A Combinatorial Code for CPEB-Mediated c-myc Repression.

During early embryonic development, the RNA-binding protein CPEB mediates cytoplasmic polyadenylation and translational activation through a combinatorial code defined by the cy-toplasmic polyadenylation element (CPE) present in maternal mRNAs. However, in non-neuronal somatic cells, CPEB accelerates deadenylation to repress translation of the target, including c-myc mRNA, through an ill-defined cis-regulatory mechanism. Using RNA mutagenesis and electrophoretic mobility shift assays, we demonstrated that a combination of tandemly arranged consensus (cCPE) and non-consensus (ncCPE) cytoplasmic polyadenylation elements (CPEs) constituted a combinatorial code for CPEB-mediated c-myc mRNA decay.

TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation.

Oncogene-induced DNA replication stress (RS) and consequent pathogenic R-loop formation are known to impede S phase progression. Nonetheless, cancer cells continuously proliferate under such high-stressed conditions through incompletely understood mechanisms. Here, we report taurine upregulated gene 1 (TUG1) long noncoding RNA (lncRNA), which is highly expressed in many types of cancers, as an important regulator of intrinsic R-loop in cancer cells.

Oral Function for Diagnosing Oral Hypofunction in Healthy Young Adults: A Comparison with the Literature.

This study investigated decline in oral function in healthy young adults and compared it with that observed in an earlier studies employing older adults. The participants comprised 130 young healthy adults (mean age 24.1±2.

Protocol for analyzing intact mRNA poly(A) tail length using nanopore direct RNA sequencing.

Poly(A) tail metabolism contributes to post-transcriptional regulation of gene expression. Here, we present a protocol for analyzing intact mRNA poly(A) tail length using nanopore direct RNA sequencing, which excludes truncated RNAs from the measurement. We describe steps for preparing recombinant eIF4E mutant protein, purifying m7G- capped RNAs, library preparation, and sequencing.

Maxillary Obturator Prosthesis Made with Polyetherketoneketone Using Optical Impression and CAD/CAM System.

This report describes the case of a 68-year-old man who visited our department complaining of poor denture retention and difficulty masticating due to damage to the retainer of a maxillary obturator. The patient had never been satisfied with the fit of this prosthesis, which had been placed two years earlier. The obturator and the mucosal surface of the denture base were incompatible, which had caused the retainer to detach.

Systematic characterization of seed overlap microRNA cotargeting associated with lupus pathogenesis.

Background: Combinatorial gene regulation by multiple microRNAs (miRNAs) is widespread and closely spaced target sites often act cooperatively to achieve stronger repression ("neighborhood" miRNA cotargeting). While miRNA cotarget sites are suggested to be more conserved and implicated in developmental control, the pathological significance of miRNA cotargeting remains elusive.

Results: Here, we report the pathogenic impacts of combinatorial miRNA regulation on inflammation in systemic lupus erythematosus (SLE).

mTOR- and LARP1-dependent regulation of TOP mRNA poly(A) tail and ribosome loading.

Translation of 5' terminal oligopyrimidine (TOP) mRNAs encoding the protein synthesis machinery is strictly regulated by an amino-acid-sensing mTOR pathway. However, its regulatory mechanism remains elusive. Here, we demonstrate that TOP mRNA translation positively correlates with its poly(A) tail length under mTOR active/amino-acid-rich conditions, suggesting that TOP mRNAs are post-transcriptionally controlled by poly(A) tail-length regulation.

Nuclear RNA Exosome and Pervasive Transcription: Dual Sculptors of Genome Function.

The genome is pervasively transcribed across various species, yielding numerous non-coding RNAs. As a counterbalance for pervasive transcription, various organisms have a nuclear RNA exosome complex, whose structure is well conserved between yeast and mammalian cells. The RNA exosome not only regulates the processing of stable RNA species, such as rRNAs, tRNAs, small nucleolar RNAs, and small nuclear RNAs, but also plays a central role in RNA surveillance by degrading many unstable RNAs and misprocessed pre-mRNAs.

Oral function is associated with the body and muscle mass indices of middle-aged dental patients.

Objectives: Undernutrition is associated with frailty, one of the common reasons for seeking long-term care. In older adults, nutritional status is known to be associated with oral function; however, it is not yet known if there is a similar association in middle-aged adults. The present study determined the association between nutritional status and oral function in middle-aged adults.

COVID-19 Impact on Acute Ischemic Stroke Treatment at 9 Comprehensive Stroke Centers across Los Angeles.

Objective: To describe the impact of COVID-19 on acute cerebrovascular disease care across 9 comprehensive stroke centers throughout Los Angeles County (LAC).

Methods: Volume of emergency stroke code activations, patient characteristics, stroke severity, reperfusion rates, treatment times, and outcomes from February 1 to April 30, 2020, were compared against the same time period in 2019. Demographic data were provided by each participating institution.

Anoxia-induced mitophagy in the yeast Kluyveromyces marxianus.

Kluyveromyces marxianus is a thermotolerant, ethanol-producing yeast that requires oxygen for efficient ethanol fermentation. Under anaerobic conditions, glucose consumption and ethanol production are retarded, suggesting that oxygen affects the metabolic state of K. marxianus.

Widespread transcript shortening through alternative polyadenylation in secretory cell differentiation.

Most eukaryotic genes produce alternative polyadenylation (APA) isoforms. Here we report that, unlike previously characterized cell lineages, differentiation of syncytiotrophoblast (SCT), a cell type critical for hormone production and secretion during pregnancy, elicits widespread transcript shortening through APA in 3'UTRs and in introns. This global APA change is observed in multiple in vitro trophoblast differentiation models, and in single cells from placentas at different stages of pregnancy.

Efficient differentiation and purification of human induced pluripotent stem cell-derived endothelial progenitor cells and expansion with the use of inhibitors of ROCK, TGF-β, and GSK3β.

Endothelial cells (ECs) and endothelial progenitor cells (EPCs) play crucial roles in maintaining vascular health and homeostasis. Both cell types have been used in regenerative therapy as well as in various models; however, the properties of primary human ECs and EPCs are dissimilar owing to differences in genetic backgrounds and sampling techniques. Human induced pluripotent stem cells (hiPSCs) are an alternative cell source of ECs and EPCs.

The RNA-binding protein QKI-7 recruits the poly(A) polymerase GLD-2 for 3' adenylation and selective stabilization of microRNA-122.

MicroRNA-122 (miR-122) is highly expressed in hepatocytes, where it plays an important role in regulating cholesterol and fatty acid metabolism, and it is also a host factor required for hepatitis C virus replication. miR-122 is selectively stabilized by 3' adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2 (also known as PAPD4 or TENT2). However, it is unclear how GLD-2 specifically stabilizes miR-122.

Intra- and Inter-Investigator Reliability of Measurement of Lip-Seal Strength in Adults.

The purpose of this methodological study was to clarify intra- and inter-investigator reliability of lip-seal strength measurement in adults. Lip-seal strength was measured with a digital medical strain gauge using the button-pull method. The coefficient of variation (CV) of intra-investigator reliability of measurement in 24 healthy adult volunteers (16 men, 8 women; mean age, 26±3 years) ranged from 0.

A novel method for stabilizing microRNA mimics.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression at post-transcriptional level via translational repression and/or mRNA degradation. miRNAs are associated with many cellular processes, and down-regulation of miRNAs causes numerous diseases including cancer, neurological disorders, inflammation, and cardiovascular diseases, for which miRNA replacement therapy has emerged as a promising approach. This approach aims to restore down-regulated miRNAs using synthetic miRNA mimics.

Influence of chewing on expression level of human beta-defensin 2 and secretory immunoglobulin A in the epithelium.

Purpose: This study aimed to clarify the influence of chewing on human β-defensin 2 (hBD-2) and secretory immunoglobulin A (SIgA) expression levels.

Methods: We included 15 healthy males with no missing teeth (mean age, 25.5±2.

Evaluation of Factors Associated with Tongue Coating Status in Elderly with Care Needs.

The tongue surface in older people requiring nursing care is often coated with a layer believed to comprise, keratinized products of degeneration, food residue, bacteria, and leukocytes attached to the tongue papillae. Which factors affect the status of this tongue coating remain to be elucidated, however. The purpose of this study was to evaluate factors related to tongue coating status in older people requiring nursing care.

A 2-year longitudinal study of the relationship between masticatory function and progression to frailty or pre-frailty among community-dwelling Japanese aged 65 and older.

Background: An association has recently been reported between frailty and reduced masticatory function; however, the causal relationship remains unclear.

Objective: The aim of this study was to clarify the relationship between masticatory function and frailty progression.

Methods: Among 6699 individuals aged 65 and older (mean age 72.

Immunological association of inducible bronchus-associated lymphoid tissue organogenesis in Ag85B-rHPIV2 vaccine-induced anti-tuberculosis mucosal immune responses in mice.

We previously reported that Ag85B-expressing human parainfluenza type 2 virus (Ag85B-rHPIV2) was effective as a nasal vaccine against tuberculosis in mice; however, the mechanism by which it induces an immune response remains to be investigated. In the present study, we found that organogenesis of inducible bronchus-associated lymphoid tissue (iBALT) played a role in the induction of antigen-specific T cells and IgA antibody responses in the lung of mice intra-nasally administered Ag85B-rHPIV2. We found that expression of Ag85B was dispensable for the development of iBALT, suggesting that HPIV2 acted as an iBALT-inducing vector.

NRDE-2, the human homolog of fission yeast Nrl1, prevents DNA damage accumulation in human cells.

The RNA helicase Mtr4 is a versatile protein that is a crucial component of several distinct RNA surveillance complexes. Here we describe a novel complex that contains Mtr4, but has a role distinct from any of those previously described. We found that Mtr4 association with the human homolog of fission yeast Nrl1, NRDE-2, defines a novel function for Mtr4 in the DNA damage response pathway.

RNA surveillance by the nuclear RNA exosome: mechanisms and significance.

The nuclear RNA exosome is an essential and versatile machinery that regulates maturation and degradation of a huge plethora of RNA species. The past two decades have witnessed remarkable progress in understanding the whole picture of its RNA substrates and the structural basis of its functions. In addition to the exosome itself, recent studies focusing on associated co-factors have been elucidating how the exosome is directed towards specific substrates.

MicroRNP-mediated translational activation of nonadenylated mRNAs in a mammalian cell-free system.

MicroRNAs are small noncoding RNAs that regulate translation and mRNA stability by binding target mRNAs in complex with Argonaute (AGO) proteins. AGO interacts with a member of the TNRC6 family proteins to form a microRNP complex, which recruits the CCR4-NOT complex to accelerate deadenylation and inhibits translation. MicroRNAs primarily repress translation of target mRNAs but have been shown to enhance translation of a specific type of target reporter mRNAs in various experimental systems: G0 quiescent mammalian cells, Xenopus laevis oocytes, Drosophila embryo extracts, and HeLa cells.