Search for: All records

Abstract As the circadian clock regulates fundamental biological processes, disrupted clocks are often observed in patients and diseased tissues. Determining the circadian time of the patient or the tissue of focus is essential in circadian medicine and research. Here we present tauFisher, a computational pipeline that accurately predicts circadian time from a single transcriptomic sample by finding correlations between rhythmic genes within the sample. We demonstrate tauFisher’s performance in adding timestamps to both bulk and single-cell transcriptomic samples collected from multiple tissue types and experimental settings. Application of tauFisher at a cell-type level in a single-cell RNAseq dataset collected from mouse dermal skin implies that greater circadian phase heterogeneity may explain the dampened rhythm of collective core clock gene expression in dermal immune cells compared to dermal fibroblasts. Given its robustness and generalizability across assay platforms, experimental setups, and tissue types, as well as its potential application in single-cell RNAseq data analysis, tauFisher is a promising tool that facilitates circadian medicine and research. 

The novel bench-stableN-quaternized keteneN,O-acetal, C₁₆H₁₉N₂O⁺·CF₃O₃S⁻, was synthesized and its structure determined. The title compound is a rare example of a pyridinium ketene hemiaminal for which a crystal structure has been determined, joining the 2-chloro-1-(1-ethyoxyethenyl)pyridin-1-ium trifluoromethanesulfonate salt from which it was synthesized. The cationic species of the title compound can be defined by three individually planar fragments assembling into a non-coplanar cation. The phenyl substituent extending from the amino nitrogen atom and the ethyoxyvinyl substituent extending from the pyridine N atom are oriented on the same side of the molecule and maintain the closest coplanar relationship of the three fragments. Supramolecular interactions are dominated by C—H...O interactions from the cation to the SO₃side of the trifluoromethanesulfonate anion, forming a two-dimensional substructure. 

Comprehending cutaneous lupus Cutaneous lupus erythematosus (CLE) is a disfiguring skin condition that affects most patients with systemic lupus erythematosus (SLE) and can be resistant to treatment even when systemic disease is responsive. Billi et al. analyzed CLE lesions and paired normal-appearing skin biopsies, as well as circulating immune cell subsets, to better understand changes in the skin that drive CLE pathogenesis. Using single-cell RNA sequencing and spatial RNA sequencing, they identified a type I IFN–rich signature in prelesional, normal-looking skin that influenced transcription and cell-cell communication for all major skin cell types. CD16 + dendritic cells, which are associated with SLE, were also shaped by the type I IFN environment, and cells in these sites shifted toward a proinflammatory phenotype. Together, these data provide insights into transcriptional changes in the skin that contribute to CLE pathogenesis. 

Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease characterized by a diverse cadre of clinical presentations. CLE commonly occurs in patients with systemic lupus erythematosus (SLE), and CLE can also develop in the absence of systemic disease. Although CLE is a complex and heterogeneous disease, several studies have identified common signaling pathways, including those of type I interferons (IFNs), that play a key role in driving cutaneous inflammation across all CLE subsets. However, discriminating factors that drive different phenotypes of skin lesions remain to be determined. Thus, we sought to understand the skin-associated cellular and transcriptional differences in CLE subsets and how the different types of cutaneous inflammation relate to the presence of systemic lupus disease. In this study, we utilized two distinct cohorts comprising a total of 150 CLE lesional biopsies to compare discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus (ACLE) in patients with and without associated SLE. Using an unbiased approach, we demonstrated a CLE subtype-dependent gradient of B cell enrichment in the skin, with DLE lesions harboring a more dominant skin B cell transcriptional signature and enrichment of B cells on immunostaining compared to ACLE and SCLE. Additionally, we observed a significant increase in B cell signatures in the lesional skin from patients with isolated CLE compared with similar lesions from patients with systemic lupus. This trend was driven primarily by differences in the DLE subgroup. Our work thus shows that skin-associated B cell responses distinguish CLE subtypes in patients with and without associated SLE, suggesting that B cell function in skin may be an important link between cutaneous lupus and systemic disease activity. 

The building industry has a major impact on the US economy and accounts for: $1 trillion in annual spending; 40% of the nation’s primary energy use; and 9 million jobs. Despite its massive impact, the industry has been criticized for poor productivity compared with other industries and billions of dollars in annual waste because of poor interoperability. Furthermore, the industry has been approaching a “labor cliff”: there are not enough new individuals entering the industry to offset the vacancies left by an aging, retiring workforce. To remain effective, this critical industry will need to do better with less. In order to prepare civil engineering students for careers in this industry, educators have aimed to replicate the processes associated with real-world projects through design/build educational activities like the Department of Energy’s (DOE) Solar Decathlon, Sacramento Municipal Utility District’s (SMUD) Tiny House Competition, and DOE’s Challenge Home Competition. These learning experiences help situate civil engineering concepts in an authentic learning environment. Unfortunately, not all universities have the financial resources necessary to fund this type of hands-on project. Technology has the potential to mitigate some of these inequities. Thus, the multi-faceted objective of this project is to: develop mixed reality (MR) technology aimed at sufficiently replicating physical design and construction learning environments to enable access to students at institutions without sufficient resources; and assess the impact of a MR-facilitated cyberlearning environment on promoting cognitive-, affective-, and skill-based learning that occurs during traditional (in-persona) design and construction activities. This research will explore a fundamental question: Can MR technology enable educators to simulate physical design and construction activities at low costs to enable students at all institutions to gain exposure to these types of hands-on learning environments? In order to address this question, we employ an iterative development approach according to Human Centered Design principles to support learning according to the Carnegie Foundation’s Three Apprenticeships Model (i.e., learning related to “Head”, “Hand”, and “Heart”). In order to achieve these aims, the research team uses MR technology (i.e., a Microsoft HoloLens®) to understand the extent to which this mode of education allows students to demonstrate knowledge similar to that which is gained through physical design and construction learning environments. This paper will presents highlights from the first year of this project. 

While the building industry has a major impact on the US economy, it is one that is often criticized for poor productivity and waste resulted from interoperability. Additionally, the impending labor shortage requires that this is industry becomes one that can do more with less in order to remain effective. As part of preparing civil engineering students for careers in this industry and to design/build infrastructure that is responsive to changing societal needs, educators have aimed to replicate the processes associated with real-world projects through design/build educational activities (like the Department of Energy’s (DOE) Solar Decathlon, Sacramento Municipal Utility District’s (SMUD) Tiny House Competition, and DOE’s Challenge Home Competition) as part of helping students situate civil engineering concepts in an authentic learning environment. Unfortunately, not all universities have the financial resources necessary to fund these types of hands-on projects. Thankfully, technology has the potential to mitigate some of these inequities. This paper presents an update on a three-year NSF-funded project that aims to: develop mixed reality (MR) technology aimed at sufficiently replicating physical design and construction learning environments to enable access to students at institutions without sufficient resources; and assess the impact of a MR-facilitated cyberlearning environment on cognitive-, affective-, and skill-based learning that occurs during traditional (in-person) design and construction activities. Human Centered Design principles and the tenets of the Carnegie Foundation’s Three Apprenticeships Model (i.e., learning related to “Head”, “Hand”, and “Heart”) inform the design, development, and assessments in this project. Highlights from the first year and future plans will be discussed. 

Makerspaces have the potential to revolutionize engineering education by providing a platform for students to nurture their tacit knowledge. This unique space allows for students to work with advanced prototyping equipment, develop specialized skills and create community. Although makerspaces could become an important dimension of engineering education, it is unclear whether these spaces are inclusive for all engineering students, especially those from underrepresented groups. Specifically, this study aims to understand the experiences of diverse female engineering students in makerspaces. For this study, we analyzed interview transcripts of ten women from multiple U.S. universities housing engineering academic makerspaces—those anchored to and supported by the engineering department/school specifically—and found common themes across their stories. These themes include the perception of gender bias, as well as an intimidating, hostile, and non-inclusive environment. Although the results of this study demonstrate gender bias and marginalization occur in makerspaces, female engineering students still find value in the makerspace through access to resources, opportunities to learn, increased confidence, and female makerspace staff. 

The circadian clock coordinates a variety of immune responses with signals from the external environment to promote survival. We investigated the potential reciprocal relationship between the circadian clock and skin inflammation. We treated mice topically with the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ) to activate IFN-sensitive gene (ISG) pathways and induce psoriasiform inflammation. IMQ transiently altered core clock gene expression, an effect mirrored in human patient psoriatic lesions. In mouse skin 1 d after IMQ treatment, ISGs, including the key ISG transcription factor IFN regulatory factor 7 ( Irf7), were more highly induced after treatment during the day than the night. Nuclear localization of phosphorylated-IRF7 was most prominently time-of-day dependent in epidermal leukocytes, suggesting that these cell types play an important role in the diurnal ISG response to IMQ. Mice lacking Bmal1 systemically had exacerbated and arrhythmic ISG /Irf7 expression after IMQ. Furthermore, daytime-restricted feeding, which affects the phase of the skin circadian clock, reverses the diurnal rhythm of IMQ-induced ISG expression in the skin. These results suggest a role for the circadian clock, driven by BMAL1, as a negative regulator of the ISG response, and highlight the finding that feeding time can modulate the skin immune response. Since the IFN response is essential for the antiviral and antitumor effects of TLR activation, these findings are consistent with the time-of-day–dependent variability in the ability to fight microbial pathogens and tumor initiation and offer support for the use of chronotherapy for their treatment.