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1.
Plant J ; 119(1): 84-99, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38578218

ABSTRACT

Tuta absoluta ("leafminer"), is a major pest of tomato crops worldwide. Controlling this insect is difficult due to its efficient infestation, rapid proliferation, and resilience to changing weather conditions. Furthermore, chemical pesticides have only a short-term effect due to rapid development of T. absoluta strains. Here, we show that a variety of tomato cultivars, treated with external phenylalanine solutions exhibit high resistance to T. absoluta, under both greenhouse and open field conditions, at different locations. A large-scale metabolomic study revealed that tomato leaves absorb and metabolize externally given Phe efficiently, resulting in a change in their volatile profile, and repellence of T. absoluta moths. The change in the volatile profile is due to an increase in three phenylalanine-derived benzenoid phenylpropanoid volatiles (BPVs), benzaldehyde, phenylacetaldehyde, and 2-phenylethanol. This treatment had no effect on terpenes and green leaf volatiles, known to contribute to the fight against insects. Phe-treated plants also increased the resistance of neighboring non-treated plants. RNAseq analysis of the neighboring non-treated plants revealed an exclusive upregulation of genes, with enrichment of genes related to the plant immune response system. Exposure of tomato plants to either benzaldehyde, phenylacetaldehyde, or 2-phenylethanol, resulted in induction of genes related to the plant immune system that were also induced due to neighboring Phe-treated plants. We suggest a novel role of phenylalanine-derived BPVs as mediators of plant-insect interactions, acting as inducers of the plant defense mechanisms.


Subject(s)
Phenylalanine , Plant Leaves , Solanum lycopersicum , Volatile Organic Compounds , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Solanum lycopersicum/parasitology , Phenylalanine/metabolism , Volatile Organic Compounds/metabolism , Animals , Plant Leaves/metabolism , Plant Leaves/drug effects , Plant Leaves/parasitology , Benzaldehydes/metabolism , Benzaldehydes/pharmacology , Acetaldehyde/analogs & derivatives , Acetaldehyde/metabolism , Acetaldehyde/pharmacology , Moths/physiology , Moths/drug effects , Plant Diseases/parasitology , Plant Diseases/immunology , Manduca/physiology
2.
Nucleic Acids Res ; 51(5): 2298-2318, 2023 03 21.
Article in English | MEDLINE | ID: mdl-36807739

ABSTRACT

An elevated frequency of DNA replication defects is associated with diabetes and cancer. However, data linking these nuclear perturbations to the onset or progression of organ complications remained unexplored. Here, we report that RAGE (Receptor for Advanced Glycated Endproducts), previously believed to be an extracellular receptor, upon metabolic stress localizes to the damaged forks. There it interacts and stabilizes the minichromosome-maintenance (Mcm2-7) complex. Accordingly, RAGE deficiency leads to slowed fork progression, premature fork collapse, hypersensitivity to replication stress agents and reduction of viability, which was reversed by the reconstitution of RAGE. This was marked by the 53BP1/OPT-domain expression and the presence of micronuclei, premature loss-of-ciliated zones, increased incidences of tubular-karyomegaly, and finally, interstitial fibrosis. More importantly, the RAGE-Mcm2 axis was selectively compromised in cells expressing micronuclei in human biopsies and mouse models of diabetic nephropathy and cancer. Thus, the functional RAGE-Mcm2/7 axis is critical in handling replication stress in vitro and human disease.


Subject(s)
Diabetes Mellitus , Minichromosome Maintenance Complex Component 2 , Neoplasms , Receptor for Advanced Glycation End Products , Animals , Humans , Mice , Cell Cycle Proteins/metabolism , DNA Replication/genetics , Minichromosome Maintenance Complex Component 2/genetics , Minichromosome Maintenance Complex Component 2/metabolism , Minichromosome Maintenance Proteins/metabolism , Receptor for Advanced Glycation End Products/metabolism
3.
Plant J ; 113(4): 833-850, 2023 02.
Article in English | MEDLINE | ID: mdl-36582174

ABSTRACT

The plant immune system perceives a diversity of carbohydrate ligands from plant and microbial cell walls through the extracellular ectodomains (ECDs) of pattern recognition receptors (PRRs), which activate pattern-triggered immunity (PTI). Among these ligands are oligosaccharides derived from mixed-linked ß-1,3/ß-1,4-glucans (MLGs; e.g. ß-1,4-D-(Glc)2 -ß-1,3-D-Glc, MLG43) and cellulose (e.g. ß-1,4-D-(Glc)3 , CEL3). The mechanisms behind carbohydrate perception in plants are poorly characterized except for fungal chitin oligosaccharides (e.g. ß-1,4-d-(GlcNAc)6 , CHI6), which involve several receptor kinase proteins (RKs) with LysM-ECDs. Here, we describe the isolation and characterization of Arabidopsis thaliana mutants impaired in glycan perception (igp) that are defective in PTI activation mediated by MLG43 and CEL3, but not by CHI6. igp1-igp4 are altered in three RKs - AT1G56145 (IGP1), AT1G56130 (IGP2/IGP3) and AT1G56140 (IGP4) - with leucine-rich-repeat (LRR) and malectin (MAL) domains in their ECDs. igp1 harbors point mutation E906K and igp2 and igp3 harbor point mutation G773E in their kinase domains, whereas igp4 is a T-DNA insertional loss-of-function mutant. Notably, isothermal titration calorimetry (ITC) assays with purified ECD-RKs of IGP1 and IGP3 showed that IGP1 binds with high affinity to CEL3 (with dissociation constant KD  = 1.19 ± 0.03 µm) and cellopentaose (KD  = 1.40 ± 0.01 µM), but not to MLG43, supporting its function as a plant PRR for cellulose-derived oligosaccharides. Our data suggest that these LRR-MAL RKs are components of a recognition mechanism for both cellulose- and MLG-derived oligosaccharide perception and downstream PTI activation in Arabidopsis.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Protein Serine-Threonine Kinases/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Leucine/metabolism , Glucans/metabolism , Cellulose/metabolism , Plant Immunity/genetics , Plants/metabolism , Oligosaccharides/metabolism
4.
EMBO J ; 39(11): e103477, 2020 06 02.
Article in English | MEDLINE | ID: mdl-32338774

ABSTRACT

Diabetes-associated organ fibrosis, marked by elevated cellular senescence, is a growing health concern. Intriguingly, the mechanism underlying this association remained unknown. Moreover, insulin alone can neither reverse organ fibrosis nor the associated secretory phenotype, favoring the exciting notion that thus far unknown mechanisms must be operative. Here, we show that experimental type 1 and type 2 diabetes impairs DNA repair, leading to senescence, inflammatory phenotypes, and ultimately fibrosis. Carbohydrates were found to trigger this cascade by decreasing the NAD+ /NADH ratio and NHEJ-repair in vitro and in diabetes mouse models. Restoring DNA repair by nuclear over-expression of phosphomimetic RAGE reduces DNA damage, inflammation, and fibrosis, thereby restoring organ function. Our study provides a novel conceptual framework for understanding diabetic fibrosis on the basis of persistent DNA damage signaling and points to unprecedented approaches to restore DNA repair capacity for resolution of fibrosis in patients with diabetes.


Subject(s)
DNA End-Joining Repair , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/metabolism , A549 Cells , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/pathology , Fibrosis , HEK293 Cells , Humans
5.
BMC Womens Health ; 24(1): 169, 2024 Mar 09.
Article in English | MEDLINE | ID: mdl-38461235

ABSTRACT

BACKGROUND: We conducted a systematic review and meta-analysis to compare the neutrophil lymphocyte ratio (NLR) levels between women with post-menopausal osteopenia or osteoporosis to those with normal bone mineral density (BMD). METHODS: We used Web of Science, PubMed, and Scopus to conduct a systematic search for relevant publications published before June 19, 2022, only in English language. We reported standardized mean difference (SMD) with a 95% confidence interval (CI). Because a significant level of heterogeneity was found, we used the random-effects model to calculate pooled effects. We used the Newcastle-Ottawa scale for quality assessment. RESULTS: Overall, eight articles were included in the analysis. Post-menopausal women with osteoporosis had elevated levels of NLR compared to those without osteoporosis (SMD = 1.03, 95% CI = 0.18 to 1.88, p = 0.017, I2 = 98%). In addition, there was no difference between post-menopausal women with osteopenia and those without osteopenia in neutrophil lymphocyte ratio (NLR) levels (SMD = 0.58, 95% CI=-0.08 to 1.25, p = 0.085, I2 = 96.8%). However, there was no difference between post-menopausal women with osteoporosis and those with osteopenia in NLR levels (SMD = 0.75, 95% CI=-0.01 to 1.51, p = 0.05, I2 = 97.5%, random-effect model). CONCLUSION: The results of this study point to NLR as a potential biomarker that may be easily introduced into clinical settings to help predict and prevent post-menopausal osteoporosis.


Subject(s)
Bone Diseases, Metabolic , Osteoporosis, Postmenopausal , Osteoporosis , Humans , Female , Bone Density , Neutrophils , Postmenopause , Osteoporosis/etiology , Bone Diseases, Metabolic/complications , Lymphocytes
6.
Reprod Domest Anim ; 59(4): e14560, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38595035

ABSTRACT

Estrus identification is one of the common issues in buffaloes because of their short estrus duration and silent estrus problem. Hence, specific biomarkers facilitating in identifying the estrus stage would be helpful to buffalo farmers and researchers. In our previous studies, taurine, a non-protein amino acid that helps in the secretion of reproductive hormones such as GnRH, was found to be associated with postpartum anestrus in buffaloes. Therefore, the present study was conducted to explore the level of taurine in serum during different stages of the oestrous cycle in healthy cyclic buffaloes. Blood samples were collected from healthy cyclic buffaloes (n = 4), and taurine was estimated at the estrus (0th day), proestrus (-2nd day), metestrus (3rd day) and diestrus (+10th day) stages using TLC method. The days of the oestrous cycle were determined by ultrasonography and observation of behavioural signs by trained professionals. The results revealed that taurine was consistently present in the serum. However, the highest concentration of taurine was observed at the proestrus (0.20 ± 0.03 mg/mL) stage, which was greater (p < .05) than metestrus (0.10 ± 0.05 mg/mL) and diestrus (0.13 ± 0.03 mg/mL) stages, but comparable with the estrus stage. These results were also validated in the simulated population datasets of population size 6 to 10,000. Further, ROC curve analysis for the large simulated population indicated the efficiency of taurine to distinguish proestrus from metestrus and diestrus stages at a lower cutoff value of <0.1643 mg/mL with 60% sensitivity and specificity. Therefore, the present study concludes that serum taurine concentration could help in detecting proestrus stage of buffalo estrous cycle.


Subject(s)
Bison , Buffaloes , Female , Animals , Taurine , Estrous Cycle , Estrus , Diestrus , Proestrus
7.
Australas Psychiatry ; 32(4): 365-369, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38597339

ABSTRACT

OBJECTIVE: To reflect on the importance of teaching formulation skills in psychiatry training and explore how creative writing, particularly writing poetry, can help achieve this goal. CONCLUSIONS: It is vital that formulation skills are embedded throughout psychiatry training. Formulations have an artistic element, and writing poetry can help foster a capacity for curiosity that can assist trainees in developing these skills.


Subject(s)
Creativity , Poetry as Topic , Psychiatry , Writing , Humans , Psychiatry/education , Education, Medical/methods
8.
Inorg Chem ; 62(51): 21101-21114, 2023 Dec 25.
Article in English | MEDLINE | ID: mdl-38091715

ABSTRACT

In search of new multifunctional hybrid materials and in order to investigate the influence of chemical modification on the possible synergy between properties, the carboxylate and sulfonate derivatives of photo- and thermochromic N-salicylidene aniline were successfully inserted into Co(II)- and Zn(II)-based layered simple hydroxides, resulting in four novel hybrids: Co-N-Sali-COO, Co-N-Sali-SO3, Zn-N-Sali-COO, and Zn-N-Sali-SO3. All synthesized hybrids adopt a double organic layered configuration, which prevents the cis-trans photoisomerization ability of N-Sali-R molecules in the hybrids. However, the Zn hybrids exhibit fluorescence upon exposure to UV light due to the excited-state intramolecular proton transfer (ESIPT) mechanism. The thermally stimulated keto-enol tautomerization of N-salicylidene aniline in the hybrids was related with the changes in interlamellar spacings observed by temperature-dependent PXRD. This tautomerization process was prominently evident in the Co-N-Sali-SO3 hybrid (about 11% increase in d-spacing upon decreasing the temperature to -180 °C). Finally, the Co-N-Sali-R hybrids exhibit the typical magnetic behavior associated with Co(II)-based LSHs (ferrimagnetic ordering at TN = 6.8 and 7.7 K for Co-N-Sali-COO and Co-N-Sali-SO3, respectively). This work offers insights into isomerization in LSHs and the ESIPT mechanism's potential in new luminescent materials and prospects for designing new multifunctional materials.

9.
Environ Sci Technol ; 57(31): 11572-11582, 2023 08 08.
Article in English | MEDLINE | ID: mdl-37496264

ABSTRACT

Aromatic hydrocarbons (ArHCs) and oxygenated aromatic hydrocarbons (ArHC-OHs) are emitted from a variety of anthropogenic activities and are important precursors of secondary organic aerosol (SOA) in urban areas. Here, we analyzed and compared the composition of SOA formed from the oxidation of a mixture of aromatic VOCs by OH and NO3 radicals. The VOC mixture was composed of toluene (C7H8), p-xylene + ethylbenzene (C8H10), 1,3,5-trimethylbenzene (C9H12), phenol (C6H6O), cresol (C7H8O), 2,6-dimethylphenol (C8H10O), and 2,4,6-trimethylphenol (C9H12O) in a proportion where the aromatic VOCs were chosen to approximate day-time traffic-related emissions in Delhi, and the aromatic alcohols make up 20% of the mixture. These VOCs are prominent in other cities as well, including those influenced by biomass combustion. In the NO3 experiments, large contributions from CxHyOzN dimers (C15-C18) were observed, corresponding to fast SOA formation within 15-20 min after the start of chemistry. Additionally, the dimers were a mixture of different combinations of the initial VOCs, highlighting the importance of exploring SOAs from mixed VOC systems. In contrast, the experiments with OH radicals yielded gradual SOA mass formation, with CxHyOz monomers (C6-C9) being the dominant constituents. The evolution of SOA composition with time was tracked and a fast degradation of dimers was observed in the NO3 experiments, with concurrent formation of monomer species. The rates of dimer decomposition in NO3 SOA were ∼2-3 times higher compared to those previously determined for α-pinene + O3 SOA, highlighting the dependence of particle-phase reactions on VOC precursors and oxidants. In contrast, the SOA produced in the OH experiments did not dramatically change over the same time frame. No measurable effects of humidity were observed on the composition and evolution of SOA.


Subject(s)
Air Pollutants , Hydrocarbons, Aromatic , Volatile Organic Compounds , Air Pollutants/analysis , Volatile Organic Compounds/chemistry , Aerosols/analysis , Toluene
10.
Proc Natl Acad Sci U S A ; 117(1): 573-583, 2020 01 07.
Article in English | MEDLINE | ID: mdl-31852820

ABSTRACT

Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial (CE) degeneration resulting in impaired visual acuity. It is a genetically complex and age-related disorder, with higher incidence in females. In this study, we established a nongenetic FECD animal model based on the physiologic outcome of CE susceptibility to oxidative stress by demonstrating that corneal exposure to ultraviolet A (UVA) recapitulates the morphological and molecular changes of FECD. Targeted irradiation of mouse corneas with UVA induced reactive oxygen species (ROS) production in the aqueous humor, and caused greater CE cell loss, including loss of ZO-1 junctional contacts and corneal edema, in female than male mice, characteristic of late-onset FECD. UVA irradiation caused greater mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage in female mice, indicative of the sex-driven differential response of the CE to UVA, thus accounting for more severe phenotype in females. The sex-dependent effect of UVA was driven by the activation of estrogen-metabolizing enzyme CYP1B1 and formation of reactive estrogen metabolites and estrogen-DNA adducts in female but not male mice. Supplementation of N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS), diminished the morphological and molecular changes induced by UVA in vivo. This study investigates the molecular mechanisms of environmental factors in FECD pathogenesis and demonstrates a strong link between UVA-induced estrogen metabolism and increased susceptibility of females for FECD development.


Subject(s)
Cytochrome P-450 CYP1B1/metabolism , DNA Adducts/radiation effects , DNA Damage/radiation effects , Estrogens/metabolism , Fuchs' Endothelial Dystrophy/etiology , Ultraviolet Rays/adverse effects , Acetylcysteine/administration & dosage , Animals , Aqueous Humor/drug effects , Aqueous Humor/metabolism , Aqueous Humor/radiation effects , DNA Adducts/metabolism , DNA Damage/drug effects , DNA, Mitochondrial/metabolism , DNA, Mitochondrial/radiation effects , Disease Models, Animal , Endothelium, Corneal/drug effects , Endothelium, Corneal/pathology , Endothelium, Corneal/radiation effects , Female , Free Radical Scavengers/administration & dosage , Fuchs' Endothelial Dystrophy/diagnosis , Fuchs' Endothelial Dystrophy/drug therapy , Fuchs' Endothelial Dystrophy/pathology , Humans , Male , Mice , Oxidative Stress/radiation effects , Reactive Oxygen Species/metabolism , Severity of Illness Index
11.
Neuromodulation ; 26(6): 1256-1262, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37318432

ABSTRACT

OBJECTIVES: Among patients with cancer with moderate to severe, intractable pain, intrathecal drug delivery using an intrathecal drug delivery system (IDDS) offers effective pain control. In this study, we evaluate the trends of IDDS therapy among patients with cancer, associated comorbidities, complications, and outcomes, using a large representative US administrative inpatient data base. MATERIALS AND METHODS: The Nationwide Inpatient Sample (NIS) data base contains data from 48 states and the District of Columbia. The NIS was used to identify patients with cancer who underwent IDDS implantation between 2016 and 2019. Patients with cancer with intrathecal pumps for the treatment of chronic pain were identified using administrative codes. Baseline demographics, hospital characteristics, type of cancer associated with IDDS implantation, palliative care encounters, hospitalization costs, length of stay, and prevalence of bone pain were evaluated in the study. RESULTS: A total of 22,895 (0.32%) individuals with hospital admission for IDDS surgery were included for analysis among 7.06 million individuals with cancer in the final cohort. The IDDS cohort consisted of patients predominantly in the 65-to-79 years age group (40.49%), female sex (50.42%), and Caucasian ethnicity (75.82%). The top five cancers in patients receiving IDDS were lung (27.15%), colorectal (24.9%), liver (16.44%), bone (8.01%), and liver (7.99%) cancer. In addition, the length of stay was six days (interquartile range [IQR] four-nine days) and the median cost of hospital admission was $29,062 (IQR $19,413-$42,261) in the patients who received an IDDS. These factors were greater than those in patients without IDDS. CONCLUSIONS: A very few patients with cancer received IDDS in the US during the study period. Despite recommendations supporting its use, there are significant racial and socioeconomic disparities in IDDS use.


Subject(s)
Cancer Pain , Neoplasms , Pain, Intractable , Humans , Female , Cancer Pain/drug therapy , Cancer Pain/epidemiology , Infusion Pumps, Implantable/adverse effects , Drug Delivery Systems/adverse effects , Pain, Intractable/drug therapy , Neoplasms/drug therapy , Neoplasms/epidemiology , Injections, Spinal/adverse effects
12.
Environ Monit Assess ; 196(1): 84, 2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38147167

ABSTRACT

Air pollution has become a major concern due to its detrimental effects on living beings. The present study is aimed at assessing the current status of air pollution in Lucknow city using lichen transplantation technique and assesing its effect on physiology of Pyxine cocoes. The samples of P. cocoes were collected from relatively pollution-free area Malihabad and transplanted in 10 designated sites in five regions for 30 days. Various parameters such as heavy metals, chlorophyll pigments, carotenoid, chlorophyll degradation, and electrolyte conductivity were estimated in transplanted lichens. The study revealed that the concentration of all 10 heavy metals was higher in all transplanted samples than in the control sample, which was found in order of Al > Fe > Mn > Zn > Cu > Cr > Pb > Ni > Co > Cd. Among all 10 transplanted sites, the significantly increased accumulation of aluminum (5.11 to 5.47 µg L-1), iron (4.73 to 5.46 µg L-1), manganese (110.99 to 144.58 µg g-1), and zinc (87.96 to 97.40 µg g-1) was found in Charbagh, Qaisarbagh, and Alambagh sites. Further, in all samples, chlorophyll a (3.98 µg L-1), chlorophyll b (1.22 µg L-1), total chlorophyll (5.20 µg L-1), and chlorophyll degradation (0.55 µg g-1) were significantly decreased, whereas elevated levels of carotenoid (0.71 µg g-1), and electrolyte conductivity (64.99 µS cm-1), were observed. The scanning electron microscope (SEM) investigated the morphological changes in transplanted lichen samples, and significant damage to the anatomy of mycelium was found in most of the polluted site's samples, which correlated with the pollution levels. The present study clearly demonstrated that the transplanted lichen P. cocoes is an efficient bioaccumulator and bioindicator of air quality in urban environments.


Subject(s)
Lichens , Metals, Heavy , Chlorophyll A , Environmental Monitoring , Carotenoids , Chlorophyll , Electrolytes
13.
Anesth Analg ; 134(4): 843-852, 2022 04 01.
Article in English | MEDLINE | ID: mdl-34914642

ABSTRACT

BACKGROUND: Spinal cord stimulation (SCS) has been shown to reduce opioid consumption, reduce pain, improve quality of life compared to conventional therapy, and be more effective than spine reoperation in carefully selected patients. In this study, we evaluate readmissions after SCS implantation procedures, costs, predictors, and etiologies for readmission following implantation procedures. METHODS: The study was a retrospective cohort using the National Readmissions Database from 2013 to 2017. Administrative billing codes were used to identify patients undergoing SCS implantation procedures. The primary outcome of our study was 30-day readmission following the SCS implantation procedure. Continuous outcomes were compared between groups using the Student t test or Wilcoxon rank sum test. In addition, multivariable predictors of 30-day readmission were assessed by hierarchical logistic regression analysis. RESULTS: A total of 3737 (26.7% open surgical SCS implants [OS-SCS]) individuals admitted to the hospital for SCS implantation were included in the final cohort analysis. The cohort consisted of predominantly female patients (58.71%) and in the 50- to 64-year age group (35.46%). Patients who underwent open surgical SCS implantation had a longer length of stay during the initial admission and a higher 30-day readmission rate (9.4% vs 7% P = .01). OS-SCS, older age, lower socioeconomic status, patients with specific comorbidities (ie, hypertension or chronic obstructive pulmonary disease [COPD]), and home discharge are associated with readmission. CONCLUSIONS: Readmission rates after SCS implantation are around 7.7% in the United States. Infection and postoperative complications remain the top etiologies for readmission. Open surgical SCS implantation is associated with more extended initial hospitalization and a higher rate of readmission when compared to percutaneous SCS implantation procedures.


Subject(s)
Patient Readmission , Quality of Life , Cohort Studies , Female , Humans , Male , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Spinal Cord , Time Factors , United States/epidemiology
14.
Plant J ; 104(1): 226-240, 2020 09.
Article in English | MEDLINE | ID: mdl-32645754

ABSTRACT

Flowers are the most vulnerable plant organ to infection by the necrotrophic fungus Botrytis cinerea. Here we show that pre-treatment of chrysanthemum (Chrysanthemum morifolium) flowers with phenylalanine (Phe) significantly reduces their susceptibility to B. cinerea. To comprehend how Phe treatment induces resistance, we monitored the dynamics of metabolites (by GC/LC-MS) and transcriptomes (by RNAseq) in flowers after Phe treatment and B. cinerea infection. Phe treatment resulted in accumulation of 3-phenyllactate and benzaldehyde, and in particular induced the expression of genes related to Ca2+ signaling and receptor kinases, implicating an induction of the defense response. Interestingly, the main effects of Phe treatment were observed in flowers exposed to B. cinerea infection, stabilizing the global fluctuations in the levels of metabolites and transcripts while reducing susceptibility to the fungus. We suggest that Phe-induced resistance is associated to cell priming, enabling rapid and targeted reprogramming of cellular defense responses to resist disease development. After Phe pre-treatment, the levels of the anti-fungal volatiles phenylacetaldehyde and eugenol were maintained and the level of coniferin, a plausible monolignol precursor in cell wall lignification, was strongly increased. In addition, Phe pre-treatment reduced ROS generation, prevented ethylene emission, and caused changes in the expression of a minor number of genes related to cell wall biogenesis, encoding the RLK THESEUS1, or involved in Ca2+ and hormonal signaling processes. Our findings point to Phe pre-treatment as a potential orchestrator of a broad-spectrum defense response which may not only provide an ecologically friendly pest control strategy but also offers a promising way of priming plants to induce defense responses against B. cinerea.


Subject(s)
Botrytis , Chrysanthemum/physiology , Flowers/physiology , Phenylalanine/physiology , Plant Diseases/immunology , Chrysanthemum/immunology , Chrysanthemum/microbiology , Ethylenes/metabolism , Flowers/immunology , Phenylalanine/metabolism , Plant Diseases/microbiology , Plant Growth Regulators/metabolism , Reactive Oxygen Species
15.
Value Health ; 24(6): 839-845, 2021 06.
Article in English | MEDLINE | ID: mdl-34119082

ABSTRACT

OBJECTIVES: To evaluate alternative methods to calculate and/or attribute economic surplus in the cost-effectiveness analysis of single or short-term therapies. METHODS: We performed a systematic literature review of articles describing alternative methods for cost-effectiveness analysis of potentially curative therapies whose assessment using traditional methods may suggest unaffordable valuations owing to the magnitude of estimated long-term quality-adjusted life-year (QALY) gains or cost offsets. Through internal deliberation and discussion with staff at the Health Technology Assessment bodies in England and Canada, we developed the following 3 alternative methods for further evaluation: (1) capping annual costs in the comparator arm at $150 000 per year; (2) "sharing" the economic surplus with the health sector by apportioning only 50% of cost offsets or 50% of cost offsets and QALY gains to the value of the therapy; and (3) crediting the therapy with only 12 years of the average annual cost offsets or cost offsets and QALY gains over the lifetime horizon. The impact of each alternative method was evaluated by applying it in an economic model of 3 hypothetical condition-treatment scenarios meant to reflect a diversity of chronicity and background healthcare costs. RESULTS: The alternative with greatest impact on threshold price for the fatal pediatric condition spinal muscular atrophy type 1 was the 12-year cutoff scenario. For a hypothetical one-time treatment for hemophilia A, capping cost offsets at $150 000 per year had the greatest impact. For chimeric antigen receptor T-cell treatment of non-Hodgkin's lymphoma, capping cost offsets or using 12-year threshold had little impact, whereas 50% sharing of surplus including QALY gains and cost offsets greatly reduced threshold pricing. CONCLUSIONS: Health Technology Assessment bodies and policy makers will wrestle with how to evaluate single or short-term potentially curative therapies and establish pricing and payment mechanisms to ensure sustainability. Scenario analyses using alternative methods for calculating and apportioning economic surplus can provide starkly different assessment results. These methods may stimulate important societal dialogue on fair pricing for these novel treatments.


Subject(s)
Drug Therapy/economics , Genetic Therapy/economics , Health Care Costs , Immunotherapy, Adoptive/economics , Technology Assessment, Biomedical/economics , Antibodies, Bispecific/economics , Antibodies, Bispecific/therapeutic use , Antibodies, Monoclonal, Humanized/economics , Antibodies, Monoclonal, Humanized/therapeutic use , Biological Products/economics , Biological Products/therapeutic use , Cost Savings , Cost-Benefit Analysis , Drug Costs , Genetic Therapy/adverse effects , Hemophilia A/drug therapy , Hemophilia A/economics , Humans , Immunotherapy, Adoptive/adverse effects , Lymphoma, Non-Hodgkin/economics , Lymphoma, Non-Hodgkin/therapy , Models, Economic , Quality-Adjusted Life Years , Recombinant Fusion Proteins/economics , Recombinant Fusion Proteins/therapeutic use , Remission Induction , Spinal Muscular Atrophies of Childhood/economics , Spinal Muscular Atrophies of Childhood/genetics , Spinal Muscular Atrophies of Childhood/therapy , Time Factors , Treatment Outcome
16.
Physiol Plant ; 172(1): 19-28, 2021 May.
Article in English | MEDLINE | ID: mdl-33161590

ABSTRACT

Lisianthus (Eustoma grandiflorum), a leading plant in the cut flower industry, is scentless. Here we show that lisianthus flowers have potential to produce several fragrant benzenoid-phenylpropanoids when substrate availability is not limited. To enable hyperaccumulation of substrates for the production of volatile benzenoid-phenylpropanoids, lisianthus commercial hybrid "Excalibur Pink" was transformed via floral dipping with a feedback-insensitive Escherichia coli DAHP synthase (AroG*) and Clarkia breweri benzyl alcohol acetyltransferase (BEAT), under constitutive promoters. The T1 progeny of "Excalibur Pink" plants segregated into four visual phenotypes, with pink or white colored petals and multiple or single petal layers. Interestingly, transformation with AroG* and BEAT caused no significant effect in the pigment composition among phenotypes, but did increase the levels of down-stream fragrant volatile benzenoids. All the transgenic lines exclusively accumulated methyl benzoate, a fragrant benzenoid, either in their petals or leaves. Furthermore, feeding with benzyl alcohol resulted in the accumulation of two novel benzenoids, benzyl acetate (the product of BEAT) and benzoate, as well as a dramatic increase in the concentrations of additional benzenoid-phenylpropanoid volatiles. Presumably, the degree of benzaldehyde overproduction after benzyl alcohol feeding in both leaves and flowers revealed their reverse conversion in lisianthus plants. These findings demonstrate the concealed capability of lisianthus plants to produce a wide array of fragrant benzenoid-phenylpropanoids, given high substrate concentrations, which could in turn open opportunities for future scent engineering.


Subject(s)
Flowers , Odorants , Pigmentation , Plant Leaves , Plants
17.
Appl Opt ; 60(26): 8145-8153, 2021 Sep 10.
Article in English | MEDLINE | ID: mdl-34613078

ABSTRACT

One of the major science goals of the Visible Emission Line Coronagraph (VELC) payload aboard the Aditya-L1 mission is to map the coronal magnetic field topology and quantitative estimation of longitudinal magnetic field on a routine basis. The infrared channel of VELC is equipped with a polarimeter to carry out full Stokes spectropolarimetric observations in the Fe xiii line at 1074.7 nm. The polarimeter is in a dual-beam setup with a continuously rotating wave plate as the polarization modulator. Detection of circular polarization due to the Zeeman effect and depolarization of linear polarization in the presence of a magnetic field due to the saturated Hanle effect in the Fe xiii line require a high signal-to-noise ratio (SNR). Due to the limited number of photons, long integration times are expected to build the required SNR. In other words, signals from a large number of modulation cycles are to be averaged to achieve the required SNR. This poses several difficulties. One is the increase in data volume and the other is the change in the modulation matrix in successive modulation cycles. The latter effect arises due to a mismatch between the retarder's rotation period and the length of the signal detection time in the case of the VELC spectropolarimeter. It is shown in this paper that by appropriately choosing the number of samples per half rotation, the data volume can be optimized. A potential solution is suggested to account for modulation matrix variation from one cycle to another.

18.
J Microencapsul ; 38(5): 263-275, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33719838

ABSTRACT

AIM: The present work involves encapsulation of herbal drug nanocurcumin into the virosomes and compared with a liposome in terms of their in vitro anti-proliferative, anti-inflammatory, and anti-migratory efficacy. METHODS: The anti-proliferative, anti-inflammatory, and anti-migratory efficacy of virosome and liposome were compared in HepG2 and CaCo2 cells by using MTT, Nitric oxide scavenging, and Wound healing assay, respectively. RESULTS: Size of the optimised NC-Virosome and NC-Liposome was 70.06 ± 1.63 and 265.80 ± 1.64 nm, respectively. The prepared NC-Virosome can be stored at -4 °C up to six months. The drug encapsulation efficiency of NC-Virosome and NC-Liposome was found to be 84.66 ± 1.67 and 62.15 ± 1.75% (w/w). The evaluated minimum inhibitory concentration (IC50 value) for NC-Virosome was 102.7 µg/ml and 108.1 µg/ml, while NC-Liposome showed 129.2 µg/ml and 160.1 µg/ml for HepG2 and CaCo2 cells, respectively. Morphological examination depicts detachment of the cells from substratum after exposure to NC-Virosome for 48 h. CONCLUSION: The prepared NC-Virosome provides remarkable in vitro efficacy in both the cell lines with site-specific drug-targeting potential as compared to the liposome, results proved its potential as a drug delivery vehicle for future therapy with reduced toxicity.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Liposomes/chemistry , Virosomes/chemistry , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antineoplastic Agents, Phytogenic/administration & dosage , Caco-2 Cells , Cell Movement/drug effects , Curcumin/administration & dosage , Curcumin/therapeutic use , Drug Delivery Systems , Excipients , Hep G2 Cells , Humans , Microbial Sensitivity Tests , Neoplasms/drug therapy , Nitric Oxide/chemistry , Tetrazolium Salts , Thiazoles , Wound Healing/drug effects
19.
Neuromodulation ; 24(1): 126-134, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32929856

ABSTRACT

OBJECTIVES: Chronic pain spinal implantable electronic devices (CPSIEDs) include devices that provide spinal cord stimulation and intrathecal drug therapy. In this study, we sought to evaluate the trends of CPSIED infections, related complications, and outcomes following the treatment of infection. MATERIALS AND METHODS: The Nationwide Inpatient Sample database contains data from 48 states, and the District of Columbia was used to identify patients with a primary diagnosis of CPSIED infection during the years 2005-2014. Patients with intrathecal pumps for the treatment of spasticity were excluded to limit the study population to patients with chronic pain disorders. Treatments were categorized as: 1) without device removal, 2) pulse generator or pump only removal, 3) intrathecal pump system removal, and 4) spinal cord stimulation system removal. Complications associated with CPSIED infections were identified using administrative billing codes. RESULTS: During the study period 2005-2014, a total of 11,041 patients were admitted to the hospital with CPSIED infections. The majority of the patients were treated without surgical intervention (56%), and a smaller proportion underwent complete system explantation (22.7%). In-hospital mortality or permanent disability due to paralysis after CPSIED infection was around 1.83% and 2.77%, respectively. Infectious complications such as meningitis, abscess formation, and osteomyelitis occurred in 4.93%, 5.08%, and 1.5%, respectively. The median cost of hospitalization was around US $14,118.00, and the median length of stay was approximately six days (interquartile range = 4-13 days). CONCLUSIONS: The complications of CPSIED infection were higher among patients that did not undergo device removal.


Subject(s)
Chronic Pain , Spinal Cord Stimulation , Chronic Pain/epidemiology , Chronic Pain/therapy , Electronics , Humans , Infusion Pumps, Implantable , Inpatients , Muscle Spasticity , Spinal Cord Stimulation/adverse effects
20.
Physiol Mol Biol Plants ; 27(5): 923-944, 2021 May.
Article in English | MEDLINE | ID: mdl-34092945

ABSTRACT

Glutaredoxins (Grxs) are short, cysteine-rich glutathione (GSH)-mediated oxidoreductases. In this study, a chickpea (Cicer arietinum L.) glutaredoxin [LOC101493651 (CaGrx)] gene has been selected based on screening experiments with two contrasting varieties of chickpea, PUSA-362 (drought-tolerant) and ICC-1882 (drought-sensitive) under drought and salinity. The tolerant variety showed higher CaGrx gene expression, as compared to less in the sensitive variety, under both the stresses. The CaGrx gene was then over-expressed in Arabidopsis thaliana and were exposed to drought and salinity. The over-expression of CaGrx elevated the activity of glutaredoxin, which induced antioxidant enzymes (glutathione reductase; GR, glutathione peroxidase; GPX, catalase; CAT, ascorbate peroxidase; APX, glutathione-S-transferase; GST, superoxide dismutase; SOD, monodehydroascorbate reductase; MDHAR, and dehydroascorbate reductase; DHAR), antioxidants (GSH and ascorbate) and stress-responsive amino acids (cysteine and proline). Enhancement in the antioxidant defense system possibly administered tolerance in transgenics against both stresses. CaGrx reduced stress markers (H2O2, TBARS, and electrolyte leakage) and enhanced root growth, seed germination, and survival against both stresses. The physiological parameters (net photosynthesis; P N, water use efficiency; WUE, stomatal conductance; g s, transpiration; E, electron transport rate; ETR, and photochemical quenching; qP), chlorophylls and carotenoids, were improved in the transgenics during both stresses, that maintained the photosynthetic apparatus and protected the plants from damage. The enhanced activity of the cysteine biosynthesis enzyme, o-acetylserine (thiol) lyase (OAS-TL), increased the cysteine level in the transgenics, which elevated glutathione biosynthesis to maintain the ascorbate-glutathione cycle under both stresses. This investigation verified that the CaGrx gene provides tolerance against salinity and drought, maintaining physiological and morphological performances, and could be exploited for genetic engineering approaches to overcome both the stresses in various crops. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-00999-z.

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