Bioinformatic Analysis of Actin-Binding Proteins in the Nucleolus During Heat Shock.

Background/objectives: Actin plays a crucial role not only in the cytoplasm, but also in the nucleus, influencing various cellular behaviors, including cell migration and gene expression. Recent studies reveal that nuclear actin dynamics is altered by cellular stresses, such as DNA damage; however, the effect of heat shock on nuclear actin dynamics, particularly in the nucleolus, remains unclear. This study aims to elucidate the contribution of nucleolar actin to cellular responses under heat shock conditions.

Distributional hypothesis as isomorphism between word-word co-occurrence and analogical parallelograms.

Most of the modern natural language processing (NLP) techniques are based on the vector space models of language, in which each word is represented by a vector in a high dimensional space. One of the earliest successes was demonstrated by the four-term analogical reasoning task: what is to C as B is to A? The trained word vectors form "parallelograms" representing the quadruple of words in analogy. This discovery in NLP offers us insight into our understanding of human semantic representation of words via analogical reasoning.

Non-canonical olfactory pathway activation induces cell fusion of cervical cancer cells.

Multinucleation occurs in various types of advanced cancers and contributes to their malignant characteristics, including anticancer drug resistance. Therefore, inhibiting multinucleation can improve cancer prognosis; however, the molecular mechanisms underlying multinucleation remain elusive. Here, we introduced a genetic mutation in cervical cancer cells to induce cell fusion-mediated multinucleation.

Myelination by signaling through Arf guanine nucleotide exchange factor.

During myelination, large quantities of proteins are synthesized and transported from the endoplasmic reticulum (ER)-trans-Golgi network (TGN) to their appropriate locations within the intracellular region and/or plasma membrane. It is widely believed that oligodendrocytes uptake neuronal signals from neurons to regulate the endocytosis- and exocytosis-mediated intracellular trafficking of major myelin proteins such as myelin-associated glycoprotein (MAG) and proteolipid protein 1 (PLP1). The small GTPases of the adenosine diphosphate (ADP) ribosylation factor (Arf) family constitute a large group of signal transduction molecules that act as regulators for intracellular signaling, vesicle sorting, or membrane trafficking in cells.

GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region.

Here we report the largest Asian genome-wide association study (GWAS) for systemic sclerosis performed to date, based on data from Japanese subjects and comprising of 1428 cases and 112,599 controls. The lead SNP is in the FCGR/FCRL region, which shows a penetrating association in the Asian population, while a complete linkage disequilibrium SNP, rs10917688, is found in a cis-regulatory element for IRF8. IRF8 is also a significant locus in European GWAS for systemic sclerosis, but rs10917688 only shows an association in the presence of the risk allele of IRF8 in the Japanese population.

Extraction of the pull force from inertial sensors during the pull test for Parkinson's disease: A reliability study.

Objective: To examine the inter- and intra-rater reliability of the pull test in patients with Parkinson's disease (PD) using the extracted pull force.

Methods: In this inter- and intra-rater reliability study, two raters performed a pull test on 30 patients with PD. The pull force was quantified using inertial sensors attached to the rater's right hand and the patient's lower trunk.

Trends in Dietary Micronutrient Adequacy in Young Adults Over the Latest 25 Years in Japan.

Background: It has been assumed that economically developed countries are well nourished compared to developing countries, but little is known about how economic status affects dietary micronutrient intake in the future childbearing generation.

Objective: We analyzed the trend of dietary micronutrient adequacy in young adults in Japan, as one of the representative countries with advanced dietary habits and economic progress.

Methods: We conducted a retrospective analysis using 2 web-accessible databases, namely the Japanese National Health and Nutrition Survey and the World Development Indicators.

Loss of p53 function promotes DNA damage-induced formation of nuclear actin filaments.

Tumor suppressor p53 plays a central role in response to DNA damage. DNA-damaging agents modulate nuclear actin dynamics, influencing cell behaviors; however, whether p53 affects the formation of nuclear actin filaments remains unclear. In this study, we found that p53 depletion promoted the formation of nuclear actin filaments in response to DNA-damaging agents, such as doxorubicin (DOXO) and etoposide (VP16).

Molecular Pathogenic Mechanisms of Hypomyelinating Leukodystrophies (HLDs).

Hypomyelinating leukodystrophies (HLDs) represent a group of congenital rare diseases for which the responsible genes have been identified in recent studies. In this review, we briefly describe the genetic/molecular mechanisms underlying the pathogenesis of HLD and the normal cellular functions of the related genes and proteins. An increasing number of studies have reported genetic mutations that cause protein misfolding, protein dysfunction, and/or mislocalization associated with HLD.

Lethal adulthood myelin breakdown by oligodendrocyte-specific Ddx54 knockout.

Multiple sclerosis (MS) is a leading disease that causes disability in young adults. We have previously shown that a DEAD-box RNA helicase Ddx54 binds to mRNA and protein isoforms of myelin basic protein (MBP) and that Ddx54 siRNA blocking abrogates oligodendrocyte migration and myelination. Herein, we show that MBP-driven Ddx54 knockout mice (), after the completion of normal postnatal myelination, gradually develop abnormalities in behavioral profiles and learning ability, inner myelin sheath breakdown, loss of myelinated axons, apoptosis of oligodendrocytes, astrocyte and microglia activation, and they die within 7 months but show minimal peripheral immune cell infiltration.

FTD/ALS Type 7-Associated Thr104Asn Mutation of CHMP2B Blunts Neuronal Process Elongation, and Is Recovered by Knockdown of Arf4, the Golgi Stress Regulator.

Frontotemporal dementia and/or amyotrophic lateral sclerosis type 7 (FTD/ALS7) is an autosomal dominant neurodegenerative disorder characterized by the onset of FTD and/or ALS, mainly in adulthood. Patients with some types of mutations, including the Thr104Asn (T104N) mutation of charged multivesicular body protein 2B (CHMP2B), have predominantly ALS phenotypes, whereas patients with other mutations have predominantly FTD phenotypes. A few mutations result in patients having both phenotypes approximately equally; however, the reason why phenotypes differ depending on the position of the mutation is unknown.

The iron chelator deferriferrichrysin induces paraptosis via extracellular signal-related kinase activation in cancer cells.

Cancer cells generally exhibit increased iron uptake, which contributes to their abnormal growth and metastatic ability. Iron chelators have thus recently attracted attention as potential anticancer agents. Here, we show that deferriferrichrysin (Dfcy), a natural product from Aspergillus oryzae acts as an iron chelator to induce paraptosis (a programmed cell death pathway characterized by ER dilation) in MCF-7 human breast cancer cells and H1299 human lung cancer cells.

Extracellular HSPA5 is autocrinally involved in the regulation of neuronal process elongation.

The molecular mechanisms by which neuronal processes grow are extremely complicated, involving fine-tuned regulation of extracellular and intracellular signals. It remains to be elucidated which molecules are contained in the regulation. Herein, we report for the first time that heat shock protein family A member 5 (HSPA5, also called immunoglobulin heavy chain binding endoplasmic reticulum [ER] protein [BiP]) is secreted from mouse primary dorsal neuronal ganglion (DRG) cells or neuronal cell line N1E-115, a frequently used neuronal differentiation model.

A new species of Enchytraeus (Enchytraeidae, Clitellata) from sewage sludge of a plum processing plant in Japan.

Enchytraeus ohtakai sp. nov. (Enchytraeidae, Clitellata, Oligochaeta) was discovered in the organic matter of a wastewater treatment facility of a plums processing plant in Honshu, Japan.

Simple and fast screening for structure-selective G-quadruplex ligands.

Structural selectivity of G-quadruplex ligands is essential for cellular applications since there is an excess of nucleic acids forming duplex structures compared to G-quadruplex structures in living cells. In this study, we developed new structure-selective G-quadruplex ligands utilizing a simple and fast screening system. The affinity, selectivity, enzymatic inhibitory activity and cytotoxicity of the structure-selective G-quadruplex ligands were demonstrated along with a structural selectivity-cytotoxicity relationship of G-quadruplex ligands.

Long-Term Nutritional Counseling for a Patient with Lipoprotein Lipase Deficiency.

A one-year-and-nine-month-old Japanese boy was admitted with hypertriglyceridemia (fasting triglycerides 2548 mg/dL). After close examination, he was diagnosed with lipoprotein lipase (LPL) deficiency (compound heterozygous) and was immediately started on a fat-restricted dietary therapy. He responded well to the regimen (1200 kcal/day, 20 g fat/day) and his triglycerides decreased to 628 mg/dL within 7 days of starting the dietary therapy.

Identification of Tau protein as a novel marker for maturation and pathological changes of oligodendrocytes.

Microtubule-associated protein Tau is primarily expressed in axons of neurons, but also in Olig2-positive oligodendrocytes in adult rodent and monkey brains. In this study, we sought to determine at what cell stage Tau becomes expressed in the oligodendrocyte lineage. We performed immunostaining of adult mouse brain sections using well-known markers of oligodendrocyte lineage and found that Tau is expressed in mature oligodendrocytes, but not in oligodendrocyte progenitors and immature pre-oligodendrocytes.

Hypomyelinating Leukodystrophy 10 (HLD10)-Associated Mutations of PYCR2 Form Large Size Mitochondria, Inhibiting Oligodendroglial Cell Morphological Differentiation.

Hypomyelinating leukodystrophy 10 (HLD10) is an autosomal recessive disease related to myelin sheaths in the central nervous system (CNS). In the CNS, myelin sheaths are derived from differentiated plasma membranes of oligodendrocytes (oligodendroglial cells) and surround neuronal axons to achieve neuronal functions. Nucleotide mutations of the pyrroline-5-carboxylate reductase 2 (PYCR2) gene are associated with HLD10, likely due to PYCR2's loss-of-function.

Optimal integration of kinematic and ball-flight information when perceiving the speed of a moving ball.

In order to intercept a moving target such as a baseball with high spatio-temporal accuracy, the perception of the target's movement speed is important for estimating when and where the target will arrive. However, it is unclear what sources of information are used by a batter to estimate ball speed and how those sources of information are integrated to facilitate successful interception. In this study, we examined the degree to which kinematic and ball-flight information are integrated when estimating ball speed in baseball batting.

Gastrointestinal cancer occurs as extramuscular manifestation in FSHD1 patients.

Facioscapulohumeral dystrophy type1 (FSHD1) patients with a shortened D4Z4 repeat containing the DUX4 gene have a broad spectrum of clinical manifestations. In addition, high expression of DUX4 protein with an aberrant C terminus is frequently identified in B cell acute lymphoblastic leukemia. We investigated clinical manifestations in 31 FSHD1 patients and 30 non-affected individuals.

Controlling liquid-liquid phase separation of G-quadruplex-forming RNAs in a sequence-specific manner.

We constructed a minimum liquid-liquid phase separation model system to form liquid droplets using only G-quadruplex-forming oligonucleotides and R- and G-rich oligopeptides. We found that the G-quadruplex structure is an essential component for RNA to form droplets with the peptide. Based on this model system and our findings, droplet redissolution structure transition from a G-quadruplex to a duplex was achieved in a sequence-specific manner.

The organization of microtubules and Tau in oligodendrocytes: Tau pathology in damaged oligodendrocytes.

Tau is abundantly expressed in neurons, however previous reports and our recent study showed tau also exist in oligodendrocytes. Also the expression levels of tau are dramatical changed in hypomyelination model rat and in demyelination region of stroke model mice. The review demonstrate microtubule and its binding partner Tau might be necessary for oligodendrocyte function based on previous reports.