BACKGROUND AND PURPOSEStudies have demonstrated that a moderate intake of amino acids is associated with development of bone health. Methionine, a sulphur-containing essential amino acid, has been largely implicated for improving cartilage formation, however its physiological significance on bone integrity and functionality have not been elucidated. We investigated whether methionine can prevent osteoporotic bone loss. EXPERIMENTAL APPROACHThe anti-resorptive effect of methionine, (250 mg kg −1 body wt administered in drinking water for 10 weeks), was evaluated in ovariectomized (OVX) rats by monitoring changes in bone turnover, formation of osteoclasts from blood-derived mononuclear cells and changes in the synthesis of pro-osteoclastogenic cytokines. KEY RESULTSMethionine improved bone density and significantly decreased the degree of osteoclast development from blood mononuclear cells in OVX rats, as indicated by decreased production of osteoclast markers tartarate resistant acid phosphatase b (TRAP5b) and MIP-1α. siRNA-mediated knockdown of myeloid differentiation primary response 88 [MyD88], a signalling molecule in the toll-like receptor (TLR) signalling cascade, abolished the synthesis of both TRAP5b and MIP-1α in developing osteoclasts. Methionine supplementation disrupted osteoclast development by inhibiting TLR-4/MyD88/NF-κB pathway. CONCLUSIONS AND IMPLICATIONSTLR-4/MyD88/NF-κB signalling pathway is integral for osteoclast development and this is down-regulated in osteoporotic system on methionine treatment. Methionine treatment could be beneficial for the treatment of postmenopausal osteoporosis. AbbreviationsCTX, C-terminal telopeptides; MIP-1α, macrophage inhibitory protein-1α; MyD88, myeloid differentiation primary response gene 88; NFATc1, nuclear factor of activated T-cells; OVX, ovariectomized; TNFSF11, receptor activator of NF-κB ligand (also known as RANKL); TLR, toll-like receptor; TRAP5b, tartrate-resistant acid phosphatase 5b

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Although accumulating evidence indicates that tolerance is a plant defence strategy against pathogens as widespread as resistance, how plants evolve tolerance is poorly understood. Theory predicts that hosts will evolve to maximize tolerance or resistance, but not both. Remarkably, most experimental works failed in finding this trade-off. We tested the hypothesis that the evolution of tolerance to one virus is traded-off against tolerance to others, rather than against resistance and identified the associated mechanisms. To do so, we challenged eighteen Arabidopsis thaliana genotypes with Turnip mosaic virus (TuMV) and Cucumber mosaic virus (CMV). We characterized plant life-history trait modifications associated with reduced effects of TuMV and CMV on plant seed production (fecundity tolerance) and life period (mortality tolerance), both measured as a norm of reaction across viral loads (range tolerance). Also, we analysed resistance-tolerance and tolerance-tolerance trade-offs. Results indicate that tolerance to TuMV is associated with changes in the length of the pre-reproductive and reproductive periods, and tolerance to CMV with resource reallocation from growth to reproduction; and that tolerance to TuMV is traded-off against tolerance to CMV in a virulence-dependent manner. Thus, this work provides novel insights on the mechanisms of plant tolerance and highlights the importance of considering the combined effect of different pathogens to understand how plant defences evolve.

The human biliary system is formed from the hepatic diverticulum, a structure which develops from the embryonic foregut in the fourth week of gestation. The cephalic portion of the hepatic diverticulum lies within the septum transversum, and gives rise to entodermal cells which become the primitive hepatocytes. The caudal part of the hepatic diverticulum is molded by mesenchyme to form the gallbladder, cystic duct, and extrahepatic bile duct. The gallbladder is initially tubular in shape, and undergoes morphological changes to become saccular during the 11th week of gestation. The extrahepatic bile duct elongates and widens as gestation progresses, and intramural mucus glands develop. There is no solid stage during the development of the extrahepatic bile duct. The extrahepatic bile duct is a well-defined tubular structure by the 6th week of gestation, whereas the intrahepatic biliary system during this period of gestation is represented by the primitive ductal plate. The ductal plate undergoes structural changes from the 11th week of gestation, beginning at the porta hepatis and progressing through gestation to the periphery of the liver. This remodeling process shapes the ductal plate from a flat sheath of biliary epithelium surrounding the portal vein branches into a network of interconnecting tubular structures. Mesenchyme plays an important role in ductal plate remodeling. The intrahepatic biliary system is in luminal continuity with the extrahepatic bile duct throughout gestation at the porta hepatis. The major bile ducts at the porta hepatis are fully formed by the 16th week of gestation.