polarity is introduced by Dicer processing of short substrate RNAs

Synthetic RNA duplexes that are substrates for Dicer are potent triggers of RNA interference (RNAi). Blunt 27mer duplexes can be up to 100-fold more potent than traditional 21mer duplexes (1). Not all 27mer duplexes show increased potency. Evaluation of the products of in vitro dicing reactions using electrospray ionization mass spectrometry reveals that a variety of products can be produced by Dicer cleavage. Use of asymmetric duplexes having a single 2-base 3′-overhang restricts the heterogeneity that results from dicing. Inclusion of DNA residues at the ends of blunt duplexes also limits heterogeneity. Combination of asymmetric 2-base 3′-overhang with 3′-DNA residues on the blunt end result in a duplex form which directs dicing to predictably yield a single primary cleavage product. It is therefore possible to design a 27mer duplex which is processed by Dicer to yield a specific, desired 21mer species. Using this strategy, two different 27mers can be designed that result in the same 21mer after dicing, one where the 3′-overhang resides on the antisense (AS) strand and dicing proceeds to the ‘right’ (‘R’) and one where the 3′-overhang resides on the sense (S) strand and dicing proceeds to the ‘left’ (‘L’). Interestingly, the ‘R’ version of the asymmetric 27mer is generally more potent in reducing target gene levels than the ‘L’ version 27mer. Strand targeting experiments show asymmetric strand utilization between the two different 27mer forms, with the ‘R’ form favoring S strand and the ‘L’ form favoring AS strand silencing. Thus, Dicer processing confers functional polarity within the RNAi pathway

‘Hygienic’ Lymphocytes Convey Increased Cancer Risk

Risk of developing inflammation-associated cancers has increased in industrialized countries during the past 30 years. One possible explanation is societal hygiene practices with use of antibiotics and Caesarian births that provide too few early life exposures of beneficial microbes. Building upon a ‘hygiene hypothesis’ model whereby prior microbial exposures lead to beneficial changes in CD4+ lymphocytes, here we use an adoptive cell transfer model and find that too few prior microbe exposures alternatively result in increased inflammation-associated cancer growth in susceptible recipient mice. Specifically, purified CD4+ lymphocytes collected from ‘restricted flora’ donors increases multiplicity and features of malignancy in intestinal polyps of recipient Apc[superscript Min/+] mice, coincident with increased inflammatory cell infiltrates and instability of the intestinal microbiota. We conclude that while a competent immune system serves to maintain intestinal homeostasis and good health, under hygienic rearing conditions CD4+ lymphocytes instead exacerbate inflammation-associated tumorigenesis, subsequently contributing to more frequent cancers in industrialized societies.National Institutes of Health (U.S.) (Grant P30-ES002109)National Institutes of Health (U.S.) (Grant U01 CA164337)National Institutes of Health (U.S.) (Grant RO1CA108854