Histone modifications such as methylation and acetylation play a significant role in controlling gene expression in unstressed and stressed plants. Genome-wide analysis of such stress-responsive modifications and genes in non-model crops is limited. We report the genome-wide profiling of histone methylation (H3K9me2) and acetylation (H4K12ac) in common bean (Phaseolus vulgaris L.) under rust (Uromyces appendiculatus) stress using two high-throughput approaches, chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq). ChIP-Seq analysis revealed 1,235 and 556 histone methylation and acetylation responsive genes from common bean leaves treated with the rust pathogen at 0, 12 and 84 hour-after-inoculation (hai), while RNA-Seq analysis identified 145 and 1,763 genes differentially expressed between mock-inoculated and inoculated plants. The combined ChIP-Seq and RNA-Seq analyses identified some key defense responsive genes (calmodulin, cytochrome p450, chitinase, DNA Pol II, and LRR) and transcription factors (WRKY, bZIP, MYB, HSFB3, GRAS, NAC, and NMRA) in bean-rust interaction. Differential methylation and acetylation affected a large proportion of stress-responsive genes including resistant (R) proteins, detoxifying enzymes, and genes involved in ion flux and cell death. The genes identified were functionally classified using Gene Ontology (GO) and EuKaryotic Orthologous Groups (KOGs). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified a putative pathway with ten key genes involved in plant-pathogen interactions. This first report of an integrated analysis of histone modifications and gene expression involved in the bean-rust interaction as reported here provides a comprehensive resource for other epigenomic regulation studies in non-model species under stress.
When standard optimization methods fail to find a satisfactory solution for a parameter fitting problem, a tempting recourse is to adjust parameters manually. While tedious, this approach can be surprisingly powerful in terms of achieving optimal or near-optimal solutions. This paper outlines an optimization algorithm, Adaptive Stochastic Descent (ASD), that has been designed to replicate the essential aspects of manual parameter fitting in an automated way. Specifically, ASD uses simple principles to form probabilistic assumptions about (a) which parameters have the greatest effect on the objective function, and (b) optimal step sizes for each parameter. We show that for a certain class of optimization problems (namely, those with a moderate to large number of scalar parameter dimensions, especially if some dimensions are more important than others), ASD is capable of minimizing the objective function with far fewer function evaluations than classic optimization methods, such as the Nelder-Mead nonlinear simplex, Levenberg-Marquardt gradient descent, simulated annealing, and genetic algorithms. As a case study, we show that ASD outperforms standard algorithms when used to determine how resources should be allocated in order to minimize new HIV infections in Swaziland.
Neuronal membrane potential resonance (MPR) is associated with subthreshold and network oscillations. A number of voltage-gated ionic currents can contribute to the generation or amplification of MPR, but how the interaction of these currents with linear currents contributes to MPR is not well understood. We explored this in the pacemaker PD neurons of the crab pyloric network. The PD neuron MPR is sensitive to blockers of H- (IH) and calcium-currents (ICa). We used the impedance profile of the biological PD neuron, measured in voltage clamp, to constrain parameter values of a conductance-based model using a genetic algorithm and obtained many optimal parameter combinations. Unlike most cases of MPR, in these optimal models, the values of resonant- (fres) and phasonant- (fϕ = 0) frequencies were almost identical. Taking advantage of this fact, we linked the peak phase of ionic currents to their amplitude, in order to provide a mechanistic explanation the dependence of MPR on the ICa gating variable time constants. Additionally, we found that distinct pairwise correlations between ICa parameters contributed to the maintenance of fres and resonance power (QZ). Measurements of the PD neuron MPR at more hyperpolarized voltages resulted in a reduction of fres but no change in QZ. Constraining the optimal models using these data unmasked a positive correlation between the maximal conductances of IH and ICa. Thus, although IH is not necessary for MPR in this neuron type, it contributes indirectly by constraining the parameters of ICa.
At our Historically-Black University, about 89% of first-year students place into developmental mathematics, negatively impacting retention and degree completion. In 2012, an NSF-funded learning enrichment project began offering the introductory and developmental mathematics courses on-line over the summer to incoming science, technology, engineering and mathematics (STEM) majors at no cost. Passing rates for the summer on-line classes were around 80%, and students in the on-line classes scored equivalently on the common departmental final exams as students taking the classes in the traditional format. For students who passed the on-line classes, their performance in the following classes (College Algebra and Trigonometry) exceeded that of students who progressed to those courses by taking the traditional series of in-person courses. Three years of data show that students who started college with an on-line mathematics course in a summer bridge program had a higher first year GPA, a better first year retention rate and earned significantly more credits in their first year than the overall population of STEM students. These results suggest that offering introductory mathematics courses on-line as part of a freshman bridge program is an effective, scalable intervention to increase the academic success of students who enter college under-prepared in mathematics. The positive results are particularly exciting since the students in our project were 87% minority.
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