BUD13 Promotes a Type I Interferon Response by Countering Intron Retention in Irf7

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Global patterns in fine root decomposition: climate,chemistry, mycorrhizal association and woodiness

Fine root decomposition constitutes a critical yet poorly understood flux of carbon and nutrients in terrestrial ecosystems. Here, we present the first large‐scale synthesis of species trait effects on the early stages of fine root decomposition at both global and local scales. Based on decomposition rates for 279 plant species across 105 studies and 176 sites, we found that mycorrhizal association and woodiness are the best categorical traits for predicting rates of fine root decomposition. Consistent positive effects of nitrogen and phosphorus concentrations and negative effects of lignin concentration emerged on decomposition rates within sites. Similar relationships were present across sites, along with positive effects of temperature and moisture. Calcium was not consistently related to decomposition rate at either scale. While the chemical drivers of fine root decomposition parallel those of leaf decomposition, our results indicate that the best plant functional groups for predicting fine root decomposition differ from those predicting leaf decomposition.     

Interferon‐gamma production in Lyme arthritis synovial tissue promotes differentiation of fibroblast‐like synoviocytes into immune effector cells

Lyme arthritis (LA), a late disease manifestation of Borrelia burgdorferi infection, usually resolves with antibiotic therapy. However, some patients develop proliferative synovitis lasting months to several years after spirochetal killing, called postinfectious LA. In this study, we phenotyped haematopoietic and stromal cell populations in the synovial lesion ex vivo and used these findings to generate an in vitro model of LA using patient‐derived fibroblast‐like synoviocytes (FLS). Ex vivo analysis of synovial tissue revealed high abundance of IFNγ‐producing T cells and NK cells. Similar to marked IFNγ responses in tissue, postinfectious LA synovial fluid also had high levels of IFNγ. HLA‐DR‐positive FLS were present throughout the synovial lesion, particularly in areas of inflammation. FLS stimulated in vitro with B. burgdorferi, which were similar to conditions during infection, expressed 68 genes associated primarily with innate immune activation and neutrophil recruitment. In contrast, FLS stimulated with IFNγ, which were similar to conditions in the postinfectious phase, expressed >2,000 genes associated with pathogen sensing, inflammation, and MHC Class II antigen presentation, similar to the expression profile in postinfectious synovial tissue. Furthermore, costimulation of FLS with B. burgdorferi and IFNγ induced greater expression of IL‐6 and other innate immune response proteins and genes than with IFNγ stimulation alone. These results suggest that B. burgdorferi infection, in combination with IFNγ, initiates the differentiation of FLS into a highly inflammatory phenotype. We hypothesise that overexpression of IFNγ by lymphocytes within synovia perpetuates these responses in the postinfectious period, causing proliferative synovitis and stalling appropriate repair of damaged tissue.     

Big cats at large: Density,structure, and spatio-temporal patterns of a leopard population free of anthropogenic mortality

Human impact is near pervasive across the planet and studies of wildlife populations free of anthropogenic mortality are increasingly scarce. This is particularly true for large carnivores that often compete with and, in turn, are killed by humans. Accordingly, the densities at which carnivore populations occur naturally, and their role in shaping and/or being shaped by natural processes, are frequently unknown. We undertook a camera-trap survey in the Sabi Sand Game Reserve (SSGR), South Africa, to examine the density, structure and spatio-temporal patterns of a leopard Panthera pardus population largely unaffected by anthropogenic mortality. Estimated population density based on spatial capture–recapture models was 11.8 ± 2.6 leopards/100 km². This is likely close to the upper density limit attainable by leopards, and can be attributed to high levels of protection (particularly, an absence of detrimental edge effects) and optimal habitat (in terms of prey availability and cover for hunting) within the SSGR. Although our spatio-temporal analyses indicated that leopard space use was modulated primarily by “bottom-up” forces, the population appeared to be self-regulating and at a threshold that is unlikely to change, irrespective of increases in prey abundance. Our study provides unique insight into a naturally-functioning carnivore population at its ecological carrying capacity. Such insight can potentially be used to assess the health of other leopard populations, inform conservation targets, and anticipate the outcomes of population recovery attempts.     

Oxygen‐dependent delayed fluorescence of protoporphyrin IX measured in the stomach and duodenum during upper gastrointestinal endoscopy

Protoporphyrin IX‐triplet state lifetime technique (PpIX‐TSLT) is a method used to measure oxygen (PO₂) in human cells. The aim of this study was to assess the technical feasibility and safety of measuring oxygen‐dependent delayed fluorescence of 5‐aminolevulinic acid (ALA)‐induced PpIX during upper gastrointestinal (GI) endoscopy. Endoscopic delayed fluorescence measurements were performed 4 hours after oral administration of ALA in healthy volunteers. The ALA dose administered was 0, 1, 5 or 20 mg/kg. Measurements were performed at three mucosal spots in the gastric antrum, duodenal bulb and descending duodenum with the catheter above the mucosa and while applying pressure to induce local ischemia and monitor mitochondrial respiration. During two endoscopies, measurements were performed both before and after intravenous administration of butylscopolamine. Delayed fluorescence measurements were successfully performed during all 10 upper GI endoscopies. ALA dose of 5 mg/kg showed adequate signal‐to‐noise ratio (SNR) values >20 without side effects. All pressure measurements showed significant prolongation of delayed fluorescence lifetime compared to measurements performed without pressure (P < .001). Measurements before and after administration of butylscopolamine did not differ significantly in the duodenal bulb and descending duodenum. Measurements of oxygen‐dependent delayed fluorescence of ALA‐induced PpIX in the GI tract during upper GI endoscopy are technically feasible and safe.     

A dynamic multi‐scale occupancy model to estimate temporal dynamics and hierarchical habitat use for nomadic species

Distribution models are increasingly being used to understand how landscape and climatic changes are affecting the processes driving spatial and temporal distributions of plants and animals. However, many modeling efforts ignore the dynamic processes that drive distributional patterns at different scales, which may result in misleading inference about the factors influencing species distributions. Current occupancy models allow estimation of occupancy at different scales and, separately, estimation of immigration and emigration. However, joint estimation of local extinction, colonization, and occupancy within a multi‐scale model is currently unpublished. We extended multi‐scale models to account for the dynamic processes governing species distributions, while concurrently modeling local‐scale availability. We fit the model to data for lark buntings and chestnut‐collared longspurs in the Great Plains, USA, collected under the Integrated Monitoring in Bird Conservation Regions program. We investigate how the amount of grassland and shrubland and annual vegetation conditions affect bird occupancy dynamics and local vegetation structure affects fine‐scale occupancy. Buntings were prevalent and longspurs rare in our study area, but both species were locally prevalent when present. Buntings colonized sites with preferred habitat configurations, longspurs colonized a wider range of landscape conditions, and site persistence of both was higher at sites with greener vegetation. Turnover rates were high for both species, quantifying the nomadic behavior of the species. Our model allows researchers to jointly investigate temporal dynamics of species distributions and hierarchical habitat use. Our results indicate that grassland birds respond to different covariates at landscape and local scales suggesting different conservation goals at each scale. High turnover rates of these species highlight the need to account for the dynamics of nomadic species, and our model can help inform how to coordinate management efforts to provide appropriate habitat configurations at the landscape scale and provide habitat targets for local managers.     

A comparison of two in vitro maturation media for use with adult porcine oocytes for adult somatic cell nuclear transfer

Two media used to mature adult porcine oocytes for somatic cell nuclear transfer were compared. In the first experiment, parthenogenetic embryos were produced using a maturation medium used by us previously to clone pigs (OMM199) and that described by Kühholzer et al. (2001) to transport oocytes overnight (BOMED). There was no difference in maturation rates between the two different media. However, BOMED medium increased the percentage of parthenogenetic embryos that developed to the blastocyst stage compared with OMM199 (49% vs. 29%, respectively). In a second experiment, BOMED medium increased the percentage of SCNT embryos that developed to the blastocyst stage compared with OMM199 (22% vs. 8%, respectively). The efficiency of our cloning protocol using adult oocytes matured in BOMED medium was then determined by transferring SCNT embryos reconstructed using adult fibroblasts to synchronized recipients. Primary cultures of adult fibroblasts were obtained from two adult male pigs and used for SCNT (passages 2-4). Between 82 and 146 fused couplets were transferred to seven recipients synchronized 1 day behind the embryos. Five recipients (71% pregnancy rate) subsequently farrowed a total of 23 piglets (4.4 average litter size). Overall efficiencies (liveborn/embryos transferred) were 3.2% for all transfers and 4.3% for animals that gave birth.     

Toxoplasma gondii targets a protein phosphatase 2C to the nuclei of infected host cells

Intracellular pathogens have evolved a wide array of mechanisms to invade and co-opt their host cells for intracellular survival. Apicomplexan parasites such as Toxoplasma gondii employ the action of unique secretory organelles named rhoptries for internalization of the parasite and formation of a specialized niche within the host cell. We demonstrate that Toxoplasma gondii also uses secretion from the rhoptries during invasion to deliver a parasite-derived protein phosphatase 2C (PP2C-hn) into the host cell and direct it to the host nucleus. Delivery to the host nucleus does not require completion of invasion, as evidenced by the fact that parasites blocked in the initial stages of invasion with cytochalasin D are able to target PP2C-hn to the host nucleus. We have disrupted the gene encoding PP2C-hn and shown that PP2C-hn-knockout parasites exhibit a mild growth defect that can be rescued by complementation with the wild-type gene. The delivery of parasite effector proteins via the rhoptries provides a novel mechanism for Toxoplasma to directly access the command center of its host cell during infection by the parasite.     

Thermodynamic stability and folding of proteins from hyperthermophilic organisms

Life grows almost everywhere on earth, including in extreme environments and under harsh conditions. Organisms adapted to high temperatures are called thermophiles (growth temperature 45-75 degrees C) and hyperthermophiles (growth temperature >or= 80 degrees C). Proteins from such organisms usually show extreme thermal stability, despite having folded structures very similar to their mesostable counterparts. Here, we summarize the current data on thermodynamic and kinetic folding/unfolding behaviors of proteins from hyperthermophilic microorganisms. In contrast to thermostable proteins, rather few (i.e. less than 20) hyperthermostable proteins have been thoroughly characterized in terms of their in vitro folding processes and their thermodynamic stability profiles. Examples that will be discussed include co-chaperonin proteins, iron-sulfur-cluster proteins, and DNA-binding proteins from hyperthermophilic bacteria (i.e. Aquifex and Theromotoga) and archea (e.g. Pyrococcus, Thermococcus, Methanothermus and Sulfolobus). Despite the small set of studied systems, it is clear that super-slow protein unfolding is a dominant strategy to allow these proteins to function at extreme temperatures.