Mitochondria as a Potential Antifungal Target for Isocyanide Compounds

The discovery of antibiotics and antifungals greatly impacted medicine and human health, allowing the effective treatment of infections that were previously deadly. However, due to routine and sometimes excessive usage of these compounds, the development of antimicrobial resistance has created a need for new antibiotic and antifungal compounds. Isocyanide compounds have been shown to have antibacterial, antifungal, and anti-cancer properties, but very little is known about their biochemical effects. Our research aims to understand the mechanism of action of isocyanide compounds. We have conducted a genetic screen of a Saccharomyces gene-deletion (“knockout”) collection on media containing an easily synthesized model isocyanide compound, para-nitrophenyl isocyanide (p-NPIC). This allowed us to identify genes which, when deleted, render the mutant strains resistant or hypersensitive to the compound. Based on our genetic screen for hypersensitive mutants, we hypothesize that the isocyanides impact mitochondrial function, specifically altering the function of the Cu++-containing respiratory complex, Cytochrome C Oxidase (Complex IV). Our findings provide new information on the mechanism(s) of action of this class of antimicrobials and will help guide the development of new molecules based on lead-compounds such as p-NPIC

Lectotypification of names in the genus Eragrostis Wolf (Poaceae)

In the present work 3 names within the genus Eragrostis viz, Eragrostis coarctata, E. plana and E. superba have been typified. Lectotypification has been performed for E. coarctata and Second-step lectotypification has been done for the names E. plana and E. superba. For lectotypification, rules and recommendations proposed by the International Code of Nomenclature for algae, fungi and plants (ICN), have been strictly followed. The selection of lectotypes are explained and the images of selected lectotypes are provided

Mitochondria as a Potential Antifungal Target for Isocyanide Compounds

The discovery of antibiotics and antifungals greatly impacted medicine and human health, allowing the effective treatment of infections that were previously deadly. However, due to routine and sometimes excessive usage of these compounds, the development of antimicrobial resistance has created a need for new antibiotic and antifungal compounds. Isocyanide compounds have been shown to have antibacterial, antifungal, and anti-cancer properties, but very little is known about their biochemical effects. Our research aims to understand the mechanism of action of isocyanide compounds. We have conducted a genetic screen of a Saccharomyces gene-deletion (“knockout”) collection on media containing an easily synthesized model isocyanide compound, para-nitrophenyl isocyanide (p-NPIC). This allowed us to identify genes which, when deleted, render the mutant strains resistant or hypersensitive to the compound. Based on our genetic screen for hypersensitive mutants, we hypothesize that the isocyanides impact mitochondrial function, specifically altering the function of the Cu++-containing respiratory complex, Cytochrome C Oxidase (Complex IV). Our findings provide new information on the mechanism(s) of action of this class of antimicrobials and will help guide the development of new molecules based on lead-compounds such as p-NPIC

Changes in an Enzyme Ensemble During Catalysis Observed by High Resolution XFEL Crystallography

Enzymes populate ensembles of structures with intrinsically different catalytic proficiencies that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography (MISC) at an X-ray free electron laser (XFEL) to observe catalysis in a designed mutant (G150T) isocyanide hydratase (ICH) enzyme that enhances sampling of important minor conformations. The active site exists in a mixture of conformations and formation of the thioimidate catalytic intermediate selects for catalytically competent substates. A prior proposal for active site cysteine charge-coupled conformational changes in ICH is validated by determining structures of the enzyme over a range of pH values. A combination of large molecular dynamics simulations of the enzyme in crystallo and timeresolved electron density maps shows that ionization of the general acid Asp17 during catalysis causes additional conformational changes that propagate across the dimer interface, connecting the two active sites. These ionization-linked changes in the ICH conformational ensemble permit water to enter the active site in a location that is poised for intermediate hydrolysis. ICH exhibits a tight coupling between ionization of active site residues and catalysis-activated protein motions, exemplifying a mechanism of electrostatic control of enzyme dynamics

ДОСЛІДЖЕННЯ ВИКОРИСТАННЯ ПЛАСТИКОВИХ ВІДХОДІВ ЯК ДОБАВКИ ДЛЯ БІТУМНОГО БЕТОНУ ПРИ ЗАСТОСУВАННІ МОКРОГО ПРОЦЕСУ ЗМІШУВАННЯ

Purpose. Plastic waste has become a major environmental issue of concern due to its exponential growth due to rapid urbanization. The paper investigates utility of plastic waste as an additive for bituminous concrete using wet process of mixing. Methodology. The methodology for the present paper has been designed with complex research consisting of Marshall mix design of the bituminous mix added with plastic waste for modifying bitumen using wet process of mixing, performing the tests on the samples and analyzing the results in the form of table and figures. In the present paper LDPE and HDPE type of plastic waste are used to modify the bitumen. Finding. The results show that addition of 6 percent of bitumen improves the Marshall properties of the mix. Use of plastic to modify the bitumen not only makes the road surface more durable but also it is an eco-friendly way of proper disposal of plastic waste. Originality. The processes used for mixing the plastic waste to the bitumen are dry process and wet process. Dry process of mixing the plastic waste to the bituminous mix is most common and lot of study is carried out on its application. In the present paper wet process of mixing has not yet been studied much. Practical Value. The practical application of utilizing the plastic waste to modify bitumen in the bituminous mix improves the stability values resulting in the more durable road surface. Also the method ensures the proper disposal of plastic waste in eco-friendly way.Цель. Пластмассовые отходы стали серьезной экологической проблемой, вызванной их экспоненциальным ростом из-за быстрой урбанизации. В качестве решения проблемы используются отходы для создания прочной дорожной поверхности. Для смешивания пластиковых отходов с битумом употребляются сухой и влажный процессы. Сухой процесс смешивания пластиковых отходов с битумной смесью является наиболее распространенным, проводится много исследований по его применению. В данной работе целью является исследование пластиковых отходов в качестве добавки для битумного бетона с использованием мокрого процесса смешивания. Методика. Технология настоящей работы была разработана в ходе комплексного исследования, в том числе изучающего состав битумной смеси Marshall. Данный компонент добавлялся к пластмассовым отходам. Модификация битума, полученная при использовании мокрого процесса смешивания, испытывалась на опытных образцах. Анализ результатов также представлялся в форме таблицы и рисунков. В настоящей работе для переработки битума используются полиэтиленовые отходы LDPE и HDPE. Результаты. Полученные результаты показывают, что добавление 6 % битума улучшает свойства смеси Marshall. Использование пластика для модификации битума не только делает дорожную поверхность более долговечной, но также является экологически чистым способом правильной утилизации пластиковых отходов. Научная новизна. Расширено представление о преимуществе использования пластиковых отходов в качестве компонентов битумного бетона при применении мокрого процесса смешивания. В то же время авторы подчеркивают, что в настоящей работе мокрый процесс смешивания еще не изучен в полном объеме. Практическая значимость. Практическое применение утилизации пластиковых отходов для модификации битума в битумной смеси повышает значения стабильности, что приводит к использованию более прочной дорожной поверхности. Кроме того, метод обеспечивает надлежащую утилизацию пластиковых отходов экологически безопасным способом.Мета. Пластмасові відходи стали серйозною екологічною проблемою, викликаною їх експоненціальним ростом через швидку урбанізацію. В якості вирішення проблеми використовуються відходи для створення міцної дорожньої поверхні. Для змішування пластикових відходів із бітумом вживаються сухий та вологий процеси. Сухий процес змішування пластикових відходів із бітумною сумішшю є найбільш поширеним, проводиться багато досліджень по його застосуванню. Метою даної роботи є дослідження пластикових відходів у якості добавки для бітумного бетону з використанням мокрого процесу змішування. Методика. Технологія цієї роботи була розроблена в ході комплексного дослідження, яка в тому числі вивчає склад бітумної суміші Marshall. Даний компонент додавався до пластмасових відходів. Модифікація бітуму, отримана при використанні мокрого процесу змішування, випробовувалася на дослідних зразках. Аналіз результатів також представлявся у формі таблиці та малюнків. У цій роботі для переробки бітуму використовуються поліетиленові відходи LDPE і HDPE. Результати. Отримані результати показують, що додавання 6 % бітуму покращує властивості суміші Marshall. Використання пластика для модифікації бітуму не тільки робить дорожню поверхню більш довговічною, але також є екологічно чистим способом правильної утилізації пластикових відходів. Наукова новизна. Розширено уявлення про перевагу використання пластикових відходів у якості компонентів бітумного бетону при застосуванні мокрого процесу змішування. У той же час автори підкреслюють, що в даній роботі мокрий процес змішування ще не вивчений у повному обсязі. Практична значимість. Практичне застосування утилізації пластикових відходів для модифікації бітуму в бітумній суміші підвищує значення стабільності, що призводить до більш міцної дорожньої поверхні. Крім того, метод забезпечує належну утилізацію пластикових відходів екологічно безпечним способом

INVESTIGATION ON UTILITY OF PLASTIC WASTE AS AN ADDITIVE FOR BITUMINOUS CONCRETE USING WET PROCESS OF MIXING

Purpose. Plastic waste has become a major environmental issue of concern due to its exponential growth due to rapid urbanization. The paper investigates utility of plastic waste as an additive for bituminous concrete using wet process of mixing. Methodology. The methodology for the present paper has been designed with complex research consisting of Marshall mix design of the bituminous mix added with plastic waste for modifying bitumen using wet process of mixing, performing the tests on the samples and analyzing the results in the form of table and figures. In the present paper LDPE and HDPE type of plastic waste are used to modify the bitumen. Finding. The results show that addition of 6 percent of bitumen improves the Marshall properties of the mix. Use of plastic to modify the bitumen not only makes the road surface more durable but also it is an eco-friendly way of proper disposal of plastic waste. Originality. The processes used for mixing the plastic waste to the bitumen are dry process and wet process. Dry process of mixing the plastic waste to the bituminous mix is most common and lot of study is carried out on its application. In the present paper wet process of mixing has not yet been studied much. Practical Value. The practical application of utilizing the plastic waste to modify bitumen in the bituminous mix improves the stability values resulting in the more durable road surface. Also the method ensures the proper disposal of plastic waste in eco-friendly way

Spatio-Temporal Patterns of Mass Changes in Himalayan Glaciated Region from EOF Analyses of GRACE Data

The nature of hydrological seasonality over the Himalayan Glaciated Region (HGR) is complex due to varied precipitation patterns. The present study attempts to exemplify the spatio-temporal variation of hydrological mass over the HGR using time-variable gravity from the Gravity Recovery and Climate Experiment (GRACE) satellite for the period of 2002–2016 on seasonal and interannual timescales. The mass signal derived from GRACE data is decomposed using empirical orthogonal functions (EOFs), allowing us to identify the three broad divisions of HGR, i.e., western, central, and eastern, based on the seasonal mass gain or loss that corresponds to prevailing climatic changes. Further, causative relationships between climatic variables and the EOF decomposed signals are explored using the Granger causality algorithm. It appears that a causal relationship exists between total precipitation and total water storage from GRACE. EOF modes also indicate certain regional anomalies such as the Karakoram mass gain, which represents ongoing snow accumulation. Our causality result suggests that the excessive snowfall in 2005–2008 has initiated this mass gain. However, as our results indicate, despite the dampening of snowfall rates after 2008, mass has been steadily increasing in the Karakorum, which is attributed to the flattening of the temperature anomaly curve and subsequent lower melting after 2008