A meningococcal factor H binding protein mutant that eliminates factor H binding enhances protective antibody responses to vaccination

Certain pathogens recruit host complement inhibitors such as factor H (fH) to evade the immune system. Microbial complement inhibitor-binding molecules can be promising vaccine targets by eliciting Abs that neutralize this microbial defense mechanism. One such Ag, meningococcal factor H-binding protein (fHbp), was used in clinical trials before the protein was discovered to bind fH. The potential effect of fH binding on vaccine immunogenicity had not been assessed in experimental animals because fHbp binds human fH specifically. In this study, we developed a human fH transgenic mouse model. Transgenic mice immunized with fHbp vaccine had 4- to 8-fold lower serum bactericidal Ab responses than those of control mice whose native fH did not bind the vaccine. In contrast, Ab responses were unimpaired in transgenic mice immunized with a control meningococcal group C polysaccharide-protein conjugate vaccine. In transgenic mice, immunization with an fH nonbinding mutant of fHbp elicited Abs with higher bactericidal activity than that of fHbp vaccination itself. Abs elicited by the mutant fHbp more effectively blocked fH binding to wild-type fHbp than Abs elicited by fHbp that bound fH. Thus, a mutant fHbp vaccine that does not bind fH but that retains immunogenicity is predicted to be superior in humans to an fHbp vaccine that binds human fH. In the case of mutant fHbp vaccination, the resultant Ab responses may be directed more at epitopes in or near the fH binding site, which result in greater complement-mediated serum bactericidal activity; these epitopes may be obscured when human fH is bound to the wild-type fHbp vaccine.     

The miR-30 MicroRNA Family Targets smoothened to Regulate Hedgehog Signalling in Zebrafish Early Muscle Development

The importance of microRNAs in development is now widely accepted. However, identifying the specific targets of individual microRNAs and understanding their biological significance remains a major challenge. We have used the zebrafish model system to evaluate the expression and function of microRNAs potentially involved in muscle development and study their interaction with predicted target genes. We altered expression of the miR-30 microRNA family and generated phenotypes that mimicked misregulation of the Hedgehog pathway. Inhibition of the miR-30 family increases activity of the pathway, resulting in elevated ptc1 expression and increased numbers of superficial slow-muscle fibres. We show that the transmembrane receptor smoothened is a target of this microRNA family. Our results indicate that fine coordination of smoothened activity by the miR-30 family allows the correct specification and differentiation of distinct muscle cell types during zebrafish embryonic development.     

Schistosoma japonicum Soluble Egg Antigens Attenuate Invasion in a First Trimester Human Placental Trophoblast Model

Background

Schistosomiasis affects nearly 40 million women of reproductive age, and is known to elicit a pro-inflammatory signature in the placenta. We have previously shown that antigens from schistosome eggs can elicit pro-inflammatory cytokine production from trophoblast cells specifically; however, the influence of these antigens on other characteristics of trophoblast function, particularly as it pertains to placentation in early gestation, is unknown. We therefore sought to determine the impact of schistosome antigens on key characteristics of first trimester trophoblast cells, including migration and invasion.

Methods

First trimester HTR8/SVneo trophoblast cells were co-cultured with plasma from pregnant women with and without schistosomiasis or schistosome soluble egg antigens (SEA) and measured cytokine, cellular migration, and invasion responses.

Results

Exposure of HTR8 cells to SEA resulted in a pro-inflammatory, anti-invasive signature, characterized by increased pro-inflammatory cytokines (IL-6, IL-8, MCP-1) and TIMP-1. Additionally, these cells displayed 62% decreased migration and 2.7-fold decreased invasion in vitro after treatment with SEA. These results are supported by increased IL-6 and IL-8 in the culture media of HTR8 cells exposed to plasma from Schistosoma japonica infected pregnant women.

Conclusions

Soluble egg antigens found in circulation during schistosome infection increase pro-inflammatory cytokine production and inhibit the mobility and invasive characteristics of the first trimester HTR8/SVneo trophoblast cell line. This is the first study to assess the impact of schistosome soluble egg antigens on the behavior of an extravillous trophoblast model and suggests that schistosomiasis in the pre-pregnancy period may adversely impact placentation and the subsequent health of the mother and newborn.     

Defining null expectations for animal site fidelity

Site fidelity—the tendency to return to previously visited locations—is widespread across taxa. Returns may be driven by several mechanisms, including memory, habitat selection, or chance; however, pattern-based definitions group different generating mechanisms under the same label of ‘site fidelity’, often assuming memory as the main driver. We propose an operational definition of site fidelity as patterns of return that deviate from a null expectation derived from a memory-free movement model. First, using agent-based simulations, we show that without memory, intrinsic movement characteristics and extrinsic landscape characteristics are key determinants of return patterns and that even random movements may generate substantial probabilities of return. Second, we illustrate how to implement our framework empirically to establish ecologically meaningful, system-specific null expectations for site fidelity. Our approach provides a conceptual and operational framework to test hypotheses on site fidelity across systems and scales.     

A landscape approach for identifying potential reestablishment sites for extirpated stream fishes: an example with Arctic grayling (Thymallus arcticus) in Michigan

Hydrobiologia - Habitat degradation combined with climate change increases the threat of extinction for stream fishes. In response to these threats, efforts to reestablish species within formerly...     

Effects of age,sex, and ENSO phase on foraging and flight performance in Nazca boobies

Age‐related changes in survival and reproduction are common in seabirds; however, the underlying causes remain elusive. A lack of experience for young individuals, and a decline in foraging performance for old birds, could underlie age‐related variation in reproduction because reproductive success is connected closely to provisioning offspring. For seabirds, flapping flight during foraging trips is physiologically costly; inexperience or senescent decline in performance of this demanding activity might cap delivery of food to the nest, providing a proximate explanation for poor breeding success in young and old age, respectively. We evaluated the hypothesis that young and old Nazca boobies (Sula granti), a Galápagos seabird, demonstrate deficits in foraging outcomes and flight performance. We tagged incubating male and female adults across the life span with both accelerometer and GPS loggers during the incubation periods of two breeding seasons (years), during the 2015 El Niño and the following weak La Niña. We tested the ability of age, sex, and environment to explain variation in foraging outcomes (e.g., mass gained) and flight variables (e.g., wingbeat frequency). Consistent with senescence, old birds gained less mass while foraging than middle‐aged individuals, a marginal effect, and achieved a slower airspeed late in a foraging trip. Contrary to expectations, young birds showed no deficit in foraging outcomes or flight performance, except for airspeed (contingent on environment). Young birds flew slower than middle‐aged birds in 2015, but faster than middle‐aged birds in 2016. Wingbeat frequency, flap–glide ratio, and body displacement (approximating wingbeat strength) failed to predict airspeed and were unaffected by age. Sex influenced nearly all aspects of performance. Environment affected flight performance and foraging outcomes. Boobies'' foraging outcomes were better during the extreme 2015 El Niño than during the 2016 weak La Niña, a surprising result given the negative effects tropical seabirds often experience during extreme El Niños.     

Mafb and c-Maf Have Prenatal Compensatory and Postnatal Antagonistic Roles in Cortical Interneuron Fate and Function

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A meta-analysis of elevated [CO2] effects on soybean (Glycine max) physiology, growth and yield

The effects of elevated [CO₂] on 25 variables describing soybean physiology, growth and yield are reviewed using meta‐analytic techniques. This is the first meta‐analysis to our knowledge performed on a single crop species and summarizes the effects of 111 studies. These primary studies include numerous soybean growth forms, various stress and experimental treatments, and a range of elevated [CO₂] levels (from 450 to 1250 p.p.m.), with a mean of 689 p.p.m. across all studies. Stimulation of soybean leaf CO₂ assimilation rate with growth at elevated [CO₂] was 39%, despite a 40% decrease in stomatal conductance and a 11% decrease in Rubisco activity. Increased leaf CO₂ uptake combined with an 18% stimulation in leaf area to provide a 59% increase in canopy photosynthetic rate. The increase in total dry weight was lower at 37%, and seed yield still lower at 24%. This shows that even in an agronomic species selected for maximum investment in seed, several plant level feedbacks prevent additional investment in reproduction, such that yield fails to reflect fully the increase in whole plant carbon uptake. Large soil containers (> 9 L) have been considered adequate for assessing plant responses to elevated [CO₂]. However, in open‐top chamber experiments, soybeans grown in large pots showed a significant threefold smaller stimulation in yield than soybeans grown in the ground. This suggests that conclusions about plant yield based on pot studies, even when using very large containers, are a poor reflection of performance in the absence of any physical restriction on root growth. This review supports a number of current paradigms of plant responses to elevated [CO₂]. Namely, stimulation of photosynthesis is greater in plants that fix N and have additional carbohydrate sinks in nodules. This supports the notion that photosynthetic capacity decreases when plants are N‐limited, but not when plants have adequate N and sink strength. The root : shoot ratio did not change with growth at elevated [CO₂], sustaining the charge that biomass allocation is unaffected by growth at elevated [CO₂] when plant size and ontogeny are considered.