The Predictive Nature of Individual Differences in Early Associative Learning and Emerging Social Behavior

Across the first year of life, infants achieve remarkable success in their ability to interact in the social world. The hierarchical nature of circuit and skill development predicts that the emergence of social behaviors may depend upon an infant's early abilities to detect contingencies, particularly socially-relevant associations. Here, we examined whether individual differences in the rate of associative learning at one month of age is an enduring predictor of social, imitative, and discriminative behaviors measured across the human infant's first year. One-month learning rate was predictive of social behaviors at 5, 9, and 12 months of age as well as face-evoked discriminative neural activity at 9 months of age. Learning was not related to general cognitive abilities. These results underscore the importance of early contingency learning and suggest the presence of a basic mechanism underlying the ontogeny of social behaviors

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Sexual Dimorphism in MAPK-Activated Protein Kinase-2 (MK2) Regulation of RANKL-Induced Osteoclastogenesis in Osteoclast Progenitor Subpopulations

<div><p>Osteoclasts (OCs) are bone-resorptive cells critical for maintaining skeletal integrity through coupled bone turnover. OC differentiation and activation requires receptor activator of NF-kB ligand (RANKL) signaling through the p38 MAPK pathway. However the role of the p38 MAPK substrate, MAPK-activated protein kinase 2 (MK2), is not clearly delineated. Within the bone marrow exists a specific subpopulation of defined osteoclast progenitor cells (dOCPs) with surface expression of B220^-Gr1^-CD11b^lo/-CD115⁺(dOCP^lo/-). In this study, we isolated dOCPs from male and female mice to determine sex-specific effects of MK2 signaling in osteoclastogenesis (OCgen). Male <i>Mk2^-/-</i> mice display an increase in the dOCP^lo cell population when compared to <i>Mk2^+/+</i> mice, while female <i>Mk2^-/-</i> and <i>Mk2^+/+</i> mice exhibit no difference. Defined OCPs from male and female <i>Mk2^+/+</i> and <i>Mk2^-/-</i> bone marrow were treated with macrophage colony stimulation factor (M-CSF) and RANKL cytokines to promote OCgen. RANKL treatment of dOCP^lo cells stimulated p38 and MK2 phosphorylation. Tartrate-resistant acid phosphatase (TRAP) assays were used to quantify OC number, size, and TRAP enzyme activity post-RANKL stimulation. MK2 signaling was critical for male dOCP^lo OCgen, yet MK2 signaling regulated OCgen from female dOCP^- and CD11b^hi subpopulations as well. The functional gene, <i>Ctsk</i>, was attenuated in both male and female <i>Mk2^-/-</i> dOCP^lo-derived OCs. Conversely, MK2 signaling was only critical for gene expression of pre-OC fusion genes, <i>Oc-stamp</i> and<i>Tm7sf4</i>, in male OCgen. Therefore, these data suggest there is a sexual dimorphism in MK2 signaling of OCP subpopulations.</p></div

MK2 signaling differentially regulates osteoclast size and number from defined OCP cells.

<p>Cells were fixed, TRAP stained, and visualized by light microscopy. (A) Representative 100x images of female (top) and male (bottom) mouse bone marrow cells defined by CD11b surface expression driven to form osteoclasts (OCs) with M-CSF (25ng/mL) and RANKL (50 ng/mL). Female OCs (black arrow) were magnified 3x and inset (top). TRAP positive cells with three or more nuclei (OCs) from (B) female and (C) male mice were enumerated from three random images at days 3 (top) and 5 (bottom) of RANKL treatment. Osteoclast size from female (B, right) and male (C, right) was measured by pixels per osteoclast using Adobe PhotoShop CS. Data are expressed as means ± SE compared to <i>Mk2</i>^<i>+/+</i> controls (*<i>P</i>≤0.05, **<i>P</i>≤0.01, ***<i>P</i>≤0.001).</p

MK2 deficiency does not regulate NFATc1 colocalization.

<p>(A) Representative confocal images of male dOCP^<i>lo</i> cells treated with M-CSF (control) or M-CSF and RANKL for 30 minutes. A 3x magnified portion of p-p38 was inset (middle,left). (B) Pearson’s r correlation coefficients for NFATc1 and DAPI colocalization. (C) Pearson’s r correlation coefficients for p-p38 and DAPI colocalization. (D) Pearson’s r correlation coefficients for NFATc1 and p-p38 colocalization. Data are expressed as means ± SE compared to <i>Mk2</i>^<i>+/+</i> controls (*<i>P</i>≤0.05).</p

RANKL stimulates MK2 phosphorylation in dOCP^<i>lo</i> pre-osteoclasts.

<p>(A) Representative western blot of pre-osteoclasts from male mice primed with M-CSF (10 ng/mL) for two days and stimulated with RANKL (100 ng/mL) for the indicated minutes (min). Densiometric analysis of (B) p38 (left) and (C) p-p38 (right) as a percent of GAPDH. Data are expressed as means ± SE compared to <i>Mk2</i>^<i>+/+</i> controls (*<i>P</i>≤0.05).</p

MK2 signaling regulates osteoclast fusion genes from male mice during osteoclast maturation.

<p>(A-D) Cells were treated as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125387#pone.0125387.g001" target="_blank">Fig 1</a> for three days. Gene expression was determined by RT-qPCR in osteoclasts from (A) female and (B) male mice. (C) TRAP activity was assessed in female (left) and male (right) osteoclasts on day 3 and 5 post M-CSF and RANKL stimulation using the Takara TRACP Kit. (D) Nuclei were enumerated in female (left) and male (right) in osteoclasts, defined as TRAP positive cells with three or more nuclei. Data are expressed as means ± SE (*<i>P</i>≤0.05, **<i>P</i>≤0.01, ***<i>P</i>≤0.001).</p

Ablation of MK2 increases dOCP^lo cells in male mice, but not female mice.

<p>(A) Representative flow cytometry of bone marrow from male and female <i>Mk2</i>^<i>+/+</i> and <i>Mk2</i>^<i>-/-</i> mice. (B) Enumeration of Gr-1^-CD11b^lo cells as a percent of the hematopoietic stem cell population (HSC, top) and CD115+ as a percent of Gr-1^-CD11b^<i>lo</i> cells (bottom). (C) Enumeration of CD11b surface expression in female (left) and male (right) mouse bone marrow cells. Data are expressed as means ± SE compared to <i>Mk2</i>^<i>+/+</i> controls (*<i>P</i>≤0.05).</p

Do cultural tourism firms perform better than their rivals?

Previous studies assume that cultural tourism attract higher socioeconomic groups with higher cultural capital. Accordingly, most cultural tourists are regarded and described as ‘‘up-scaled’’ (mature aged with high education and high income earnings). Bearing this in mind, it might be expected that firms operating in cultural tourism activities earn higher profits and perform better than other kinds of tourism activities. Since there are differences in firm performance, within countries, that are not captured by national aggregates, this paper performs a financial analysis of cultural tourism firms operating in Northern Portugal in 2002-2017 and compares their financial performance with other kinds of tourism firms. Firm level data are collected from the National Tourism Registry and SABI databases. Firms operating in more than one tourism typology were withdrawn. From the registered 732 firms, 74% operate exclusively in cultural tourism, 17% in nautical tourism and 9% operate in nature/adventure tourism. A set of indicators of profitability and financial structure and leverage are applied to a sample of 386 firms. Results show that firms operating in cultural tourism activities have higher average profits, make a more efficient usage of investors’ funds and display a better liquidity position, though the analysis across business cycles appear to indicate that these firms are more vulnerable to periods of crisis and expansion than the remaining tourism firms. Also, the analysis for larger firms shows that cultural tourism firms display better financial structures.info:eu-repo/semantics/publishedVersio