Hierarchy of effects of the MHC and T cell receptor beta-chain genes in susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease.

Intracerebral inoculation of susceptible mice with Theiler's murine encephalomyelitis virus induces a demyelinating disease that is similar to human multiple sclerosis. This murine model for human multiple sclerosis is apparently immune-mediated and the genes involved in the immune response influence the outcome of disease susceptibility as observed with human multiple sclerosis. These genes include the MHC and TCR genes. However, the functional relationships among these genes on the disease susceptibility has not yet been studied. In this study, we demonstrate that the effect of the H-2s genotype from susceptible SJL/J mice overrides the resistant effect of the BALB/c TCR beta-chain gene in CXJ recombinant-inbred and BALB.S congenic mice. These results strongly suggest the presence of a hierarchy of genes involved in the immune response in Theiler's murine encephalomyelitis virus-induced demyelinating disease.     

Role of kallikrein-kininogen system in insulin-stimulated glucose transport after muscle contractions.

Serum proteins [molecular weight (MW) > 10,000] are essential for increased insulin-stimulated glucose transport after in vitro muscle contractions. We investigated the role of the kallikrein-kininogen system, including bradykinin, which is derived from kallikrein (MW > 10,000)-catalyzed degradation of serum protein kininogen (MW > 10,000), on this contraction effect. In vitro electrical stimulation of rat epitrochlearis muscles was performed in 1) rat serum +/- kallikrein inhibitors; 2) human plasma (normal or kallikrein-deficient); 3) rat serum +/- bradykinin receptor-2 inhibitors; or 4) serum-free buffer +/- bradykinin. 3-O-methylglucose transport (3-MGT) was measured 3.5 h later. Serum +/- kallikrein inhibitors tended (P = 0.08) to diminish postcontraction insulin-stimulated 3-MGT. Contractions in normal plasma enhanced insulin-stimulated 3-MGT vs. controls, but contractions in kallikrein-deficient plasma did not. Supplementing rat serum with bradykinin receptor antagonist HOE-140 during contraction did not alter insulin-stimulated 3-MGT. Muscles stimulated to contract in serum-free buffer plus bradykinin did not have enhanced insulin-stimulated 3-MGT. Bradykinin was insufficient for postcontraction-enhanced insulin sensitivity. However, results with kallikrein inhibitors and kallikrein-deficient plasma suggest kallikrein plays a role in this improved insulin action.     

The phosphorus/oxygen ratio of mitochondrial oxidative phosphorylation.

The transport of ATP out of mitochondria and uptake of ADP and Pi into the matrix are coupled to the uptake of one proton (Klingenberg, M., and Rottenberg, H. (1977) Eur. J. Biochem. 73, 125--130). According to the chemiosmotic hypothesis of oxidative phosphorylation this coupling of nucleotide and Pi transport to proton transport implies that the P/O ratio for the synthesis and transport of ATP to the external medium is less than the P/O ratio for the synthesis of ATP inside mitochondria. A survey of previous determinations of the P/O ratio of intact mitochondria showed little convincing evidence in support of the currently accepted values of 3 with NADH-linked substrates and 2 with succinate. We have measured P/O ratios in rat liver mitochondria by the ADP pulse method and by 32 Pi esterification, measuring oxygen uptake with an oxygen electrode, and find values close to 2 with beta-hydroxybutyrate as substrate and 1.3 with succinate as substrate in the presence of rotenone to inhibit NADH oxidation. These values were largely independent of pH, temperature, Mg2+ ion concentration, Pi concentration, ADP pulse size, or amount of mitochondria used. We suggest that these are the true values of the P/O ratio for ATP synthesis and transport by mitochondria, and that previously reported higher values resulted from errors in the determination of oxygen uptake and the use of substrates which lead to ATP synthesis by succinate thiokinase.     

Melanocortin‐1 receptor structure and functional regulation

The melanogenic actions of the melanocortins are mediated by the melanocortin‐1 receptor (MC1R). MC1R is a member of the G‐protein‐coupled receptors (GPCR) superfamily expressed in cutaneous and hair follicle melanocytes. Activation of MC1R by adrenocorticotrophin or α‐melanocyte stimulating hormone is positively coupled to the cAMP signaling pathway and leads to a stimulation of melanogenesis and a switch from the synthesis of pheomelanins to the production of eumelanic pigments. The functional behavior of the MC1R agrees with emerging concepts in GPCR signaling including dimerization, coupling to more than one signaling pathway and a high agonist‐independent constitutive activity accounting for inverse agonism phenomena. In addition, MC1R displays unique properties such as an unusually high number of natural variants often associated with clearly visible phenotypes and the occurrence of endogenous peptide antagonists. Therefore MC1R is an ideal model to study GPCR function. Here we review our current knowledge of MC1R structure and function, with emphasis on information gathered from the analysis of natural variants. We also discuss recent data on the regulation of MC1R function by paracrine and endocrine factors and by external stimuli such as ultraviolet light.     

Modulatory effect of Lactobacillus acidophilus KLDS 1.0738 on intestinal short‐chain fatty acids metabolism and GPR41/43 expression in β‐lactoglobulin–sensitized mice

We investigated the correlation between the beneficial effect of Lactobacillus acidophilus on gut microbiota composition, metabolic activities, and reducing cow's milk protein allergy. Mice sensitized with β‐lactoglobulin (β‐Lg) were treated with different doses of L. acidophilus KLDS 1.0738 for 4 weeks, starting 1 week before allergen induction. The results showed that intake of L. acidophilus significantly suppressed the hypersensitivity responses, together with increased fecal microbiota diversity and short‐chain fatty acids (SCFAs) concentration (including propionate, butyrate, isobutyrate, and isovalerate) when compared with the allergic group. Moreover, treatment with L. acidophilus induced the expression of SCFAs receptors, G‐protein–coupled receptors 41 (GPR41) and 43 (GPR43), in the spleen and colon of the allergic mice. Further analysis revealed that the GPR41 and GPR43 messenger RNA expression both positively correlated with the serum concentrations of transforming growth factor‐β and IFN‐γ (p < .05), but negatively with the serum concentrations of IL‐17, IL‐4, and IL‐6 in the L. acidophilus–treated group compared with the allergic group (p < .05). These results suggested that L. acidophilus protected against the development of allergic inflammation by improving the intestinal flora, as well as upregulating SCFAs and their receptors GPR41/43.     

Automated extraction of bank angles from bird‐borne video footage using open‐source software

The use of miniaturized video cameras to study the at‐sea behavior of flying seabirds has increased in recent years. These cameras allow researchers to record several behaviors that were not previously possible to observe. However, video recorders produce large amounts of data and videos can often be time‐consuming to analyze. We present a new technique using open‐source software to extract bank angles from bird‐borne video footage. Bank angle is a key facet of dynamic soaring, which allows albatrosses and petrels to efficiently search vast areas of ocean for food. Miniaturized video cameras were deployed on 28 Wandering Albatrosses (Diomedea exulans) on Marion Island (one of the two Prince Edward Islands) from 2016 to 2018. The OpenCV library for the Python programming language was used to extract the angle of the horizon relative to the bird’s body (= bank angle) from footage when the birds were flying using a series of steps focused on edge detection. The extracted angles were not significantly different from angles measured manually by three independent observers, thus being a valid method to measure bank angles. Image quality, high wind speeds, and sunlight all influenced the accuracy of angle estimates, but post‐processing eliminated most of these errors. Birds flew most often with cross‐winds (58%) and tailwinds (39%), resulting in skewed distributions of bank angles when birds turned into the wind more often. Higher wind speeds resulted in extreme bank angles (maximum observed was 94°). We present a novel method for measuring postural data from seabirds that can be used to describe the fine‐scale movements of the dynamic‐soaring cycle. Birds appeared to alter their bank angle in response to varying wind conditions to counter wind drift associated with the prevailing westerly winds in the Southern Ocean. These data, in combination with fine‐scale positional data, may lead to new insights into dynamic‐soaring flight.     

Chromosome evolution and phylogeny in Ronderosia (Orthoptera,Acrididae, Melanoplinae): clues of survivors to the challenge of sympatry?

In an attempt to unveil the origin of neo‐sex chromosomes in Ronderosia Cigliano grasshoppers, we performed a combined phylogenetic analysis based on morphological (external morphology and male genitalia) and molecular data (COI, COII, 16S and ITS2) to explore the chromosome evolution within the genus. We also analysed the distributional patterns of the various Ronderosia species and considered the possible role of chromosome rearrangements (CRs) in speciation processes within the genus in the light of ‘suppressed‐recombination’ models. We mapped the states of three chromosomal characters on the combined tree topology. The combined evidence supported Ronderosia as a monophyletic group. The cytogenetic analyses of the genus demonstrated the importance of rearranged karyotypes with single, complex and multiples neo‐sex chromosome determination systems in all species. The chromosome character optimisation suggests X‐autosome centric fusion as the mechanism responsible for neo‐sex chromosome formation in most Ronderosia species, except in R. dubia and R. bergii. Similar autosomes were involved in fusions with the ancestral X chromosome in Ronderosia, supporting previous hypotheses on the unique origin of X‐autosome fusion for the sex chromosome in the genus. As a source of chromosome variation, autosome‐autosome centric fusion played a secondary role in Ronderosia compared with other Dichroplini. Given the homogeneity in the morphological features, the sympatric distribution of closely related species and the intrinsic property of centric fusion as suppressors of the crossing over, we suggest that CRs may have played a key role during the speciation process within Ronderosia.