Murine CD93 (C1qRp) contributes to the removal of apoptotic cells in vivo but is not required for C1q-mediated enhancement of phagocytosis

Human CD93 (known as C1qRp) has been shown to be a phagocytic receptor involved in the in vitro C1q-dependent enhancement of phagocytosis. However, binding of CD93 to C1q and its function remain controversial. In this study, we have generated CD93-deficient mice (CD93(-/-)) to investigate its biological role(s). The CD93(-/-) mice were viable and showed no gross abnormalities in their development. Thioglycolate-elicited peritoneal macrophages deficient in CD93 showed a similar enhancement in complement- and FcgammaR-dependent uptake of RBC to the wild-type macrophages when plated on C1q-coated surfaces suggesting that the lack of this receptor had no effect on these C1q-mediated events. There was no impairment in either complement- or FcgammaR-dependent phagocytic assays in vivo. By contrast, the CD93(-/-) mice had a significant phagocytic defect in the clearance of apoptotic cells in vivo (human Jurkat T cells and murine thymocytes: p=0.0006 and p=0.0079, respectively) compared with strain-matched controls. However, in vitro, the CD93(-/-) macrophages showed similar engulfment of apoptotic cells to wild-type macrophages. Furthermore, no supporting evidence for a role of CD93 as an adhesion molecule was found using intravital microscopy or analyzing peritoneal cell recruitment in response to three different inflammatory stimuli (thioglycolate, zymosan A, and IL-1beta). Thus, our findings indicate that murine CD93 is expressed on the peritoneal macrophage, especially on thioglycolate-elicited cells, but does not appear to play a key role in C1q-mediated enhancement of phagocytosis or in the intercellular adhesion events tested. However, our results suggest that it may contribute to the in vivo clearance of dying cells.     

Dung beetle species interactions and multifunctionality are affected by an experimentally warmed climate

While substantial effort has been invested in modelling changes in species distribution with climate change, less attention has been given to how climate warming will affect interactions among co‐occurring species, and the cascading functional consequences. In this study, realistic dung beetle communities were subjected to an experimental warming treatment and the net effect on the functions of dung decomposition (in terms of dung mass) and plant productivity (in terms of biomass production of ryegrass grown on soil from underneath the dung pats) were examined. A priori, we hypothesized that the largest tunneling species would be functionally dominant, and be differently affected by experimental warming compared to pat‐dwelling, smaller species. In terms of dung decomposition, the largest beetles did prove to be the functionally most important, with the qualitative pattern unaffected by experimental warming. In contrast, for plant productivity all species appeared equally important under ambient conditions. However, the effects of single species on plant productivity were reduced as temperature increased: In a warmed climate, a combination of both tunneling and pat‐dwelling species came the closest to returning ecosystem functioning to levels found in the ambient treatment. These results suggest different roles for different species, and highlight the importance of maintaining multiple species within an ecosystem – particularly when systems are perturbed.     

Evidence of a landlocked reproducing population of the marine pejerrey Odontesthes argentinensis (Actinopterygii; Atherinopsidae)

In South America, the order Atheriniformes includes the monophyletic genus Odontesthes with 20 species that inhabit freshwater, estuarine and coastal environments. Pejerrey Odontesthes argentinensis is widely distributed in coastal and estuarine areas of the Atlantic Ocean and is known to foray into estuaries of river systems, particularly in conditions of elevated salinity. However, to our knowledge, a landlocked self-sustaining population has never been recorded. In this study, we examined the pejerrey population of Salada de Pedro Luro Lake (south-east of Buenos Aires Province, Argentina) to clarify its taxonomic identity. An integrative taxonomic analysis based on traditional meristic, landmark-based morphometrics and genetic techniques suggests that the Salada de Pedro Luro pejerrey population represents a novel case of physiological and morphological adaptation of a marine pejerrey species to a landlocked environment and emphasises the environmental plasticity of this group of fishes.     

Effects of storage,mucilage presence,photoperiod, thermoperiod and salinity on germination of Farsetia aegyptia Turra (Brassicaceae) seeds: implications for restoration and seed banks in Arabian Desert

Seed viability and germination are key factors in the success of restoration efforts, especially when stored seeds are used. However, the effect of seed storage on germination of most of the native Arabian species is not well documented. We investigated the effect of storage time and role of the seed mucilage in regulating germination, dormancy, salinity tolerance and consequential survival strategy of F. aegyptia in an unpredictable arid desert setting. Effect of light and temperature during germination was studied under two photoperiods and two thermoperiods using intact and de-mucilaged seeds. Presence of mucilage and thermoperiod did not affect the germination. However, seed collection year and photoperiod had a highly significant effect on the germination. Increasing salinity levels decreased the germination of F. aegyptia but ungerminated seeds were able to germinate when salinity stress was alleviated. Seed storage at room temperature enhances the germination percentage, indicating that F. aegyptia seeds have physiological dormancy and it can be alleviated by after-ripening at dry storage. In addition, F. aegyptia seeds show ability to germinate at lower salinity concentration and remain viable even at higher saline conditions, indicating their adaptability to cope with such harsh environmental conditions.     

The Net Landscape Carbon Balance—Integrating terrestrial and aquatic carbon fluxes in a managed boreal forest landscape in Sweden

The boreal biome exchanges large amounts of carbon (C) and greenhouse gases (GHGs) with the atmosphere and thus significantly affects the global climate. A managed boreal landscape consists of various sinks and sources of carbon dioxide (CO₂), methane (CH₄), and dissolved organic and inorganic carbon (DOC and DIC) across forests, mires, lakes, and streams. Due to the spatial heterogeneity, large uncertainties exist regarding the net landscape carbon balance (NLCB). In this study, we compiled terrestrial and aquatic fluxes of CO₂, CH₄, DOC, DIC, and harvested C obtained from tall‐tower eddy covariance measurements, stream monitoring, and remote sensing of biomass stocks for an entire boreal catchment (~68 km²) in Sweden to estimate the NLCB across the land–water–atmosphere continuum. Our results showed that this managed boreal forest landscape was a net C sink (NLCB = 39 g C m^?2 year^?1) with the landscape–atmosphere CO₂ exchange being the dominant component, followed by the C export via harvest and streams. Accounting for the global warming potential of CH₄, the landscape was a GHG sink of 237 g CO₂‐eq m^?2 year^?1, thus providing a climate‐cooling effect. The CH₄ flux contribution to the annual GHG budget increased from 0.6% during spring to 3.2% during winter. The aquatic C loss was most significant during spring contributing 8% to the annual NLCB. We further found that abiotic controls (e.g., air temperature and incoming radiation) regulated the temporal variability of the NLCB whereas land cover types (e.g., mire vs. forest) and management practices (e.g., clear‐cutting) determined their spatial variability. Our study advocates the need for integrating terrestrial and aquatic fluxes at the landscape scale based on tall‐tower eddy covariance measurements combined with biomass stock and stream monitoring to develop a holistic understanding of the NLCB of managed boreal forest landscapes and to better evaluate their potential for mitigating climate change.     

Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis

Multiple sclerosis (MS) is a complex disease of the central nervous system of unknown etiology. The human leukocyte antigen (HLA) locus on chromosome 6 confers a considerable part of the susceptibility to MS, and the most important factor is the class II allele HLA-DRB1*15:01. In addition, we and others have previously established a protective effect of HLA-A*02. Here, we genotyped 1,784 patients and 1,660 healthy controls from Scandinavia for the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes and investigated their effects on MS risk by logistic regression. Several allele groups were found to exert effects independently of DRB1*15 and A*02, in particular DRB1*01 (OR = 0.82, p = 0.034) and B*12 (including B*44/45, OR = 0.76, p = 0.0028), confirming previous reports. Furthermore, we observed interaction between allele groups: DRB1*15 and DRB1*01 (multiplicative: OR = 0.54, p = 0.0041; additive: AP = 0.47, p = 4 × 10(-06)), DRB1*15 and C*12 (multiplicative: OR = 0.37, p = 0.00035; additive: AP = 0.58, p = 2.6 × 10(-05)), indicating that the effect size of these allele groups varies when taking DRB1*15 into account. Analysis of inferred haplotypes showed that almost all DRB1*15 bearing haplotypes were risk haplotypes, and that all A*02 bearing haplotypes were protective as long as they did not carry DRB1*15. In contrast, we found one class I haplotype, carrying A*02-C*05-B*12, which abolished the risk of DRB1*15. In conclusion, these results confirms a complex role of HLA class I and II genes that goes beyond DRB1*15 and A*02, in particular by including all three classical HLA class I genes as well as functional interactions between DRB1*15 and several alleles of DRB1 and class I genes.     

Embryonic fibroblasts from Gpx4+/- mice: a novel model for studying the role of membrane peroxidation in biological processes

A previous study using mice null for Gpx4 indicates that PHGPx plays a critical role in antioxidant defense and is essential for the survival of the mouse. In the present study, we further analyzed the stress response of MEFs (murine embryonic fibroblasts) derived from mice heterozygous for the Gpx4 gene (Gpx4(+/-) mice). MEFs from Gpx4(+/-) mice have a 50% reduction in PHGPx expression without any changes in the activities of other major antioxidant defense enzymes. Compared to MEFs from Gpx4(+/+) mice, MEFs from Gpx4(+/-) mice were more sensitive to exposure to the oxidizing agent t-butyl hydroperoxide (t-BuOOH), and t-BuOOH exposure induced increased apoptosis in MEFs from Gpx4(+/-) mice. When cultured at low cell density, MEFs from Gpx4(+/-) mice also showed retarded growth under normal culture conditions (20% oxygen) that was reversed by culturing under low oxygen (2% oxygen). In addition, oxidative damage was increased in the MEFs from the Gpx4(+/-) mice, as indicated by increased levels of F(2)-isoprostanes and 8-oxo-2-deoxyguanosine in these cells. Our data demonstrate that MEFs from Gpx4(+/-) mice are more sensitive to oxidative stress because of reduced expression of PHGPx.     

Posttranslational regulation of tristetraprolin subcellular localization and protein stability by p38 mitogen-activated protein kinase and extracellular signal-regulated kinase pathways

The p38 mitogen-activated protein kinase (MAPK) signaling pathway, acting through the downstream kinase MK2, regulates the stability of many proinflammatory mRNAs that contain adenosine/uridine-rich elements (AREs). It is thought to do this by modulating the expression or activity of ARE-binding proteins that regulate mRNA turnover. MK2 phosphorylates the ARE-binding and mRNA-destabilizing protein tristetraprolin (TTP) at serines 52 and 178. Here we show that the p38 MAPK pathway regulates the subcellular localization and stability of TTP protein. A p38 MAPK inhibitor causes rapid dephosphorylation of TTP, relocalization from the cytoplasm to the nucleus, and degradation by the 20S/26S proteasome. Hence, continuous activity of the p38 MAPK pathway is required to maintain the phosphorylation status, cytoplasmic localization, and stability of TTP protein. The regulation of both subcellular localization and protein stability is dependent on MK2 and on the integrity of serines 52 and 178. Furthermore, the extracellular signal-regulated kinase (ERK) pathway synergizes with the p38 MAPK pathway to regulate both stability and localization of TTP. This effect is independent of kinases that are known to be synergistically activated by ERK and p38 MAPK. We present a model for the actions of TTP and the p38 MAPK pathway during distinct phases of the inflammatory response.