Functional role of hedgehog pathway in osteoarthritis

The hedgehog signalling pathway is one of the key regulators of metazoan development, and it plays an important role in the regulation of a variety of developmental and physiological processes. But it is aberrantly activated in many human diseases, including osteoarthritis (OA). In this study, we have reviewed the association of hedgehog signalling pathway in the development and progression of OA and evaluated the efforts to target this pathway for the prevention of OA. Usually in OA, activation of hedgehog induces up-regulation of the expression of hypertrophic markers, including type X collagen, increases production of nitric oxide and prostaglandin E2, several matrix-degrading enzymes including matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motifs in human knee joint cartilage leading to cartilage degeneration, and thus contributes in OA. Targeting hedgehog signalling might be a viable strategy to prevent or treat OA. Chemical inhibitors of hedgehog signalling is promising, but they cause severe side effects. Knockdown of HH gene is not an option for OA treatment in humans because it is not possible to delete HH in larger animals. Efficient knockdown of HH achieved by local delivery of small interfering RNA in future studies utilizing large animal OA models might be a more efficient approach for the prevention of OA. However, it remains a major problem to develop one single scaffold due to the different physiological functions of cartilage and subchondral bones possess. More studies are necessary to identify selective inhibitors for efficiently targeting the hedgehog pathway in clinical conditions.     

Recent H3N2 Influenza Virus Clinical Isolates Rapidly Acquire Hemagglutinin or Neuraminidase Mutations When Propagated for Antigenic Analyses

Prior to serological testing, influenza viruses are typically propagated in eggs or cell culture. Recent human H3N2 strains bind to cells with low avidity. Here, we isolated nine primary H3N2 viral isolates from respiratory secretions of children. Upon propagation in vitro, five of these isolates acquired hemagglutinin or neuraminidase mutations that increased virus binding to cell surfaces. These mutations can potentially confound serological assays commonly used to identify antigenically novel influenza viruses.     

Accuracy of predicting genomic breeding values for carcass merit traits in Angus and Charolais beef cattle

Accuracy of predicting genomic breeding values for carcass merit traits including hot carcass weight, longissimus muscle area (REA), carcass average backfat thickness (AFAT), lean meat yield (LMY) and carcass marbling score (CMAR) was evaluated based on 543 Angus and 400 Charolais steers genotyped on the Illumina BovineSNP50 Beadchip. For the genomic prediction within Angus, the average accuracy was 0.35 with a range from 0.32 (LMY) to 0.37 (CMAR) across different training/validation data‐splitting strategies and statistical methods. The within‐breed genomic prediction for Charolais yielded an average accuracy of 0.36 with a range from 0.24 (REA) to 0.46 (AFAT). The across‐breed prediction had the lowest accuracy, which was on average near zero. When the data from the two breeds were combined to predict the breeding values of either breed, the prediction accuracy averaged 0.35 for Angus with a range from 0.33 (REA) to 0.39 (CMAR) and averaged 0.33 for Charolais with a range from 0.18 (REA) to 0.46 (AFAT). The prediction accuracy was slightly higher on average when the data were split by animal's birth year than when the data were split by sire family. These results demonstrate that the genetic relationship or relatedness of selection candidates with the training population has a great impact on the accuracy of predicting genomic breeding values under the density of the marker panel used in this study.     

Evaluation of Mercury Contamination in Fungi Boletus Species from Latosols,Lateritic Red Earths,and Red and Yellow Earths in the Circum-Pacific Mercuriferous Belt of Southwestern China

For the first time, highly elevated levels of mercury (Hg) have been documented for several species of the edible Fungi genus Boletus growing in latosols, lateritic red earths, and red and yellow earths from the Yunnan province of China. Analysis of Hg concentrations in the genus suggests that geogenic Hg is the dominant source of Hg in the fungi, whereas anthropogenic sources accumulate largely in the organic layer of the forest soil horizon. Among the 21 species studied from 32 locations across Yunnan and 2 places in Sichuan Province, the Hg was found at elevated level in all samples from Yunnan but not in the samples from Sichuan, which is located outside the mercuriferous belt. Particularly abundant in Hg were the caps of fruiting bodies of Boletus aereus (up to 13 mg kg^-1 dry matter), Boletus bicolor (up to 5.5 mg kg^-1 dry matter), Boletus edulis (up to 22 mg kg^-1 dry matter), Boletus luridus (up to 11 mg kg^-1 dry matter), Boletus magnificus (up to 13 mg kg^-1 dry matter), Boletus obscureumbrinus (up to 9.4 mg kg^-1 dry matter), Boletus purpureus (up to 16 mg kg^-1 dry matter), Boletus sinicus (up to 6.8 mg kg^-1 dry matter), Boletus speciosus (up to 4.9mg kg^-1 dry matter), Boletus tomentipes (up to 13 mg kg^-1 dry matter), and Boletus umbriniporus (up to 4.9 mg kg^-1 dry matter). Soil samples of the 0–10 cm topsoil layer from the widely distributed locations had mercury levels ranging between 0.034 to 3.4 mg kg^-1 dry matter. In Yunnan, both the soil parent rock and fruiting bodies of Boletus spp. were enriched in Hg, whereas the same species from Sichuan, located outside the mercuriferous belt, had low Hg concentrations, suggesting that the Hg in the Yunnan samples is mainly from geogenic sources rather than anthropogenic sources. However, the contribution of anthropogenically-derived Hg sequestered within soils of Yunnan has not been quantified, so more future research is required. Our results suggest that high rates of consumption of Boletus spp. from Yunnan can deliver relatively high doses of Hg to consumers, but that rates can differ widely because of large variability in mercury concentrations between species and locations.     

Overexpression of Tau Downregulated the mRNA Levels of Kv Channels and Improved Proliferation in N2A Cells

Microtubule binding protein tau has a crucial function in promoting the assembly and stabilization of microtubule. Besides tuning the action potentials, voltage-gated K⁺ channels (Kv) are important for cell proliferation and appear to play a role in the development of cancer. However, little is known about the possible interaction of tau with Kv channels in various tissues. In the present study, tau plasmids were transiently transfected into mouse neuroblastoma N2A cells to explore the possible linkages between tau and Kv channels. This treatment led to a downregulation of mRNA levels of several Kv channels, including Kv2.1, Kv3.1, Kv4.1, Kv9.2, and KCNH4, but no significant alteration was observed for Kv5.1 and KCNQ4. Furthermore, the macroscopic currents through Kv channels were reduced by 36.5% at +60 mV in tau-tranfected N2A cells. The proliferation rates of N2A cells were also improved by the induction of tau expression and the incubation of TEA (tetraethylammonium) for 48 h by 120.9% and 149.3%, respectively. Following the cotransfection with tau in HEK293 cells, the mRNA levels and corresponding currents of Kv2.1 were significantly declined compared with single Kv2.1 transfection. Our data indicated that overexpression of tau declined the mRNA levels of Kv channels and related currents. The effects of tau overexpression on Kv channels provided an alternative explanation for low sensitivity to anti-cancer chemicals in some specific cancer tissues.     

Extraction Optimization,Characterization and Bioactivities of a Major Polysaccharide from Sargassum thunbergii

Sargassum thunbergii is a kind of natural edible algae. STP (S. thunbergii polysaccharides) was considered as the main bioactive compounds in S. thunbergii. To obtain the optimal processing conditions for maximum total sugar yield, single factor investigation and response surface methodology (RSM) were employed. The optimal processing conditions were as follows: liquid to solid ratio 120 mL/g, extraction time 210 min, extraction temperature 97°C. The experimental yield 7.53% under optimized conditions was closely agreed with the predicted yield 7.85% of the model. The major polysaccharide fraction from S. thunbergii (named STP-II) was purified by DEAE-Sepharose CL-6B column chromatography. High-performance size-exclusion chromatography (HPSEC), gas chromatography (GC) and high-performance liquid chromatography (HPLC) were used to identify its characterizations, and in vitro antioxidant assays and cytotoxicity assays were used to research its bioactivities. The purified fraction STP-II (63.75%) was a single peak in HPSEC with Sugar KS-804 column, had a molecular weight of 550KD, and comprised mainly of fucose, xylose, galactose, glucose and glucuronic acid. STP-II had higher scavenging activities on hydroxyl radical (76.72% at 0.7 mg/mL) and superoxide radical (95.17% at 2 mg/mL) than Vitamin C (Vc). STP-II also exhibited the capability of anti-proliferation in Caco-2 cells. STP-II possessed good antioxidant and inhibitory activity against human colon cancer Caco-2 cells in vitro and could be explored as novel natural functional food.