Fascioloides magna (Bassi, 1875) in feral swine from southern Texas.

Between 1971 and 1975, Fascioloides magna was found in 46 of 67 (69%) feral swine (Sus scrofa) in southern Texas. Flukes were recovered from swine in areas where F. magna commonly has been recovered from white-tailed deer and cattle. One to 12 flukes were recovered from each infected animal. Their presence was indicated by black hematin pigment on the liver and various other internal organs. Eggs were not detected in the gallbladder or feces of infected animals although mature flukes and eggs were recovered in the livers suggesting that, like cattle, feral swine can be infected but are aberrant hosts for the parasite and do not disseminate eggs.     

Hydrogen sulfide:A novel component in Arabidopsis peroxisomes which triggers catalase inhibition

Plant peroxisomes have the capacity to generate different reactive oxygen and nitrogen species(ROS and RNS),such as H_2O_2,superoxide radical(O_2~-),nitric oxide and peroxynitrite(ONOO~-).These organelles have an active nitrooxidative metabolism which can be exacerbated by adverse stress conditions.Hydrogen sulfide(H_2S)is a new signaling gasotransmitter which can mediate the posttranslational modification(PTM)persulfidation.We used Arabidopsis thaliana transgenic seedlings expressing cyan fluorescent protein(CFP)fused to a canonical peroxisome targeting signal 1(PTS1)to visualize peroxisomes in living cells,as well as a specific fluorescent probe which showed that peroxisomes contain H_2S.H_2S was also detected in chloroplasts under glyphosate-induced oxidative stress conditions.Peroxisomal enzyme activities,including catalase,photorespiratory H_2O_2-generating glycolate oxidase(GOX)and hydroxypyruvate reductase(HPR),were assayed in vitro with a H_2S donor.In line with the persulfidation of this enzyme,catalase activity declined significantly in the presence of the H_2S donor.To corroborate the inhibitory effect of H_2S on catalase activity,we also assayed pure catalase from bovine liver and pepper fruit-enriched samples,in which catalase activity was inhibited.Taken together,these data provide evidence of the presence of H_2S in plant peroxisomes which appears to regulate catalase activity and,consequently,the peroxisomal H_2O_2 metabolism.     

The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages

Antagonistic interactions are likely important driving forces of the evolutionary process underlying bacterial genome complexity and diversity. We hypothesized that the ability of evolved bacteria to escape specific components of host innate immunity, such as phagocytosis and killing by macrophages (MΦ), is a critical trait relevant in the acquisition of bacterial virulence. Here, we used a combination of experimental evolution, phenotypic characterization, genome sequencing and mathematical modeling to address how fast, and through how many adaptive steps, a commensal Escherichia coli (E. coli) acquire this virulence trait. We show that when maintained in vitro under the selective pressure of host MΦ commensal E. coli can evolve, in less than 500 generations, virulent clones that escape phagocytosis and MΦ killing in vitro, while increasing their pathogenicity in vivo, as assessed in mice. This pathoadaptive process is driven by a mechanism involving the insertion of a single transposable element into the promoter region of the E. coli yrfF gene. Moreover, transposition of the IS186 element into the promoter of Lon gene, encoding an ATP-dependent serine protease, is likely to accelerate this pathoadaptive process. Competition between clones carrying distinct beneficial mutations dominates the dynamics of the pathoadaptive process, as suggested from a mathematical model, which reproduces the observed experimental dynamics of E. coli evolution towards virulence. In conclusion, we reveal a molecular mechanism explaining how a specific component of host innate immunity can modulate microbial evolution towards pathogenicity.     

Small-world networks decrease the speed of Muller's ratchet

Muller's ratchet is an evolutionary process that has been implicated in the extinction of asexual species, the evolution of non-recombining genomes, such as the mitochondria, the degeneration of the Y chromosome, and the evolution of sex and recombination. Here we study the speed of Muller's ratchet in a spatially structured population which is subdivided into many small populations (demes) connected by migration, and distributed on a graph. We studied different types of networks: regular networks (similar to the stepping-stone model), small-world networks and completely random graphs. We show that at the onset of the small-world network - which is characterized by high local connectivity among the demes but low average path length - the speed of the ratchet starts to decrease dramatically. This result is independent of the number of demes considered, but is more pronounced the larger the network and the stronger the deleterious effect of mutations. Furthermore, although the ratchet slows down with increasing migration between demes, the observed decrease in speed is smaller in the stepping-stone model than in small-world networks. As migration rate increases, the structured populations approach, but never reach, the result in the corresponding panmictic population with the same number of individuals. Since small-world networks have been shown to describe well the real contact networks among people, we discuss our results in the light of the evolution of microbes and disease epidemics.     

Mitogen activated protein kinase plays a significant role in metaphase II arrest, spindle morphology, and maintenance of maturation promoting factor activity in bovine oocytes

Mammalian oocytes are arrested at the G2/M transition of the first meiotic division from which, after reaching full size and subsequent to an LH surge, they undergo final maturation. Oocyte maturation, which involves germinal vesicle breakdown, progression through metaphase I (MI), and arrest at MII, is triggered and regulated by the coordinated action of two kinases, maturation promoting factor (MPF) and mitogen activated protein kinase (MAPK). The importance of the role of MPF in mammalian oocyte maturation is well established, while the role of MAPK, although well understood in mouse oocytes, has not been fully elucidated in oocytes of large domestic species, especially bovine oocytes. Here we show that injection of MKP-1 mRNA, which encodes a dual specificity MAPK phosphatase, into germinal vesicle stage bovine oocytes prevents the activation of MAPK during maturation. Despite the lack of MAPK activity, MKP-1-injected oocytes resume and progress through meiosis, although they are unable to arrest at MII stage and, by 22-26-hour post-maturation, exhibit decondensed pronucleus-like chromatin, a clear sign of parthenogenetic activation. MKP-1-injected bovine oocytes exhibit normal activation of MPF activity; however, by 18-hour post-maturation, MPF activity starts to decline and by 22-26 hr MPF activity is absent. MKP-1-injected oocytes also show disorganized MII spindles with poorly aligned chromosomes. In summary, our results demonstrate that in bovine oocytes MAPK activity is required for MII arrest, maintenance of MPF activity, and spindle organization.     

IL-11 and IL-11Rα immunolocalisation at primate implantation sites supports a role for IL-11 in placentation and fetal development

Embryo implantation, endometrial stromal cell decidualization and formation of a functional placenta are critical processes in the establishment and maintenance of pregnancy. Interleukin (IL)-11 signalling is essential for adequate decidualization in the mouse uterus and IL-11 promotes decidualization in the human. IL-11 action is mediated via binding to the specific IL-11 receptor α (IL-11Rα). The present study examined immunoreactive IL-11 and IL-11Rα in cycling rhesus monkey endometrium, at implantation sites in cynomolgus and rhesus monkeys and in human first trimester decidua and defined distinct spatial and temporal patterns. In cycling rhesus monkey endometrium, IL-11 and IL-11Rα increased in both basalis and functionalis regions during the secretory compared with the proliferative phase, with changing cellular locations in luminal and glandular epithelium and stroma. The patterns were similar overall to those previously described in human endometrium. Differences were seen in immunostaining during implantation in cynomologus and rhesus monkey. In the cynomolgus, very little staining for IL-11 or IL-11Rα was seen in syncytio- and cyto-trophoblast cells in the villi between days 12 and 150 of pregnancy although there was moderate staining in cytotrophoblast in the shell between days 12 and 17 and in subpopulations of cytotrophoblast cells invading the arteries at day 17. By contrast in the rhesus monkey between days 24 and 35 of pregnancy and in human first trimester placenta, cyto- and syncytio-trophoblast in the villi but not cytotrophoblast in the shell were positively stained. The most intense staining for both IL-11 and IL-11Rα was present within the decidua in the maternal component of implantation sites in all three primates but moderate staining was also present in maternal vascular smooth muscle and glands perivascular cells and epithelial plaques. These results are consistent with a role for IL-11 both during decidualization and placentation in primates.     

Injection of sperm cytosolic factor into mouse metaphase II oocytes induces different developmental fates according to the frequency of [Ca(2+)](i) oscillations and oocyte age

Intracellular calcium ([Ca(2+)](i)) rises are a hallmark of mammalian fertilization and are associated with normal activation of embryonic development. Injection of mammalian sperm cytosolic factor (SCF) into oocytes has been shown to trigger [Ca(2+)](i) rises similar to those observed during fertilization, and to initiate normal embryonic development. However, Ca(2+) release has also been shown to be associated with cell death, but the mechanisms of the detrimental effects of Ca(2+) stimulation on development have not yet been investigated. Thus, studies were undertaken using SCF to test the effects of [Ca(2+)](i) oscillations on oocyte activation in freshly ovulated and aged oocytes. Injections of 1 mg/ml SCF into freshly ovulated mouse metaphase II oocytes, which evoked Ca(2+) responses with low frequency and short duration, induced normal activation and cleavage to the two-cell stage. Conversely, injection of 15 mg/ml SCF, which triggered high-frequency and persistent Ca(2+) responses, induced abnormal activation that was characterized by abnormal chromatin configurations, inhibition of DNA synthesis, and lack of first mitotic spindle assembly. More importantly, fertilization-like Ca(2+) responses induced by injection of 1 mg/ml SCF triggered cell death, rather than activation, in in vitro-aged oocytes. These oocytes exhibited extensive cytoplasmic and DNA fragmentation that was accompanied by activation of protein caspases, all of which are signs of apoptotic cell death. Fewer similarly aged oocytes that were either unstimulated or activated with 7% ethanol underwent fragmentation. Together, these results suggest that [Ca(2+)](i) oscillations are required to activate freshly ovulated oocytes, but if initiated at abnormally high frequency and duration or if induced in aged oocytes, the [Ca(2+)](i) oscillations may trigger premature termination of embryonic development.     

RATES OF FITNESS DECLINE AND REBOUND SUGGEST PERVASIVE EPISTASIS

Unraveling the factors that determine the rate of adaptation is a major question in evolutionary biology. One key parameter is the effect of a new mutation on fitness, which invariably depends on the environment and genetic background. The fate of a mutation also depends on population size, which determines the amount of drift it will experience. Here, we manipulate both population size and genotype composition and follow adaptation of 23 distinct Escherichia coli genotypes. These have previously accumulated mutations under intense genetic drift and encompass a substantial fitness variation. A simple rule is uncovered: the net fitness change is negatively correlated with the fitness of the genotype in which new mutations appear—a signature of epistasis. We find that Fisher's geometrical model can account for the observed patterns of fitness change and infer the parameters of this model that best fit the data, using Approximate Bayesian Computation. We estimate a genomic mutation rate of 0.01 per generation for fitness altering mutations, albeit with a large confidence interval, a mean fitness effect of mutations of ?0.01, and an effective number of traits nine in mutS^? E. coli. This framework can be extended to confront a broader range of models with data and test different classes of fitness landscape models.     

Accelerated hand bone mineral density loss is associated with progressive joint damage in hands and feet in recent-onset rheumatoid arthritis

Introduction

To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years.

Methods

In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years.

Results

68% of the patients had accelerated hand BMD loss (>-0.003 g/cm²) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage.

Conclusions

In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year.