Tissue-specific suppression of thyroid hormone signaling in various mouse models of aging

DNA damage contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair. Thyroid state changes during aging, but underlying mechanisms remain elusive. Since thyroid hormone (TH) is a key regulator of metabolism, changes in TH signaling have widespread effects. Here, we reveal a significant common transcriptomic signature in livers from hypothyroid mice, DNA repair-deficient mice with severe (Csbm/m/Xpa-/-) or intermediate (Ercc1-/Δ-7) progeria and naturally aged mice. A strong induction of TH-inactivating deiodinase D3 and decrease of TH-activating D1 activities are observed in Csbm/m/Xpa-/- livers. Similar findings are noticed in Ercc1-/Δ-7, in naturally aged animals and in wild-type mice exposed to a chronic subtoxic dose of DNAdamaging agents. In contrast, TH signaling in muscle, heart and brain appears unaltered. These data show a strong suppression of TH signaling in specific peripheral organs in premature and normal aging, probably lowering metabolism, while other tissues appear to preserve metabolism. D3-mediated TH inactivation is unexpected, given its expression mainly in fetal tissues. Our studies highlight the importance of DNA damage as the underlying mechanism of changes in thyroid state. Tissue-specific regulation of deiodinase activities, ensuring diminished TH signaling, may contribute importantly to the protective metabolic response in aging

Development of biocontrol methods for camellia flower blight caused by Ciborinia camelliae Kohn

Camellia flower blight is caused by the sclerotial-forming fungus Ciborinia camelliae Kohn, and is specific to flowers of most species of camellias. An investigation was conducted into the feasibility of a wide range of biological methods for control of the pathogen by attacking soil-borne sclerotia and thereby preventing apothecial production, and protecting camellia flowers against ascospore infection. Two methods were developed to assess the viability of C. camelliae sclerotia for subsequent use in sclerotial parasitism assays. One method involved washing and rinsing sclerotia twice in 13.5% NaOCl, followed by immersion in antibiotics, bisection of sclerotia fragments onto potato dextrose agar, and identification of C. camelliae mycelium after incubation. Another method used sclerotial softness as an indicator of viability. Softness was determined from the energy required to push a 2.76 diameter penetrometer with a force of 40 N into a 6 mm thick segment of healthy sclerotia (17 and 14 Nmm for medium and large sizes). This method was modified by recording as parasitised those sclerotia that were pierced under a 1-kg probe with a footprint of 6.2 mm², which delivered a pressure 1.6 MPa. The known mycoparasites Trichoderma virens, T. hamatum, T. stromaticum, Clonostachys rosea, Coniothyrium minitans and Sporidesmium sclerotivorum were not effective in reducing sclerotia viability. However, in screens of 400 candidate microorganisms isolated from sclerotial baits and decaying sclerotia, two isolates of Trichoderma and an isolate of Fusarium lateritium reduced the number of viable sclerotia by 38-50%. This indicated that moderately parasitic micro-antagonists were present in soil under camellia bushes. A range of soil treatments, which were postulated to stimulate micro-parasitic activity, was investigated in an attempt to reduce the viability and germination potential of the overwintering sclerotia. Urea, applied to soil at 50 kg N/ha, with Bio-Start soil conditioners in February and again in June reduced field populations of sclerotia from 294 to 105 sclerotia/m² by the following November. Covering soil under camellia bushes with 100 mm thick tree mulches for 9 months resulted in total suppression of apothecia and a 77% reduction in the population density of soil-borne sclerotia, compared to bare soil. However, tree mulches had no effect on the new generation of C. camellia sclerotia developing in fallen flowers. Mulches amended with lignin-degrading white-rot fungi offered potential for decay of newly formed sclerotia. In laboratory assays, pine (Pinus radiata) sawdust amended with Phanerochaete cordylines LU900 led to a 77-83% reduction in viability of sclerotia after 12 weeks, compared to a 1-7% reduction in sclerotia embedded in sawdust alone. Ligninolytic enzymes released by the isolate were shown to degrade the rinds of sclerotia, exposing them to microbial parasitism. The practical application of P. cordylines is dependent upon confirmation that it is non-pathogenic to camellia. Integration of the three soil treatments offers potential for longterm control of camellia blight. A single application of the fertiliser calcium cyanamide at 500-1000 kg/ha to soil under camellia bushes immediately before flowering (August), gave complete suppression of apothecial production, and can be used for short-term control of the disease. Potassium bicarbonate and ammonium bicarbonate at 300 kg/ha was less effective. Attempts to protect camellia flowers from infection by C. camelliae ascospores were only partially successful. Although isolates of Bacillus, Pseudomonas, Aureobasidium and Cladosporium spp. provided almost complete protection against camellia blight in petal assays, they did not prevent symptoms in whole flowers on camellia bushes, even after repeated applications with or without adjuvants. Weekly applications of the elicitor acibenzolar-S-methyl to camellia bushes, 3 weeks before and during flowing to induce systemic acquired resistance, were also not effective in controlling camellia blight. The genetic diversity of C. camelliae isolates was investigated using a universally primed polymerase chain reaction DNA fingerprinting technique. The 27 isolates from four regions in New Zealand were found to be distinctly different to those from United States, which comprised three isolates each from Georgia, Oregon and Virginia. However, a low level of genetic variation (<20%) existed between isolates, suggesting that biocontrol agents are likely to be effective for control of all isolates of C. camelliae. The successful control strategies developed in this study could be integrated into a programme for effective control of camellia blight. Urea applied to soil beneath camellia bushes followed by a 100 mm thick layer of tree mulch should result in total suppression of apothecia, thereby preventing infection in flowers, and resulting in a gradual decline in numbers of soil-borne sclerotia. Amendment of the mulch with lignin-degrading white-rot fungi may control newly formed sclerotia developing in fallen flowers that have been infected by air-borne inoculum from adjacent untreated areas. Alternatively, apothecial production can be totally suppressed with calcium cyanamide applied to soil under camellia bushes immediately before flowering each year

A Pseudoscorpion's Promising Pinch: The venom of Chelifer cancroides contains a rich source of novel compounds

With pedipalps modified for venom injection, some pseudoscorpions possess a unique venom delivery system, which evolved independently from those of other arachnids like scorpions and spiders. Up to now, only a few studies have been focused on pseudoscorpion venom, which either identified a small fraction of venom compounds, or were based on solely transcriptomic approaches. Only one study addressed the bioactivity of pseudoscorpion venom. Here, we expand existing knowledge about pseudoscorpion venom by providing a comprehensive proteomic and transcriptomic analysis of the venom of Chelifer cancroides. We identified the first putative genuine toxins in the venom of C. cancroides and we showed that a large fraction of the venom comprises novel compounds. In addition, we tested the activity of the venom at specific ion channels for the first time. These tests demonstrate that the venom of C. cancroides causes inhibition of a voltage-gated insect potassium channel (Shaker IR) and modulates the inactivation process of voltage-gated sodium channels from Varroa destructor. For one of the smallest venomous animals ever studied, today's toolkits enabled a comprehensive venom analysis. This is demonstrated by allocating our identified venom compounds to more than half of the prominent ion signals in MALDI-TOF mass spectra of venom samples. The present study is a starting point for understanding the complex composition and activity of pseudoscorpion venom and provides a potential rich source of bioactive compounds useable for basic research and industrial application.Copyright: © The Authors. This document is the authors' submitted version of the journal article. You are advised to consult the published version if you wish to cite from it

A Pseudoscorpion's Promising Pinch: The venom of Chelifer cancroides contains a rich source of novel compounds

With pedipalps modified for venom injection, some pseudoscorpions possess a unique venom delivery system, which evolved independently from those of other arachnids like scorpions and spiders. Up to now, only a few studies have been focused on pseudoscorpion venom, which either identified a small fraction of venom compounds, or were based on solely transcriptomic approaches. Only one study addressed the bioactivity of pseudoscorpion venom. Here, we expand existing knowledge about pseudoscorpion venom by providing a comprehensive proteomic and transcriptomic analysis of the venom of Chelifer cancroides. We identified the first putative genuine toxins in the venom of C. cancroides and we showed that a large fraction of the venom comprises novel compounds. In addition, we tested the activity of the venom at specific ion channels for the first time. These tests demonstrate that the venom of C. cancroides causes inhibition of a voltage-gated insect potassium channel (Shaker IR) and modulates the inactivation process of voltage-gated sodium channels from Varroa destructor. For one of the smallest venomous animals ever studied, today's toolkits enabled a comprehensive venom analysis. This is demonstrated by allocating our identified venom compounds to more than half of the prominent ion signals in MALDI-TOF mass spectra of venom samples. The present study is a starting point for understanding the complex composition and activity of pseudoscorpion venom and provides a potential rich source of bioactive compounds useable for basic research and industrial application

Pathogenicity of Gaeumannomyces graminis var. tritici increased by nitrogen applied to soil to enhance the decomposition rate of wheat residues

Soil cores removed after harvest of a wheat crop infected with the fungus, Gaeumannomyces graminis var. tritici (Ggt), were amended with nitrogen and fungal saprophytes to increase decay of crop residues and subsequently reduce soil inoculum. The cores were treated with one application of 50 kg nitrogen (N) per ha, Trichoderma strains, or both. Cores were assessed 0, 2, 4 and 7 months after harvest. At 7 months, the crop residues had decayed to a third of their original mass, with the decay not influenced by the treatments. DNA analysis confirmed Ggt DNA was present in the stubble stems, crowns and roots. The pathogenicity of Ggt was increased by N, as shown by a 5 to 8-fold increase in take-all severity in indicator wheat seedlings planted in the N-treated cores 2 to 4 months after harvest, compared with those without N. Ggt remained viable in all treatments to infect wheat seedlings 7 months after harvest

Tissue-Specific Suppression of Thyroid Hormone Signaling in Various Mouse Models of Aging

DNA damage contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair. Thyroid state changes during aging, but underlying mechanisms remain elusive. Since thyroid hormone (TH) is a key regulator of metabolism, changes in TH signaling have widespread effects. Here, we reveal a significant common transcriptomic signature in livers from hypothyroid mice, DNA repair-deficient mice with severe (Csbm/m/Xpa-/-) or intermediate (Ercc1-/Δ-7) progeria and naturally aged mice. A strong induction of TH-inactivating deiodinase D3 and decrease of TH-activating D1 activities are observed in Csbm/m/Xpa-/- livers. Similar findings are noticed in Ercc1-/Δ-7, in naturally aged animals and in wild-type mice exposed to a chronic subtoxic dose of DNA-damaging agents. In contrast, TH signaling in muscle, heart and brain appears unaltered. These data show a strong suppression of TH signaling in specific peripheral organs in premature and normal aging, probably lowering metabolism, while other tissues appear to preserve metabolism. D3-mediated TH inactivation is unexpected, given its expression mainly in fetal tissues. Our studies highlight the importance of DNA damage as the underlying mechanism of changes in thyroid state. Tissue-specific regulation of deiodinase activities, ensuring diminished TH signaling, may contribute importantly to the protective metabolic response in aging.status: publishe

Tissue-specific suppression of thyroid hormone signaling in various mouse models of aging

DNA damage contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair. Thyroid state changes during aging, but underlying mechanisms remain elusive. Since thyroid hormone (TH) is a key regulator of metabolism, changes in TH signaling have widespread effects. Here, we reveal a significant common transcriptomic signature in livers from hypothyroid mice, DNA repair-deficient mice with severe (Csbm/m/Xpa-/-) or intermediate (Ercc1-/Δ-7) progeria and naturally aged mice. A strong induction of TH-inactivating deiodinase D3 and decrease of TH-activating D1 activities are observed in Csbm/m/Xpa-/- livers. Similar findings are noticed in Ercc1-/Δ-7, in naturally aged animals and in wild-type mice exposed to a chronic subtoxic dose of DNAdamaging agents. In contrast, TH signaling in muscle, heart and brain appears unaltered. These data show a strong suppression of TH signaling in specific peripheral organs in premature and normal aging, probably lowering metabolism, while other tissues appear to preserve metabolism. D3-mediated TH inactivation is unexpected, given its expression mainly in fetal tissues. Our studies highlight the importance of DNA damage as the underlying mechanism of changes in thyroid state. Tissue-specific regulation of deiodinase activities, ensuring diminished TH signaling, may contribute importantly to the protective metabolic response in aging