Fluvial CO2 and CH4 patterns across wildfire‐disturbed ecozones of subarctic Canada: Current status and implications for future change

Despite occupying a small fraction of the landscape, fluvial networks are disproportionately large emitters of CO₂ and CH₄, with the potential to offset terrestrial carbon sinks. Yet the extent of this offset remains uncertain, because current estimates of fluvial emissions often do not integrate beyond individual river reaches and over the entire fluvial network in complex landscapes. Here we studied broad patterns of concentrations and isotopic signatures of CO₂ and CH₄ in 50 streams in the western boreal biome of Canada, across an area of 250,000 km². Our study watersheds differ starkly in their geology (sedimentary and shield), permafrost extent (sporadic to extensive discontinuous) and land cover (large variability in lake and wetland extents). We also investigated the effect of wildfire, as half of our study streams drained watersheds affected by megafires that occurred 3 years prior. Similar to other boreal regions, we found that stream CO₂ concentrations were primarily associated with greater terrestrial productivity and warmer climates, and decreased downstream within the fluvial network. No effects of recent wildfire, bedrock geology or land cover composition were found. The isotopic signatures suggested dominance of biogenic CO₂ sources, despite dominant carbonate bedrock in parts of the study region. Fluvial CH₄ concentrations had a high variability which could not be explained by any landscape factors. Estimated fluvial CO₂ emissions were 0.63 (0.09–6.06, 95% CI) and 0.29 (0.17–0.44, 95% CI) g C m^?2 year^?1 at the landscape scale using a stream network modelling and a mass balance approach, respectively, a small but potentially important component of the landscape C balance. These fluvial CO₂ emissions are lower than in other northern regions, likely due to a drier climate. Overall, our study suggests that fluvial CO₂ emissions are unlikely to be sensitive to altered fire regimes, but that warming and permafrost thaw will increase emissions significantly.     

Terminal uridyltransferase enzyme Zcchc11 promotes cell proliferation independent of its uridyltransferase activity

Zcchc11 is a uridyltransferase protein with enzymatic activity directed against diverse RNA species. On the basis of its known uridylation targets, we hypothesized that Zcchc11 might regulate cell proliferation. Confirming this, loss-of-function and complementary gain-of-function experiments consistently revealed that Zcchc11 promotes the transition from G(1) to S phase of the cell cycle. This activity takes place through both Rb-dependent and Rb-independent mechanisms by promoting the expression of multiple G(1)-associated proteins, including cyclins D(1) and A and CDK4. Surprisingly, a Zcchc11 construct with point mutations inactivating the uridyltransferase domain enhanced cell proliferation as effectively as wild-type Zcchc11. Furthermore, truncated mutant constructs revealed that the cell cycle effects of Zcchc11 were driven by the N-terminal region of the protein that lacks the RNA-binding domains and uridyltransferase activity of the full protein. Therefore, the N-terminal portion of Zcchc11, which lacks nucleotidyltransferase capabilities, is biologically active and mediates a previously unrecognized role for Zcchc11 in facilitating cell proliferation.     

Specific integrin subunits in bovine oocytes, including novel sequences for alpha 6 and beta 3 subunits

Integrins facilitate attachment of cells to the extra-cellular matrix, often binding the arginine-glycine-aspartic acid tri-peptide motif, thus facilitating cell migration, mediating cell-cell adhesion, linking the extracellular matrix (ECM) with cytoskeletal elements, and acting as signaling molecules. Adhesion activates signaling mechanisms that regulate integrin function, cytoskeletal assembly, cell behavior, and protein synthesis. Immunofluorescence was used to determine the presence of integrin alpha and beta subunits on the surface of bovine oocytes using a panel of monoclonal antibodies (mAbs) specific for alphaL, alphaM, alphaX, alphaV, alpha2, alpha4, alpha6, beta1, beta2, and beta3 antigens, with multiple antibodies for each subunit. Confocal microscopy indicated the presence of alphaV, alpha6, alpha4, alpha2, ss1, and ss3 integrin subunits on the plasma membrane of bovine oocytes. The presence of these subunits was verified by RT-PCR analysis using primers designed based on known gene sequences of bovine integrin subunits, or by using sequence information using bovine expressed sequence tags (EST) compared with known human and murine integrin subunit gene sequence information. Previously unpublished sequence information for bovine alpha6 and beta3 integrins was determined. The presence of these integrin subunits on the bovine oocyte vitelline membrane supports the hypothesis that sperm-oocyte interactions in the bovine are mediated by integrins.     

Forests on thawing permafrost: fragmentation,edge effects,and net forest loss

Much of the world's boreal forest occurs on permafrost (perennially cryotic ground). As such, changes in permafrost conditions have implications for forest function and, within the zone of discontinuous permafrost (30–80% permafrost in areal extent), distribution. Here, forested peat plateaus underlain by permafrost are elevated above the surrounding permafrost‐free wetlands; as permafrost thaws, ground surface subsidence leads to waterlogging at forest margins. Within the North American subarctic, recent warming has produced rapid, widespread permafrost thaw and corresponding forest loss. Although permafrost thaw‐induced forest loss provides a natural analogue to deforestation occurring in more southerly locations, we know little about how fragmentation relates to subsequent permafrost thaw and forest loss or the role of changing conditions at the edges of forested plateaus. We address these knowledge gaps by (i) examining the relationship of forest loss to the degree of fragmentation in a boreal peatland in the Northwest Territories, Canada; and (ii) quantifying associated biotic and abiotic changes occurring across forest‐wetland transitions and extending into the forested plateaus (i.e., edge effects). We demonstrate that the rate of forest loss correlates positively with the degree of fragmentation as quantified by perimeter to area ratio of peat plateaus (edge : area). Changes in depth of seasonal thaw, soil moisture, and effective leaf area index (LAI_e) penetrated the plateau forests by 3–15 m. Water uptake by trees was sevenfold greater in the plateau interior than at the edges with direct implications for tree radial growth. A negative relationship existed between LAI_e and soil moisture, suggesting that changes in vegetation physiological function may contribute to changing edge conditions while simultaneously being affected by these changes. Enhancing our understanding of mechanisms contributing to differential rates of permafrost thaw and associated forest loss is critical for predicting future interactions between the land surface processes and the climate system in high‐latitude regions.     

Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics

Introduction

Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Currently, the relationship between pathogenic molecular drivers of disease in RA and therapeutic response is poorly understood.

Methods

We analyzed synovial tissue samples from two RA cohorts of 49 and 20 patients using a combination of global gene expression, histologic and cellular analyses, and analysis of gene expression data from two further publicly available RA cohorts. To identify candidate serum biomarkers that correspond to differential synovial biology and clinical response to targeted therapies, we performed pre-treatment biomarker analysis compared with therapeutic outcome at week 24 in serum samples from 198 patients from the ADACTA (ADalimumab ACTemrA) phase 4 trial of tocilizumab (anti-IL-6R) monotherapy versus adalimumab (anti-TNFα) monotherapy.

Results

We documented evidence for four major phenotypes of RA synovium – lymphoid, myeloid, low inflammatory, and fibroid - each with distinct underlying gene expression signatures. We observed that baseline synovial myeloid, but not lymphoid, gene signature expression was higher in patients with good compared with poor European league against rheumatism (EULAR) clinical response to anti-TNFα therapy at week 16 (P =0.011). We observed that high baseline serum soluble intercellular adhesion molecule 1 (sICAM1), associated with the myeloid phenotype, and high serum C-X-C motif chemokine 13 (CXCL13), associated with the lymphoid phenotype, had differential relationships with clinical response to anti-TNFα compared with anti-IL6R treatment. sICAM1-high/CXCL13-low patients showed the highest week 24 American College of Rheumatology (ACR) 50 response rate to anti-TNFα treatment as compared with sICAM1-low/CXCL13-high patients (42% versus 13%, respectively, P =0.05) while anti-IL-6R patients showed the opposite relationship with these biomarker subgroups (ACR50 20% versus 69%, P =0.004).

Conclusions

These data demonstrate that underlying molecular and cellular heterogeneity in RA impacts clinical outcome to therapies targeting different biological pathways, with patients with the myeloid phenotype exhibiting the most robust response to anti-TNFα. These data suggest a path to identify and validate serum biomarkers that predict response to targeted therapies in rheumatoid arthritis and possibly other autoimmune diseases.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01119859","term_id":"NCT01119859"}}NCT01119859     

Disruption of epidermal specific gene expression and delayed skin development in AP-2 gamma mutant mice

Summary Sentence: Conditional ablation of AP-2γ results in a delay in skin development and abnormal expression of p63, K14, K1, filaggrin, repetin and secreted Ly6/Plaur domain containing 1, key genes required for epidermal development and differentiation.The development of the epidermis, a stratified squamous epithelium, is dependent on the regulated differentiation of keratinocytes. Differentiation begins with the initiation of stratification, a process tightly controlled through proper gene expression. AP-2γ is expressed in skin and previous research suggested a pathway where p63 gene induction results in increased expression of AP-2γ, which in turn is responsible for induction of K14. This study uses a conditional gene ablation model to further explore the role of AP-2γ in skin development. Mice deficient for AP-2γ exhibited delayed expression of p63, K14, and K1, key genes required for development and differentiation of the epidermis. In addition, microarray analysis of E16.5 skin revealed delayed expression of additional late epidermal differentiation genes: filaggrin, repetin and secreted Ly6/Plaur domain containing 1, in mutant mice. The genetic delay in skin development was further confirmed by a functional delay in the formation of an epidermal barrier. These results document an important role for AP-2γ in skin development, and reveal the existence of regulatory factors that can compensate for AP-2γ in its absence.     

Direct and indirect climate change effects on carbon dioxide fluxes in a thawing boreal forest–wetland landscape

In the sporadic permafrost zone of northwestern Canada, boreal forest carbon dioxide (CO₂) fluxes will be altered directly by climate change through changing meteorological forcing and indirectly through changes in landscape functioning associated with thaw‐induced collapse‐scar bog (‘wetland’) expansion. However, their combined effect on landscape‐scale net ecosystem CO₂ exchange (NEE_LAND), resulting from changing gross primary productivity (GPP) and ecosystem respiration (ER), remains unknown. Here, we quantify indirect land cover change impacts on NEE_LAND and direct climate change impacts on modeled temperature‐ and light‐limited NEE_LAND of a boreal forest–wetland landscape. Using nested eddy covariance flux towers, we find both GPP and ER to be larger at the landscape compared to the wetland level. However, annual NEE_LAND (?20 g C m^?2) and wetland NEE (?24 g C m^?2) were similar, suggesting negligible wetland expansion effects on NEE_LAND. In contrast, we find non‐negligible direct climate change impacts when modeling NEE_LAND using projected air temperature and incoming shortwave radiation. At the end of the 21st century, modeled GPP mainly increases in spring and fall due to reduced temperature limitation, but becomes more frequently light‐limited in fall. In a warmer climate, ER increases year‐round in the absence of moisture stress resulting in net CO₂ uptake increases in the shoulder seasons and decreases during the summer. Annually, landscape net CO₂ uptake is projected to decline by 25 ± 14 g C m^?2 for a moderate and 103 ± 38 g C m^?2 for a high warming scenario, potentially reversing recently observed positive net CO₂ uptake trends across the boreal biome. Thus, even without moisture stress, net CO₂ uptake of boreal forest–wetland landscapes may decline, and ultimately, these landscapes may turn into net CO₂ sources under continued anthropogenic CO₂ emissions. We conclude that NEE_LAND changes are more likely to be driven by direct climate change rather than by indirect land cover change impacts.