Miracle-dz/UniFAR-FTUs huggingface dataset:
Bradykinin stimulates the ERK→Elk-1→Fos/AP-1 pathway in mesangial cells.

Among its diverse biological actions, the vasoactive peptide bradykinin (BK) induces the transcription factor AP-1 and proliferation of mesangial cells (S. S. El-Dahr, S. Dipp, I. V. Yosipiv, and W. H. Baricos. Kidney Int. 50: 1850-1855, 1996). In the present study, we examined the role of protein tyrosine phosphorylation and the mitogen-activated protein kinases, ERK1/2,in mediating BK-induced AP-1 and DNA replication in cultured rat mesangial cells. BK (10-9 to 10-7 M) stimulated a rapid increase in tyrosine phosphorylation of multiple proteins with an estimated molecular mass of 120-130, 90-95, and 44-42 kDa. Immunoblots using antibodies specific for ERK or tyrosine-phosphorylated ERK revealed a shifting of p42 ERK2 to a higher molecular weight that correlated temporally with an increase in tyrosine-phosphorylated ERK2. Genistein, a specific tyrosine kinase inhibitor, prevented the phosphorylation of ERK2 by BK. In-gel kinase assays indicated that BK-induced tyrosine phosphorylation of ERK2 is accompanied by fourfold activation of its phosphotransferase activity toward the substrate PHAS-I ( P < 0.05). Furthermore, BK stimulated a 2.5-fold increase ( P < 0.05) in phosphorylation of Elk-1, a transcription factor required for growth factor-induced c-fos transcription. In accord with the stimulation of Elk-1 phosphorylation, BK induced c-fos gene expression and the production of Fos/AP-1 complexes. In addition, thymidine incorporation into DNA increased twofold ( P < 0.05) following BK stimulation. Each of these effects was blocked by tyrosine kinase inhibition with genistein or herbimycin A. Similarly, antisense oligodeoxynucleotide targeting of ERK1/2 mRNA inhibited BK-stimulated DNA synthesis. In contrast, protein kinase C inhibition or depletion had no effect on BK-induced c-fos mRNA, AP-1-DNA binding activity, or DNA synthesis. Collectively, these data demonstrate that BK activates the ERK→Elk-1→AP-1 pathway and that BK mitogenic signaling is critically dependent on protein tyrosine phosphorylation.
Role of Titin Missense Variants in Dilated Cardiomyopathy

Background The titin gene (TTN) encodes the largest human protein, which plays a central role in sarcomere organization and passive myocyte stiffness. TTN truncating mutations cause dilated cardiomyopathy (DCM); however, the role of TTN missense variants in DCM has been difficult to elucidate because of the presence of background TTN variation. Methods and Results A cohort of 147 DCM index subjects underwent DNA sequencing for 313 TTN exons covering the N2B and N2BA cardiac isoforms of TTN. Of the 348 missense variants, we identified 44 “severe” rare variants by using a bioinformatic filtering process in 37 probands. Of these, 5 probands were double heterozygotes (additional variant in another DCM gene) and 7 were compound heterozygotes (2 TTN “severe” variants). Segregation analysis allowed the classification of the “severe” variants into 5 “likely” (cosegregating), 5 “unlikely” (noncosegregating), and 34 “possibly” (where family structure precluded segregation analysis) disease‐causing variants. Patients with DCM carrying “likely” or “possibly” pathogenic TTN “severe” variants did not show a different outcome compared with “unlikely” and noncarriers of a “severe” TTN variant. However, the “likely” and “possibly” disease‐causing variants were overrepresented in the C‐zone of the A‐band region of the sarcomere. Conclusions TTN missense variants are common and present a challenge for bioinformatic classification, especially when informative families are not available. Although DCM patients carrying bioinformatically “severe” TTN variants do not appear to have a worse clinical course than noncarriers, the nonrandom distribution of “likely” and “possibly” disease‐causing variants suggests a potential biological role for some TTN missense variants.
Reward sensitivity, impulse control, and social cognition as mediators of the link between childhood family adversity and externalizing behavior in eight countries

Abstract Using data from 1,177 families in eight countries (Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States), we tested a conceptual model of direct effects of childhood family adversity on subsequent externalizing behaviors as well as indirect effects through psychological mediators. When children were 9 years old, mothers and fathers reported on financial difficulties and their use of corporal punishment, and children reported perceptions of their parents’ rejection. When children were 10 years old, they completed a computerized battery of tasks assessing reward sensitivity and impulse control and responded to questions about hypothetical social provocations to assess their hostile attributions and proclivity for aggressive responding. When children were 12 years old, they reported on their externalizing behavior. Multigroup structural equation models revealed that across all eight countries, childhood family adversity had direct effects on externalizing behaviors 3 years later, and childhood family adversity had indirect effects on externalizing behavior through psychological mediators. The findings suggest ways in which family-level adversity poses risk for children's subsequent development of problems at psychological and behavioral levels, situated within diverse cultural contexts.
Body movement and physical activity energy expenditure in children and adolescents: how to adjust for differences in body size and age.

BACKGROUND Physical activity data in children and adolescents who differ in body size and age are influenced by whether physical activity is expressed in terms of body movement or energy expenditure. OBJECTIVE We examined whether physical activity expressed as body movement (ie, accelerometer counts) differs from physical activity energy expenditure (PAEE) as a function of body size and age. DESIGN This was a cross-sectional study in children [n = 26; (+/-SD) age: 9.6 +/- 0.3 y] and adolescents (n = 25; age: 17.6 +/- 1.5 y) in which body movement and total energy expenditure (TEE) were simultaneously measured with the use of accelerometry and the doubly labeled water method, respectively. PAEE was expressed as 1) unadjusted PAEE [TEE minus resting energy expenditure (REE); in MJ/d], 2) PAEE adjusted for body weight (BW) (PAEE. kg(-1). d(-1)), 3) PAEE adjusted for fat-free mass (FFM) (PAEE. kg FFM(-1). d(-1)), and 4) the physical activity level (PAL = TEE/REE). RESULTS Body movement was significantly higher (P = 0.03) in children than in adolescents. Similarly, when PAEE was normalized for differences in BW or FFM, it was significantly higher in children than in adolescents (P = 0.03). In contrast, unadjusted PAEE and PAL were significantly higher in adolescents (P < 0.01). CONCLUSIONS PAEE should be normalized for BW or FFM for comparison of physical activity between children and adolescents who differ in body size and age. Adjusting PAEE for FFM removes the confounding effect of sex, and therefore FFM may be the most appropriate body-composition variable for normalization of PAEE. Unadjusted PAEE and PAL depend on body size.
Relatedness of medically important strains of Saccharomyces cerevisiae as revealed by phylogenetics and metabolomics

Ten medically important Saccharomyces strains, comprising six clinical isolates of Saccharomyces cerevisiae and four probiotic strains of Saccharomyces boulardii, were characterized at the genetic and metabolic level and compared with non‐medical, commercial yeast strains used in baking and wine‐making. Strains were compared by genetic fingerprinting using amplified fragment length polymorphism (AFLP) analysis, by ribosomal DNA ITS1 sequencing and by metabolic footprinting using both direct injection mass spectrometry (DIMS) and gas chromatography–time of flight–mass spectrometry (GC–ToF–MS). Overall, the clinical isolates fell into different groupings when compared with the non‐medical strains, with good but not perfect correlation amongst strains at both the genetic and metabolic levels. Probiotic strains of S. boulardii that are used therapeutically to treat human gastro‐intestinal tract disorders showed tight clustering both genetically and metabolically. Metabolomics was found to be of value both as a taxonomic tool and as a means to investigate anomalous links between genotype and phenotype. Key discriminatory metabolites were identified when comparing the three main groups of clinical, probiotic and non‐medical strains and included molecules such as trehalose, myo‐inositol, lactic acid, fumaric acid and glycerol 3‐phosphate. This study confirmed the link between a subset of clinical isolates and baking or probiotic strains but also highlighted that in general the clinical strains were more diverse at both the genomic and metabolic levels. Copyright © 2008 John Wiley & Sons, Ltd.
Sex Steroid-Mediated Control of Oviductal Function in Cattle

In cattle, the oviduct is a tubular organ that connects the ovary and the uterus. The oviduct lumen stages a dynamic set of cellular and molecular interactions to fulfill the noble role of generating a new individual. Specific anatomical niches along the oviduct lumen provide the appropriate microenvironment for final sperm capacitation, oocyte capture and fertilization, and early embryo development and transport. To accomplish such complex tasks, the oviduct undergoes spatially and temporally-regulated morphological, biochemical, and physiological changes that are associated with endocrine events of the estrous cycle. Specifically, elevated periovulatory concentrations of estradiol (E2) and progesterone (P4) influence gene expression and morphological changes that have been associated positively to fertility in beef cattle. In this review, we explore how E2 and P4 influence oviductal function in the beginning of the estrous cycle, and prepare the oviductal lumen for interactions with gametes and embryos.
Total body potassium differs by sex and race across the adult age span.

BACKGROUND Total body potassium (TBK) is an index of fat-free mass. Data describing changes in TBK in African American, Asian, or Hispanic populations have not been reported. OBJECTIVE The aim was to investigate possible sex and racial differences in TBK in adults over an age range of 70 y. DESIGN The study used longitudinal and cross-sectional data collected in a body-composition unit from 973 men and 1368 women of African American, Asian, white, and Hispanic race-ethnicity. Random coefficient models in which baseline weight and height were taken into account were applied to estimate sex-specific changes in TBK among the 4 racial-ethnic groups. RESULTS The ages of 30 and 31 y were identified for women and men, respectively, as the cutoffs after which TBK began to decline. Both sexes had similar racial-ethnic patterns for expected mean TBK at the age cutoffs: African Americans had the highest value, followed by whites, Hispanics, and Asians. After the age cutoffs, the decline in TBK differed by race and sex. In women, African Americans showed the most rapid decline, whereas Asians had the lowest. In men, Hispanics had the most rapid decline in TBK, followed by African Americans, whites, and Asians. CONCLUSION Significant sex and racial differences exist in the rate of change in TBK with age. Further studies are needed to explore the associations of declining TBK with health risks.
Hair removal on dermoscopy images

Digital Dermoscopy is a tool commonly used by dermatologists for assisting the diagnosis of skin lesions. The presence of hair in such dermoscopic images frequently occludes significant diagnostic information and reduces their value. In this work we propose algorithms that successfully identify and remove hair from the dermoscopic images. The proposed algorithms consist of two parts; the first deals with the identification of hair, while the second part concerns the image restoration using interpolation. For the evaluation of the algorithms we used ground truth images with synthetic hair and compared the results with the commonly used in the literature DullRazor tool. According to the experimental results the proposed hair removal algorithms can be used successfully in the detection and removal of both dark and light colored hair.
PD-L1 expression and presence of TILs in small intestinal neuroendocrine tumours

Background The extent of resistance to immune surveillance in patients with well-differentiated (Wd) (grade 1/2) small-intestinal neuroendocrine tumours (Si-NETs) is unknown. Methods Patients diagnosed with Wd Si-NETs (excluding appendix, which are considered to have a different biology to other midgut NETs) were eligible. Tumoural programmed death (PD)-ligand(L) 1 (PD-L1)/PD-L2/PD-1 and tumour infiltrating lymphocytes (TILs) [presence and phenotype] were analysed in archival tissue by immunohistochemistry (IHC); reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used for confirmation of IHC results. Results Of 109 patients screened, 62 were eligible: 54.8% were male; median age was 63.7 years (95%-CI 59.7-67.2); disease stage II: 4.8%, III: 40.3% and IV: 54.8%; 41.9% were functional. Analysed samples (67.1% from primary tumours, 32.9% from metastases) were of grade 1 (67.1%) or 2 (32.86%) with a median Ki-67 of 2%. From the total of 62 eligible patients, 70 and 63 samples were suitable for IHC and RT-qPCR analysis, respectively. PD-L1 expression within tumour cells and TILs were identified in 12.8% and 24.3% of samples respectively; 30% of samples showed PD-L1 expression within tumour cells and/or TILs. PD-1 was present in TILs in 22.8% of samples. Majority of samples showed significant presence of CD4+ (focal 42.86%; moderate 2.86%) and CD8+ (focal 92.86%; moderate 4.29%) TILs. IHC findings were confirmed with RT-qPCR; which showed higher expression levels of PD-L1 (p-value 0.007) and PD-1 (p-value 0.001) in samples positive for IHC compared to negative-IHC. Conclusions Thirty-percent of patients express PD-L1 within tumour cells and/or TILs. Identification of presence of TILs was also significant and warrant the investigation of immunotherapy in this setting.
Effects of Deposition Temperature on the Properties of Ga-Doped ZnO Thin Films

A compound of 97wt% ZnO and 3wt% Ga2O3 (GZO) was sintered at 1400°C as a target and deposited on glass using a radio frequency magnetron sputtering system. The effects of deposition temperature (from room temperature, RT, to ~300°C) on the crystallization size, lattice constant (c), resistivity, carrier concentration, carrier mobility, and optical transmission property of the GZO thin films were studied. The variations in the films' optical band gap (Eg) values were evaluated from plots of (ahv)^2 = c(hv-Eg), revealing that the measured Eg values increased with increasing deposition temperature. The Burstein-Moss shift was observed and used to prove that defects in the GZO thin films decreased with increasing deposition temperature and reached a minimum at 200°C.
Patterns of excitation-contraction coupling in arterioles: dependence on time and concentration.

We sought to understand the excitation-contraction coupling process in arterioles. KCl or phenylephrine (PE) was applied via the superfusion solution or by brief pulsatile ejections from a micropipette onto unpressurized arterioles (in vitro) from either the guinea pig small intestine or hamster cheek pouch. With either mode of application, KCl caused depolarizations that were tightly and predictably correlated with subsequent constrictions (electromechanical coupling). In contrast, the relationship between membrane potential and vasoconstriction in response to phenylephrine was dependent on both stimulus duration and agonist concentration. Application of short pulses of PE (<1 s) produced mechanical responses that were dominated by pharmacomechanical coupling (i.e., they were not associated with changes in membrane potential). With longer PE stimuli, electromechanical coupling became more important and dominated microvessel responses. We conclude that adequate understanding of the signaling process in microvessels requires a consideration of both concentration and duration of application. Both the mode and duration of agonist application affect the relative degree of electromechanical or pharmacomechanical coupling in response to a vasomotor stimulus. These observations have important implications for intracellular and intercellular signaling.
A longitudinal large-scale objective sleep data analysis revealed a seasonal sleep variation in the Japanese population

ABSTRACT In the contemporary era, when life habits are largely determined by social needs and individual preferences, sleep is nevertheless affected by seasonal environmental changes. Japan has large seasonal and geographical alterations of photoperiod and climate. Japan does not adopt the daylight saving time (DST) system, making it a suitable country for the study of seasonal variations in natural human sleep. The aim of this study was to analyze the seasonal changes in the sleep properties (timing and quality) and identify their relationship with environmental changes. Here, we report an analysis of objective sleep data of 691 161 nights collected from 1856 Japanese participants (age 20–79 years, male 91%, female 9%) for 3 years using contactless biomotion sensors. Sleep onset time did not show clear seasonal variation, but sleep offset time showed a seasonal change with a single latest peak in winter. Seasonal variation was larger during weekends than during weekdays. Sleep offset time well correlated with sunrise time but was different in spring and autumn even when the sunrise time was same, suggesting the role of temperature difference. Sleep quality, estimated by wake time after sleep onset and sleep efficiency, showed seasonal changes with the lowest trough around mid-summer. In conclusion, despite profound social influences, the timing and quality of sleep showed seasonal fluctuation indicating that they were influenced by climate factors even in the developed country.
Stearic acid absorption and its metabolizable energy value are minimally lower than those of other fatty acids in healthy men fed mixed diets.

Compared with other saturated fatty acids, stearic acid appears to have different metabolic effects with respect to its impact on risk for cardiovascular disease. These differences may in part reflect biologically important differences in absorption. This study was designed to compare the absorption and the metabolizable energy value of stearic acid with other fatty acids from mixed diets fed to healthy humans. Healthy men (n = 11) were fed four diets with multiple fat sources that contained approximately 15% of energy (en%) from protein, 46 en% from carbohydrate and 39 en% from fat with 8 en% substitution across diets of the following: trans monoenes, oleic acid, saturated fatty acids (lauric + myristic + palmitic) or stearic acid fed as triacylglycerides. Fats were incorporated into mixed diets comprised of foods typically consumed in the United States. After a 14-d adaptation period, volunteers collected all feces for 7 d. Across diets, absorption of stearic acid (94.1 +/- 0.2%) was lower (P < 0.0002) than that of palmitic acid (97.3 +/- 0.2%) and higher than generally reported. Absorption of lauric, myristic, oleic, linoleic and trans 18:1 monoenes did not differ from each other (>99%) but was higher than that of stearic and palmitic acids (P < 0.001). Metabolizable energy values were similar for all fatty acids. Although absorption of palmitic and stearic acids was affected by diet treatment, the magnitudes of the differences were small and do not appear to be biologically important, at least in terms of lipoprotein metabolism. On the basis of these results, reduced stearic acid absorption does not appear to be responsible for the differences in plasma lipoprotein responses to stearic acid relative to other saturated or unsaturated fatty acids.
Reaction times can reflect habits rather than computations

Reaction times (RTs) are assumed to reflect the underlying computations required for making decisions and preparing actions. Recent work, however, has shown that movements can be initiated earlier than typically expressed without affecting performance; hence, the RT may be modulated by factors other than computation time. Consistent with that view, we demonstrated that RTs are influenced by prior experience: when a previously performed task required a specific RT to support task success, this biased the RTs in future tasks. This effect is similar to the use-dependent biases observed for other movement parameters such as speed or direction. Moreover, kinematic analyses revealed that these RT biases could occur without changing the underlying computations used to perform the action. Thus the RT is not solely determined by computational requirements but is an independent parameter that can be habitually set by prior experience.
Interferon-γ decreases barrier function in T84 cells by reducing ZO-1 levels and disrupting apical actin.

The effects of interferon-γ (IFN-γ) on tight junctions in T84 human intestinal epithelial cells were investigated. Treatment of T84 cells with IFN-γ caused a dose- and time-dependent increase in monolayer permeability as assessed by transepithelial electrical resistance measurements. Examination of specific proteins associated with tight junctions by immunoblotting and confocal microscopy revealed changes in the expression levels and localization of some of these proteins after exposure of the cells to IFN-γ. Specifically, IFN-γ treatment resulted in an almost total loss of zonula occludens (ZO)-1, whereas the levels of ZO-2 and occludin showed relatively modest decreases compared with untreated cells. Loss of ZO-1 was associated with the altered localization of ZO-2 and occludin. In IFN-γ-treated cells, ZO-2 and occludin were diffusely distributed, whereas, in control cells, they, along with ZO-1, were predominantly localized to the tight junctions. Analysis of ZO-1 protein and RNA by pulse chase and RT-PCR, respectively, showed an increase in protein turnover, a decrease in protein synthesis, and a reduction in RNA levels following IFN-γ treatment. In contrast to ZO-1, ZO-2 and occludin did not show any major changes in these parameters. In addition, the organization of actin in the apical and tight junction regions, but not in the mid- or basal regions, of the cells was also perturbed by IFN-γ treatment of cells. Time-course analysis of IFN-γ-induced alterations in ZO-1 expression and apical actin perturbation indicated that these two effects were intimately linked and could not be dissociated. These results suggest that IFN-γ affects barrier function in T84 cells by decreasing the levels of ZO-1 and perturbing apical actin organization, which leads to a disorganization of the tight junction and an increase in paracellular permeability.