Craniodental mechanics and diet in Asian colobines: Morphological evidence of mature seed predation and sclerocarpy

Folivory has been accepted as the general dietary pattern for colobines. However, recent ecological studies have revealed that extensive seed eating is found in some colobine species. The ripeness of foraged seeds is also reported to differ between seed eaters. As seeds are generally stress‐limited and may pose greater mechanical demands, seed‐eating species are predicted to exhibit morphological features adaptive for seed predation. In addition, species that feeds on seeds from unripe fruits with hard pericarp is predicted to exhibit increased leverage for anterior dentition. To test these hypotheses, we compared the craniodental morphology of seed‐eating Asian colobines (Presbytis rubicunda and Trachypithecus phayrei) with those of species that rarely exploit seeds (Presbytis comata, Trachypithecus obscurus, and Semnopithecus vetulus). The results show that the seed‐eating colobines possess a masticatory system with enhanced leverage at postcanine bite points. The sclerocarpic forager P. rubicunda also exhibits markedly greater masticatory leverage at anterior dental bite points, while the mature‐seed‐eating T. phayrei shows no such advantage for canine and incisor use. These observations suggest that P. rubicunda is well adapted to husking the resistant pericarps of unripe fruits, using the anterior dentition and to gain access to the immature seeds, whereas such sclerocarpic feeding behavior may be less important for T. phayrei. Our findings indicate that the distinctive craniodental variations of colobines may be linked to mature and/or immature seed eating and suggest the significance of seed predation for the evolution of colobine monkeys. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.     

Interaction of angiotensin II type 1 receptor blockers with P-gp substrates in Caco-2 cells and hMDR1-expressing membranes

AimsThe inhibitory effect of angiotensin II type 1 receptor blockers (ARBs) on P-glycoprotein (P-gp) was examined to evaluate their clinical drug–drug interaction (DDI) potential.Main methodsWe performed an inhibition study on the vectorial transport of digoxin, a typical substrate for P-gp, using a human colonic adenocarcinoma cell line, Caco-2 cells, and verapamil-stimulated ATPase activity using human multidrug resistance 1 (hMDR1)-expressing membrane.Key findingsThe vectorial transport of digoxin was inhibited by candesartan cilexetil, irbesartan and telmisartan with the IC₅₀ values of 14.7, 34.0 and 2.19 µM, respectively. Those values were 7.4–426-fold higher than their theoretical clinical gastrointestinal concentration [I] at doses in clinical DDI studies. Other ARBs failed to show interaction with P-gp.SignificanceIt was demonstrated that candesartan cilexetil, irbesartan and telmisartan had the potential to inhibit the transport of various drugs via P-gp. Telmisartan, which caused an increase in the serum digoxin concentration in humans, had a sufficiently high [I]/IC₅₀ value, suggesting that DDI between digoxin and telmisartan was caused by the inhibition of digoxin efflux via intestinal P-gp.     

Tea catechins reduce inflammatory reactions via mitogen-activated protein kinase pathways in toll-like receptor 2 ligand-stimulated dental pulp cells

AimsIn this study, we evaluated whether catechins could inhibit the expression of pro-inflammatory mediators induced by dental caries-related bacteria, Streptococci, or pathogen-associated molecular patterns (PAMPs) stimulation in human dental pulp fibroblasts (HDPF). We further determined the mechanisms of the anti-inflammatory activity of catechins.Main methodsStreptococci or PAMP-stimulated HDPF were treated with catechin, and then the expression and production of pro-inflammatory mediators were determined by RT-PCR and ELISA. Furthermore, the signal transduction pathways activated with toll-like receptor (TLR)2 ligand were assessed by Immunoblot and ELISA using blocking assay with specific inhibitors.Key findingsIncreased expressions of pro-inflammatory mediators are found in inflamed dental pulp, especially in HDPF. We recently reported that dental pulpal innate immune responses may mainly result from the predominantly-expressed TLR2 signaling. Catechins, polyphenolic compounds in green tea, exert protective and healing effects through multiple mechanisms, including antioxidative and anti-inflammatory effects. However, there are no reports concerning the effects of catechins on dental pulp. In this study, we demonstrated that the up-regulated expressions of IL-8 or PGE₂ in Streptococci or PAMP-stimulated HDPF were inhibited by catechins, (?)-epicatechin gallate (ECG) and (?)-epigallocatechin gallate (EGCG). In TLR2 ligand-stimulated HDPF, specific inhibitors of extracellular signal regulated kinase (ERK)1/2, p38, c-jun NH₂-terminal kinase (SAP/JNK), NF-κB or catechins markedly reduced the level of pro-inflammatory mediators and the phosphorylation of these signal transduction molecules was suppressed by catechins.SignificanceThese findings suggest that catechins might be useful therapeutically as an anti-inflammatory modulator of dental pulpal inflammation.     

Quinone-dependent D-lactate dehydrogenase Dld (Cg1027) is essential for growth of <Emphasis Type="Italic">Corynebacterium glutamicum</Emphasis> on D-lactate

Background  

Corynebacterium glutamicum is able to grow with lactate as sole or combined carbon and energy source. Quinone-dependent L-lactate dehydrogenase LldD is known to be essential for utilization of L-lactate by C. glutamicum. D-lactate also serves as sole carbon source for C. glutamicum ATCC 13032.     

The Mek1 phosphorylation cascade plays a role in meiotic recombination of Schizosaccharomyces pombe

Mek1 is a Chk2/Rad53/Cds1-related protein kinase that is required for proper meiotic progression of Schizosaccharomyces pombe. However, the molecular mechanisms of Mek1 regulation and Mek1 phosphorylation targets are unclear. Here, we report that Mek1 is phosphorylated at serine-12 (S12), S14 and threonine-15 (T15) by Rad3 (ATR) and/or Tel1 (ATM) kinases that are activated by meiotic programmed double-strand breaks (DSBs). Mutations of these sites by alanine replacement caused abnormal meiotic progression and recombination rates. Phosphorylation of these sites triggers autophosphorylation of Mek1; indeed, alanine replacement mutations of Mek1-T318 and -T322 residues in the activation loop of Mek1 reduced Mek1 kinase activity and meiotic recombination rates. Substrates of Mek1 include Mus81-T275, Rdh54-T6 and Rdh54-T673. Mus81-T275 is known to regulate the Mus81 function in DNA cleavage, whereas Rdh54-T6A/T673A mutant cells showed abnormal meiotic recombination. Taken together, we conclude that the phosphorylation of Mek1 by Rad3 or Tel1, Mek1 autophosphorylation and Mus81 or Rdh54 phosphorylation by Mek1 regulate meiotic progression in S. pombe.Key words: Mek1, meiotic recombination, phosphorylation, Rdh54, Mus81     

Persistence of caliciviruses in artificially contaminated oysters during depuration

The fate of calicivirus in oysters in a 10-day depuration was assessed. The norovirus gene was persistently detected from artificially contaminated oysters during the depuration, whereas feline calicivirus in oysters was promptly eliminated. The prolonged observation of norovirus in oysters implies the existence of a selective retention mechanism for norovirus within oysters.     

A high-throughput and generic assay method for the determination of substrate specificities of thermophilic alpha-aminotransferases

For the determination of substrate specificities of thermophilic alpha-aminotransferases (AATs), a novel high-throughput assay method was developed. In this method, a thermophilic omega-aminotransferase (OAT) and a thermophilic aldehyde dehydrogenase (ALDH) are coupled to the AAT reaction. Glutamic acid is used as an amino group donor for the AAT reaction yielding 2-oxoglutalic acid. 2-Oxoglutalic acid produced by the AAT reaction is used as an amino group acceptor in the OAT reaction regenerating glutamic acid. The amino group donor of the OAT reaction is 5-aminopentanoic acid yielding pentanedioic acid semialdehyde which is oxidized by ALDH to pentanedioic acid with concomitant reduction of NADP(+) to NADPH. NADPH thus produced then reduces colorless tetrazolium salt into colored formazan. To construct such a reaction system, the genes for a thermophilic AAT, a thermophilic OAT and a thermophilic ALDH were cloned and expressed in Escherichia coli. These enzymes were subsequently purified and used to determine the activities of AAT for the synthesis of unnatural amino acids. This method allowed the clear detection of the AAT activities as it measures the increase in the absorbance on a low background absorbance reading.     

Rat organic solute carrier protein 1 (rOscp1) mediated the transport of organic solutes in Xenopus laevis oocytes: isolation and pharmacological characterization of rOscp1

Rat organic solute carrier protein 1 (rOscp1) was isolated from a rat testis cDNA library. Isolated rOscp1 cDNA consisted of 1089 base pairs that encoded a 363-amino acid protein, and the amino acid sequence was 88% and 93% identical to that of human OSCP1 (hOSCP1) and mouse Oscp1 (mOscp1), respectively. The message for rOscp1 is highly detected in rat testis. When expressed in X. oocytes, rOscp1 mediated the high affinity transport of p-aminohippurate (PAH) with a Km value of 15.7+/-1.9 microM, and rOscp1-mediated organic solutes were exhibited in time- and Na+-independent manners. rOscp1 also transported various structurally heterogenous compounds such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), and taurocholate with some differences in substrate specificity compared with hOSCP1. Immunohistochemical analysis revealed that the rOscp1 protein is localized in the basal membrane side of Sertoli cells as observed in mouse testis [Kobayashi et al., 2007; Kobayashi, Y., Tsuchiya, A., Hayashi, T., Kohyama, N., Ohbayashi, M., Yamamoto, T., 2007. Isolation and characterization of polyspecific mouse organic solute carrier protein 1 (mOscp1). Drug Metabolism and Disposition 35 (7), 1239-1245]. Thus, the present results indicate that a newly isolated cDNA clone, rOscp1, is a polyspecific organic solute carrier protein with some differences in substrate specificity compared with human and mouse OSCP1.