PKA17-A Coarse-Grain Grid-Based Methodology and Web-Based Software for Predicting Protein pK a Shifts.

We have developed and tested PKA17, a coarse-grain grid-based model for predicting protein pK a shifts. Our pK a predictor is currently deployed via a website interface. We have carried out parameter fitting using 442 Asp, Glu, His, Lys, and Arg residues for which experimental results are available in the literature. PROPKA software has been used for benchmarking. The average unsigned error and root-mean-square deviation (RMSD) have been found to be 0.628 and 0.831 pH units, respectively, for PKA17. The corresponding results with PROPKA are 0.761 and 1.063 units. We have assessed the robustness of the developed PKA17 methodology with a number of tests and have also explored the possibility of using a combination of PROPKA and PKA17 calculations in order to improve the accuracy of predicted pK a values for protein residues. We have also once again confirmed that protein acidity constants are influenced almost entirely by residues in the immediate spatial proximity of the ionizable amino acids. The resulting PKA17 software has been deployed online with a web-based interface at http://users.wpi.edu/~jpcvitkovic/pka_calc.html. © 2019 Wiley Periodicals, Inc.

Dietary Intake of Pregnant Women with and without Inflammatory Bowel Disease in the United States.

BACKGROUND: Pregnancy is a vulnerable time where the lives of mother and baby are affected by diet, especially high-risk pregnancies in women with inflammatory bowel disease (IBD). Limited research has examined diet during pregnancy with IBD. AIMS: Describe and compare the diet quality of pregnant women with and without IBD, and examine associations between dietary intake and guidelines during pregnancy. METHODS: Three 24 h recalls were utilized to assess the diets of pregnant women with IBD (n = 88) and without IBD (n = 82) during 27-29 weeks of gestation. A customized frequency questionnaire was also administered to measure pre- and probiotic foods. RESULTS: Zinc intake (p = 0.02), animal protein (g) (p = 0.03), and ounce equivalents of whole grains (p = 0.03) were significantly higher in the healthy control (HC) group than the IBD group. Nutrients of concern with no significant differences between groups included iron (3% IBD and 2% HC met the goals), saturated fat (only 1% of both groups met the goals), choline (23% IBD and 21% HC met the goals), magnesium (38% IBD and 35% HC met the goals), calcium (48% IBD and 60% HC met the goals), and water intake (49% IBD and 48% HC met the goals). CONCLUSIONS: Most pregnant women in this cohort fell short of the dietary nutrients recommended in pregnancy, especially concerning for women with IBD.

Diverged morphology changes of astrocytic and neuronal primary cilia under reactive insults.

Primary cilia are centriole-derived sensory organelles that are present in most mammalian cells, including astrocytes and neurons. Evidence is emerging that astrocyte and neuronal primary cilia demonstrate a dichotomy in the mature mouse brain. However, it is unknown how astrocytic and neuronal primary cilia change their morphology and ciliary proteins when exposed to reactive insults including epilepsy and traumatic brain injury. We used a double transgenic mouse strain (Arl13b-mCherry; Centrin2-GFP), in which we found spontaneous seizures, and a cortical injury model to examine the morphological changes of astrocytic and neuronal primary cilia under reactive conditions. Transgenic overexpression of Arl13b drastically increases the length of astrocytic and neuronal primary cilia in the hippocampus, as well as the cilia lengths of cultured astrocytes and neurons. Spontaneous seizures shorten Arl13b-positive astrocytic cilia and AC3-positive neuronal cilia in the hippocampus. In a cortical injury model, Arl13b is not detectable in primary cilia, but Arl13b protein relocates to the cell body and has robust expression in the proximity of injured tissues. In contrast, the number of AC3-positive cilia near injured tissues remains unchanged, but their lengths become shorter. These results on astrocytic cilia implicate Arl13b in regulating astrocyte proliferation and tissue regeneration, while the shortening of AC3-positive cilia suggests adaptive changes of neuronal primary cilia under excitotoxicity.