Tmc1 point mutation affects Ca2+ sensitivity and block by dihydrostreptomycin of the mechanoelectrical transducer current of mouse outer hair cells

The transduction of sound into electrical signals depends on mechanically sensitive ion channels in the stereociliary bundle. The molecular composition of this mechanoelectrical transducer (MET) channel is not yet known. Transmembrane channel-like protein isoforms 1 (TMC1) and 2 (TMC2) have been proposed to form part of the MET channel, although their exact roles are still unclear. Using Beethoven (Tmc1Bth/Bth) mice, which have an M412K point mutation in TMC1 that adds a positive charge, we found that Ca2+ permeability and conductance of the MET channel of outer hair cells (OHCs) were reduced. Tmc1Bth/Bth OHCs were also less sensitive to block by the permeant MET channel blocker dihydrostreptomycin, whether applied extracellularly or intracellularly. These findings suggest that the amino acid that is mutated in Bth is situated at or near the negatively charged binding site for dihydrostreptomycin within the permeation pore of the channel. We also found that the Ca2+ dependence of the operating range of the MET channel was altered by the M412K mutation. Depolarization did not increase the resting open probability of the MET current of Tmc1Bth/Bth OHCs, whereas raising the intracellular concentration of the Ca2+ chelator BAPTA caused smaller increases in resting open probability in Bth mutant OHCs than in wild-type control cells. We propose that these observations can be explained by the reduced Ca2+ permeability of the mutated MET channel indirectly causing the Ca2+ sensor for adaptation, at or near the intracellular face of the MET channel, to become more sensitive to Ca2+ influx as a compensatory mechanism

Heroin type, injecting behavior, and HIV transmission. A simulation model of HIV incidence and prevalence.

Background and aimsUsing mathematical modeling to illustrate and predict how different heroin source-forms: "black tar" (BTH) and powder heroin (PH) can affect HIV transmission in the context of contrasting injecting practices. By quantifying HIV risk by these two heroin source-types we show how each affects the incidence and prevalence of HIV over time. From 1997 to 2010 PH reaching the United States was manufactured overwhelmingly by Colombian suppliers and distributed in the eastern states of the United States. Recently Mexican cartels that supply the western U.S. states have started to produce PH too, replacing Colombian distribution to the east. This raises the possibility that BTH in the western U.S. may be replaced by PH in the future.DesignWe used an agent-based model to evaluate the impact of use of different heroin formulations in high- and low-risk populations of persons who inject drugs (PWID) who use different types of syringes (high vs. low dead space) and injecting practices. We obtained model parameters from peer-reviewed publications and ethnographic research.ResultsHeating of BTH, additional syringe rinsing, and subcutaneous injection can substantially decrease the risk of HIV transmission. Simulation analysis shows that HIV transmission risk may be strongly affected by the type of heroin used. We reproduced historic differences in HIV prevalence and incidence. The protective effect of BTH is much stronger in high-risk compared with low-risk populations. Simulation of future outbreaks show that when PH replaces BTH we expect a long-term overall increase in HIV prevalence. In a population of PWID with mixed low- and high-risk clusters we find that local HIV outbreaks can occur even when the overall prevalence and incidence are low. The results are dependent on evidence-supported assumptions.ConclusionsThe results support harm-reduction measures focused on a reduction in syringe sharing and promoting protective measures of syringe rinsing and drug solution heating

Stable Hydrazone-Linked Covalent Organic Frameworks Containing O,N,O'-Chelating Sites for Fe(III) Detection in Water.

Two stable crystalline hydrazone-linked covalent organic frameworks (COFs) (Bth-Dha and Bth-Dma) containing functional O,N,O'-chelating sites have been designed and successfully synthesized by the Schiff-base condensation reactions between benzene-1,3,5-tricarbohydrazide (Bth) and 2,5-dihydroxyterephthalaldehyde (Dha) or 2,5-dimethoxyterephthal-aldehyde (Dma), respectively. Bth-Dma exhibits strong fluorescence in the solid state and in an aqueous dispersion, while no fluorescence can be observed for Bth-Dha. Interestingly, the as-synthesized Bth-Dma can be used as a turn-off fluorescence sensor for the Fe(III) ion in aqueous solution with outstanding selectivity and sensitivity. The recognition process can be attributed to the coordination interaction between Fe(III) ion and the O,N,O'-chelating sites in the pore wall of Bth-Dma COF, as verified by X-ray photoelectron spectroscopy and 1H NMR spectroscopy. To the best of our knowledge, this is the first report on the rational design of luminescent COF with predesigned O,N,O'-chelating sites as a fluorescence sensor for highly selective and sensitive metal ion detection. This work may pave the way for designing luminescent COF sensors with functional binding sites for detecting specific metal ions

Biochemical attributes of Indian mustard (Brassica juncea) and rapeseed (B. napus) as influenced by salicylic acid and benzothiadiazole

A field experiment was conducted during 2011-12 at Punjab Agricultural University, Ludhiana, India to assess the effect of foliar application of elicitors viz., salicylic acid (SA) and benzothiadiazole (BTH) on biochemical constituents of Brassica seeds. Seeds of Brassica juncea and B. napus were sown in the field during rabi season. Four different treatments of elicitors along with a fungicide and control were given to 10 week old plants up to four consecutive weeks. After harvesting, the seeds were analyzed for oil, total soluble protein and glucosinolate content. Results indicated that the elicitor treatments increased the oil, total soluble protein and glucosinolate content in seeds of both the Brassica species. In B. juncea, BTH (7 ppm) + SA (17 ppm) showed 12.5% higher oil content than control. In B. napus, the combinations of elicitors viz., BTH (3 ppm) + SA (33 ppm) and BTH (7 ppm) + SA (17 ppm) exhibited 15% increase in oil content compared to control. Treatment containing BTH (3 ppm) + SA (33 ppm) showed 18.72 and 15.86% higher total soluble protein content in B. juncea and B. napus seeds, respectively compared to control. In B. juncea, BTH (3 ppm) + SA (33 ppm) exhibited 7.13% higher glucosinolate content compared to control. In B. napus, BTH (7 ppm) + SA (17 ppm) showed 11.23% higher glucosinolate content than control. In conclusion, the application of elicitors, i.e., SA and BTH could be a useful tool for improving the nutritive value of B. juncea and B. napus seeds

Foliar application of systemic acquired resistance (SAR) inducers for controlling grape anthracnose caused by Sphaceloma ampelinum de Bary in Thailand

Chitosan and benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) are active-elicitors that induce protection in grapevine against several diseases. In this study, treatment of grapevine with chitosan and BTH provided protection to anthracnose, caused by Sphaceloma ampelinum. Chitosan and BTH treatment also increased chitinase, ß-1,3-glucanase and peroxidase activities levels in leaves over non-treated plants. Differential accumulation of these traits was more rapid and pronounced when chitosan and BTH treated plants were infected with S. ampelinum; this pattern indicating priming. The induced resistance by chitosan and BTH was also associated with increased production of salicylic acid (SA) in grapevine leaves, suggesting that SA-dependent signaling pathways are systemically triggered by these compounds. Apart from proteins with defense-related function, most of the proteins induced by chitosan and BTH were involved in defense mechanism, reflecting the strong direct positive effect that chitosan and BTH has on grapevine tolerance to anthracnose disease infection.Keywords: Anthracnose, grapevine, induce resistance, systemic acquired resistance (SAR) biochemical markers, Sphaceloma ampelinumAfrican Journal of Biotechnology Vol. 12(33), pp. 5148-515

Induced Systemic Resistance in Tomato Plants against Meloidogyne spp by Seed Treatment with Beta, Amino Butyric Acid and Benzothiadiazol

Treatments of tomato seeds with BABA or BTH significantly (p=0.05) reduced nematode infestation of tomato plants. BABA treatment produced significantly the lowest average root gall index (RGI), 2.44 followed by BTH, 3.22 and 3.55 for the untreated nematode infested control plants 15 days after nematode inoculation(ANI).Treatments with BABA and BTH for 30, 60 and 120 min. also caused significantly (p=0.05) less nematode infestation compared with the untreated control plants. BABA caused significantly the lowest average RGI, 1.77 compared with 3.66 and 4.55 for BTH and control respectively. The 120 min  BABA treatment recorded significantly the lowest average number or J2 in the roots of tomato plants compared with 75.55 and 116.66 J2 in the roots BTH and control plants respectively. When seeds were socked for 120 min, root average fresh weight (RFW) and root dry weight (RDW) were significantly less, 2.58 and 0.14g in BTH treatments of seeds compared with 1.86, 0.10g for BABA and 5.01 and 0.29g for control respectively 50 days ANI. When seeds were socked for 120 min, the highest average SFW and SDW were, 8.05, 0.68g in BABA treatments, followed by 3.29, 0.22 and 2.43, 0.12g in BTH and control treatments respectively. The highest average SFW and SFW were also recorded for BABA treatments, 2.43, 0.12g followed by 1.5, 0,093 and 1.59, 0.092g in BTH and control respectively 15 days ANI. Similarly, BABA caused the highest average shoot weights 30 and 50 days ANI followed by BTH and control treatments. Keywords: Induced  resistance, Meloidogyne spp, ?,amino butyric acid, Benzothaiadiazole, Seed treatment, Tomato

Benzothiadiazole induces the accumulation of phenolics and improves resistance to powdery mildew in strawberries

Benzothiadiazole (BTH) enhanced the accumulation of soluble and cell-wall-bound phenolics in strawberry leaves and also improved the resistance to powdery mildew infection under greenhouse conditions. The most pronounced change was seen in the levels of ellagitannins, which increased up to 2- to 6-fold 4 days after the BTH application, but persisted only in the inoculated plants. The induction of phenolic metabolism by BTH was also reflected in the fruits, several compounds being increased in inoculated, BTH-treated plants. Basal salicylic acid (SA) content was high in strawberry leaves, but increased in a similar fashion to other phenolics after the treatments. Several phenolic compounds were identified in strawberries for the first time. For example, ellagic acid deoxyhexose, three agrimoniin-like ellagitannins, sanguiin H-10- and lambertianin C-like ellagitannins in the leaves, ellagic acid, p-coumaric acid, gallic acid, and kaempferol hexose in the cell-wall-bound fraction of the leaves, and kaempferol malonylglucoside in the fruits. The findings show that BTH can enhance the accumulation of phenolics in strawberry plants which may then be involved in the BTH-induced resistance to powdery mildew

Does afforestation deteriorate haze pollution in Beijing-Tianjin-Hebei (BTH), China?

Although aggressive emission control strategies have been implemented recently in the Beijing-Tianjin-Hebei area (BTH), China, pervasive and persistent haze still frequently engulfs the region during wintertime. Afforestation in BTH, primarily concentrated in the Taihang and Yan Mountains, has constituted one of the controversial factors exacerbating the haze pollution due to its slowdown of the surface wind speed. We report here an increasing trend of forest cover in BTH during 2001-2013 based on long-term satellite measurements and the impact of the afforestation on the fine-particle (PM2.5) level. Simulations using the Weather Research and Forecast model with chemistry reveal that afforestation in BTH since 2001 has generally been deteriorating the haze pollution in BTH to some degree, enhancing PM2.5 concentrations by up to 6% on average. Complete afforestation or deforestation in the Taihang and Yan Mountains would increase or decrease the PM2.5 level within 15% in BTH. Our model results also suggest that implementing a large ventilation corridor system would not be effective or beneficial to mitigate the haze pollution in Beijing

Induction of Resistance with Benzothiadiazole in Sunflower: a Comparison of Biotrophic vs. Necrotrophic Pathosystems

In the present work we aimed at comparing the effect of benzothiadiazole (BTH) treatment on defence reactions of sunflower plants to downy mildew and white rot diseases. BTH treatment resulted in reduced disease symptoms in biotrophic and in the early stage of the necrotrophic interactions. To get a better insight into the effect of BTH, changes in the activities of polyphenol oxidase and peroxidase enzymes, as well as the expression of the host response-associated sunflower genes were examined in the plants. Inoculation with Plasmopara halstedii enhanced the polyphenol oxidase and peroxidase enzyme activities, while inoculation with Sclerotinia sclerotiorum did it only at 4 dpi. However, most importantly, in each case extracts from BTH pretreated and inoculated plants showed the highest polyphenol oxidase and peroxidase enzyme activities. Similarly, the accumulation of GST and PDF transcripts was detected following inoculations with both biotrophic and necrotrophic pathogens, and again, BTH pre-treatment enhanced GST and defensine gene activities in the inoculated plants. We suggest that induction of enzyme activities, as well as of the elevated expression of GST, PDF and PR5 genes by BTH pre-treatment may be a significant part of the induced resistance of sunflower to downy mildew and white rot (white mold)