Co-application of Difenoconazole with Thymol Results in Suppression of a Parastagonospora Nodorum Mutant Strain Resistant to this Triazole

Results of in vitro study of thymol, a natural chemosensitizer, as a potential agent for overcoming of difenoconazole resistance of Parastagonospora nodorum causing glume and leaf blotch of wheat are first reported. The level of difenoconazole resistance of a natural mutant PNm1 strain with low sensitivity to the Dividend fungicide (a.i. difenoconazole) was determined by the cultivation of this isolate on potato dextrose agar in the presence of the fungicide at sub-lethal and lethal (in relation to the initial fungicide-sensitive strain) concentrations. A principal possibility of the thymol use to overcome resistance of P. nodorum to DMI (demethylation inhibitors) fungicides is shown. Co-application of this compound with Dividend SC, 3 % resulted in a significant reduction of resistance of the mutant strain and enhancement of its sensitivity to difenoconazole up to the level corresponding to the initial non-resistant isolate

Minimization of Fungicidal Applications Against Potato Late Blight in the North Caucasian Region: Use of the “Agrodozor” System

Late blight is considered to be the most devastating potato disease, which control requires application of fungicides able to significantly contaminate the environment and accumulate in agricultural products. Pesticide load on potato fields can be reduced via optimization of the scheme of protective treatments. Such optimization can be performed using a mathematical simulator describing the dependence of late blight-caused yield losses on the weather data and an “Agrodozor” decision support system (DSS). The performed analysis of a situation in the regions of the North Caucasus allowed us to determine three zones differing in the disease harmfulness and characterized by potential yield losses at the level of <10, 10-20, and >20 % and the probability of disease appearance in field during 30, 77, and 90 % of seasons, respectively. Using the “Agrodozor” DSS, we calculated the optimum dates of fungicidal treatments for these zones and showed that, comparing to the commonly used routine scheme of treatments, the use of this DSS provides a significant reduction of the number of such treatments and, therefore, the corresponding costs for their arrangement, as well as reduction of the total toxicity index of the required protective measures

Polarography of Te (IV) Anions in Neutral Solutions in Presence of 2,2'- Dipyridyl and Fe(dipy)3 2+ - Complexes

The electroreduction of Te (IV) ions in neutral non-buffer solutions containing 2,2'-dipyridyl (4в‹…10-5- 4в‹…10-3 M) or tris-dipyridyl iron (II) complexes is studied by the polarographic method. NaF (0.01-0.5 M) or NaNO3 (0.1-1 M) are used as supporting electrolytes. The mechanism of electrochemical reactions of Te (IV) anions on mercury electrodes in the presence of the additives is discussed. The electroreduction of Te (IV) anions is shown to proceed through electron transfer and proton addition. The obtained results point to a considerable influence of electric double layer structure on electrochemical reactions of Te (IV) ions in the presence of inorganic and specifically adsorbed organic compounds in the electrolyte. It is shown, that 2,2'-dipyridyl does not form complexes with Te (IV) anions. Having been adsorbed on the surface of mercury electrode, 2,2'-dipyridyl complexes increase negative ОЁ'-potential that results in a shift of Te (IV) electroreduction wave to more negative potentials and decrease in the current of Te (IV) wave and peak at -1.19 V. It is shown that 2,2'-dipyridyl molecules at Оµ > 0, (Оµ вЂ“ charge of an electrode) are adsorbed in plane orientation, and at Оµ < 0, plane or vertical. Vertically adsorbed molecules cause a significant decrease in the double layer capacitance. At negative potentials orientation of 2,2'-dipyridyl molecules changes from plane to vertical with the increasing 2,2'-dipyridyl concentration. This change of orientation results in a typical maximum capacitance emerging in the potential range of -0.7 to -1.2 V. It is shown that the supporting electrolyte, 2,2'-dipyridyl and Fe(dipy)32+ В have influence on the electroreduction of Te (IV) anions in neutral non-buffer solutions through a change in the ОЁ'-potential of mercury electrode

Новый высокопродуктивный штамм Propionibacterium acidipropionici FL-48 с повышенной устойчивостью к пропионовой кислоте и масштабирование технологии его наработки в промышленных биореакторах

Propionic acid bacteria, including Propionibacterium acidipropionici, are widely used in the chemical industry to produce propionic acid and also for food and feed preservation. However, the efficiency of the industrial production of these bacteria is limited by their sensitivity to high concentrations of propionic acid excreted into the cultivation medium. Therefore, the development of new biotechnological processes and strains able to overcome this limitation and to improve the profitability of the microbiological production remains  a relevant problem. A new P. acidipropionici FL-48 strain characterized by an increased resistance to 10 g/L of propionic acid (the number of viable cells after 24-h cultivation reached 1.05 × 106) was developed by a two-step induced mutagenesis using UV and diethyl sulphate from the P. acidipropionici VKPM B-5723 strain. The mutant strain exceeded the parental strain in the biomass accumulation rate and the amount of produced propionic and acetic acids by 35%, 20%, and 16%, respectively. The stability of such important characteristics as the biomass accumulation rate and the viability on media containing heightened concentrations of propionic acid was confirmed by three sequential monoclonal subculturings on a medium supplemented with 10 g/L of propionic acid. The optimization of the cultivation technology made it possible to determine the optimum seed inoculum dose (10% of the fermentation medium volume) and the best pH level for the active growth stage (6.1 ± 0.1). The scaling up of the fermentation to a 100-L bioreactor under observance of optimum cultivation conditions demonstrated a high biomass growth rate with a sufficient reproducability; after 20 h of fermentation, the number of viable cells in the culture broth exceeded 1 × 1010 CFU/mL. The new strain could be interesting as the component of silage and haylage biopreservatives and also could be used as an efficient producer of propionic acid.Пропионовокислые бактерии, в том числе Propionibacterium acidipropionici, широко используются в химической промышленности для получения пропионовой кислоты, а также для консервирования пищи и заготовки зерна и зеленых кормов. Однако эффективность промышленного производства биомассы пропионовокислых бактерий ограничена их чувствительностью к высоким концентрациям в среде пропионовой кислоты. Таким образом, актуальной задачей является разработка новых биотехнологических процессов и штаммов, позволяющих преодолеть это ограничение и повысить рентабельность микробиологического производства. Методом двухступенчатого индуцированного мутагенеза с применением УФ-облучения и диэтилсульфата получен новый мутантный штамм P. acidipropionici ФЛ-48, обладающий повышенной резистентностью к 10 г/л пропионовой кислоты (количество жизнеспособных клеток через 24 ч культивирования достигало 1,05 × 106) и превосходящий родительский штамм P. acidipropionici ВКПМ В-5723 по скорости накопления биомассы и количеству продуцируемых пропионовой и уксусной кислот на 35%, 20% и 16%, соответственно. Стабильность характеристик нового штамма (скорость накопления биомассы и жизнеспособность на средах с повышенной концентрацией пропионовой кислоты) подтверждена трехкратным последовательным моноклональным рассевом на среду, содержащую 10 г/л пропионовой кислоты. Выполненная оптимизация технологии культивирования штамма позволила определить оптимальную дозу инокулюма для засева биореактора (10% от объема ферментационной среды) и поддерживаемый в течение первых 12 ч уровень рН среды, обеспечивающий максимальный прирост биомассы (6,1 ± 0,1). Проведенное масштабирование ферментации до 100-литрового биореактора с соблюдением оптимальных условий культивирования показало сохранение высокой скорости роста штамма в условиях пониженного рН; уже к 20-му часу ферментации количество жизнеспособных клеток в культуральной жидкости превышало 1 × 1010 КОЕ/мл. Полученные результаты показали хорошую воспроизводимость. Новый штамм представляет интерес в качестве компонента биоконсервантов для силоса и сенажа, а также может быть использован в качестве эффективного продуцента пропионовой кислоты. Пропионовокислые бактерии, в том числе Propionibacterium acidipropionici, широко используются в химической промышленности для получения пропионовой кислоты, а также для консервирования пищи и заготовки зерна и зеленых кормов. Однако эффективность промышленного производства биомассы пропионовокислых бактерий ограничена их чувствительностью к высоким концентрациям в среде пропионовой кислоты. Таким образом, актуальной задачей является разработка новых биотехнологических процессов и штаммов, позволяющих преодолеть это ограничение и повысить рентабельность микробиологического производства. Методом двухступенчатого индуцированного мутагенеза с применением УФ-облучения и диэтилсульфата получен новый мутантный штамм P. acidipropionici ФЛ-48, обладающий повышенной резистентностью к 10 г/л пропионовой кислоты (количество жизнеспособных клеток через 24 ч культивирования достигало 1,05 × 106) и превосходящий родительский штамм P. acidipropionici ВКПМ В-5723 по скорости накопления биомассы и количеству продуцируемых пропионовой и уксусной кислот на 35%, 20% и 16%, соответственно. Стабильность характеристик нового штамма (скорость накопления биомассы и жизнеспособность на средах с повышенной концентрацией пропионовой кислоты) подтверждена трехкратным последовательным моноклональным рассевом на среду, содержащую 10 г/л пропионовой кислоты. Выполненная оптимизация технологии культивирования штамма позволила определить оптимальную дозу инокулюма для засева биореактора (10% от объема ферментационной среды) и поддерживаемый в течение первых 12 ч уровень рН среды, обеспечивающий максимальный прирост биомассы (6,1 ± 0,1). Проведенное масштабирование ферментации до 100-литрового биореактора с соблюдением оптимальных условий культивирования показало сохранение высокой скорости роста штамма в условиях пониженного рН; уже к 20-му часу ферментации количество жизнеспособных клеток в культуральной жидкости превышало 1 × 1010 КОЕ/мл. Полученные результаты показали хорошую воспроизводимость. Новый штамм представляет интерес в качестве компонента биоконсервантов для силоса и сенажа, а также может быть использован в качестве эффективного продуцента пропионовой кислоты.

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

(E)-1,5-Diphenylpent-2-en-4-yn-1-one

The title compound, C17H12O, has an E conformation about the C=C bond. The C&#8212;C[triple-bond]C&#8212;C torsion angle is 7.7&#8197;(2)&#176;, and the mean planes of the phenylethylenone [r.m.s. deviation&#160;= 0.059&#8197;(1)&#8197;&#197;] and phenylacetylene [r.m.s. deviation&#160;= 0.023&#8197;(1)&#8197;&#197;] fragments form a dihedral angle of 14.16&#8197;(7)&#176;. In the crystal, weak C&#8212;H...O interactions link the molecules into zigzag chains propagated in [010]

Co-application of Difenoconazole with Thymol Results in Suppression of A Parastagonospora Nodorum Mutant Strain Resistant to This Triazole

Results of in vitro study of thymol, a natural chemosensitizer, as a potential agent for overcoming of difenoconazole resistance of Parastagonospora nodorum causing glume and leaf blotch of wheat are first reported. The level of difenoconazole resistance of a natural mutant PNm1 strain with low sensitivity to the Dividend fungicide (a.i. difenoconazole) was determined by the cultivation of this isolate on potato dextrose agar in the presence of the fungicide at sub-lethal and lethal (in relation to the initial fungicide-sensitive strain) concentrations. A principal possibility of the thymol use to overcome resistance of P. nodorum to DMI (demethylation inhibitors) fungicides is shown. Co-application of this compound with Dividend SC, 3 % resulted in a significant reduction of resistance of the mutant strain and enhancement of its sensitivity to difenoconazole up to the level corresponding to the initial non-resistant isolate

6-(4-Chlorophenyl)-3-methylimidazo[2,1-b]thiazole

In the title compound, C12H9ClN2S, the imidazo[2,1-b]thiazole fragment is planar (r.m.s. deviation = 0.003&#8197;&#197;), and the benzene ring is twisted slightly [by 5.65&#8197;(6)&#176;] relative to this moiety. In the crystal, molecules are linked by &#960;&#8211;&#960; stacking interactions into columns along [010]. The molecules within the columns are arranged alternatively by their planar rotation of 180&#176;. Thus, in the columns, there are the two types of &#960;&#8211;&#960; stacking interactions, namely, (i) between two imidazo[2,1-b]thiazole fragments [interplanar distance = 3.351&#8197;(2)&#8197;&#197;] and (ii) between an imidazo[2,1-b]thiazole fragment and the phenyl ring [interplanar distance = 3.410&#8197;(5)&#8197;&#197;]. There are no short contacts between the columns

3-Bromo-2-[4-(methylsulfanyl)phenyl]-5,6,7,8-tetrahydro-1,3-benzothiazolo[3,2-a]imidazole

In the title molecule, C16H15BrN2S2, the central imidazo[2,1-b]thiazole fragment is almost planar (r.m.s. deviation = 0.012 Å), and the fused 5,6,7,8-tetrahydrobenzene ring adopts an unsymmetrical half-chair conformation. The dihedral angle between the imidazo[2,1-b]thiazole and benzene planes is 18.25 (4)°. The terminal methylsulfanyl substituent lies practically within the benzene plane [the dihedral angle between the corresponding planes is 7.20 (10)°] and is turned toward the C—Br bond. In the crystal, molecules form infinite chains along [100] via secondary Br...N interactions [3.1861 (16) Å]. The chains are arranged at van der Waals distances

Minimization of Fungicidal Applications Against Potato Late Blight in the North Caucasian Region: Use of the “Agrodozor” System

Late blight is considered to be the most devastating potato disease, which control requires application of fungicides able to significantly contaminate the environment and accumulate in agricultural products. Pesticide load on potato fields can be reduced via optimization of the scheme of protective treatments. Such optimization can be performed using a mathematical simulator describing the dependence of late blight-caused yield losses on the weather data and an “Agrodozor” decision support system (DSS). The performed analysis of a situation in the regions of the North Caucasus allowed us to determine three zones differing in the disease harmfulness and characterized by potential yield losses at the level of &lt;10, 10-20, and &gt;20 % and the probability of disease appearance in field during 30, 77, and 90 % of seasons, respectively. Using the “Agrodozor” DSS, we calculated the optimum dates of fungicidal treatments for these zones and showed that, comparing to the commonly used routine scheme of treatments, the use of this DSS provides a significant reduction of the number of such treatments and, therefore, the corresponding costs for their arrangement, as well as reduction of the total toxicity index of the required protective measures