iGATE analysis improves the interpretability of single-cell immune landscape of influenza infection.

Influenza poses a persistent health burden worldwide. To design equitable vaccines effective across all demographics, it is essential to better understand how host factors such as genetic background and aging affect the single-cell immune landscape of influenza infection. Cytometry by time-of-flight (CyTOF) represents a promising technique in this pursuit, but interpreting its large, high-dimensional data remains difficult.

Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk.

Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm.

Discrimination of textures with spatial correlations and multiple gray levels.

Analysis of visual texture is important for many key steps in early vision. We study visual sensitivity to image statistics in three families of textures that include multiple gray levels and correlations in two spatial dimensions. Sensitivities to positive and negative correlations are approximately independent of correlation sign, and signals from different kinds of correlations combine quadratically.

Imaging Mass Cytometry Reveals Predominant Innate Immune Signature and Endothelial-Immune Cell Interaction in Juvenile Myositis Compared to Lupus Skin.

Objective: Cutaneous inflammation can signal disease in juvenile dermatomyositis (DM) and childhood-onset systemic lupus erythematosus (cSLE), but we do not fully understand cellular mechanisms of cutaneous inflammation. In this study, we used imaging mass cytometry to characterize cutaneous inflammatory cell populations and cell-cell interactions in juvenile DM as compared to cSLE.

Methods: We performed imaging mass cytometry analysis on skin biopsy samples from juvenile DM patients (n = 6) and cSLE patients (n = 4).

Primary central nervous system lymphoma: a real-world comparison of therapy access and outcomes by hospital setting.

Background: This study analyzes sociodemographic barriers for primary CNS lymphoma (PCNSL) treatment and outcomes at a public safety-net hospital versus a private tertiary academic institution. We hypothesized that these barriers would lead to access disparities and poorer outcomes in the safety-net population.

Methods: We reviewed records of PCNSL patients from 2007-2020 ( = 95) at a public safety-net hospital ( = 33) and a private academic center ( = 62) staffed by the same university.

Nonlesional lupus skin contributes to inflammatory education of myeloid cells and primes for cutaneous inflammation.

Cutaneous lupus erythematosus (CLE) is a disfiguring and poorly understood condition frequently associated with systemic lupus. Previous studies suggest that nonlesional keratinocytes play a role in disease predisposition, but this has not been investigated in a comprehensive manner or in the context of other cell populations. To investigate CLE immunopathogenesis, normal-appearing skin, lesional skin, and circulating immune cells from lupus patients were analyzed via integrated single-cell RNA sequencing and spatial RNA sequencing.

B Cell Signatures Distinguish Cutaneous Lupus Erythematosus Subtypes and the Presence of Systemic Disease Activity.

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.

Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination.

Metastasis is the primary cause of cancer mortality, and cancer frequently metastasizes to the liver. It is not clear whether liver immune tolerance mechanisms contribute to cancer outcomes. We report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models.

Modulation of Drug Release from Natural Polymer Matrices by Response Surface Methodology: in vitro and in vivo Evaluation.

Purpose: The present work aimed at challenging the efficacy of natural gums, karaya and locust bean gum, as matrix-forming polymers for the formulation of sustained-release tablets of diltiazem, a model drug.

Methods: Central design composite was adopted for the formulation and optimization of tablet formulations. The two gums have been selected as independent variables.

Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis.

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-γ, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton's tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS.

Yeast Intracellular Staining (yICS): Enabling High-Throughput, Quantitative Detection of Intracellular Proteins Flow Cytometry for Pathway Engineering.

The complexities of pathway engineering necessitate screening libraries to discover phenotypes of interest. However, this approach is challenging when desirable phenotypes cannot be directly linked to growth advantages or fluorescence. In these cases, the ability to rapidly quantify intracellular proteins in the pathway of interest is critical to expedite the clonal selection process.

The Repressor Function of the Late Regulator EUO Is Enhanced by the Plasmid-Encoded Protein Pgp4.

A critical step in intracellular infection is the production of infectious progeny through the expression of late genes. This differentiation step involves conversion from a reticulate body (RB), which is the replicating form of the bacterium, into an elementary body (EB), which is the developmental form that spreads the infection to a new host cell. EUO is an important chlamydial transcription factor that controls the expression of late genes, but the mechanisms that regulate EUO are not known.

Factors Affecting the Outcomes of Arthroscopic Capsular Release for Idiopathic Adhesive Capsulitis.

Background: Arthroscopic capsular release has been shown to provide excellent short- and long-term outcomes in patients with idiopathic frozen shoulder. Some surgeons delay surgery in the belief that operating in the early stages of adhesive capsulitis results in a poorer prognosis. However, it is unclear which factors, particularly the stage of the disorder, affect the surgical outcome of this procedure.

Enhancing the Yield and Quality of Influenza Virus-like Particles (VLPs) Produced in Insect Cells by Inhibiting Cytopathic Effects of Matrix Protein M2.

To provide broader protection and eliminate the need for annual update of influenza vaccines, biomolecular engineering of influenza virus-like particles (VLPs) to display more conserved influenza proteins such as the matrix protein M2 has been explored. However, achieving high surface density of full-length M2 in influenza VLPs has been left unrealized. In this study, we show that the ion channel activity of M2 induces significant cytopathic effects in (Sf9) insect cells when expressed using M2-encoding baculovirus.

The female-biased factor VGLL3 drives cutaneous and systemic autoimmunity.

Autoimmune disease is 4 times more common in women than men. This bias is largely unexplained. Female skin is "autoimmunity prone," showing upregulation of many proinflammatory genes, even in healthy women.

Image segmentation driven by elements of form.

While luminance, contrast, orientation, and terminators are well-established features that are extracted in early visual processing and support the parsing of an image into its component regions, the role of more complex features, such as closure and convexity, is less clear. A main barrier in understanding the roles of such features is that manipulating their occurrence typically entails changes in the occurrence of more elementary features as well. To address this problem, we developed a set of synthetic visual textures, constructed by replacing the binary coloring of standard maximum-entropy textures with tokens (tiles) containing curved or angled elements.

Engineering Arabidopsis long-chain acyl-CoA synthetase 9 variants with enhanced enzyme activity.

Long-chain acyl-CoA synthetase (LACS, EC 6.2.1.

Two representations of a high-dimensional perceptual space.

Unlabelled: A perceptual space is a mental workspace of points in a sensory domain that supports similarity and difference judgments and enables further processing such as classification and naming. Perceptual spaces are present across sensory modalities; examples include colors, faces, auditory textures, and odors. Color is perhaps the best-studied perceptual space, but it is atypical in two respects.

Microtubule-associated proteins, Bik1 and Bim1, are required for faithful partitioning of the endogenous 2 micron plasmids in budding yeast.

The 2 μ plasmid of budding yeast shows high mitotic stability similar to that of chromosomes by using its self-encoded systems, namely partitioning and amplification. The partitioning system consists of the plasmid-borne proteins Rep1, Rep2 and a cis-acting locus STB that, along with several host factors, ensures efficient segregation of the plasmid. The plasmids show high stability as they presumably co-segregate with chromosomes through utilization of various host factors.