MESR4 targets bam to mediate intestinal homeostasis and aging in adult flies.

The Drosophila melanogaster (fruit fly) misexpression suppressor of Ras 4 (MESR4) gene encodes a potential transcription factor and plays critical roles in various biological processes, including embryonic development, lipid metabolism, eye-antennal development, and germline stem cell differentiation. However, whether it is involved in modulating intestinal homeostasis remains elusive. In this study, we provide compelling evidence demonstrating that MESR4 is a bona fide regulator in preventing age-onset intestinal leakage and dysbiosis in adult flies.

Drosophila eIF3f1 mediates host immune defense by targeting dTak1.

Eukaryotic translation initiation factors have long been recognized for their critical roles in governing the translation of coding RNAs into peptides/proteins. However, whether they harbor functional activities at the post-translational level remains poorly understood. Here, we demonstrate that eIF3f1 (eukaryotic translation initiation factor 3 subunit f1), which encodes an archetypal deubiquitinase, is essential for the antimicrobial innate immune defense of Drosophila melanogaster.

Toll-mediated airway homeostasis is essential for fly survival upon injection of RasV12-GFP oncogenic cells.

Toll signaling is well known for its pivotal role in the host response against the invasion of external pathogens. Here, we investigate the potential involvement of Toll signaling in the intersection between the host and oncogenic cells. We show that loss of myeloid differentiation factor 88 (Myd88) leads to drastic fly death after the injection of RasV12-GFP oncogenic cells.

Ubiquitin C-Terminal Hydrolase L5 Plays an Essential Role in the Fly Innate Immune Defense against Bacterial Infection.

Background: ubiquitin carboxy-terminal hydrolase L5 (Uch-L5) functions as a critical component of the 26S proteasome to mediate degradation of polyubiquitinated proteins. It was recently shown to modulate tissue/organ development by targeting the Smoothened protein in the hedgehog pathway. However, whether it plays a role in controlling organismal immune response remains largely unknown.

Dietary Supplementation of Aspirin Promotes Defense against Viral Infection.

Aspirin, also known as acetylsalicylic acid, is widely consumed as a pain reliever and an anti-inflammatory as well as anti-platelet agent. Recently, our studies using the animal model of demonstrated that the dietary supplementation of aspirin renovates age-onset intestinal dysfunction and delays organismal aging. Nevertheless, it remains probable that aspirin plays functional roles in other biological activities, for instance antiviral defense reactions.

Single Cell Analysis of the Fate of Injected Oncogenic RasV12 Cells in Adult Wild Type Drosophila.

We have injected dish-cultured oncogenic RasV12 cells into adult male flies and analyzed by single cell transcriptomics their destiny within the host after 11 days. We identified in the preinjection samples and in the 11-day postinjection samples in all 16 clusters of cells, of which 5 disappeared during the experiment in the host. The other cell clusters expanded and expressed genes involved in the regulation of cell cycle, metabolism, and development.

A Toll-dependent Bre1/Rad6-cact feedback loop in controlling host innate immune response.

The Toll signaling pathway was initially identified for its involvement in the control of early embryogenesis. It was later shown to be also part of a major innate immune pathway controlling the expression of anti-microbial peptides in many eukaryotes including humans; cactus, the essential negative regulator of this pathway in flies, was found to be induced in parallel to the Toll-dependent activation process during immune defenses. We were interested in the mechanisms of this dual effect and provide here evidence that upon pathogenic stimuli, dorsal, one of the transcription factors of the fly Toll pathway, can induce the expression of the E3 ligase Bre1.

E3 ligase Cul2 mediates Drosophila early germ cell differentiation through targeting Bam.

Drosophila ovary has been one of the most mature and excellent systems for studying the in vivo regulatory mechanisms of stem cell fate determination. It has been well-known that the bone morphogenetic protein (BMP) signaling released by the niche cells promotes the maintenance of germline stem cells (GSCs) through inhibiting the transcription of the bag-of-marbles (bam) gene, which encodes a key factor for GSC differentiation. However, whether Bam is regulated at the post-translational level remains largely unknown.

Corrigendum: A feedback regulatory loop involving dTrbd/dTak1 in controlling IMD signaling in .

[This corrects the article DOI: 10.3389/fimmu.2022.

A Feedback Regulatory Loop Involving dTrbd/dTak1 in Controlling IMD Signaling in .

Negative regulators of the inflammatory responses are essential for the maintenance of immune homeostasis and organismal fitness. In , the deubiquitinase (Dub) dTrbd selectively restricts the K63-linked ubiquitination modification of dTak1, a pivotal kinase of the IMD signaling pathway, to regulate the IMD innate immune response. However, which domain and how it functions to enable dTrbd's activity remain unexplored.

Aspirin Positively Contributes to Intestinal Homeostasis and Delays Aging through Targeting Imd.

The intestine, a high-turnover tissue, plays a critical role in regulating aging and health in both vertebrates and invertebrates. Maintaining the epithelial barrier function of the intestine by preserving innate immune homeostasis significantly delays aging and prevents mortality. In an effort to explore effective chemicals and materials that can improve intestinal integrity, we performed a nonbiased screen utilizing as an animal model.

Theaflavin-regulated Imd condensates control intestinal homeostasis and aging.

Black tea is the most widely consumed tea drink in the world and has consistently been reported to possess anti-aging benefits. However, whether theaflavins, one type of the characteristic phytochemicals in black tea extracts, are involved in regulating aging and lifespan in consumers remains largely unknown. In this study, we show that theaflavins play a beneficial role in preventing age-onset intestinal leakage and dysbiosis, thus delaying aging in .

LC Domain-Mediated Coalescence Is Essential for Otu Enzymatic Activity to Extend Drosophila Lifespan.

In eukaryotic cells, RNA-binding proteins (RBPs) interact with RNAs to form ribonucleoprotein complexes (RNA granules) that have long been thought to regulate RNA fate or activity. Emerging evidence suggests that some RBPs not only bind RNA but also possess enzymatic activity related to ubiquitin regulation, raising important questions of whether these RBP-formed RNA granules regulate ubiquitin signaling and related biological functions. Here, we show that Drosophila Otu binds RNAs and coalesces to membrane-less biomolecular condensates via its intrinsically disordered low-complexity domain, and coalescence represents a functional state for Otu exerting deubiquitinase activity.

Early and late stage profiles for a chemotaxis model with density-dependent jump probability.

In this paper, we derive a chemotaxis model with degenerate diffusion and density-dependent chemotactic sensitivity, and we provide a more realistic description of cell migration process for its early and late stages. Different from the existing studies focusing on the case of non-degenerate diffusion, this model with degenerate diffusion causes us some essential difficulty on the boundedness estimates and the propagation behavior of its compact support. In the presence of logistic damping, for the early stage before tumour cells spread to the whole domain, we first estimate the expanding speed of tumour region as O(t^β) for 0 < β < 1/2 .

Membrane targeting of inhibitory Smads through palmitoylation controls TGF-β/BMP signaling.

TGF-β/BMP (bone morphogenetic protein) signaling pathways play conserved roles in controlling embryonic development, tissue homeostasis, and stem cell regulation. Inhibitory Smads (I-Smads) have been shown to negatively regulate TGF-β/BMP signaling by primarily targeting the type I receptors for ubiquitination and turnover. However, little is known about how I-Smads access the membrane to execute their functions.

Bam-dependent deubiquitinase complex can disrupt germ-line stem cell maintenance by targeting cyclin A.

germ-line stem cells (GSCs) provide an excellent model to study the regulatory mechanisms of stem cells in vivo. () has been demonstrated to be necessary and sufficient to promote GSC and cystoblast differentiation. Despite extensive investigation of its regulation and genetic functions, the biochemical nature of the Bam protein has been unknown.

Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation.

Many stem cell populations are tightly regulated by their local microenvironment (niche), which comprises distinct types of stromal cells. However, little is known about mechanisms by which niche subgroups coordinately determine the stem cell fate. Here we identify that Yki, the key Hippo pathway component, is essential for escort cell (EC) function in promoting germline differentiation in Drosophila ovary.

Cell-surface localization of Pellino antagonizes Toll-mediated innate immune signalling by controlling MyD88 turnover in Drosophila.

Innate immunity mediated by Toll signalling has been extensively studied, but how Toll signalling is precisely controlled in balancing innate immune responses remains poorly understood. It was reported that the plasma membrane localization of Drosophila MyD88 is necessary for the recruitment of cytosolic adaptor Tube to the cell surface, thus contributing to Toll signalling transduction. Here we demonstrate that Drosophila Pellino functions as a negative regulator in Toll-mediated signalling.

Pedobacter xinjiangensis sp. nov., from desert, Xinjiang.

A Gram-negative, rod-shaped, gliding, aerobic bacterium, designated 12157(T), was isolated from the desert of Xinjiang, China and subjected to a polyphasic taxonomic study. The strain 12157(T) grew optimally at pH 7.0 and 30 degrees Celsius.

Dyadobacter alkalitolerans sp. nov., isolated from desert sand.

A polyphasic taxonomic approach was used to study strain 12116T, which was isolated from desert sand in Xinjiang, China. Cells of the isolate were Gram-negative, non-motile, rod-shaped and aerobic. MK-7 was the predominant respiratory menaquinone.