Identification, crystallization, and first X-ray structure analyses of phenyl boronic acid-based inhibitors of human carbonic anhydrase-II.

Human carbonic anhydrases (hCAs) play a central role in various physiological processes in the human body. HCAs catalyze the reversible hydration of CO2 into HCO3-, and hence maintains the fluid and pH balance. Overexpression of CA II is associated with diseases, such as glaucoma, and epilepsy. Therefore, CAs are important clinical targets and inhibition of different isoforms, especially hCA II is used in treatment of glaucoma, altitude sickness, and epilepsy. Therapeutically used CA inhibitors (CAI) are sulfonamide-based, such as acetazolamide, dichlorphenamide, methazolamide, ethoxzolamide, etc. However, they exhibit several undesirable effects such as numbness, tingling of extremities, malaise, metallic taste, fatigue, renal calculi, and metabolic acidosis. Therefore, there is an urgent need to identify safe and effective inhibitors of the hCAs. In this study, different phenyl boronic acids 1-5 were evaluated against bovine (bCA II) and hCA II. Among all, compound 1 (4-acetylphenyl boronic acid) was found to be active against bCAII and hCA II with IC50 values of 246 ± 0.48 and 281.40 ± 2.8 µM, respectively, while the remaining compounds were found in-active. Compound 1 was identified as competitive inhibitor of hCA II enzyme (Ki = 283.7 ± 0.002 µM). Additionally, compound 1 was found to be non-toxic against BJ Human fibroblast cell line. The X-ray crystal structure for hCA II in-complex with compound 1 was evaluated to a resolution of 2.6 Å. In fact, this the first structural analysis of a phenyl boron-based inhibitor bound to hCA II, allowing an additional structure-activity analysis of the compounds. Compound 1 was found to be directly bound in the active site of hCA II by interacting with His94, His119, and Thr199 residues. In addition, a bond of 3.11 Å between the zinc ion and coordinated boron atom of the boronic acid moiety of compound 1 was also observed, contributing to binding affinity of compound 1 for hCA II. PDB ID: 8IGF.

Investigating seasonal air quality variations consequent to the urban vegetation in the metropolis of Faisalabad, Pakistan.

Urban atmospheric pollution is global problem and and have become increasingly critical in big cities around the world. Issue of toxic emissions has gained significant attention in the scientific community as the release of pollutants into the atmosphere rising continuously. Although, the Pakistani government has started the Pakistan Clean Air Program to control ambient air quality however, the desired air quality levels are yet to be reached. Since the process of mapping the dispersion of atmospheric pollutants in urban areas is intricate due to its dependence on multiple factors, such as urban vegetation and weather conditions. Therefore, present research focuses on two essential items: (1) the relationship between urban vegetation and atmospheric variables (temperature, relative humidity (RH), sound intensity (SI), CO, CO2, and particulate matter (PM0.5, PM1.0, and PM2.5) and (2) the effect of seasonal change on concentration and magnitude of atmospheric variables. A geographic Information System (GIS) was utilized to map urban atmospheric variables dispersion in the residential areas of Faisalabad, Pakistan. Pearson correlation and principal component analyses were performed to establish the relationship between urban atmospheric pollutants, urban vegetation, and seasonal variation. The results showed a positive correlation between urban vegetation, metrological factors, and most of the atmospheric pollutants. Furthermore, PM concentration showed a significant correlation with temperature and urban vegetation cover. GIS distribution maps for PM0.5, PM1.0, PM2.5, and CO2 pollutants showed the highest concentration of pollutants in poorly to the moderated vegetated areas. Therefore, it can be concluded that urban vegetation requires a rigorous design, planning, and cost-benefit analysis to maximize its positive environmental effects.

Detrimental Effects of Induced Soil Compaction on Morphological Adaptation and Physiological Plasticity of Selected Multipurpose Tree Species.

Soil compaction has become a global problem affecting soil worldwide. With an increased population, more demands for food and wood have resulted in intensive cultivation and increased mechanization of our farmlands and irrigated plantations. The use of heavy machinery results in soil compaction, which affects the entire soil ecosystem. This study was conducted to analyze the impact of compacted soil on germination and initial growth stages of four major agro-forest trees of central Punjab, Pakistan. Morpho-physiological traits of all selected species (Eucalyptus camaldulensis, Albizia lebbeck, Vachellia nilotica, and Zyziphus mauritiana) were measured against soil compaction. Results indicated that the root and shoot length, biomass, root-shoot ratio, diameter at root collar, no. of leaves and branches, leaf area, germination, and survival %, and physiological traits (i.e., photosynthetic rate, transpiration rate, stomatal conductance, internal CO2 concentration, and photosynthetic water use efficiency) were significantly affected by the induced soil compaction. Eucalyptus camaldulensis Dehnh. performed better and exhibited 96% germination percentage under (1.40 mg m-3) compaction level and gradually decreased by 11% with the increase of compaction level (1.80 mg m-3). It shows that the shorter roots developed due to soil compaction decreased water use efficiency, photosynthesis, and whole-plant physiological performance. The findings concluded that judicious use of machinery is highly desired for sustainable and good-quality wood production from farm trees.

Assessing the effects of limestone dust and lead pollution on the ecophysiology of some selected urban tree species.

Soil and air pollution caused by heavy metals and limestone dust are prevalent in urban environments and they are an alarming threat to the environment and humans. This study was designed to investigate the changes in morphological and physiological traits of three urban tree species seedlings (Bombax ceiba, Conocarpus lancifolius, and Eucalyptus camaldulensis) under the individual as well as synergetic effects of heavy metal lead (Pb) and limestone dust toxicities. The tree species were grown under controlled environmental conditions with nine treatments consisting of three levels of dust (0, 10, and 20 g) and three levels of Pb contaminated water irrigation (0, 5, and 10 mg L-1). The results depicted that the growth was maximum in T1 and minimum in T9 for all selected tree species. B. ceiba performed better under the same levels of Pb and limestone dust pollution as compared with the other two tree species. The B. ceiba tree species proved to be the most tolerant to Pb and limestone pollution by efficiently demolishing oxidative bursts by triggering SOD, POD, CAT, and proline contents under different levels of lead and dust pollution. The photosynthetic rate, stomatal conductance, evapotranspiration rate, and transpiration rate were negatively influenced in all three tree species in response to different levels of lead and dust applications. The photosynthetic rate was 1.7%, 3.1%, 7.0%, 11.03%, 16.2%, 23.8%, 24.8%, and 30.7%, and the stomatal conductance was 5%, 10.5%, 23.5%, 40%, 50.01%, 61.5%, 75%, and 90.9%, greater in T2, T3, T4, T5, T6, T7, T8, and T9 plants of B. ceiba, respectively, as compared to T1. Based on the findings, among these three tree species, B. ceiba is strongly recommended for planting in heavy metal and limestone dust-polluted areas followed by E. camaldulensis and C. lancifolius due to their better performance and efficient dust and heavy metal-scavenging capability.

State-of-the-art OMICS strategies against toxic effects of heavy metals in plants: A review.

Environmental pollution of heavy metals (HMs), mainly due to anthropogenic activities, has received growing attention in recent decades. HMs, especially the non-essential carcinogenic ones, including chromium (Cr), cadmium (Cd), mercury (Hg), aluminum (Al), lead (Pb), and arsenic (As), have appeared as the most significant air, water, and soil pollutants, which adversely affect the quantity, quality, and security of plant-based food all over the world. Plants exposed to HMs could experience significant decline in growth and yield. To avoid or tolerate the toxic effects of HMs, plants have developed complicated defense mechanisms, including absorption and accumulation of HMs in cell organelles, immobilization by forming complexes with organic chelates, extraction by using numerous transporters, ion channels, signalling cascades, and transcription elements, among others. OMICS strategies have developed significantly to understand the mechanisms of plant transcriptomics, genomics, proteomics, metabolomics, and ionomics to counter HM-mediated stress stimuli. These strategies have been considered to be reliable and feasible for investigating the roles of genomics (genomes), transcriptomic (coding), mRNA transcripts (non-coding), metabolomics (metabolites), and ionomics (metal ions) to enhance stress resistance or tolerance in plants. The recent developments in the mechanistic understandings of the HMs-plant interaction in terms of their absorption, translocation, and toxicity invasions at the molecular and cellular levels, as well as plants' response and adaptation strategies against these stressors, are summarized in the present review. Transcriptomics, genomics, metabolomics, proteomics, and ionomics for plants against HMs toxicities are reviewed, while challenges and future recommendations are also discussed.

Determining the appropriate level of farmyard manure biochar application in saline soils for three selected farm tree species.

Salinity is a global problem, and almost more than 20% of the total cultivated area of the world is affected by salt stress. Phytoremediation is one of the most suitable practices to combat salinity and recently biochar has showed the tremendous potential to alleviate salt-affected soils and enhance vegetation. Trees improve the soil characteristics by facilitating the leaching of salts and releasing organic acids in soil. Moreover, in the presence of trees, higher transpiration rates and lower evaporation rates are also helpful in ameliorating salt affected soils. This study was designed to check the effect of different levels of biochar on the morph-physiological characteristics of three important agroforestry tree species: Eucalyptus camaldulensis, Vachellia nilotica, and Dalbergia sissoo, in saline soils. Farmyard manure biochar was applied at the rate of 3% (w/w), 6% (w/w), and 9% (w/w) to find appropriate levels of biochar for promoting the early-stage trees growth under saline conditions. Results of the current study revealed that maximum shoot length (104.77 cm), shoot dry weight (23.72 g), leaves dry weight (28.23 g), plant diameter (12.32 mm), root length (20.89 cm), root dry weight (18.90 g), photosynthetic rate (25.33 µ moles CO2 m-2s-1) and stomatal conductance (0.12 mol H2O m-2 s-1) were discovered in the plants of Eucalyptus camaldulensis at the rate of 6% (w/w). All tree species showed better results for growth and physiological characteristics when biochar was applied at the rate of 6% (w/w). In comparison, a decreasing trend in growth parameters was found in the excessive amount of biochar when the application rate was increased from 6% (w/w) to 9% (w/w) for all three species. So, applying an appropriate level of biochar is important for boosting plant growth in saline soils. Among different tree species, Vachellia nilotica and Eucalyptus camaldulensis both showed very promising results to remediate salt affected soils with Vachellia nilotica showing maximum potential to absorb sodium ions.

Effect of Organic Amendments in Soil on Physiological and Biochemical Attributes of Vachellia nilotica and Dalbergia sissoo under Saline Stress.

Vachellia nilotica (L.) P.J.H. Hurther & Mabb. and Dalbergia sissoo Roxb. are two of the most important multipurpose agroforestry tree species of the Indian sub-continent, but their growth in saline soils is greatly reduced. Recently, organic amendments have showed the potential to increase plant growth in salt-affected soils; however, the influence of using these amendments for growing the above-mentioned tree species under saline conditions is not yet quantified. Therefore, an experiment was devised to analyze the interactive effects of organic amendments in saline soils on the growth of V. nilotica and D. sissoo. Under controlled conditions, a pot experiment was conducted in sandy loam saline soils (EC = 20.5 dSm-1). Organic amendments from four diverse sources: farmyard manure (FYM), poultry manure (PM), slurry (SL), and farmyard manure biochar (FYMB) were employed in this study. At the harvesting time, data regarding morphological, physiological, ionic, and biochemical parameters were obtained. The current study results indicated that both tree species reacted differently, but positively, to diverse applied amendments. The maximum increment in total above-ground biomass, total below-ground biomass, and shoot length for V. nilotica (163.8%, 116.3%, and 68.2%, respectively) was observed in FYM amended soils, while the maximum increment for D. sissoo (128%, 86%, and 107%, respectively) was observed in FYMB amended soils, as compared to control. Minimum plant growth of both species was observed in untreated soils (saline soils). Likewise, the maximum potassium ion and minimum sodium ion concentrations were present in the root and shoots of plants (both species) treated with FYMB. The use of organic amendments resulted in decreased concentrations of malondialdehyde and hydrogen peroxide, and increased concentrations of antioxidant enzymes such as SOD, POD, and CAT. Moreover, higher photosynthetic rates and stomatal conductance were observed in the plants grown in amended soils. The findings of this study can be used to include the above-mentioned high-value tree species for future afforestation programs under saline conditions.

Effect of three different types of biochars on eco-physiological response of important agroforestry tree species under salt stress.

Soil reclamation through afforestation along with soil amendments is one of the most suitable practices to combat soil salinity while the use of biochar may have potential to ameliorate salt-affected soils. This study was designed to check effects of different biochars on the physico-chemical properties of soil and characteristics of three important agroforestry trees species: Eucalyptus camaldulensis, Vachellia nilotica and Dalbergia sissoo, in saline soils. Farmyard manure biochar (FYMB), sugarcane bagasse biochar (SCB), woodchips biochar (WCB) were applied (6% w/w) to check their effects on plants under saline conditions. Results revealed that FYMB was the best for promoting all growth and physiological parameters of three tree species while E. camaldulensis was the best suited species. Different types of biochars influenced the growth of agroforestry species differently as SCB showed better results for D. sissoo as compared to WCB but for V. nilotica and WCB was more effective than SCB. Trend of growth and other physiological attributes for E. camaldulensis and V. nilotica was FYMB > WCB > SCB > control whereas D. sissoo showed trend as FYMB > SCB > WCB > control. Biochar was helpful in improving physicochemical characteristics of saline soils by lowering values of soil EC and SAR but type of biochar has a differential effect on tree growth.Novelty statement: Biochar may be a potential source for the amelioration of salt affected soils while less is known about the effects of different types of biochars on the soil and eco-physiological response of important agroforestry trees species in saline soils. In this study, although all types of biochar ameliorated the soil conditions and enhanced the plant growth, but farmyard manure biochar was the most efficient treatment among three types of used biochars.

MILAMP: Multiple Instance Prediction of Amyloid Proteins.

Amyloid proteins are implicated in several diseases such as Parkinson's, Alzheimer's, prion diseases, etc. In order to characterize the amyloidogenicity of a given protein, it is important to locate the amyloid forming hotspot regions within the protein as well as to analyze the effects of mutations on these proteins. The biochemical and biological assays used for this purpose can be facilitated by computational means. This paper presents a machine learning method that can predict hotspot amyloidogenic regions within proteins and characterize changes in their amyloidogenicity due to point mutations. The proposed method called MILAMP (Multiple Instance Learning of AMyloid Proteins) achieves high accuracy for identification of amyloid proteins, hotspot localization, and prediction of mutation effects on amyloidogenicity by integrating heterogenous data sources and exploiting common predictive patterns across these tasks through multiple instance learning. The paper presents comprehensive benchmarking experiments to test the predictive performance of MILAMP in comparison to previously published state of the art techniques for amyloid prediction. The python code for the implementation and webserver for MILAMP is available at the URL: http://faculty.pieas.edu.pk/fayyaz/software.html#MILAMP.

Uptake and distribution of minerals and heavy metals in commonly grown leafy vegetable species irrigated with sewage water.

Heavy metal uptake and accumulation behavior in dietary vegetables irrigated with sewage waters is an important issue worldwide. The main objective of this study was to examine and compare the physiological and growth responses of leafy vegetables irrigated with sewage water. A pot experiment was conducted in a wire house with three leafy vegetables, coriander (Coriandrum sativum), mint (Mentha arvensis), and fenugreek (Trigonella foenum), grown under ambient conditions. Plants were irrigated with different concentrations, 0, 50 (T 1), and 100 % (T 2), of sewage water. After harvesting, morphological and physiological parameters of plants were measured. Heavy metal (Cd, Cu, Pb, and Zn) concentrations in the sewage water were found much higher than safer limits. The results revealed that the highest plant biomass and lowest metal contents were observed in control treatments in all studied vegetables. The biomass of all the vegetables were negatively affected when irrigated with sewage water. In T 2, coriander accumulated maximum Cd (µg g(-1) DW) in shoots (4.97) as compared to other vegetables. The maximum Pb and Cu concentrations were accumulated in mint roots (44 and 3.9, respectively) as compared to coriander and fenugreek. Zinc was accumulated in the sequence of leaves > roots > shoots under polluted water irrigation. The concentrations of potassium increased in leaves, shoots, and roots in all vegetables, while phosphorous concentrations varied with species and plant parts with increasing sewage water concentration. It was found that the leafy vegetables grown with sewage water irrigation may cause severe human health problems.