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Interstitial macrophages (IMs) reside in the lung tissue surrounding key structures including airways, vessels, and alveoli. Recent work has described IM heterogeneity during homeostasis, however, there are limited data on IMs during inflammation. We sought to characterize IM origin, subsets, and transcriptomic profiles during homeostasis and lipopolysaccharide (LPS) induced acute lung inflammation. During homeostasis, we used three complementary methods, spectral flow cytometry, single-cell RNA-sequencing, and gene regulatory network enrichment, to demonstrate that IMs can be divided into two core subsets distinguished by surface and transcriptional expression of folate receptor β ( Folr2/FRβ). These subsets inhabited distinct niches within the lung interstitium. Within FRβ+ IMs we identified a subpopulation marked by coexpression of LYVE1. During acute LPS-induced inflammation, lung IM numbers expand. Lineage tracing revealed IM expansion was due to recruitment of monocyte-derived IMs. At the peak of inflammation, recruited IMs were comprised two unique subsets defined by expression of genes associated with interferon signaling and glycolytic pathways. As recruited IMs matured, they adopted the overall transcriptional state of FRβ− resident IMs but retained expression in several origin-specific genes, such as IL-1β. FRβ+ IMs were of near-pure resident origin. Taken together our data show that during LPS-induced inflammation, there are distinct populations of IMs that likely have unique functions. FRΒ+ IMs comprise a stable, resident population, whereas FRβ− ΙΜs represent a mixed population of resident and recruited IMs.

Specificity of ARV7 and ARv567es antibodies.

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that treatment with a small-molecule Sigma1 inhibitor prevented 5α- dihydrotestosterone-mediated nuclear translocation of AR and induced proteasomal degradation of AR and ARV, suppressing the transcriptional activity and protein levels of both full-length and splice-variant AR. Consistent with these data, RNAi knockdown of Sigma1 resulted in decreased AR levels and transcriptional activity. Furthermore, Sigma1 physically associated with ARV7 and ARv567es as well as full-length AR. Treatment of mice xenografted with ARV-driven CRPC tumors with a drug-like small-molecule Sigma1 inhibitor significantly inhibited tumor growth associated with elimination of AR and ARV7 in responsive tumors. Together, our data show that Sigma1 modulators can be used to suppress AR/ARV–driven prostate cancer cells via regulation of pharmacologically responsive Sigma1-AR/ARV interactions, both in vitro and in vivo. Cancer Res; 77(9); 2439–52. ©2017 AACR.

Nuclear hormone receptors that are not eliminated by small molecule Sigma1 inhibitor (IPAG).

RNAi mediated knockdown of ATG5 does not prevent IPAG induced decrease in AR levels.

CT-189 Chemical, ADME, and Pharmacokinetics Properties.

Quantification of immunoblot band densities in Figure 3B.

The acute respiratory distress syndrome (ARDS) is a major healthcare problem, accounting for significant mortality and long-term disability. Approximately 25% of patients with ARDS will develop an overexuberant fibrotic response, termed fibroproliferative ARDS (FP-ARDS) that portends a poor prognosis and increased mortality. The cellular pathological processes that drive FP-ARDS remain incompletely understood. We have previously shown that the transmembrane receptor-type tyrosine phosphatase protein tyrosine phosphatase-α (PTPα) promotes pulmonary fibrosis in preclinical murine models through regulation of transforming growth factor-β (TGF-β) signaling. In this study, we examine the role of PTPα in the pathogenesis of FP-ARDS in a preclinical murine model of acid (HCl)-induced acute lung injury. We demonstrate that although mice genetically deficient in PTPα ( Ptpra−/−) are susceptible to early HCl-induced lung injury, they exhibit markedly attenuated fibroproliferative responses. In addition, early profibrotic gene expression is reduced in lung tissue after acute lung injury in Ptpra−/− mice, and stimulation of naïve lung fibroblasts with the BAL fluid from these mice results in attenuated fibrotic outcomes compared with wild-type littermate controls. Transcriptomic analyses demonstrate reduced extracellular matrix (ECM) deposition and remodeling in mice genetically deficient in PTPα. Importantly, human lung fibroblasts modified with a CRISPR-targeted deletion of PTPRA exhibit reduced expression of profibrotic genes in response to TGF-β stimulation, demonstrating the importance of PTPα in human lung fibroblasts. Together, these findings demonstrate that PTPα is a key regulator of fibroproliferative processes following acute lung injury and could serve as a therapeutic target for patients at risk for poor long-term outcomes in ARDS.

Objective To estimate the association between subchorionic hematoma (SCH) on ultrasound and pregnancy outcomes in in vitro fertilization (IVF) pregnancies. Design Institutional Review Board–approved, retrospective cohort study. Setting Tertiary care university-based facility. Patient(s) In this study, 1,004 patients who underwent IVF with a viable singleton pregnancy from January 1, 2009 through December 31, 2017. Intervention(s) Subchorionic hematoma versus no hematoma diagnosed on first-trimester ultrasound. Main Outcome Measure(s) Live birth, preterm birth, and spontaneous abortion. Result(s) We found that 1,004 women met the criteria and 187 (18.6%) had an SCH. In bivariate and multivariate regression models, there were no associations between SCH and the outcomes of live birth, preterm birth, or birth weight. Conclusion(s) Subchorionic hematoma detected on first-trimester ultrasound after IVF is not associated with probability of live birth, probability of preterm birth, or infant birth weight in this patient population.

Objective: MicroRNA-126-3p (miR-126) is required for angiogenesis during organismal development or the repair of injured arterial vasculature. The role of miR-126 in lung microvascular endothelial cells, which are essential for gas exchange and for lung injury repair and regeneration, remains poorly understood. Considering the significant heterogeneity of endothelial cells from different vascular beds, we aimed to determine the role of miR-126 in regulating lung microvascular endothelial cell function and to elucidate its downstream signaling pathways. Approach and Results: Overexpression and knockdown of miR-126 in primary human lung microvascular endothelial cells (HLMVEC) were achieved via transfections of miR-126 mimics and antisense inhibitors. Increasing miR-126 levels in HLMVEC reduced cell proliferation, weakened tube formation, and increased cell apoptosis, whereas decreased miR-126 levels stimulated cell proliferation and tube formation. Whole-genome RNA sequencing revealed that miR-126 was associated with an antiangiogenic and proapoptotic transcriptomic profile. Using validation assays and knockdown approaches, we identified that the effect of miR-126 on HLMVEC angiogenesis was mediated by the LAT1 (L-type amino acid transporter 1), via regulation of mTOR (mammalian target of rapamycin) signaling. Furthermore, downregulation of miR-126 in HLMVEC inhibited cell apoptosis and improved endothelial tube formation during exposure to environmental insults such as cigarette smoke. Conclusions: miR-126 inhibits HLMVEC angiogenic function by targeting the LAT1-mTOR signaling axis, suggesting that miR-126 inhibition may be useful for conditions associated with microvascular loss, whereas miR-126 augmentation may help control unwanted microvascular angiogenesis.

Objective To investigate factors associated with early IVF treatment discontinuation. Design Retrospective cohort study. Setting Academic medical center. Patient(s) Six hundred sixty-nine first-attempt IVF patients who did not have a live birth. Intervention(s) None. Main Outcome Measure(s) Treatment discontinuation and time to return for a second IVF cycle. Result(s) Women without IVF insurance coverage were more likely to discontinue treatment than women with insurance coverage (adjusted odds ratio [aOR] = 3.12; 95% confidence interval [CI], 2.22–4.40). African-American women were more likely to discontinue treatment (aOR = 2.95; 95% CI, 1.54–5.66) and returned for treatment more slowly (adjusted hazard ratio [aHR] = 0.44; 95% CI, 0.28–0.71) than non-Hispanic white women, regardless of IVF insurance coverage or income. Women with a poor prognosis were more likely to discontinue treatment than women with a good prognosis. Older women with IVF insurance coverage or a good prognosis had a shorter time to return for a second IVF cycle than older women without IVF insurance coverage or with a poor prognosis. Estimated income, distance to clinic, fertility diagnosis, number of oocytes retrieved, and history of previous live birth were not associated with treatment discontinuation or time to return for a second IVF cycle after adjustment for covariates. Conclusion(s) IVF insurance coverage, race, age, and future treatment prognosis are associated with IVF treatment discontinuation and time to return.

In 2008, the Mulberry River, a National Wild and Scenic River, was listed as impaired due to low pH (below pH 6.0). Over the last 50 years, the volume of conifers in the Ozark region has increased 115% since 1978 which may result in the acidification of nearby aquatic ecosystems. The objective of this study was to determine if differences exist in soil and litter chemical properties between deciduous and coniferous tree stands. Aboveground litter (n = 200) and soil (n = 400) at 0- to 5- and 5- to 15-cm depths were collected at paired deciduous and coniferous stands at 10 locations within the Mulberry River watershed and analyzed for a suite of chemical parameters. There were no differences (P 0.05) in several measures of soil acidity between deciduous and coniferous stands. Litter collected from the coniferous stands was more acidic than deciduous litter (4.4 vs 4.7; P 0.05). Cation exchange capacity, exchangeable Ca and Mg, and water-soluble P and Mg contents differed (P 0.05) by stand and depth. Cation exchange capacity and exchangeable Ca and Mg were greatest in the 0- to 5-cm depth interval of the coniferous stands. Water-soluble P and Mg contents were greatest within the 0- to 5-cm depth interval which did not differ (P 0.05) between stand but were greater than the 5- to 15-cm depth interval. Although limited to the top 15-cm of soil, the similarity in soil acidity between stands suggests that conifer growth may not be a substantial source of acidity to the Mulberry River.

Gaseous emissions from poultry litter causes production problems for producers as well as the environment, by contributing to climate change and reducing air quality. Novel methods of reducing ammonia (NH3) and greenhouse gas (GHG) emissions in poultry facilities are needed. As such, our research evaluated GHG emissions over a 42 d period. Three separate flocks of 1000 broilers were used for this study. The first flock was used only to produce litter needed for the experiment. The second and third flocks were allocated to 20 pens in a randomized block design with four replicated of five treatments. The management practices studied included an unamended control, a conventional practice of incorporating aluminum sulfate (referred to as alum) at 98 kg/100 m2), a novel litter amendment made from alum mud, bauxite, and sulfuric acid (alum mud litter amendment, AMLA) applied at different rates (49 and 98 kg/100 m2) and methods (surface applied or incorporated). Nitrous oxide emissions were low for all treatments in flocks 2 and 3 (0.40 and 0.37 mg m2 hr−1, respectively). The formation of caked litter (due to excessive moisture) during day 35 and 42 caused high variability in CH4 and CO2 emissions. Alum mud litter amendment and alum did not significantly affect GHGs emissions from litter, regardless of the amendment rate or application method. In fact, litter amendments such as alum and AMLA typically lower GHG emissions from poultry facilities by reducing ventilation requirements to maintain air quality in cooler months due to lower NH3 levels, resulting in less propane use and concomitant reductions in CO2 emissions.

Background Regeneration of complex patterned structures is well described amongst, although limited to a small sampling of, amphibians. This limitation impedes our understanding of the full range of regenerative competencies within this class of vertebrates, according to phylogeny, developmental life stage and age. To broaden the phylogenetic breath of this research, we characterized the regenerative capacity of the Texas blind salamander (Eurycea rathbuni), a protected salamander native to the Edwards Aquifer of San Marcos, Texas and colonized by the San Marcos Aquatic Resource Center. As field observations suggested regenerative abilities in this population, the forelimb stump of a live captured female was amputated in the hopes of restoring the structure, and thus locomotion in the animal. Tails were clipped from two males to additionally document tail regeneration. Results We show that the Texas blind salamander exhibits robust limb and tail regeneration, like all other studied Plethodontidae. Regeneration in this species is associated with wound epithelium formation, blastema formation and subsequent patterning and differentiation of the regenerate. Conclusions The study has shown that the Texas blind salamander is a valuable model to study regenerative processes, and that therapeutic surgeries offer a valuable means to help maintain and conserve this vulnerable species. This article is protected by copyright. All rights reserved.

A 16-year-old white boy with a history of chronic lung disease of prematurity, cough-variant asthma, and incidental lung nodules presented to the emergency center in spring 2020 with acute onset dry cough, shortness of breath, and fever. An initial history, gathered from his mother because of the patient’s respiratory distress, revealed no recent travel. However, his mother is a health care worker at a hospital, and sick contacts included ongoing contact with a friend with cold-like symptoms. He had a variety of animals at home, including a dog, cats, fish, rodents, and reptiles. He had a history of vaping tobacco products >6 months ago. Fever and respiratory symptoms were associated with fatigue, chest tightness, abdominal pain, and myalgias. On examination, he was ill appearing and had tachycardia, tachypnea, borderline hypoxia with an oxygen saturation of 91% on room air, diminished breath sounds at the lung bases, and unremarkable abdominal examination results. A chest radiograph was consistent with the lung examination, revealing bilateral lower lobe hazy infiltrates. He showed initial improvement for 48 hours with antibiotics, intravenous fluid resuscitation, oxygen via nasal cannula, albuterol, and prednisone. Subsequently, he worsened with persistent high fever, increasing respiratory distress with pulmonary findings, and severe persistent epigastric pain, which added a layer of diagnostic complexity. As this patient’s clinical course evolved and further history became available, pulmonary medicine and infectious diseases services were consulted to guide diagnostic evaluation and treatment of this patient early in the era of coronavirus disease 2019.

Treating manure with aluminum sulfate (alum) is a best management practice (BMP) which reduces ammonia (NH3) emissions and phosphorus (P) runoff from poultry litter. However, the price of alum has increased markedly in recent years, creating a need for less expensive products to control NH3 volatilization. The objective of this study was to evaluate the effects of a new litter amendment made from alum mud, bauxite, and sulfuric acid (alum mud litter amendment or AMLA) on NH3 emissions, litter chemistry, and poultry production in a pen trial. Three separate flocks of 1000 broilers were used for this study. The first flock of birds was used to produce the poultry litter needed for the experiment. The second and third flocks of birds were allocated to 20 pens in a randomized block design with four replicates of five treatments: (1) control, (2) 49 kg AMLA/100 m2 incorporated, (3) 98 kg AMLA/100 m2 incorporated, (4) 98 kg AMLA/100 m2 surface applied, and (5) 98 kg alum/100 m2 incorporated. Ammonia flux measurements and litter samples were collected from each pen at day 0, 7, 14, 21, 28, 35, and 42. The average litter pH for both flocks was higher in untreated litter (7.92) compared to incorporating alum (7.32) or AMLA (7.18). The two flocks&rsquo, average NH4-N concentrations at day 42 were 38% and 30% higher for the high rates of incorporated alum and AMLA compared to the untreated litter. Compared with untreated litter, AMLA reduced overall NH3 emissions by 27% to 52% which was not significantly different from reductions in emissions by alum (35%). Alum mud litter amendment reduced cumulative NH3 losses from litter as much as, and in some cases more than, alum applied at the same rate. These data indicate that AMLA, which can be manufactured for lower price than alum, is an effective alternative litter amendment for reducing NH3 emissions from poultry litter.

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that treatment with a small-molecule Sigma1 inhibitor prevented 5α- dihydrotestosterone-mediated nuclear translocation of AR and induced proteasomal degradation of AR and ARV, suppressing the transcriptional activity and protein levels of both full-length and splice-variant AR. Consistent with these data, RNAi knockdown of Sigma1 resulted in decreased AR levels and transcriptional activity. Furthermore, Sigma1 physically associated with ARV7 and ARv567es as well as full-length AR. Treatment of mice xenografted with ARV-driven CRPC tumors with a drug-like small-molecule Sigma1 inhibitor significantly inhibited tumor growth associated with elimination of AR and ARV7 in responsive tumors. Together, our data show that Sigma1 modulators can be used to suppress AR/ARV–driven prostate cancer cells via regulation of pharmacologically responsive Sigma1-AR/ARV interactions, both in vitro and in vivo. Cancer Res; 77(9); 2439–52. ©2017 AACR.

Producers in Northwest Arkansas and globally need alternative management practices to ensure long-term sustainable and economical use of poultry litter, which is an abundant source of valuable carbon (C), nitrogen (N) and phosphorus (P). Project objectives were to measure the efficacy of conservation management practices (i.e., pasture aeration and subsurface litter incorporation) to reduce nutrient runoff compared to poultry litter surface applications from small watersheds under rainfed and grazed conditions. Watersheds (0.23 ha each) were assigned a treatment [pasture aeration, subsurface litter incorporation, or surface application of litter (positive control)] on a Leadvale (fine-silty, siliceous, thermic Typic Fragiudult) silt loam. Poultry litter was applied annually to each watershed from 2007-2012. Over the 4-yr study period, runoff loads of NO3–N, total nitrogen (TN), soluble reactive phosphorus (SRP), and total phosphorus (TP) varied per conservation practice (P ≤ 0.05). Specifically, average annual loads of NO3–N, TN, SRP, and TP loads were reduced 49, 42, 28, and 35% following pasture aeration and by 78, 72, 55, and 59% from subsurface applying poultry litter, relative to surface applications, respectively. Greatest annual N loads and runoff corresponded with surface poultry litter applications, followed by pasture aeration, with subsurface incorporation of poultry litter resulting in lowest (P ≤ 0.05) TN and NO3–N loads. Overall, subsurface incorporation of poultry litter and pasture aeration are two promising conservation practices for reducing non-point source pollution in watersheds with nutrient imbalances. Further work needs to be done on factors influencing the efficacy of these conservation practices under rainfed conditions, as well as the economic feasibility of these conservation agricultural practices., Nutrient loads; Best management practices; Grazing systems; Nitrogen; Phosphorus, Poultry litter.

Many aquatic species produce chemical alarm cues that serve as a warning to nearby conspecifics. In mixed-species aggregations, individuals may also benefit by ‘eavesdropping’ on the chemical alarm cues of other species that are in the same prey guild. Rainbow Darters (Etheostoma caeruleum) are benthic fish that co-occur with native Ozark Minnows (Notropis nubilus), recently introduced Western Mosquitofish (Gambusia affinis), and native Oklahoma Salamanders (Eurycea tyrnerensis), all of whom are vulnerable to the same predators. We tested the responses of darters to the damage-released alarm cues of conspecifics (positive control), minnows, and mosquitofish; alarm cues from Bumblebee Gobies (Brachygobius doriae) served as a negative (allopatric) control. We also tested the response of sympatric and allopatric darters to the damage-released alarm cues of Oklahoma Salamander. Darters exhibited a fright response to conspecific and minnow alarm cues, but not to cues from mosquitofish or gobies. Lack of response to mosquitofish cues could be because they are introduced or because they typically occur higher in the water column than darters. Darters that were sympatric with the salamander exhibited a fright response to the alarm cues of the salamander, while allopatric darters did not. Rainbow Darters can develop responses to the alarm cues of syntopic species (minnows and Oklahoma Salamander) within their prey guild.

Adding alum to poultry litter is a best management practice used to stabilize P in less soluble forms, reducing nonpoint-source P runoff. However, little research has been conducted on how alum additions to litter affect subsequent leaching of P from soil. The objective of this study was to evaluate the effects of alum-treated versus untreated poultry litter on P leaching from soil cores receiving long-term poultry litter applications. Two intact soil cores were taken from each of 52 plots in a long-term study with 13 treatments: a control, four rates each of untreated and alum-treated litter (2.24, 4.49, 6.72, and 8.96 Mg ha⁻¹), and four rates of ammonium nitrate (65, 130, 195, and 260 kg N ha⁻¹). One core from each plot received the same fertilizer as for the previous 20 yr, whereas the other was unfertilized in the study year, resulting in a total of 25 treatments. Cores were exposed to natural rainfall, and P leaching was measured for 1 yr. The average soluble reactive P concentrations in the leachate varied from 0.16 to 0.44 mg P L⁻¹ in fertilized alum-treated cores, whereas leachate from cores fertilized with untreated litter ranged from 0.40 to 2.64 mg P L⁻¹. At the highest litter rate (8.96 Mg ha⁻¹), alum reduced total dissolved P and total P concentrations in leachate by 83 and 80%, respectively, compared with untreated litter. These results indicate that alum additions to poultry litter significantly reduced soluble and total P fractions in leachate.

Fig. 1. was amended to reduce the size of the map and improve formatting of the manuscript. The authors claim this amendment does not affect the information being conveyed.

Background Thrombelastography (TEG) is a viscoelastic hemostatic assay. We have observed that end-stage renal disease (ESRD) and trauma-induced coagulopathy (TIC) produce distinctive TEG tracings. We hypothesized that rigorously definable TEG patterns could discriminate between healthy controls and patients with ESRD and TIC. Methods TEG was performed on blood from ESRD patients (n = 54) and blood from trauma patients requiring a massive blood transfusion (n = 16). Plots of independent TEG parameters were analyzed for patterns coupled to disease state, compared with controls. Decision trees for taxonomic classification were then built using the “R-Project” statistical software. Results Minimally overlapping clusters of TEG results were observed for the three patient groups when coordinate pairs of maximum amplitude (MA) and TEG-activated clotting time (ACT) were plotted on orthogonal axes. Based on these groupings, a taxonomical classification tree was constructed using MA and TEG ACT. Branch points were set at an ACT of 103 s, and these branches subdivided for MA at 60.8 mm for the high ACT branch and 72.6 mm for the low ACT branch, providing a correct classification rate of 93.4%. Conclusions ESRD and TIC demonstrate distinct TEG patterns. The coagulopathy of ESRD is typified by a prolonged enzymatic phase of clot formation, with normal-to-elevated final clot strength. Conversely, TIC is typified by prolonged clot formation and weakened clot strength. Our taxonomic categorization constitutes a rigorous system for the algorithmic interpretation of TEG based on cluster analysis. This will form the basis for clinical decision support software for viscoelastic hemostatic assays.

Coagulase-negative staphylococci (CoNS) are the most common cause of late-onset sepsis in the neonatal intensive care unit (NICU) and usually require vancomycin treatment. Our objective was to determine whether CoNS are associated with neonatal morbidity and mortality. This was a retrospective cohort study of very-low-birth-weight (VLBW, ≤ 1500 g) infants from 1989 to 2015. Exclusion criteria were major congenital anomaly or death within 72 h. CoNS was considered a pathogen if recovered from ≥ 2 cultures, or 1 culture if treated for ≥ 5 days and signs of sepsis were present. Logistic regression was used to examine factors associated with morbidity and mortality. Of 2242 VLBW infants, 285 (12.7%) had late-onset sepsis. CoNS (125, 44%), Staphylococcus aureus (52, 18%), and Escherichia coli (36, 13%) were the most commonly recovered organisms. In multivariate analysis, CoNS sepsis was not associated with mortality [OR 0.6 (95% CI 0.2–2.6)), but sepsis with other organisms was [OR 4.5 (95% CI 2.6–8.0)]. CoNS sepsis was associated with longer hospitalization but not risk for bronchopulmonary dysplasia, intraventricular hemorrhage, or retinopathy of prematurity. CoNS sepsis was not associated with mortality or morbidities other than length of stay. These findings support vancomycin-reduction strategies in the NICU.

The purpose of this paper is to share lessons learned from a collaborative, community-informed mixed-methods approach to adapting an evidence-based intervention to meet the needs of Latinos with chronic disease and minor depression and their family members. Mixed-methods informed by community-based participatory research (CBPR) were employed to triangulate multiple stakeholders' perceptions of facilitators and barriers of implementing the adapted intervention in community settings. Community partners provided an insider perspective to overcome methodological challenges. The study's community informed mixed-methods: research approach offered advantages to a single research methodology by expanding or confirming research findings and engaging multiple stakeholders in data collection. This approach also allowed community partners to collaborate with academic partners in key research decisions.

To the Editor: In a recent article, Divers et al.1 describe the interaction between apolipoprotein L1 (APOL1) genotypes and JC viruria, and their relationship with nondiabetic nephropathy in African Americans. The authors found that in African Americans with two APOL1 risk alleles, the prevalence of kidney disease was lower for those with JC viruria compared with those without JC viruria. In a cohort of 282 renal transplant recipients (80% white, 239 JC negative and 43 JC positive), we found that isolated JC viruria, without JC or BK viremia, was associated with protection from acute renal allograft rejection (13.8% for JC− vs. 2.3% for JC+, P=0.04). Kaplan–Meier analysis for acute rejection–free survival was also favorable for JC+ compared with that for JC− (log-rank P=0.05) recipients. There was no difference for death-censored graft survival (P=0.6) or patient survival (P=0.1). JC+ recipients tended to be less likely to be coinfected with BK virus (7% for JC+ vs. 14.2% for JC−, P=0.2). Divers et al.,1 and an accompanying editorial by Kopp2 speculate that JC virus may protect against other polyomaviruses that are associated with kidney disease or it may alter cellular function rendering the kidney less susceptible to damage. Our findings support their speculations for the protective role of isolated JC viruria and expand the implications to the kidney transplant population in addition to the African-American population.