Macrophage phenotype in response to ECM bioscaffolds

Macrophage presence and phenotype are critical determinants of the healing response following injury. Downregulation of the pro-inflammatory macrophage phenotype has been associated with the therapeutic use of bioscaffolds composed of extracellular matrix (ECM), but phenotypic characterization of macrophages has typically been limited to small number of non-specific cell surface markers or expressed proteins. The present study determined the response of both primary murine bone marrow derived macrophages (BMDM) and a transformed human mononuclear cell line (THP-1 cells) to degradation products of two different, commonly used ECM bioscaffolds; urinary bladder matrix (UBM-ECM) and small intestinal submucosa (SIS-ECM). Quantified cell responses included gene expression, protein expression, commonly used cell surface markers, and functional assays. Results showed that the phenotype elicited by ECM exposure (MECM) is distinct from both the classically activated IFNγ + LPS phenotype and the alternatively activated IL-4 phenotype. Furthermore, the BMDM and THP-1 macrophages responded differently to identical stimuli, and UBM-ECM and SIS-ECM bioscaffolds induced similar, yet distinct phenotypic profiles. The results of this study not only characterized an MECM phenotype that has anti-inflammatory traits but also showed the risks and challenges of making conclusions about the role of macrophage mediated events without consideration of the source of macrophages and the limitations of individual cell markers

Criteria for effective zero-deforestation commitments

Zero-deforestation commitments are a type of voluntary sustainability initiative that companies adopt to signal their intention to reduce or eliminate deforestation associated with commodities that they produce, trade, and/or sell. Because each company defines its own zero-deforestation commitment goals and implementation mechanisms, commitment content varies widely. This creates challenges for the assessment of commitment implementation or effectiveness. Here, we develop criteria to assess the potential effectiveness of zero-deforestation commitments at reducing deforestation within a company supply chain, regionally, and globally. We apply these criteria to evaluate 52 zero-deforestation commitments made by companies identified by Forest 500 as having high deforestation risk. While our assessment indicates that existing commitments converge with several criteria for effectiveness, they fall short in a few key ways. First, they cover just a small share of the global market for deforestation-risk commodities, which means that their global impact is likely to be small. Second, biome-wide implementation is only achieved in the Brazilian Amazon. Outside this region, implementation occurs mainly through certification programs, which are not adopted by all producers and lack third-party near-real time deforestation monitoring. Additionally, around half of all commitments include zero-net deforestation targets and future implementation deadlines, both of which are design elements that may reduce effectiveness. Zero-net targets allow promises of future reforestation to compensate for current forest loss, while future implementation deadlines allow for preemptive clearing. To increase the likelihood that commitments will lead to reduced deforestation across all scales, more companies should adopt zero-gross deforestation targets with immediate implementation deadlines and clear sanction-based implementation mechanisms in biomes with high risk of forest to commodity conversion.ISSN:0959-3780ISSN:1872-949

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Long-Term Continental Changes in Wing Length, but Not Bill Length, of a Long-Distance Migratory Shorebird

We compiled a >50‐year record of morphometrics for semipalmated sandpipers (Calidris pusilla), a shorebird species with a Nearctic breeding distribution and intercontinental migration to South America. Our data included >57,000 individuals captured 1972–2015 at five breeding locations and three major stopover sites, plus 139 museum specimens collected in earlier decades. Wing length increased by ca. 1.5 mm (>1%) prior to 1980, followed by a decrease of 3.85 mm (nearly 4%) over the subsequent 35 years. This can account for previously reported changes in metrics at a migratory stopover site from 1985 to 2006. Wing length decreased at a rate of 1,098 darwins, or 0.176 haldanes, within the ranges of other field studies of phenotypic change. Bill length, in contrast, showed no consistent change over the full period of our study. Decreased body size as a universal response of animal populations to climate warming, and several other potential mechanisms, are unable to account for the increasing and decreasing wing length pattern observed. We propose that the post‐WWII near‐extirpation of falcon populations and their post‐1973 recovery driven by the widespread use and subsequent limitation on DDT in North America selected initially for greater flight efficiency and latterly for greater agility. This predation danger hypothesis accounts for many features of the morphometric data and deserves further investigation in this and other species

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Green for gold: social and ecological tradeoffs influencing the sustainability of the Brazilian soy industry

In this study we assess the sustainability of the Brazilian soy industry over the past 40 years in comparison to alternative land uses. We conclude that Brazilian soy production performs as well as or better than sugarcane or cattle production in a number of areas, including macroeconomic contributions, local economic development and land use efficiency, though it involves similar tradeoffs between growth and equity, and food production and conservation. While there is no evidence that soy has reduced food security in Brazil, tax redistributions and value-added activities from soy remain limited, particularly in comparison to sugarcane production. Emerging environmental governance measures have helped to reduce the land cover impacts from soy; however, little effort has been taken to minimize the impacts of intensification

Sustainable intensification in the Brazilian cattle industry: the role for reduced slaughter age

The cattle industry in the Brazilian Amazon causes vast deforestation while producing at only one-third of the sustainable capacity. Slaughtering cattle at a younger age directly increases production per hectare per year, all else equal, and provides a potential path for sustainable intensification. Here we show that slaughter age is decreasing in the Amazon biome, but this increase in productivity varies across space and throughout the cattle supply chain. We characterize the properties and municipalities that have reduced slaughter age, providing insights into the incentives and barriers to this form of intensification. Most notably, reductions in slaughter age occurred in regions with low remaining forest cover and on properties with little current deforestation, suggesting that ranchers intensify via slaughter age as an alternative to deforestation. We then estimate how changing production practices to reduce slaughter age can reduce enteric methane emissions, accounting for production of additional feed. Our results indicate that reducing slaughter age through improved pasture and feed sources are a path to lower global GHG emissions from cattle production, particularly as beef is increasingly produced in developing countries with historically higher emissions. Yet in the Amazon, deforestation remains the leading source of GHG emissions, necessitating that any effort to reduce slaughter age must be coupled with strict enforcement of zero-deforestation policy. Our findings demonstrate the potential of policy limiting deforestation as a means to reduce both emissions from deforestation and enteric emissions from cattle