Phytophthora austrocedrae sp. nov., a new species associated with Austrocedrus chilensis mortality in Patagonia (Argentina)

Phytophthora austrocedrae is a new species isolated from necrotic lesions of stem and roots of Austrocedrus chilensis. It is a homothallic species characterized by semipapillate sporangia, oogonia with amphigynous antheridia, and very slow growth (1–2 mm d⁻¹ on V-8 agar at 17.5 °C optimum temperature). Phylogenetic analysis of ITS rDNA sequence indicates that its closest relative is Phytophthora syringae, another species frequently isolated from soil and streams in A. chilensis forests.     

Chemiluminescent optical fiber immunosensor for detection of autoantibodies to ovarian and breast cancer-associated antigens

We report herein the development of an optical fiber based chemiluminescent immunosensor for detection of the native autoimmune response to GIPC-1, a PDZ containing protein involved in regulation of G-protein signaling. The recombinant protein GIPC-1 was expressed in bacteria, purified, refolded and conjugated to the tip of an optical fiber. A human monoclonal 27.B1 IgM isolated from a breast cancer patient, which targets the GIPC-1 protein, was used for calibration of the immunosensor and was detected down to a concentration of 30 pg/ml. We determined that the fiber-optic immunosensor had a detection limit 50 times lower than chemiluminescent ELISA, and approximately 500 times lower than colorimetric ELISA. In addition, sera from 11 ovarian cancer patients, 22 breast cancer patients and asymptomatic controls were tested for the presence of IgM anti-GIPC-1 autoantibodies in their serum using the two methods. The immunosensor assay detected 54% and 77% GIPC-1 positive sera within ovarian and breast cancer patients, respectively, as compared to chemiluminescent ELISA, which only detected 18% and 27%, respectively. We envision that this immunosensor may serve as a diagnostic tool for screening women for ovarian and breast cancer at an early stage, thus increasing their chance of survival.     

Season of diagnosis is a predictor of cancer survival. Sun-induced vitamin D may be involved: a possible role of sun-induced Vitamin D

The calcidiol level in a group of Norwegians (14,000 individuals, age range 16–80) was found to be highest in late summer. The seasonal variation was larger for young than for old persons. The calcitriol concentration was practically constant throughout the year. Younger persons had less calcidiol and more calcitriol than older persons, indicating that the conversion of calcidiol to calcitriol is more efficient in younger persons.

A seasonal variation of prognosis of cancer (colon-, breast-, prostate- cancer and Hodgkin lymphoma) was found. The survival is highest for summer and autumn diagnosis, corresponding to maximal calcidiol levels. Thus, calcidiol may act synergistically with traditional treatment modalities.

In view of these calcitriol and calcidiol data, the seasonal variation of cancer survival may be related to the calcidiol gradient, indicating that this Vitamin D metabolite may be more important than believed so far.     

Amino acid residues responsible for the recognition of dichloroacetate by pyruvate dehydrogenase kinase 2

Dichloroacetate (DCA) is a promising anticancer and antidiabetic compound targeting the mitochondrial pyruvate dehydrogenase kinase (PDHK). This study was undertaken in order to map the DCA-binding site of PDHK2. Here, we present evidence that R114, S83, I157 and, to some extent, H115 are essential for DCA binding. We also show that Y80 and D117 are required for the communication between the DCA-binding site and active site of PDHK2. These observations provide important insights into the mechanism of DCA action that may be useful for the design of new, more potent therapeutic compounds.     

Molecular Genetic Causes and Clinical Description of Branchio-Oto-renal Syndrome

Russian Journal of Genetics - Branchio-oto-renal (BOR) syndrome is an autosomal dominant disease characterized by a combination of hearing impairment with preauricular pits, cervical fistulas or...     

Sulfamides as novel histone deacetylase inhibitors

The sulfamide moiety has been utilized to design novel HDAC inhibitors. The potency and selectivity of these inhibitors were influenced both by the nature of the scaffold, and the capping group. Linear long-chain-based analogs were primarily HDAC6-selective, while analogs based on the lysine scaffold resulted in potent HDAC1 and HDAC6 inhibitors.     

Human plasma-mediated hypoxic activation of indolequinone-based naloxone pro-drugs

Hypoxia is known to occur in tissues in response to narcotic analgesic therapy using as a result of respiratory depression. The aim of this study was to synthesize a narcotic antagonist pro-drug that can be activated by tissue hypoxia to prevent the damage associated with respiratory depression. We synthesized three different pro-drugs of the narcotic antagonist naloxone utilizing indolequinone as the hypoxia-sensitive moiety. The indolequinone structure in the pro-drugs was designed to have an open reactive point at the N-1 position offering the possibility of further conjugation with macromolecules to modify the bio-availability of these pro-drugs in vivo. A pro-drug (labeled 1) where naloxone and the indolequinone moiety were linked through a carbonate bond was rapidly hydrolyzed in phosphate buffered saline. However, two additional pro-drugs (labeled 2 and 3) having carbamate linkers were stable in phosphate buffered saline for 24 h. The reductive release of naloxone from the pro-drugs was achieved in the presence of the bio-reductive enzyme DT-Diaphorase, with about 80% release occurring from the two pro-drugs in 24 h. More than 99% of naloxone was released from pro-drug 2 in 30% human plasma, however the release only occurred under hypoxic conditions. This system provides a potential means for feedback control to counter critical respiratory depression induced by narcotic analgesics.     

Seasonal variation of 1,25-dihydroxyvitamin D and its association with body mass index and age

Under most normal conditions the serum level of 1,25-dihydroxyvitamin D is constant throughout the year, due to tight biochemical regulation. In contrast to this, the level of 25-hydroxyvitamin D is variable through the year, being largest in late summer, due to photosynthesis in the skin. The vitamin D status is usually assessed by measuring the level of the latter vitamin D derivative, rather than that of the presumably most active derivative 1,25(OH)₂ vitamin D.We here show that for persons with a high body mass index (BMI) there is a significant seasonal variation, not only of 25(OH) vitamin D, but also of 1,25(OH)₂ vitamin D. The variation seems to be largest for those with the poorest vitamin D status. Furthermore, there seems to be a correlation between the levels of the two vitamin D metabolites, indicating that the regulation of 1,25(OH)₂ vitamin D is not always tight, notably in persons with high BMI.     

Amiodarone inhibits multiple drug resistance in yeast <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis>

Amiodarone is a widely used antiarrhythmic drug. There is also evidence that amiodarone decreases multidrug resistance in human cell lines. In this paper, we have shown that amiodarone has similar effect on yeast, Saccharomyces cerevisiae, decreasing multiple drug resistance. Amiodarone stimulates the accumulation of ethidium bromide by inhibiting its efflux from the cells. The effect of amiodarone is much stronger on wild-type cells compared to the mutant with inactivated ABC-transporters. Interestingly, the action of amiodarone is additive with the one of chloroquine, a known inhibitor of ABC-transporters. We speculate that these findings could help in the development of antifungal drug mixes.