Overproduction of Escherichia coli DNA polymerase DinB (Pol IV) inhibits replication fork progression and is lethal

Escherichia coli dinB encodes the specialized DNA polymerase DinB (Pol IV), which is induced as part of the SOS stress-response system and functions in translesion synthesis (TLS) to relieve the replicative Pol III that is stalled at DNA lesions. As the number of DinB molecules, even in unstressed cells, is greater than that required to accomplish TLS, it is thought that dinB plays some additional physiological role. Here, we overexpressed dinB under the tightly regulable arabinose promoter and looked for a distinct phenotype. Upon induction of dinB expression, progression of the replication fork was immediately inhibited at random genomic positions, and the colony-forming ability of the cells was reduced. Overexpression of mutated dinB alleles revealed that the structural requirements for these two inhibitory effects and for TLS were distinct. The extent of in vivo inhibition displayed by a mutant DinB matched the extent of its in vitro impedance, at near-physiological concentration, of a moving Pol III. We suggest that DinB targets Pol III, thereby acting as a brake on replication fork progression. Because the brake operates when cells have excess DinB, as they do under stress conditions, it may serve as a checkpoint that modulates replication to safeguard genome stability.     

Somatosensory graviception inhibits the soleus H-reflex in standing man - a parabolic flight experiment-

The purpose of this study was to investigate how gravity level affects the excitability of the soleus muscle (SOL) motoneuron pool to la afferent input while erect posture is maintained in humans. Three healthy male subjects participated in an experiment whereby three different gravity conditions (micro gravity (MG), normal gravity (NG), and hyper gravity) were imposed using a parabolic flight procedure. The SOL H-reflex was evoked every 2 seconds while the subjects kept an erect posture. The background electromyographic activity (BGA) of the SOL was almost absent during MG. The SOL H-reflex amplitude was significantly larger during MG than during NG. These results suggest that the somatosensory systems detecting a load at the lower limbs and/or vertebral column play a role in reducing the excitability of the SOL motoneuron pool to la afferent inputs by presynaptic inhibition.     

Functional characterization of aminotransferase involved in serine and aspartate metabolism in a halotolerant cyanobacterium,Aphanothece halophytica

Protoplasma - Aminotransferases catalyze the reversible pyridoxal phosphate–dependent transfer of amino groups from amino acids to oxo acids and play important roles for the balance between...     

Quality control of Photosystem II: Cleavage and aggregation of heat-damaged D1 protein in spinach thylakoids

Moderate heat stress (40 °C, 30 min) on spinach thylakoids induced cleavage of the D1 protein, producing an N-terminal 23-kDa fragment, a C-terminal 9-kDa fragment, and aggregation of the D1 protein. A homologue of Arabidopsis FtsH2 protease, which is responsible for degradation of the damaged D1 protein, was abundant in the stroma thylakoids. Two processes occurred in the thylakoids in response to heat stress: dephosphorylation of the D1 protein in the stroma thylakoids, and aggregation of the phosphorylated D1 protein in the grana. Heat stress also induced the release of the extrinsic PsbO, P and Q proteins from Photosystem II, which affected D1 degradation and aggregation significantly. The cleavage and aggregation of the D1 protein appear to be two alternative processes influenced by protein phosphorylation/dephosphorylation, distribution of FtsH, and intactness of the thylakoids.     

Vulnerability to cavitation differs between current‐year and older xylem: non‐destructive observation with a compact magnetic resonance imaging system of two deciduous diffuse‐porous species

Development of xylem embolism during water stress in two diffuse‐porous hardwoods, Katsura (Cercidiphyllum japonicum) and Japanese white birch (Betula platyphylla var. japonica), was observed non‐destructively under a compact magnetic resonance imaging (MRI) system in addition to conventional quantitation of hydraulic vulnerability to cavitation from excised stem segments. Distribution of white and dark areas in MR images corresponded well to the distribution of water‐filled/embolized vessels observed by cryo‐scanning electron microscopy in both species. Water‐filled vessels were observed in MR images as white areas in Katsura and as white dots in Japanese white birch, respectively, and embolisms could be detected as a change to dark areas. The increase in the relative embolized area (REA: %) in the cross‐sectional area of total xylem during water stress, which was estimated from the binarized MR images, was consistent with the hydraulic vulnerability curves of these species. From the non‐destructive MRI observations, cavitation induced by water stress was shown to develop earlier in 1‐ or 2‐year‐old xylem than in the current‐year xylem in both species; that is, the vulnerability to cavitation differs between vessels in the current‐year xylem and those in older annual rings.     

Saireito (TJ-114), a Japanese Traditional Herbal Medicine,Reduces 5-Fluorouracil-Induced Intestinal Mucositis in Mice by Inhibiting Cytokine-Mediated Apoptosis in Intestinal Crypt Cells

Clinical chemotherapy frequently causes intestinal mucositis as a side effect, which is accompanied by severe diarrhea. We recently showed that the cytokine-mediated apoptotic pathway might be important for the development of intestinal mucositis induced by 5-fluorouracil (5-FU). Saireito, the traditional Japanese herbal (Kampo) medicine, is widely used to treat diarrhea and various inflammatory diseases in Japan. In the present study, we investigated the effect of saireito on 5-FU-induced intestinal mucositis in mice, especially in relation to apoptosis in the intestinal crypt. Male C57BL/6 mice were given 5-FU (50 mg/kg), i.p. once daily for 6 days. Intestinal mucositis was evaluated histochemically. Saireito (100–1000 mg/kg) was administered p.o. twice daily for 6 days. Repeated 5-FU treatment caused severe intestinal mucositis including morphological damage, which was accompanied by body weight loss and diarrhea. Daily administration of saireito reduced the severity of intestinal mucositis in a dose-dependent manner. Body weight loss and diarrhea during 5-FU treatment were also significantly attenuated by saireito administration. The number of apoptotic and caspase-3-activated cells in the intestinal crypt was increased, and was accompanied by up-regulated tumor necrosis factor (TNF)-α and interleukin (IL)-1β mRNA within 24 h of the first 5-FU injection. However, all of these measures were significantly lower after saireito administration. These results suggest that saireito attenuates 5-FU-induced intestinal mucositis. This action may come from the reduction of apoptosis in the intestinal crypt via suppression of the up-regulation of inflammatory cytokines. Therefore, saireito may be clinically useful for the prevention of intestinal mucositis during cancer chemotherapy.     

The anorexic effect of alpha-melanocyte-stimulating hormone is mediated by corticotrophin-releasing factor in chicks

Alpha-melanocyte-stimulating hormone (alpha-MSH) is recognized as an anorexic peptide in the brain of vertebrates, but its mechanism of action has not been identified in birds. Therefore, we investigated whether the anorexic effect of alpha-MSH is mediated by corticotrophin-releasing factor (CRF) in the domestic chick. Firstly, we found that intracerebroventricular (i.c.v.) injection of alpha-MSH dose dependently increased plasma corticosterone (CORT) concentration. This effect was partly attenuated by co-injection of astressin, a CRF receptor antagonist, demonstrating that alpha-MSH stimulated CORT secretion by activating CRF neurons. The alpha-MSH-elicited CORT release was not attenuated by the injection of agouti-related protein, an endogenous melanocortin-4 (MC4) receptor antagonist, suggesting that alpha-MSH stimulated CRF neurons through MC4 receptor-independent pathways. Finally, we found that the anorexic effect of alpha-MSH was partly attenuated by astressin. The present results suggest that the anorexic effect of alpha-MSH in the chick brain is mediated in part by activation of CRF neurons.