Life in Burrows Channelled the Morphological Evolution of the Skull in Rodents: the Case of African Mole-Rats (Bathyergidae,Rodentia)

African mole-rats are fossorial rodents that consist of five chisel-tooth digging genera (Heterocephalus, Heliophobius, Georychus, Fukomys, and Cryptomys) and one scratch digger (Bathyergus). They are characterized by striking physiological, morphological, and behavioral adaptations intimately related to their subterranean life. The influence of their mode of life in shaping the cranial morphology has yet to be evaluated in comparison to other Ctenohystrica, especially fossorial genera, which include the subterranean genera Spalacopus and Ctenomys. In our study, we seek to determine to what extent subterranean life affects the morpho-functional properties of the skull among fossorial ctenohystricans. 3D geometric morphometric analyses were performed on 277 skulls, encompassing 63 genera of Ctenohystrica, and complemented by biomechanical studies. African mole-rats and other subterranean Ctenohystrica, especially chisel-tooth diggers, have a short snout, a wide cranium with enlarged zygomatic arches, and a strongly hystricognathous mandible. Even if convergences are also manifest between most fossorial Ctenohystrica, subterranean rodents departed from the main ctenohystrican allometric trends in having a skull shape less size-dependent, but under stronger directional selection with intense digging activity as a major constraint. African mole-rats, notably chisel-tooth diggers, show important mechanical advantage for the temporalis muscles favoring higher forces at the bite point, while mechanical advantage of the superficial masseter muscles is lower compared to other Ctenohystrica. If subterranean species can be clearly discriminated based on their skull morphology, the intrinsic mosaic of anatomical characters of each genus (e.g., skull, teeth, and muscles) can be understood only in the light of their ecology and evolutionary history.     

Noemi Controls Production of Flavonoid Pigments and Fruit Acidity and Illustrates the Domestication Routes of Modern Citrus Varieties

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Sowing of margin strips rich in floral resources improves herbivore control in adjacent crop fields

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Growth of an anaerobic sulfate-reducing bacterium sustained by oxygen respiratory energy conservation after O2-driven experimental evolution

Desulfovibrio species are representatives of microorganisms at the boundary between anaerobic and aerobic lifestyles, since they contain the enzymatic systems required for both sulfate and oxygen reduction. However, the latter has been shown to be solely a protective mechanism. By implementing the oxygen-driven experimental evolution of Desulfovibrio vulgaris Hildenborough, we have obtained strains that have evolved to grow with energy derived from oxidative phosphorylation linked to oxygen reduction. We show that a few mutations are sufficient for the emergence of this phenotype and reveal two routes of evolution primarily involving either inactivation or overexpression of the gene encoding heterodisulfide reductase. We propose that the oxygen respiration for energy conservation that sustains the growth of the O₂-evolved strains is associated with a rearrangement of metabolite fluxes, especially NAD⁺/NADH, leading to an optimized O₂ reduction. These evolved strains are the first sulfate-reducing bacteria that exhibit a demonstrated oxygen respiratory process that enables growth.     

Role of the Spatzle Pro-domain in the generation of an active toll receptor ligand

The cytokine Sp?tzle is the ligand for Drosophila Toll, the prototype of an important family of membrane receptors that function in embryonic patterning and innate immunity. A dimeric precursor of Sp?tzle is processed by an endoprotease to produce a form (C-106) that cross-links Toll receptor ectodomains and establishes signaling. Here we show that before processing the pro-domain of Sp?tzle is required for correct biosynthesis and secretion. We mapped two loss-of-function mutations of Sp?tzle to a discrete site in the pro-domain and showed that the phenotype arises because of a defect in biosynthesis rather than signaling. We also report that the pro-domain and C-106 remain associated after cleavage and that this processed complex signals with the same characteristics as the C-terminal fragment. These results suggest that before activation the determinants on C-106 that bind specifically to Toll are sequestered by the pro-domain and that proteolytic processing causes conformational rearrangements that expose these determinants and enables binding to Toll. Furthermore, we show that the pro-domain is released when the Toll extracellular domain binds to the complex, a finding that has implications for the generation of a signaling-competent Toll dimer.     

Thiacetazone, an antitubercular drug that inhibits cyclopropanation of cell wall mycolic acids in mycobacteria

Background

Mycolic acids are a complex mixture of branched, long-chain fatty acids, representing key components of the highly hydrophobic mycobacterial cell wall. Pathogenic mycobacteria carry mycolic acid sub-types that contain cyclopropane rings. Double bonds at specific sites on mycolic acid precursors are modified by the action of cyclopropane mycolic acid synthases (CMASs). The latter belong to a family of S-adenosyl-methionine-dependent methyl transferases, of which several have been well studied in Mycobacterium tuberculosis, namely, MmaA1 through A4, PcaA and CmaA2. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence of M. tuberculosis. While several antitubercular agents inhibit mycolic acid synthesis, to date, the CMASs have not been shown to be drug targets.

Methodology/Principle Findings

We have employed various complementary approaches to show that the antitubercular drug, thiacetazone (TAC), and its chemical analogues, inhibit mycolic acid cyclopropanation. Dramatic changes in the content and ratio of mycolic acids in the vaccine strain Mycobacterium bovis BCG, as well as in the related pathogenic species Mycobacterium marinum were observed after treatment with the drugs. Combination of thin layer chromatography, mass spectrometry and Nuclear Magnetic Resonance (NMR) analyses of mycolic acids purified from drug-treated mycobacteria showed a significant loss of cyclopropanation in both the α- and oxygenated mycolate sub-types. Additionally, High-Resolution Magic Angle Spinning (HR-MAS) NMR analyses on whole cells was used to detect cell wall-associated mycolates and to quantify the cyclopropanation status of the cell envelope. Further, overexpression of cmaA2, mmaA2 or pcaA in mycobacteria partially reversed the effects of TAC and its analogue on mycolic acid cyclopropanation, suggesting that the drugs act directly on CMASs.

Conclusions/Significance

This is a first report on the mechanism of action of TAC, demonstrating the CMASs as its cellular targets in mycobacteria. The implications of this study may be important for the design of alternative strategies for tuberculosis treatment.