MODULATION OF PROTEIN DYNAMICS BY LIGAND BINDING AND SOLVENT COMPOSITION

Many proteins undergo conformational switching in order to perform their cellular functions. A multitude of factors may shift the energy landscape and alter protein dynamics with varying effects on the conformations they explore. We apply atomistic molecular dynamics simulations to a variety of biomolecular systems in order to investigate how factors such as pressure, the chemical environment, and ligand binding at distant binding pockets affect the structure and dynamics of these protein systems. Further, we examine how such changes should be characterized. We first investigate how pressure and solvent modulate ligand access to the active site of a bacterial lipase by probing the dynamics in a variety of pressures and DMSO-water solvent mixtures. By measuring the gorge leading to the binding pocket we find small amounts of DMSO and high atmospheric pressure optimize the ability of lipids to reach the catalytic interior. Next, we examine the allosteric mechanism behind cooperative and anti-cooperative binding of nuclear hormone receptor RXR and two of its binding partners (TR and CAR). We detail why ligands of the RXR:TR (9c and t3) complex bind anti-cooperatively while ligands of RXR:CAR (9c and tcp) bind cooperatively. Finally, we describe how an intrinsically disordered protein, α-synuclein, alters its conformational dynamics in a pH-dependent manner increasing the likelihood of pathogenic aggregation and neurodegenerative disease at low pH. In each case, we apply contact analysis to uncover the collective motions underlying conformational change triggered by environmental factors or ligand binding

Infiltration and short-term movement of nitrogen in a silt-loam soil typical of rice cultivation in Arkansas

Rice production in Arkansas is one of the top three crop commodities in terms of cash receipts. Researchers and farmers report that nitrogen (N) needs to be managed according to a variety of factors with two important ones being soil and fertilizer type. The objectives of this experiment were to determine: 1) the degree to which floodwater-incorporated N applied as urea or as ammonium sulfate infiltrates intact cores (7.2-cm dia., 10-cm depth) containing DeWitt siltloam soil, and 2) the distribution of N during 12 h of ponding. Inorganic-N concentrations were analyzed at 2-cm depth intervals in cores following removal of the flood. Nitrogen from applied fertilizer was recovered as ammonium. Ammonium sulfate-N remained in the top 4 cm of soil with concentrations of 375 µg N g-1 in the surface 2 cm and 300 µg N g-1 at the 2 - 4 cm depth after 12 hr of ponding. At all depth intervals below 4 cm, ammonium sulfate-N remained below 30 µg N g-1. In contrast, after 12 h of ponding, N in soil receiving urea was 105 µg N g-1 in the top 2 cm and 173 µg N g-1 at 2-4 cm. At 4-6, 6-8, and 8-10 cm, N was 109, 108, and 35 µg N g-1, respectively, after 12 h of ponding. These results demonstrate immediate and deeper movement of ammonium into silt loam soil receiving urea as compared to ammonium sulfate, demonstrating how the form of N in fertilizer affects its movement into the soil profile

Why would a special FM process exist in adults, when it does not appear to exist in children?

Cooper Greve, and Henson (this issue)  caution restraint before accepting that a fast mapping (FM) process exists in adults. We welcome this, but would also add that the original rationale for studying FM in adults is not currently supported by developmental research. Despite the claims of several adult FM researchers, there is little evidence from developmental word learning research for a special hippocampus-independent FM process critical for children’s word learning

Breed-specific SNP and genomic regions associated with equine recurrent exertional rhabdomyolysis susceptibility overlapping withup- and down-regulatory histone modifications

Recurrent exertional rhabdomyolysis (RER) is a myopathy characterised by episodes of exercise-induced myofibre necrosis, muscle stiffness and fasciculations, with extreme cases resulting in kidney failure or death. There is a genetic component attributed to RER1-3, but specific causative genes and mutations have not been identified. Due to the disease’s metabolic nature, we hypothesised that regulatory regions of the genome may be implicated4. We aimed to identify genetic markers for RER in Thoroughbreds (TB), Warmbloods (WB) and Connemara ponies (CP). Since many of these were located in non-coding regions we compared their location with peaks in the publicly-available equine ChIP-seq data obtained from the FAANG portal5.33 CP (17 cases, 16 controls) and 94 WB (50 cases, 44 controls) were genotyped using a 670k genotyping array. GWAS, regional heritability mapping (RHM) and FST analyses were thenrun both across and within breeds. Various window sizes around significant and suggestive markers from these analyses, and 26 previously-identified US TB RER markers2 re-mapped to EquCab3.0, were compared to locations of histone markers identified in longissimus dorsi samples from two horses in the FAANG data using bedtools. No ChIP-seq peaks directly overlapped TB QTLs, but 6 in CPs and 2 in WBs overlapped with significant and suggestive significant SNPs for RER susceptibility. Within 10 kb of TB QTLs there were significantly fewer H3K27me3 and more H3K4me3 peaks than expected, whilst WB RHM regions contained significantly more H3K27me3 peaks and fewer H3K4me1 peaks than expected. No Bonferroni-corrected significant differences were identified in CP alone. <br/

Trends in the Black-White Achievement Gap:Clarifying the Meaning of Within- and Between-School Achievement Gaps

We decompose black-white achievement gap trends between 1971 and 2004 into trends in within- and between-school differences. We show that the previous finding that narrowing within-school inequality explains most of the decline in the black-white achievement gap between 1971 and 1988 is sensitive to methodology. Employing a more detailed partition of achievement differences, we estimate that 40 percent of the narrowing of the gap through the 1970s and 1980s is attributable to the narrowing of within-school differences between black and white students. Further, the consequences for achievement of attending a high minority school became increasingly deleterious between 1971 and 1999.