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Winter cover crops have been proposed as a potential climate mitigation practice, but a recent study concluded that cover crops may increase local temperature by up to 3°C. Here, we present agronomic context and data on cover crop morphology to ground-truth the scenarios simulated in this study. We conclude that the scenario of cover crop morphology on which the study’s headline claim is based is unlikely to be found in contemporary production systems. The most realistic scenario simulated did not result in significant local warming. Therefore, we argue that widespread planting of cover crops is unlikely to substantially increase local winter temperatures.

Aim: Characterizing the response to myocardial infarction (MI) in the regenerative sheep fetus heart compared to the post-natal non-regenerative adolescent heart may reveal key morphological and molecular differences that equate to the response to MI in humans. We hypothesized that the immediate response to injury in (a) infarct compared with sham, and (b) infarct, border, and remote tissue, in the fetal sheep heart would be fundamentally different to the adolescent, allowing for repair after damage.Methods: We used a sheep model of MI induced by ligating the left anterior descending coronary artery. Surgery was performed on fetuses (105 days) and adolescent sheep (6 months). Sheep were randomly separated into MI (n = 5) or Sham (n = 5) surgery groups at both ages. We used magnetic resonance imaging (MRI), histological/immunohistochemical staining, and qRT-PCR to assess the morphological and molecular differences between the different age groups in response to infarction.Results: Magnetic resonance imaging showed no difference in fetuses for key functional parameters; however there was a significant decrease in left ventricular ejection fraction and cardiac output in the adolescent sheep heart at 3 days post-infarction. There was no significant difference in functional parameters between MRI sessions at Day 0 and Day 3 after surgery. Expression of genes involved in glucose transport and fatty acid metabolism, inflammatory cytokines as well as growth factors and cell cycle regulators remained largely unchanged in the infarcted compared to sham ventricular tissue in the fetus, but were significantly dysregulated in the adolescent sheep. Different cardiac tissue region-specific gene expression profiles were observed between the fetal and adolescent sheep.Conclusion: Fetuses demonstrated a resistance to cardiac damage not observed in the adolescent animals. The manipulation of specific gene expression profiles to a fetal-like state may provide a therapeutic strategy to treat patients following an infarction.

Despite the popularity of multispecies cover crop mixtures, there is little published evidence of their effects on subsequent crop yields, especially for multiple crops grown in rotation. We examined the effects of fall-planted cover crops—both mixtures and their component monocultures—on subsequent crop yields in an organically managed maize ( L.)–soybean [ (L.) Merr.]–winter wheat ( L.) rotation in central Pennsylvania. We hypothesized that cover crop biomass C/N ratio would be negatively correlated with crop yields. This held true for maize ( = 0.134, < 0.0001), but there was no cover crop effect on soybean or wheat yields. All multispecies mixtures produced high biomass, and none affected maize yield relative to fallow. Our findings suggest that both multispecies cover crops and diverse crop rotations may increase opportunities to gain the benefits of cover crops with high biomass and C/N ratio—such as erosion control, weed suppression, N retention, and soil C accumulation—without compromising yield.

Cover crops are increasingly being adopted to provide multiple ecosystem services such as improving soil health, managing nutrients, and decreasing soil erosion. It is not uncommon for weeds to emerge in and become a part of a cover crop plant community. Since the role of cover cropping is to supplement ecosystem service provisioning, we were interested in assessing the impacts of weeds on such provisioning. To our knowledge, no research has examined how weeds in cover crops may impact the provision of ecosystem services and disservices. Here, we review services and disservices associated with weeds in annual agroecosystems and present two case studies from the United States to illustrate how weeds growing in fall-planted cover crops can provide ground cover, decrease potential soil losses, and effectively manage nitrogen. We argue that in certain circumstances, weeds in cover crops can enhance ecosystem service provisioning. In other circumstances, such as in the case of herbicide-resistant weeds, cover crops should be managed to limit weed biomass and fecundity. Based on our case studies and review of the current literature, we conclude that the extent to which weeds should be allowed to grow in a cover crop is largely context-dependent.

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although this genocopy of relatively lower hematocrit in Andean highlanders parallels well-replicated findings in Tibetans, it likely involves distinct pathway responses based on a protein-coding versus noncoding variants, respectively. These findings illuminate how unique variants at EPAS1 contribute to the same phenotype in Tibetans and a subset of Andean highlanders despite distinct evolutionary trajectories.

Brodie’s abscess is a subacute form of osteomyelitis which generally occurs in the metaphysis of the femur and tibia in the pediatric population. Pathogens are most commonly Gram-positive bacteria, notably Staphylococcus and Streptococcus. In this article, we describe a young pediatric patient presenting with subacute ankle pain with a subsequent diagnosis of Brodie’s abscess of the talus secondary to Morganella morganii. We review the presentation, diagnosis, and treatment of this unique patient. To our knowledge, this is the first report of Morganella morganii as a cause of Brodie’s abscess.

Agroecosystems are increasingly expected to provide multiple ecosystem services. We tested whether and how cover crop selection (identity and number of species) affects provisioning of multiple services (multifunctionality). In a 3-yr study of 10 cover crop treatments and eight ecosystem services, certain services consistently co-occurred. One such service “bundle” included cover crop biomass production, weed suppression, and nitrogen retention. Another set of bundled services included cash crop production, nitrogen supply, and profitability. We also identified trade-offs: as some services increased, other disservices arose, limiting multifunctionality. However, functionally diverse mixtures ameliorated disservices associated with certain monocultures, thereby increasing cover crop multifunctionality.

The tissue-engineered heart valve portends a new era in the field of valve replacement. Decellularized heart valves are of great interest as a scaffold for the tissue-engineered heart valve due to their naturally bioactive composition, clinical relevance as a stand-alone implant, and partial recellularization in vivo. However, a significant challenge remains in realizing the tissue-engineered heart valve: assuring consistent recellularization of the entire valve leaflets by phenotypically appropriate cells. Many creative strategies have pursued complete biological valve recellularization; however, identifying the optimal recellularization method, including in situ or in vitro recellularization and chemical and/or mechanical conditioning, has proven difficult. Furthermore, while many studies have focused on individual parameters for increasing valve interstitial recellularization, a general understanding of the interacting dynamics is likely necessary to achieve success. Therefore, the purpose of this review is to explore and compare the various processing strategies used for the decellularization and subsequent recellularization of tissue-engineered heart valves.

Microglia are the brain-resident immune cells responsible for surveilling and protecting the central nervous system. These cells can express a wide array of immune genes, and that expression can become highly dynamic in response to changes in the environment, such as traumatic injury or neurological disease. Though microglial immune responses are well studied, we still do not know many mechanisms and regulators underlying all the varied microglial responses. Serpin E2 is a serine protease inhibitor that acts on a wide variety of serine proteases, with particularly potent affinity for the blood clotting enzyme thrombin. In the brain, Serpin E2 is highly expressed by many cell types, especially glia, and loss of Serpin E2 leads to behavioral changes as well as deficits in synaptic plasticity. To determine whether Serpin E2 is important for maintaining homeostasis in glia, we performed RNA sequencing of microglia and astrocytes from Serpin E2-deficient mice in a healthy state or under immune activation due to lipopolysaccharide (LPS) injection. We found that microglia in Serpin E2-deficient mice had higher expression of antimicrobial genes, while astrocytes did not display any robust changes in transcription. Furthermore, the lack of Serpin E2 did not affect transcriptional responses to LPS in either microglia or astrocytes. Overall, we find that Serpin E2 is a regulator of antimicrobial genes in microglia.

Manganese superoxide dismutase, encoded by the Sod2 gene, is a ubiquitously expressed mitochondrial antioxidant enzyme that is essential for mammalian life. Mice born with constitutive genetic knockout of Sod2 do not survive the neonatal stage, which renders the longitudinal study of the biochemical and metabolic effects of Sod2 loss difficult. However, multiple studies have demonstrated that tissue-specific knockout of Sod2 in murine liver yields no observable gross pathology or injury to the mouse. We hypothesized that Sod2 loss may have sub-pathologic effects on liver biology, including the acquisition of reactive oxygen species-mediated mitochondrial DNA mutations. To evaluate this, we established and verified a hepatocyte-specific knockout of Sod2 in C57/B6 mice using Cre-LoxP recombination technology. We utilized deep sequencing to identify possible mutations in Sod2−/− mitochondrial DNA as compared to wt, and both RT-PCR and traditional biochemical assays to evaluate baseline differences in redox-sensitive pathways in Sod2−/− hepatocytes. Surprisingly, no mutations in Sod2−/− mitochondrial DNA were detected despite measurable increases in dihydroethidium staining in situ and concomitant decreases in complex II activity indicative of elevated superoxide in the Sod2−/− hepatocytes. In contrast, numerous compensatory alterations in gene expression were identified that suggest hepatocytes have a remarkable capacity to adapt and overcome the loss of Sod2 through transcriptional means. Taken together, these results suggest that murine hepatocytes have a large reserve capacity to cope with the presence of additional mitochondrial reactive oxygen species.

In health economics, costs can be divided into both direct and indirect categories. Direct costs tend to consist of medical costs, which are those directly attributed to health care interventions (e.g., hospitalizations, pharmaceuticals, devices), and non-medical direct costs such as monitoring and professional caregiving. Indirect costs tend to comprise those related to lost productivity due to illness (or treatment), burden on systems outside of the healthcare domain, and other costs that can sometimes outweigh the entire sum of direct healthcare costs. The most common life-threatening complication of lung and hematopoietic stem-cell transplantation (HSCT) is bronchiolitis obliterans syndrome (BOS). BOS is currently diagnosed as a 20% decline in the forced expiratory volume in one second (FEV1) from the best (baseline) post-transplantation value, and is a major cause of morbidity and mortality amongst lung and stem cell transplant patients. BOS affects half of all lung transplant patients within the first 5 years post-transplant, rising to the majority of patients (~80%) within the first decade following transplant. We estimated both direct and indirect costs for the first 10 years following BOS diagnosis, a viewpoint that highlights a tremendous imbalance between healthcare and non-healthcare costs. The lost workforce resulting from BOS-related infirmity will cost society more than $3.7 Billion over the next decade, a figure that is more than double the estimated 10-year cost of treating BOS ($1.4B), including diagnostics, immunosuppressives, and additional complications. As such, BOS is estimated to present a burden of cost that must be evaluated in a new light to include the wider societal perspective.

With advances in organ matching and preventing acute graft-versus-host-disease (aGvHD), chronic graft-versus-host disease (cGvHD) following allogeneic hematopoietic stem cell transplantation (HSCT) has become a focus of transplant-related morbidity and mortality. Given that cGvHD often presents years following a transplant, our objective was to estimate its burden of cost resulting from allogeneic HSCT based on published estimates of incidence, morbidity, the value of lost work time and survivorship. Our choice of a ten-year time horizon is novel to the field of rare disease and was determined to be meaningful after consultations with present co-authors, including five physicians, one of whom is a transplant surgeon. A total of 44 450 cGvHD patients in the United States were estimated to require treatment over the next decade (from 2015 to 2025). This estimate is based on the last 5 years of trends reported in the transplant registries. What is not reported in any registry is that these patients will accrue a total of 605 631 years of lost wages, a collective lost productivity that will cost society over $27 Billion in the decade ahead: more than five times ($27B vs. $5.2B) the estimated ten-year cost of treating the condition.

There is increasing global demand for food, bioenergy feedstocks and a wide variety of bio-based products. In response, agriculture has advanced production, but is increasingly depleting soil regulating and supporting ecosystem services. New production systems have emerged, such as no-tillage, that can enhance soil services but may limit yields. Moving forward, agricultural systems must reduce trade-offs between production and soil services. Soil functional zone management (SFZM) is a novel strategy for developing sustainable production systems that attempts to integrate the benefits of conventional, intensive agriculture and no-tillage. SFZM creates distinct functional zones within crop row and inter-row spaces. By incorporating decimetre-scale spatial and temporal heterogeneity, SFZM attempts to foster greater soil biodiversity and integrate complementary soil processes at the sub-field level. Such integration maximizes soil services by creating zones of ‘active turnover’, optimized for crop growth and yield (provisioning services); and adjacent zones of ‘soil building’, that promote soil structure development, carbon storage and moisture regulation (regulating and supporting services). These zones allow SFZM to secure existing agricultural productivity while avoiding or minimizing trade-offs with soil ecosystem services. Moreover, the specific properties of SFZM may enable sustainable increases in provisioning services via temporal intensification (expanding the portion of the year during which harvestable crops are grown). We present a conceptual model of ‘virtuous cycles’, illustrating how increases in crop yields within SFZM systems could create self-reinforcing feedback processes with desirable effects, including mitigation of trade-offs between yield maximization and soil ecosystem services. Through the creation of functionally distinct but interacting zones, SFZM may provide a vehicle for optimizing the delivery of multiple goods and services in agricultural systems, allowing sustainable temporal intensification while protecting and enhancing soil functioning.

The encapsulation of biomolecules in solid materials that retain the native properties of the molecule is a desired feature for the development of biosensors and biocatalysts. In the current study, protein entrapment in silica-based materials is explored using the sol-gel technique. This work surveys the effects of silica confinement on the structure of several model polypeptides, including apomyoglobin, copper-zinc superoxide dismutase, polyglutamine, polylysine, and type I antifreeze protein. Changes in the secondary structure of each protein following encapsulation are monitored by circular dichroism spectroscopy. In many cases, silica confinement reduces the fraction of properly-folded protein relative to solution, but addition of a secondary solute or modification of the silica surface leads to an increase in structure. Refinement of the glass surface by addition of a monosubstituted alkoxysilane during sol-gel processing is shown to be a valuable tool for testing the effects of surface chemistry on protein structure. Because silica entrapment prevents protein aggregation by isolating individual protein molecules in the pores of the glass material, one may monitor aggregation-prone polypeptides under solvent conditions that are prohibited in solution, as demonstrated with polyglutamine and a disease-related variant of superoxide dismutase.

In the originally published version of this Article, the affiliation details for Kevin P. White inadvertently omitted ‘Tempus Labs, Chicago, IL, 60654, USA’. This has now been corrected in both the PDF and HTML versions of the Article.

IntroductionSingle-stage revision arthroplasty for periprosthetic joint infection (PJI) may yield comparable infection-free survivorship with two-stage revision arthroplasty. It is unclear if the most common mode of failure of single-stage revision arthroplasty is infection or aseptic loosening. In this meta-analysis, we sought to (1) determine survivorship and (2) compare rates of different etiologies of failure of single-stage revision total hip arthroplasty (THA) and total knee arthroplasty (TKA).MethodsPreferred Reporting Items for Systematic Review and Meta-analyses guidelines search was done using search terms for "single stage revision," "exchange arthroplasty," "periprosthetic infection," "PJI," and "single stage." Patient demographics such as age, body mass index, and mean follow-up time were recorded. Overall survivorship and rates of revision surgery were aggregated using a random-effects model. Comparison of septic and aseptic loosening rates was done by risk difference and associated 95% confidence interval (CI) calculation.ResultsTwenty-four studies were identified with 2,062 and 147 single-stage revision THA and TKA procedures performed between 1984 and 2019, respectively. The weighted mean follow-up and age were 69.8 months and 66.3 years, respectively, with 55% men overall. The all-cause revision surgery rate was 11.1% and 11.8% for THA and TKA, respectively. The revision surgery rate secondary to infection and aseptic loosening and associated 95% CI for the risk difference for THA and TKA was 5.5% and 3.3% (-1.7% to 5.0%), and 3% and 8.8% (-11.4% to 2.3%), respectively. Revision surgeries due to instability and fracture combined and mortality rate were both less than 3%.DiscussionSingle-stage revision THA and TKA for PJI demonstrated overall high rates of survivorship, low mortality, and revision surgeries secondary to infection and aseptic loosening to be equivalent. Aseptic loosening after single-stage revision TKA might be higher than in primary TKA. As implant survivorship from infection improves in PJI, surgeons should be aware of aseptic loosening as an equally common mode of failure.

PURPOSE:The analysis of exosome/microvesicle (extracellular vesicles (EVs)) and the RNA packaged within them (exoRNA) has the potential to provide a non-invasive platform to detect and monitor disease related gene expression potentially in lieu of more invasive procedures such as biopsy. However, few studies have tested the diagnostic potential of EV analysis in humans. EXPERIMENTAL DESIGN:The ability of EV analysis to accurately reflect prostate tissue mRNA expression was examined by comparing urinary EV TMPRSS2:ERG exoRNA from pre-radical prostatectomy (RP) patients versus corresponding RP tissue in 21 patients. To examine the differential expression of TMPRSS2:ERG across patient groups a random urine sample was taken without prostate massage from a cohort of 207 men including prostate biopsy negative (Bx Neg, n = 39), prostate biopsy positive (Bx Pos, n = 47), post-radical prostatectomy (post-RP, n = 37), un-biopsied healthy age-matched men (No Bx, n = 44), and young male controls (Cont, n = 40). The use of EVs was also examined as a potential platform to non-invasively differentiate Bx Pos versus Bx Neg patients via the detection of known prostate cancer genes TMPRSS2:ERG, BIRC5, ERG, PCA3 and TMPRSS2. RESULTS:In this technical pilot study urinary EVs had a sensitivity: 81% (13/16), specificity: 80% (4/5) and an overall accuracy: 81% (17/21) for non-invasive detection of TMPRSS2:ERG versus RP tissue. The rate of TMPRSS2:ERG exoRNA detection was found to increase with age and the expression level correlated with Bx Pos status. Receiver operator characteristic analyses demonstrated that various cancer-related genes could differentiate Bx Pos from Bx Neg patients using exoRNA isolated from urinary EVs: BIRC5 (AUC 0.674 (CI:0.560-0.788), ERG (AUC 0.785 (CI:0.680-0.890), PCA3 (AUC 0.681 (CI:0.567-0.795), TMPRSS2:ERG (AUC 0.744 (CI:0.600-0.888), and TMPRSS2 (AUC 0.637 (CI:0.519-0.754). CONCLUSION:This pilot study suggests that urinary EVs have the potential to be used as a platform to non-invasively differentiate patients with prostate cancer with very good accuracy. Larger studies are needed to confirm the potential for clinical utility.

Yield stability is fundamental to global food security in the face of climate change, and better strategies are needed for buffering crop yields against increased weather variability. Regional- scale analyses of yield stability can support robust inferences about buffering strategies for widely-grown staple crops, but have not been accomplished. We present a novel analytical approach, synthesizing 2000-2014 data on weather and soil factors to quantify their impact on county-level maize yield stability in four US states that vary widely in these factors (Illinois, Michigan, Minnesota and Pennsylvania). Yield stability is quantified as both 'downside risk' (minimum yield potential, MYP) and 'volatility' (temporal yield variability). We show that excessive heat and drought decreased mean yields and yield stability, while higher precipitation increased stability. Soil water holding capacity strongly affected yield volatility in all four states, either directly (Minnesota and Pennsylvania) or indirectly, via its effects on MYP (Illinois and Michigan). We infer that factors contributing to soil water holding capacity can help buffer maize yields against variable weather. Given that soil water holding capacity responds (within limits) to agronomic management, our analysis highlights broadly relevant management strategies for buffering crop yields against climate variability, and informs region-specific strategies.

Post-traumatic osteoarthritis can develop as a result of the initial mechanical impact causing the injury and also as a result of chronic changes in mechanical loading of the joint. Aberrant mechanical loading initiates excessive production of reactive oxygen species, oxidative damage, and stress that appears to damage mitochondria in the surviving chondrocytes. To probe the benefits of increasing superoxide removal with small molecular weight superoxide dismutase mimetics under severe loads, we applied both impact and overload injury scenarios to bovine osteochondral explants using characterized mechanical platforms with and without GC4403, MnTE-2-PyP, and MnTnBuOE-2-PyP. In impact scenarios, each of these mimetics provides some dose-dependent protection from cell death and loss of mitochondrial content while in repeated overloading scenarios only MnTnBuOE-2-PyP provided a clear benefit to chondrocytes. These results support the hypothesis that superoxide is generated in excess after impact injuries and suggest that superoxide production within the lipid compartment may be a critical mediator of responses to chronic overload. This is an important nuance distinguishing roles of superoxide, and thus superoxide dismutases, in mediating damage to cellular machinery in hyper-acute impact scenarios compared to chronic scenarios.

Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es) characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy.We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤ 5 initial metastases resected with curative intent.Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP) and low rate of progression (LRP); the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset.Oligo- and poly- metastasis are distinct entities at the clinical and molecular level.

Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by ≤ 5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy.Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy.Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression.These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.

Traditionally IFN/STAT1 signaling is connected with an anti-viral response and pro-apoptotic tumor-suppressor functions. Emerging functions of a constitutively activated IFN/STAT1 pathway suggest an association with an aggressive tumor phenotype. We hypothesized that tumor clones that constitutively overexpress this pathway are preferentially selected by the host microenvironment due to a resistance to STAT1-dependent cytotoxicity and demonstrate increased metastatic ability combined with increased resistance to genotoxic stress.Here we report that clones of B16F1 tumors grown in the lungs of syngeneic C57BL/6 mice demonstrate variable transcriptional levels of IFN/STAT1 pathway expression. Tumor cells that constitutively overexpress the IFN/STAT1 pathway (STAT1(H) genotype) are selected by the lung microenvironment. STAT1(H) tumor cells also demonstrate resistance to IFN-gamma (IFNgamma), ionizing radiation (IR), and doxorubicin relative to parental B16F1 and low expressors of the IFN/STAT1 pathway (STAT1(L) genotype). Stable knockdown of STAT1 reversed the aggressive phenotype and decreased both lung colonization and resistance to genotoxic stress.Our results identify a pathway activated by tumor-stromal interactions thereby selecting for pro-metastatic and therapy-resistant tumor clones. New therapies targeted against the IFN/STAT1 signaling pathway may provide an effective strategy to treat or sensitize aggressive tumor clones to conventional cancer therapies and potentially prevent distant organ colonization.

BACKGROUND: The distribution of Palmer's oak (Quercus palmeri Engelm.) includes numerous isolated populations that are presumably relicts of a formerly larger range that has contracted due to spreading aridity following the end of the Pleistocene. PRINCIPAL FINDINGS: We investigated a recently discovered disjunct population of Palmer's oak in the Jurupa Mountains of Riverside County, California. Patterns of allozyme polymorphism, morphological homogeneity, widespread fruit abortion, and evidence of fire resprouting all strongly support the hypothesis that the population is a single clone. The size of the clone and estimates of annual growth from multiple populations lead us to conclude that the clone is in excess of 13,000 years old. CONCLUSIONS: The ancient age of the clone implies it originated during the Pleistocene and is a relict of a vanished vegetation community. Range contraction after climate change best explains the modern disjunct distribution of Q. palmeri and perhaps other plants in California.

Astrocytes are critical for the development and function of synapses. There are notable species differences between human astrocytes and commonly used animal models. Yet, it is unclear whether astrocytic genes involved in synaptic function are stable or exhibit dynamic changes associated with disease states and age in humans, which is a barrier in understanding human astrocyte biology and its potential involvement in neurologic diseases. To better understand the properties of human astrocytes, we acutely purified astrocytes from the cerebral cortices of over 40 humans across various ages, sexes, and disease states. We performed RNA sequencing to generate transcriptomic profiles of these astrocytes and identified genes associated with these biological variables. We found that human astrocytes in tumor-surrounding regions downregulate genes involved in synaptic function and sensing of signals in the microenvironment, suggesting involvement of peritumor astrocytes in tumor-associated neural circuit dysfunction. In aging, we also found downregulation of synaptic regulators and upregulation of markers of cytokine signaling, while in maturation we identified changes in ionic transport with implications for calcium signaling. In addition, we identified subtle sexual dimorphism in human cortical astrocytes, which has implications for observed sex differences across many neurologic disorders. Overall, genes involved in synaptic function exhibit dynamic changes in the peritumor microenvironment and aging. These data provide powerful new insights into human astrocyte biology in several biologically relevant states that will aid in generating novel testable hypotheses about homeostatic and reactive astrocytes in humans.SIGNIFICANCE STATEMENT Astrocytes are an abundant class of cells playing integral roles at synapses. Astrocyte dysfunction is implicated in a variety of human neurologic diseases. Yet our knowledge of astrocytes is largely based on mouse studies. Direct knowledge of human astrocyte biology remains limited. Here, we present transcriptomic profiles of human cortical astrocytes, and we identified molecular differences associated with age, sex, and disease state. We found that peritumor and aging astrocytes downregulate genes involved in astrocyte-synapse interactions. These data provide necessary insight into human astrocyte biology that will improve our understanding of human disease.