Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.2014

Ecosystems and human well-being

■ Human well-being has several key components: the basic material needs for a good life, freedom and choice, health, good social relations, and personal security. Well-being exists on a continuum with poverty, which has been defined as"pronounced deprivation in well-being."
■ How well-being and ill-being, or poverty, are expressed and experienced is context- and situation-dependent, reflecting local social and personal factors such as geography, ecology, age, gender,and culture.These concepts are complex and value-laden.
■ Ecosystems are essential for human well-being through their provisioning, regulating, cultural, and supporting services. Evidence in recent decades of escalating human impacts. on ecological systems worldwide raises concerns about the consequences of ecosystem changes for human well-being.
■ Human well-being can be enhanced through sustainable human interaction with ecosystems with the support of appropriate instruments, institutions, organizations, and technology. creation of these through participation and transparency may contribute to people's freedoms and choices and to increased economic, social,and ecological security.
■ Some believe that the problems from the depletion and degradation of ecological capital can be largely overcome by the substitution of physical and human capital. Others believe that there are more significant limits to such substitutions.The scope for substitutions varies by socioeconomic status.
■ We identify direct and indirect pathways between ecosystem change and human well-being,whether it be positive or negative.lndirect effects are characterized by more complex webs of causation, involving social, economic, and political threads. Threshold points exist beyond which rapid changes to human well-being can occur.
■ Indigent poorly resourced, and otherwise disadvantaged communities are generally the most vulnerable to adverse ecosystem change. Spirals, both positive and negative, can occur for any population, but the poor are more vulnerable.      
■ Functioning institutions are vital to enable equitable access to ecosystem services. lnstitutions sometimes fail or remain undeveloped because of powerful individuals or groups. Bodies that mediate the distribution of goods and services may also be appropriated for the benefit of powerful minorities.
■ For poor people, the greatest gains in well-being will occur through more equitable and secure access to ecosystem services. In the long run, the rich can contribute greatly to human well-being by reducing their substantial impacts on ecosystems and by facilitating greater access to ecosystem services by the poor.
■ We argue ecological security warrants recognition as a sixth freedom of equal weight with participative freedom, economic   facilities, social opportunities, transparency guarantees, and protective security.

Exercise training increases lipid metabolism gene expression in human skeletal muscle

The effects of a single bout of exercise and exercise training on the expression of genes necessary for the transport and beta -oxidation of fatty acids (FA), together with the gene expression of transcription factors implicated in the regulation of FA homeostasis were investigated. Seven human subjects (3 male, 4 female, 28.9 ± 3.1 yr of age, range 20-42 yr, body mass index 22.6 kg/m², range 17-26 kg/m²) underwent a 9-day exercise training program of 60 min cycling per day at 63% peak oxygen uptake (V_{O2 peak}; 104 ± 14 W). On days 1 and 9 of the program, muscle biopsies were sampled from the vastus lateralis muscle at rest, at the completion of exercise, and again 3 h postexercise. Gene expression of key components of FA transport [FA translocase (FAT/CD36), plasma membrane-associated FA-binding protein], beta -oxidation [carntine palmitoyltransferase(CPT) I, beta -hydroxyacyl-CoA dehydrogenase] and transcriptional control [peroxisome proliferator-activated receptor (PPAR)alpha , PPARgamma , PPARgamma coactivator 1, sterol regulatory element-binding protein-1c] were unaltered by exercise when measured at the completion and at 3 h postexercise. Training increased total lipid oxidation by 24% (P < 0.05) for the 1-h cycling bout. This increased capacity for lipid oxidation was accompanied by an increased expression of FAT/CD36 and CPT I mRNA. Similarly, FAT/CD36 protein abundance was also upregulated by exercise training. We conclude that enhanced fat oxidation after exercise training is most closely associated with the genes involved in regulating FA uptake across the plasma membrane (FAT/CD36) and across the mitochondrial membrane (CPT I).

Frequency distribution of TATA box and extension sequences on human promoters

TATA box is one of the most important transcription factor binding sites. But the exact sequences of TATA box are still not very clear yet. In this study, we conducted a dedicated analysis on the frequency distribution of TATA Box and its extension sequences on human promoters. Sixteen TATA elements derived from TATA Box motif, TATAWAWN, were classified into three distribution patterns: peak, bottom-peak and bottom. Fourteen TATA extension sequences (up to two base extensions) were predicted to be the new TATA Box elements because of their high motif factors, which indicate their statistical significance. Statistical analysis on the promoters of mouse, zebrafish and drosophila melanogaster verified seven of these elements. It was also observed that the distribution of TATA elements on the promoters of housekeeping genes are very similar with their distribution on the promoters of tissue specific genes in human.

Role of dietary factors in the development of basal cell cancer and squamous cell cancer of the skin

The role of dietary factors in the development of skin cancer has been investigated for many years; however, the results of epidemiologic studies have not been systematically reviewed. This article reviews human studies of basal cell cancer (BCC) and squamous cell cancer (SCC) and includes all studies identified in the published scientific literature investigating dietary exposure to fats, retinol, carotenoids, vitamin E, vitamin C, and selenium. A total of 26 studies were critically reviewed according to study design and quality of the epidemiologic evidence. Overall, the evidence suggests a positive relationship between fat intake and BCC and SCC, an inconsistent association for retinol, and little relation between ß-carotene and BCC or SCC development. There is insufficient evidence on which to make a judgment about an association of other carotenoids with skin cancer. The evidence for associations between vitamin E, vitamin C, and selenium and both BCC and SCC is weak. Many of the existing studies contain limitations, however, and further well-designed and implemented studies are required to clarify the role of diet in skin cancer. Additionally, the role of other dietary factors, such as flavonoids and other polyphenols, which have been implicated in skin cancer development in animal models, needs to be investigated.

Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise

Endurance exercise improves insulin sensitivity and increases fat oxidation, which are partly facilitated by the induction of metabolic transcription factors. Next to exercise, increased levels of FFA's also increase the gene expression of transcription factors, hence making it difficult to discern the effects from contractile signals produced during exercise, from those produced by increased circulatory FFA's. We aimed to investigate, in human skeletal muscle, whether acute exercise affects gene expression of metabolic transcriptional co-activators and transcription factors, including PGC-1α, PRC, PPARα, β/δ, and γ and RXR, SREBP-1c and FKHR, and to discern the effect of exercise per se from those of elevated levels of FFA. Two hours of endurance exercise was performed either in the fasted state, or following carbohydrate ingestion prior to and during exercise, thereby blunting the fasting-induced increase in FA availability and oxidation. Of the genes measured, PGC-1α and PRC mRNA increased immediately after, while PPARβ/δ and FKHR mRNA increased 1–4 h after exercise, irrespective of the increases in FFA's. Our results suggest that the induction in vivo of metabolic transcription factors implicated in mitochondrial biogenesis are under the control of inherent signals, (PGC-1α, PRC), while those implicated in substrate selection are under the control of associated signals (PPARβ/δ, FKHR) stimulated from the contracting skeletal muscle that are independent of circulating FFA levels.

Applying domain analysis to the investigation of web-enabled human resource projects

Designing a successful web project requires understanding not only of its owner's business and technological needs, as well as having the substantial management and development experience, but it also depends on a thorough knowledge of the system's application domain and of other existing systems in the domain. In order to gather such domain knowledge, it is necessary to identify the nature of the proposed web services venture with regards to other similar services offered in the domain, the business setting of enterprises that initiate such ventures, the various types of customers involved, and how these factors translate into requirements. In this paper, we present an approach to studying the domain of web-enabled Human Resource and payroll services with the aim of attaining design knowledge that would ensure customer satisfaction and could eventually pave the way to the successful implementation of web-enabled services.

Career progression, human capital and pay equity in Australian public sector labour markets

This study uses data from the Victorian Public Sector Census 2004 to identify the extent of equity in pay and career progression (promotion). A system of three equations is developed to capture the endogeneity between human capital and promotion and the interdependence between promotion, pay and human capital. The results indicate that there are substantial differences in the average wages earned by public sector employees in different Equal Employment Opportunity (EEO) groups. While some of these differences arise from factors beyond the control of the public sector employers, others arise from bias in the public sector employment system and procedures. The earnings of individual employees in the public sector are determined in a systematic way by the wage structures in the different sub-sectors, the skill base of the employee on recruitment, sub-sector specific promotion rates, acquisition of formal and informal training and the apparent bias within recruitment and promotion systems in dealing with particular groups. The apparent bias of recruitment and promotion systems is complex in makeup and varies within EEO groups as well as between EEO groups. Most of the difference in pay across employees can be explained as an outcome of individual choice and labour market conditions external to the public sector. After adjusting for sectoral wage differences, skill base when recruited, sectoral promotion rate differences, experience in the public sector, whether individuals are employed on a full-time or part-time basis and individual training decisions, the statistical evidence is consistent with the finding that public sector recruitment and promotion systems tends to be biased, on average, against females and those from culturally diverse backgrounds. Achievements in formal education are important for salary progression. This is particularly the case for women. The main drivers of participation in formal education were employer support in both financial and non-financial terms. Promotion rates were important factors in explaining wage differences. Women tended to receive slightly fewer promotions than men, but women received, on average, greater rewards for each promotion.

Distribution of an alien aquatic snail in relation to flow variability, human activities and water quality

1. Disturbance and anthropogenic land use changes are usually considered to be key factors facilitating biological invasions. However, specific comparisons of invasion success between sites affected to different degrees by these factors are rare.

2. In this study we related the large-scale distribution of the invading New Zealand mud snail (Potamopyrgus antipodarum) in southern Victorian streams, Australia, to anthropogenic land use, flow variability, water quality and distance from the site to the sea along the stream channel.

3. The presence of P. antipodarum was positively related to an index of flow-driven disturbance, the coefficient of variability of mean daily flows for the year prior to the study.

4. Furthermore, we found that the invader was more likely to occur at sites with multiple land uses in the catchment, in the forms of grazing, forestry and anthropogenic developments (e.g. towns and dams), compared with sites with low-impact activities in the catchment. However, this relationship was confounded by a higher likelihood of finding this snail in lowland sites close to the sea.

5. We conclude that P. antipodarum could potentially be found worldwide at sites with similar ecological characteristics. We hypothesise that its success as an invader may be related to an ability to quickly re-colonise denuded areas and that population abundances may respond to increased food resources. Disturbances could facilitate this invader by creating spaces for colonisation (e.g. a possible consequence of floods) or changing resource levels (e.g. increased nutrient levels in streams with intense human land use in their catchments).

A preliminary study on human resource management in international construction

As construction companies continue to explore foreign construction markets, various international construction projects are being undertaken in all corners of the world. In an international construction project with many unique and complicated characteristics, human resource management can play a significant role in promoting the efficient use of complex human resources. The aim of this paper is to establish a valid foundation for further research on measuring the impact of human resource management economically for international construction projects. The paper examines human resource management literature and identifies the application of the related management techniques to the construction industry. In addition, the paper uses the literature analysis to describe the nature of human resource management with particular reference to international construction projects. In particular, the research described in this paper identifies economic performance factors in the implementation human resource management in international construction projects. This paper also identifies the social effects of human resource management practices.

Impaired expression of notch signaling genes in aged human skeletal muscle

Notch signaling is essential for myogenesis and the regenerative potential of skeletal muscle: however, its regulation in human muscle is yet to be fully characterized. Increased expression of Notch3, Jagged1. Hes1, and Hes6 gene transcripts were observed during differentiation of cultured human skeletal muscle cells. Furthermore, significantly lower expressions of Notch1, Jagged1, Numb, and Delta-like 1 were evident in muscle biopsies from older men (60-75 years old) compared to muscle from younger men (18-25 years old). Importantly, with supervised resistance exercise training, expression of Notch1 and Hes6 genes were increased and Delta-like 1 and Numb expression were decreased. The differences in Notch expression between the age groups were no longer evident following training. These results provide further evidence to support the role of Notch in the impaired regulation of muscle mass with age and suggest that some of the benefits provided by resistance training may be mediated through the Notch signaling pathway.

Altering dietary nutrient intake that reduces glycogen content leads to phosphorylation of nuclear p38 MAP kinase in human skeletal muscle: association with IL-6 gene transcription during contraction

To determine the effect of glycogen availability and contraction on intracellular signaling and IL-6 gene transcription, eight males performed 60 min of exercise on two occasions: either with prior ingestion of a normal (Con) or low carbohydrate (LCHO) diet that reduced pre-exercise muscle glycogen content. Muscle biopsies were obtained and analyzed for IL-6 mRNA. In addition, nuclear proteins were isolated from the samples and analyzed for the mitogen- activated protein kinases (MAPK) c-jun amino-terminal kinase (JNK) 1 and 2 and p38 MAPK. Nuclear fractions were also analyzed for the phosphorylated forms of JNK (p-JNK) and p38 MAPK (p-p38 MAPK) and the abundance of the nuclear transcription factors nuclear factor of activated T cells (NFAT) and nuclear factor kappa-β (NF-κβ). No differences were observed in the protein abundance of total JNK 1/2, p38 MAPK, NFAT, or NF-κβ before exercise, but the nuclear abundance of p-p38 MAPK was higher (P<0.05) in LCHO. Contraction resulted in an increase (P<0.05) in nuclear p-JNK 1/2, but there were no differences when comparing CON with LCHO. The fold increase in IL-6 mRNA with contraction was potentiated (P<0.05) in LCHO. A correlation between pre-exercise nuclear phosphorylated p38 MAPK and contraction-induced fold increase in IL-6 mRNA was performed, revealing a highly significant correlation (r=0.96; P<0.01). We next incubated L6 myotubes in ionomycin (a compound known to induce IL-6 mRNA) with or without the pyridinylimidazole p38 MAPK inhibitor SB203580. Treatments did not affect total nuclear p38 MAPK, but ionomycin increased (P<0.05) both nuclear p-p38 MAPK and IL-6 mRNA. The addition of SB203580 to ionomycin decreased (P<0.05) nuclear p-p38 MAPK and totally abolished (P<0.05) the ionomycin- induced increase in IL-6 mRNA. These data suggest that reduced carbohydrate intake that results in low intramuscular glycogen leads to phosphorylation of p38 MAPK at the nucleus. Furthermore, phosphorylation of p38 MAPK in the nucleus appears to be an upstream target for IL-6, providing new insights into the regulation of IL-6 gene transcription.