Adaptation of codon usage to tRNA I34 modification controls translation kinetics and proteome landscape.

Codon usage bias is a universal feature of all genomes and plays an important role in regulating protein expression levels. Modification of adenosine to inosine at the tRNA anticodon wobble position (I34) by adenosine deaminases (ADATs) is observed in all eukaryotes and has been proposed to explain the correlation between codon usage and tRNA pool. However, how the tRNA pool is affected by I34 modification to influence codon usage-dependent gene expression is unclear.

Identification of significant genes with prognostic influence in clear cell renal cell carcinoma via bioinformatics analysis.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of kidney with high mortality. The pathogenesis of ccRCC is complicated and effective prognostic predictors for clinical practice are still limited. This study aimed to identify significant genes with prognostic influence in ccRCC via bioinformatics analysis.

Suppressive effect of environmental tobacco smoke on murine Th2 cell-mediated nasal eosinophilic inflammation.

Background: Environmental tobacco smoke (ETS) exposure is recognized as a risk factor for the development of various respiratory diseases.

Objective: In this study, the effect of ETS on allergen-immunized and allergen-specific Th2 cell-transferred murine eosinophilic inflammation models and that of cigarette smoke extract (CSE) and nicotine on allergen-induced Th2 cell proliferation and interleukin (IL)-4 production were investigated.

Methods: Ovalbumin (OVA)-immunized and OVA-specific Th2 cell-transferred BALB/c mice were exposed to ETS and were challenged with OVA.

Data on mitochondrial ultrastructure of photoreceptors in pig, rabbit, and mouse retinas.

Photoreceptors are one of the most energy-consuming cell types within the human body. To meet their high energy demand, photoreceptors possess a mitochondrial cluster in the inner segment of the cell. Interestingly, in several species, the inner segment of cone photoreceptors contains extremely large mitochondria that exceed 2 µm in diameter, called mega-mitochondria.

In vivo stress granule misprocessing evidenced in a FUS knock-in ALS mouse model.

Many RNA-binding proteins, including TDP-43, FUS, and TIA1, are stress granule components, dysfunction of which causes amyotrophic lateral sclerosis (ALS). However, whether a mutant RNA-binding protein disrupts stress granule processing in vivo in pathogenesis is unknown. Here we establish a FUS ALS mutation, p.

Protein ligand interaction analysis against new CaMKK2 inhibitors by use of X-ray crystallography and the fragment molecular orbital (FMO) method.

CaMKK2 (calcium/calmodulin dependent protein kinase kinase 2) is a serine/threonine protein kinase that regulates phosphorylation of CaM kinases (CaMKs) such as CaMKI, CaMKIV, and AMP-activated protein kinase (AMPK). From a pathological perspective, CaMKK2 plays a role in obesity, diabetes, and prostate cancer. Therefore, CaMKK2 is an attractive target protein for drug design.

and Xanthine Oxidase Inhibitory Activity of Selected Phytochemicals Widely Present in Various Edible Plants.

Aim And Objective: The present study was designed to evaluate the xanthine oxidase (XO) inhibitory and antioxidant activities of 30 bioactive compounds present in edible food plants for the possible treatment of hyperuricemia.

Materials And Methods: The XO inhibitory, SO and DPPH radical scavenging activities of selected dietary polyphenols were determined by using colorimetric assays. The molecular docking analysis was performed to evaluate the insight into inhibitory mode of action of bioactive compounds against XO.

Identification and characterization of novel antioxidant peptides from mackerel (Scomber japonicus) muscle protein hydrolysates.

Antioxidant peptides are commonly used as functional ingredient in the pharmaceutical industries. Here, we characterized the antioxidant peptides from mackerel muscle protein hydrolysates (MPHs). MPHs showing higher bioactivities were separated into seven groups by FPLC.

Regulatory myeloid cells paralyze T cells through cell-cell transfer of the metabolite methylglyoxal.

Regulatory myeloid immune cells, such as myeloid-derived suppressor cells (MDSCs), populate inflamed or cancerous tissue and block immune cell effector functions. The lack of mechanistic insight into MDSC suppressive activity and a marker for their identification has hampered attempts to overcome T cell inhibition and unleash anti-cancer immunity. Here, we report that human MDSCs were characterized by strongly reduced metabolism and conferred this compromised metabolic state to CD8 T cells, thereby paralyzing their effector functions.

Single-cell multiomic analysis of in vivo and in vitro matured human oocytes.

Study Question: Are there any differences between in vivo (IVV) and in vitro (IVT) matured metaphase II (MII) oocytes at the molecular level?

Summary Answer: Between IVV and IVT oocytes, 507 differentially expressed genes (DEGs) were identified; the non-CpG methylomes were significantly different, but the CpG methylomes and genomic copy number variations (CNVs) were similar.

What Is Known Already: A previous study using microarray and single-cell RNA-seq analysis revealed that numerous genes were differentially expressed between IVV and IVT oocytes. Independent studies of DNA methylation profiling in human oocytes have revealed negative correlations between gene transcription and the DNA methylation level at gene promoter regions.

an3-Mediated Compensation Is Dependent on a Cell-Autonomous Mechanism in Leaf Epidermal Tissue.

Leaves are formed by coordinated growth of tissue layers driven by cell proliferation and expansion. Compensation, in which a defect in cell proliferation induces compensated cell enlargement (CCE), plays an important role in cell-size determination during leaf development. We previously reported that CCE triggered by the an3 mutation is observed in epidermal and subepidermal layers in Arabidopsis thaliana (Arabidopsis) leaves.

Defective arginine metabolism impairs mitochondrial homeostasis in Caenorhabditiselegans.

Arginine catabolism involves enzyme-dependent reactions in both mitochondria and the cytosol, defects in which may lead to hyperargininemia, a devastating developmental disorder. It is largely unknown if defective arginine catabolism has any effects on mitochondria. Here we report that normal arginine catabolism is essential for mitochondrial homeostasis in Caenorhabditiselegans.

Dissecting Programmed Cell Death with Small Molecules.

Programmed cell death (PCD) is fundamentally an indispensable process in all cellular activities, including cell development, wound healing, and immune surveillance of tumors (Galluzzi, L. et al. 2018, 25, 486-541).

Practical Synthesis of [F]Pitavastatin and Evaluation of Hepatobiliary Transport Activity in Rats by Positron Emission Tomography.

We developed a practical synthetic method for fluorine-18 (F)-labeled pitavastatin ([F]PTV) as a positron emission tomography (PET) tracer to assess hepatobiliary transporter activity and conducted a PET scan as a preclinical study for proof-of-concept in rats. This method is a one-pot synthesis involving aromatic F-fluorination of an arylboronic acid ester followed by deprotection under acidic conditions, which can be reproduced in general clinical sites equipped with a standard radiolabeling system due to the simplified procedure. PET imaging confirmed that intravenously administered [F]PTV was rapidly accumulated in the liver and gradually transferred into the intestinal lumen through the bile duct.

Molecular typing of conjunctivitis-causing adenoviruses in Hanoi, Vietnam from 2017 to 2019 and complete genome analysis of the most prevalent type (HAdV-8).

Adenoviral conjunctivitis is a common epidemic worldwide. In Vietnam, up to 80,000 patients are infected with adenoviral conjunctivitis annually. However, there are few investigations on the pathogenic adenoviruses that cause conjunctivitis.

Life science database cross search: A single window system for dispersed biological databases.

A comprehensive search system for the bioscience databases is in progress. We constructed a search service, Life science database cross search system (https://biosciencedbc.jp/dbsearch/index.

Discovery of a Vertebrate-Specific Factor that Processes Flagellar Glycolytic Enolase during Motile Ciliogenesis.

Motile cilia and flagella require ATP for their formation and function. Although glycolytic enzymes are components of flagellar proteomes, how they translocate to flagella is unknown. Here we show that the expression pattern of the functionally nonannotated gene 4833427G06Rik (C11orf88), which is found only in vertebrates and is designated here as Hoatzin (Hoatz), suggests a functional association of its product with motile cilia and flagella.

CDK1 dependent phosphorylation of hTERT contributes to cancer progression.

The telomerase reverse transcriptase is upregulated in the majority of human cancers and contributes directly to cell transformation. Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1. Clinicopathological analyses reveal that phosphorylation of hTERT at threonine 249 occurs more frequently in aggressive cancers.

Disease mechanisms and gene therapy for Usher syndrome.

Usher syndrome (USH) is a major cause of deaf-blindness in humans, affecting ∼400 000 patients worldwide. Three clinical subtypes, USH1-3, have been defined, with 10 USH genes identified so far. In recent years, in addition to identification of new Usher genes and diagnostic tools, major progress has been made in understanding the role of Usher proteins and how they cooperate through interaction networks to ensure proper development, architecture and function of the stereociliary bundle at the apex of sensory hair cells in the inner ear.

Inactivation of the Prolyl Isomerase Pin1 Sensitizes BRCA1-Proficient Breast Cancer to PARP Inhibition.

PARP inhibitor monotherapies are effective to treat patients with breast, ovary, prostate, and pancreatic cancer with BRCA1 mutations, but not to the much more frequent BRCA wild-type cancers. Searching for strategies that would extend the use of PARP inhibitors to BRCA1-proficient tumors, we found that the stability of BRCA1 protein following ionizing radiation (IR) is maintained by postphosphorylational prolyl-isomerization adjacent to Ser1191 of BRCA1, catalyzed by prolyl-isomerase Pin1. Extinction of Pin1 decreased homologous recombination (HR) to the level of BRCA1-deficient cells.

A novel approach to conducting clinical trials in the community setting: utilizing patient-driven platforms and social media to drive web-based patient recruitment.

Background: Participant recruitment for clinical research studies remains a significant challenge for researchers. Novel approaches to recruitment are necessary to ensure that populations are easier to reach. In the context of rare diseases, social media provides a unique opportunity for connecting with patient groups that have representatively lower diagnosis rates when compared with more common diseases or illness.