Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using peptides mimicking endogenously citrullinated fibrinogen antigens

IntroductionWe have previously identified endogenously citrullinated peptides derived from fibrinogen in rheumatoid arthritis (RA) synovial tissues. In this study, we have investigated the auto-antigenicity of four of those citrullinated peptides, and explored their feasibility to target anti-citrullinated protein/peptide antibodies (ACPA).MethodsThe autoantigenic potential of the fibrinogen peptides was investigated by screening 927 serum samples from the Epidemiological Investigation of RA (EIRA) cohort on a peptide microarray based on the ImmunoCAP ISAC® system. In order to assay for ACPA blocking, two independent pools of purified ACPA were incubated with the respective targeting peptide prior to binding to cyclic citrullinated peptide (CCP)2 using the CCPlus® ELISA kit.ResultsTwo peptides derived from the fibrinogen α chain, Arg573Cit (563-583) and Arg591Cit (580-600), referred to as Cit573 and Cit591, and two peptides from the fibrinogen β chain, Arg72Cit (62-81) and Arg74Cit (62-81) (Cit72 and Cit74), displayed 65 %, 15 %, 35 %, and 53 % of immune reactivity among CCP2-positive RA sera, respectively. In CCP2-negative RA sera, a positive reactivity was detected in 5 % (Cit573), 6 % (Cit591), 8 % (Cit72), and 4 % (Cit74). In the competition assay, Cit573 and Cit591 peptides reduced ACPA binding to CCP2 by a maximum of 84 % and 63 % respectively. An additive effect was observed when these peptides were combined. In contrast, Cit74 and Cit72 were less effective. Cyclization of the peptide structure containing Cit573 significantly increased the blocking efficiency.ConclusionsHere we demonstrate extensive autoantibody reactivity against in vivo citrullinated fibrinogen epitopes, and further show the potential use of these peptides for antagonizing ACPA.     

Fatty Acid Competition as a Mechanism by Which Enterobacter cloacae Suppresses Pythium ultimum Sporangium Germination and Damping-Off

Interactions between plant-associated microorganisms play important roles in suppressing plant diseases and enhancing plant growth and development. While competition between plant-associated bacteria and plant pathogens has long been thought to be an important means of suppressing plant diseases microbiologically, unequivocal evidence supporting such a mechanism has been lacking. We present evidence here that competition for plant-derived unsaturated long-chain fatty acids between the biological control bacterium Enterobacter cloacae and the seed-rotting oomycete, Pythium ultimum, results in disease suppression. Since fatty acids from seeds and roots are required to elicit germination responses of P. ultimum, we generated mutants of E. cloacae to evaluate the role of E. cloacae fatty acid metabolism on the suppression of Pythium sporangium germination and subsequent plant infection. Two mutants of E. cloacae EcCT-501R3, Ec31 (fadB) and EcL1 (fadL), were reduced in β-oxidation and fatty acid uptake, respectively. Both strains failed to metabolize linoleic acid, to inactivate the germination-stimulating activity of cottonseed exudate and linoleic acid, and to suppress Pythium seed rot in cotton seedling bioassays. Subclones containing fadBA or fadL complemented each of these phenotypes in Ec31 and EcL1, respectively. These data provide strong evidence for a competitive exclusion mechanism for the biological control of P. ultimum-incited seed infections by E. cloacae where E. cloacae prevents the germination of P. ultimum sporangia by the efficient metabolism of fatty acid components of seed exudate and thus prevents seed infections.     

Unraveling the Genetic Etiology of Adult Antisocial Behavior: A Genome-Wide Association Study

Crime poses a major burden for society. The heterogeneous nature of criminal behavior makes it difficult to unravel its causes. Relatively little research has been conducted on the genetic influences of criminal behavior. The few twin and adoption studies that have been undertaken suggest that about half of the variance in antisocial behavior can be explained by genetic factors. In order to identify the specific common genetic variants underlying this behavior, we conduct the first genome-wide association study (GWAS) on adult antisocial behavior. Our sample comprised a community sample of 4816 individuals who had completed a self-report questionnaire. No genetic polymorphisms reached genome-wide significance for association with adult antisocial behavior. In addition, none of the traditional candidate genes can be confirmed in our study. While not genome-wide significant, the gene with the strongest association (p-value = 8.7×10⁻⁵) was DYRK1A, a gene previously related to abnormal brain development and mental retardation. Future studies should use larger, more homogeneous samples to disentangle the etiology of antisocial behavior. Biosocial criminological research allows a more empirically grounded understanding of criminal behavior, which could ultimately inform and improve current treatment strategies.     

Caenorhabditis nematodes colonize ephemeral resource patches in neotropical forests

Factors shaping the distribution and abundance of species include life‐history traits, population structure, and stochastic colonization–extinction dynamics. Field studies of model species groups help reveal the roles of these factors. Species of Caenorhabditis nematodes are highly divergent at the sequence level but exhibit highly conserved morphology, and many of these species live in sympatry on microbe‐rich patches of rotten material. Here, we use field experiments and large‐scale opportunistic collections to investigate species composition, abundance, and colonization efficiency of Caenorhabditis species in two of the world''s best‐studied lowland tropical field sites: Barro Colorado Island in Panamá and La Selva in Sarapiquí, Costa Rica. We observed seven species of Caenorhabditis, four of them known only from these collections. We formally describe two species and place them within the Caenorhabditis phylogeny. While these localities contain species from many parts of the phylogeny, both localities were dominated by globally distributed androdiecious species. We found that Caenorhabditis individuals were able to colonize baits accessible only through phoresy and preferentially colonized baits that were in direct contact with the ground. We estimate the number of colonization events per patch to be low.     

No evidence that polyandry benefits females in Drosophila melanogaster

Understanding the evolution of polyandry (mating with multiple males) is a major issue in the study of animal breeding systems. We examined the adaptive significance of polyandry in Drosophila melanogaster, a species with well-documented costs of mating in which males generally cannot force copulations. We found no direct fitness advantages of polyandry. Females that mated with multiple males had no greater mean fitness and no different variance in fitness than females that mated repeatedly with the same male. Subcomponents of reproductive success, including fecundity, egg hatch rate, larval viability, and larval development time, also did not differ between polyandrous and monogamous females. Polyandry had no affect on progeny sex ratios, suggesting that polyandry does not function against costly sex-ratio distorters. We also found no evidence that polyandry functions to favor the paternity of males successful in precopulatory sexual selection. Experimentally controlled opportunities for precopulatory sexual selection had no effect on postcopulatory sperm precedence. Although these results were generally negative, they are supported with substantial statistical power and they help narrow the list of evolutionary explanations for polyandry in an important model species.     

Soil biotic processes remain remarkably stable after 100-year extreme weather events in experimental grassland and heath

Climate change will increase the recurrence of extreme weather events such as drought and heavy rainfall. Evidence suggests that extreme weather events pose threats to ecosystem functioning, particularly to nutrient cycling and biomass production. These ecosystem functions depend strongly on below-ground biotic processes, including the activity and interactions among plants, soil fauna, and micro-organisms. Here, experimental grassland and heath communities of three phytodiversity levels were exposed either to a simulated single drought or to a heavy rainfall event. Both weather manipulations were repeated for two consecutive years. The magnitude of manipulations imitated the local 100-year extreme weather event. Heavy rainfall events increased below-ground plant biomass and stimulated soil enzyme activities as well as decomposition rates for both plant communities. In contrast, extreme drought did not reduce below-ground plant biomass and root length, soil enzyme activities, and cellulose decomposition rate. The low responsiveness of the measured ecosystem properties in face of the applied weather manipulations rendered the detection of significant interactions between weather events and phytodiversity impossible. Our data indicate on the one hand the close interaction between below ground plant parameters and microbial turnover processes in soil; on the other hand it shows that the plant–soil system can buffer against extreme drought events, at last for the period of investigation.