Measurement of intracellular strain on deformable substrates with texture correlation.

Mechanical stimuli are important factors that regulate cell proliferation, survival, metabolism and motility in a variety of cell types. The relationship between mechanical deformation of the extracellular matrix and intracellular deformation of cellular sub-regions and organelles has not been fully elucidated, but may provide new insight into the mechanisms involved in transducing mechanical stimuli to biological responses. In this study, a novel fluorescence microscopy and image analysis method was applied to examine the hypothesis that mechanical strains are fully transferred from a planar, deformable substrate to cytoplasmic and intranuclear regions within attached cells. Intracellular strains were measured in cells derived from the anulus fibrosus of the intervertebral disc when attached to an elastic silicone membrane that was subjected to tensile stretch. Measurements indicated cytoplasmic strains were similar to those of the underlying substrate, with a strain transfer ratio (STR) of 0.79. In contrast, nuclear strains were much smaller than those of the substrate, with an STR of 0.17. These findings are consistent with previous studies indicating nuclear stiffness is significantly greater than cytoplasmic stiffness, as measured using other methods. This study provides a novel method for the study of cellular mechanics, including a new technique for measuring intranuclear deformations, with evidence of differential magnitudes and patterns of strain transferred from the substrate to cell cytoplasm and nucleus

Accrual-based and real earnings management and political connections

This study examines whether the trade-off between real and accrual-based management strategies differs between firms with and without political connections. We argue that politically connected firms are more likely to substitute real earnings management for accrual-based earnings management than non-connected firms. Although real earnings management is more costly, we expect that politically connected firms prefer this strategy because of its higher secrecy and potential to mask political favors. Using a unique panel data set of 5493 publicly traded firms in 30 countries, our results show that politically connected firms are more likely to substitute real earnings management strategies for accrual-based earnings management strategies than non-connected firms. We also find that when public monitoring and, therefore, the risk of detection increases, politically connected firms are more likely to resort to less detectable real earnings management strategies. Our finding that political connections play a significant role in the choice between accrual-based and real earnings management strategies suggests that focusing only on accrual-based measurements underestimates the total earnings management activities of politically connected firms

MUC5B levels in submandibular gland saliva of patients treated with radiotherapy for head-and-neck cancer: A pilot study

<p>Abstract</p> <p>Background</p> <p>The salivary mucin MUC5B, present in (sero)mucous secretions including submandibular gland (SMG) saliva, plays an important role in the lubrication of the oral mucosa and is thought to be related to the feeling of dry mouth. We investigated if MUC5B levels in SMG saliva could distinguish between the presence or absence of severe dry mouth complaints 12 months after radiotherapy (RT) for head-and-neck cancer (HNC).</p> <p>Findings</p> <p>Twenty-nine HNC patients with a residual stimulated SMG secretion rate of ≥0.2 ml/10 min at 12 months after RT were analyzed. MUC5B (in U; normalized to 1) and total protein levels (mg/ml) were measured in SMG saliva at baseline and 12 months after RT using ELISA and BCA protein assay, respectively. Overall, median MUC5B levels decreased after RT from 0.12 to 0.03 U (<it>p</it> = 0.47). Patients were dichotomized into none/mild xerostomia (n = 12) and severe xerostomia (n = 17) based on a questionnaire completed at 12 months. SMG and whole saliva flow rates decreased after RT but were comparable in both groups. The median MUC5B level was higher in patients with no or mild xerostomia compared to patients with severe xerostomia (0.14 vs 0.01 U, <it>p</it> = 0.22). Half of the patients with severe xerostomia had no detectable MUC5B at 12 months after RT. No differences in total protein levels were observed.</p> <p>Conclusions</p> <p>Qualitative saliva parameters like MUC5B need further investigation in RT-induced xerostomia. This pilot study showed a trend towards lower MUC5B levels in the SMG saliva of patients with severe xerostomia 12 months after RT for HNC.</p

Consequences of perinatal treatment with l-arginine and antioxidants for the renal transcriptome in spontaneously hypertensive rats

Treating spontaneously hypertensive rats (SHR) with l-arginine, taurine, and vitamins C and E (ATCE) during nephrogenesis (2 weeks before to 4 weeks after birth) persistently lowers blood pressure. Hypothetically, differential gene expression in kidney of SHR vs. normotensive Wistar–Kyoto rats (WKY) is partially corrected by maternal ATCE in SHR. Differential gene expression in 2-days, 2-weeks, and 48-week-old rats was studied using oligonucleotide chips. Transcription factor binding sites (TFBS) of differentially expressed genes were analyzed in silico. Differential gene expression varied between SHR+ATCE and SHR, suggesting both direct and indirect effects; but, few genes were modulated toward WKY level and there was little overlap between ages. TFBS analysis suggests less Elk-1-driven gene transcription in both WKY and SHR+ATCE vs. SHR at 2 days and 2 weeks. Concluding, in SHR, persistent antihypertensive effects of maternal ATCE are not primarily due to persistent corrective transcription. Less Elk-1-driven transcription at 2 days and 2 weeks may be involved

The global bacterial regulator H-NS promotes transpososome formation and transposition in the Tn5 system

The histone-like nucleoid structuring protein (H-NS) is an important regulator of stress response and virulence genes in gram-negative bacteria. In addition to binding regulatory regions of genes in a structure-specific manner, H-NS also binds in a structure-specific manner to sites in the Tn10 transpososome, allowing it to act as a positive regulator of Tn10 transposition. This is the only example to date of H-NS regulating a transposition system by interacting directly with the transposition machinery. In general, transposition complexes tend to include segments of deformed DNA and given the capacity of H-NS to bind such structures, and the results from the Tn10 system, we asked if H-NS might regulate another transposition system (Tn5) by directly binding the transposition machinery. We show in the current work that H-NS does bind Tn5 transposition complexes and use hydroxyl radical footprinting to characterize the H-NS interaction with the Tn5 transpososome. We also show that H-NS can promote Tn5 transpososome formation in vitro, which correlates with the Tn5 system showing a dependence on H-NS for transposition in vivo. Taken together the results suggest that H-NS might play an important role in the regulation of many different bacterial transposition systems and thereby contribute directly to lateral gene transfer

Evaluation of energy and dietary intake estimates from a food frequency questionnaire using independent energy expenditure measurement and weighed food records

<p>Abstract</p> <p>Background</p> <p>We have developed a food frequency questionnaire (FFQ) for the assessment of habitual diet, with special focus on the intake of fruit, vegetables and other antioxidant-rich foods and beverages. The aim of the present study was to evaluate the relative validity of the intakes of energy, food and nutrients from the FFQ.</p> <p>Methods</p> <p>Energy intake was evaluated against independent measures of energy expenditure using the ActiReg^®system (motion detection), whereas 7-days weighed food records were used to study the relative validity of food and nutrient intake. The relationship between methods was investigated using correlation analyses and cross-classification of participants. The visual agreement between the methods was evaluated using Bland-Altman plots.</p> <p>Results</p> <p>We observed that the FFQ underestimated the energy intake by approximately 11% compared to the energy expenditure measured by the ActiReg^®. The correlation coefficient between energy intake and energy expenditure was 0.54 and 32% of the participants were defined as under-reporters. Compared to the weighed food records the percentages of energy from fat and added sugar from the FFQ were underestimated, whereas the percentage of energy from total carbohydrates and protein were slightly overestimated. The intake of foods rich in antioxidants did not vary significantly between the FFQ and weighed food records, with the exceptions of berries, coffee, tea and vegetables which were overestimated. Spearman's Rank Order Correlations between FFQ and weighed food records were 0.41 for berries, 0.58 for chocolate, 0.78 for coffee, 0.61 for fruit, 0.57 for fruit and berry juices, 0.40 for nuts, 0.74 for tea, 0.38 for vegetables and 0.70 for the intake of wine.</p> <p>Conclusions</p> <p>Our new FFQ provides a good estimate of the average energy intake and it obtains valid data on average intake of most antioxidant-rich foods and beverages. Our study also showed that the FFQs ability to rank participants according to intake of total antioxidants and most of the antioxidant-rich foods was good.</p

Classical nitriding of heat treatable steel

Thermochemical Surface Engineering of Steels provides a comprehensive scientific overview of the principles and different techniques involved in thermochemical surface engineering, including thermodynamics, kinetics principles, process technologies and techniques for enhanced performance of steel

Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed