Correction: The Condition for Generous Trust.

[This corrects the article DOI: 10.1371/journal.pone.0166437.].

Labor union members play an OLG repeated game.

Humans are capable of cooperating with one another even when it is costly and a deviation provides an immediate gain. An important reason is that cooperation is reciprocated or rewarded and deviations are penalized in later stages. For cooperation to be sustainable, not only must rewards and penalties be strong enough but individuals should also have the right incentives to provide rewards and punishments. Codes of conduct with such properties have been studied extensively in game theory (as repeated game equilibria), and the literature on the evolution of cooperation shows how equilibrium behavior might emerge and proliferate in society. We found that community unions, a subclass of labor unions that admits individual affiliations, are ideal to corroborate these theories with reality, because (i) their activities are simple and (ii) they have a structure that closely resembles a theoretical model, the overlapping generations repeated game. A detailed case study of a community union revealed a possible equilibrium that can function under the very limited observability in the union. The equilibrium code of conduct appears to be a natural focal point based on simple heuristic reasoning. The union we studied was created out of necessity for cooperation, without knowing or anticipating how cooperation might be sustained. The union has successfully resolved about 3,000 labor disputes and created a number of offspring.

Protein microarray analysis identifies cyclic nucleotide phosphodiesterase as an interactor of Nogo-A.

Nogo-A, a neurite outgrowth inhibitor, is expressed exclusively on oligodendrocytes and neurons in the CNS. The central domain of Amino-Nogo spanning amino acids 567-748 in the human Nogo-A designated NIG, mediates persistent inhibition of axonal outgrowth and induces growth cone collapse by signaling through an as yet unidentified NIG receptor. We identified 82 NIG-interacting proteins by screening a high-density human protein microarray composed of 5000 proteins with a recombinant NIG protein as a probe. Following an intensive database search, we selected 12 neuron/oligodendrocyte-associated NIG interactors. Among them, we verified the molecular interaction of NIG with 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP), a cell type-specific marker of oligodendrocytes, by immunoprecipitation and cell imaging analysis. Although CNP located chiefly in the cytoplasm of oligodendrocytes might not serve as a cell-surface NIG receptor, it could act as a conformational stabilizer for the intrinsically unstructured large segment of Amino-Nogo.

Stable expression of neurogenin 1 induces LGR5, a novel stem cell marker, in an immortalized human neural stem cell line HB1.F3.

Neural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat spinal cord injury, stroke, and neurodegenerative diseases. To efficiently induce neuronal lineage cells from NSC for neuron replacement therapy, we should clarify the intrinsic genetic programs involved in a time- and place-specific regulation of human NSC differentiation. Recently, we established an immortalized human NSC clone HB1.F3 to provide an unlimited NSC source applicable to genetic manipulation for cell-based therapy. To investigate a role of neurogenin 1 (Ngn1), a proneural basic helix-loop-helix (bHLH) transcription factor, in human NSC differentiation, we established a clone derived from F3 stably overexpressing Ngn1. Genome-wide gene expression profiling identified 250 upregulated genes and 338 downregulated genes in Ngn1-overexpressing F3 cells (F3-Ngn1) versus wild-type F3 cells (F3-WT). Notably, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a novel stem cell marker, showed an 167-fold increase in F3-Ngn1, although transient overexpression of Ngn1 did not induce upregulation of LGR5, suggesting that LGR5 is not a direct transcriptional target of Ngn1. KeyMolnet, a bioinformatics tool for analyzing molecular relations on a comprehensive knowledgebase, suggests that the molecular network of differentially expressed genes involves the complex interaction of networks regulated by multiple transcription factors. Gene ontology (GO) terms of development and morphogenesis are enriched in upregulated genes, while those of extracellular matrix and adhesion are enriched in downregulated genes. These results suggest that stable expression of a single gene Ngn1 in F3 cells induces not simply neurogenic but multifunctional changes that potentially affect the differentiation of human NSC via a reorganization of complex gene regulatory networks.

Snake venom Vascular Endothelial Growth Factors (VEGF-Fs) exclusively vary their structures and functions among species.

Vascular endothelial growth factor (VEGF-A) and its family proteins are crucial regulators of blood vessel formation and vascular permeability. Snake venom has recently been shown to be an exogenous source of unique VEGF (known as VEGF-F), and now, two types of VEGF-F with distinct biochemical properties have been reported. Here, we show that VEGF-Fs (venom-type VEGFs) are highly variable in structure and function among species, in contrast to endogenous tissue-type VEGFs (VEGF-As) of snakes. Although the structures of tissue-type VEGFs are highly conserved among venomous snake species and even among all vertebrates, including humans, those of venom-type VEGFs are extensively variegated, especially in the regions around receptor-binding loops and C-terminal putative coreceptor-binding regions, indicating that highly frequent variations are located around functionally key regions of the proteins. Genetic analyses suggest that venom-type VEGF gene may have developed from a tissue-type gene and that the unique sequence of its C-terminal region was generated by an alteration in the translation frame in the corresponding exons. We further verified that a novel venom-type VEGF from Bitis arietans displays unique properties distinct from already known VEGFs. Our results may provide evidence of a novel mechanism causing the generation of multiple snake toxins and also of a new model of molecular evolution.

Gene expression profiling of human neural progenitor cells following the serum-induced astrocyte differentiation.

Neural stem cells (NSC) with self-renewal and multipotent properties could provide an ideal cell source for transplantation to treat spinal cord injury, stroke, and neurodegenerative diseases. However, the majority of transplanted NSC and neural progenitor cells (NPC) differentiate into astrocytes in vivo under pathological environments in the central nervous system, which potentially cause reactive gliosis. Because the serum is a potent inducer of astrocyte differentiation of rodent NPC in culture, we studied the effect of the serum on gene expression profile of cultured human NPC to identify the gene signature of astrocyte differentiation of human NPC. Human NPC spheres maintained in the serum-free culture medium were exposed to 10% fetal bovine serum (FBS) for 72 h, and processed for analyzing on a Whole Human Genome Microarray of 41,000 genes, and the microarray data were validated by real-time RT-PCR. The serum elevated the levels of expression of 45 genes, including ID1, ID2, ID3, CTGF, TGFA, METRN, GFAP, CRYAB and CSPG3, whereas it reduced the expression of 23 genes, such as DLL1, DLL3, PDGFRA, SOX4, CSPG4, GAS1 and HES5. Thus, the serum-induced astrocyte differentiation of human NPC is characterized by a counteraction of ID family genes on Delta family genes. Coimmunoprecipitation analysis identified ID1 as a direct binding partner of a proneural basic helix-loop-helix (bHLH) transcription factor MASH1. Luciferase assay indicated that activation of the DLL1 promoter by MASH1 was counteracted by ID1. Bone morphogenetic protein 4 (BMP4) elevated the levels of ID1 and GFAP expression in NPC under the serum-free culture conditions. Because the serum contains BMP4, these results suggest that the serum factor(s), most probably BMP4, induces astrocyte differentiation by upregulating the expression of ID family genes that repress the proneural bHLH protein-mediated Delta expression in human NPC.

Neuromyelitis optica/Devic's disease: gene expression profiling of brain lesions.

Neuromyelitis optica (NMO), also known as Devic's disease, is an inflammatory demyelinating disease that affects selectively the optic nerves and the spinal cord, possibly mediated by an immune mechanism distinct from that of multiple sclerosis (MS). Recent studies indicate that NMO also involves the brain. Here, we studied gene expression profile of brain lesions of a patient with NMO by using DNA microarray, along with gene expression profile of the brains of Parkinson disease and amyotrophic lateral sclerosis patients. We identified more than 200 genes up-regulated in NMO brain lesions. The top 20 genes were composed of the molecules closely associated with immune regulation, among which marked up-regulation of interferon gamma-inducible protein 30 (IFI30), CD163, and secreted phosphoprotein 1 (SPP1, osteopontin) was validated by real time RT-PCR, Northern blot and Western blot analysis. Pathologically, CD68(+) macrophages and microglia expressed intense immunoreactivities for IFI30 and CD163 in NMO lesions, consisting of inflammatory demyelination, axonal loss, necrosis, cavity formation, and vascular fibrosis. KeyMolnet, a bioinformatics tool for analyzing molecular interaction on the curated knowledge database, suggested that the molecular network of up-regulated genes in NMO brain lesions involves transcriptional regulation by the nuclear factor-kappaB (NF-kappaB) and B-lymphocyte-induced maturation protein-1 (Blimp-1). These results suggest that profound activation of the macrophage-mediated proinflammatory immune mechanism plays a pivotal role in development of NMO brain lesions.