Predicted wind and solar energy expansion has minimal overlap with multiple conservation priorities across global regions.

Protected areas and renewable energy generation are critical tools to combat biodiversity loss and climate change, respectively. Over the coming decades, expansion of the protected area network to meet conservation objectives will be occurring alongside rapid deployment of renewable energy infrastructure to meet climate targets, driving potential conflict for a finite land resource. Renewable energy infrastructure can have negative effects on wildlife, and co-occurrence may mean emissions targets are met at the expense of conservation objectives. Here, we assess current and projected overlaps of wind and solar photovoltaic installations and important conservation areas across nine global regions using spatially explicit wind and solar data and methods for predicting future renewable expansion. We show similar levels of co-occurrence as previous studies but demonstrate that once area is accounted for, previous concerns about overlaps in the Northern Hemisphere may be largely unfounded, although they are high in some biodiverse countries (e.g., Brazil). Future projections of overlap between the two land uses presented here are generally dependent on priority threshold and region and suggest the risk of future conflict can be low. We use the best available data on protected area degradation to corroborate this level of risk. Together, our findings indicate that while conflicts between renewables and protected areas inevitably do occur, renewables represent an important option for decarbonization of the energy sector that would not significantly affect area-based conservation targets if deployed with appropriate policy and regulatory controls.

Effect of drought stress during seed development on charcoal rot and yield of soybean.

The primary controls for charcoal rot in soybean, caused by the fungal pathogen Macrophomina phaseolina, are to avoid drought stress and to plant a moderately resistant cultivar. The effects of irrigation and cultivar were determined in 2011 and 2013 at the Lon Mann Cotton Research Station, Marianna, AR. Four soybean cultivars (Hutcheson, Osage, Ozark, and R01581F), were planted in plots with or without added M. phaseolina inoculum and subjected to three furrow irrigation regimes: full season irrigation (Full), irrigation terminated at R5 (CutR5), and non-irrigated (NonIrr). Normalized difference vegetative index (NDVI) was measured at R3 and R6. At harvest, plants and yields were collected. Roots and stems were split and the extent of visible colonization by M. phaseolina microsclerotia was assessed in the roots with a 1-5 scale (RSS) and the percent plant height stem discoloration (PHSD) measured. Precipitation in September and October was 54 and 65% below the 30-year average in 2011 and 2013, respectively. The CutR5 irrigation treatment resulted in one less irrigation than Full each year, but CutR5 NDVI's at R6 and yields were significantly lower than those with Full and not significantly different than those of NonIrr. The CutR5 RSS ratings were greater than either Full or NonIrr. Plant colonization by M. phaseolina was negatively correlated to yield in 2011 but not in 2013. No premature plant death caused by charcoal rot was observed in either year. These results indicated that late season drought stress may be more important to charcoal rot development than drought stress throughout the season, but other factors are needed to trigger early plant death and subsequent yield losses observed in grower fields.

The influence of the global electric power system on terrestrial biodiversity.

Given its total contribution to greenhouse gas emissions, the global electric power sector will be required to undergo a fundamental transformation over the next decades to limit anthropogenic climate change to below 2 °C. Implications for biodiversity of projected structural changes in the global electric power sector are rarely considered beyond those explicitly linked to climate change. This study uses a spatially explicit consumption-based accounting framework to examine the impact of demand for electric power on terrestrial vertebrate biodiversity globally. We demonstrate that the biodiversity footprint of the electric power sector is primarily within the territory where final demand for electric power resides, although there are substantial regional differences, with Europe displacing its biodiversity threat along international supply chains. The relationship between size of individual components of the electric power sector and threat to biodiversity indicates that a shift to nonfossil sources, such as solar and wind, could reduce pressures on biodiversity both within the territory where demand for power resides and along international supply chains. However, given the current levels of deployment of nonfossil sources of power, there is considerable uncertainty as to how the impacts of structural changes in the global electric power system will scale. Given the strong territorial link between demand and associated biodiversity impacts, development of strong national governance around the electric power sector represents a clear route to mitigate threats to biodiversity associated with efforts to decarbonize society over the coming century.

The effect of overexpression of Lrp5 on orthodontic tooth movement.

OBJECTIVE: To analyse the effect of gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (Lrp5) on orthodontic tooth movement (OTM). SETTING AND SAMPLE POPULATION: A split-mouth study design was utilized. Thirty-two male Lrp5-high bone mass (HBM) knock-in mice including A214V and G171V mutants (n = 16/group) and sixteen C57BL/6 wild-type (WT) mice were included in the study. MATERIALS AND METHODS: A mouse model of OTM was used for mesial movement of the maxillary first molar using a closed-coil nickel titanium (NiTi) spring attached between the molar and the incisors. After 21 days, the dissected maxillae were scanned for micro-computed tomography (micro-CT) analyses and embedded in methyl methacrylate and paraffin for histological staining and imaging. Histological analyses included immunohistochemistry for sclerostin (Sost), tartrate-resistant acid phosphatase (TRAP) staining for osteoclasts and fluorescent imaging. RESULTS: OTM in the A214V and G171V groups was significantly less than the WT group. Bone volume (BV), per cent bone volume (BV/TV) and trabecular thickness (Tb.Th) were significantly increased in both A241V and G171V animals compared to the WT animals. On the compression side, decreased osteoclast activity was seen in both A214V and G171V groups compared to the WT group. Fluorescent labelling demonstrated that the pattern of bone deposition in the A214V animals was periosteal whereas the G171V animals added bone endocortically. CONCLUSION: Gain-of-function mutations of Lrp5 decrease orthodontic tooth movement by increasing alveolar bone mass and reducing osteoclast-mediated bone resorption.

Effects of Soybean Cultivar, Foliar Application of Azoxystrobin, and Year on Seed Vigor and Microflora Under Delayed Harvest Conditions.

The effects of cultivar and foliar fungicide applications on soybean seed germination, vigor, microflora, and yield after delayed harvest were determined at the University of Arkansas Vegetable Research Station in Kibler, AR, from 2008 to 2010. Seven cultivars with varying levels of resistance to Diaporthe spp. or Cercospora spp. were treated or not treated with a foliar application of azoxystrobin at the R5 growth stage. Plots were harvested 3 weeks after the plants had reached harvest maturity. Yields were recorded, samples of seed were collected, and standard germination (SG) and accelerated aging (AA) were assessed. Seeds were also assayed for infection by fungi on modified potato dextrose agar and by bacteria on nutrient agar. Seed vigor was significantly reduced by infection with Diaporthe spp., Fusarium spp., and Bacillus subtilis, but not with Cercospora spp. Cultivar had a significant impact on yield, seed vigor, and seed infection levels. The cultivar Osage had consistently high seed vigor and low overall seed infection incidence throughout the study. MO/PSD-0259, AG 4403, and UA 4805 also had relatively high seed vigor and low seed infection rates. PI 80837 had a low incidence of seed infection by Diaporthe spp. and Fusarium spp. in 2008 and 2010, but high levels in 2009, when environmental conditions were especially favorable for these pathogens. AP 350 and Suweon97 had relatively high seed infection incidences, particularly of Diaporthe spp. and Fusarium spp., and relatively low seed vigor. Application of the foliar fungicide azoxystrobin at the R5 growth stage significantly increased AA across years and cultivars and increased seed infection by Diaporthe spp. in 2009 across cultivars. There were significant negative correlations between yield and seed infection by Diaporthe spp. and Bacillus subtilis during 1 year and with Fusarium spp. during all 3 years. Overall, resistance to seed infection can persist even when harvest is delayed. In addition to Diaporthe spp., other seedborne pathogens may reduce seed vigor and yield.

Collagenolytic matrix metalloproteinases antagonize proteinase-activated receptor-2 activation, providing insights into extracellular matrix turnover.

The collagenase subfamily of matrix metalloproteinases (MMPs) have important roles in the remodeling of collagenous matrices. The proteinase-activated receptor (PAR) family has a unique mechanism of activation requiring proteolysis of an extracellular domain forming a neo-N terminus that acts as a tethered ligand, a process that has been associated with the development of arthritis. Canonical PAR2 activation typically occurs via a serine proteinase at Arg36-Ser37, but other proteinases can cleave PARs downstream of the tethered ligand and "disarm" the receptor. To identify additional cleavage sites within PAR2, we synthesized a 42-amino-acid peptide corresponding to the extracellular region. We observed that all three soluble MMP collagenases, MMP-1, MMP-8, and MMP-13, cleave PAR2 and discovered a novel cleavage site (Ser37-Leu38). Metalloproteinases from resorbing bovine nasal cartilage and recombinant human collagenases could cleave a quenched fluorescent peptide mimicking the canonical PAR2 activation region, and kinetic constants were determined. In PAR2-overexpressing SW1353 chondrocytes, we demonstrated that the activator peptide SLIGKV-NH2 induces rapid calcium flux, inflammatory gene expression (including MMP1 and MMP13), and the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 kinase. The corresponding MMP cleavage-derived peptide (LIGKVD-NH2) exhibited no canonical activation; however, we observed phosphorylation of ERK, providing evidence of biased agonism. Importantly, we demonstrated that preincubation with active MMP-1 reduced downstream PAR2 activation by a canonical activator, matriptase, but not SLIGKV-NH2 These results support a role for collagenases as proteinases capable of disarming PAR2, revealing a mechanism that suppresses PAR2-mediated inflammatory responses.

Osteoblast differentiation during orthodontic tooth movement.

OBJECTIVES: To analyse the expression of osteoblast differentiation markers and osteoclast activity in the periodontal ligament (PDL) following 2, 4 and 7 days of orthodontic tooth movement (OTM) in an animal model. SETTING AND SAMPLE POPULATION: Eighteen C57BL/6 wild-type mice. MATERIAL AND METHODS: For the OTM model, orthodontic force was applied to the maxillary right first molar using a closed-coil NiTi spring activated between the molar and incisors. The left side served as the control. Following OTM, the dissected tissues were scanned for micro-computed tomography (micro-CT) analysis and processed for histology. Histological stains included tartrate-resistant acid phosphatase (TRAP) staining for osteoclasts and immunohistochemistry for osteoblast markers alpha-smooth muscle actin (α-SMA), osteopontin (OP) and osteocalcin (OC). RESULTS: Micro-CT analysis showed increasing OTM on days 2, 4 and 7 days as well as decrease in bone volume and per cent bone volume at 4 and 7 days. Statistically significant increases in osteoblast marker expression were seen in all groups when compared to the control. TRAP expression was highest at 4 and 7 days, α-SMA was highest at 2 days and OP/OC was highest at 4 days. CONCLUSION: During OTM, proliferation of pre-osteoblasts peaks at 2 days while mineralization of the osteoid peaks at 4 days. The osteoclast response is delayed.

Global impacts of energy demand on the freshwater resources of nations.

The growing geographic disconnect between consumption of goods, the extraction and processing of resources, and the environmental impacts associated with production activities makes it crucial to factor global trade into sustainability assessments. Using an empirically validated environmentally extended global trade model, we examine the relationship between two key resources underpinning economies and human well--being-energy and freshwater. A comparison of three energy sectors (petroleum, gas, and electricity) reveals that freshwater consumption associated with gas and electricity production is largely confined within the territorial boundaries where demand originates. This finding contrasts with petroleum, which exhibits a varying ratio of territorial to international freshwater consumption, depending on the origin of demand. For example, although the United States and China have similar demand associated with the petroleum sector, international freshwater consumption is three times higher for the former than the latter. Based on mapping patterns of freshwater consumption associated with energy sectors at subnational scales, our analysis also reveals concordance between pressure on freshwater resources associated with energy production and freshwater scarcity in a number of river basins globally. These energy-driven pressures on freshwater resources in areas distant from the origin of energy demand complicate the design of policy to ensure security of fresh water and energy supply. Although much of the debate around energy is focused on greenhouse gas emissions, our findings highlight the need to consider the full range of consequences of energy production when designing policy.

Global evidence of positive impacts of freshwater biodiversity on fishery yields.

AIM: An often-invoked benefit of high biodiversity is the provision of ecosystem services. However, evidence for this is largely based on data from small-scale experimental studies of relationships between biodiversity and ecosystem function that may have little relevance to real-world systems. Here, large-scale biodiversity datasets are used to test the relationship between the yield of inland capture fisheries and species richness from 100 countries. LOCATION: Inland waters of Africa, Europe and parts of Asia. METHODS: A multimodel inference approach was used to assess inland fishery yields at the country level against species richness, waterside human population, area, elevation and various climatic variables, to determine the relative importance of species richness to fisheries yields compared with other major large-scale drivers. Secondly, the mean decadal variation in fishery yields at the country level for 1981-2010 was regressed against species richness to assess if greater diversity reduces the variability in yields over time. RESULTS: Despite a widespread reliance on targeting just a few species of fish, freshwater fish species richness is highly correlated with yield (R2 = 0.55) and remains an important and statistically significant predictor of yield once other macroecological drivers are controlled for. Freshwater richness also has a significant negative relationship with variability of yield over time in Africa (R2 = 0.16) but no effect in Europe. MAIN CONCLUSIONS: The management of inland waters should incorporate the protection of freshwater biodiversity, particularly in countries with the highest-yielding inland fisheries as these also tend to have high freshwater biodiversity. As these results suggest a link between biodiversity and stable, high-yielding fisheries, an important win-win outcome may be possible for food security and conservation of freshwater ecosystems. However, findings also highlight the urgent need for more data to fully understand and monitor the contribution of biodiversity to inland fisheries globally.

Impact of alternative metrics on estimates of extent of occurrence for extinction risk assessment.

In International Union for Conservation of Nature (IUCN) Red List assessments, extent of occurrence (EOO) is a key measure of extinction risk. However, the way assessors estimate EOO from maps of species' distributions is inconsistent among assessments of different species and among major taxonomic groups. Assessors often estimate EOO from the area of mapped distribution, but these maps often exclude areas that are not habitat in idiosyncratic ways and are not created at the same spatial resolutions. We assessed the impact on extinction risk categories of applying different methods (minimum convex polygon, alpha hull) for estimating EOO for 21,763 species of mammals, birds, and amphibians. Overall, the percentage of threatened species requiring down listing to a lower category of threat (taking into account other Red List criteria under which they qualified) spanned 11-13% for all species combined (14-15% for mammals, 7-8% for birds, and 12-15% for amphibians). These down listings resulted from larger estimates of EOO and depended on the EOO calculation method. Using birds as an example, we found that 14% of threatened and near threatened species could require down listing based on the minimum convex polygon (MCP) approach, an approach that is now recommended by IUCN. Other metrics (such as alpha hull) had marginally smaller impacts. Our results suggest that uniformly applying the MCP approach may lead to a one-time down listing of hundreds of species but ultimately ensure consistency across assessments and realign the calculation of EOO with the theoretical basis on which the metric was founded.

Global diversity patterns and cross-taxa convergence in freshwater systems.

Whereas global patterns and predictors of species diversity are well known for numerous terrestrial taxa, our understanding of freshwater diversity patterns and their predictors is much more limited. Here, we examine spatial concordance in global diversity patterns for five freshwater taxa (i.e. aquatic mammals, aquatic birds, fishes, crayfish and aquatic amphibians) and investigate the environmental factors driving these patterns at the river drainage basin grain. We find that species richness and endemism patterns are significantly correlated among taxa. We also show that cross-taxon congruence patterns are often induced by common responses of taxa to their contemporary and historical environments (i.e. convergent patterns). Apart from some taxa distinctiveness (i.e. fishes), the 'climate/productivity' hypothesis is found to explain the greatest variance in species richness and endemism patterns, followed by factors related to the 'history/dispersion' and 'area/environmental heterogeneity' hypotheses. As aquatic amphibians display the highest levels of congruency with other taxa, this taxon appears to be a good 'surrogate' candidate for developing global freshwater conservation planning at the river drainage basin grain.

A Sequence- and Ligation-Independent Cloning (SLIC) Procedure for the Insertion of Genes into a Plasmid Vector.

Molecular cloning is a routine technique for many laboratories with applications from genetic engineering to recombinant protein expression. While restriction-ligation cloning can be slow and inefficient, ligation-independent cloning uses long single-stranded overhangs generated by T4 DNA polymerase's 3' exonuclease activity to anneal the insert and plasmid vector prior to transformation. This chapter describes a fast, high-efficiency protocol for inserting one or more genes into a vector using sequence- and ligation-independent cloning (SLIC).

Using a Consensus-Driven Approach to Incorporate Holistic Review Into an Internal Medicine Residency Program.

Background: Despite growing interest in incorporating holistic review within residency admissions, implementation by residency programs remains challenging. Objective: To incorporate holistic review into the internal medicine residency program at the University of Wisconsin and to report initial feasibility and acceptability data. Methods: During the 2020-2021 application cycle, residency stakeholders performed a consensus-driven process to identify highly valued applicant attributes. We used a holistic review process to identify the presence of these attributes among applicants and updated our rank list algorithm to incorporate these attributes. We modified our interview screening criteria and rank list algorithm to de-emphasize other metrics. We surveyed stakeholders to assess time required for this process and compared our final rank list to what it would have been using our prior system. Results: The final list of 10 prioritized applicant attributes included extraordinary leadership, community service, and grit, among others. Among 25 matched residents, 8 (32%) were recognized to have exceptional achievement within one of these 10 attributes. Four members of the incoming intern class (16%) would have been in a rank position lower than our historical matched resident cutoff had they not received additional points for these attributes. Faculty reported that holistic review of applications took an additional 3.8 minutes on average. It was felt that current application materials limit the ability to implement a fully holistic review. Conclusions: The addition of holistic review to our residency admissions process was achieved using a consensus-driven approach and showed favorable feasibility and acceptability data.

Randomized, double-blind, placebo-controlled trial of ISC 17536, an oral inhibitor of transient receptor potential ankyrin 1, in patients with painful diabetic peripheral neuropathy: impact of preserved small nerve fiber function.

ABSTRACT: Patients with chronic pain syndromes, such as those with painful peripheral neuropathy due to diabetes mellitus, have limited treatment options and suffer ongoing attrition of their quality of life. Safer and more effective treatment options are needed. One therapeutic approach encompasses phenotypic characterization of the neuropathic pain subtype, combined with the selection of agents that act on relevant mechanisms. ISC 17536 is a novel, orally available inhibitor of the widely expressed pain receptor, transient receptor potential ankyrin 1, which mediates nociceptive signaling in peripheral small nerve fibers. In this randomized, placebo-controlled, proof-of-concept trial, we assessed the safety and efficacy of 28-day administration of ISC 17536 in 138 patients with chronic, painful diabetic peripheral neuropathy and used quantitative sensory testing to characterize the baseline phenotype of patients. The primary end point was the change from baseline to end of treatment in the mean 24-hour average pain intensity score based on an 11-point pain intensity numeric rating scale. The study did not meet the primary end point in the overall patient population. However, statistically significant and clinically meaningful improvement in pain were seen with ISC 17536 in an exploratory hypothesis-generating subpopulation of patients with preserved small nerve fiber function defined by quantitative sensory testing. These results may provide a mechanistic basis for targeted therapy in specific pain phenotypes in line with current approaches of "precision medicine" or personalized pain therapeutics. The hypothesis is planned to be tested in a larger phase 2 study.

Spatial covariation between freshwater and terrestrial ecosystem services.

To inform the design and implementation of land-use policies that consider the variety of goods and services people derive from ecosystems, it is essential to understand spatial patterns of individual services, how multiple services relate to each other, and how these relationships vary across spatial scales and localities. Despite the importance of freshwater as a determinant of regional economic and human demographic patterns, there are surprisingly few studies that map the provision of a range of services associated with the quality of the aquatic environment. Here we examine relationships between indicators of riverine water and associated habitat quality, freshwater biodiversity, three terrestrial ecosystem services, and terrestrial biodiversity across England and Wales. The results indicate strong associations between our indicators of freshwater services. However, a comparison of these indicators of freshwater services with other ecosystem services (carbon storage, agricultural production, recreation) and biodiversity of species of conservation concern in the surrounding terrestrial landscape shows no clear relationships. While there are potential policy "win-wins" for the protection of multiple services shown by associations between indicators of freshwater services and carbon storage in upland areas of Britain, the other ecosystem services showed either negative or no relationships with the indicators of freshwater services. We also consider the influence that spatial scale has on these relationships using River Basin Districts. Our results indicate that relationships between indicators of services can change dramatically depending on the societal pressures and other regional conditions. Thus, the delivery of multiple ecosystem services requires the development of regional strategies, or of national strategies that take account of regional variation.

Republished original article: Resident-initiated interventions to improve inpatient heart-failure management.

BACKGROUND: Third-year internal medicine residents participating in a quality improvement rotation identified gaps between the Joint Commission's ORYX quality guidelines and clinical practices for the inpatient management of heart failure (HF) at the William S. Middleton Memorial Veterans Hospital. Residents focused on the performance metrics associated with tobacco-cessation counselling documentation, ejection fraction assessment and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescriptions. METHODS: After analysing data collected by the External Peer Review Program, residents reviewed the institution's admissions and discharge processes with the aim of improving quality and compliance. In redesigning these processes, residents created an admissions template and a discharge face sheet, and compared specific ORYX measure compliance rates before and after institution-wide implementation. RESULTS: Following implementation of the tobacco-cessation admissions template, 100% of HF patients who used tobacco received documented cessation counselling, compared with 59% prior to intervention (p<0.01, n=32). Following implementation of the mandatory discharge face sheet, 97% of HF patients (compared with 92% preintervention, p>0.05) received comprehensive discharge instruction; LV function assessment went from 98% to 100% (p>0.05); and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription for left ventricular systolic dysfunction at discharge (or documentation of a contra-indication) went from 82% to 100% (p<0.01, n=48). DISCUSSION: By implementing a standardised admissions template and a mandatory discharge face sheet, the hospital improved its processes of documentation and increased adherence to quality-performance measures. By strengthening residents' learning and commitment to quality improvement, the hospital created a foundation for future changes in the systems that affect patient care.

The Effect of Overexpression of Lrp5 on the Temporomandibular Joint.

OBJECTIVE: The temporomandibular joint (TMJ) is a unique fibrocartilaginous joint that adapts to mechanical loading through cell signaling pathways such as the Wnt pathway. Increased expression of low-density lipoprotein receptor-related protein 5 (Lrp5), a co-receptor of the Wnt pathway, is associated with a high bone mass (HBM) phenotype. The objective of this study was to analyze the effect of overexpression of Lrp5 on the subchondral bone and cartilage of the TMJ in mice exhibiting the HBM phenotype. DESIGN: Sixteen-week-old Lrp5 knock-in transgenic mice carrying either the A214V (EXP-A) or G171V (EXP-G) missense mutations, and wildtype controls (CTRL) were included in this study. Fluorescent bone labels, calcein, alizarin complexone, and demeclocycline were injected at 3.5, 7.5, and 11.5 weeks of age, respectively. The left mandibular condyle was used to compare the subchondral bone micro-computed tomography parameters and the right TMJ was used for histological analyses. Cartilage thickness, matrix proteoglycan accumulation, and immunohistochemical localization of Lrp5 and sclerostin were compared between the groups. RESULTS: Subchondral bone volume (BV) and percent bone volume (BV/TV) were significantly increased in both EXP-A and EXP-G compared with CTRL (P < 0.05) whereas trabecular spacing (Tb.Sp) was decreased. Cartilage thickness, extracellular matrix production, and expression of Lrp5 and Sost were all increased in the experimental groups. The separation between the fluorescent bone labels indicated increased endochondral maturation between 3.5 and 7.5 weeks. CONCLUSIONS: These data demonstrate that Lrp5 overexpression leads to adaptation changes in the mandibular condylar cartilage of the TMJ to prevent cartilage degradation.

Impacts of rising temperatures and farm management practices on global yields of 18 crops.

Understanding the impact of changes in temperature and precipitation on crop yields is a vital step in developing policy and management options to feed the world. As most existing studies are limited to a few staple crops, we implemented global statistical models to examine the influence of weather and management practices on the yields of 18 crops, accounting for 70% of crop production by area and 65% by calorific intake. Focusing on the impact of temperature, we found considerable heterogeneity in the responses of yields across crops and countries. Irrigation was found to alleviate negative implications from temperature increases. Countries where increasing temperature causes the most negative impacts are typically the most food insecure, with the lowest calorific food supply and average crop yield. International action must be coordinated to raise yields in these countries through improvement and modernization of agricultural practices to counteract future adverse impacts of climate change.