Confirmation of FWT1 as a Wilms’ tumour susceptibility gene and phenotypic characteristics of Wilms’ tumour attributable to FWT1

A susceptibility gene for Wilms’ tumour (WT), designated FWT1, was previously mapped to chromosome 17q12–q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score=5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score=2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT. Received: 24 April 1998 / Accepted: 8 July 1998     

Examining Students’ Perception of Classroom Openness as a Predictor of Civic Knowledge: A Cross-National Analysis of 38 Countries

Civic knowledge is critical to interpreting various policy and candidate issues that are necessary to participating in certain political activities, such as voting in elections or attending public demonstrations. Various studies have examined students’ perceptions of classroom openness, which reflects perceived levels of political discussion supported by peers in the classrooms, to understand how this measure relates to students’ civic behaviors. This study analyzes data from the 2009 International Civic and Citizenship Education Study, in which approximately 134,000 students were sampled from 38 countries across Europe, Asia, and Latin America. Results from three-level hierarchal linear modeling suggest that students’ perceptions of classroom openness are strongly related to their civic knowledge scores. Further analyses indicate that the relationship strength between these two measures do not vary across students from different socioeconomic backgrounds. These findings reaffirm the importance of curricular approaches that emphasize political discussions in classrooms to prepare students for active citizenship.     

Is Occupation a Good Predictor of Self-Rated Health in China?

Background

China’s rapidly changing economic landscape has led to widening social inequalities. Occupational status in terms of occupational type and prestige may reflect these socio-structural shifts of social position and be more predictive of self-rated health status than income and education, which may only reflect more gradual acquisitions of social status over time. The goals of this study were to understand the role of occupational status in predicting self-rated health, which is well known to be associated with long-term mortality, as well as compare the occupational status to the other major socioeconomic indicators of income and education.

Methods

Data from the 2010 baseline surveys of the China Family Panel Studies, which utilized multi-stage probability sampling with implicit stratification was used. Logistic regression was used to examine the relationship of various socioeconomic indicators (i.e. occupational status, income, and education) with self-rated health as the primary outcome of interest. A series of models considered the associations of occupational category or occupational prestige with self-rated health.

Results

The final sample consisted of 14,367 employed adults aged 18–60, which was nationally representative of working adults in China. We found that occupation was not a major predictor of self-rated health in China when age, ethnicity, location, marital status, physical and mental health status were controlled for, with the exception of women working in lower grade management and professional jobs (OR = 1.82, 95% CI: 1.03–3.22). In comparison, income followed by education exhibited greater association with self-rated health. The highest income group had the least probability to report poor health (In men: OR = 0.30, 95% CI: 0.21–0.43. In women: OR = 0.44, 95% CI: 0.26–0.73). People educated with junior high school had better self-rated health than those with primary and below education level (In men: OR = 0.62, 95% CI: 0.50–0.75. In women: OR = 0.53, 95% CI: 0.42–0.68). Income, education and occupation were correlated with each other.

Conclusions

Within the context of rapid societal changes in China, income and its implications for greater healthcare access and benefits had the greatest association with self-rated health followed by education. Occupational status was not associated. Occupational categories and prestige should be better adapted to reflect China’s unique sociopolitical and historical context.     

What Is the Relevance of the Tip-Apex Distance as a Predictor of Lag Screw Cut-Out?

Using a simple mathematical formulation, the relationship between the position of the lag screw tip (relevant to both intramedullary and extramedullary devices) and the concept of tip-apex distance (TAD) was derived. TAD is widely used in operating theaters as a surgical guideline in relation to the fixation of trochanteric fractures, and in clinical studies as a predictor of lag screw cut-out. In order to visualize better this concept, the locus of points having the same TAD was plotted and the dependence of TAD on the location of the lag screw tip was also reported. It was shown that TAD should be adjusted for the size of the femoral head (a variable which varies a lot according to the sex of the patient) while no correlation was found between TAD and bone morphometry indices obtained from micro-CT data (BV/TV and Tb.Th). Therefore, these results seem to suggest that TAD lacks mechanical justification and that predictors which are based on mechanical properties, such as bone density, should be investigated further.     

Wilms’ Tumor Gene 1 (WT1) Silencing Inhibits Proliferation of Malignant Peripheral Nerve Sheath Tumor sNF96.2 Cell Line

Wilms’ tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumor suppressor gene or an oncogene depending on the cellular context. WT1 expression has been variably reported in both benign and malignant peripheral nerve sheath tumors (MPNSTs) by means of immunohistochemistry. The aim of the present study was to characterize its potential pathogenetic role in these relatively uncommon malignant tumors. Firstly, immunohistochemical analyses in MPNST sNF96.2 cell line showed strong WT1 staining in nuclear and perinuclear areas of neoplastic cells. Thus, we investigated the effects of silencing WT1 by RNA interference. Through Western Blot analysis and proliferation assay we found that WT1 knockdown leads to the reduction of cell growth in a time- and dose-dependent manner. siWT1 inhibited proliferation of sNF96.2 cell lines likely by influencing cell cycle progression through a decrease in the protein levels of cyclin D1 and inhibition of Akt phosphorylation compared to the control cells. These results indicate that WT1 knockdown attenuates the biological behavior of MPNST cells by decreasing Akt activity, demonstrating that WT1 is involved in the development and progression of MPNSTs. Thus, WT1 is suggested to serve as a potential therapeutic target for MPNSTs.     

Infant SES as a Predictor of Personality—Is the Association Mediated by Intelligence?

Background

Although research into the continuity and change of personality traits during a lifespan has been fairly extensive, little research has been conducted on childhood predictors of adult personality.

Purpose

We aimed to investigate the association between infant socioeconomic status (SES), and Eysenck personality traits in adulthood. An additional aim was to investigate whether intelligence and education may mediate this association.

Methods

SES of 9125 children in the Copenhagen Perinatal Cohort was recorded at a 1-year examination. A subsample of this cohort, comprising 1182 individuals, participated in a follow-up at 20–34 years and was administered the Eysenck Personality Questionnaire (EPQ) which includes measures of neuroticism, extraversion, psychoticism and the so-called lie-scale. Associations of SES with each of the four personality traits were analysed by bivariate and partial correlations, and the mediating effects of intelligence and years of education were analysed.

Results

Higher SES in infancy was associated with lower neuroticism (r = −0.06; p = 0.05), lower lie-scale scores (r = −0.11; p = 0.0002), and higher psychoticism (r = 0.09; p = 0.003). However, analyses of mediation revealed no direct effect of infant SES on any of the adult personality traits, but only indirect effects mediated by intelligence and years of education, with intelligence being the main mediating factor.

Conclusion

Only weak associations were observed between infant SES and personality in young adulthood, and the observed associations were mediated by adult intelligence and educational level. Thus, factors associated with infant SES or family background appears to have weak direct effects on personality development.     

Curcumin as a Potent and Selective Inhibitor of 11β-Hydroxysteroid Dehydrogenase 1: Improving Lipid Profiles in High-Fat-Diet-Treated Rats

Background

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activates glucocorticoid locally in liver and fat tissues to aggravate metabolic syndrome. 11β-HSD1 selective inhibitor can be used to treat metabolic syndrome. Curcumin and its derivatives as selective inhibitors of 11β-HSD1 have not been reported.

Methodology

Curcumin and its 12 derivatives were tested for their potencies of inhibitory effects on human and rat 11β-HSD1 with selectivity against 11β-HSD2. 200 mg/kg curcumin was gavaged to adult male Sprague-Dawley rats with high-fat-diet-induced metabolic syndrome for 2 months.

Results and Conclusions

Curcumin exhibited inhibitory potency against human and rat 11β-HSD1 in intact cells with IC₅₀ values of 2.29 and 5.79 µM, respectively, with selectivity against 11β-HSD2 (IC₅₀, 14.56 and 11.92 µM). Curcumin was a competitive inhibitor of human and rat 11β-HSD1. Curcumin reduced serum glucose, cholesterol, triglyceride, low density lipoprotein levels in high-fat-diet-induced obese rats. Four curcumin derivatives had much higher potencies for Inhibition of 11β-HSD1. One of them is (1E,4E)-1,5-bis(thiophen-2-yl) penta-1,4-dien-3-one (compound 6), which had IC₅₀ values of 93 and 184 nM for human and rat 11β-HSD1, respectively. Compound 6 did not inhibit human and rat kidney 11β-HSD2 at 100 µM. In conclusion, curcumin is effective for the treatment of metabolic syndrome and four novel curcumin derivatives had high potencies for inhibition of human 11β-HSD1 with selectivity against 11β-HSD2.     

The Canine Cuteness Effect: Owner-Perceived Cuteness as a Predictor of Human–Dog Relationship Quality

ABSTRACT

The modern domestic dog's primary function is as a human companion. A strong human–dog relationship may be beneficial to both parties but not all relationships are successful. There is currently no consensus on why some dog–owner relationships flourish and others fail, but relationship quality may be partly influenced by canine characteristics. The extent to which canine cuteness and canine personality factors predict human–dog relationship quality was examined. In study 1, 668 dog owners completed two relationship-quality surveys, rated their dog's personality and physical cuteness, and were invited to submit a photograph of their dog. Personality measures and cuteness ratings predicted each measure of relationship quality, with cuteness being the strongest unique predictor in three of seven standard multiple regression models (all p<0.001). In study 2, 873 independent participants were presented with one of 42 images selected from those provided in study 1. Participants rated the dog's cuteness and its likely personality attributes. Strangers (M=6.69, SD=0.83) typically rated each dog as being less cute than did the owner (M=8.93, SD=1.80; t(41₎=7.39, p<0.001, two tailed), and how cute they perceived the dog to be influenced their ratings of some aspects of its likely personality. Measures of relationship quality provided by owners were not significantly associated with stranger cuteness ratings or with the degree of difference between owner and stranger cuteness ratings. These results suggest a bi-directional relationship between perceived cuteness and other attributes: cute dogs are perceived to have more desirable personality traits, but having a strong relationship with a dog may also inflate its perceived cuteness. These findings have implications for those involved in dog breeding, selection, and training, as well as shelter management.     

Physiological functions of Wilms’ tumor 1-associating protein and its role in tumourigenesis

The Wilms’ tumor-associated gene WT1 encodes a tumor suppressor gene, which is implicated in renal differentiation and development of adult urogenital system. Wilms’ tumor 1-associating protein (WTAP) is initially identified as a nuclear protein that specifically interacts with WT1 in both in vitro and in vivo assays. WTAP is ubiquitously expressed in different tissues and various growth periods, and its expression is involved in cell cycle, RNA splicing and stabilization, N6-methyladenosine RNA modification, cell proliferation, and apoptosis as well as embryonic development. In the present review, we aimed to summarize the functions of WTAP in various physiological and pathological processes, in particular with regard to the current knowledge about the role of WTAP in tumorigenesis of different cancers.     

Primary School Teachers’ Assessment Profiles in Mathematics Education

The aim of this study was to contribute to knowledge about classroom assessment by identifying profiles of teachers’ assessment of their students’ understanding of mathematics. For carrying out this study we used data of a nationwide teacher survey (N = 960) in the Netherlands. The data were collected by an online questionnaire. Through exploratory factor analyses the underlying structure of what is measured by this questionnaire was uncovered as consisting of five factors: Goal centeredness of assessment, Authentic nature of assessment, Perceived usefulness of assessment, Diversity of assessment problem format, and Allocated importance of assessing skills and knowledge. By using a latent class analysis four different assessment profiles of teachers were identified: Enthusiastic assessors, Mainstream assessors, Non-enthusiastic assessors, and Alternative assessors. The findings suggest that teachers with particular assessment profiles have qualitatively different assessment practices. The paper concludes with discussing theoretical implications of these assessment profiles and indications these profiles can offer both for designing material for professional development in classroom assessment and for evaluating changes in teachers’ classroom assessment practice.     

Ecto-5’-Nucleotidase Overexpression Reduces Tumor Growth in a Xenograph Medulloblastoma Model

Background

Ecto-5’-nucleotidase/CD73 (ecto-5’-NT) participates in extracellular ATP catabolism by converting adenosine monophosphate (AMP) into adenosine. This enzyme affects the progression and invasiveness of different tumors. Furthermore, the expression of ecto-5’-NT has also been suggested as a favorable prognostic marker, attributing to this enzyme contradictory functions in cancer. Medulloblastoma (MB) is the most common brain tumor of the cerebellum and affects mainly children.

Materials and Methods

The effects of ecto-5’-NT overexpression on human MB tumor growth were studied in an in vivo model. Balb/c immunodeficient (nude) 6 to 14-week-old mice were used for dorsal subcutaneous xenograph tumor implant. Tumor development was evaluated by pathophysiological analysis. In addition, the expression patterns of adenosine receptors were verified.

Results

The human MB cell line D283, transfected with ecto-5’-NT (D283hCD73), revealed reduced tumor growth compared to the original cell line transfected with an empty vector. D283hCD73 generated tumors with a reduced proliferative index, lower vascularization, the presence of differentiated cells and increased active caspase-3 expression. Prominent A₁ adenosine receptor expression rates were detected in MB cells overexpressing ecto-5’-NT.

Conclusion

This work suggests that ecto-5’-NT promotes reduced tumor growth to reduce cell proliferation and vascularization, promote higher differentiation rates and initiate apoptosis, supposedly by accumulating adenosine, which then acts through A₁ adenosine receptors. Therefore, ecto-5’-NT might be considered an important prognostic marker, being associated with good prognosis and used as a potential target for therapy.     

Investigation of Long Non-coding RNA Expression Profiles in the Substantia Nigra of Parkinson’s Disease

Genetics is considered as an important risk factor in the pathological changes of Parkinson’s disease (PD). Substantia nigra (SN) is thought to be the most vulnerable area in this process. In recent decades, however, few related long non-coding RNAs (lncRNAs) in the SN of PD patients had been identified and the functions of those lncRNAs had been studied even less. In this study, we sought to investigate the lncRNA expression profiles and their potential functions in the SN of PD patients. We screened lncRNA expression profiles in the SN of PD patients using the lncRNA mining approach from the ArrayExpress database, which included GSE20295. The samples were from 11 of PD and 14 of normal tissue samples. We identified 87 lncRNAs that were altered significantly in the SN during the occurrence of PD. Among these lncRNAs, lncRNA AL049437 and lncRNA AK021630 varied most dramatically. AL049437 was up-regulated in the PD samples, while AK021630 was down-regulated. Based on the results, we focused on the potential roles of the two lncRNAs in the pathogenesis of PD by the knockdown of the expression of AL049437 or AK021630 in human neuroblastoma SH-SY5Y cell line. Results indicated that the reduction in AL049437 level increased cell viability, mitochondrial transmembrane potential (Δψm), mitochondrial mass, and tyrosine hydroxylase (TyrH) secretion. By contrast, the knockdown of AK021630 resulted in the opposite effect. Based on these results, we speculated that lncRNA AL049437 likely contributed to the risk of PD, while lncRNA AK021630 likely inhibited the occurrence of PD.     

Cell Therapy as a Way to Correct Impaired Neurogenesis in the Adult Brain in a Model of Alzheimer’s Disease

Journal of Evolutionary Biochemistry and Physiology - This work is based on the hypothesis of an impairment in neurogenesis during aging, which may be one of the causes of neurodegenerative...     

Adaptive Timing as a Component of a Mosquito-Eating predator’s Specialization Profile

Evarcha culicivora, a salticid spider from East Africa, is a mosquito specialist which feeds indirectly on vertebrate blood by actively choosing blood-carrying mosquitoes as preferred prey and by actively choosing Anopheles as preferred mosquitoes. Here we investigate for the first time whether specialization by this predator is also expressed in the timing of its predatory activity. With data from field sampling and from systematically observing E. culicivora under semi-field conditions, we show that instances of predation tend to be most common in the early morning hours, this being when especially many night-feeding anthropophilic anopheline mosquitoes are resting while digesting blood acquired during the night. Experimental data show that E. culicivora is significantly more responsive to prey in the morning than in the afternoon, where ‘responsive’ includes being significantly more inclined to eat living prey, choose the preferred prey, approach a source of prey odor in the absence of visible prey and approach lures made from dead prey that can be seen but not touched or smelled. We found no significant diel pattern in E. culicivora’s inclination to mate and, although mate, plant and human odors are all known to be salient to E. culicivora, we found no significant diel pattern in response to any of these odors. Our findings suggest that E. culicivora’s innate pattern of predatory activity is adaptively adjusted in a way that facilitates predation on its preferred prey.