MAP3K4 promotes fetal and placental growth by controlling the receptor tyrosine kinases IGF1R/IR and Akt signaling pathway.

Disruption of fetal growth results in severe consequences to human health, including increased fetal and neonatal morbidity and mortality, as well as potential lifelong health problems. Molecular mechanisms promoting fetal growth represent potential therapeutic strategies to treat and/or prevent fetal growth restriction (FGR). Here, we identify a previously unknown role for the mitogen-activated protein kinase kinase kinase 4 (MAP3K4) in promoting fetal and placental growth. We demonstrate that inactivation of MAP3K4 kinase activity causes FGR due in part to placental insufficiency. Significantly, MAP3K4 kinase-inactive mice display highly penetrant lethality prior to weaning and persistent growth reduction of surviving adults. Additionally, we elucidate molecular mechanisms by which MAP3K4 promotes growth through control of the insulin-like growth factor 1 receptor (IGF1R), insulin receptor (IR), and Akt signaling pathway. Specifically, MAP3K4 kinase inactivation in trophoblast stem (TS) cells results in reduced IGF1R and IR expression and decreased Akt activation. We observe these changes in TS cells also occur in differentiated trophoblasts created through in vitro differentiation of cultured TS cells and in vivo in placental tissues formed by TS cells. Furthermore, we show that MAP3K4 controls this pathway by promoting Igf1r transcript expression in TS cells through activation of CREB-binding protein (CBP). In the MAP3K4 kinase-inactive TS cells, Igf1r transcripts are repressed because of reduced CBP activity and increased histone deacetylase 6 expression and activity. Together, these data demonstrate a critical role for MAP3K4 in promoting fetal and placental growth by controlling the activity of the IGF1R/IR and Akt signaling pathway.

GALNT3 Maintains the Epithelial State in Trophoblast Stem Cells.

O-GalNAc glycosylation is initiated in the Golgi by glycosyltransferases called GALNTs. Proteomic screens identified >600 O-GalNAc-modified proteins, but the biological relevance of these modifications has been difficult to determine. We have discovered a conserved function for GALNT3 in trophoblast stem (TS) cells, blastocyst trophectoderm, and human mammary epithelial cells (HMECs). The loss of GALNT3 expression in these systems reduces O-GalNAc glycosylation and induces epithelial-mesenchymal transition. Furthermore, Galnt3 expression is reduced in aggressive, mesenchymal claudin-low breast cancer cells. We show that GALNT3 expression controls the O-GalNAc glycosylation of multiple proteins, including E-cadherin in both TS cells and HMECs. The loss of GALNT3 results in the intracellular retention of E-cadherin in the Golgi. Significantly, re-expression of GALNT3 in TS cells increases O-GalNAc glycosylation and restores the epithelial state. Together, these data demonstrate the critical biological role of GALNT3 O-GalNAc glycosylation to promote the epithelial phenotype in TS cells, blastocyst trophectoderm, and HMECs.

Correction: Growth and survival relationships of 71 tree species with nitrogen and sulfur deposition across the conterminous U.S.

[This corrects the article DOI: 10.1371/journal.pone.0205296.].

Growth and survival relationships of 71 tree species with nitrogen and sulfur deposition across the conterminous U.S.

Atmospheric deposition of nitrogen (N) influences forest demographics and carbon (C) uptake through multiple mechanisms that vary among tree species. Prior studies have estimated the effects of atmospheric N deposition on temperate forests by leveraging forest inventory measurements across regional gradients in deposition. However, in the United States (U.S.), these previous studies were limited in the number of species and the spatial scale of analysis, and did not include sulfur (S) deposition as a potential covariate. Here, we present a comprehensive analysis of how tree growth and survival for 71 species vary with N and S deposition across the conterminous U.S. Our analysis of 1,423,455 trees from forest plots inventoried between 2000 and 2016 reveals that the growth and/or survival of the vast majority of species in the analysis (n = 66, or 93%) were significantly affected by atmospheric deposition. Species co-occurred across the conterminous U.S. that had decreasing and increasing relationships between growth (or survival) and N deposition, with just over half of species responding negatively in either growth or survival to increased N deposition somewhere in their range (42 out of 71). Averaged across species and conterminous U.S., however, we found that an increase in deposition above current rates of N deposition would coincide with a small net increase in tree growth (1.7% per Δ kg N ha-1 yr-1), and a small net decrease in tree survival (-0.22% per Δ kg N ha-1 yr-1), with substantial regional and among-species variation. Adding S as a predictor improved the overall model performance for 70% of the species in the analysis. Our findings have potential to help inform ecosystem management and air pollution policy across the conterminous U.S., and suggest that N and S deposition have likely altered forest demographics in the U.S.

Reforestation can sequester two petagrams of carbon in US topsoils in a century.

Soils are Earth's largest terrestrial carbon (C) pool, and their responsiveness to land use and management make them appealing targets for strategies to enhance C sequestration. Numerous studies have identified practices that increase soil C, but their inferences are often based on limited data extrapolated over large areas. Here, we combine 15,000 observations from two national-level databases with remote sensing information to address the impacts of reforestation on the sequestration of C in topsoils (uppermost mineral soil horizons). We quantify C stocks in cultivated, reforesting, and natural forest topsoils; rates of C accumulation in reforesting topsoils; and their contribution to the US forest C sink. Our results indicate that reforestation increases topsoil C storage, and that reforesting lands, currently occupying >500,000 km2 in the United States, will sequester a cumulative 1.3-2.1 Pg C within a century (13-21 Tg C·y-1). Annually, these C gains constitute 10% of the US forest sector C sink and offset 1% of all US greenhouse gas emissions.

Estimating litter carbon stocks on forest land in the United States.

Forest ecosystems are the largest terrestrial carbon sink on earth, with more than half of their net primary production moving to the soil via the decomposition of litter biomass. Therefore, changes in the litter carbon (C) pool have important implications for global carbon budgets and carbon emissions reduction targets and negotiations. Litter accounts for an estimated 5% of all forest ecosystem carbon stocks worldwide. Given the cost and time required to measure litter attributes, many of the signatory nations to the United Nations Framework Convention on Climate Change report estimates of litter carbon stocks and stock changes using default values from the Intergovernmental Panel on Climate Change or country-specific models. In the United States, the country-specific model used to predict litter C stocks is sensitive to attributes on each plot in the national forest inventory, but these predictions are not associated with the litter samples collected over the last decade in the national forest inventory. Here we present, for the first time, estimates of litter carbon obtained using more than 5000 field measurements from the national forest inventory of the United States. The field-based estimates mark a 44% reduction (2081±77Tg) in litter carbon stocks nationally when compared to country-specific model predictions reported in previous United Framework Convention on Climate Change submissions. Our work suggests that Intergovernmental Panel on Climate Change defaults and country-specific models used to estimate litter carbon in temperate forest ecosystems may grossly overestimate the contribution of this pool in national carbon budgets.

Temperature drives global patterns in forest biomass distribution in leaves, stems, and roots.

Whether the fraction of total forest biomass distributed in roots, stems, or leaves varies systematically across geographic gradients remains unknown despite its importance for understanding forest ecology and modeling global carbon cycles. It has been hypothesized that plants should maintain proportionally more biomass in the organ that acquires the most limiting resource. Accordingly, we hypothesize greater biomass distribution in roots and less in stems and foliage in increasingly arid climates and in colder environments at high latitudes. Such a strategy would increase uptake of soil water in dry conditions and of soil nutrients in cold soils, where they are at low supply and are less mobile. We use a large global biomass dataset (>6,200 forests from 61 countries, across a 40 °C gradient in mean annual temperature) to address these questions. Climate metrics involving temperature were better predictors of biomass partitioning than those involving moisture availability, because, surprisingly, fractional distribution of biomass to roots or foliage was unrelated to aridity. In contrast, in increasingly cold climates, the proportion of total forest biomass in roots was greater and in foliage was smaller for both angiosperm and gymnosperm forests. These findings support hypotheses about adaptive strategies of forest trees to temperature and provide biogeographically explicit relationships to improve ecosystem and earth system models. They also will allow, for the first time to our knowledge, representations of root carbon pools that consider biogeographic differences, which are useful for quantifying whole-ecosystem carbon stocks and cycles and for assessing the impact of climate change on forest carbon dynamics.

Status and future of the forest health indicators program of the USA.

For two decades, the US Department of Agriculture, Forest Service, has been charged with implementing a nationwide field-based forest health monitoring effort. Given its extensive nature, the monitoring program has been gradually implemented across forest health indicators and inventoried states. Currently, the Forest Service's Forest Inventory and Analysis program has initiated forest health inventories in all states, and most forest health indicators are being documented in terms of sampling protocols, data management structures, and estimation procedures. Field data from most sample years and indicators are available on-line with numerous analytical examples published both internally and externally. This investment in national forest health monitoring has begun to yield dividends by allowing evaluation of state/regional forest health issues (e.g., pollution and invasive pests) and contributing substantially to national/international reporting efforts (e.g., National Report on Sustainability and US EPA Annual Greenhouse Gas Estimates). With the emerging threat of climate change, full national implementation and remeasurement of a forest health inventory should allow for more robust assessment of forest communities that are undergoing unprecedented changes, aiding future land management and policy decisions.