Telling the Agricultural Story

I have regarded your Rueben Brigham Award highly ever since I helped select a recipient for it several years ago

Fast and Accurate Modeling of Molecular Atomization Energies with Machine Learning

We introduce a machine learning model to predict atomization energies of a diverse set of organic molecules, based on nuclear charges and atomic positions only. The problem of solving the molecular Schr\"odinger equation is mapped onto a non-linear statistical regression problem of reduced complexity. Regression models are trained on and compared to atomization energies computed with hybrid density-functional theory. Cross-validation over more than seven thousand small organic molecules yields a mean absolute error of ~10 kcal/mol. Applicability is demonstrated for the prediction of molecular atomization potential energy curves

Virtual screening for PPAR-gamma ligands using the ISOAK molecular graph kernel and gaussian processes

For a virtual screening study, we introduce a combination of machine learning techniques, employing a graph kernel, Gaussian process regression and clustered cross-validation. The aim was to find ligands of peroxisome-proliferator activated receptor gamma (PPAR-y). The receptors in the PPAR family belong to the steroid-thyroid-retinoid superfamily of nuclear receptors and act as transcription factors. They play a role in the regulation of lipid and glucose metabolism in vertebrates and are linked to various human processes and diseases. For this study, we used a dataset of 176 PPAR-y agonists published by Ruecker et al. ..

Gaps and forks in DNA replication: Rediscovering old models

Most current models for replication past damaged lesions envisage that translesion synthesis occurs at the replication fork. However older models suggested that gaps were left opposite lesions to allow the replication fork to proceed, and these gaps were subsequently sealed behind the replication fork. Two recent articles lend support to the idea that bypass of the damage occurs behind the fork. In the first paper, electron micrographs of DNA replicated in UV-irradiated yeast cells show regions of single-stranded DNA both at the replication forks and behind the fork, the latter being consistent with the presence of gaps in the daughter-strands opposite lesions. The second paper describes an in vitro DNA replication system reconstituted from purified bacterial proteins. Repriming of synthesis downstream from a blocked fork occurred not only on the lagging strand as expected, but also on the leading strand, demonstrating that contrary to widely accepted beliefs, leading strand synthesis does not need to be continuous

Response to somatic cell count-based selection for mastitis resistance in a divergent selection experiment in sheep

A divergent selection experiment in sheep was implemented to study the consequences of log-transformed somatic cell score (SCS)-based selection on resistance to natural intramammary infections. Using dams and progeny-tested rams selected for extreme breeding values for SCS, we created 2 groups of ewes with a strong divergence in SCS of approximately 3 genetic standard deviations. A survey of 84 first-lactation ewes of both the High and Low SCS lines indicated favorable responses to SCS-based selection on resistance to both clinical and subclinical mastitis. All clinical cases (n = 5) occurred in the High SCS line. Additionally, the frequency of chronic clinical mastitis,as detected by the presence of parenchymal abscesses, was much greater in the High SCS line (n = 21) than in the Low SCS line (n = 1). According to monthly milk bacterio-logical examinations of udder halves, the prevalence of infection was significantly greater (odds ratio = 3.1) in the High SCS line than in the Low SCS line, with predicted probabilities of 37 and 16%, respectively. The most frequently isolated bacteria responsible for mastitis were staphylococci: Staphylococcus auricularis(42.6% of positive samples), Staphylococcus simulans, Staphylococcus haemoliticus, Staphylococcus xylosus, Staphylococcus chromogenes, Staphylococcus lentus, Staphylococcus warneri, and Staphylococcus aureus. The incidence of positive bacteriology was greater in the High SCS line (39%) than in the Low SCS line (12%)at lambing, indicating that High SCS line ewes were especially susceptible to postpartum subclinical mastitis. Negativation of bacteriological results from one sampling time point to the next was markedly different between lines after weaning (e.g., 41 and 84% in the High and Low SCS lines, respectively). This result was consistent with differences in the duration of infection, which was much greater in the High SCS line compared with the Low SCS line. Finally, ewes from the High SCS line consistently had greater SCS in positive milk samples than did ewes from the Low SCS line (+2.04 SCS, on average), with an especially large difference between lines during the suckling period (+3.42 SCS). Altogether, the preliminary results suggest that the better resistance of Low SCS line ewes, compared with High SCS line ewes, was principally characterized by a better ability to limit infections during the peripartum period, to eliminate infections during lactation, and quantitatively to limit the inflammation process and its clinical consequences

Stage-specific histone modification profiles reveal global transitions in the Xenopus embryonic epigenome.

Vertebrate embryos are derived from a transitory pool of pluripotent cells. By the process of embryonic induction, these precursor cells are assigned to specific fates and differentiation programs. Histone post-translational modifications are thought to play a key role in the establishment and maintenance of stable gene expression patterns underlying these processes. While on gene level histone modifications are known to change during differentiation, very little is known about the quantitative fluctuations in bulk histone modifications during development. To investigate this issue we analysed histones isolated from four different developmental stages of Xenopus laevis by mass spectrometry. In toto, we quantified 59 modification states on core histones H3 and H4 from blastula to tadpole stages. During this developmental period, we observed in general an increase in the unmodified states, and a shift from histone modifications associated with transcriptional activity to transcriptionally repressive histone marks. We also compared these naturally occurring patterns with the histone modifications of murine ES cells, detecting large differences in the methylation patterns of histone H3 lysines 27 and 36 between pluripotent ES cells and pluripotent cells from Xenopus blastulae. By combining all detected modification transitions we could cluster their patterns according to their embryonic origin, defining specific histone modification profiles (HMPs) for each developmental stage. To our knowledge, this data set represents the first compendium of covalent histone modifications and their quantitative flux during normogenesis in a vertebrate model organism. The HMPs indicate a stepwise maturation of the embryonic epigenome, which may be causal to the progressing restriction of cellular potency during development