Optimizing end-labeled free-solution electrophoresis by increasing the hydrodynamic friction of the drag-tag

We study the electrophoretic separation of polyelectrolytes of varying lengths by means of end-labeled free-solution electrophoresis (ELFSE). A coarse-grained molecular dynamics simulation model, using full electrostatic interactions and a mesoscopic Lattice Boltzmann fluid to account for hydrodynamic interactions, is used to characterize the drag coefficients of different label types: linear and branched polymeric labels, as well as transiently bound micelles. It is specifically shown that the label's drag coefficient is determined by its hydrodynamic size, and that the drag per label monomer is largest for linear labels. However, the addition of side chains to a linear label offers the possibility to increase the hydrodynamic size, and therefore the label efficiency, without having to increase the linear length of the label, thereby simplifying synthesis. The third class of labels investigated, transiently bound micelles, seems very promising for the usage in ELFSE, as they provide a significant higher hydrodynamic drag than the other label types. The results are compared to theoretical predictions, and we investigate how the efficiency of the ELFSE method can be improved by using smartly designed drag-tags.Comment: 32 pages, 11 figures, submitted to Macromolecule

Casein Kinase 1 Proteomics Reveal Prohibitin 2 Function in Molecular Clock

Throughout the day, clock proteins synchronize changes in animal physiology (e.g., wakefulness and appetite) with external cues (e.g., daylight and food). In vertebrates, both casein kinase 1 delta and epsilon (CK1δ and CK1ε) regulate these circadian changes by phosphorylating other core clock proteins. In addition, CK1 can regulate circadian-dependent transcription in a non-catalytic manner, however, the mechanism is unknown. Furthermore, the extent of functional redundancy between these closely related kinases is debated. To further advance knowledge about CK1δ and CK1ε mechanisms of action in the biological clock, we first carried out proteomic analysis of both kinases in human cells. Next, we tested interesting candidates in a cell-based circadian readout which resulted in the discovery of PROHIBITIN 2 (PHB2) as a modulator of period length. Decreasing the expression of PHB2 increases circadian-driven transcription, thus revealing PHB2 acts as an inhibitor in the molecular clock. While stable binding of PHB2 to either kinase was not detected, knocking down CK1ε expression increases PHB2 protein levels and, unexpectedly, knocking down CK1δ decreases PHB2 transcript levels. Thus, isolating CK1 protein complexes led to the identification of PHB2 as an inhibitor of circadian transcription. Furthermore, we show that CK1δ and CK1ε differentially regulate the expression of PHB2

Inverse association of colorectal cancer prevalence to serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in a large Appalachian population

Background Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the development and progression of colorectal cancer (CRC). However, the link between these compounds and CRC remains unknown. In this cross-sectional study, we investigated the association of CRC diagnosis to PFOA and PFOS blood levels in a large Appalachian population. Methods Participants were 47,359 adults ≥ 21 years of age and residing in six PFOA-contaminated water districts in the mid-Ohio Valley (N = 47,151 cancer-free adults, 208 cases of primary CRC). All participants completed a comprehensive health survey between 2005 and 2006; serum levels of PFOA, PFOS, and a range of other blood markers were also measured. Medical history was assessed via self report and cancer diagnosis confirmed via chart review. Results CRC showed a strong inverse, dose–response association with PFOS serum levels (odds ratio (OR) adjusted for potential confounders = 0.2, 95% confidence interval (CI) 0.2,0.3) for highest vs. lowest quartile of PFOS, P-trend \u3c 0.00001) and a significant, but more modest inverse association with PFOA (adjusted OR = 0.6 (CI 0.4, 0.9) for highest vs. lowest quartile, P-trend = 0.001). These inverse associations were stronger in those diagnosed within the previous 6 years and resident in the same water district for a minimum of 10–15 years preceding assessment. The relationship between PFOA and CRC was also more pronounced in men and leaner adults, and showed a stronger linear trend at lower exposure levels. Conclusions In this large cross-sectional study, we found a strong, inverse association between PFOS and likelihood of CRC diagnosis and a significant, although more modest inverse association between PFOA and CRC. If confirmed in prospective investigations, these findings may aid in identifying new strategies for CRC prevention and treatment and inform future studies regarding mechanisms underlying CRC pathogenesis

Social disparities in exposures to bisphenol A and polyfluoroalkyl chemicals: a cross-sectional study within NHANES 2003-2006

<p>Abstract</p> <p>Background</p> <p>Bisphenol A (BPA) and polyfluoroalkyl chemicals (PFCs) are suspected endocrine disrupting compounds known to be ubiquitous in people's bodies. Population disparities in exposure to these chemicals have not been fully characterized.</p> <p>Methods</p> <p>We analyzed data from the 2003-2006 National Health and Nutrition Examination Survey. Using multivariable linear regression we examined the association between urinary concentrations of BPA, serum concentrations of four PFCs, and multiple measures of socioeconomic position (SEP): family income, education, occupation, and food security. We also examined associations with race/ethnicity.</p> <p>Results</p> <p>All four PFCs were positively associated with family income, whereas BPA was inversely associated with family income. BPA concentrations were higher in people who reported very low food security and received emergency food assistance than in those who did not. This association was particularly strong in children: 6-11 year-olds whose families received emergency food had BPA levels 54% higher (95% CI, 13 to 112%) than children of families who did not. For BPA and PFCs we saw smaller and less consistent associations with education and occupation. Mexican Americans had the lowest concentrations of any racial/ethnic group of both types of chemicals; for PFCs, Mexican Americans not born in the U.S. had much lower levels than those born in the U.S.</p> <p>Conclusions</p> <p>People with lower incomes had higher body burdens of BPA; the reverse was true for PFCs. Family income with adjustment for family size was the strongest predictor of chemical concentrations among the different measures of SEP we studied. Income, education, occupation, and food security appear to capture different aspects of SEP that may be related to exposure to BPA and PFCs and are not necessarily interchangeable as measures of SEP in environmental epidemiology studies. Differences by race/ethnicity were independent of SEP.</p

MLL2 Is Required in Oocytes for Bulk Histone 3 Lysine 4 Trimethylation and Transcriptional Silencing

Conditional knockout mouse strategies identify the histone methyltranferase MLL2 as a key player in epigenetic reprogramming of female gametes

Urinary bisphenol A concentrations in girls from rural and urban Egypt: a pilot study

Abstract Background Exposure to endocrine active compounds, including bisphenol A (BPA), remains poorly characterized in developing countries despite the fact that behavioral practices related to westernization have the potential to influence exposure. BPA is a high production volume chemical that has been associated with metabolic dysfunction as well as behavioral and developmental effects in people, including children. In this pilot study, we evaluate BPA exposure and assess likely pathways of exposure among girls from urban and rural Egypt. Methods We measured urinary concentrations of total (free plus conjugated) species of BPA in spot samples in urban (N = 30) and rural (N = 30) Egyptian girls, and compared these concentrations to preexisting data from age-matched American girls (N = 47) from the U.S. National Health and Nutrition Examination Survey (NHANES). We also collected anthropometric and questionnaire data regarding food storage behaviors to assess potential routes of exposure. Results Urban and rural Egyptian girls exhibited similar concentrations of urinary total BPA, with median unadjusted values of 1.00 and 0.60 ng/mL, respectively. Concentrations of urinary BPA in this group of Egyptian girls (median unadjusted: 0.70 ng/mL) were significantly lower compared to age-matched American girls (median unadjusted: 2.60 ng/mL) according to NHANES 2009-2010 data. Reported storage of food in plastic containers was a significant predictor of increasing concentrations of urinary BPA. Conclusions Despite the relatively low urinary BPA concentrations within this Egyptian cohort, the significant association between food storage behaviors and increasing urinary BPA concentration highlights the need to understand food and consumer product patterns that may be closing the gap between urban and rural lifestyles.http://deepblue.lib.umich.edu/bitstream/2027.42/112495/1/12940_2011_Article_523.pd

Stable transmission of reversible modifications: maintenance of epigenetic information through the cell cycle

Even though every cell in a multicellular organism contains the same genes, the differing spatiotemporal expression of these genes determines the eventual phenotype of a cell. This means that each cell type contains a specific epigenetic program that needs to be replicated through cell divisions, along with the genome, in order to maintain cell identity. The stable inheritance of these programs throughout the cell cycle relies on several epigenetic mechanisms. In this review, DNA methylation and histone methylation by specific histone lysine methyltransferases (KMT) and the Polycomb/Trithorax proteins are considered as the primary mediators of epigenetic inheritance. In addition, non-coding RNAs and nuclear organization are implicated in the stable transfer of epigenetic information. Although most epigenetic modifications are reversible in nature, they can be stably maintained by self-recruitment of modifying protein complexes or maintenance of these complexes or structures through the cell cycle

Global baryon number conservation encoded in net-proton fluctuations measured in Pb–Pb collisions at √sNN = 2.76 TeV

Experimental results are presented on event-by-event net-proton fluctuation measurements in Pb–Pb collisions at √SNN=2.76 TeV, recorded by the ALICE detector at the CERN LHC. These measurements have as their ultimate goal an experimental test of Lattice QCD (LQCD) predictions on second and higher order cumulants of net-baryon distributions to search for critical behavior near the QCD phase boundary. Before confronting them with LQCD predictions, account has to be taken of correlations stemming from baryon number conservation as well as fluctuations of participating nucleons. Both effects influence the experimental measurements and are usually not considered in theoretical calculations. For the first time, it is shown that event-by-event baryon number conservation leads to subtle long-range correlations arising from very early interactions in the collisions.publishedVersio

Search for a common baryon source in high-multiplicity pp collisions at the LHC

We report on the measurement of the size of the particle-emitting source from two-baryon correlations with ALICE in high-multiplicity pp collisions at s=13 TeV. The source radius is studied with low relative momentum p–p, p‾–p‾, p–Λ, and p‾–Λ‾ pairs as a function of the pair transverse mass mT considering for the first time in a quantitative way the effect of strong resonance decays. After correcting for this effect, the radii extracted for pairs of different particle species agree. This indicates that protons, antiprotons, Λ s, and Λ‾ s originate from the same source. Within the measured mT range (1.1–2.2) GeV/c2the invariant radius of this common source varies between 1.3 and 0.85 fm. These results provide a precise reference for studies of the strong hadron–hadron interactions and for the investigation of collective properties in small colliding systems. © 2020 CERN for the benefit of the ALICE CollaborationPeer reviewe