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Summary: Immune‐mediated thrombotic thrombocytopenic purpura (iTTP) is a rare condition caused by severe ADAMTS13 deficiency, leading to platelet aggregation and thrombosis. Despite treatment, patients are prone to cognitive impairment and depression. We investigated brain changes in iTTP patients during remission using advanced magnetic resonance imaging (MRI) techniques, correlating these changes with mood and neurocognitive tests. Twenty iTTP patients in remission (30 days post‐haematological remission) were compared with six healthy controls. MRI scans, including standard and specialized sequences, were conducted to assess white matter health. Increased T1 relaxation times were found in the cingulate cortex (p < 0.05), and elevated T2 relaxation times were observed in the cingulate cortex, frontal, parietal and temporal lobes (p < 0.05). Pathological changes in these areas are correlated with impaired cognitive and depressive scores in concentration, short‐term memory and verbal memory. This study highlights persistent white matter damage in iTTP patients, potentially contributing to depression and cognitive impairment. Key regions affected include the frontal lobe and cingulate cortex. These findings have significant implications for the acute and long‐term management of iTTP, suggesting a need for re‐evaluation of treatment approaches during both active phases and remission. Further research is warranted to enhance our understanding of these complexities. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles (α- Fe2O3) were synthesized using an unconventional, eco-friendly technique utilizing a Hibiscus rosa sinensis flower (common name, China rose) extract as a reducer and stabilizer agent. The microwave method was successfully used for the synthesis of iron oxide nanoparticles. Various volume ratios of iron chloride tetrahydrate to the extract were taken and heated by the microwave oven for different periods to optimize iron oxide nanoparticle production. The synthesized iron oxide nanoparticles were characterized using the ultraviolet-visible spectrometer (UV-Vis), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and X-ray diffraction (XRD). X-ray diffraction confirmed the formation of α- Fe2O3 nanoparticles (hematite). The average size of iron oxide nanoparticles was found to be 51 nm. The antibacterial activity of the synthesized iron nanoparticles was investigated against different bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, and Escherichia coli. The results showed that the synthesized iron nanoparticles exhibited an inhabitation effect on all studied bacteria. [ABSTRACT FROM AUTHOR]

Copyright of Eastern Mediterranean Health Journal is the property of World Health Organization and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract The cDNA of a type 1 ADP-ribosylation factor (ARF) from the desert locust, Locusta migratoria was cloned, sequenced and compared to ARF1 genes of other species. The locust ARF1 protein is 100% identical with the ARF1 protein of the fruit fly Drosophila melanogaster even though the DNA sequences are only 79% identical. The significance of this finding in relation to the considerable evolutionary distance between hemimetabolous and holometabolous insects is discussed. [ABSTRACT FROM AUTHOR]

Reports the cases of two patients with long-standing poorly controlled diabetes in whom nicotinic acid (NA) has been used to decrease the occurrence of hypoglycemic episodes. Medical records of the patients; Response of the patients to NA treatment.

Pathogen attacks can cause significant damage to plants, posing a threaten to global food production. Plants have developed exquisite methods to rapidly store a key defensive hormone jasmonate (JA), which stimulates their entire evolutionary adaptive response to pathogen attack. However, understanding how plants initiate JA biosynthesis in response to pathogen attacks has remained elusive. In this review, we discuss the newly discovered JAV1-JAZ8-WRKY51 (JJW) complex, which plays a crucial role in regulating JA production to deter insect attacks. The JJW complex inhibits JA production in plants, maintaining a low baseline level of JA that promotes optimal plant development. However, when plants are attacked by insects, a rapid influx of calcium stimulates the JAV1 calcium-dependent protein phosphate, leading to the breakdown of the JJW complex and the activation of JA production. This surge in JA levels, initiates plant defense mechanisms against the invading insects. These findings shed light on the intricate defense system that plants have evolved to combat diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development of heavy metals, particularly chromium (Cr)-tolerant crop cultivars, is hampered due to lack of understanding of the mechanisms behind Cr stress tolerance. In this study, two Brassica napus cultivars, ZS758 and ZD622, were compared for Cr stress resistance by using the chlorophyll a fluorescence technique and biochemical characteristics. In both cultivars, Cr stress dramatically decreased PSII and PSI efficiency, biomass accumulation, and antioxidant enzyme levels. Although, cultivar ZS758 showed reduction in oxidative stress by decreasing the production of reactive oxygen species (ROS) in terms of reduced H 2 O 2 and MDA content and increased enzymatic activities of key antioxidants enzymes including SOD, APX, CAT, and POD activities that play a crucial role in the regulation of numerous transcriptional pathways involved in oxidative stress responses. Higher non-photochemical quenching (NPQ) and QY were found in tolerant ZS758 cultivar under Cr stress, indicating that tolerant cultivar had a greater capacity to preserve PSII activity under Cr stress by enhancing heat dissipation as a photo-protective component of NPQ. Lower PSI activity and electron transfer from PSII were confirmed by lower PSI efficiency and higher donor end limitation of PSI in both rapeseed cultivars. The Cr concentration was greater in the ZD622 as compared to ZS758, which affected the mineral nutrients profile and damaged the cellular ultrastructure and related gene expression levels. However, current study suggest that cultivar ZS758 is more resistant to Cr stress than ZD622 due to improved metabolism and structural integrity and Cr stress tolerance that is linked with the increased PSII activity, NPQ, and antioxidant potential; these physiological characteristics can be exploited to select cultivars for Cr stress tolerance., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The impact of functionality of biochar on pressing environmental issue of cadmium (Cd) and lead (Pb) co-contamination in simultaneous soil and water systems has not sufficiently reported. This study investigated the impact of Fe- and Mg-functionalized wheat straw biochar (Fe-WSBC and Mg-WSBC) on Cd and Pb adsorption/immobilization through batch sorption and column leaching trials. Importantly, Fe-WSBC was more effective in adsorbing Cd and Pb (82.84 and 111.24 mg g -1 ), regeneration ability (removal efficiency 94.32 and 92.365), and competitive ability under competing cations (83.15 and 84.36%) compared to other materials (WSBC and Mg-WSBC). The practical feasibility of Fe-WSBC for spiked river water verified the 92.57% removal of Cd and 85.73% for Pb in 50 mg L -1 and 100 mg L -1 contamination, respectively. Besides, the leaching of Cd and Pb with Fe-WSBC under flow-through conditions was lowered to (0.326 and 17.62 mg L -1 ), respectively as compared to control (CK) (0.836 and 40.40 mg L -1 ). In short, this study presents the applicable approach for simultaneous remediation of contaminated water and soil matrices, offering insights into environmentally friendly green remediation strategies for heavy metals co-contaminated matrices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cadmium contamination poses severe environmental and health threats, necessitating effective mitigation strategies. Rice husk biochar (BC) and nanoparticle (NP) treatments are emerging strategies with limited research on their synergistic benefits. This study assesses BC, silicon NPs (nSi), and iron NPs (nFe) modifications (B-nSi, B-nFe, and B-nSi-nFe) to reduce Cd-bioavailability in soil and its toxicity in maize, not reported before. Characterization of amendments validated, nSi and nFe attachment to BC, forming new mineral crystals to adsorb Cd. We found that B-nSi-nFe induced Cd-immobilization in soil by the formation of Cd-ligand complexes with the effective retention of NPs within microporous structure of BC. B-nSi-nFe increased soil pH by 0.76 units while reducing bioavailable Cd by 49 %, than Ck-Cd. Resultantly, B-nSi-nFe reduced Cd concentrations in roots and shoots by 51 % and 75 %, respectively. Moreover, the application of B-nSi-nFe significantly enhanced plant biomass, antioxidant activities, and upregulated the expression of antioxidant genes [ZmAPX (3.28 FC), ZmCAT (3.20 FC), ZmPOD (2.58 FC), ZmSOD (3.08 FC), ZmGSH (3.17 FC), and ZmMDHAR (3.80 FC)] while downregulating Cd transporter genes [ZmNramp5 (3.65 FC), ZmHMA2 (2.92 FC), and ZmHMA3 (3.40 FC)] compared to Ck-Cd. Additionally, confocal microscopy confirmed the efficacy of B-nSi-nFe in maintaining cell integrity due to reduced oxidative stress. SEM and TEM observations revealed alleviation of Cd toxicity to stomata, guard cells, and ultracellular structures with B-nSi-nFe treatment. Overall, this study demonstrated the potential of B-nSi-nFe for reducing Cd mobility in soil-plant system, mitigating Cd-toxicity in plants and improving enzymatic activities in soil., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chromium (Cr) is a highly toxic heavy metal that is extensively released into the soil and drastically reduces plant yield. Silicon nanoparticles (Si NPs) were chosen to mitigate Cr toxicity due to their ability to interact with heavy metals and reduce their uptake. This manuscript explores the mechanisms of Cr-induced toxicity and the potential of Si NPs to mitigate Cr toxicity by regulating photosynthesis, oxidative stress, and antioxidant defence, along with the role of transcription factors and heavy metal transporter genes in rapeseed (Brassica napus L.). Rapeseed plants were grown hydroponically and subjected to hexavalent Cr stress (50 and 100 μM) in the form of K 2 Cr 2 O 7 solution. Si NPs were foliar sprayed at concentrations of 50, 100 and 150 μM. The findings showed that 100 μM Si NPs under 100 μM Cr stress significantly increased the leaf Si content by 169% while reducing Cr uptake by 92% and 76% in roots and leaves, respectively. The presence of Si NPs inside the plant leaf cells was confirmed by using energy-dispersive spectroscopy, inductively coupled plasma‒mass spectrometry, and confocal laser scanning microscopy. The study's findings showed that Cr had adverse effects on plant growth, photosynthetic gas exchange attributes, leaf mesophyll ultrastructure, PSII performance and the activity of enzymatic and nonenzymatic antioxidants. However, Si NPs minimized Cr-induced toxicity by reducing total Cr accumulation and decreasing oxidative damage, as evidenced by reduced ROS production (such as H 2 O 2 and MDA) and increased enzymatic and nonenzymatic antioxidant activities in plants. Interestingly, Si NPs under Cr stress effectively increased the NPQ, ETR and QY of PSII, indicating a robust protective response of PSII against stress. Furthermore, the enhancement of Cr tolerance facilitated by Si NPs was linked to the upregulation of genes associated with antioxidant enzymes and transcription factors, alongside the concurrent reduction in metal transporter activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Plants being sessile in nature, are exposed to unwarranted threats as a result of constantly changing environmental conditions. These adverse factors can have negative impacts on their growth, development, and yield. Hormones are key signaling molecules enabling cells to respond rapidly to different external and internal stimuli. In plants, melatonin (MT) plays a critical role in the integration of various environmental signals and activation of stress-response networks to develop defense mechanisms and plant resilience. Additionally, melatonin can tackle the stress-induced alteration of cellular redox equilibrium by regulating the expression of redox hemostasis-related genes and proteins. The purpose of this article is to compile and summarize the scientific research pertaining to MT's effects on plants' resilience to biotic and abiotic stresses. Here, we have summarized that MT exerts a synergistic effect with other phytohormones, for instance, ethylene, jasmonic acid, and salicylic acid, and activates plant defense-related genes against phytopathogens. Furthermore, MT interacts with secondary messengers like Ca 2+ , nitric oxide, and reactive oxygen species to regulate the redox network. This interaction triggers different transcription factors to alleviate stress-related responses in plants. Hence, the critical synergic role of MT with diverse plant hormones and secondary messengers demonstrates phytomelatonin's importance in influencing multiple mechanisms to contribute to plant resilience against harsh environmental factors., Competing Interests: Declaration of competing interest All authors declare no conflict of interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Exposure of crops to low temperature (LT) during emerging and reproductive stages influences their growth and development. In this study, we have isolated a cold induced, nucleus-localized lipid A gene from rice named OsLPXC, which encodes a protein of 321 amino acids. Knockout of OsLPXC resulted in enhance sensitivity to LT stress in rice, with increased accumulation of reactive oxygen species (ROS), malondialdehyde and electrolyte leakage, while expression and activities of antioxidant enzymes were significantly suppressed. The accumulation of chlorophyll content and net photosynthetic rate of knockout plants were also decreased compared with WT under LT stress. The functional analysis of differentially expressed genes (DEGs), showed that numerous genes associated with antioxidant defense, photosynthesis, cold signaling were solely expressed and downregulated in oslpxc plants compared with WT under LT. The accumulation of methyl jasmonate (MeJA) in leave and several DEGs related to the jasmonate biosynthesis pathway were significantly downregulated in OsLPXC knockout plants, which showed differential levels of MeJA regulation in WT and knockout plants in response to cold stress. These results indicated that OsLPXC positively regulates cold tolerance in rice via stabilizing the expression and activities of ROS scavenging enzymes, photosynthetic apparatus, cold signaling genes, and jasmonate biosynthesis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Foliar-application of nano-particles enhanced the foliar nutrient status and crop growth and yield. It is hypothesized that being second messenger molecule, supplementation of Ca 2+ via calcium nanoparticles (Ca-NPs) can trigger various signaling pathways of physiological processes which can lead to alleviate the adverse effects of drought stress on the growth of canola (Brassica napus L.). Nano-enabled foliar-application could be an ideal strategy for advancing agricultural productivity. The present study explored the role of calcium nanoparticles (Ca-NPs) in alleviating drought stress in hydroponic Brassica napus (B. napus) plants. The foliar applied Ca-NPs were spherically shaped with an average size of 86 nm. Foliar application of 100 mg L -1 Ca-NPs enhanced biomass of canola plants and considered as optimal dose. Ca-NPs at 100 mg L -1 has a greater favorable impact on mesophyll ultrastructure, PSI and PSII efficacy, gas exchange parameters, chlorophyll content, and mineral absorption. The Ca-NPs treatment increased NPQ and Y(NPQ) under drought condition, indicating a higher PSII protective response to stressed conditions with better heat dissipation as a photoprotective component of NPQ. Ca-NPs application also reduced oxidative stress damage as measured by a reduction in reactive oxygen species (ROS) generation in terms of hydrogen peroxide and malondialdehyde (H 2 O 2 and MDA). Furthermore, Ca-NPs induced drought tolerance response corresponded to an increased in key antioxidative defense enzymes (SOD, POD, CAT, APX), as well as non-enzymatic components (protease, lipoxygenase, proline, total soluble protein contents, endogenous hormonal biosynthesis), and secondary metabolite expression in B. napus plants. Taken together, the results of this study offer new insights into the physiological and molecular mechanisms by which B. napus responds to Ca-NPs exposure., Competing Interests: Declaration of Competing Interest Authors declared there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purple-stem Brassica napus ( B. napus ) is a phenotype with unique color because of its high anthocyanins content. Anthocyanins are naturally occurring plant pigments that have antioxidants activity and play important role in plant defense against abiotic and biotic stresses. In the present study, drought induced effects on plants were investigated in hydroponically grown seedlings of green stem (GS) and purple stem (PS) genotypes of B. napus . The results of this study showed that the major function of anthocyanins accumulation during drought was to enhance the antioxidant capability and stress tolerance in B. napus plants. Our results showed that drought significantly inhibited the plant growth in terms of decreased biomass accumulation in both genotypes, although marked decline was observed in GS genotype. The reduction in photosynthetic attributes was more noticeable in the GS genotype, whereas the PS genotype showed better performance under drought stress. Under stressful conditions, both the genotype showed excessive accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher levels of antioxidant enzymes activities. Under drought conditions, the GS genotype showed apparent damages on chloroplast deformation like in thylakoid membrane and grana structural distortion and fewer starch grains and bigger plastoglobuli. Moreover, during drought stress, the PS genotype exhibited maximum expression levels of anthocyanins biosynthesis genes and antioxidant enzymes accompanied by higher stress tolerance relative to GS genotype. Based on these findings, it can be concluded that GS genotype found more sensitive to drought stress than the PS genotype. Furthermore this research paper also provides practical guidance for plant biologists who are developing stress-tolerant crops by using anthocyanin biosynthesis or regulatory genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Miao, Ayyaz, Hannan, Huang, Ulhassan, Zhou, Islam, Hong, Farooq and Zhou.)

Melatonin (MT) and selenium (Se) application known to decrease heavy metal uptake and toxicity in plants. By mixing the Se in MT medium a new complex MT-Se nanoparticles (MT-Se NPs) was synthesized and we investigated the role of MT-Se NPs on B. napus growth and tolerance against As stress. The MT-Se particles significantly enhanced the plant growth and other associated physiological attributes under As stress. The As treatment at 80 μM was more phytotoxic, however MT-Se NPs application resulted in a substantial increase in leaf chlorophyll fluorescence, biomass accumulation, and decreased ROS relative to As stressed plants. The use of MT-Se NPs to As stressed plants reduced photosynthetic inhibition and oxidative stress and attenuated the increase in MDA and H 2 O 2 contents. The application of MT-Se NPs also boosted the antioxidant enzymes activities such as SOD, POD and CAT as well as the APX, GR and GSH activates under As stress. The results also showed MT-Se NPs treatments alleviated the growth inhibition induced by As and reduced the accumulation of As in leaves and roots of B. napus seedlings. Moreover, treatment with MT-Se NPs improved the plant growth more successfully than treatment of MT and Se alone. This study explored the mechanism of melatonin and selenium efficiency in the composition can be jointly encouraged to exert synergistic effects and boost plant enzymatic activities., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Mussel shell (MS) and biochar (BC) are commonly used for the remediation of metal contaminated soil. However, less research has been focused to examine the efficacy of their combinations to reduce metal toxicity in crop plants. This study was therefore conducted to investigate the effects of BC, MS and their activated concoctions on the soil properties, enzyme activities and nickel (Ni) immobilization in aged Ni contaminated soil. Moreover, the growth, photosynthetic pigments and anti-oxidative machnery of Brassica napus plants has also been investigated in order to determine amendments efficiency in reducing soil Ni toxicity for plants. The results showed that the application of Ni adversely affected soil health and trigged stress responses by inducing oxidative stress in B. napus. However, the incorporation of amendments reduced the bioavailability of Ni, and the concoctions of BC and MS showed promising results in the immobilization of Ni. Among various combinations of BC and MS, treatment with BC + MS (3:1) significantly reduced Ni uptake, decreased reactive oxygen species (ROS) and enhanced antioxidant defense of B. napus plants. Results showed that amendment's combinations stimulated the transcriptional levels of ROS scavenging enzymes and suppressed the expression level of Ni transporters. The morphological and physical characterization techniques (i.e. SEM, BET, EDS, FTIR and X-ray diffraction analyses) showed that amendment's combinations had relatively higher Ni adsorption capacity, indicating that BC and MS concoctions are efficient immobilizing agents for minimizing Ni availability, preventing oxidative toxicity and promoting growth and biomass production in rapeseed plants under metal stress conditions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In-situ stabilization has been considered an effective way to remediate metal contaminated soil. Thus, pot experiments were undertaken to investigate the effectiveness of multiple stabilization agents such as biochar (BC), mussel shell (MS), zeolite (ZE) and limestone (LS) on the immobilization of Ni, physicochemical features and enzyme activities in polluted soil. Results showed that the sole application of Ni adversely affected the rapeseed growth, photosynthetic pigments, and antioxidative defense. However, the addition of amendments to the contaminated soil significantly reduced Ni bioavailability. The XRD analysis confirmed the formation of Ni related ligands and FTIR showed the presence of hydroxyl, carboxyl and sulfur functional groups, as well as complexation and adsorption of Ni on amendments. Among multiple amendments, biochar significantly enhanced plant biomass attributes and total chlorophyll content. Moreover, addition of amendments also strengthened the antioxidant defense by decreasing Ni induced oxidative stress (H 2 O 2 and O 2 .- ), increased macronutrient availability, reduced Ni uptake and improved soil health. The qPCR analysis showed that the Ni transporters were significantly suppressed by amendments, which is correlated with the lower accumulation of Ni in rapeseed. The present study showed that immobilizing agents, especially biochar, is an effective amendment to immobilize Ni in soil, which restricts its entry into the food chain., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Climate change, food insecurity, water scarcity, and population growth are some of today's world's frightening problems. Drought stress exerts a constant threat to field crops and is often seen as a major constraint on global agricultural productivity; its intensity and frequency are expected to increase in the near future. The present study investigated the effects of drought stress (15% w/v polyethylene glycol PEG-6000) on physiological and biochemical changes in five Brassica napus cultivars (ZD630, ZD622, ZD619, GY605, and ZS11). For drought stress induction, 3-week-old rapeseed oil seedlings were treated with PEG-6000 in full strength Hoagland nutrient solution for 7 days. PEG treatment significantly decreased the plant growth and photosynthetic efficiency, including primary photochemistry (Fv/Fm) of PSII, intercellular CO 2 , net photosynthesis, chlorophyll contents, and water-use efficiency of all studied B. napus cultivars; however, pronounced growth retardations were observed in cultivar GY605. Drought-stressed B. napus cultivars also experienced a sharp rise in H 2 O 2 generation and malondialdehyde (MDA) content. Additionally, the accumulation of ROS was accompanied by increased activity of enzymatic antioxidants (superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, glutathione reductase, and monodehydroascorbate reductase), although the increase was more obvious in ZD622 and ZS11. Drought stress also caused an increased endogenous hormonal biosynthesis (abscisic acid, jasmonic acid, salicylic acid) and accumulation of total soluble proteins and proline content, but the extent varies in B. napus cultivars. These results suggest that B. napus cultivars have an efficient drought stress tolerance mechanism, as shown by improved antioxidant enzyme activities, photosynthetic and hormonal regulation., (© 2021 Scandinavian Plant Physiology Society.)

Background: The use of 96-well plates is ubiquitous in preclinical studies. Corner and edge wells have been observed to be more prone to evaporation compared to interior wells., Methods: Mammalian cells were cultured in 96-well plates over a period of 72 h. VWR and Greiner plates were tested. MTS reagent was added, and metabolic activity was determined after 2 h., Results: When using VWR plates, cells showed a highly heterogeneous pattern of cell growth. The outer wells showed 35% lower metabolic activity than the central wells. Cells grown in rows two and three also grew sub-optimally (25% and 10% reduction compared to central wells). Greiner plates showed better homogeneity. Cells grown in the outer wells showed 16% lower metabolic activity while cells in rows two and three showed reductions of 7 and 1%, respectively. This edge effect was partially mitigated by storing the plates in loosely sealed wrapping during incubation. Placing a buffer between the wells of the plate further improved homogeneity for the Greiner plates., Conclusion: Different brands of 96-well plates show different levels of the edge effect. Some clearly are inappropriate for such studies., General Significance: Each laboratory needs to determine their own optimum conditions for culturing cells empirically before continuing to use multiwell plates. Otherwise, large artifacts may arise, affecting the quality of data, with the potential of introducing type I or type II errors., Competing Interests: This research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2021 The Authors. Published by Elsevier B.V.)

Arsenic (As) a non-essential element is of particular concern with respect to harmful effects on plant metabolism. While extensive studies have been conducted on the physiological responses of plants to increase As concentrations, however, molecular differences elucidating species-specific changes remain largely unknown. In the present experiment, two oilseed Brassica napus (B. napus) cultivars, ZS758 and ZD622, were treated by elevated As concentration. Their responses to the As stress have been investigated through pulse amplitude modulated fluorometer and isobaric tags based proteomic (iTRAQ) analysis. The chlorophyll fluorescence attributes showed that As stress significantly decrease the photochemical efficiency of photosystem II (PSII) and photosystem I (PSI) as well as the comparatively closed stomata observed under scanning electron microscopy (SEM). In this study, 65 proteins displayed increased abundance and 52 down-regulated were found in the control vs As comparison in cultivar ZS758, while 44 up and 67 down-regulated proteins were found in the control vs As comparison in ZD622. Metabolic pathways, followed by ribosome and biosynthesis of secondary metabolites were the dominant functional annotation categories among the differentially expressed protein (DEPs). Many genes involved in primary metabolism, stress and defense were found to be As-responsive DEPs and/or DEPs between these two cultivars. Based on these results, a schematic description of key processes involved in As tolerance in ZS758 and ZD622 is proposed, which suggests that higher tolerance in ZS758 depends on a multilevel coordination of efficient defense and energy metabolism. Real-time quantitative PCR supported the expression patterns of several genes encoding a protein similar to their corresponding DEPs. In addition, these findings could shed light in unraveling the molecular mechanisms of B. napus exposed to As stress and provide or improve essential understandings in the development of advanced B. napus cultivars against As resistance., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Crops frequently encounter abiotic stresses, and salinity is a prime factor that suppresses plant growth and crop productivity, globally. Ursolic acid (UA) is a potential signaling molecule that alters physiology and biochemical processes and activates the defense mechanism in numerous animal models; however, effects of UA in plants under stress conditions and the underlying mechanism of stress alleviation have not been explored yet. This study examined the effects of foliar application of UA (100 μM) to mitigate salt stress in three rice cultivars (HZ, 712, and HAY). A pot experiment was conducted in a climate-controlled greenhouse with different salt stress treatments. The results indicated that exposure to NaCl-induced salinity reduces growth of rice cultivars by damaging chlorophyll pigment and chloroplast, particularly at a higher stress level. Application of UA alleviated adverse effects of salinity by suppressing oxidative stress (H 2 O 2 , O 2- ) and stimulating activities of enzymatic and non-enzymatic antioxidants (APX, CAT, POD, GR, GSH, AsA, proline, glycinebutane), as well as protecting cell membrane integrity (MDA, LOX, EL). Furthermore, UA application brought about a significant increase in the concentration of leaf nitric oxide (NO) by modulating the expression of NR and NOS enzymes. It seems that UA application also influenced Na + efflux and maintained a lower cytosolic Na + /K + ratio via concomitant upregulation of OsSOS1 and OsHKT1;5 in rice cultivars. The results of pharmacological tests have shown that supply of the NO scavenger (PTI) completely reversed the UA-induced salt tolerance in rice cultivars by quenching endogenous NO and triggering oxidative stress, Na + uptake, and lipid peroxidation. The PTI application with UA and sodium nitroprusside (SNP) also caused growth retardation and a significant increase in Na + uptake and oxidative stress in rice cultivars. This suggests that UA promoted salt tolerance of rice cultivars by triggering NO production and limiting toxic ion and reactive oxygen species (ROS) accumulation. These results revealed that both UA and NO are together required to develop a salt tolerance response in rice., (Copyright © 2020 Long, Shou, Wang, Hu, Hannan, Mwamba, Farooq, Zhou and Islam.)

Background: Breast cancer is the most common malignancy in women worldwide. About 5%-10% are due to hereditary predisposition. The contribution of BRCA1/2 mutations to familial breast cancer in Bahrain has not been explored. The objective of this study was to investigate the spectrum of BRCA1/2 genetic variants and estimate their frequencies in familial breast cancer. We also aim to test the efficiency of the next-generation sequencing (NGS) as a powerful tool for detecting genetic variation within BRCA1/2 genes., Methods: Twenty-five unrelated female patients diagnosed with familial breast cancer were screened for BRCA1/2 variants. All targeted coding exons and exon-intron boundaries of BRCA1/2 genes were amplified with 167 pairs of primers by NGS., Results: We have identified two deleterious BRCA1/2 variants in two patients, one in BRCA1 gene (c.4850C>A) and other in BRCA2 gene (c.67+2T>C). In addition to the deleterious variants, we identified 24 distinct missense variants of uncertain significance, 10 of them are seen to confer minor but cumulatively significant risk of breast cancer., Conclusion: Our data suggest that BRCA1/2 variants may contribute to the pathogenesis of familial breast cancer in Bahrain. It also shows that NGS is useful tool for screening BRCA1/2 genetic variants of probands and unaffected relatives., (© 2019 RCSI BAHRAIN. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Cadmium (Cd) is a well-known and widespread toxic heavy metal while the effects of biochar (BC) on Cd bioavailability and toxicity in wheat, especially in soils with aged contamination are largely unknown. In the present study, the effect of rice straw BC on Cd immobilization in soil and uptake by wheat in an agricultural contaminated-soil was investigated. Different levels of rice straw BC (0%, 1.5%, 3.0% and 5% w/w) were incorporated into the soil and incubated for two weeks. After this, wheat plants were grown in the amended soil until maturity. The results show that the BC treatments increased the soil and soil solution pH and silicon contents in the plant tissues and in the soil solution while decreased the bioavailable Cd in soil. The BC application increased the plant-height, spike-length, shoot and root dry mass and grain yield in a dose additive manner when compared with control treatment. As compared to control, BC application increased the photosynthetic pigments and gas exchange parameters in leaves. Biochar treatments decreased the oxidative stress while increased the activities of antioxidant enzymes in shoots compared to the control. The BC treatments decreased the Cd and Ni while increased Zn and Mn concentrations in shoots, roots, and grains of wheat compared to the control. As compared to the control, Cd concentration in wheat grains decreased by 26%, 42%, and 57% after the application of 1.5%, 3.0%, and 5.0% BC respectively. Overall, the application of rice straw BC might be effective in immobilization of metal in the soil and reducing its uptake and translocation to grains., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Maize (Zea mays L.) has been widely adopted for phytomanagement of cadmium (Cd)-contaminated soils due to its high biomass production and Cd accumulation capacity. This paper reviewed the toxic effects of Cd and its management by maize plants. Maize could tolerate a certain level of Cd in soil while higher Cd stress can decrease seed germination, mineral nutrition, photosynthesis and growth/yields. Toxicity response of maize to Cd varies with cultivar/varieties, growth medium and stress duration/extent. Exogenous application of organic and inorganic amendments has been used for enhancing Cd tolerance of maize. The selection of Cd-tolerant maize cultivar, crop rotation, soil type, and exogenous application of microbes is a representative agronomic practice to enhance Cd tolerance in maize. Proper selection of cultivar and agronomic practices combined with amendments might be successful for the remediation of Cd-contaminated soils with maize. However, there might be the risk of food chain contamination by maize grains obtained from the Cd-contaminated soils. Thus, maize cultivation could be an option for the management of low- and medium-grade Cd-contaminated soils if grain yield is required. On the other hand, maize can be grown on Cd-polluted soils only if biomass is required for energy production purposes. Long-term field trials are required, including risks and benefit analysis for various management strategies aiming Cd phytomanagement with maize.

Chromium (Cr) is among the most toxic pollutants in the environment that adversely affect the living organisms and physiological processes in different plants. The present study investigated the effect of 15 mg L -1 of 5-aminolevulinic acid (ALA) on morpho-physiological attributes of cauliflower (Brassica oleracea botrytis L.) under different Cr concentrations (0, 10, 100, and 200 μM) in the growth medium. The results showed that Cr stress decreased the growth, biomass, photosynthetic, and gas exchange parameters. Chromium stress enhanced the activities of enzymatic antioxidants, catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) in response to oxidative stress caused by the elevated levels of malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ), and electrolyte leakage (EL) in both roots and leaves of cauliflower. Chromium concentrations and total Cr uptake were increased in leaves, stems, and roots with increasing Cr levels in the culture medium. Foliar application of ALA increased the plant growth parameters, biomass, gas exchange parameters, and photosynthetic pigments under Cr stress compared to the treatments without ALA. Foliar application ALA decreased the levels of MDA, EL, and H 2 O 2 while further improved the performance of antioxidant in both leaves and roots compared to only Cr-stressed plant. Chromium concentrations and total Cr uptake were decreased by the ALA application compared to treatments without ALA application. The results of the present study indicated that foliar application of ALA might be beneficial in minimizing Cr uptake and its toxic effects in cauliflower.

Calcareous soil, high pH, and low organic matter are the major factors that limit iron (Fe) availability to rice crop. The present study was planned with the aim to biofortified rice grain with Fe, by integrated use of chemical and organic amendments in pH-manipulated calcareous soil. The soil pH was reduced (pH L2 ) by using elemental sulfur (S) at the rate of 0.25 % (w/w). The organic amendments, biochar (BC) and poultry manure (PM) [1 % (w/w)], along with ferrous sulfate at the rate of 7.5 mg kg -1 soil were used. The incorporation of Fe with BC in soil at pH L2 significantly improved plant biomass, photosynthetic rate, and paddy yield up to 99, 97, and 36 %, respectively, compared to control. A significant increase in grain Fe (190 %), protein (58 %), and ferritin (400 %) contents was observed while anti-nutrients, i.e., polyphenols (37 %) and phytate (21 %) were significantly decreased by the addition of Fe and BC in soil at pH L2 relative to control. Among the organic amendments, PM significantly increased Cd, Pb, Ni, and Cr concentrations in rice grain relative to control but their concentration values were below as compared to the toxic limits of hazard quotients and hazard index (HQ and HI). Hence, this study implies that Fe applied with BC in the soil at pH L2 can be considered as an effective strategy to augment Fe bioavailability and to reduce non-essential heavy metal accumulation in rice grain.

Cadmium (Cd) is one of the main pollutants in paddy fields, and its accumulation in rice (Oryza sativa L.) and subsequent transfer to food chain is a global environmental issue. This paper reviews the toxic effects, tolerance mechanisms, and management of Cd in a rice paddy. Cadmium toxicity decreases seed germination, growth, mineral nutrients, photosynthesis, and grain yield. It also causes oxidative stress and genotoxicity in rice. Plant response to Cd toxicity varies with cultivars, growth condition, and duration of Cd exposure. Under Cd stress, stimulation of antioxidant defense system, osmoregulation, ion homeostasis, and over production of signaling molecules are important tolerance mechanisms in rice. Several strategies have been proposed for the management of Cd-contaminated paddy soils. One such approach is the exogenous application of hormones, osmolytes, and signaling molecules. Moreover, Cd uptake and toxicity in rice can be decreased by proper application of essential nutrients such as nitrogen, zinc, iron, and selenium in Cd-contaminated soils. In addition, several inorganic (liming and silicon) and organic (compost and biochar) amendments have been applied in the soils to reduce Cd stress in rice. Selection of low Cd-accumulating rice cultivars, crop rotation, water management, and exogenous application of microbes could be a reasonable approach to alleviate Cd toxicity in rice. To draw a sound conclusion, long-term field trials are still required, including risks and benefit analysis for various management strategies.

Cadmium (Cd) accumulation in wheat (Triticum aestivum L.) and its subsequent transfer to food chain is a major environmental issue worldwide. Understanding wheat response to Cd stress and its management for aiming to reduce Cd uptake and accumulation in wheat may help to improve wheat growth and grain quality. This paper reviewed the toxic effects, tolerance mechanisms, and management of Cd stress in wheat. It was concluded that Cd decreased germination, growth, mineral nutrients, photosynthesis and grain yield of wheat and plant response to Cd toxicity varies with cultivars, growth conditions and duration of stress applied. Cadmium caused oxidative stress and genotoxicity in wheat plants. Stimulation of antioxidant defense system, osmoregulation, ion homeostasis and over production of signalling molecules are important adaptive strategies of wheat under Cd stress. Exogenous application of plant growth regulators, inorganic amendments, proper fertilization, silicon, and organic, manures and biochar, amendments are commonly used for the reduction of Cd uptake in wheat. Selection of low Cd-accumulating wheat cultivars, crop rotation, soil type, and exogenous application of microbes are among the other agronomic practices successfully employed in reducing Cd uptake by wheat. These management practices could enhance wheat tolerance to Cd stress and reduce the transfer of Cd to the food chain. However, their long-term sustainability in reducing Cd uptake by wheat needs further assessment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The initial discovery of resistin and resistin-like molecules (RELMs) in rodents suggested a role for these adipocytokines in molecular linkage of obesity, Type 2 Diabetes mellitus and metabolic syndrome. Since then, it became apparent that the story of resistin and RELMs was very much of mice and men. The putative role of this adipokine family evolved from that of a conveyor of insulin resistance in rodents to instigator of inflammatory processes in humans. Structural dissimilarity, variance in distribution profiles and a lack of corroborating evidence for functional similarities separate the biological functions of resistin in humans from that of rodents. Although present in gross visceral fat deposits in humans, resistin is a component of inflammation, being released from infiltrating white blood cells of the sub-clinical chronic low grade inflammatory response accompanying obesity, rather than from the adipocyte itself. This led researchers to further explore the functions of the resistin family of proteins in inflammatory-related conditions such as atherosclerosis, as well as in cancers such as endometrial and gastric cancers. Although elevated levels of resistin have been found in these conditions, whether it is causative or as a result of these conditions still remains to be determined.

Auditory neuropathy is a rare form of deafness characterized by an absent or abnormal auditory brainstem response with preservation of outer hair cell function. We have identified Diaphanous homolog 3 (DIAPH3) as the gene responsible for autosomal dominant nonsyndromic auditory neuropathy (AUNA1), which we previously mapped to chromosome 13q21-q24. Genotyping of additional family members narrowed the interval to an 11-Mb, 3.28-cM gene-poor region containing only four genes, including DIAPH3. DNA sequencing of DIAPH3 revealed a c.-172G>A, g. 48G>A mutation in a highly conserved region of the 5' UTR. The c.-172G>A mutation occurs within a GC box sequence element and was not found in 379 controls. Using genome-wide expression arrays and quantitative RT-PCR, we demonstrate a 2- to 3-fold overexpression of DIAPH3 mRNA in lymphoblastoid cell lines from affected individuals. Likewise, a significant increase (approximately 1.5-fold) in DIAPH3 protein was found by quantitative immunoblotting of lysates from lymphoblastoid cell lines derived from affected individuals in comparison with controls. In addition, the c.-172G>A mutation is sufficient to drive overexpression of a luciferase reporter. Finally, the expression of a constitutively active form of diaphanous protein in the auditory organ of Drosophila melanogaster recapitulates the phenotype of impaired response to sound. To date, only two genes, the otoferlin gene OTOF and the pejvakin gene PJVK, are known to underlie nonsyndromic auditory neuropathy. Genetic testing for DIAPH3 may be useful for individuals with recessive as well as dominant inheritance of nonsyndromic auditory neuropathy.

Objectives: This study capitalizes on the unique molecular and developmental similarities between the auditory organs of Drosophila and mammals, to investigate genes implicated in human syndromic and nonsyndromic hearing loss in a genetically tractable experimental animal model, the fruit fly Drosophila., Methods: The Drosophila counterparts of 3 human deafness genes (DIAPH1/DFNA1, ESPN/DFNB36, and TMHS/DF-NB67) were identified by sequence similarity. An electrophysiological assay was used to record sound-evoked potentials in response to an acoustic stimulus, the Drosophila courtship song., Results: Flies with mutations affecting the diaphanous,forked, and CG12026/TMHS genes displayed significant reductions in the amplitude of sound-evoked potentials compared to wild-type flies (p < 0.05 to p < 0.005). The mean responses were reduced from approximately 500 to 600 microV in wild-type flies to approximately 100 to 300 microV in most mutant flies., Conclusions: The identification of significant auditory dysfunction in Drosophila orthologs of human deafness genes will facilitate exploration of the molecular biochemistry of auditory mechanosensation. This may eventually allow for novel diagnostic and therapeutic approaches to human hereditary hearing loss.

Neurofibromatosis type 1 (NF1) is a dominant genetic disorder that causes tumors of the peripheral nervous system. In addition, >40% of afflicted children have learning difficulties. The NF1 protein contains a highly conserved GTPase-activating protein domain that inhibits Ras activity, and the C-terminal region regulates cAMP levels via G-protein-dependent activation of adenylyl cyclase. Behavioral analysis indicates that learning is disrupted in both Drosophila and mouse NF1 models. Our previous work has shown that defective cAMP signaling leads to the learning phenotype in Drosophila Nf1 mutants. In the present report, our experiments showed that in addition to learning, long-term memory was also abolished in Nf1 mutants. However, altered NF1-regulated Ras activity is responsible for this defect rather than altered cAMP levels. Furthermore, by expressing clinically relevant human NF1 mutations and deletions in Drosophila Nf1-null mutants, we demonstrated that the GAP-related domain of NF1 was necessary and sufficient for long-term memory, whereas the C-terminal domain of NF1 was essential for immediate memory. Thus, we show that two separate functional domains of the same protein can participate independently in the formation of two distinct memory components.

Neurofibromatosis type I (NFI) is a common genetic disorder that causes nervous system tumors, and learning and memory defects in humans, and animal models. We identify a novel growth factor stimulated adenylyl cyclase (AC) pathway in the Drosophila brain, which is disrupted by mutations in the epidermal growth factor receptor (EGFR), neurofibromin (NF1) and Ras, but not Galpha(s). This is the first demonstration in a metazoan that a receptor tyrosine kinase (RTK) pathway, acting independently of the heterotrimeric G-protein subunit Galpha(s), can activate AC. We also show that Galpha(s) is the major Galpha isoform in fly brains, and define a second AC pathway stimulated by serotonin and histamine requiring NF1 and Galpha(s), as well as a third, classical Galpha(s)-dependent AC pathway, which is stimulated by Phe-Met-Arg-Phe-amide (FMRFamide) and dopamine. Using mutations and deletions of the human NF1 protein (hNF1) expressed in Nf1 mutant flies, we show that Ras activation by hNF1 is essential for growth factor stimulation of AC activity. Further, we demonstrate that sequences in the C-terminal region of hNF1 are sufficient for NF1/Galpha(s)-dependent neurotransmitter stimulated AC activity, and for rescue of body size defects in Nf1 mutant flies.

Vitamin D deficiency and primary hyperparathyroidism (PHPT) are relatively common disorders. The coexistence of these conditions should be considered, as depletion of vitamin D may alter the clinical expression of autonomous parathyroid disease. We report details of a vitamin D deficient patient in whom replacement therapy led to the unmasking of occult PHPT.

To study the representation of olfactory information in higher brain centers, we expressed a green fluorescent protein-based Ca2+ sensor, G-CaMP, in the Drosophila mushroom body (MB). Using two-photon microscopy, we imaged odor-evoked G-CaMP fluorescence transients in MB neurons [Kenyon cells (KCs)] with single-cell resolution. Odors produced large fluorescence transients in a subset of KC somata and in restricted regions of the calyx, the neuropil of the MB. In different KCs, odor-evoked fluorescence transients showed diverse changes with odor concentration: in some KCs, fluorescence transients were evoked by an odor at concentrations spanning several orders of magnitude, whereas in others only at a narrow concentration range. Different odors produced fluorescence transients in different subsets of KCs. The spatial distributions of KCs showing fluorescence transients evoked by a given odor were similar across individuals. For some odors, individual KCs with fluorescence transients evoked by a particular odor could be found in similar locations in different flies with spatial precisions on the order of the size of KC somata. These results indicate that odor-evoked activity can have remarkable spatial specificity in the MB.

Notch (N) is a cell surface receptor that mediates an evolutionarily ancient signaling pathway to control an extraordinarily broad spectrum of cell fates and developmental processes. To gain insights into the functions of N signaling in the adult brain, we examined the involvement of N in Drosophila olfactory learning and memory. Long-term memory (LTM) was disrupted by blocking N signaling in conditional mutants or by acutely induced expression of a dominant-negative N transgene. In contrast, neither learning nor early memory were affected. Furthermore, induced overexpression of a wild-type (normal) N transgene specifically enhanced LTM formation. These experiments demonstrate that N signaling contributes to LTM formation in the Drosophila adult brain.

Neurofibromatosis type 1 (NF1) is a dominant genetic disorder characterized by multiple benign and malignant nervous system tumors, and by learning defects in 45% of children with NF1 mutations. Studies of neurofibromin, the protein encoded by NF1, have focused on its functions in tumorigenesis and regulation of Ras activity; however, Drosophila NF1 regulates both Ras and cyclic AMP (cAMP) pathways. Expression of a human NF1 transgene rescued cAMP-related phenotypes in NF1 mutant flies (small body size and G protein-stimulated adenylyl cyclase (AC) activity defects), and neuropeptide- and G protein-stimulated AC activity were lower in Nf1-/- as compared to Nf1+/- mouse brains, demonstrating that neurofibromin regulates AC activity in both mammals and flies.

The tumour-suppressor gene Neurofibromatosis 1 (Nf1) encodes a Ras-specific GTPase activating protein (Ras-GAP). In addition to being involved in tumour formation, NF1 has been reported to cause learning defects in humans and Nf1 knockout mice. However, it remains to be determined whether the observed learning defect is secondary to abnormal development. The Drosophila NF1 protein is highly conserved, showing 60% identity of its 2,803 amino acids with human NF1 (ref. 12). Previous studies have suggested that Drosophila NF1 acts not only as a Ras-GAP but also as a possible regulator of the cAMP pathway that involves the rutabaga (rut)-encoded adenylyl cyclase. Because rut was isolated as a learning and short-term memory mutant, we have pursued the hypothesis that NF1 may affect learning through its control of the Rut-adenylyl cyclase/cAMP pathway. Here we show that NF1 affects learning and short-term memory independently of its developmental effects. We show that G-protein-activated adenylyl cyclase activity consists of NF1-independent and NF1-dependent components, and that the mechanism of the NF1-dependent activation of the Rut-adenylyl cyclase pathway is essential for mediating Drosophila learning and memory.