OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages

Ovarian cancer G protein-coupled receptor 1 (OGR1) is a proton-sensing molecule that can detect decreases in extracellular pH that occur during inflammation. Although OGR1 has been shown to have pro-inflammatory functions in various diseases, its role in autoimmunity has not been examined. We therefore sought to determine whether OGR1 has a role in the development of T cell autoimmunity by contrasting the development of experimental autoimmune encephalomyelitis between wild type and OGR1-knockout mice. OGR1-knockout mice showed a drastically attenuated clinical course of disease that was associated with a profound reduction in the expansion of myelin oligodendrocyte glycoprotein 35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effectors in the central nervous system. We determined that these impaired T cell responses in OGR1-knockout mice associated with a reduced frequency and number of dendritic cells in draining lymph nodes during EAE and a higher production of nitric oxide by macrophages. Our studies suggest that OGR1 plays a key role in regulating T cell responses during autoimmunity.     

Geometric morphometric analysis of the effect of temperature on wing size and shape in Aedes albopictus

Wing geometry helps to identify mosquito species, even cryptic ones. On the other hand, temperature has a well‐known effect on insect metric properties. Can such effects blur the taxonomic signal embedded in the wing? Two strains of Aedes albopictus (laboratory and field strain) were examined under three different rearing temperatures (26, 30 and 33 °C) using landmark‐ and outline‐based morphometric approaches. The wings of each experimental line were compared with Aedes aegypti. Both approaches indicated similar associations between wing size and temperature. For the laboratory strain, the wing size significantly decreased as the temperature increased. For the field strain, the largest wings were observed at the intermediate temperature. The two morphometric approaches describing shape showed different sensibilities to temperature. For both strains and sexes, the landmark‐based approach disclosed significant wing shape changes with temperature changes. The outline‐based approach showed lesser effects, detecting significant changes only in laboratory females and in field males. Despite the size and shape changes induced by temperature, the two strains of Ae. albopictus were always distinguished from Ae. aegypti. The present study confirms the lability of size. However, it also suggests that, despite environmentally‐induced variation, the architecture of the wing still provides a strong taxonomic signal.     

Composition and stability of the vervet monkey milk microbiome

The human milk microbiome is vertically transmitted to offspring during the postnatal period and has emerged as a critical driver of infant immune and metabolic development. Despite this importance in humans, the milk microbiome of nonhuman primates remains largely unexplored. This dearth of comparative work precludes our ability to understand how species‐specific differences in the milk microbiome may differentially drive maternal effects and limits how translational models can be used to understand the role of vertically transmitted milk microbes in human development. Here, we present the first culture‐independent data on the milk microbiome of a nonhuman primate. We collected milk and matched fecal microbiome samples at early and late lactation from a cohort of captive lactating vervet monkeys (N = 15). We found that, similar to humans, the vervet monkey milk microbiome comprises a shared community of taxa that are universally present across individuals. However, unlike in humans, this shared community is dominated by the genera Lactobacillus, Bacteroides, and Prevotella. We also found that, in contrast to previous culture‐dependent studies in humans, the vervet milk microbiome exhibits greater alpha‐diversity than the gut microbiome across lactation. Finally, we did not find support for the translocation of microbes from the gut to the mammary gland within females (i.e., “entero‐mammary pathway”). Taken together, our results show that the vervet monkey milk microbiome is taxonomically diverse, distinct from the gut microbiome, and largely stable. These findings demonstrate that the milk microbiome is a unique substrate that may selectively favor the establishment and persistence of particular microbes across lactation and highlights the need for future experimental studies on the origin of microbes in milk.     

Inter-monomer electron transfer is too slow to compete with monomeric turnover in bc1 complex

The homodimeric bc₁ complexes are membrane proteins essential in respiration and photosynthesis. The ~ 11 Å distance between the two b_L-hemes of the dimer opens the possibility of electron transfer between them, but contradictory reports make such inter-monomer electron transfer controversial. We have constructed in Rhodobacter sphaeroides a heterodimeric expression system similar to those used before, in which the bc₁ complex can be mutated differentially in the two copies of cyt b to test for inter-monomer electron transfer, but found that genetic recombination by cross-over then occurs to produce wild-type homodimer. Selection pressure under photosynthetic growth always favored the homodimer over heterodimeric variants enforcing inter-monomer electron transfer, showing that the latter are not competitive. These results, together with kinetic analysis of myxothiazol titrations, demonstrate that inter-monomer electron transfer does not occur at rates competitive with monomeric turnover. We examine the results from other groups interpreted as demonstrating rapid inter-monomer electron transfer, conclude that similar mechanisms are likely to be in play, and suggest that such claims might need to be re-examined.