MicroRNA-351 Regulates Two-Types of Cell Death,Necrosis and Apoptosis,Induced by 5-fluoro-2'-deoxyuridine

Cell-death can be necrosis and apoptosis. We are investigating the mechanisms regulating the cell death that occurs on treatment of mouse cancer cell-line FM3A with antitumor 5-fluoro-2''-deoxyuridine (FUdR): necrosis occurs for the original clone F28-7, and apoptosis for its variant F28-7-A. Here we report that a microRNA (miR-351) regulates the cell death pattern. The miR-351 is expressed strongly in F28-7-A but only weakly in F28-7. Induction of a higher expression of miR-351 in F28-7 by transfecting an miRNA mimic into F28-7 resulted in a change of the death mode; necrosis to apoptosis. Furthermore, transfection of an miR-351 inhibitor into F28-7-A resulted in the morphology change, apoptosis to necrosis, in this death-by-FUdR. Possible mechanism involving lamin B1 in this miR-351’s regulatory action is discussed.     

INFERRING THE RATES OF BRANCHING AND EXTINCTION FROM MOLECULAR PHYLOGENIES

Molecular techniques provide ancestral phylogenies of extant taxa with estimated branching times. Here we studied the pattern of ancestral phylogeny of extant taxa produced by branching (or cladogenesis) and extinction of taxa, assuming branching processes with time-dependent rates. (1) If the branching rate b and extinction rate c are constant, the semilog plot of the number of ancestral lineages over time is not a straight line but is curvilinear, with increasing slope toward the end, implying that ancestral phylogeny shows apparent increase in the branching rate near the present. The estimate of b and c based on nonlinear fitting is examined by computer simulation. The estimate of branching rate can be usable for a large phylogeny if b is greater than c, but the estimate of extinction rate c is unreliable because of large bias and variance. (2) Gradual decrease in the slope of the semilog plot of the number of ancestral lineages over time, as was observed in a phylogeny of bird families based on DNA hybridization data, can be explained equally well by either the decreasing branching rate or the increasing extinction rate. Infinitely many pairs of branching and extinction rates as functions of time can produce the same ancestral phylogeny. (3) An explosive branching event in the past would appear as a quick increase in the number of ancestral lineages. In contrast, mass extinction occurring in a brief period, if not accompanied by an increase in branching rate, does not produce any rapid change in the number of ancestral lineages at the time. (4) The condition in which the number of ancestral lineages of extant species changes in parallel with the actual number of species in the past is derived.     

Effects of winter flooding on phosphorus dynamics in rice fields

Limnology - Controlling phosphorous (P) loads from rice fields is important for the conservation of aquatic ecosystems, in part because P is relatively concentrated at its sources. Recently, winter...     

Identification of two metabolites induced by a butyrolactone autoregulator IM-2 in Streptomyces sp. FRI-5

Abstract In order to determine whether non-elastase-producing strains of Pseudomonas aeruginosa such as N-10, PA103 and IFO3080 can express foreign elastase genes, we introduced elastase genes from P. aeruginosa IFO3455 (elastase-producing) as well as from PA103 and N-10 into non-elastase-producing P. aeruginosa strains. Results suggested that gene expression, secretion, and precursor processing systems of elastase were essentially normal in P. aeruginosa N-10 and IFO3080. Our studies using various elastase genes showed that both the elastase structural gene and 5'-upstream regions of P. aeruginosa PA103 were also normal. This was confirmed by the finding that P. aeruginosa N-10 and IFO3080 which carry the PA103 elastase gene produced elastase. Several deleted or chimeric genes were constructed using the 5'-upstream regions of elastase genes from P. aeruginosa N-10 or PA103 and studies of expression revealed that two individual DNA bases seem to be important in suppressing P. aeruginosa N-10 elastase gene expression. Possible reasons for the lack of elastase in these non-elastase-producing strains are discussed.     

A Novel Acylaminoimidazole Derivative,WN1316, Alleviates Disease Progression via Suppression of Glial Inflammation in ALS Mouse Model

Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron degenerative disease. Given that oxidative stress and resulting chronic neuronal inflammation are thought to be central pathogenic, anti-oxidative agents and modulators of neuronal inflammation could be potential therapies for ALS. We report here that the novel small molecular compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) selectively suppresses oxidative stress-induced cell death and neuronal inflammation in the late-stage ALS mice. WN1316 has high blood-brain-barrier permeability and water solubility, and boosts both neuronal apoptosis inhibitory protein (NAIP) and NF-E2-related factor 2 (Nrf2) which governed glutathione (GSH)-related anti-oxidation pathway protecting motor neurons against oxidative injuries. Post-onset oral administration of low dose (1–100 µg/kg/day) WN1316 in ALS(SOD1^H46R) and ALS(SOD1^G93A) mice resulted in sustained improved motor function and post onset survival rate. Immunohistochemical analysis revealed less DNA oxidative damage and motor neuronal inflammation as well as repression of both microgliosis and astrocytosis, concomitant down regulation of interleukin-1β and inducible nitric oxide synthase, and preservation of the motoneurons in anterior horn of lumbar spinal cord and skeletal muscle (quadriceps femoris). Thus, WN1316 would be a novel therapeutic agent for ALS.     

Gender and Age Differences in the Suppressive Effect of a 50 Hz Electric Field on the Immobilization-Induced Increase of Plasma Glucocorticoid in Mice

We developed an experimental system to characterize the suppressive effect of extremely low-frequency (ELF) electric fields (EFs) on the stress response. We assessed differences in the EF effects by age and gender. Control, EF-alone, immobilization-alone, and co-treated groups were subjected to an EF (50 Hz, 10 kV/m). Co-treated mice were exposed to the EF for 60 min, with immobilization during the latter half. Our results indicate that the suppressive effects of ELF EFs on the stress response in immobilized mice occur regardless of gender or age. As stress plays an important role in the onset and progression of various diseases, these findings may have broad implications for understanding the efficacy of EFs in animal, and perhaps human, health. Bioelectromagnetics. 2020;41:156–163. © 2019 Bioelectromagnetics Society.     

Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche

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Substrate selection by the proteasome through initiation regions

Proteins in the cell have to be eliminated once their function is no longer desired or they become damaged. Most regulated protein degradation is achieved by a large enzymatic complex called the proteasome. Many proteasome substrates are targeted for degradation by the covalent attachment of ubiquitin molecules. Ubiquitinated proteins can be bound by the proteasome, but for proteolysis to occur the proteasome needs to find a disordered tail somewhere in the target at which it initiates degradation. The initiation step contributes to the specificity of proteasomal degradation. Here, we review how the proteasome selects initiation sites within its substrates and discuss how the initiation step affects physiological processes.