Metabolic Fitness of NAC1-Deficient Regulatory T Cells in the Tumor Microenvironment Fuels Tumor Growth.

The nucleus accumbens-associated protein-1 (NAC1) has recently emerged as a pivotal factor in oncogenesis by promoting glycolysis. Deletion of NAC1 in regulatory T cells (Tregs) has been shown to enhance FoxP3 stability, a suppressor of glycolysis. This study delves into the intriguing dual role of NAC1, uncovering that Tregs-specific deletion of NAC1 fosters metabolic fitness in Tregs, thereby promoting tumorigenesis.

CYP1B1-AS1 regulates CYP1B1 to promote pathogenesis by inhibiting ROS and host cell death.

(Cb), the causative agent of Q fever, replicates within host macrophages by modulating immune responses through poorly understood mechanisms. Long non-coding RNAs (lncRNAs) are emerging as critical regulators of inflammation, yet their role in Cb pathogenesis remains largely unexplored. Here, we employed a global transcriptomic approach to identify lncRNAs specific to Cb infection in THP-1 derived macrophages, compared to 15 other microbial infections.

Harnessing Bacterial Agents to Modulate the Tumor Microenvironment and Enhance Cancer Immunotherapy.

Cancer immunotherapy has revolutionized cancer treatment by leveraging the immune system to attack tumors. However, its effectiveness is often hindered by the immunosuppressive tumor microenvironment (TME), where a complex interplay of tumor, stromal, and immune cells undermines antitumor responses and allows tumors to evade immune detection. This review explores innovative strategies to modify the TME and enhance immunotherapy outcomes, focusing on the therapeutic potential of engineered bacteria.

NOVAsort for error-free droplet microfluidics.

High-throughput screening techniques are pivotal to unlocking the mysteries of biology. Yet, the promise of droplet microfluidics in enabling single-cell resolution, ultra-high-throughput screening remains largely unfulfilled. Droplet sorting errors caused by polydisperse droplet sizes that are often inevitable in multi-step assays have severely limited the effectiveness and utility of this technique, especially when screening large libraries.

μREACT: A microfluidic system for rapid evaluation of trans-kingdom interactions.

Trans-kingdom interactions between cells play pivotal roles in shaping intricate ecological and biological networks. However, our grasp of these interactions remains incomplete. Specifically, the vast phylogenetic spectrum of microorganisms capable of interacting with a given host cell type remains obscure, primarily due to the absence of efficient, high-throughput, single-cell resolution systems that can rapidly decipher these interactions.

Brucella-driven host N-glycome remodeling controls infection.

Many powerful methods have been employed to elucidate the global transcriptomic, proteomic, or metabolic responses to pathogen-infected host cells. However, the host glycome responses to bacterial infection remain largely unexplored, and hence, our understanding of the molecular mechanisms by which bacterial pathogens manipulate the host glycome to favor infection remains incomplete. Here, we address this gap by performing a systematic analysis of the host glycome during infection by the bacterial pathogen Brucella spp.

NLRC5/MHC class I transactivator: A key target for immune escape by SARS-CoV-2.

Antigen presentation to CD8+ T cells by MHC class I molecules is essential for host defense against viral infections. Various mechanisms have evolved in multiple viruses to escape immune surveillance and defense to support viral proliferation in host cells. Through in vitro SARS-CoV-2 infection studies and analysis of COVID-19 patient samples, we found that SARS-CoV-2 suppresses the induction of the MHC class I pathway by inhibiting the expression and function of NLRC5, a major transcriptional regulator of MHC class I genes.

Targeted demethylation and activation of augment cancer immunogenicity through MHC class I.

Impaired expression of MHC (major histocompatibility complex) class I in cancers constitutes a major mechanism of immune evasion. It has been well documented that the low level of MHC class I is associated with poor prognosis and resistance to checkpoint blockade therapies. However, there is lmited approaches to specifically induce MHC class I to date.

Control of CD4 T cells to restrain inflammatory diseases via eukaryotic elongation factor 2 kinase.

CD4 T cells, particularly IL-17-secreting helper CD4 T cells, play a central role in the inflammatory processes underlying autoimmune disorders. Eukaryotic Elongation Factor 2 Kinase (eEF2K) is pivotal in CD8 T cells and has important implications in vascular dysfunction and inflammation-related diseases such as hypertension. However, its specific immunological role in CD4 T cell activities and related inflammatory diseases remains elusive.

Enzyme-functionalized alginate microparticles enable anaerobic culture under ambient oxygen.

Methods for culturing oxygen-sensitive cells and organisms under anaerobic conditions are vital to biotechnology research. Here, we report a biomaterial-based platform for anaerobic culture that consists of glucose oxidase (GOX) functionalized alginate microparticles (ALG-GOX), which are designed to deplete dissolved [O ] through enzymatic activity. ALG-GOX microparticles were synthesized via a water-in-oil emulsion and had a size of 132.

NAC1 confines virus-specific memory formation of CD4 T cells through the ROCK1-mediated pathway.

Nucleus accumbens-associated protein 1 (NAC1), a transcriptional cofactor, has been found to play important roles in regulating regulatory T cells, CD8 T cells, and antitumor immunity, but little is known about its effects on T-cell memory. In this study, we found that NAC1 expression restricts memory formation of CD4 T cells during viral infection. Analysis of CD4 T cells from wild-type (WT) and NAC1-deficient ( ) mice showed that NAC1 is essential for T-cell metabolism, including glycolysis and oxidative phosphorylation, and supports CD4 T-cell survival in vitro.

Engineering live attenuated vaccines: Old dogs learning new tricks.

Autoimmune diseases such as rheumatoid arthritis and type 1 diabetes are increasingly common global problems. Concerns about increases in the prevalence of such diseases and the limited efficacy of conventional treatment regimens necessitates new therapies to address these challenges. Autoimmune disease severity and dysbiosis are interconnected.

Neural network based integration of assays to assess pathogenic potential.

Limited data significantly hinders our capability of biothreat assessment of novel bacterial strains. Integration of data from additional sources that can provide context about the strain can address this challenge. Datasets from different sources, however, are generated with a specific objective and which makes integration challenging.

Soil Properties Correlate with Microbial Community Structure in Qatari Arid Soils.

This is the first detailed characterization of the microbiota and chemistry of different arid habitats from the State of Qatar. Analysis of bacterial 16S rRNA gene sequences showed that in aggregate, the dominant microbial phyla were (32.3%), (24.

A metabolically engineered bacterium controls autoimmunity and inflammation by remodeling the pro-inflammatory microenvironment.

Immunotherapy has led to impressive advances in the treatment of autoimmune and pro-inflammatory disorders; yet, its clinical outcomes remain limited by a variety of factors including the pro-inflammatory microenvironment (IME). Discovering effective immunomodulatory agents, and the mechanisms by which they control disease, will lead to innovative strategies for enhancing the effectiveness of current immunotherapeutic approaches. We have metabolically engineered an attenuated bacterial strain (i.

An automated system for interrogating the evolution of microbial endosymbiosis.

Inter-kingdom endosymbiotic interactions between bacteria and eukaryotic cells are critical to human health and disease. However, the molecular mechanisms that drive the emergence of endosymbiosis remain obscure. Here, we describe the development of a microfluidic system, named SEER (S̲ystem for the E̲volution of E̲ndosymbiotic R̲elationships), that automates the evolutionary selection of bacteria with enhanced intracellular survival and persistence within host cells, hallmarks of endosymbiosis.

Microfluidic Dielectrophoretic Method Enables On-Demand Spatial Arrangement of Bacteria-Encapsulated Agarose Gel Microparticles.

Microbial interactions within a natural or engineered consortium of microbes play an important role in the functions of the consortium. Better understanding these interactions is also important for engineering microbial consortia for specific applications. As such, tools that can enable investigating microbial interactions are highly valuable.

Breaking down antibiotic resistance in methicillin-resistant : Combining antimicrobial photodynamic and antibiotic treatments.

The widespread use of antibiotics drives the evolution of antimicrobial-resistant bacteria (ARB), threatening patients and healthcare professionals. Therefore, the development of novel strategies to combat resistance is recognized as a global healthcare priority. The two methods to combat ARB are development of new antibiotics or reduction in existing resistances.

FIDELITY: A quality control system for droplet microfluidics.

Droplet microfluidic systems have been widely deployed to interrogate biological and chemical systems. The major limitations of these systems are the relatively high error rates from critical droplet manipulation functions. To address these limitations, we describe the development of FIDELITY (Flotation and Interdigitated electrode forces on Droplets to Enable Lasting system IntegriTY), a highly sensitive and accurate size-based droplet bandpass filter that leverages the natural buoyancy of aqueous droplets and highly localized dielectrophoretic force generated by interdigitated electrode arrays.

NAC1 modulates autoimmunity by suppressing regulatory T cell-mediated tolerance.

We report here that nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the Broad-complex, Tramtrack, Bric-a-brac/poxvirus and zinc finger (BTB/POZ) gene family, is a negative regulator of FoxP3 in regulatory T cells (T) and a critical determinant of immune tolerance. Phenotypically, NAC1 mice showed substantial tolerance to the induction of autoimmunity and generated a larger amount of CD4 T that exhibit a higher metabolic profile and immune-suppressive activity, increased acetylation and expression of FoxP3, and slower turnover of this transcription factor. Treatment of T with the proinflammatory cytokines interleukin-1β or tumor necrosis factor-α induced a robust up-regulation of NAC1 but evident down-regulation of FoxP3 as well as the acetylated FoxP3.

Elongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8 T cells.

eEF-2K has important roles in stress responses and cellular metabolism. We report here a previously unappreciated but critical role of eEF-2K in regulating the fate and cytocidal activity of CD8 T cells. CD8 T cells from eEF-2K KO mice were more proliferative but had lower survival than their wild-type counterparts after their activation, followed by occurrence of premature senescence and exhaustion.