Thymic stromal lymphopoietin contributes to endometriotic lesion proliferation and disease-associated inflammation.

Endometriosis is a chronic disorder in which endometrial-like tissue presents outside the uterus. Patients with endometriosis have been shown to exhibit aberrant immune responses within the lesion microenvironment and in circulation which contribute to the development of endometriosis. Thymic stromal lymphopoietin (TSLP) is an alarmin involved in cell proliferation and the induction of T helper 2 (Th2) inflammation in various diseases, such as asthma, atopic dermatitis, and pancreatic and breast cancer.

RTF1 mediates epigenetic control of Th17 cell differentiation via H2B monoubiquitination.

A gene encoding the transcription factor RTF1 has been associated with an increased risk of ulcerative colitis (UC). In this study, we investigated its function in modulating T cells expressing interleukin-17A (Th17 cells), a cardinal cell type promoting intestinal inflammation. Our results indicate that Rtf1 deficiency disrupts the differentiation of Th17 cells, while leaving regulatory T cells (Treg) unaffected.

SYK negatively regulates ITAM-mediated human NK cell signaling and CD19-CAR NK cell efficacy.

Natural killer (NK) cells express activating receptors that signal through ITAM (immunoreceptor tyrosine-based activation motif)-bearing adapter proteins. The phosphorylation of each ITAM creates binding sites for SYK and ZAP70 protein tyrosine kinases to propagate downstream signaling including the induction of Ca2+ influx. While all immature and mature human NK cells coexpress SYK and ZAP70, clonally driven memory or adaptive NK cells can methylate SYK genes, and signaling is mediated exclusively using ZAP70.

The aryl hydrocarbon receptor controls IFN-γ-induced immune checkpoints PD-L1 and IDO via the JAK/STAT pathway in lung adenocarcinoma.

While immunotherapy has shown some efficacy in lung adenocarcinoma (LUAD) patients, many respond only partially or not at all. One limitation in improving outcomes is the lack of a complete understanding of immune checkpoint regulation. Here, we investigated a possible link between an environmental chemical receptor implicated in lung cancer and immune regulation, the AhR, a known but counterintuitive mediator of immunosuppression (interferon (IFN)-γ), and regulation of two immune checkpoints (PD-L1 and IDO).

T-bet-expressing B cells promote atherosclerosis in apolipoprotein E-deficient mice.

The humoral immune system influences the development of atherosclerosis, but the contributions of specific memory B cell subsets and IgG isotypes are poorly understood. We assessed the relationship between atherosclerosis and age-associated B cells (ABCs), a T-bet-expressing memory B cell subset that is enriched for IgG2c production and implicated in humoral autoimmunity. We found increased numbers of splenic CD11c+ ABCs in 6-mo-old, chow-fed Apoe-/- mice versus C57BL/6 control mice, which were exacerbated by high-fat diet.

UFL1 promotes survival and function of virtual memory CD8 T cells.

In naïve mice, a fraction of CD8 T cells displaying high affinity for self-MHC peptide complexes develop into virtual memory T (TVM) cells. Due to self-reactivity, TVM cells are exposed to persistent antigenic stimulation, a condition known to induce T cell exhaustion. However, TVM cells do not exhibit characteristics similar to exhausted CD8 T (TEX) cells.

Quantitative detection of the HVEM-BTLA checkpoint receptor cis-complex in human lymphocytes.

The herpesvirus entry mediator (HVEM) (TNFRSF14) engagement of the checkpoint inhibitory receptor B and T lymphocyte attenuator (BTLA) limits immune responses of T and B lymphocytes. HVEM and BTLA form signaling complexes in trans and when coexpressed, complexes in cis, creating a unique immune checkpoint. The function of the HVEM-BTLA cis-complex is not well understood primarily due to a lack of reagents that specifically measure the HVEM-BTLA cis-complex.

Gut IgA-antibody secreting cells segregate into four Blimp1+ subsets based on differential expression of IgA and Ki-67 and are retained following prolonged αCD20 B cell depletion in mice.

B cell depletion is an efficacious therapy for multiple sclerosis, but its long-term safety profile in the gastrointestinal tract has not been specifically studied. This is of importance because the gut is the largest reservoir of IgA in the body, which maintains gut homeostasis in part by regulating the composition of the gut microbiota. This was addressed by development of a prolonged B cell depletion model using human CD20 transgenic mice and B cell depletion with the anti-human CD20 antibodies rituximab, a humanized mouse monoclonal, and 2H7, the mouse precursor to ocrelizumab.

Comparison of human macrophages derived from peripheral blood and bone marrow.

Macrophage differentiation, phenotype, and function have been assessed extensively in vitro by predominantly deriving human macrophages from peripheral blood. It is accepted that there are differences between macrophages isolated from different human tissues; however, the importance of anatomical source for in vitro differentiation and characterization is less clear. Here, phenotype and function were evaluated between human macrophages derived from bone marrow or peripheral blood.

In vivo antibody labeling route and fluorophore dictate labeling efficiency, sensitivity, and longevity.

Leukocytes migrate through the blood and extravasate into organs to surveil the host for infection or cancer. Recently, we demonstrated that intravenous (IV) anti-CD45.2 antibody labeling allowed for precise tracking of leukocyte migration.

Depletion of eosinophils during sensitization but not challenge phase in mice blocks the development of food allergy early in life.

Food allergy can be life threatening and often develops early in life, especially in infants and children with atopic dermatitis. Food allergy is induced in neonatal mice with skin barrier mutations (Flaky Tail, FT+/- mice with filaggrin and mattrin gene mutations) by epicutaneous sensitization with co-exposures to the food allergen peanut extract (PNE), the environmental allergen Alternaria alternata (Alt), and detergent (4% SDS); oral PNE-challenge induces anaphylaxis. Sensitization in these neonates also induces eosinophil infiltration into the skin and elevates skin expression of eotaxins (CCL11 and CCL24).

Absence of c-Maf and IL-10 enables type I IFN enhancement of innate responses to LPS in alveolar macrophages.

Alveolar macrophages (AMs) are lung-resident myeloid cells and airway sentinels for inhaled pathogens and environmental particles. While AMs can be highly inflammatory in response to respiratory viruses, they do not mount proinflammatory responses to all airborne pathogens. For example, we previously showed that AMs fail to mount a robust proinflammatory response to Mycobacterium tuberculosis.

Differential shaping of T cell responses elicited by heterologous ChAd68/self-amplifying mRNA SIV vaccine in macaques in combination with αCTLA4, αPD-1, or FLT3R agonist.

While therapeutic vaccines are a promising strategy for inducing human immunodeficiency virus (HIV) control, HIV vaccines tested to date have offered limited benefit to people living with HIV. The barriers to success may include the use of vaccine platforms and/or immunogens that drive weak or suboptimal immune responses, immune escape and/or immune dysfunction associated with chronic infection despite effective antiretroviral therapy. Combining vaccines with immune modulators in a safe manner may address some of the challenges and thus increase the efficacy of therapeutic HIV vaccines.

General and individualized changes in T cell immunity during aging.

Functional alterations with age are observed in all human systems, but the aging of the adaptive immune system displays both general changes affecting all individuals, and idiosyncratic changes that are unique to individuals. In the T cell compartment, general aging manifests in three ways: (1) the reduction of naïve T cells, (2) the accumulation of differentiated memory T cells, and (3) a reduced overall T cell receptor (TCR) repertoire. Idiosyncratic impacts of aging, such as changes in the TCR repertoires of altered memory and naïve T cells are shaped by each person's life exposures.

Is There Polyamorphism in Amorphous Indomethacin? Investigating the Physicochemical Properties of Amorphous Indomethacin with Different Thermal History.

Polyamorphism in organic molecules is a poorly understood and controversial phenomenon related to amorphous materials. Although very few studies, including our own, have demonstrated the existence of polyamorphism in drug molecules, this solid-state phenomenon is still very elusive and the investigation of its occurrence in other drugs is fundamental to understand its formation. Indomethacin (IND) has been recently discussed in the literature as a potential drug exhibiting polyamorphism.

Single-cell eQTL mapping in yeast reveals a tradeoff between growth and reproduction.

Expression quantitative trait loci (eQTLs) provide a key bridge between noncoding DNA sequence variants and organismal traits. The effects of eQTLs can differ among tissues, cell types, and cellular states, but these differences are obscured by gene expression measurements in bulk populations. We developed a one-pot approach to map eQTLs in by single-cell RNA sequencing (scRNA-seq) and applied it to over 100,000 single cells from three crosses.

Stable colonization of the model kissing bug Rhodnius prolixus by Trypanosoma cruzi Y strain.

Trypanosoma cruzi is a single-celled eukaryotic parasite responsible for Chagas disease, a major cause of morbidity and mortality in Central and South America. While the host-pathogen interactions of T. cruzi have been extensively studied in vertebrate models, investigations into its interactions within its insect host remain limited.

Deciphering the structural consequences of R83 and R152 methylation on DNA polymerase β using molecular modeling.

DNA polymerase β, a member of the X-family of DNA polymerases, undergoes complex regulations both in vitro and in vivo through various posttranslational modifications, including phosphorylation and methylation. The impact of these modifications varies depending on the specific amino acid undergoing alterations. In vitro, methylation of DNA polymerase β with the enzyme protein arginine methyltransferase 6 (PRMT6) at R83 and R152 enhances polymerase activity by improving DNA binding and processivity.

The impacts of product characteristics and regulatory environment on smokers' preferences for tobacco and alcohol: Evidence from a volumetric choice experiment.

Objective: Concurrent use of alcohol and cigarettes is well-documented in the literature. However, it is unclear how e-cigarette regulations in a growing number of localities impact the use of tobacco and alcohol in the US. This study aims to evaluate the impacts of excise taxes, tobacco use restrictions in restaurants/bars, and availability of alcohol flavor in e-cigarettes on tobacco consumption, and their cross impacts on alcohol consumption.

Microfluidic isolation and release of live disseminated breast tumor cells in bone marrow.

Breast cancer represents a significant therapeutic challenge due to its aggressive nature and resistance to treatment. A major cause of treatment failure in breast cancer is the presence of rare, low-proliferative disseminated tumor cells (DTCs) in distant organs including the bone marrow. This study introduced a microfluidic-based approach to improve the immunodetection and isolation of these rare DTCs for downstream analysis, with an emphasis on optimizing immunocapture, release, and enrichment methods of live DTCs as compared to the standard approach for blood-borne circulating tumor cells (CTCs).

Association between PM2.5 and skin redness features in Taiwan.

Air pollution, particularly fine particulate matter (PM2.5), has been associated with various health issues, but its effects on skin health, specifically skin redness, remain underexplored. This study aims to examine the relationship between PM2.

Inter-nesting area use, migratory routes, and foraging grounds for hawksbill turtles (Eretmochelys imbricata) in the Western Caribbean.

The hawksbill turtle, Eretmochelys imbricata, has been at risk of extinction for more than 40 years and remains critically endangered. While nesting beach protection is important for hatchling production, identifying inter-nesting, migratory, and foraging habitats is crucial for mitigating threats to population recovery. We report the use of satellite telemetry to monitor movements of 15 hawksbill turtles in the Western Caribbean.

Comparison between Go-GutDx, a novel diagnostic stool test kit with potential impact in low-income countries, and BioFire test.

Introduction: Infectious diarrheal diseases are one of the leading causes of worldwide morbidity and mortality. The incidence of diarrhea is higher in Low-Middle-Income Countries (LMIC), where more than 90% of deaths from diarrheal diseases occur. Diagnostic tests for infectious diarrhea are not readily available in Low-Middle-Income Countries.

Effects of mental fatigue on isometric mid-thigh pull performance and muscle activities.

This study investigated the effects of mental fatigue on rate of force development (RFD) and peak force during an isometric mid-thigh pull (IMTP), as well as its impact on muscle activation measured by electromyography (EMG) median frequency. Sixteen healthy, resistance-trained males completed two sessions: a control condition and a mentally fatigued state induced by a 30-minute modified Stroop task. IMTP performance and muscle activation were assessed before and after the mental fatigue task.

Extant life detection using label-free video microscopy in analog aquatic environments.

The ability of microbial active motion, morphology, and optical properties to serve as biosignatures was investigated by in situ video microscopy in a wide range of extreme field sites where such imaging had not been performed previously. These sites allowed for sampling seawater, sea ice brines, cryopeg brines, hypersaline pools and seeps, hyperalkaline springs, and glaciovolcanic cave ice. In all samples except the cryopeg brine, active motion was observed without any sample treatment.