Systematic discovery and engineering of synthetic immune receptors in plants.

Plants deploy a diverse array of pattern recognition receptors (PRRs), which perceive microbe-associated molecular patterns to activate immune responses. Leucine-rich repeat receptor-like kinase subgroup XII (LRR-RLK-XII) represents one of the largest PRR families owing to lineage-specific diversification. Through bioinformatics and synthetic biology approaches, we characterized LRR-RLK-XIIs from 285 plant species and identified a receptor, "SCORE," that perceives cold shock protein (CSP) peptides.

Lubiprostone in chronic kidney disease: Insights into mitochondrial function and polyamines from a randomized phase 2 clinical trial.

Chronic kidney disease (CKD) is a life-threatening condition, and constipation is a progressive risk factor. We evaluated changes in uremic toxins, renal function, and the safety of lubiprostone, a selective chloride channel activator, in patients with CKD. In this phase 2, randomized, double-blind, placebo-controlled trial across nine centers in Japan, 150 patients with stage IIIb-IV CKD received lubiprostone (8 or 16 micrograms) or placebo for 24 weeks.

C-mannosylation promotes ADAMTS1 activation and secretion in human testicular germ cell tumor NEC8 cells.

C-mannosylation is a protein glycosylation that regulates the functions of target proteins. Although it has been reported that a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), an important spermatogenesis factor, is C-mannosylated, the roles of C-mannosylation in ADAMTS1 in testicular cells are still unclear. In this study, we found that ADAMTS1 is C-mannosylated at Trp and Trp in testis germ NEC8 cells.

Mitochondrial hyper-acetylation induced by an engineered acetyltransferase promotes cellular senescence.

Protein acetylation plays crucial roles in diverse biological functions, including mitochondrial metabolism. Although SIRT3 catalyzes the removal of acetyl groups in mitochondria, the addition of the acetyl groups is thought to be primarily controlled in an enzyme-independent manner due to the absence of potent acetyltransferases. In this study, we developed an engineered mitochondria-localized acetyltransferase, named engineered mitochondrial acetyltransferase (eMAT).

Comparative proteomics of HepG2 cells reveals NGLY1 as an important regulator of ferroptosis resistance and iron uptake.

NGLY1 deficiency is a rare genetic disorder caused by mutations in the NGLY1 gene. This disorder presents a wide range of clinical symptoms, and its severity varies among affected individuals. Previous studies have focused on understanding the influence of NGLY1 on energy metabolism, revealing dysregulation in lipid metabolism following NGLY1 deletion.

Transmission of maternal oral pathobionts to the infant gut predisposes offspring to exacerbated enteritis.

Infants acquire maternal microbes from various body sites, which become early colonizers of the infant gut. Consequently, disruption of healthy maternal microbiota, particularly maternal gut dysbiosis, can influence the composition of offspring's gut microbiota and affect their health outcomes. However, the effects of non-gut maternal microbes on infant health and disease remain largely unexplored.

Natural Lysine-Reactive Meroterpenoids, Stachybenzals A-C, as Covalent Asparagine Synthetase Inhibitors.

Asparagine synthetase (ASNS) is a promising molecular target for cancer chemotherapy. We previously reported bisabosqual A (Bis A), a natural covalent ASNS inhibitor that binds to K556 of ASNS. In this study, to discover other natural covalent ASNS inhibitors, we used a Lys derivative (-Boc-l-Lys) to target Lys-reactive metabolites in crude extract of the fungus RF-6853.

Polyamines stimulate the protein synthesis of the translation initiation factor eIF5A2, participating in mRNA decoding, distinct from eIF5A1.

Polyamines are present in all living organisms, and their homeostasis is closely associated with human health and disease. Furthermore, they are small aliphatic cations that exhibit multifunctional activities through interactions with acidic substances, thereby precluding our understanding of their molecular functions in biological processes. eIF5A1 and eIF5A2 share high amino acid sequence similarity, and hypusination, using spermidine, is essential for their functions.

Mitochondria-Homing Drug Mitochonic Acid 5 Improves Barth Syndrome Myopathy in a Human-Induced Pluripotent Stem Cell Model and Barth Syndrome Drosophila Model.

Barth syndrome (BTHS) is a rare disease caused by mutations in the tafazzin gene that affects the heart and muscles; however, to date, no clinically effective drugs are available. In BTHS, mitochondrial function is reduced owing to changes in cardiolipin metabolism. We developed mitochonic acid 5 (MA-5), a small-molecule compound that increases ATP levels, improves mitochondrial dynamics, and is effective in treating mitochondrial and muscle diseases.

Congenital Pulmonary Airway Malformation with Pulmonary Arteriovenous Malformation in Adulthood: A Case Report.

Introduction: Congenital pulmonary airway malformation (CPAM) is a congenital condition rarely detected in adults because most cases of CPAM are found through prenatal testing or through testing for recurrent pneumonia or lung abscesses in childhood. Pulmonary arteriovenous malformation (PAVM) is an abnormal vascular connection between the pulmonary arteries and veins, which is often related to hereditary hemorrhagic telangiectasia, but can also be induced by infections, trauma, or thoracic surgery. Herein, we report an adult case of coexisting CPAM and PAVM.

Biochemical and phylogenetic analyses of light-harvesting complexes from Tetraselmis striata.

Oxygenic photosynthetic organisms employ light-harvesting complexes (LHCs) to capture solar energy and regulate excess excitation. Tetraselmis species belong to Chlorodendrophyceae, one of the earliest-diverging lineages within core Chlorophyta. While these organisms exhibit distinctive pigment compositions, their LHC organization and function remain largely uncharacterized.

Structure of a photosystem I supercomplex from close to an ancestral red alga.

Red algae exhibit unique photosynthetic adaptations, characterized by photosystem I (PSI) supercomplexes containing light-harvesting complexes (LHCs), forming PSI-LHCI supercomplexes. In this study, we solved the PSI-LHCI structure of NIES-3638 at 2.19-angstrom resolution using cryo-electron microscopy, revealing a PSI monomer core associated with seven LHCI subunits.

Characteristics of Global Methylation Changes in F1 Mice Sperm DNA Induced by Gestational Arsenic Exposure Are Re-Established in F2 Somatic Cells but Not in F2 Germ Cells.

Gestational exposure to chemicals has been reported to transmit epigenetic modifications of germ cells not only to somatic cells but also to the germ cells of the next generation, resulting in adverse effects. Arsenic is one of the environmental chemicals of greatest concern, but it is not precisely clarified whether and how epigenetic modifications of F1 sperm caused by gestational exposure are transmitted to the next generation of somatic cells and germ cells. In the present study, we examined the effects of arsenic exposure during gestation on DNA methylation in germ line and somatic cells of the F2.

Cleavage cascade of the sigma regulator FecR orchestrates TonB-dependent signal transduction.

TonB-dependent signal transduction is a versatile mechanism observed in gram-negative bacteria that integrates energy-dependent substrate transport with signal relay. In , the TonB-ExbBD motor complex energizes the TonB-dependent outer membrane transporter FecA, facilitating ferric citrate import. FecA also acts as a sensor, transmitting signals to the cytoplasmic membrane protein FecR, which eventually activates the cytoplasmic sigma factor FecI, driving transcription of the operon.

[Food Ingredients and Hygiene: Exploring the Functions of Food Ingredients Through Hygiene Studies].

Hygiene is a field of study that aims to "protect health" and "protect lifestyle" of people from external factors such as bacteria, poor nutrition, and toxic chemicals, as well as internal factors such as lifestyle and stress. In the early days of hygiene science in Japan, the results of nutritional epidemiology research by Dr. Kanehiro Takaki, a naval doctor who studied medicine in Kagoshima, on the prevention of beriberi, a national disease at the time, were highly regarded internationally.

Hypoglycemia and hyperinsulinemia induced by phenolic uremic toxins in CKD and DKD patients.

Patients with end-stage renal disease have lower fasting plasma glucose and HbA1c levels, with significantly higher insulin levels. For a long time, it has been believed that this higher insulin level in renal failure is due to decreased insulin clearance caused by reduced renal function. However, here we reported that accumulation of the gut microbiota-derived uremic toxin, phenyl sulfate (PS) in the renal failure, increased insulin secretion from the pancreas by enhanced glucose-stimulated insulin secretion.

Peripheral neuropathy in systemic sclerosis with proximal nerve involvement: Diagnostic challenges and response to corticosteroid therapy.

Peripheral neuropathy is a complication in systemic sclerosis (SSc) that is occasionally encountered in clinical settings. The mechanisms underlying this condition remain unclear and treatment strategies have not yet been established, making management challenging. Here, we report a case of peripheral neuropathy associated with SSc that was successfully treated with corticosteroid therapy despite the absence of conventional inflammatory findings on histopathology or blood tests.

Biochemical evidence for the diversity of LHCI proteins in PSI-LHCI from the red alga Galdieria sulphuraria NIES-3638.

Red algae are photosynthetic eukaryotes whose light-harvesting complexes (LHCs) associate with photosystem I (PSI). In this study, we examined characteristics of PSI-LHCI, PSI, and LHCI isolated from the red alga Galdieria sulphuraria NIES-3638. The PSI-LHCI supercomplexes were purified using anion-exchange chromatography followed by hydrophobic-interaction chromatography, and finally by trehalose density gradient centrifugation.

Expression of spider silk protein in tobacco improves drought tolerance with minimal effects on its mechanotype.

Spider silk, especially dragline silk from golden silk spiders (Trichonephila clavipes), is an excellent natural material with remarkable mechanical properties. Many studies have focused on the use of plants as biofactories for the production of recombinant spider silk. However, the effects of this material on the mechanical properties or physiology of transgenic plants remain poorly understood.

Acquired sperm hypomethylation by gestational arsenic exposure is re-established in both the paternal and maternal genomes of post-epigenetic reprogramming embryos.

Background: DNA methylation plays a crucial role in mammalian development. While methylome changes acquired in the parental genomes are believed to be erased by epigenetic reprogramming, accumulating evidence suggests that methylome changes in sperm caused by environmental factors are involved in the disease phenotypes of the offspring. These findings imply that acquired sperm methylome changes are transferred to the embryo after epigenetic reprogramming.

Arsenite exposure induces premature senescence and senescence-associated secretory phenotype (SASP) in human hepatocyte-derived cell line Huh-7.

Background: Chronic arsenite exposure has been known to induce cancer in various organs; however, the underlying mechanisms remain elusive. The characteristic feature of carcinogenesis due to arsenic exposure is that the disease develops after a prolonged latent period, even after cessation of exposure. Our previous study revealed that arsenite exposure induces premature senescence in hepatic stellate cells and suggests that the senescence-associated secretory phenotype (SASP) factors from the senescent cells promote hepatic carcinogenesis.

Ultrasound irradiation in the presence of microbubbles may enhance the antitumor effect of chemotherapeutic agents against bladder cancer.

Intravesical instillation of chemotherapy has been performed to reduce the risk of intravesical recurrence of bladder cancer. However, its antitumor effect is not necessarily sufficient, which may be partially due to inadequate delivery of intravesically administered chemotherapeutic agents to bladder tumors. Ultrasound irradiation to target tissues in the presence of microbubbles is a technique to transiently enhance cell membrane permeability and achieve efficient drug delivery to the desired sites without damage to non-target areas; this technique has been used in chemotherapy, immunotherapy, gene therapy, and radiotherapy for the treatment of various cancers.

Identification of C-mannosylation in a receptor tyrosine kinase AXL.

C-mannosylation is a unique type of glycosylation in which a mannose is added to tryptophan in a protein. However, the biological function of C-mannosylation is still largely unknown. AXL is a receptor tyrosine kinase, and its overexpression contributes to tumor malignancy.

Discovery of a Compound That Inhibits IRE1α -Nitrosylation and Preserves the Endoplasmic Reticulum Stress Response under Nitrosative Stress.

Inositol-requiring enzyme 1α (IRE1α) is a sensor of endoplasmic reticulum (ER) stress and drives ER stress response pathways. Activated IRE1α exhibits RNase activity and cleaves mRNA encoding X-box binding protein 1, a transcription factor that induces the expression of genes that maintain ER proteostasis for cell survival. Previously, we showed that IRE1α undergoes -nitrosylation, a post-translational modification induced by nitric oxide (NO), resulting in reduced RNase activity.