Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs. We sequenced three human genomes with this platform, generating an average of 45- to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high accuracy, affordable cost of $4400 for sequencing consumables, and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.

Gene expression profiling identified human melanoma cells demonstrating increased cell motility and invasiveness. The gene WNT5A best determined in vitro invasive behavior. Melanoma cells were transfected with vectors constitutively overexpressing Wnt5a. Consistent changes included actin reorganization and increased cell adhesion. No increase in beta-catenin expression or nuclear translocation was observed. There was, however, a dramatic increase in activated PKC. In direct correlation with Wnt5a expression and PKC activation, there was an increase in melanoma cell invasion. Blocking this pathway using antibodies to Frizzled-5, the receptor for Wnt5a, inhibited PKC activity and cellular invasion. Furthermore, Wnt5a expression in human melanoma biopsies directly correlated to increasing tumor grade. These observations support a role for Wnt5a in human melanoma progression.

Previous studies on green human resource management (GHRM) are mainly positioned at theoretical or qualitative level. There is urgent need to develop a valid measurement of GHRM and then to offer more insights into the implication of it on individual or organizational performance. The aim of this study was to propose and validate an instrument to measure GHRM. Based on exploratory analysis (study 1), it was established that GHRM includes five dimensions: green recruitment and selection, green training, green performance management, green pay and reward, and green involvement. Confirmatory factor analysis (study 2) was used to confirm the factor structure of study 1. The results indicated that the proposed measurement is valid. This study is the first and also the most comprehensive one to measure main human resource practices for environmental management, which can provide broader focus for further research and for practitioners.

We have shown that Wnt5A increases the motility of melanoma cells. To explore cellular pathways involving Wnt5A, we compared gain-of-function (WNT5A stable transfectants) versus loss-of-function (siRNA knockdown) of WNT5A by microarray analysis. Increasing WNT5A suppressed the expression of several genes, which were re-expressed after small interference RNA-mediated knockdown of WNT5A. Genes affected by WNT5A include KISS-1, a metastasis suppressor, and CD44, involved in tumor cell homing during metastasis. This could be validated at the protein level using both small interference RNA and recombinant Wnt5A (rWnt5A). Among the genes up-regulated by WNT5A was the gene vimentin, associated with an epithelial to mesenchymal transition (EMT), which involves decreases in E-cadherin, due to up-regulation of the transcriptional repressor, Snail. rWnt5A treatment increases Snail and vimentin expression, and decreases E-cadherin, even in the presence of dominant-negativeTCF4, suggesting that this activation is independent of Wnt/␤-catenin signaling. Because Wnt5A can signal via protein kinase C (PKC), the role of PKC in Wnt5A-mediated motility and EMT was also assessed using PKC inhibition and activation studies. Treating cells expressing low levels of Wnt5A with phorbol ester increased Snail expression inhibiting PKC in cells expressing high levels of Wnt5A decreased Snail. Furthermore, inhibition of PKC before Wnt5A treatment blocked Snail expression, implying that Wnt5A can potentiate melanoma metastasis via the induction of EMT in a PKC-dependent manner.The molecular mechanisms that govern the motility and metastasis of melanoma cells are not well understood. The prognosis for patients with recurrent melanoma has shown no improvement over the past 50 years. Many of these tumors are histopathologically quite similar but can be subclassified based upon their gene expression profiles (1, 2). In a study by Bittner et al. (1), the gene that best separated highly aggressive tumors from less aggressive tumors was WNT5A, which was consistently underexpressed in the less motile tumors. Wnt5A is a member of the Wnt family of proteins, which were first identified during studies of development in Drosophila (3) and in studies of the mouse mammary tumor virus (4). Unlike its family members Wnt1 and Wnt3A, which signal via the canonical Wnt pathway, resulting in the nuclear translocation of ␤-catenin, Wnt5A acts via G-protein-coupled receptors to activate protein kinase C (PKC) 6 and intracellular calcium (5, 6). The interplay between these two pathways is not well understood, but it does appear that the non-canonical Wnt pathway can inhibit ␤-catenin stabilization both in vitro in human HEK293 cells and in vivo in zebrafish (7,8).In melanoma cells with low motility and low expression of WNT5A, overexpressing WNT5A resulted in an increase in both the activation of PKC and an increase in motility (9). High expression of WNT5A in melanoma patients also correlated to poor outcome in this study. In addition, many studies have highligh...

Using a sample of 162 R&D teams, we investigated the influence of HRM systems for knowledgeintensive teamwork on external team knowledge acquisition and internal team knowledge sharing. This study also examined the interactive effect of HRM systems and knowledge tacitness and the combined influence of HRM systems and empowering leadership. HRM systems for knowledge-intensive teamwork were positively associated with team knowledge acquisition and team knowledge sharing. Knowledge tacitness moderated the HRM-knowledge acquisition relationship, reducing the influence of HRM systems. Further, empowering leadership appeared to substitute for the effect of HRM systems. Our findings suggest that an integration of strategic HRM and knowledge teamwork literatures will prove useful for advancing our understanding of knowledge-based competition. Furthermore, by investigating HRM systems and leadership behaviors in tandem, we gain new insights about the interplay between these two important aspects of organizational life.

C-type lectin receptors (CLRs) play critical roles as pattern-recognition receptors (PRRs) for sensing Candida albicans infection, which can be life-threatening for immunocompromised individuals. Here we have shown that Dectin-3 (also called CLECSF8, MCL, or Clec4d), a previously uncharacterized CLR, recognized α-mannans on the surfaces of C. albicans hyphae and induced NF-κB activation. Mice with either blockade or genetically deleted Dectin-3 were highly susceptible to C. albicans infection. Dectin-3 constantly formed heterodimers with Dectin-2, a well-characterized CLR, for recognizing C. albicans hyphae. Compared to their respective homodimers, Dectin-3 and Dectin-2 heterodimers bound α-mannans more effectively, leading to potent inflammatory responses against fungal infections. Together, our study demonstrates that Dectin-3 forms a heterodimeric PRR with Dectin-2 for sensing fungal infection and suggests that different CLRs may form different hetero- and homodimers, which provide different sensitivity and diversity for host cells to detect various microbial infections.

Recent advances in whole genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, Long Fragment Read (LFR) technology, similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ~100 pg of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants (SNVs) were assembled into long haplotype contigs. Removal of false positive SNVs not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 Mb. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications.

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