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To best prepare students for the real-world research environment, key skills, including experimental design, data analysis, communication of results, and critical thinking, should be key components of undergraduate science courses. Furthermore, the impact of the COVID-19 pandemic on in-person teaching has resulted in a need to develop courses that enable flexible learning. This paper details the laboratory component of a senior-level toxicology class that was developed to emphasize all these skills and allow for flexible learning. The aim of the laboratory class was for students to determine how curcumin protected against acetaminophen-induced hepatoxicity. To stimulate critical thinking, students were required to choose a maximum of four experiments from the six on offer. Before conducting an experiment, students stated a hypothesis and selected the appropriate treatment groups. Once an experiment was completed, students were given access to a complete dataset, on which they performed statistical analysis and drew conclusions. Students who were unable to attend the laboratory session in person were able to complete the required pre-lab work and access the dataset. Following each experiment, students could write a lab summary, and receive thorough feedback. The final assessment was a written manuscript of their findings as well as a chance to respond to reviewer comments. This teaching approach prioritized the critical thinking, analysis, and experimental design aspects of scientific research. Overall, this structure was well received by students and it could easily be adapted for use on other life science courses.

Question-asking is a crucial tool for acquiring information about unseen entities, such as viruses; thus, examining children’s questions within the context of COVID-19 is particularly important for understanding children’s learning about the coronavirus. The study examined 3-12-year-old children’s questions and teachers’ responses about the COVID-19 pandemic in Türkiye, a non-Western developing context, and the United States, a Western cultural context. A total of 119 teachers from Türkiye and 95 teachers from the US participated in the study. Teachers completed an online survey consisting of a demographic form and a questionnaire asking them to report three questions about COVID-19 asked by children in their classrooms and their responses to these questions. We analyzed children’s questions and teachers’ responses for their type and content and examined demographic factors associated with children’s questions and teachers’ responses. Consistent with the literature, children from Türkiye asked fewer explanation-seeking (i.e., why/how) questions than children from the United States. Children asked questions about viruses and precautions. Teachers responded to children’s questions realistically in both countries. The findings have important implications for how children gain knowledge from teachers when discussing health, disease, and virus topics in two countries.

BackgroundLow grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.AimWe examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.MethodsParticipants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index).ResultsMean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed.ConclusionsGrip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer's disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.

Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

Do children think of genetic inheritance as deterministic or probabilistic? In two novel tasks, children viewed the eye colors of animal parents and judged and selected possible phenotypes of offspring. Across three studies (N = 353, 162 girls, 172 boys, 2 non-binary; 17 did not report gender) with predominantly White U.S. participants collected in 2019-2021, 4- to 12-year-old children showed a probabilistic understanding of genetic inheritance, and they accepted and expected variability in the genetic inheritance of eye color. Children did not show a mother bias but they did show two novel biases: perceptual similarity and sex-matching. These results held for unfamiliar animals and several physical traits (e.g., eye color, ear size, and fin type), and persisted after a lesson.

Prior work has shown that many undergraduate students have misconceptions about genetic inheritance, even after they take genetics courses. Visual representations, such as pedigree diagrams, are commonly used in genetics instruction, and they help students quickly visualize the phenotypes of multiple generations. In Study 1, we examined whether presenting a pedigree diagram of a wolf’s eye color in a rich and realistic manner (i.e., with rich perceptual images that resemble real animals) or in an abstract manner (i.e., with circles and squares representing animals) would help undergraduates learn from a brief, online lesson on inheritance of the wolf’s eye color, and whether they would transfer what they learned when reasoning about eye color in other species (near transfer) and other traits in other species (mid- and far transfer). Counter to our hypothesis, students transferred more with the rich diagram. In Study 2, we compared the rich diagram from Study 1 to a perceptually bland diagram (i.e., with color and textural features removed). There were no differences in students’ learning or transfer between the diagrams. These results suggest that realistic elements that are attention grabbing and easily interpretable by students can be beneficial for transfer in online lessons.

People often display essentialist biases, which can lead them to underestimate within-species variability. This bias is especially pronounced when traits are described as advantageous for survival. However, it is unclear whether this bias is limitedto the specified trait or encompasses complex trait interactions. We used Markov Chain Monte Carlo with People (MCMCp) to analyze people's representations of biological variability, using ladybeetles as a model species. Participants either received contextual information about the benefits of ladybeetle color for survival, or survival-irrelevant information. Overall, participants held consistent beliefs about ladybeetle features,but those with survival-relevant context produced lighter and larger ladybeetles; this difference was consistent with survey responses. However, we found no significant interaction between MCMCp variability and essentialism scores, given our context manipulation. We discuss potential explanations for these results and highlight advantages of MCMCp for assessing biological variability, particularly when studying the development of essentialist biases.

Recent work using neural networks and crowd-sourced perceptual judgements has shown that human figure drawings contain latent structure that can predict many characteristics of the artist including parent-reported motor function and perceived gender. We extend these approaches to two-dimensional renderings of three-dimensional cubes, assessing whether latent structure in these cube drawings likewise predicts demographic characteristics and motor function measured via a paper-folding task. Drawings produced with marker and paper showed a large predictive relationship with paper-folding (accounting for 59% of the offset variance, 62% of the angle variance, ps < .01). We also observed a complex interaction with gender: better cube-drawings predicted better paper-folding for male-identifying participants, but this relationship was reversed for female-identifying participants, who demonstrated better paper folding abilities overall. The results suggest that cube drawings contain richer structure than previously recognized and can provide a useful nonverbal metric for characterizing aspects of cognitive and motor abilities.

Do children think of genetic inheritance as deterministic or probabilistic? In two novel tasks, children viewed the eye colors of animal parents and judged and selected possible phenotypes of offspring. Across three studies (N = 353, 162 girls, 172 boys, 2 non-binary; 17 did not report gender) with predominantly White U.S. participants collected in 2019-2021, 4- to 12-year-old children showed a probabilistic understanding of genetic inheritance, and they accepted and expected variability in the genetic inheritance of eye color. Children did not show a mother bias but they did show two novel biases: perceptual similarity and sex-matching. These results held for unfamiliar animals and several physical traits (e.g., eye color, ear size, and fin type), and persisted after a lesson.

Background and Purpose Cold beverage intake (carbonated drinks, fruit juice/drinks, and water) may be important population-level exposures relevant to stroke risk and prevention. We sought to explore the association between intake of these beverages and stroke. Methods INTERSTROKE is an international matched case-control study of first stroke. Participants reported beverage intake using food frequency questionnaires or were asked “How many cups do you drink each day of water?” Multivariable conditional logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations with stroke. Results We include 13,462 cases and 13,488 controls; mean age was 61.7±13.4 years and 59.6% (n=16,010) were male. After multivariable adjustment, carbonated beverages were linearly associated with ischemic stroke (OR 2.39 [95% CI 1.64–3.49]); only consumption once/day was associated with intracerebral hemorrhage (ICH) (OR 1.58 [95% CI 1.23–2.03]). There was no association between fruit juice/drinks and ischemic stroke, but increased odds of ICH for once/day (OR 1.37 [95% CI 1.08–1.75)] or twice/day (OR 3.18 [95% CI 1.69–5.97]). High water intake (>7 cups/day) was associated ischemic stroke (OR 0.82 [95% CI 0.68–0.99]) but not ICH. Associations differed by Eugeographical region—increased odds for carbonated beverages in some regions only; opposing directions of association of fruit juices/drinks with stroke in selected regions. Conclusion Carbonated beverages were associated with increased odds of ischemic stroke and ICH, fruit juice/drinks were associated with increased odds of ICH, and high water consumption was associated with reduced odds of ischemic stroke, with important regional differences. Our findings suggest optimizing water intake, minimizing fruit juice/drinks, and avoiding carbonated beverages.

According to Finnish national housing policy, social rental housing (ARA) plays a key role in providing affordable housing and combating segregation in growing urban regions, in particular in Finland’s three largest urban regions (Helsinki, Tampere and Turku), which are the focus of our study. However, the proportion of social housing in Finland has declined, with an internal structural shift towards housing for special groups. Moreover, in the large cities, the ARA housing stock has not been completed to the extent called for in the housing programmes. Our paper addresses these contradictions. We examine the views of key actors responsible for housing policy and social housing implementation with data from three separate research projects between 2017 and 2022. We ask: What reasons do key actors see as to why the supply of social housing has stagnated and declined? Furthermore, we identify the possible barriers to promoting social rental housing in current policies and practices. Our analysis reveals several market-, policy- and practice-based constraints to the promotion of social rental housing. Above all, Finnish housing policy has always been secondary to other policy objectives, which makes it unpredictable. Therefore, the guiding regulations at the national level and the implementation of housing programmes at the local level seem to be out of step with each other. However, local governments are politically more stable and have attempted to promote social housing objectives, but there are clear and path-dependent differences between the cities in our study in this respect. Despite this, the representatives of social housing companies did not see the need for a broader housing policy reform in Finland. Instead, they asked for long-term commitment and predictability.

This article analyses municipal tenants’ neighbourhood satisfaction (NS) in the Helsinki metropolitan area. If social mixing has managed to equalise differences related to the residential environment across different social groups, perceived neighbourhood conditions among tenure groups should be similar. We know, however, that even in a Nordic capital with a conscious and long-term effort at small-scale mixing, social housing is not geographically spread out evenly and that clustering of social tenants occurs. We also know that objective resources among social tenants are lower than in other tenures, contributing to subjective wellbeing, of which NS is a component. We examine the Helsinki metropolitan area’s objective and subjective neighbourhood conditions using a large residential survey and national register data. Our results show that neighbourhood amenities and locational characteristics do not differ across tenure groups in the Helsinki metropolitan area – however, tenants in municipal social housing report lower NS than other tenure groups. Social mixing appears to promote spatial justice at the neighbourhood level better than it has managed to equalise differences in subjective experiences across tenure groups. This study contributes to understanding NS as a component of subjective wellbeing. It also highlights the unequal distribution of social housing in the Helsinki metropolitan area, which we see as a risk for accelerating segregation across tenure groups. Differences in perceived satisfaction with neighbourhood across tenure groups may reflect differences in micro-scale environments, suggesting a need for policies improving spatial justice at a sub-neighbourhood or residential level.

Synthetic cannabinoids are a rapidly evolving, diverse class of new psychoactive substances. Synthetic cannabinoid use results in a higher likelihood of adverse events and hospitalization when compared to cannabis use. The mechanisms behind synthetic cannabinoid toxicity remain elusive. Furthermore, poly-substance use may be a significant contributing factor in many cases. This scoping review aimed to identify the key characteristics of synthetic cannabinoid co-exposure cases and discuss the potential implications of poly-substance use in humans. There were 278 human cases involving 64 different synthetic cannabinoids extracted from the databases. Cases involved a total of 840 individual co-exposures, with an average of four substances involved in each case. The most common co-exposures were alcohol (11.4%), opioids (11.2%), and cannabis (11.1%). When analyzed by case outcome, co-exposure to either antipsychotics/antidepressants, alcohol, or tobacco were significantly associated with mortality as an outcome (p < 0.05). Drug-use history (63.4%), mental illness (23.7%), and hypertensive and atherosclerotic cardiovascular disease (20.1%) were prevalent patient histories in the case cohort. There are several potential pharmacodynamic and pharmacokinetic interactions between co-exposure drugs and synthetic cannabinoids that could worsen clinical presentation and toxicity in synthetic cannabinoid users. Individuals with substance-use disorders or psychiatric illness would be especially vulnerable to these multi-drug interactions. Further research into these complex exposures is needed for the successful prevention and treatment of synthetic cannabinoid-related harms.

Depression is a common psychiatric disorder and a leading cause of disability worldwide. Here we conducted a genome-wide association study meta-analysis of six datasets, including >1.3 million individuals (371,184 with depression) and identified 243 risk loci. Overall, 64 loci were new, including genes encoding glutamate and GABA receptors, which are targets for antidepressant drugs. Intersection with functional genomics data prioritized likely causal genes and revealed new enrichment of prenatal GABAergic neurons, astrocytes and oligodendrocyte lineages. We found depression to be highly polygenic, with ~11,700 variants explaining 90% of the single-nucleotide polymorphism heritability, estimating that >95% of risk variants for other psychiatric disorders (anxiety, schizophrenia, bipolar disorder and attention deficit hyperactivity disorder) were influencing depression risk when both concordant and discordant variants were considered, and nearly all depression risk variants influenced educational attainment. Additionally, depression genetic risk was associated with impaired complex cognition domains. We dissected the genetic and clinical heterogeneity, revealing distinct polygenic architectures across subgroups of depression and demonstrating significantly increased absolute risks for recurrence and psychiatric comorbidity among cases of depression with the highest polygenic burden, with considerable sex differences. The risks were up to 5- and 32-fold higher than cases with the lowest polygenic burden and the background population, respectively. These results deepen the understanding of the biology underlying depression, its disease progression and inform precision medicine approaches to treatment.

Regional land use, housing, and transport (MAL) agreements between the Finnish state and municipalities in growth regions guide urban policy in the Helsinki metropolitan area towards regional cooperation and densification. Alongside economic growth and connectivity goals, segregation prevention is a visible but ill-defined social sustainability goal in these agreements, and anti-segregation measures lean heavily on providing new social housing in accessible locations. This tool, in turn, leans on a combination of social mixing, a traditional preventive tool in fighting segregation, and a new tool, maximising spatial justice through transit-oriented development. We argue that there is a discrepancy between these goals: while on an individual level, public transport accessibility is meant to reduce transport poverty and provide equal opportunities for employment and services, accessible areas fare lower than others in socioeconomic status. Therefore, increasing social rental housing in areas with lower socioeconomic status may unintentionally amplify segregation. This article asks how actors of different governance levels view concentrating social housing in accessible locations as a risk to segregation. Interviews show a concern of social challenges not being sufficiently addressed.

Summary: Background: Transportation noise has been linked with cardiometabolic outcomes, yet whether it is a risk factor for atrial fibrillation (AF) remains inconclusive. We aimed to assess whether transportation noise was associated with AF in a large, pooled Nordic cohort. Methods: We pooled data from 11 Nordic cohorts, totaling 161,115 participants. Based on address history from five years before baseline until end of follow-up, road, railway, and aircraft noise was estimated at a residential level. Incident AF was ascertained via linkage to nationwide patient registries. Cox proportional hazards models were utilized to estimate associations between running 5-year time-weighted mean transportation noise (Lden) and AF after adjusting for sociodemographics, lifestyle, and air pollution. Findings: We identified 18,939 incident AF cases over a median follow-up of 19.6 years. Road traffic noise was associated with AF, with a hazard ratio (HR) and 95% confidence interval (CI) of 1.02 (1.00–1.04) per 10-dB of 5-year mean time-weighted exposure, which changed to 1.03 (1.01–1.06) when implementing a 53-dB cut-off. In effect modification analyses, the association for road traffic noise and AF appeared strongest in women and overweight and obese participants. Compared to exposures ≤40 dB, aircraft noise of 40.1–50 and > 50 dB were associated with HRs of 1.04 (0.93–1.16) and 1.12 (0.98–1.27), respectively. Railway noise was not associated with AF. We found a HR of 1.19 (1.02–1.40) among people exposed to noise from road (≥45 dB), railway (>40 dB), and aircraft (>40 dB) combined. Interpretation: Road traffic noise, and possibly aircraft noise, may be associated with elevated risk of AF. Funding: NordForsk.

Background Overweight and obesity are increasing globally with aging, as are life expectancy and aging‐associated disorders, including calcific aortic stenosis (AS). Studies investigating the correlation between high body mass index (BMI) and AS are contradictory and inconclusive. This study examines a potential association between BMI and AS in women. Methods and Results By linking the Swedish Medical Birth Register and the Swedish National Patient Register, we included women aged 18 to 55 years with a first childbirth from 1981 to 2020. Diagnosis of AS and comorbidities were defined according to the International Classification of Diseases (ICD) codes. The women were divided into groups on the basis of BMI. Cox proportional hazards regression models were used to investigate the difference in the risk of being diagnosed with AS, with reference BMI 20 to

Abstract Background Most studies infer increasing incidence of proximal humeral fractures (PHF) from the 1950´s until the 1990´s. Recent time trends are less clear. Objectives Our primary objective was to identify time trends in the age- and sex-adjusted adult incidence of PHF in Malmö, Sweden, from year 1944 until 2020. Our secondary objectives were to describe the variation in incidence according to age, the monthly distribution, and to compare data from the two most recent decades with earlier. Study design and methods Malmö has one emergency hospital where acute fractures are treated. We identified PHF in adult patients (≥ 18 years) by reviewing relevant radiology examinations during 17 sample years from year 1944 to 2020. We used jointpoint analyses to estimate time trends. Results We identified 3 031 PHF during the study period (3 231 161 person years), 73% were sustained by women with mean age of 69 years (mean age in men 59). Joinpoint analyses indicated an increase in the age- and sex-adjusted incidence of PHF from year 1944 (52 per 100 000 person years) until 1977 (120 per 100 000) and thereafter a decrease until 2020 (85 per 100 000). A seasonal variation with more fractures during winter months, was apparent in earlier but not recent decades. Conclusions The age- and sex-adjusted incidence of PHF increased in Malmö, Sweden, from the 1940´s until year 1977 and thereafter decreased until 2020. More fractures were seen during winter months in earlier but not recent decades.

Abstract Background Video consultations between hospital-based neurologists and Emergency Medical Services (EMS) have potential to increase precision of decisions regarding stroke patient assessment, management and transport. In this study we explored the use of real-time video streaming for neurologist–EMS consultation from the ambulance, using highly realistic full-scale prehospital simulations including role-play between on-scene EMS teams, simulated patients (actors), and neurologists specialized in stroke and reperfusion located at the remote regional stroke center. Methods Video streams from three angles were used for collaborative assessment of stroke using the National Institutes of Health Stroke Scale (NIHSS) to assess symptoms affecting patient’s legs, arms, language, and facial expressions. The aim of the assessment was to determine appropriate management and transport destination based on the combination of geographical location and severity of stroke symptoms. Two realistic patient scenarios were created, with severe and moderate stroke symptoms, respectively. Each scenario was simulated using a neurologist acting as stroke patient and an ambulance team performing patient assessment. Four ambulance teams with two nurses each all performed both scenarios, for a total of eight cases. All scenarios were video recorded using handheld and fixed cameras. The audio from the video consultations was transcribed. Each team participated in a semi-structured interview, and neurologists and actors were also interviewed. Interviews were audio recorded and transcribed. Results Analysis of video-recordings and post-interviews (n = 7) show a more thorough prehospital patient assessment, but longer total on-scene time, compared to a baseline scenario not using video consultation. Both ambulance nurses and neurologists deem that video consultation has potential to provide improved precision of assessment of stroke patients. Interviews verify the system design effectiveness and suggest minor modifications. Conclusions The results indicate potential patient benefit based on a more effective assessment of the patient’s condition, which could lead to increased precision in decisions and more patients receiving optimal care. The findings outline requirements for pilot implementation and future clinical tests.

Abstract Natriuretic peptides (NPs) are cardio-derived hormones that have a crucial role in maintaining cardiovascular homeostasis. Physiological effects of NPs are mediated by binding to natriuretic peptide receptors 1 and 2 (NPR1/2), whereas natriuretic peptide receptor 3 (NPR3) acts as a clearance receptor that removes NPs from the circulation. Mouse studies have shown that local NP-signaling in the kidney glomerulus is important for the maintenance of renal homeostasis. In this study we examined the expression of NPR3 in kidney tissue and explored its involvement in renal physiology and disease by generating podocyte-specific knockout mice (NPR3 podKO ) as well as by using an NPR3 inhibitor (NPR3i) in rodent models of kidney disease. NPR3 was highly expressed by podocytes. NPR3 podKO animals showed no renal abnormalities under healthy conditions and responded similarly to nephrotoxic serum (NTS) induced glomerular injury. However, NPR3i showed reno-protective effects in the NTS-induced model evidenced by decreased glomerulosclerosis and reduced podocyte loss. In a ZSF1 rat model of diabetic kidney injury, therapy alone with NPR3i did not have beneficial effects on renal function/histology, but when combined with losartan (angiotensin receptor blocker), NPR3i potentiated its ameliorative effects on albuminuria. In conclusion, these results suggest that NPR3 may contribute to kidney disease progression.