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Macroautophagy (autophagy) is a crucial cellular stress response for degrading defective macromolecules and organelles, as well as providing bioenergetic intermediates during hypoxia and nutrient deprivation. Here we report a thiol-dependent process that may account for impaired autophagy during aging. This is through direct oxidation of key autophagy-related (Atg) proteins Atg3 and Atg7. When inactive Atg3 and Atg7 are protected from oxidation due to stable covalent interaction with their substrate LC3. This interaction becomes transient upon activation of Atg3 and Atg7 due to transfer of LC3 to phosphatidylethanolamine (lipidation), a process crucial for functional autophagy. However, loss in covalent-bound LC3 also sensitizes the catalytic thiols of Atg3 and Atg7 to inhibitory oxidation that prevents LC3 lipidation, observed in vitro and in mouse aorta. Here findings provide a thiol-dependent process for negatively regulating autophagy that may contribute to the process of aging, as well as therapeutic targets to regulate autophagosome maturation. A dysfunction of autophagy can be detected in aged tissues, but how this is regulated is unclear. Here, the authors show in vitro and in aged mice aorta, that inhibition of LC3 lipidation under conditions of oxidative stress causes oxidation of Atg3 and Atg7, preventing autophagosome maturation.

Earth system models predict large increases in global terrestrial net primary productivity (NPP) over the next century, largely reflecting positive effects of climate change and increasing atmospheric carbon dioxide concentrations on plant growth. However, while theory predicts that soil phosphorus (P) availability may keep pace with P demand as the climate warms, we lack experimental evidence to support this prediction. Here, using a set of laboratory experiments and incubations, we measured both the effect of temperature on the mechanism of biochemical P mineralization—phosphatase (Ptase) enzyme activities—and on rates of soil P mineralization in soils from a range of ecosystem types from the tropics to the Arctic. Consistent with temperature effects on soil nitrogen (N) mineralization, we found that both Ptase activities and P availability in soil increased with temperature following macromolecular rate theory (MMRT) based kinetics. However, across all sites and temperatures, there was no relationship between Ptase activity and mineralized P, indicating that the potential responses of P mineralization with warming vary among ecosystems. The lack of relationship between Ptase and P availability with increasing temperature is consistent with previous work showing that P mineralization rates are also strongly affected by other biotic and abiotic factors, including organic P substrate availability and the geochemical properties of soil. However, our results indicate that the use of Ptase temperature kinetics alone as a proxy for soil P mineralization in terrestrial ecosystems is insufficient to predict future P availability accurately, and modeling efforts that do so will likely overestimate the effects of temperature on soil P availability.

• Primary production in the Southern Ocean is dominated by diatom-rich phytoplankton assemblages, whose individual physiological characteristics and community composition are strongly shaped by the environment, yet knowledge on how diatoms allocate cellular energy in response to ocean acidification (OA) is limited. Understanding such changes in allocation is integral to determining the nutritional quality of diatoms and the subsequent impacts on the trophic transfer of energy and nutrients. • Using synchrotron-based Fourier transform infrared microspectroscopy, we analysed the macromolecular content of selected individual diatom taxa from a natural Antarctic phytoplankton community exposed to a gradient of fCO₂ levels (288–1263 μatm). • Strong species-specific differences in macromolecular partitioning were observed under OA. Large taxa showed preferential energy allocation towards proteins, while smaller taxa increased both lipid and protein stores at high fCO₂. • If these changes are representative of future Antarctic diatom physiology, we may expect a shift away from lipid-rich large diatoms towards a community dominated by smaller taxa, but with higher lipid and protein stores than their present-day contemporaries, a response that could have cascading effects on food web dynamics in the Antarctic marine ecosystem.

Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. Motile cilia propel sperm or extracellular fluids, and their dysfunction causes primary ciliary dyskinesia. Non-motile cilia serve as sensory/signalling antennae on most cell types, and their disruption causes single-organ ciliopathies such as retinopathies or multi-system syndromes. CFAP20 is a ciliopathy candidate known to modulate motile cilia in unicellular eukaryotes. We demonstrate that in zebrafish, cfap20 is required for motile cilia function, and in C. elegans , CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development. Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy. Hence, CFAP20 functions within a structural/functional hub centered on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associated domains or macromolecular complexes. Our findings suggest an uncharacterised pathomechanism for retinal dystrophy, and potentially for motile and non-motile ciliopathies in general. Motile and non-motile cilia have distinct functions and protein complexes associated with them. Here, the authors show the conserved protein CFAP20 is important for both motile and non-motile cilia and is distinct from other ciliopathy-associated domains or macromolecular complexes.

Background The therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to humoral factors such as growth factors, cytokines, and chemokines. Human term placental tissue-derived MSCs (PlaMSCs), or conditioned medium left over from cultures of these cells, have been reported to enhance angiogenesis. Recently, the exosome, which can transport a diverse suite of macromolecules, has gained attention as a novel intercellular communication tool. However, the potential role of the exosome in PlaMSC therapeutic action is not well understood. The purpose of this study was to evaluate PlaMSC-derived exosome angiogenesis promotion in vitro and in vivo. Methods MSCs were isolated from human term placental tissue by enzymatic digestion. Conditioned medium was collected after 48-h incubation in serum-free medium (PlaMSC-CM). Angiogenic factors present in PlaMSC-CM were screened by a growth factor array. Exosomes were prepared by ultracentrifugation of PlaMSC-CM, and confirmed by transmission electron microscopy, dynamic light scattering, and western blot analyses. The proangiogenic activity of PlaMSC-derived exosomes (PlaMSC-exo) was assessed using an endothelial tube formation assay, a cell migration assay, and reverse transcription-PCR analysis. The in-vivo angiogenic activity of PlaMSC-exo was evaluated using a murine auricle ischemic injury model. Results PlaMSC-CM contained both angiogenic and angiostatic factors, which enhanced endothelial tube formation. PlaMSC-exo were incorporated into endothelial cells; these exosomes stimulated both endothelial tube formation and migration, and enhanced angiogenesis-related gene expression. Laser Doppler blood flow analysis showed that PlaMSC-exo infusion also enhanced angiogenesis in an in-vivo murine auricle ischemic injury model. Conclusions PlaMSC-exo enhanced angiogenesis in vitro and in vivo, suggesting that exosomes play a role in the proangiogenic activity of PlaMSCs. PlaMSC-exo may be a novel therapeutic approach for treating ischemic diseases.

Temperature plays a fundamental role in determining phytoplankton community structure, distribution, and abundance. With climate models predicting increases in ocean surface temperatures of up to 3.2°C by 2100, there is a genuine need to acquire data on the phenotypic plasticity, and thus performance, of phytoplankton in relation to temperature. We investigated the effects of temperature (14–28°C) on the growth, morphology, productivity, silicification and macromolecular composition of the marine diatom Thalassiosira pseudonana. Optimum growth rate and maximum P:R ratio were obtained around 21°C. Cell volume and chlorophyll a increased with temperature, as did lipids and proteins. One of the strongest temperature-induced shifts was the higher silicification rates at low temperature. Our results reveal temperature-driven responses in physiological, morphological and biochemical traits in T. pseudonana; whereby at supra-optimal temperatures cells grew slower, were larger, had higher chlorophyll and protein content but reduced silicification, while those exposed to sub-optimal temperatures were smaller, heavily silicified with lower lipid and chlorophyll content. If these conserved across species, our findings indicate that as oceans warm, we may see shifts in diatom phenotypes and community structure, with potential biogeochemical consequences of higher remineralisation and declines in carbon and silicon export to the ocean interior.