Life cycle assessment of forest biomass energy feedstock in the Northeast United States

Life cycle assessment (LCA) was combined with primary data from nine forest harvesting operations in New York, Maine, Massachusetts, and Vermont, from 2013 to 2019 where forest biomass (FB) for bioenergy was one of several products. The objective was to conduct a data‐driven study of greenhouse gas emissions associated with FB feedstock harvesting operations in the Northeast United States. Deterministic and stochastic LCA models were built to simulate the current FB bioenergy feedstock supply chain in the Northeast US with a cradle‐to‐gate scope (forest harvest through roadside loading) and a functional unit of 1.0 Mg of green FB feedstock at a 50% moisture content. Baseline LCA, sensitivity analysis, and uncertainty analyses were conducted for three different FB feedstock types—dirty chips, clean chips, and grindings—enabling an empirically driven investigation of differences between feedstock types, individual harvesting process contributions, and literature comparisons. The baseline LCA average impacts were lower for grindings (4.57 kg CO_2eq/Mg) and dirty chips (7.16 kg CO_2eq/Mg) than for clean chips (23.99 kg CO_2eq/Mg) under economic allocation, but impacts were of similar magnitude under mass allocation, ranging from 24.42 to 27.89 kg CO_2eq/Mg. Uncertainty analysis showed a wider range of probable results under mass allocation compared to economic allocation. Sensitivity analysis revealed the impact of variations in the production masses and total economic values of primary products of forest harvests on the LCA results due to allocation of supply chain emissions. The high variability in fuel use between logging contractors also had a distinct influence on LCA results. The results of this study can aid decision‐makers in energy policy and guide emissions reductions efforts while informing future LCAs that expand the system boundary to regional FB energy pathways, including electricity generation, transportation fuels, pellets for heat, and combined heat and power.     

Predicting soil carbon changes in switchgrass grown on marginal lands under climate change and adaptation strategies

The United States Great Lakes Region (USGLR) is a critical geographic area for future bioenergy production. Switchgrass (Panicum virgatum) is widely considered a carbon (C)‐neutral or C‐negative bioenergy production system, but projected increases in air temperature and precipitation due to climate change might substantially alter soil organic C (SOC) dynamics and storage in soils. This study examined long‐term SOC changes in switchgrass grown on marginal land in the USGLR under current and projected climate, predicted using a process‐based model (Systems Approach to Land‐Use Sustainability) extensively calibrated with a wealth of plant and soil measurements at nine experimental sites. Simulations indicate that these soils are likely a net C sink under switchgrass (average gain 0.87 Mg C ha^?1 year^?1), although substantial variation in the rate of SOC accumulation was predicted (range: 0.2–1.3 Mg C ha^?1 year^?1). Principal component analysis revealed that the predicted intersite variability in SOC sequestration was related in part to differences in climatic characteristics, and to a lesser extent, to heterogeneous soils. Although climate change impacts on switchgrass plant growth were predicted to be small (4%–6% decrease on average), the increased soil respiration was predicted to partially negate SOC accumulations down to 70% below historical rates in the most extreme scenarios. Increasing N fertilizer rate and decreasing harvest intensity both had modest SOC sequestration benefits under projected climate, whereas introducing genotypes better adapted to the longer growing seasons was a much more effective strategy. Best‐performing adaptation scenarios were able to offset >60% of the climate change impacts, leading to SOC sequestration 0.7 Mg C ha^?1 year^?1 under projected climate. On average, this was 0.3 Mg C ha^?1 year^?1 more C sequestered than the no adaptation baseline. These findings provide crucial knowledge needed to guide policy and operational management for maximizing SOC sequestration of future bioenergy production on marginal lands in the USGLR.     

Melanocortin‐1 receptor (MC1R) genotypes do not correlate with size in two cohorts of medium‐to‐giant congenital melanocytic nevi

Congenital melanocytic nevi (CMN) are cutaneous malformations whose prevalence is inversely correlated with projected adult size. CMN are caused by somatic mutations, but epidemiological studies suggest that germline genetic factors may influence CMN development. In CMN patients from the U.K., genetic variants in MC1R, such as p.V92M and loss‐of‐function variants, have been previously associated with larger CMN. We analyzed the association of MC1R variants with CMN characteristics in two distinct cohorts of medium‐to‐giant CMN patients from Spain (N = 113) and from France, Norway, Canada, and the United States (N = 53), similar at the clinical and phenotypical level except for the number of nevi per patient. We found that the p.V92M or loss‐of‐function MC1R variants either alone or in combination did not correlate with CMN size, in contrast to the U.K. CMN patients. An additional case–control analysis with 259 unaffected Spanish individuals showed a higher frequency of MC1R compound heterozygous or homozygous variant genotypes in Spanish CMN patients compared to the control population (15.9% vs. 9.3%; p = .075). Altogether, this study suggests that MC1R variants are not associated with CMN size in these non‐UK cohorts. Additional studies are required to define the potential role of MC1R as a risk factor in CMN development.     

Induced pluripotent stem cell‐derived myeloid cells expressing OX40 ligand amplify antigen‐specific T cells in advanced melanoma

Immune checkpoint inhibitors improved the survival rate of patients with unresectable melanoma. However, some patients do not respond, and variable immune‐related adverse events have been reported. Therefore, more effective and antigen‐specific immune therapies are urgently needed. We previously reported the efficacy of an immune cell therapy with immortalized myeloid cells derived from induced pluripotent stem cells (iPS‐ML). In this study, we generated OX40L‐overexpressing iPS‐ML (iPS‐ML‐Zsgreen‐OX40L) and investigated their characteristics and in vivo efficacy against mouse melanoma. We found that iPS‐ML‐Zsgreen‐OX40L suppressed the progression of B16‐BL6 melanoma, and prolonged survival of mice with ovalbumin (OVA)‐expressing B16 melanoma (MO4). The number of antigen‐specific CD8⁺ T cells was higher in spleen cells treated with OVA peptide‐pulsed iPS‐ML‐Zsgreen‐OX40L than in those without OX40L. The OVA peptide‐pulsed iPS‐ML‐Zsgreen‐OX40L significantly increased the number of tumor‐infiltrating T lymphocytes (TILs) in MO4 tumor. Flow cytometry showed decreased regulatory T cells but increased effector and effector memory T cells among the TILs. Although we plan to use allogeneic iPS‐ML in the clinical applications, iPS‐ML showed the tumorgenicity in the syngeneic mice model. Incorporating the suicide gene is necessary to ensure the safety in the future study. Collectively, these results indicate that iPS‐ML‐Zsgreen‐OX40L therapy might be a new method for antigen‐specific cancer immunotherapy.     

Do innate killing mechanisms activated by inflammasomes have a role in treating melanoma?

Melanoma, as for many other cancers, undergoes a selection process during progression that limits many innate and adaptive tumor control mechanisms. Immunotherapy with immune checkpoint blockade overcomes one of the escape mechanisms but if the tumor is not eliminated other escape mechanisms evolve that require new approaches for tumor control. Some of the innate mechanisms that have evolved against infections with microorganisms and viruses are proving to be active against cancer cells but require better understanding of how they are activated and what inhibitory mechanisms may need to be targeted. This is particularly so for inflammasomes which have evolved against many different organisms and which recruit a number of cytotoxic mechanisms that remain poorly understood. Equally important is understanding of where these mechanisms will fit into existing treatment strategies and whether existing strategies already involve the innate killing mechanisms.     

A genome‐wide linkage map for the house sparrow (Passer domesticus) provides insights into the evolutionary history of the avian genome

The house sparrow is an important model species for studying physiological, ecological and evolutionary processes in wild populations. Here, we present a medium density, genome wide linkage map for house sparrow (Passer domesticus) that has aided the assembly of the house sparrow reference genome, and that will provide an important resource for ongoing mapping of genes controlling important traits in the ecology and evolution of this species. Using a custom house sparrow 10 K iSelect Illumina SNP chip we have assigned 6,498 SNPs to 29 autosomal linkage groups, based on a mean of 430 informative meioses per SNP. The map was constructed by combining the information from linkage with that of the physical position of SNPs within scaffold sequences in an iterative process. Averaged between the sexes; the linkage map had a total length of 2,004 cM, with a longer map for females (2,240 cM) than males (1,801 cM). Additionally, recombination rates also varied along the chromosomes. Comparison of the linkage map to the reference genomes of zebra finch, collared flycatcher and chicken, showed a chromosome fusion of the two avian chromosomes 8 and 4A in house sparrow. Lastly, information from the linkage map was utilized to conduct analysis of linkage disequilibrium (LD) in eight populations with different effective population sizes (N_e) in order to quantify the background level LD. Together, these results aid the design of future association studies, facilitate the development of new genomic tools and support the body of research that describes the evolution of the avian genome.     

Development of a 3D Tissue‐Engineered Skeletal Muscle and Bone Co‐culture System

In vitro 3D tissue‐engineered (TE) structures have been shown to better represent in vivo tissue morphology and biochemical pathways than monolayer culture, and are less ethically questionable than animal models. However, to create systems with even greater relevance, multiple integrated tissue systems should be recreated in vitro. In the present study, the effects and conditions most suitable for the co‐culture of TE skeletal muscle and bone are investigated. High‐glucose Dulbecco's modified Eagle medium (HG‐DMEM) supplemented with 20% fetal bovine serum followed by HG‐DMEM with 2% horse serum is found to enable proliferation of both C2C12 muscle precursor cells and TE85 human osteosarcoma cells, fusion of C2C12s into myotubes, as well as an upregulation of RUNX2/CBFa1 in TE85s. Myotube formation is also evident within indirect contact monolayer cultures. Finally, in 3D co‐cultures, TE85 collagen/hydroxyapatite constructs have significantly greater expression of RUNX2/CBFa1 and osteocalcin/BGLAP in the presence of collagen‐based C2C12 skeletal muscle constructs; however, fusion within these constructs appears reduced. This work demonstrates the first report of the simultaneous co‐culture and differentiation of 3D TE skeletal muscle and bone, and represents a significant step toward a full in vitro 3D musculoskeletal junction model.