New palaeontological assemblage, sedimentological and chronological data from the Pleistocene Ma U''Oi cave (northern Vietnam)

This paper describes recent material gathered during the second fieldwork at Ma U'Oi in November 2002 by a Vietnamese–French–Japanese team. The Ma U'Oi cave, located in the province of Hoà Binh (60 km SW from Hanoi), northern Vietnam, belongs to a karstic network developed in Triassic dark-grey limestones.

The cave is filled with coarse-grained breccias containing numerous fossil remains, partially preserved at several loci inside the cave (wall, vault and ground). We describe new teeth which confirm the occurrence of mammal taxa already mentioned at Ma U'Oi (Bacon et al., 2004)[Bacon, A-M., Demeter, F., Schuster, M., Long, V.T., Thuy, N.K., Antoine, P-O., Sen, S., Nga, H.H., Huong, N.T.M., 2004. The Pleistocene Ma U'Oi cave, northern Vietnam: palaeontology, sedimentology and palaeoenvironments. Geobios 37, 305–314], while others, mainly microvertebrates, emphasize the occurrence of new species for the Pleistocene of Vietnam. We report here, for the first time, the occurrence of these microvertebrates of different groups (primates, rodents, insectivores, small reptiles and amphibians) in the faunal assemblage. Among mammal taxa, the presence of one more hominid affiliated to archaic Homo is also attested by our findings. U/Th dating carried out on 2 samples extracted from breccia speleothems confirms the biochronological estimate, with fossiliferous fillings ranging from late Middle Pleistocene to Late Pleistocene.     

The relationship between consumption of tyrosine and phenylalanine as precursors of catecholamine at breakfast and the circadian typology and mental health in Japanese infants aged 2 to 5 years

Background

This study aims to examine the relationship between tyrosine and phenylalanine intake at breakfast as precursors of dopamine, and scores on the Torsvall-Åkerstedt Diurnal Type Scale and of mental health in Japanese infants aged 2 to 5 years.

Results

An integrated questionnaire was administered to parents of 1,367 infants attending one of ten nursery schools governed by Kochi City or a kindergarten affiliated with the Faculty of Education at Kochi University (775 answers for analysis: 56.7%) in May and June 2008. Questionnaires included the Torsvall-Åkerstedt Diurnal Type Scale and questions on sleep habits (onset, offset, quality, quantity, and so on), meal habits (content and regularity of timing), and mental health (depressive states). Amount of tyrosine and phenylalanine intake was calculated based on a breakfast content questionnaire and data on the components of amino acids in foods. Infants who ingested more than 800 mg of tyrosine or phenylalanine at breakfast per meal were more morning-type than those who ingested less than 800 mg (ANOVA: P= 0.005). However, this relationship disappeared in the ANCOVA analysis (with the covariance of tryptophan intake, P= 0.894). Infants who ingested more than 800 mg of the two amino acids at breakfast showed significantly higher mental health scores (lower frequency of depressive states) than those who ingested less than 800 mg (ANOVA: P = 0.004). This relationship remained significant when ANCOVA analysis was performed with the covariance of tryptophan (ANCOVA: P= 0.017).

Conclusions

These results suggest that tyrosine and phenylalanine ingested at breakfast are not related with circadian phase, but are relate with mental health in infants.     

Crystal structure of the C-terminal domain of Mu phage central spike and functions of bound calcium ion

Bacteriophage Mu, which has a contractile tail, is one of the most famous genus of Myoviridae. It has a wide host range and is thought to contribute to horizontal gene transfer. The Myoviridae infection process is initiated by adhesion to the host surface. The phage then penetrates the host cell membrane using its tail to inject its genetic material into the host. In this penetration process, Myoviridae phages are proposed to puncture the membrane of the host cell using a central spike located beneath its baseplate. The central spike of the Mu phage is thought to be composed of gene 45 product (gp45), which has a significant sequence homology with the central spike of P2 phage (gpV). We determined the crystal structure of shortened Mu gp45Δ1-91 (Arg92–Gln197) at 1.5 Å resolution and showed that Mu gp45 is a needlelike structure that punctures the membrane. The apex of Mu gp45 and that of P2 gpV contained iron, chloride, and calcium ions. Although the C-terminal domain of Mu gp45 was sufficient for binding to the E. coli membrane, a mutant D188A, in which the Asp amino acid residue that coordinates the calcium ion was replaced by Ala, did not exhibit a propensity to bind to the membrane. Therefore, we concluded that calcium ion played an important role in interaction with the host cell membrane.     

Paclitaxel-Induced Apoptosis Is BAK-Dependent,but BAX and BIM-Independent in Breast Tumor

Paclitaxel (Taxol)-induced cell death requires the intrinsic cell death pathway, but the specific participants and the precise mechanisms are poorly understood. Previous studies indicate that a BH3-only protein BIM (BCL-2 Interacting Mediator of cell death) plays a role in paclitaxel-induced apoptosis. We show here that BIM is dispensable in apoptosis with paclitaxel treatment using bim^−/− MEFs (mouse embryonic fibroblasts), the bim^−/− mouse breast tumor model, and shRNA-mediated down-regulation of BIM in human breast cancer cells. In contrast, both bak ^−/− MEFs and human breast cancer cells in which BAK was down-regulated by shRNA were more resistant to paclitaxel. However, paclitaxel sensitivity was not affected in bax^−/− MEFs or in human breast cancer cells in which BAX was down-regulated, suggesting that paclitaxel-induced apoptosis is BAK-dependent, but BAX-independent. In human breast cancer cells, paclitaxel treatment resulted in MCL-1 degradation which was prevented by a proteasome inhibitor, MG132. A Cdk inhibitor, roscovitine, blocked paclitaxel-induced MCL-1 degradation and apoptosis, suggesting that Cdk activation at mitotic arrest could induce subsequent MCL-1 degradation in a proteasome-dependent manner. BAK was associated with MCL-1 in untreated cells and became activated in concert with loss of MCL-1 expression and its release from the complex. Our data suggest that BAK is the mediator of paclitaxel-induced apoptosis and could be an alternative target for overcoming paclitaxel resistance.     

Eligibility for Bevacizumab as an Independent Prognostic Factor for Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Cohort Study

Background

Bevacizumab requires some unique eligibility criteria, such as absence of hemoptysis and major blood vessel invasion by the tumor. The prognostic impact of these bevacizumab-specific criteria has not been evaluated.

Methods

Patients with stage IIIB/IV, non-squamous non-small cell lung cancer who started chemotherapy before the approval of bevacizumab were reviewed. Patients with impaired organ function, poor performance status or untreated/symptomatic brain metastasis were excluded before the evaluation of bevacizumab eligibility. We compared overall survival and time to treatment failure among patients who were eligible (Group A) or ineligible (Group B) to receive bevacizumab.

Results

Among 283 patients with stage IIIB/IV non-squamous non-small cell lung cancer, eligibility for bevacizumab was evaluated in 154 patients. Fifty-seven patients were considered ineligible (Group B) based on one or more of a history of hemoptysis (n = 20), major blood vessel invasion (n = 43) and cardiovascular disease (n = 8). The remaining 97 patients were classified into Group A. Overall survival was significantly better in Group A (median, 14.6 months) than in Group B (median, 7.1 months; p<0.0001). Time to treatment failure was also significantly longer in Group A (median, 6.9 months) than in Group B (median, 3.0 months; p<0.0001). Adjusted hazard ratios of bevacizumab eligibility for overall survival and time to treatment failure were 0.48 and 0.38 (95% confidence intervals, 0.33–0.70 and 0.25–0.58), respectively.

Conclusion

Eligibility for bevacizumab itself represents a powerful prognostic factor for patients with non-squamous non-small cell lung cancer. The proportion of patients who underwent first-line chemotherapy without disease progression or unacceptable toxicity can also be biased by bevacizumab eligibility. Selection bias can be large in clinical trials of bevacizumab, so findings from such trials should be interpreted with extreme caution.     

Intracellular Lipase Formation by Washed Mycelium Biochemical Studies on Sclerotinia Libertiana. Part 13

Intracellular lipase of the fungus Sclerotina Libertiana Fcl. could be formed powerfully by washed mycelium during shaking in a plain buffer solution, just as well as in the case of shaking culture. Experiments showed revealed it to be favourable to set the mycelium in the experiment harvested at the end of its stationary phase of growth, and that the addition of various respiratory carbon sources had inhibiting effects, while several surface active agents and some enzyme preparations accelerating effects on the lipase formation. Also, the quality and the quantity of consumed cell-materials in the shaking experiment were investigated in relation to lipase formation.     

Investigations on the Influence of a Low Casein Diet on the Free Fatty Acids in Liver Homogenate by a Method with Some Devices in Purification Procedure Using KOH

Previously, some changes were noticed in energy metabolism of rats fed a low casein diet. In connection with these phenomena, influence of a low casein diet on the composition and amounts of free fatty acids in liver homogenate after autolyzing for a few hours was investigated. For the measurement of free fatty acids, they were purified by a method with some devices in purification procedure using KOH. It was found that amounts of free fatty acids in liver homogenate after autolyzing for a few hours were lower in rats fed a low casein diet.     

Structural Studies on “Isosclerotan”, a New Glucan Isolated from Sclerotinia Fungus,by Physical,Chemical and Enzymatic Methods

“Isosclerotan”, a polysaccharide constituent extracted with a sodium hydroxide solution from sclerotia of Sclerotinia libertiana, could be purified by the successive precipitation with the followings; a mixture of copper sulfate and sodium hydroxide, ammonium sulfate, and ethyl alcohol. The preparation proved homogeneous by ultracentrifugal analysis. From sedimentation and viscosity measurements, the molecular weight of isosclerotan was calculated as 6.13 × 10⁶, andas 1.60 × 10⁵ after treatment with a dilute oxalic acid solution. Isosclerotan was scarecely soluble in cold water but soluble in hot water, yielding a highly viscous solution. It exhibited a low positive optical rotation, + 23.0° (in water), and infrared spectrum had a sharp absorption at 890~898 cm^?1, which indicated the prevalence of the β-glycosidic linkage in isosclerotan. Through degradation by acids and enzymes of isosclerotan, there were obtained various oligosaccharides containing β-1.3, β-1.4, and β-1.6 linkages. From results obtained by periodate oxidation and methylation, it is assumed that the polysaccharide involves the 1.3, 1.4, and 1.6 linkages in 47.7%, 16.6% and 35.7%, respectively, and a branching structure about 12.5%.     

Structure of Succinoglucan: Fragmentation by Partial Acid Hydrolysis

Succinoglucan, a succinylated polysaccharide produced by Alcaligenes faecalis var. myxogenes 10C3, was partially hydrolyzed with acid. Fractionation of the neutral oligosaccharides gave cellobiose, gentiobiose, laminaribiose, laminaritriose, 6-O-β-laminaribiosylglucose, 6-O-β-laminaritriosylglucose, and 3-O-β-cellobiosylgalactose, confirming the previous results that the polysaccharide consists of β-(l→3)-linked, (1→4)-linked and (1 →6)-linked d-glucose residues, and β-(1→3)-linked d-galactose residues.

Possible structural features of succinoglucan were discussed on the basis of the above and previous results obtained by Smith degradation.