The effect of endocervical PGE2-gel (Prepidil™) gel on plasma levels of 13,14-dihydro-15-keto-PGE2(PGEM) in women at term

Term pregnant patients undergoing preinduction cervical softening were randomized to receive no treatment (controls) or 0.5 mg PGE₂-triacetin gel (Prepidil™ gel) endocervically. Plasma samples containing PGEM collected 4 hrs post-treatment and converted to the stable bicyclo degradation product (bicyclo-PGEM) were assayed by RIA. Positive clinical effect (responders) during 12 hrs after treatment (Bishop score increase≥3, in labor or delivered) were assessed. All evaluations were blind.In nonresponders (n=35), the means of the bicyclo-PGEM variables (mean, maximum, area under the curve) were all about 18% higher in gel-treated patients (n=6) than controls (n.s.). In responders (n=38), the variables were all about 80% higher in gel-treated women (n=32) than controls (p<.01). In controls (n=35), the responders (n=6) had 50% higher levels than nonresponders (n.s.). In the gel-treated women (n=38), responders (n=32) had about 140% higher levels than nonresponders (<.01).The results suggest that both exogenous and endogenous bicyclo-PGEM were measured. Differences in pairwise comparisons suggest that there may be substantially less exogenous bicyclo-PGEM in the gel nonresponders than in gel responders or substantially more endogenous bicyclo-PGEM in gel responders than in control-responders.     

A meta-analysis of changes in bacterial and archaeal communities with time

Ecologists have long studied the temporal dynamics of plant and animal communities with much less attention paid to the temporal dynamics exhibited by microbial communities. As a result, we do not know if overarching temporal trends exist for microbial communities or if changes in microbial communities are generally predictable with time. Using microbial time series assessed via high-throughput sequencing, we conducted a meta-analysis of temporal dynamics in microbial communities, including 76 sites representing air, aquatic, soil, brewery wastewater treatment, human- and plant-associated microbial biomes. We found that temporal variability in both within- and between-community diversity was consistent among microbial communities from similar environments. Community structure changed systematically with time in less than half of the cases, and the highest rates of change were observed within ranges of 1 day to 1 month for all communities examined. Microbial communities exhibited species–time relationships (STRs), which describe the accumulation of new taxa to a community, similar to those observed previously for plant and animal communities, suggesting that STRs are remarkably consistent across a broad range of taxa. These results highlight that a continued integration of microbial ecology into the broader field of ecology will provide new insight into the temporal patterns of microbial and ‘macro''-bial communities alike.     

Trichomonas vaginalis Lipophosphoglycan Exploits Binding to Galectin-1 and -3 to Modulate Epithelial Immunity

Trichomoniasis is the most common non-viral sexually transmitted infection caused by the vaginotropic extracellular protozoan parasite Trichomonas vaginalis. The infection is recurrent, with no lasting immunity, often asymptomatic, and linked to pregnancy complications and risk of viral infection. The molecular mechanisms of immune evasion by the parasite are poorly understood. We demonstrate that galectin-1 and -3 are expressed by the human cervical and vaginal epithelial cells and act as pathogen-recognition receptors for the ceramide phosphoinositol glycan core (CPI-GC) of the dominant surface protozoan lipophosphoglycan (LPG). We used an in vitro model with siRNA galectin knockdown epithelial clones, recombinant galectins, clinical Trichomonas isolates, and mutant protozoan derivatives to dissect the function of galectin-1 and -3 in the context of Trichomonas infection. Galectin-1 suppressed chemokines that facilitate recruitment of phagocytes, which can eliminate extracellular protozoa (IL-8) or bridge innate to adaptive immunity (MIP-3α and RANTES (regulated on activation normal T cell expressed and secreted)). Silencing galectin-1 increased and adding exogenous galectin-1 suppressed chemokine responses to Trichomonas or CPI-GC/LPG. In contrast, silencing galectin-3 reduced IL-8 response to LPG. Live Trichomonas depleted the extracellular levels of galectin-3. Clinical isolates and mutant Trichomonas CPI-GC that had reduced affinity to galectin-3 but maintained affinity to galectin-1 suppressed chemokine expression. Thus via CPI-GC binding, Trichomonas is capable of regulating galectin bioavailability and function to the benefit of its parasitic survival. These findings suggest novel approaches to control trichomoniasis and warrant further studies of galectin-binding diversity among clinical isolates as a possible source for symptom disparity in parasitic infections.     

Long Runs of Homozygosity Are Enriched for Deleterious Variation

Exome sequencing offers the potential to study the population-genomic variables that underlie patterns of deleterious variation. Runs of homozygosity (ROH) are long stretches of consecutive homozygous genotypes probably reflecting segments shared identically by descent as the result of processes such as consanguinity, population size reduction, and natural selection. The relationship between ROH and patterns of predicted deleterious variation can provide insight into the way in which these processes contribute to the maintenance of deleterious variants. Here, we use exome sequencing to examine ROH in relation to the distribution of deleterious variation in 27 individuals of varying levels of apparent inbreeding from 6 human populations. A significantly greater fraction of all genome-wide predicted damaging homozygotes fall in ROH than would be expected from the corresponding fraction of nondamaging homozygotes in ROH (p < 0.001). This pattern is strongest for long ROH (p < 0.05). ROH, and especially long ROH, harbor disproportionately more deleterious homozygotes than would be expected on the basis of the total ROH coverage of the genome and the genomic distribution of nondamaging homozygotes. The results accord with a hypothesis that recent inbreeding, which generates long ROH, enables rare deleterious variants to exist in homozygous form. Thus, just as inbreeding can elevate the occurrence of rare recessive diseases that represent homozygotes for strongly deleterious mutations, inbreeding magnifies the occurrence of mildly deleterious variants as well.     

Evolutionary histories of soil fungi are reflected in their large‐scale biogeography

Although fungal communities are known to vary along latitudinal gradients, mechanisms underlying this pattern are not well‐understood. We used high‐throughput sequencing to examine the large‐scale distributions of soil fungi and their relation to evolutionary history. We tested the Tropical Conservatism Hypothesis, which predicts that ancestral fungal groups should be more restricted to tropical latitudes and conditions than would more recently derived groups. We found support for this hypothesis in that older phyla preferred significantly lower latitudes and warmer, wetter conditions than did younger phyla. Moreover, preferences for higher latitudes and lower precipitation levels were significantly phylogenetically conserved among the six younger phyla, possibly because the older phyla possess a zoospore stage that is vulnerable to drought, whereas the younger phyla retain protective cell walls throughout their life cycle. Our study provides novel evidence that the Tropical Conservatism Hypothesis applies to microbes as well as plants and animals.     

Adjusting survival estimates for premature transmitter failure: a case study from the Sacramento-San Joaquin Delta

In telemetry studies, premature tag failure causes negative bias in fish survival estimates because tag failure is interpreted as fish mortality. We used mark-recapture modeling to adjust estimates of fish survival for a previous study where premature tag failure was documented. High rates of tag failure occurred during the Vernalis Adaptive Management Plan’s (VAMP) 2008 study to estimate survival of fall-run Chinook salmon (Oncorhynchus tshawytscha) during migration through the San Joaquin River and Sacramento-San Joaquin Delta, California. Due to a high rate of tag failure, the observed travel time distribution was likely negatively biased, resulting in an underestimate of tag survival probability in this study. Consequently, the bias-adjustment method resulted in only a small increase in estimated fish survival when the observed travel time distribution was used to estimate the probability of tag survival. Since the bias-adjustment failed to remove bias, we used historical travel time data and conducted a sensitivity analysis to examine how fish survival might have varied across a range of tag survival probabilities. Our analysis suggested that fish survival estimates were low (95% confidence bounds range from 0.052 to 0.227) over a wide range of plausible tag survival probabilities (0.48–1.00), and this finding is consistent with other studies in this system. When tags fail at a high rate, available methods to adjust for the bias may perform poorly. Our example highlights the importance of evaluating the tag life assumption during survival studies, and presents a simple framework for evaluating adjusted survival estimates when auxiliary travel time data are available.