Thioredoxin 1 as a serum marker for breast cancer and its use in combination with CEA or CA15-3 for improving the sensitivity of breast cancer diagnoses

Background

Influenza B and C are single-stranded RNA viruses that cause yearly epidemics and infections. Knowledge of RNA secondary structure generated by influenza B and C will be helpful in further understanding the role of RNA structure in the progression of influenza infection.

Findings

All available protein-coding sequences for influenza B and C were analyzed for regions with high potential for functional RNA secondary structure. On the basis of conserved RNA secondary structure with predicted high thermodynamic stability, putative structures were identified that contain splice sites in segment 8 of influenza B and segments 6 and 7 of influenza C. The sequence in segment 6 also contains three unused AUG start codon sites that are sequestered within a hairpin structure.

Conclusions

When added to previous studies on influenza A, the results suggest that influenza splicing may share common structural strategies for regulation of splicing. In particular, influenza 3′ splice sites are predicted to form secondary structures that can switch conformation to regulate splicing. Thus, these RNA structures present attractive targets for therapeutics aimed at targeting one or the other conformation.     

Discovery of genes for ginsenoside biosynthesis by analysis of ginseng expressed sequence tags

Expressed sequence tags (ESTs) provide a valuable tool that can be used to identify genes in secondary metabolite biosynthesis. Ginseng (Panax ginseng C.A Meyer) is a medicinal plant that accumulates ginsenosides in roots. We sequenced 11,636 ESTs from five ginseng libraries in order to create a gene resource for biosynthesis of ginsenosides, which are thought to be the major active component in roots. Only 59% of the ginseng ESTs exhibited significant homology to previously known polypeptide sequences. Stress- and pathogen-response proteins were most abundant in 4-year-old ginseng roots. ESTs involved in ginsenoside biosynthesis were identified by a keyword search of BLASTX results and a domain search of ginseng ESTs. We identified 4 oxidosqualene cyclase candidates involved in the cyclization reaction of 2,3-oxidosqualene, 9 nine cytochrome P450 and 12 glycosyltransferse candidates, which may be involved in modification of the triterpene backbone.Abbreviations cDNA Complementary DNA - ESTs Expressed sequence tagsCommunicated by I.S. Chung     

Synthesis and biological evaluation of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors

A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphenyl)-3-(6-methylpyridin-2-yl)-1H-pyrazole-1-carbothioamide (14n) inhibited ALK5 phosphorylation with IC(50) value of 0.57 nM and showed 94% inhibition at 100 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.     

Homogeneity of recombination rate within a conserved region on BTA3 that contains QTL

The D3S20-D3S34-D3S3 region on BTA3 contains quantitative trait loci (QTL) controlling milk production traits. This region also displays extensive conservation of synteny among several species including cattle, humans, mice and sheep. In this study, we evaluated the adjacent intervals D3S20-D3S34 and D3S34-D3S3 for differences in recombination rate (theta) among bulls in order to assess the suitability of population-based estimates of theta for marker assisted selection and to explore the relationship between variation in theta and chromosome breakpoints associated with mammalian evolution. Using sperm typing, thetaD3S20-D3S34 and theta D3S34-D3S3 were estimated for six triply heterozygous bulls. Recombination frequency ranged from 6.2 to 12.5% and from 9.7 to 19.2% for the D3S20-D3S34 and D3S34-D3S3 intervals, respectively. However, significant variation in theta was not detected between bulls for either interval (D3S20-D3S34 chi(2)5 d.f.=2.59, P < 0.90; D3S34-D3S3 chi(2)5 d.f.=3.72, P < 0.75). The observed differences in theta were most readily attributed to differences in allele-specific amplification efficiencies among bulls. Our results suggest that the positions of QTL in this region can be reliably determined from population data and therefore accurate marker-assisted selection can be performed for desirable alleles without concern for variation in theta. Furthermore, when considered with results of earlier studies, these findings support a correlation between the existence of evolutionary breakpoints or chromosome rearrangements and variation in theta.     

Comparative analysis of the anxiety-related behaviors in four inbred mice

An anxiety-related behavior is an emotional response of an organism, which is quantitatively measured by several behavioral paradigms. We employed two most frequently used behavioral tests, the open field and light-dark exploration, to comparatively analyze the anxiety-like behaviors in four inbred mice. For an accurate recording of movement, motion analysis software was developed that acquires a real-time video input to generate a behavioral path. Effects of the strains on the test results were evaluated by ANOVA with the Newman-Keuls post hoc comparison. Eight different behavioral indices, four from each tests, were grouped into two classes; the results of duration, center crossing, transition, rearing, and ambulation indicate strain differences of FVB/N>C57BL/6J>/=BALB/cA>/=CBA/N (I), while stretched-attend posture, peeping, and defecation show the tendency of FVB/N=C57BL/6J相似文献   

Effects of carbon dioxide on metabolite production and bacterial communities during kimchi fermentation

Bacterial communities and metabolites in kimchi fermented under conventional conditions (CC) compared to CO₂-rich environments (CO₂) were analyzed. After a 20-day fermentation, lactic and acetic acid productions were 54 and 69 mM under CC, and 19 and 12 mM under CO₂, respectively. The final pH of kimchi fermented under CC (CC-fermenting) and CO₂ (CO₂-fermenting) were 4.1 and 4.7, respectively. For bacterial communities, OTU and Chao1 indices were both 35 in fresh kimchi, 10 and 15 in CC-fermenting kimchi, and 8 and 24 in CO₂-fermenting kimchi, respectively. Shannon and Simpson indices were 3.47 and 0.93 in fresh kimchi, 1.87–0.06 and 0.46–0.01 in CC-fermenting kimchi, and 1.65–0.44 and 0.63–0.12 in CO₂-fermenting kimchi, respectively. Non-lactic acid bacteria were eliminated in fermenting kimchi after 12 days under CC and 6 days under CO₂. I conclude that carbon dioxide can alter bacterial communities, reduce metabolite production, and improve fermented kimchi quality.     

Green fluorescent protein as a signal for protein-protein interactions.

Green fluorescent protein (GFP) is autofluorescent. This property has made GFP useful in monitoring in vivo activities such as gene expression and protein localization. We find that GFP can be used in vitro to reveal and characterize protein-protein interactions. The interaction between the S-peptide and S-protein fragments of ribonuclease A was chosen as a model system. GFP-tagged S-peptide was produced, and the interaction of this fusion protein with S-protein was analyzed by two distinct methods: fluorescence gel retardation and fluorescence polarization. The fluorescence gel retardation assay is a rapid method to demonstrate the existence of a protein-protein interaction and to estimate the dissociation constant (Kd) of the resulting complex. The fluorescence polarization assay is an accurate method to evaluate Kd in a specified homogeneous solution and can be adapted for the high-throughput screening of protein or peptide libraries. These two methods are powerful new tools to probe protein-protein interactions.     

Constitutive RelA activation mediated by Nkx3.2 controls chondrocyte viability

During endochondral ossification, a process that accounts for the majority of bone formation in vertebrates, hypertrophic chondrocytes display a greater susceptibility to apoptosis when compared to proliferating chondrocytes. However, the molecular mechanisms underlying this phenomenon remain unclear. Nkx3.2, a member of the NK class of homeoproteins, is initially expressed in chondrogenic precursor cells, and later, during cartilage maturation, its expression is restricted to proliferating chondrocytes. Here, we show that the nuclear factor kappa B (NF-kappaB) pathway is required for chondrocyte viability and that Nkx3.2 supports chondrocyte survival by constitutively activating RelA. Although signal-dependent NF-kappaB activation has been intensively studied, ligand-independent NF-kappaB activation is poorly understood. The data presented here support a novel ligand-independent mechanism of NF-kappaB activation, whereby Nkx3.2 recruits the RelA-IkappaBalpha heteromeric complex into the nucleus by direct protein-protein interactions and activates RelA through proteasome-dependent IkappaBalpha degradation in the nucleus. Furthermore, we demonstrate that stage-specific NF-kappaB activation, mediated by Nkx3.2, regulates chondrocyte viability during cartilage maturation.