Complexes of Starchy Materials with Organic Compounds

The crystal structure of γ-cyclodextrin complexes with several organic compounds have been investigated by X-ray powder method. A two-dimensional tetragonal unit cell having a=b=27.2 Å and a two-dimensional hexagonal unit cell having a=b=32.7 Å, were reasonably proposed for hydrated and anhydrous γ-dextrin complexes, respectively. The change of the crystal structure caused by dehydration seemed to be resulted from the change of the packing arrangement of circular cylinders that are made by coaxial alignment of the dextrin molecules. Results obtained were tentatively applied to consider the 8₁-helical configuration of amylose.     

Microbial Production of d-Arabitol by n-Alkane-grown Candida tropicalis

In the course of study on citric acid fermentation by Candida tropicalis KY6224, in which n-alkane mixture (C–12 to C–15) was used as the sole source of carbon, we found that a arabitollike substance was accumulated when the medium-pH was controlled at low level (3.0 to 4.0). This substance was isolated in crystalline forms and identified as d-arabitol.

d-Arabitol production was also observed with ethanol, acetic acid and glucose as the sole source of carbon. Important factors for efficient production of d-arabitol were keeping the medium-pH at low-level (3.0 to 4.0) and the concentration of NaCl or KCl at high level (1 to 5%). This strain produced 75 mg/ml of d-arabitol in 120 hr incubation under optimal culture conditions; this corresponds to 50 % of n-alkane consumed.     

Production of Corynecins by Chloramphenicol Resistant Mutants of Corynebacterium hydrocarboclastus

The isolation of chloramphenicol resistant strains from Corynebacterium hydrocarboclastus KY 4339 (rough type) was examined to seek a good source of corynecins (analogs of chloramphenicol). Various mutants resistant to chloramphenicol were isolated in the range from 50 to 1000 µg/ml by adaptation or induced mutagenesis by N-methyl-N′-nitro-N-nitro-soguanidine. Productivities of mutants related apparently to the degree of resistance from 50 to 500 µg/ml. Highly resistant mutants capable of growing in the presence of 1000 µg of chloramphenicol per ml showed decreased productivity which might be related to their lower growth rate in the fermentation medium.

Further attempts to derive resistant mutants to structural analogs of aromatic amino acids resulted in only a slight improvement of productivity, indicating that aromatic amino acids might play minor regulatory roles in corynecins synthesis.

The increase in productivity of corynecins by the best strain was about 4.5 fold of the parental strain.     

Antiviral Effect of Theaflavins on Tobacco Mosaic Virus

Theaflavins, the oxidized products formed from tea leaf catechins during black tea fermentation, showed an antiviral activity on TMV. From the survey of the interactions of theaflavins with RNA and its related substances, it was presumed that theaflavins disturbed the replication cycle of TMV through binding to TMV-RNA.     

Production of Erythritol by n-Alkane-grown Yeasts

In the course of study on citric acid fermentation by Candida zeylanoides, in which n-alkane (a mixture of C–12 to C–15) was used as the sole source of carbon, we found that a polyol-like substance was accumulated when the medium-pH fell down to below 4.0. This was isolated in crystalline forms and identified as meso-erythritol. Comparing erythritol production among fifty yeast strains, Candida zeylanoides, particularly its glycerol-requiring mutant KY 6166, was found to be an excellent producer.

Erythritol production was also observed with ethanol or acetic acid as the sole carbon source but not with glucose. An efficient condition for large production of erythritol was to keep the medium-pH at low level (2.5 to 4.0) and the concentration of NaCl or KCl at high level (1 to 3%). Under conditions established in this work, more than 55 mg/ml of erythritol was successfully produced in 120 hr incubation in 300-ml flasks, which corresponded to 55% of the alkane used.     

Aberrant Glycogen Synthase Kinase 3β Is Involved in Pancreatic Cancer Cell Invasion and Resistance to Therapy

Background and Purpose

The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer.

Methods

Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined.

Results

Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts.

Conclusion

The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer.     

Association between Soluble (Pro)Renin Receptor Concentration in Cord Blood and Small for Gestational Age Birth: A Cross-Sectional Study

Objective

The (pro)renin receptor [(P)RR] has been recognized as a multifunctional receptor. The purpose of this study was to assess the association between plasma soluble (P)RR [s(P)RR] concentration in human cord blood (i.e., neonatal blood at birth) and small for gestational age (SGA) birth.

Methods

Participants were women with a singleton pregnancy who delivered at the National Center for Child Health and Development between January 2010 and December 2011. Inclusion criteria were availability of maternal pre-pregnancy and paternal body mass index, and the absence of structural anomalies in neonates. s(P)RR concentration in cord blood was measured in 621 neonates. The 621 pairs of mothers and neonates were categorized into four groups based on quartiles of s(P)RR concentrations in cord blood. SGA was defined as a birth weight below the 10^th percentile for gestational age. Logistic regression analysis was performed to assess the association between cord plasma s(P)RR concentration (quartiles) and incidence of SGA births.

Results

Among 621 neonates, 55 (8.9%) were diagnosed as SGA (SGA group) and 566 (91.1%) were not (non-SGA group). Average s(P)RR concentration in cord blood was 66.1±12.6 ng/ml (mean±standard deviation). There were 155 pairs in the first plasma s(P)RR concentration quartile (Q1: <58.2 ng/ml), 153 pairs in the second quartile (Q2: 58.2–65.1 ng/ml), 157 pairs in the third quartile (Q3: 65.1–73.1 ng/ml) and 156 pairs in the fourth quartile (Q4: >73.1 ng/ml). The distribution of SGA births was 18 (11.6%) in Q1, 14 (9.2%) in Q2, 16 (10.2%) in Q3 and 7 (4.5%) in Q4, respectively. The odds ratio of SGA births was 0.24 (95% confidence interval: 0.08–0.71) for the fourth quartile compared to the first quartile in multivariate models. The P-value for trend was also significant (P = 0.020).

Conclusion

High s(P)RR concentration is associated with a lower SGA birth likelihood.