Identification and dynamics of a beneficial mutation in a long-term evolution experiment with Escherichia coli

Background  

Twelve populations of E. coli were serially propagated for 20,000 generations in a glucose-supplemented minimal medium in order to study the dynamics of evolution. We sought to find and characterize one of the beneficial mutations responsible for the adaptation and other phenotypic changes, including increased cell size, in one of these populations.     

BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection

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Noncanonical Transforming Growth Factor β (TGFβ) Signaling in Cranial Neural Crest Cells Causes Tongue Muscle Developmental Defects

Microglossia is a congenital birth defect in humans and adversely impacts quality of life. In vertebrates, tongue muscle derives from the cranial mesoderm, whereas tendons and connective tissues in the craniofacial region originate from cranial neural crest (CNC) cells. Loss of transforming growth factor β (TGFβ) type II receptor in CNC cells in mice (Tgfbr2^fl/fl;Wnt1-Cre) causes microglossia due to a failure of cell-cell communication between cranial mesoderm and CNC cells during tongue development. However, it is still unclear how TGFβ signaling in CNC cells regulates the fate of mesoderm-derived myoblasts during tongue development. Here we show that activation of the cytoplasmic and nuclear tyrosine kinase 1 (ABL1) cascade in Tgfbr2^fl/fl;Wnt1-Cre mice results in a failure of CNC-derived cell differentiation followed by a disruption of TGFβ-mediated induction of growth factors and reduction of myogenic cell proliferation and differentiation activities. Among the affected growth factors, the addition of fibroblast growth factor 4 (FGF4) and neutralizing antibody for follistatin (FST; an antagonist of bone morphogenetic protein (BMP)) could most efficiently restore cell proliferation, differentiation, and organization of muscle cells in the tongue of Tgfbr2^fl/fl;Wnt1-Cre mice. Thus, our data indicate that CNC-derived fibroblasts regulate the fate of mesoderm-derived myoblasts through TGFβ-mediated regulation of FGF and BMP signaling during tongue development.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin Slows the Progression of Experimental Cutaneous Leishmaniasis in Susceptible BALB/c and SCID Mice

In a model of experimental cutaneous leishmaniasis, pre-exposure of Leishmania major-resistant mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor agonist, causes suppression of the protective anti-parasite T helper 1 response while paradoxically also reducing parasite burdens in those animals. In this study, we examined if TCDD exposure could also reduce parasite burdens in L. major-susceptible BALB/c mice. In the highest dose group (160 µg/Kg), TCDD treatment caused a significant reduction of parasite burdens by 10-fold after three weeks while also causing a significant lymphoid atrophy indicating suppression of the non-protective T helper 2 response. A dose-dependent delay of foot lesion progression was also observed such that lesion size in the highest dose group was less than half that of controls after 35 days of infection. Importantly, although TCDD exposure initially reduced disease severity and prolonged the course of disease by as much as three fold in some animals, this effect was transitory and TCDD did not induce resistance to L. major infection. Because TCDD exposure reduced L. major burdens in both resistant and susceptible mice, we hypothesized that TCDD reduces L. major burdens in mice by a mechanism that does not involve adaptive immunity. To test this, severe combined immunodeficient (SCID) mice were used. In mice infected with a moderate number of L. major (10,000), TCDD treatment caused a time- and dose-dependent decrease of parasite burdens by nearly 100-fold after six weeks in the highest dose group (200 µg/Kg). A significant and dose-dependent delay of foot lesion progression was also observed in these animals. These results indicate that TCDD exposure can reduce the severity of leishmanial disease in mice independent of adaptive immunity.     

Porcine-specific hemoglobin saturation measurements.

The determination of O(2) consumption by using arteriovenous O(2) content differences is dependent on accurate oxyhemoglobin saturation measurements. Because swine are a common experimental species, we describe the validation of CO-oximeter for porcine-specific oxyhemoglobin saturation. After developing a nonlinear mathematical model of the porcine oxyhemoglobin saturation curve, we made 366 porcine oxyhemoglobin saturation determinations with a calibrated blood-gas analyzer and a porcine-specific CO-oximeter. There was a high degree of correlation with minimal variability (r(2) = 0.99, SE of the estimate = 5.2%) between the mathematical model and the porcine-specific CO-oximeter measurements. Bland-Altman comparison showed that the CO-oximeter measurements were biased slightly lower (-0.4 vol%), and the limits of agreement (+/-2 SD) were 0.7 and -1.5 vol%. This is in contrast to a 10-20 vol% error if human-specific methods were used. The results show excellent agreement between the nonlinear model and CO-oximeter for porcine-specific oxyhemoglobin saturation measurements. In contrast, comparison of the porcine-specific oxyhemoglobin saturations with saturations obtained by using human methods highlights the necessity of species-specific measurement methodology.     

Variation of phenotype,ploidy level,and organogenic potential of in vitro regenerated polyploids of <Emphasis Type="Italic">Pyrus communis</Emphasis>

A wide range of phenotypic variation was observed among neopolyploids obtained from the diploid pear cultivar ‘Fertility’ by in vitro colchicine treatment. The variant plantlets had alterations in leaf characteristics. Neopolyploids had significantly different ratios of leaf length to leaf width compared to the diploid control. Shoot regeneration from leaf explants and rooting ability from in vitro shoots of neopolyploids was examined. Regeneration frequencies of shoots from leaf explants of seven of the nine neopolyploids were significantly decreased compared to the diploid control. The organogenic potential of neopolyploids was highly genotype-dependent for both shoots and roots. Tetraploid clone 4x − 4 failed to regenerate shoots from leaf explants and the pentaploid clone 5x − 2 failed to root from in vitro shoots. The results suggest that polyploidization caused the decrease in or loss of in vitro organogenic potential. Regenerated shoots derived from neopolyploids showed different phenotypes, depending on the ploidy of the donor plant.