Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth.

Glioblastoma stem cells (GSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. To illuminate mechanisms governing these hallmark features, we developed a de novo glioblastoma multiforme (GBM) model derived from immortalized human neural stem/progenitor cells (hNSCs) to enable precise system-level comparisons of pre-malignant and oncogene-induced malignant states of NSCs. Integrated transcriptomic and epigenomic analyses uncovered a PAX6/DLX5 transcriptional program driving WNT5A-mediated GSC differentiation into endothelial-like cells (GdECs). GdECs recruit existing endothelial cells to promote peritumoral satellite lesions, which serve as a niche supporting the growth of invasive glioma cells away from the primary tumor. Clinical data reveal higher WNT5A and GdECs expression in peritumoral and recurrent GBMs relative to matched intratumoral and primary GBMs, respectively, supporting WNT5A-mediated GSC differentiation and invasive growth in disease recurrence. Thus, the PAX6/DLX5-WNT5A axis governs the diffuse spread of glioma cells throughout the brain parenchyma, contributing to the lethality of GBM.

A solar C/O and sub-solar metallicity in a hot Jupiter atmosphere.

Measurements of the atmospheric carbon (C) and oxygen (O) relative to hydrogen (H) in hot Jupiters (relative to their host stars) provide insight into their formation location and subsequent orbital migration1,2. Hot Jupiters that form beyond the major volatile (H2O/CO/CO2) ice lines and subsequently migrate post disk-dissipation are predicted have atmospheric carbon-to-oxygen ratios (C/O) near 1 and subsolar metallicities2, whereas planets that migrate through the disk before dissipation are predicted to be heavily polluted by infalling O-rich icy planetesimals, resulting in C/O < 0.5 and super-solar metallicities1,2. Previous observations of hot Jupiters have been able to provide bounded constraints on either H2O (refs. 3-5) or CO (refs. 6,7), but not both for the same planet, leaving uncertain4 the true elemental C and O inventory and subsequent C/O and metallicity determinations. Here we report spectroscopic observations of a typical transiting hot Jupiter, WASP-77Ab. From these, we determine the atmospheric gas volume mixing ratio constraints on both H2O and CO (9.5 × 10-5-1.5 × 10-4 and 1.2 × 10-4-2.6 × 10-4, respectively). From these bounded constraints, we are able to derive the atmospheric C/H ([Formula: see text] × solar) and O/H ([Formula: see text] × solar) abundances and the corresponding atmospheric carbon-to-oxygen ratio (C/O = 0.59 ± 0.08; the solar value is 0.55). The sub-solar (C+O)/H ([Formula: see text] × solar) is suggestive of a metal-depleted atmosphere relative to what is expected for Jovian-like planets1 while the near solar value of C/O rules out the disk-free migration/C-rich2 atmosphere scenario.

Fracture of model end-linked networks.

Advances in polymer chemistry over the last decade have enabled the synthesis of molecularly precise polymer networks that exhibit homogeneous structure. These precise polymer gels create the opportunity to establish true multiscale, molecular to macroscopic, relationships that define their elastic and failure properties. In this work, a theory of network fracture that accounts for loop defects is developed by drawing on recent advances in network elasticity. This loop-modified Lake-Thomas theory is tested against both molecular dynamics (MD) simulations and experimental fracture measurements on model gels, and good agreement between theory, which does not use an enhancement factor, and measurement is observed. Insight into the local and global contributions to energy dissipated during network failure and their relation to the bond dissociation energy is also provided. These findings enable a priori estimates of fracture energy in swollen gels where chain scission becomes an important failure mechanism.

Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms.

This review proposes that physical inactivity could be considered a behavior selected by evolution for resting, and also selected to be reinforcing in life-threatening situations in which exercise would be dangerous. Underlying the notion are human twin studies and animal selective breeding studies, both of which provide indirect evidence for the existence of genes for physical inactivity. Approximately 86% of the 325 million in the United States (U.S.) population achieve less than the U.S. Government and World Health Organization guidelines for daily physical activity for health. Although underappreciated, physical inactivity is an actual contributing cause to at least 35 unhealthy conditions, including the majority of the 10 leading causes of death in the U.S. First, we introduce nine physical inactivity-related themes. Next, characteristics and models of physical inactivity are presented. Following next are individual examples of phenotypes, organ systems, and diseases that are impacted by physical inactivity, including behavior, central nervous system, cardiorespiratory fitness, metabolism, adipose tissue, skeletal muscle, bone, immunity, digestion, and cancer. Importantly, physical inactivity, itself, often plays an independent role as a direct cause of speeding the losses of cardiovascular and strength fitness, shortening of healthspan, and lowering of the age for the onset of the first chronic disease, which in turn decreases quality of life, increases health care costs, and accelerates mortality risk.

Photoelectrochemical Proton-Coupled Electron Transfer of TiO2 Thin Films on Silicon.

TiO2 thin films are often used as protective layers on semiconductors for applications in photovoltaics, molecule-semiconductor hybrid photoelectrodes, and more. Experiments reported here show that TiO2 thin films on silicon are electrochemically and photoelectrochemically reduced in buffered acetonitrile at potentials relevant to photoelectrocatalysis of CO2 reduction, N2 reduction, and H2 evolution. On both n-type Si and irradiated p-type Si, TiO2 reduction is proton-coupled with a 1e-:1H+ stoichiometry, as demonstrated by the Nernstian dependence of the Ti4+/3+ E1/2 on the buffer pKa. Experiments were conducted with and without illumination, and a photovoltage of ∼0.6 V was observed across 20 orders of magnitude in proton activity. The 4 nm films are almost stoichiometrically reduced under mild conditions. The reduced films catalytically transfer protons and electrons to hydrogen atom acceptors, based on cyclic voltammogram, bulk electrolysis, and other mechanistic evidence. TiO2/Si thus has the potential to photoelectrochemically generate high-energy H atom carriers. Characterization of the TiO2 films after reduction reveals restructuring with the formation of islands, rendering TiO2 films as a potentially poor choice as protecting films or catalyst supports under reducing and protic conditions. Overall, this work demonstrates that atomic layer deposition TiO2 films on silicon photoelectrodes undergo both chemical and morphological changes upon application of potentials only modestly negative of RHE in these media. While the results should serve as a cautionary tale for researchers aiming to immobilize molecular monolayers on "protective" metal oxides, the robust proton-coupled electron transfer reactivity of the films introduces opportunities for the photoelectrochemical generation of reactive charge-carrying mediators.

Highly Mesoporous Zr-Based MOF-Fabric Composites: A Benign Approach for Expeditious Degradation of Chemical Warfare Agents and Simulants.

Recent research has demonstrated the degradation of organophosphonates through hydrolysis using microporous UiO-66-NH2-fabric composites. Yet, challenges remain due to the limitations of organophosphonates accessing active sites in large, engineered granules. To address this, an innovative approach to integrate mesoporous UiO-66-NH2 onto various fabrics is provided, thereby overcoming previous mass transfer limitations. Mesoporosity in the UiO-66-NH2-fabric is attributed to the amphoteric cocamidopropylbetaine (CAPB) surfactant which templates the mesochannel construction. Unexpectedly, because the synthesis is aqueous, benign, low temperature (60°C), and avoids strong acids and toxic solvents, it is compatible with fragile supports such as untreated cotton. The UiO-66-NH2-fabric composite formed using treated polypropylene (PP) attains a BET specific surface area of 360 m2 g-1 comp. Remarkably, the mesoporous UiO-66-NH2-composites exhibit a pore volume as large as 0.2 cm3 g-1 comp, 33% in the mesoporous range, which is higher than other previous reports. Practically, the mesoporous UiO-66-NH2-treated PP composite enhances the rate of methyl paraoxon (DMNP) degradation, showing a t1/2 value that is 15 times faster than microporous UiO-66-NH2 composites measured under the same conditions. Similar trends are observed in the degradation of actual nerve agents. These composites hold significant potential across diverse applications, including filtration, protection, and catalysis.

Control of ZIF-62 and agZIF-62 Film Thickness within Asymmetric Tubular Supports through Pressure and Dose Time Variation of Atomic Layer Deposition.

Thin-films of metal-organic frameworks (MOFs) have widespread potential applications, especially with the emergence of glass-forming MOFs, which remove the inherent issue of grain boundaries and allow coherent amorphous films to be produced. Herein, it is established that atomic layer deposition (ALD) of zinc oxide lends excellent control over the thickness and localization of resultant polycrystalline and glass zeolitic imidazole framework-62 (ZIF-62) thin-films within tubular α-alumina supports. Through the reduction of the chamber pressure and dose times during zinc oxide deposition, the resultant ZIF-62 films are reduced from 38 µm to 16 µm, while the presence of sporadic ZIF-62 (previously forming as far as 280 µm into the support) is prevented. Furthermore, the glass transformation shows a secondary reduction in film thickness from 16 to 2 µm.

Diving into broad-scale and high-resolution population genomics to decipher drivers of structure and climatic vulnerability in a marine invertebrate.

Species with widespread distributions play a crucial role in our understanding of climate change impacts on population structure. In marine species, population structure is often governed by both high connectivity potential and selection across strong environmental gradients. Despite the complexity of factors influencing marine populations, studying species with broad distribution can provide valuable insights into the relative importance of these factors and the consequences of climate-induced alterations across environmental gradients. We used the northern shrimp Pandalus borealis and its wide latitudinal distribution to identify current drivers of population structure and predict the species' vulnerability to climate change. A total of 1514 individuals sampled across 24° latitude were genotyped at high geographic (54 stations) and genetic (14,331 SNPs) resolutions to assess genetic variation and environmental correlations. Four populations were identified in addition to finer substructure associated with local adaptation. Geographic patterns of neutral population structure reflected predominant oceanographic currents, while a significant proportion of the genetic variation was associated with gradients in salinity and temperature. Adaptive landscapes generated using climate projections suggest a larger genomic offset in the southern extent of the P. borealis range, where shrimp had the largest adaptive standing genetic variation. Our genomic results combined with recent observations point to further deterioration in southern regions and an impending vulnerable status in the regions at higher latitudes for P. borealis. They also provide rare insights into the drivers of population structure and climatic vulnerability of a widespread meroplanktonic species, which is crucial to understanding future challenges associated with invertebrates essential to ecosystem functioning.

Blockade of the mineralocorticoid receptor improves markers of human endothelial cell dysfunction and hematological indices in a mouse model of sickle cell disease.

Increased endothelin-1 (ET-1) levels in patients with sickle cell disease (SCD) and transgenic mouse models of SCD contribute to disordered hematological, vascular, and inflammatory responses. Mineralocorticoid receptor (MR) activation by aldosterone, a critical component of the Renin-Angiotensin-Aldosterone-System, modulates inflammation and vascular reactivity, partly through increased ET-1 expression. However, the role of MR in SCD remains unclear. We hypothesized that MR blockade in transgenic SCD mice would reduce ET-1 levels, improve hematological parameters, and reduce inflammation. Berkeley SCD (BERK) mice, a model of severe SCD, were randomized to either sickle standard chow or chow containing the MR antagonist (MRA), eplerenone (156 mg/Kg), for 14 days. We found that MRA treatment reduced ET-1 plasma levels (p = .04), improved red cell density gradient profile (D50 ; p < .002), and increased mean corpuscular volume in both erythrocytes (p < .02) and reticulocytes (p < .024). MRA treatment also reduced the activity of the erythroid intermediate-conductance Ca2+ -activated K+ channel - KCa 3.1 (Gardos channel, KCNN4), reduced cardiac levels of mRNAs encoding ET-1, Tumor Necrosis Factor Receptor-1, and protein disulfide isomerase (PDI) (p < .01), and decreased plasma PDI and myeloperoxidase activity. Aldosterone (10-8 M for 24 h in vitro) also increased PDI mRNA levels (p < .01) and activity (p < .003) in EA.hy926 human endothelial cells, in a manner blocked by pre-incubation with the MRA canrenoic acid (1 µM; p < .001). Our results suggest a novel role for MR activation in SCD that may exacerbate SCD pathophysiology and clinical complications.

Safer and targeted use of antipsychotics in youth: an embedded, pragmatic randomized trial.

BACKGROUND: Antipsychotic medications (AP) are inappropriately prescribed to young people. The goal of this pragmatic trial was to test a four-component approach to improved targeting of antipsychotic prescribing to people aged ≥3 and <18 years. METHODS: Clinicians in four health systems were cluster randomized by the number of previous AP orders and service line - specialty mental health and all others. Intervention arm clinicians received a best practice alert and child psychiatrist consultation and feedback. Families received system navigation and expedited access to psychotherapy. Primary outcomes were total days' supply of AP medication and proportion of youth with any AP supply at 6 months. We estimated the log-odds of AP use at 6 months and the relative rate of AP over 6 months. The Safer and Targeted Use of Antipsychotics in Youth (SUAY) trial took place between 3/2018 and 12/2020. RESULTS: The trial enrolled 733 patients. The odds ratio (OR) comparing use at 6 months was 0.75 (95% CI: 0.52, 1.09). The mean number of days using AP was 118.5 for intervention patients and 128.2 for control patients (relative risk [RR] = 0.92; 95% CI: 0.81-1.04). Exploratory heterogeneity of treatment effects (HTE) was not detected in groups defined by age, gender, provider specialty, and insurance type. HTE by race/ethnicity was present: among youth of color, mean days' supply was 103.2 for intervention arm and 131.2 for the control arm (RR 0.79, 95% CI: 0.67-0.93). Among secondary outcomes, only new psychotherapy referrals differed with 44.3% (n = 154) of intervention participants having a new order for psychotherapy compared to 33.5% (n = 129) in the control arm (OR 1.47: 95% CI: 1.01-2.14). CONCLUSIONS: This intervention did not result in less AP use at 6 months or a reduction in the days' supply of AP medication, although psychotherapy orders increased. The intervention may be effective for some subgroups.

Mechanisms underlying the associations between different types of nature exposure and sleep duration: An 18-country analysis.

Whilst green space has been linked to healthier sleep outcomes, the roles of specific types of nature exposure, potential underlying mechanisms, and between-country variations in nature-sleep associations have received little attention. Drawing on cross-sectional survey data from an 18-country sample of adults (N = 16,077) the current study examined: 1) the relative associations between six different types of nature exposure (streetscape greenery, blue view from home, green space within 1 km, coast within 1 km, green space visits, blue space visits) and insufficient sleep (<6 h vs. 7-10 h per day); 2) whether these relationships were mediated by better mental wellbeing and/or physical activity; and 3) the consistency of these pathways among the different countries. After controlling for covariates, neighbourhood nature measures (green space, coast within 1 km) were not significantly associated with insufficient sleep; but nature visible from home (streetscape greenery, blue views) and recreational visits to green and blue spaces were each associated with less insufficient sleep. Significant nature-sleep associations were mediated, to varying degrees, by better mental wellbeing, but not self-reported physical activity. Country-level heterogeneity in the strength of nature-sleep associations was observed. Increasing nature visible from the home may represent a promising strategy for promoting healthier sleep duration at the population level, whilst nature-based interventions encouraging individuals to spend time in local green/blue spaces may be an appropriate target to assist individuals affected by insufficient sleep.

Collision tumor: Multinodular and vacuolating neuronal tumor with isocitrate dehydrogenase-mutant diffuse astrocytoma.

Herein, we report a case of a collision tumor involving a multinodular and vacuolating neuronal tumor (MVNT) and a diffuse astrocytoma. A collision tumor between these two entities has not previously been reported. The patient is a 35-year-old woman who presented with new-onset hearing loss and ringing in her right ear. Magnetic resonance imaging identified a non-enhancing mass involving the gray matter and subcortical white matter of the left middle frontal gyrus. Additionally, tiny clustered nodules were noted along the underlying subcortical ribbon and superficial subcortical white matter of the left superior frontal gyrus. The patient underwent a left frontal craniotomy and complete resection of the mass. Histologic examination of the resected specimen demonstrated a collision tumor consisting of a diffuse astrocytoma (isocitrate dehydrogenase [IDH] mutant, central nervous system [CNS] World Health Organization [WHO] grade 2) and an MVNT, with the latter demonstrating characteristic morphologic and immunohistochemical features.

An ecosystem service perspective on urban nature, physical activity, and health.

Nature underpins human well-being in critical ways, especially in health. Nature provides pollination of nutritious crops, purification of drinking water, protection from floods, and climate security, among other well-studied health benefits. A crucial, yet challenging, research frontier is clarifying how nature promotes physical activity for its many mental and physical health benefits, particularly in densely populated cities with scarce and dwindling access to nature. Here we frame this frontier by conceptually developing a spatial decision-support tool that shows where, how, and for whom urban nature promotes physical activity, to inform urban greening efforts and broader health assessments. We synthesize what is known, present a model framework, and detail the model steps and data needs that can yield generalizable spatial models and an effective tool for assessing the urban nature-physical activity relationship. Current knowledge supports an initial model that can distinguish broad trends and enrich urban planning, spatial policy, and public health decisions. New, iterative research and application will reveal the importance of different types of urban nature, the different subpopulations who will benefit from it, and nature's potential contribution to creating more equitable, green, livable cities with active inhabitants.

Improving Communication with Family Members during a Global Pandemic: Effect on Patient Experience.

OBJECTIVES: Communication with patients and their families/caregivers to facilitate informed decision making is an integral part of patient/family-centered care. Due to the high coronavirus disease 2019 (COVID-19) infection rates and limited personal protective equipment, healthcare systems were forced to restrict patient visitors, limit patient-provider interactions, and implement other changes in treatment protocols that disturbed traditional communications and risked eroding patient/family-centered care and adversely affected patient satisfaction. This article focuses on changes in patient experience in two dedicated COVID-19 units of an academic medical center located in the US South as a result of the enhanced communication process implemented specifically during the COVID-19 pandemic. METHODS: This retrospective quality improvement project used data from Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys, fielded between January 1, 2021 and August 31, 2021, to understand the role of a proactive communication initiative in patient satisfaction. RESULTS: Our results show that HCAHPS scores for hospital unit hospital unit 4 (HSP4) in all categories increased over time, with the greatest improvements seen in the responsiveness of staff and care transition; however, HCAHPS scores for hospital unit HSP3 remained stable, with a small increase in responsiveness of staff. CONCLUSIONS: Our findings suggest that communication is a critical factor in patient satisfaction, demonstrating the efficacy of a swift and innovative initiative to improve communication with family/caregivers, which may have been linked to better patient experiences. Developing communication strategies is crucial for enhancing patient satisfaction.

Associations of nature contact with emotional ill-being and well-being: the role of emotion regulation.

Nature contact has associations with emotional ill-being and well-being. However, the mechanisms underlying these associations are not fully understood. We hypothesised that increased adaptive and decreased maladaptive emotion regulation strategies would be a pathway linking nature contact to ill-being and well-being. Using data from a survey of 600 U.S.-based adults administered online in 2022, we conducted structural equation modelling to test our hypotheses. We found that (1) frequency of nature contact was significantly associated with lesser emotional ill-being and greater emotional well-being, (2) effective emotion regulation was significantly associated with lesser emotional ill-being and greater emotional well-being, and (3) the associations of higher frequency of nature contact with these benefits were partly explained via emotion regulation. Moreover, we found a nonlinear relationship for the associations of duration of nature contact with some outcomes, with a rise in benefits up to certain amounts of time, and a levelling off after these points. These findings support and extend previous work that demonstrates that the associations of nature contact with emotional ill-being and well-being may be partly explained by changes in emotion regulation.

High Medicaid Nursing Homes: Contextual Factors Associated with the Availability of Specialized Resources Required to Care for Obese Residents.

Obesity is an increasingly important concern in the delivery of high-quality nursing home care. Obese nursing home residents require specialized equipment and resources. As high Medicaid nursing homes have limited financial ability, they may lack the necessary resources to address the needs of obese residents. Moreover, there are variations in the availability of obesity-related specialized resources across these facilities. This study aims to investigate the organizational and market factors associated with the availability of obesity-related specialized resources in high-Medicaid nursing homes. Survey and secondary data sources for the study period 2017-2018 were utilized. The survey data were merged with Brown University's Long Term Care Focus (LTCFocus), Nursing Home Compare, and Area Health Resource File datasets. The dependent variable was the composite score of obesity-related specialized resources, ranging from 0-19. An ordinary least square regression with propensity score weights (to adjust for potential survey non-response bias), along with appropriate organizational/market level control variables were used for our analysis. Our results suggest that payer-mix (>Medicare residents) and a higher proportion of obese residents were positively associated with the availability of obesity-related specialized resources. Policymakers should consider implementing incentives, such as increased Medicaid payments, to assist high Medicaid nursing homes in addressing the specific needs of obese residents.

Bottlebrush Networks: A Primer for Advanced Architectures.

Bottlebrush networks (BBNs) are an exciting new class of materials with interesting physical properties derived from their unique architecture. While great strides have been made in our fundamental understanding of bottlebrush polymers and networks, an interdisciplinary approach is necessary for the field to accelerate advancements. This review aims to act as a primer to BBN chemistry and physics for both new and current members of the community. In addition to providing an overview of contemporary BBN synthetic methods, we developed a workflow and desktop application (LengthScale), enabling bottlebrush physics to be more approachable. We conclude by addressing several topical issues and asking a series of pointed questions to stimulate conversation within the community.

Multi-Electron Transfer at H-Terminated p-Si Electrolyte Interfaces: Large Photovoltages under Inversion Conditions.

Photovoltages for hydrogen-terminated p-Si(111) in an acetonitrile electrolyte were quantified with methyl viologen [1,1'-(CH3)2-4,4'-bipyridinium](PF6)2, abbreviated MV2+, and [Ru(bpy)3](PF6)2, where bpy is 2,2'-bipyridine, that respectively undergo two and three one-electron transfer reductions. The reduction potentials, E°, of the two MV2+ reductions occurred at energies within the forbidden bandgap, while the three [Ru(bpy)3]2+ reductions occurred within the continuum of conduction band states. Bandgap illumination resulted in reduction that was more positive than that measured with a degenerately doped n+-Si demonstrative of a photovoltage, Vph, that increased in the order MV2+/+ (260 mV) < MV+/0 (400 mV) < Ru2+/+ (530 mV) ∼ Ru+/0 (540 mV) ∼ Ru0/- (550 mV). Pulsed 532 nm excitation generated electron-hole pairs whose dynamics were nearly constant under depletion conditions and increased markedly as the potential was raised or lowered. A long wavelength absorption feature assigned to conduction band electrons provided additional evidence for the presence of an inversion layer. Collectively, the data reveal that the most optimal photovoltage, as well as the longest electron-hole pair lifetime and the highest surface electron concentration, occurs when E° lies energetically within the unfilled conduction band states where an inversion layer is present. The bell-shaped dependence for electron-hole pair recombination with the surface potential was predicted by the time-honored SRH model, providing a clear indication that this interface provides access to all four bias conditions, i.e., accumulation, flat band, depletion, and inversion. The implications of these findings for photocatalysis applications and solar energy conversion are discussed.

CXCR4 expression is associated with proneural-to-mesenchymal transition in glioblastoma.

Glioblastoma (GBM) is the most common primary intracranial malignant tumor and consists of three molecular subtypes: proneural (PN), mesenchymal (MES) and classical (CL). Transition between PN to MES subtypes (PMT) is the glioma analog of the epithelial-mesenchymal transition (EMT) in carcinomas and is associated with resistance to therapy. CXCR4 signaling increases the expression of MES genes in glioma cell lines and promotes EMT in other cancers. RNA sequencing (RNAseq) data of PN GBMs in The Cancer Genome Atlas (TCGA) and secondary high-grade gliomas (HGGs) from an internal cohort were examined for correlation between CXCR4 expression and survival as well as expression of MES markers. Publicly available single-cell RNA sequencing (scRNAseq) data was analyzed for cell type specific CXCR4 expression. These results were validated in a genetic mouse model of PN GBM. Higher CXCR4 expression was associated with significantly reduced survival and increased expression of MES markers in TCGA and internal cohorts. CXCR4 was expressed in immune and tumor cells based on scRNAseq analysis. Higher CXCR4 expression within tumor cells on scRNAseq was associated with increased MES phenotype, suggesting a cell-autonomous effect. In a genetically engineered mouse model, tumors induced with CXCR4 exhibited a mesenchymal phenotype and shortened survival. These results suggest that CXCR4 signaling promotes PMT and shortens survival in GBM and highlights its inhibition as a potential therapeutic strategy.

A mutant cotton fatty acid desaturase 2-1d allele causes protein mistargeting and altered seed oil composition.

BACKGROUND: Cotton (Gossypium sp.) has been cultivated for centuries for its spinnable fibers, but its seed oil also possesses untapped economic potential if, improvements could be made to its oleic acid content. RESULTS: Previous studies, including those from our laboratory, identified pima accessions containing approximately doubled levels of seed oil oleic acid, compared to standard upland cottonseed oil. Here, the molecular properties of a fatty acid desaturase encoded by a mutant allele identified by genome sequencing in an earlier analysis were analyzed. The mutant sequence is predicted to encode a C-terminally truncated protein lacking nine residues, including a predicted endoplasmic reticulum membrane retrieval motif. We determined that the mutation was caused by a relatively recent movement of a Ty1/copia type retrotransposon that is not found associated with this desaturase gene in other sequenced cotton genomes. The mutant desaturase, along with its repaired isozyme and the wild-type A-subgenome homoeologous protein were expressed in transgenic yeast and stably transformed Arabidopsis plants. All full-length enzymes efficiently converted oleic acid to linoleic acid. The mutant desaturase protein produced only trace amounts of linoleic acid, and only when strongly overexpressed in yeast cells, indicating that the missing C-terminal amino acid residues are not strictly required for enzyme activity, yet are necessary for proper subcellular targeting to the endoplasmic reticulum membrane. CONCLUSION: These results provide the biochemical underpinning that links a genetic lesion present in a limited group of South American pima cotton accessions and their rare seed oil oleic acid traits. Markers developed to the mutant desaturase allele are currently being used in breeding programs designed to introduce this trait into agronomic upland cotton varieties.