Poor conditions during early development can initiate trade‐offs that favour current survival at the expense of somatic maintenance and subsequently, future reproduction. However, the mechanisms that link early and late life‐history are largely unknown. Recently it has been suggested that telomeres, the nucleoprotein structures at the terminal end of chromosomes, could link early‐life conditions to lifespan and fitness. In wild purple‐crowned fairy‐wrens, we combined measurements of nestling telomere length (TL) with detailed life‐history data to investigate whether early‐life TL predicts fitness prospects. Our study differs from previous studies in the completeness of our fitness estimates in a highly philopatric population. The association between TL and survival was age‐dependent with early‐life TL having a positive effect on lifespan only among individuals that survived their first year. Early‐life TL was not associated with the probability or age of gaining a breeding position. Interestingly, early‐life TL was positively related to breeding duration, contribution to population growth and lifetime reproductive success because of their association with lifespan. Thus, early‐life TL, which reflects growth, accumulated early‐life stress and inherited TL, predicted fitness in birds that reached adulthood but not noticeably among fledglings. These findings suggest that a lack of investment in somatic maintenance during development particularly affects late life performance. This study demonstrates that factors in early‐life are related to fitness prospects through lifespan, and suggests that the study of telomeres may provide insight into the underlying physiological mechanisms linking early‐ and late‐life performance and trade‐offs across a lifetime.

To address the problem of manure-based environmental pollution in the pork industry, we have developed the phytase transgenic pig. The saliva of these pigs contains the enzyme phytase, which allows the pigs to digest the phosphorus in phytate, the most abundant source of phosphorus in the pig diet. Without this enzyme, phytate phosphorus passes undigested into manure to become the single most important manure pollutant of pork production. We show here that salivary phytase provides essentially complete digestion of dietary phytate phosphorus, relieves the requirement for inorganic phosphate supplements, and reduces fecal phosphorus output by up to 75%. These pigs offer a unique biological approach to the management of phosphorus nutrition and environmental pollution in the pork industry.

Radiolabeled organic cations, such as triphenylphosphonium (TPP), represents a new class of radiotracers for imaging cancers and the transport function of multidrug resistance P-glycoproteins (particularly MDR1 Pgp) by single photon emission computed tomography (SPECT) or positron emission tomography (PET). This report presents the synthesis and biological evaluation of 64 Culabeled 2-(diphenylphosphoryl)ethyldiphenylphosphonium (TPEP) cations as novel PET radiotracers for tumor imaging. Biodistribution studies were performed using the athymic nude mice bearing subcutaneous U87MG human glioma xenografts to explore the impact of linkers, bifunctional chelators (BFCs) and chelates on biodistribution characteristics of the 64 Cu-labeled TPEP cations. Metabolism studies were carried out using normal athymic nude mice to determine the metabolic stability of four 64 Cu radiotracers. It was found that most 64 Cu radiotracers described in this study have significant advantages over 99m Tc-Sestamibi for their high tumor/heart and tumor/muscle ratios. Both BFCs and linkers have significant impact on biological properties of 64 Cu-labeled TPEP cations. For example, 64 Cu(DO3A-xy-TPEP) has much lower liver uptake and better tumor/liver ratios than 64 Cu(DO3A-xy-TPP), suggesting that TPEP is a better mitochondrion-targeting molecule than TPP. Replacing DO3A with DO2A results in 64 Cu(DO2A-xy-TPEP) + , which has a lower tumor uptake than 64 Cu(DO3A-xy-TPEP). Substitution of DO3A with NOTA-Bn leads to a significant decrease in tumor uptake for 64 Cu(NOTA-Bn-xy-TPEP). The use of DOTA-Bn to replace DO3A has little impact on the tumor uptake; but the tumor/liver ratio of 64 Cu(DOTA-Bn-xy-TPEP) -is not as good as that of 64 Cu(DO3A-xy-TPEP), probably due to the aromatic benzene ring in DOTA-Bn. Addition of an extra acetamido group in 64 Cu(DOTA-xy-TPEP) results in a lower liver uptake; but tumor/liver ratios of 64 Cu(DOTA-xy-TPEP) and 64 Cu(DO3A-xy-TPEP) are well comparable due to a faster tumor washout of 64 Cu(DOTA-xy-TPEP). Substitution of xylene with the PEG 2 linker also leads to a significant reduction in both tumor and liver uptake. MicroPET imaging studies on 64 Cu (DO3A-xy-TPEP) in athymic nude mice bearing U87MG glioma xenografts showed that the tumor was clearly visualized as early as 1 h postinjection with very high T/B contrast. There was very little metabolite (<2%) detectable in the urine and feces samples for 64 Cu(DO3A-xy-TPEP), 64 Cu(DOTABn-xy-TPEP) -and 64 Cu(NOTA-Bn-xy-TPEP). Considering both tumor uptake and T/B ratios (particularly tumor/heart, tumor/liver and tumor/muscle), it was concluded that 64 Cu(DO3A-xy-TPEP) is a promising PET radiotracer for imaging the MDR-negative tumors.

No abstract