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Microbially induced sedimentary structures (MISS) increase the preservation potential of vertebrate and invertebrate ichnofossils. The Colorado River forms a delta in Lake Powell at Hite, Utah, and the deltaic shoreline provides a natural laboratory to examine the development of MISS and their influence on vertebrate track preservation. Two types of MISS were identified: pustular and blister. Pustular MISS occur in proximity to the June 2020 high water line. The pustular morphology is characterized by mm-scale small mounds, or pimple-like shapes. Field emission scanning electron microscopy (FESEM) examination identified preserved filamentous cyanobacteria intertwined with fine silt- and clay-sized sediment and well-preserved freshwater diatoms. Branta canadensis (Canada goose) tracks are well developed and they vary from single tridactyl tracks to trampled horizons. Blister MISS, in contrast to pustular MISS, are present in lower elevations, forming in deeper water, greater than 0.5 m. Blisters are mm- to cm-scale irregular mounds that consist of arching mats that are detached from the underlying sediment creating a pore space. Through time the blister mat mounds are destroyed by fragmentation due to desiccation combined with wind processes. FESEM and energy-dispersive spectroscopy system (EDS) analyses indicate the presence of filamentous cyanobacteria on the exterior and palisade Bacillus-type bacteria are in the interior of the blister arch, and gypsum crystals within the mat arch. Freshwater diatoms are present in both mat types. A single human track and multiple trackways of Canis latrans (coyote) were identified on the blister mats. Weakly impressed Canada goose tracks are present. Tracks cross cutting or modifying the pustular MISS have preserved MISS surface textures except in the heavily trampled areas, whereas tracks linked to the blister mat typically do not have reserved mat texture, and usually contain fragmented mat within the impression. Because of fluctuating lake levels and desiccation, these track types had a limited temporal window where they may be produced when moisture conditions permitted MISS development, about two months. Any vertebrates through the area out of the “track window” were not recorded in sediment and mat modification. Tracks imprinted on pustular MISS in lacustrine environments will have a high preservation potential if there are annual fluctuations in lake levels.

Alternative RNA splicing is an important means of genetic control and transcriptome diversity. However, when alternative splicing events are studied independently, coordinated splicing modulated by common factors is often not recognized. As a result, the molecular mechanisms of how splicing regulators promote or repress splice site recognition in a context-dependent manner are not well understood. The functional coupling between multiple gene regulatory layers suggests that splicing is modulated by additional genetic or epigenetic components. Here, we developed a bioinformatics approach to identify causal modulators of splicing activity based on the variation of gene expression in large RNA sequencing datasets. We applied this approach in a neurological context with hundreds of dorsolateral prefrontal cortex samples. Our model is strengthened with the incorporation of genetic variants to impute gene expression in a Mendelian randomization-based approach. We identified novel modulators of the splicing factor SRSF1, including UIMC1 and the long noncoding RNA CBR3-AS1, that function over dozens of SRSF1 intron retention splicing targets. This strategy can be widely used to identify modulators of RNA-binding proteins involved in tissue-specific alternative splicing.

Alternative splicing (AS) within the β-cell has been proposed as one potential pathway that may exacerbate autoimmunity and unveil novel immunogenic epitopes in type 1 diabetes (T1D). We used a computational strategy to prioritize pathogenic splicing events in human islets treated with interleukin-1β plus interferon-γ as an ex vivo model of T1D and coupled this analysis with a k-mer–based approach to predict RNA-binding proteins involved in AS. In total, 969 AS events were identified in cytokine-treated islets, with a majority (44.8%) involving a skipped exon. ExonImpact identified 129 events predicted to affect protein structure. AS occurred with high frequency in MHC class II–related mRNAs, and targeted quantitative PCR validated reduced inclusion of exon 5 in the MHC class II gene HLA-DMB. Single-molecule RNA fluorescence in situ hybridization confirmed increased HLA-DMB splicing in β-cells from human donors with established T1D and autoantibody positivity. Serine/arginine-rich splicing factor 2 was implicated in 37.2% of potentially pathogenic events, including exon 5 exclusion in HLA-DMB. Together, these data suggest that dynamic control of AS plays a role in the β-cell response to inflammatory signals during T1D evolution.

Aging of hematopoiesis is associated with increased frequency and clonality of hematopoietic stem cells (HSCs), along with functional compromise and myeloid bias, with donor age being a significant variable in survival after HSC transplantation. No clinical methods currently exist to enhance aged HSC function, and little is known regarding how aging affects molecular responses of HSCs to biological stimuli. Exposure of HSCs from young fish, mice, nonhuman primates, and humans to 16,16-dimethyl prostaglandin E2 (dmPGE2) enhances transplantation, but the effect of dmPGE2 on aged HSCs is unknown. Here we show that ex vivo pulse of bone marrow cells from young adult (3 mo) and aged (25 mo) mice with dmPGE2 prior to serial competitive transplantation significantly enhanced long-term repopulation from aged grafts in primary and secondary transplantation (27 % increase in chimerism) to a similar degree as young grafts (21 % increase in chimerism; both p

Rapid diagnosis of concussion is essential to effective treatment and recovery. Concussion biomarker research has focused primarily on blood-based protein assays to detect markers of brain injury. However, transcriptomic data provides insight into the complex biological response to concussion. In this study, we investigated RNA-seq transcriptome analysis of whole blood in a large cohort of concussed and control collegiate athletes who were participating in the Concussion Assessment, Research and Education (CARE) Consortium. In this multicenter prospective cohort study, blood samples were collected from collegiate athletes at preseason (baseline), post-injury (0–6 hours), 24–48 hours postinjury, time of symptom resolution, 7 days after unrestricted return to play and 6 months post-injury. RNA-sequencing was performed on samples from 230 concussed, 130 contact control and 102 non-contact control athletes. Differential gene expression analysis was performed at each timepoint relative to baseline. Deconvolution analysis was used to identify differences in immune cell types. We identified key genes and pathways that were activated in response to concussion. Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points, these pathways appeared to be suppressed relative to contact controls. RNA-seq data also revealed that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion. Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following concussion could inform future treatment strategies.

The RNA-binding protein QKI belongs to the hnRNP K-homology domain protein family, a well-known regulator of pre-mRNA alternative splicing and is associated with several neurodevelopmental disorders. Qki is found highly expressed in developing and adult hearts. By employing the human embryonic stem cell (hESC) to cardiomyocyte differentiation system and generating QKI-deficient hESCs (hESCs-QKIdel) using CRISPR/Cas9 gene editing technology, we analyze the physiological role of QKI in cardiomyocyte differentiation, maturation, and contractile function. hESCs-QKIdel largely maintain normal pluripotency and normal differentiation potential for the generation of early cardiogenic progenitors, but they fail to transition into functional cardiomyocytes. In this work, by using a series of transcriptomic, cell and biochemical analyses, and the Qki-deficient mouse model, we demonstrate that QKI is indispensable to cardiac sarcomerogenesis and cardiac function through its regulation of alternative splicing in genes involved in Z-disc formation and contractile physiology, suggesting that QKI is associated with the pathogenesis of certain forms of cardiomyopathies., RNA binding protein Quaking (QKI) is known for its broad function in pre-mRNA splicing and modification and its association with several neurodevelopmental disorders. Here the authors reveal that QKI-mediated regulation of RNA splicing is indispensable to cardiac development and contractile physiology.

The development of selectively bred high and low alcohol-preferring mice (HAP and LAP, respectively) has allowed for an assessment of the polygenetic risk for pathological alcohol consumption and phenotypes associated with alcohol use disorder (AUD). Accumulating evidence indicates that the dorsal striatum (DS) is a central node in the neurocircuitry underlying addictive processes. Therefore, knowledge of differential gene, protein, and phosphorylated protein expression in the DS of HAP and LAP mice may foster new insights into how aberrant DS functioning may contribute to AUD-related phenotypes. To begin to elucidate these basal differences, a complementary and integrated analysis of DS tissue from alcohol-naïve male and female HAP and LAP mice was performed using RNA sequencing, quantitative proteomics, and phosphoproteomics. These datasets were subjected to a thorough analysis of gene ontology, pathway enrichment, and hub gene assessment. Analyses identified 2,108, 390, and 521 significant differentially expressed genes, proteins, and phosphopeptides, respectively between the two lines. Network analyses revealed an enrichment in the differential expression of genes, proteins, and phosphorylated proteins connected to cellular organization, cytoskeletal protein binding, and pathways involved in synaptic transmission and functioning. These findings suggest that the selective breeding to generate HAP and LAP mice may lead to a rearrangement of synaptic architecture which could alter DS neurotransmission and plasticity differentially between mouse lines. These rich data sets will serve as an excellent resource to inform future studies on how inherited differences in gene, protein, and phosphorylated protein expression contribute to AUD-related phenotypes.

We develop a stylized interbank market environment and use it to evaluate with experimental methods the effects of liquidity requirements. Baseline and liquidity-regulated regimes are analyzed in a simple shock environment, which features a single idiosyncratic shock, and in a compound shock environment, in which the idiosyncratic shock is followed by a randomly occurring second-stage shock. Interbank trading of the illiquid asset follows each shock. In the simple shock environment, we find that liquidity regulations reduce the incidence of bankruptcies, but at a large loss of investment efficiency. In the compound shock environment, liquidity regulations not only impose a loss of investment efficiency but also fail to reduce bankruptcies.

Radiologic techniques remain the main method for early detection for breast cancer and are critical to achieve a favorable outcome from cancer. However, more sensitive detection methods to complement radiologic techniques are needed to enhance early detection and treatment strategies. Using our recently established culturing method that allows propagation of normal and cancerous breast epithelial cells of luminal origin, flow cytometry characterization, and genomic sequencing, we show that cancer cells can be detected in breast milk. Cells derived from milk from the breast with cancer were enriched for CD49f+/EpCAM−, CD44+/CD24−, and CD271+ cancer stem–like cells (CSC). These CSCs carried mutations within the cytoplasmic retention domain of HDAC6, stop/gain insertion in MORF4L1, and deletion mutations within SWI/SNF complex component SMARCC2. CSCs were sensitive to HDAC6 inhibitors, BET bromodomain inhibitors, and EZH2 inhibitors, as mutations in SWI/SNF complex components are known to increase sensitivity to these drugs. Among cells derived from breast milk of additional ten women not known to have breast cancer, two of them contained cells that were enriched for the CSC phenotype and carried mutations in NF1 or KMT2D, which are frequently mutated in breast cancer. Breast milk–derived cells with NF1 mutations also carried copy-number variations in CDKN2C, PTEN, and REL genes. The approach described here may enable rapid cancer cell characterization including driver mutation detection and therapeutic screening for pregnancy/postpartum breast cancers. Furthermore, this method can be developed as a surveillance or early detection tool for women at high risk for developing breast cancer. Significance: These findings describe how a simple method for characterization of cancer cells in pregnancy and postpartum breast cancer can be exploited as a surveillance tool for women at risk of developing breast cancer.

For many good reasons, after natural disasters it is common to work with ‘memory’ as part of a collective catharsis and a globalized humanitarian logic. Long‐term anthropological research on the aftermath of the 2001 earthquake in Gujarat, however, also demonstrates the significance of forgetting in local practice. Immediately after the disaster, people vowed to abandon the sites of their loss, leave the ruins as monuments, and rebuild anew on safer ground. In time, though, life returned to the ruins as the terrible proximity of death receded, as memories and new salience were shaped by acts of reconstruction. The article explores some of the political and social factors that make this form of forgetting possible – or even necessary. Evidence of earlier earthquakes in the same region indicates that such ‘forgetting’ has an established history. Together, ethnographic and archival materials combine to cast doubt over the emphasis on ‘remembering’ as the only ‘memory solution’ to suffering.

BACKGROUND: Low airway surface pH is associated with many airway diseases, impairs antimicrobial host defense, and worsens airway inflammation. Inhaled Optate is designed to safely raise airway surface pH and is well tolerated in humans. Raising intracellular pH partially prevents activation of SARS-CoV-2 in primary normal human airway epithelial (NHAE) cells, decreasing viral replication by several mechanisms. METHODS: We grew primary NHAE cells from healthy subjects, infected them with SARS-CoV-2 (isolate USA-WA1/2020), and used clinical Optate at concentrations used in humans in vivo to determine whether Optate would prevent viral infection and replication. Cells were pretreated with Optate or placebo prior to infection (multiplicity of infection = 1), and viral replication was determined with plaque assay and nucleocapsid (N) protein levels. Healthy human subjects also inhaled Optate as part of a Phase 2a safety trial. RESULTS: Optate almost completely prevented viral replication at each time point between 24 h and 120 h, relative to placebo, on both plaque assay and N protein expression (P < .001). Mechanistically, Optate inhibited expression of major endosomal trafficking genes and raised NHAE intracellular pH. Optate had no effect on NHAE cell viability at any time point. Inhaled Optate was well tolerated in 10 normal subjects, with no change in lung function, vital signs, or oxygenation. CONCLUSIONS: Inhaled Optate may be well suited for a clinical trial in patients with pulmonary SARS-CoV-2 infection. However, it is vitally important for patient safety that formulations designed for inhalation with regard to pH, isotonicity, and osmolality be used. An inhalational treatment that safely prevents SARS-CoV-2 viral replication could be helpful for treating patients with pulmonary SARS-CoV-2 infection.

This paper examines potential interactions between financial stability and the monetary policy strategies and tools considered in the Federal Reserve’s review of monetary policy strategy, tools, and communication practices. Achieving the Federal Reserve’s goals of full employment and price stability promotes financial stability. A key concern, however, is that with a low equilibrium real interest rate, a low policy rate will be necessary, and in turn, these low rates may contribute to an increase in financial system vulnerabilities. Our analysis suggests that there are typically significant macroeconomic and financial stability benefits of using these tools and strategies, but there are plausible situations in which financial vulnerabilities are such that it would be desirable to limit their use. A clear communications strategy can help minimize financial vulnerabilities. Should vulnerabilities arise, they are often best addressed with macroprudential tools.

This article traces the origin of too-big-to-fail policy in modern US banking to the bailout of the $1.2b Bank of the Commonwealth in 1972. It describes this bailout and those of subsequent banks through that of Continental Illinois in 1984. During this period, market concentration due to interstate banking restrictions is a factor in most of the bailouts and systemic risk concerns were raised to justify the bailouts of surprisingly small banks. Finally, most of the bailouts in this period relied on the Federal Deposit Insurance Corporation's use of the Essentiality Doctrine and Federal Reserve lending. A discussion of this doctrine is used to illustrate how legal constraints on regulators may become less constraining over time.

This essay was written in memory of Marvin Goodfriend for a Federal Reserve Bank of Richmond book called Essays in Honor of Marvin Goodfriend: Economist and Central Banker. We discuss his Carnegie-Rochester conference paper titled "The Role of a Regional Bank in a System of Central Banks." In that paper, Marvin argued that the Federal Reserve's decentralized structure allowed for competing ideas about monetary and banking policy to develop with the central bank. In our essay, we describe how Marvin demonstrated this argument during his long career at the Federal Reserve Bank of Richmond. We also describe the institutional developments that led to this competition, including reforms that Chairman William McChesney Martin made to the operation of the Federal Open Market Committee in the 1950s and the introduction of monetary policy ideas such as monetarism and rational expectations by the Reserve Banks.

Description, Tumor tissue collection and processing under physioxia allow highly relevant detection of signaling networks and drug sensitivity., Preclinical studies of primary cancer cells are typically done after tumors are removed from patients or animals at ambient atmospheric oxygen (O2, ~21%). However, O2 concentrations in organs are in the ~3 to 10% range, with most tumors in a hypoxic or 1 to 2% O2 environment in vivo. Although effects of O2 tension on tumor cell characteristics in vitro have been studied, these studies are done only after tumors are first collected and processed in ambient air. Similarly, sensitivity of primary cancer cells to anticancer agents is routinely examined at ambient O2. Here, we demonstrate that tumors collected, processed, and propagated at physiologic O2 compared to ambient air display distinct differences in key signaling networks including LGR5/WNT, YAP, and NRF2/KEAP1, nuclear reactive oxygen species, alternative splicing, and sensitivity to targeted therapies. Therefore, evaluating cancer cells under physioxia could more closely recapitulate their physiopathologic status in the in vivo microenvironment.

Extensive portions of the human genome have unknown function, including those derived from transposable elements. One such element, the DNA transposon Hsmar1, entered the primate lineage approximately 50 million years ago leaving behind terminal inverted repeat (TIR) sequences and a single intact copy of the Hsmar1 transposase, which retains its ancestral TIR-DNA-binding activity, and is fused with a lysine methyltransferase SET domain to constitute the chimeric SETMAR gene. Here, we provide a structural basis for recognition of TIRs by SETMAR and investigate the function of SETMAR through genome-wide approaches. As elucidated in our 2.37 Å crystal structure, SETMAR forms a dimeric complex with each DNA-binding domain bound specifically to TIR-DNA through the formation of 32 hydrogen bonds. We found that SETMAR recognizes primarily TIR sequences (∼5000 sites) within the human genome as assessed by chromatin immunoprecipitation sequencing analysis. In two SETMAR KO cell lines, we identified 163 shared differentially expressed genes and 233 shared alternative splicing events. Among these genes are several pre-mRNA-splicing factors, transcription factors, and genes associated with neuronal function, and one alternatively spliced primate-specific gene, TMEM14B, which has been identified as a marker for neocortex expansion associated with brain evolution. Taken together, our results suggest a model in which SETMAR impacts differential expression and alternative splicing of genes associated with transcription and neuronal function, potentially through both its TIR-specific DNA-binding and lysine methyltransferase activities, consistent with a role for SETMAR in simian primate development.

A sequence of excited states has been established for the first time in the proton-rich nucleus 48Fe (Z=26, N=22). The technique of mirrored (i.e. analogue) one-nucleon knockout reactions was applied, in which the T z = ±2 mirror pair, 48Fe/48Ti were populated via one-neutron/one-proton knockout from the secondary beams 49Fe/49V, respectively. The analogue properties of the reactions were used to help establish the new level scheme of 48Fe. The inclusive and exclusive cross sections were determined for the populated states. Large differences between the cross sections for the two mirrored reactions were observed and have been interpreted in terms of different degrees of binding of the mirror nuclei and in the context of the recent observations of suppression of spectroscopic strength as a function of nuclear binding, for knockout reactions on light solid targets. Mirror energy differences (MED) have been determined between the analogue T = 2 states and compared with the shell model predictions. MED for this mirror pair, due to their location in the shell, are especially sensitive to excitations out of the f 7 / 2 shell, and present a stringent test of the shell-model prescription.

This chapter brings together two major research projects led respectively by Edward Simpson and Katharine Rankin: ‘Roads and the Politics of Thought: Ethnographic Approaches to Infrastructure Development in South Asia’ and ‘Infrastructures of Democracy: State Building as Everyday Practice in Nepal’s Agrarian Districts’. Simpson is an anthropologist, whose UK-based collaborative project worked comparatively across South Asia, but the contribution here is written with India centrally in mind. Rankin is a geographer trained in anthropology and planning, whose project works in partnership with Nepal-and Canada-based researchers and collaborators to explore road development in vernacular terms.

Failures and FDIC losses for community banks during the banking crises of the late 1980s and late 2000s are compared. Despite increases in risky commercial real estate (CRE) lending and more severe economic shocks in the recent crisis, failure rates were lower. We find that other changes in bank characteristics, like higher capital, made community banks more resilient to shocks. In contrast, FDIC losses on failed banks were higher. These are not explained by changes in CRE exposure or economic shocks. We find that an interest-receivable variable is predictive of failures and FDIC losses. Implications for prompt corrective action are discussed.

5 pags., 3 figs., 1 tab. -- Open Access funded by Creative Commons Atribution Licence 4.0, Gamow-Teller β decay is forbidden if the number of nodes in the radial wave functions of the initial and final states is different. This Δn=0 requirement plays a major role in the β decay of heavy neutron-rich nuclei, affecting the nucleosynthesis through the increased half-lives of nuclei on the astrophysical r-process pathway below both Z=50 (for N>82) and Z=82 (for N>126). The level of forbiddenness of the Δn=1ν1g →π0g transition has been investigated from the β decay of the ground state of Hg into the single-proton-hole nucleus Tl in an experiment at the ISOLDE Decay Station. From statistical observational limits on possible γ-ray transitions depopulating the π0g state in Tl, an upper limit of 3.9×10 % was obtained for the probability of this decay, corresponding to log⁡ft>8.8 within a 95% confidence limit. This is the most stringent test of the Δn=0 selection rule to date., Support from the European Union seventh framework through ENSAR contract no. 262010, the Science and Technology Facilities Council through grants ST/P005314/1, ST/L005743/1 and ST/J000051/1 (UK), the MINECO projects FPA2015-64969-P, FPA2015-65035-P and FPA2017-87568-P (Spain), FWO-Vlaanderen (Belgium), GOA/2015/010 (BOF KU Leuven), the Excellence of Science programme (EOS-FWO), and the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office (BriX network P7/12) is acknowledged. ZsP acknowledges support by the ExtreMe Matter Institute EMMI at the GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany. PHR and SMJ ac-knowledge support from the UK Department for Business, Energy and Industrial Strategy via the National Measurement Office.

Throughout history, technology has provided many and significant improvements to the way we live, but the current pace of development now often exceeds the ability for the full potential of any technological innovation to be explored and implemented before further innovations are introduced. This pace of change results both in missed opportunities for a technology in its ability to contribute to effective solutions in addressing issues such as reducing adverse environmental impact or improving the health of society. In considering the nature of technological innovation and development, the associated engineering design processes can themselves be characterized as being associated with a highly complex, iterative problem-solving exercises, involving the integration and synthesis of a wide range of technologies. This in turn requires the design team to manage trade-offs across a range of primary constraints, as for instance embodied energy in manufacturing, energy consumption in use, capital costs and operating and resource recovery costs. Further investigation into the complexity of societal issues and means for achieving a more effective and fuller utilization of both existing resources and technologies is necessary to place sustainability as a priority of the decision making process. To support discussion and provide context, three case studies are presented. The first case study examines a strategic framework adopting metrics aligned with environmental issues used as proxies for evaluating wellbeing and common good. The second case study examines the specific contribution of eHealth to wellbeing and the balance of technological, societal and political issues in determining outcomes. The third case study considers how technology might be embedded as part of the process of obtaining meta-data from within a small rural community to demonstrate the impact of mitigation strategies associated with the reduction of its carbon footprint, and hence on climate change. In doing so, the paper seeks to bring together issues surrounding environmental problems in relation to a technology driven engineering design process while positioning them in the context of social benefits arising from sustainable decision making.

Mass and angle distributions for the ^{52}Cr+^{198}Pt and ^{54}Cr+^{196}Pt reactions (both forming ^{250}No) were measured and subtracted, giving new information on fast quasifission mass evolution, and the first direct determination of the dependence of sticking times on angular momentum. TDHF calculations showed good agreement with average experimental values, but experimental mass distributions unexpectedly extended to symmetric splits while the peak yield remained close to the initial masses. This implies a strong role of fluctuations in mass division early in the collision, giving insights into the transition from fast energy dissipative deep-inelastic collisions to quasifission.

Both agonist studies and loss-of-function models indicate that PPARγ plays an important role in cutaneous biology. Since PPARγ has a high level of basal activity, we hypothesized that epidermal PPARγ would regulate normal homeostatic processes within the epidermis. In this current study, we performed mRNA sequencing and differential expression analysis of epidermal scrapings from knockout mice and wildtype littermates. Pparg-/-epi mice exhibited a 1.5-fold or greater change in the expression of 11.8% of 14,482 identified transcripts. Up-regulated transcripts included those for a large number of cytokines/chemokines and their receptors, as well as genes associated with inflammasome activation and keratinization. Several of the most dramatically up-regulated pro-inflammatory genes in Pparg-/-epi mouse skin included Igfl3, 2610528A11Rik, and Il1f6. RT-PCR was performed from RNA obtained from non-lesional full-thickness skin and verified a marked increase in these transcripts, as well as transcripts for Igflr1, which encodes the receptor for Igfl3, and the 2610528A11Rik receptor (Gpr15). Transcripts for Il4 were detected in Pparg-/-epi mouse skin, but transcripts for Il17 and Il22 were not detected. Down-regulated transcripts included sebaceous gland markers and a number of genes associated with lipid barrier formation. The change in these transcripts correlates with an asebia phenotype, increased transepidermal water loss, alopecia, dandruff, and the appearance of spontaneous inflammatory skin lesions. Histologically, non-lesional skin showed hyperkeratosis, while inflammatory lesions were characterized by dermal inflammation and epidermal acanthosis, spongiosis, and parakeratosis. In conclusion, loss of epidermal Pparg alters a substantial set of genes that are associated with cutaneous inflammation, keratinization, and sebaceous gland function. The data indicate that epidermal PPARγ plays an important role in homeostatic epidermal function, particularly epidermal differentiation, barrier function, sebaceous gland development and function, and inflammatory signaling.