The effects of networking on the extent of cooperation emerging in a competitive setting are studied. The evolutionary snowdrift game, which represents a realistic alternative to the well-known Prisoner's Dilemma, is studied in the Watts-Strogatz network that spans the regular, small-world, and random networks through random re-wiring. Over a wide range of payoffs, a re-wired network is found to suppress cooperation when compared with a well-mixed or fully connected system. Two extinction payoffs, that characterize the emergence of a homogeneous steady state, are identified. It is found that, unlike in the Prisoner's Dilemma, the standard deviation of the degree distribution is the dominant property in a re-wired network that governs the extinction payoffs.

Toll-like receptor4 (TLR4) plays an important role in the induction and regulation of the innate or adaptive immune responses. Thus, the genetic variation in TLR4 gene may influence the development of autoimmune diseases such as rheumatoid arthritis (RA). Several studies have investigated the roles of genetic polymorphisms of TLR4 gene in RA, but most of these studies were restricted to two cosegregating functional missense polymorphisms Asp299Gly and Thr399Ile. To determine whether non-missense genetic polymorphisms located in regulatory region of TLR4 are related to RA in a Chinese Han population, four single nucleotide polymorphisms (SNPs) situated on 3' untranslating region (UTR) and 5' UTR were genotyped in 213 RA patients and 247 unrelated ethnically matched controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing techniques. Significant genetic associations were observed with the 3' UTR SNP rs41426344 and rs7873784. The minor allele C and homozygotic variant genotype CC of rs41426344 and minor allele C of rs7873784 were identified to be risk factors for the development of RA in Chinese Han people. Furthermore, by comparing the variation allele frequencies to other populations, prevalent genetic ethnic specificity was observed in all the four SNPs. Our study suggested that the effect of non-missense polymorphisms located in regulatory region would not be neglected in disease association analysis.

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The biological response to orthopaedic wear debris is central to peri-prosthetic tissue inflammation and osteolysis, through mechanisms that include local inflammatory cytokine production. In particular, interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha|) are generated in high quantities following monocyte accumulation in periprosthetic inflammatory tissue, and these cytokine combine with other inflammatory mediators to trigger osteolysis. Since the precise mechanisms involved in debris-associated inflammation remain unclear, it is important to understand how wear debris particles initially interact with inflammatory cells. We have previously demonstrated that the severity of the inflammation response is influenced by the size, shape, and quantity of particles accumulated in tissues. The current in vitro and in vivo results indicate that heat-shock protein (Hsp) expression is elevated when monocytes are exposed to wear debris particles. We have also addressed the mechanisms by which heat-shock protein 60 (Hsp60) positively modulates inflammatory cytokines via Toll-like receptor-4 (TLR4) signal transduction pathway on mononuclear cells. Furthermore, down-regulation of TLR4 expression using antisense oligonucleotides targeted to TLR4 mRNA suppressed cytokine production in both exogenous Hsp60 and particles stimulated cultures. Collectively, these data indicate that monocytic Hsp60 is an additional inducible immunoregulatory mediator in response to particle-induced cell stress.