Inhibition of Bone Morphogenetic Protein Signal Transduction Prevents the Medial Vascular Calcification Associated with Matrix Gla Protein Deficiency

Objective: Matrix Gla protein (MGP) is reported to inhibit bone morphogenetic protein (BMP) signal transduction. MGP deficiency is associated with medial calcification of the arterial wall, in a process that involves both osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) and mesenchymal transition of endothelial cells (EndMT). In this study, we investigated the contribution of BMP signal transduction to the medial calcification that develops in MGP-deficient mice. Approach and Results MGP-deficient mice (MGP-/-) were treated with one of two BMP signaling inhibitors, LDN-193189 or ALK3-Fc, beginning one day after birth. Aortic calcification was assessed in 28-day-old mice by measuring the uptake of a fluorescent bisphosphonate probe and by staining tissue sections with Alizarin red. Aortic calcification was 80% less in MGP-/- mice treated with LDN-193189 or ALK3-Fc compared with vehicle-treated control animals (P<0.001 for both). LDN-193189-treated MGP-/- mice survived longer than vehicle-treated MGP-/- mice. Levels of phosphorylated Smad1/5 and Id1 mRNA (markers of BMP signaling) did not differ in the aortas from MGP-/- and wild-type mice. Markers of EndMT and osteogenesis were increased in MGP-/- aortas, an effect that was prevented by LDN-193189. Calcification of isolated VSMCs was also inhibited by LDN-193189. Conclusions: Inhibition of BMP signaling leads to reduced vascular calcification and improved survival in MGP-/- mice. The EndMT and osteogenic transdifferentiation associated with MGP deficiency is dependent upon BMP signaling. These results suggest that BMP signal transduction has critical roles in the development of vascular calcification in MGP-deficient mice

Crop Pests and Predators Exhibit Inconsistent Responses to Surrounding Landscape Composition

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win–win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies

Crop pests and predators exhibit inconsistent responses to surrounding landscape composition

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win–win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Modest capacity of no-till farming to offset emissions over 21st century

‘No-till’ (NT) agriculture, which eliminates nearly all physical disturbance of the soil surface on croplands, has been widely promoted as a means of soil organic carbon (SOC) sequestration with the potential to mitigate climate change. Here we provide the first global estimates of the SOC sequestration potential of NT adoption using a global land surface model (LSM). We use an LSM to simulate losses of SOC due to intensive tillage (IT) over the historical time period (1850–2014), followed by future simulations (2015–2100) assessing the SOC sequestration potential of adopting NT globally. Historical losses due to simulated IT practices ranged from 6.8 to 16.8 Gt C, or roughly 5%–13% of the 133 Gt C of global cumulative SOC losses attributable to agriculture reported elsewhere. Cumulative SOC sequestration in NT simulations over the entire 21st century was equivalent to approximately one year of current fossil fuel emissions and ranged between 6.6 and 14.4 Gt C (0.08–0.17 Gt C yr −1 ). Modeled increases in SOC sequestration under NT were concentrated in cool, humid temperate regions, with minimal SOC gains in the tropics. These results indicate that the global potential for SOC sequestration from NT adoption may be more limited than reported in some studies and promoted by policymakers. Our incorporation of tillage practices into an LSM is a major step toward integration of soil tillage as a management practice into LSMs and associated Earth system models. Future work should focus on improving process-understanding of tillage practices and their integration into LSMs, as well as resolving modeled versus observed estimates of SOC sequestration from NT adoption, particularly in the tropics

Using Twitter to Examine Stigma Against People With Dementia During COVID-19: Infodemiology Study

BackgroundDuring the pandemic, there has been significant social media attention focused on the increased COVID-19 risks and impacts for people with dementia and their care partners. However, these messages can perpetuate misconceptions, false information, and stigma. ObjectiveThis study used Twitter data to understand stigma against people with dementia propagated during the COVID-19 pandemic. MethodsWe collected 1743 stigma-related tweets using the GetOldTweets application in Python from February 15 to September 7, 2020. Thematic analysis was used to analyze the tweets. ResultsBased on our analysis, 4 main themes were identified: (1) ageism and devaluing the lives of people with dementia, (2) misinformation and false beliefs about dementia and COVID-19, (3) dementia used as an insult for political ridicule, and (4) challenging stigma against dementia. Social media has been used to spread stigma, but it can also be used to challenge negative beliefs, stereotypes, and false information. ConclusionsDementia education and awareness campaigns are urgently needed on social media to address COVID-19-related stigma. When stigmatizing discourse on dementia is widely shared and consumed amongst the public, it has public health implications. How we talk about dementia shapes how policymakers, clinicians, and the public value the lives of people with dementia. Stigma perpetuates misinformation, pejorative language, and patronizing attitudes that can lead to discriminatory actions, such as the limited provision of lifesaving supports and health services for people with dementia during the pandemic. COVID-19 policies and public health messages should focus on precautions and preventive measures rather than labeling specific population groups

The Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease

Abstract Non-alcoholic fatty liver disease (NAFLD) affects over 30% of adults in the United States. Bone morphogenetic protein (BMP) signaling is known to contribute to hepatic fibrosis, but the role of BMP signaling in the development of NAFLD is unclear. In this study, treatment with either of two BMP inhibitors reduced hepatic triglyceride content in diabetic (db/db) mice. BMP inhibitor-induced decrease in hepatic triglyceride levels was associated with decreased mRNA encoding Dgat2, an enzyme integral to triglyceride synthesis. Treatment of hepatoma cells with BMP2 induced DGAT2 expression and activity via intracellular SMAD signaling. In humans we identified a rare missense single nucleotide polymorphism in the BMP type 1 receptor ALK6 (rs34970181;R371Q) associated with a 2.1-fold increase in the prevalence of NAFLD. In vitro analyses revealed R371Q:ALK6 is a previously unknown constitutively active receptor. These data show that BMP signaling is an important determinant of NAFLD in a murine model and is associated with NAFLD in humans

Vascular calcification associated with MGP deficiency occurs in the absence of vascular inflammation.

<p>(<b>A</b>) At 27 days of age, OsteoSense-680 and Prosense-750 were injected via the tail vein of wild-type (WT) and MGP^-/- mice. Aortas were harvested 24 hours later and imaged. Although aortas from MGP^-/- mice exhibited extensive vascular calcification, this calcification was not associated with increased macrophage activity. (<b>B</b>) Aortas were harvested from WT and MGP^-/- mice at 28 days of age, sectioned, and stained for macrophages with an antibody directed towards MAC-2. Aortas from LDLR^-/- mice on a high fat diet were used as a positive control. Nuclei were stained with DAPI. Similar to WT mice, macrophages were not detected by immunohistochemistry in the aortas of MGP^-/- mice.</p