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Predicting selectivity and conversion in a confined reaction medium under photochemical conditions is highly challenging as compared to the corresponding conventional synthesis. Herein, we report the use of a simple carbohydrate-derived eutectogel to facilitate LED-light-induced regioselective synthesis of 4-arylamino-1,2-naphthoquinones in good yield. This methodology, by including a reusable reaction medium, proved to have the potential of affording the regioselective formation of various desired products in good yields.
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Materials with long afterglow (LAG) became very renowned in the field of luminescence due to their high ability to store energy. However, the development of LAG phosphors is mostly dependent on rare-earth activators, which are commercially expensive due to their limited availability across the world. On the other hand, LAG phosphors that are not based on rare-earth and are developed as an alternative cannot compete with existing rare-earth LAG phosphors. Copper-doped zinc sulfide (ZnS:Cu) phosphor developed long ago has considerable afterglow, but its development has been too tedious, and expensive, and contains usage of toxic gasses such as H2S, CS2, etc. and most of the literature refers to the cubic phase of ZnS. To overcome these issues and simplify the process, we have developed a cost-effective approach to synthesize the hexagonal phase of ZnS, without the involvement of hazardous gases. This is one of the very few reports that highlights the appearance of LAG phenomenon from the hexagonal ZnS:Cu phosphor system. Structural, morphological, and optical studies of the developed ZnS:Cu LAG phosphor have been carried out. The phosphor showed a strong green photoluminescence at 515 nm and an afterglow duration of ~ 1 h useful for specific applications of visual markings in dark conditions. The thermoluminescence spectrum shows a broad and intense glow peak at 377.15 K that indicates the electron trap depth to be at 0.75 eV, supporting our afterglow results.
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KEY MESSAGE: The CcGRXS12 gene protects plants from cellular oxidative damage that are caused by both biotic and abiotic stresses. The protein possesses GSH-disulphide oxidoreductase property but lacks Fe-S cluster assembly mechanism. Glutaredoxins (Grxs) are small, ubiquitous and multi-functional proteins. They are present in different compartments of plant cells. A chloroplast targeted Class I GRX (CcGRXS12) gene was isolated from Capsicum chinense during the pepper mild mottle virus (PMMoV) infection. Functional characterization of the gene was performed in Nicotiana benthamiana transgenic plants transformed with native C. chinense GRX (Nb:GRX), GRX-fused with GFP (Nb:GRX-GFP) and GRX-truncated for chloroplast sequences fused with GFP (Nb:Δ2MGRX-GFP). Overexpression of CcGRXS12 inhibited the PMMoV-I accumulation at the later stage of infection, accompanied with the activation of salicylic acid (SA) pathway pathogenesis-related (PR) transcripts and suppression of JA/ET pathway transcripts. Further, the reduced accumulation of auxin-induced Glutathione-S-Transferase (pCNT103) in CcGRXS12 overexpressing lines indicated that the protein could protect the plants from the oxidative stress caused by the virus. PMMoV-I infection increased the accumulation of pyridine nucleotides (PNs) mainly due to the reduced form of PNs (NAD(P)H), and it was high in Nb:GRX-GFP lines compared to other transgenic lines. Apart from biotic stress, CcGRXS12 protects the plants from abiotic stress conditions caused by H2O2 and herbicide paraquat. CcGRXS12 exhibited GSH-disulphide oxidoreductase activity in vitro; however, it was devoid of complementary Fe-S cluster assembly mechanism found in yeast. Overall, this study proves that CcGRXS12 plays a crucial role during biotic and abiotic stress in plants.
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Capsicum , Tobamovirus , Capsicum/genética , Capsicum/metabolismo , Glutarredoxinas/genética , Glutarredoxinas/metabolismo , Peróxido de Hidrógeno , Oxidación-Reducción , DisulfurosRESUMEN
BACKGROUND: In this article, we present a computerized system for the analysis and assessment of diabetic retinopathy (DR) based on retinal fundus photographs. DR is a chronic ophthalmic disease and a major reason for blindness in people with diabetes. Consistent examination and prompt diagnosis are the vital approaches to control DR. METHODS: With the aim of enhancing the reliability of DR diagnosis, we utilized the deep learning model called You Only Look Once V3 (YOLO V3) to recognize and classify DR from retinal images. The DR was classified into five major stages: normal, mild, moderate, severe, and proliferative. We evaluated the performance of the YOLO V3 algorithm based on color fundus images. RESULTS: We have achieved high precision and sensitivity on the train and test data for the DR classification and mean average precision (mAP) is calculated on DR lesion detection. CONCLUSIONS: The results indicate that the suggested model distinguishes all phases of DR and performs better than existing models in terms of accuracy and implementation time.
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Aprendizaje Profundo , Diabetes Mellitus , Retinopatía Diabética , Humanos , Retinopatía Diabética/diagnóstico , Reproducibilidad de los Resultados , Fondo de Ojo , AlgoritmosRESUMEN
A carefully designed daylight collector for a tubular skylight is necessary to serve the occupants' illumination needs under the dynamic trajectory of the sun. This work simulated an improved configuration of a passive daylight collector comprising parabolic and conical reflectors in a modeled room using the lighting software tool TracePro. Results indicated that the lighting performance of the proposed design configuration was significantly enhanced under low altitude sun in comparison with conventional tubular skylights (with revolved parabolic and cylindrical reflectors) [Light. Res. Technol.52, 495 (2020)10.1177/1477153519872794] and hemispherical transparent dome as daylight collectors by more than â¼30%-40% and â¼110%-130%, respectively.
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Surgical repair of channels between the ventricles is enhanced when the surgeon knows precisely where to place a patch, or baffle, so as to restore septal integrity. The paediatric cardiologist should provide the necessary information. Communication will be enhanced if the same words are used to account for the structures in question. Currently, however, the same term, namely "ventricular septal defect," is used to account for markedly different areas within the heart. Closure of perimembranous defects found in hearts with concordant or discordant ventriculo-arterial connections restores the integrity of the ventricular septum, at the same time separating the systemic and pulmonary blood streams. When both arterial trunks arise from the right ventricle, in contrast, the surgeon when placing a baffle so as to separate the blood streams, does not close the channel most frequently described as the "ventricular septal defect." In this review, we show that the perimembranous lesions as found in hearts with concordant or discordant ventriculo-arterial connections are the right ventricular entrances to the areas subtended beneath the hinges of the leaflets of the aortic or pulmonary valves. When both arterial trunks arise from the right ventricle, and the channel between the ventricles is directly subaortic, then the channel termed the "ventricular septal defect" is the left ventricular entrance to the comparable space subtended beneath the aortic root. We argue that recognition of these fundamental anatomical differences enhances the appreciation of the underlying morphology of the various lesions that reflect transfer, during cardiac development, of the aortic root from the morphologically right to the morphologically left ventricle.
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Defectos del Tabique Interventricular , Transposición de los Grandes Vasos , Tabique Interventricular , Niño , Humanos , Defectos del Tabique Interventricular/cirugía , Defectos del Tabique Interventricular/patología , Ventrículos Cardíacos/cirugía , Aorta/patologíaRESUMEN
BACKGROUND & AIM: The deleterious consequences of chronically elevated venous pressure in patients with profound right ventricular or biventricular dysfunction are well known, including renal and hepatic dysfunction, and volume overload. The only option for these patients, if they fail optimal medical treatment, is a heart transplant, as they are not candidates for left ventricular assist device therapy. Mean perfusion pressure (MPP) is important in the outcomes of critically ill patients with high venous pressure. The question arises whether MPP is important for the outcomes of heart transplants in patients with elevated pre-transplant venous pressure. Medical management of heart failure patients with reduced ejection fraction involves lowering the systemic afterload with vasodilators while awaiting a transplant. We hypothesised that when venous pressure is elevated prior to transplant, a substantial reduction in systemic arterial elastance (Ea) through vasodilation may significantly decrease MPP, resulting in compromised end-organ function and consequent unfavourable outcomes after heart transplantation. This study aims to investigate whether a low MPP serves as a risk factor for adverse outcomes in heart transplant recipients with high venous pressure. METHOD: A retrospective analysis was conducted on 250 heart transplant recipients undergoing isolated heart transplantation at a single institution from October 2012 to March 2020. Right atrial pressure (RAP) of more than 15 mmHg was considered high. Additionally, Ea calculated as the ratio of end-systolic pressure to stroke volume, and MPP calculated as the difference between mean arterial pressure and RAP were considered in our analysis. The outcomes of transplantation were measured in terms of 90-day mortality and survival up to 7 years. RESULTS: High RAP was a significant risk factor for short-term and medium-term survival if Ea was low (<2.7 mmHg/mL, the median value). This group had 39.39% in-hospital mortality compared to 14.49% for RAP<15 mmHg (pâ¼0.005). When Ea was high, this difference in survival was not evident: 8% for RAP<15 mmHg vs 4.8% for RAP>15 mmHg (pâ¼0.550). This effect was mediated through a lower MPP, and the mortality due to lower MPP increased strikingly with higher body surface area (BSA). A negative correlation was observed between MPP indexed to BSA (MPPI) and the Model for End-Stage Liver Disease score (râ¼-0.3580, p<0.0001) as well as creatinine (râ¼-0.3551, p<0.0001). MPPI less than 40 mmHg/m2 was associated with poorer short-term (23.2% for MPPI<40 mmHg/m2 vs 7.1% for MPPI>40 mmHg/m2, pâ¼0.001) and medium-term survival. The impact of high RAP and low Ea on survival was evident even on medium-term follow-up; only 30% survival at 7 years follow-up for high RAP and low Ea vs 75% for RAP<15 mmHg (pâ¼0.0033). CONCLUSION: The acceptable blood pressure during vasodilator therapy in patients with high RAP needs to be higher, especially in those with higher BSA. MPPI less than 40 mmHg/m2 is a risk factor for survival, in the short and medium-term, after heart transplantation.
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Enfermedad Hepática en Estado Terminal , Insuficiencia Cardíaca , Trasplante de Corazón , Humanos , Estudios Retrospectivos , Superficie Corporal , Enfermedad Hepática en Estado Terminal/complicaciones , Índice de Severidad de la Enfermedad , Presión Venosa , Vasodilatadores , PerfusiónRESUMEN
BACKGROUND: Antioxidants minimise oxidative stress and enhance sperm quality in the process of cryopreservation. OBJECTIVE: To assess the impact of Cinnamomum zeylanicum extract as an additive during the post-dilution and post-thaw stages of Murrah buffalo semen cryopreservation. MATERIALS AND METHODS: The semen sample was diluted using Tris-Egg-Yolk-Citric-Acid-Fructose-Glycerol extender and subsequently divided into three groups: Group 1, TEYCAFG without any additives or controls (C); Group 2, TEYCAFG fortified with a 50 ug/mL aqueous extract of cinnamon (T1); and Group 3, TEYCAFG fortified with a 50 ug/mL ethanolic extract of cinnamon (T2). The evaluation included an assessment of progressive motility, live spermatozoa, sperm abnormalities, HOST, CMPT, and enzyme leakage (GOT and GPT) at both the post-dilution and post-thaw stages. RESULTS: The groups that received cinnamon supplementation demonstrated statistically significant improvements (p<0.05) in various parameters, including an increase in the progressive motility, live spermatozoa, and HOS-positive spermatozoa, as well as greater distance traveled by vanguard spermatozoa compared to the control group. Furthermore, the cinnamon-added groups exhibited a significant decrease (p<0.05) in the percentage of sperm abnormalities and lower enzyme leakage (GOT and GPT) in post-thawed semen. CONCLUSION: Aqueous extract of C. zeylanicum at a concentration of 50 µg/mL provides superior protection of sperm structures and functions as compared to both the ethanolic extract of C. zeylanicum at the same concentration and the control group. Doi.org/10.54680/fr24310110712.
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Antioxidantes , Búfalos , Criopreservación , Extractos Vegetales , Semen , Masculino , Animales , Semen/citología , Semen/metabolismo , Criopreservación/veterinaria , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Trehalosa/farmacología , Antioxidantes/farmacología , Preservación de la Fertilidad/veterinariaRESUMEN
The significance of microorganisms occurring in foods is predominantly targeted due to their application for identifying a novel range of the bacterial spectrum. Diverse microbial species are capable of exhibiting potential pharmacological activities like antimicrobial and anticancer. Microbial strains capable of reducing obesity-related syndromes have also been reported. In the present study, the hypocholesterolemic efficacy of Bacillus amyloliquefaciens isolated from dairy products was scrutinised by in vitro (3T3-L1 adipose cells) and in vivo (high-fat diet-induced obese Wistar albino rats) methods. Potential cholesterol-lowering isolates were screened using a plate assay method and optimised by physical parameters. Molecular identification of the topmost five cholesterol-lowering isolates was acquired by amplification of the 16 S rRNA gene region. Bacillus amyloliquefaciens strain KAVK1, followed by strains KAVK2, KAVK3, KAVK4, and KAVK5 were molecularly determined. Further, cholesterol-lowering strains degraded the spectral patterns determined by the side chain of a cholesterol molecule. The anti-lipase activity was demonstrated using the porcine pancreatic lipase inhibitory method and compared with the reference compound Atorvastatin. Lyophilised strain KAVK1 revealed maximum pancreatic lipase inhibition. Strain KAVK1 attenuated lipid accumulation in 3T3-L1 adipose cell line predicted by Oil Red O staining method. Significant reduction of body weight and change in lipid profile was recognised after the supplement of KAVK1 to obese rats. Histopathological changes in organs were predominantly marked. The result of this study implies that the cholesterol-lowering B. amyloliquefaciens KAVK1 strain was used to treat hypercholesterolemia.
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Anticolesterolemiantes , Bacillus amyloliquefaciens , Dieta Alta en Grasa , Metabolismo de los Lípidos , Obesidad , Animales , Ratones , Ratas , Células 3T3-L1/metabolismo , Células 3T3-L1/microbiología , Adipocitos/metabolismo , Adipocitos/efectos de los fármacos , Anticolesterolemiantes/farmacología , Bacillus amyloliquefaciens/metabolismo , Colesterol/metabolismo , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Lipasa/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Obesidad/microbiología , Ratas Wistar , ARN Ribosómico 16S/genéticaRESUMEN
Retinal disorders pose a serious threat to world healthcare because they frequently result in visual loss or impairment. For retinal disorders to be diagnosed precisely, treated individually, and detected early, deep learning is a necessary subset of artificial intelligence. This paper provides a complete approach to improve the accuracy and reliability of retinal disease identification using images from OCT (Retinal Optical Coherence Tomography). The Hybrid Model GIGT, which combines Generative Adversarial Networks (GANs), Inception, and Game Theory, is a novel method for diagnosing retinal diseases using OCT pictures. This technique, which is carried out in Python, includes preprocessing images, feature extraction, GAN classification, and a game-theoretic examination. Resizing, grayscale conversion, noise reduction using Gaussian filters, contrast enhancement using Contrast Limiting Adaptive Histogram Equalization (CLAHE), and edge recognition via the Canny technique are all part of the picture preparation step. These procedures set up the OCT pictures for efficient analysis. The Inception model is used for feature extraction, which enables the extraction of discriminative characteristics from the previously processed pictures. GANs are used for classification, which improves accuracy and resilience by adding a strategic and dynamic aspect to the diagnostic process. Additionally, a game-theoretic analysis is utilized to evaluate the security and dependability of the model in the face of hostile attacks. Strategic analysis and deep learning work together to provide a potent diagnostic tool. This suggested model's remarkable 98.2% accuracy rate shows how this method has the potential to improve the detection of retinal diseases, improve patient outcomes, and address the worldwide issue of visual impairment.
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BACKGROUND: Hernia repair using robotic platforms has been on the rise in the last decade. The HUGO robotic-assisted surgery (RAS) system, introduced in 2021, is a new addition to the field. In this study, we share our experience with this innovative system for the management of ventral and groin hernias. PATIENTS AND METHODS: The aim of our study was to evaluate the feasibility and safety of using the HUGO robotic platform for hernia surgeries. We conducted a retrospective analysis of all hernia surgeries performed with the HUGO system over a 1-year study period. The study assessed various aspects, including the technical manoeuvres of the robotic system, duration of surgery, length of hospital stay, post-operative pain levels and 30-day morbidity rates. RESULTS AND CONCLUSIONS: A total of seven hernia surgeries were performed using the HUGO system, including five ventral hernias and two groin hernias. The average duration of surgery was 128 min, with a docking duration of 22.8 min. Notably, there were no intraoperative or post-operative adverse events reported during these procedures. The HUGO system features an open console that provides a panoramic view of the operating room. In addition, the individual arm carts can be easily manoeuvred around the operating table, facilitating improved access to multiple quadrants during surgery. In our case series, Robotic hernia repair using the HUGO system has demonstrated feasibility, with post-operative outcomes comparable to traditional approaches. This innovative system serves as an additional tool in the armamentarium of hernia surgery and shows potential for improving surgical outcomes. However, further investigation through large-scale prospective studies is necessary to comprehensively evaluate its efficacy and benefits.
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BACKGROUND: Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). MATERIALS AND METHODS: A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan-Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. RESULTS: Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5-7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0-4.8) were included in the final model. CONCLUSIONS: Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.
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Melanoma , Neoplasias Primarias Secundarias , Neoplasias Cutáneas , Deficiencia de Vitamina D , Humanos , Persona de Mediana Edad , Melanoma/epidemiología , Melanoma/etiología , Melanoma/diagnóstico , Vitamina D/efectos adversos , Estudios Retrospectivos , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/complicaciones , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiologíaRESUMEN
BACKGROUND: Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). MATERIALS AND METHODS: A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan-Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. RESULTS: Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5-7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0-4.8) were included in the final model. CONCLUSIONS: Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.
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Melanoma , Neoplasias Primarias Secundarias , Neoplasias Cutáneas , Deficiencia de Vitamina D , Humanos , Persona de Mediana Edad , Melanoma/epidemiología , Melanoma/etiología , Melanoma/diagnóstico , Vitamina D/efectos adversos , Estudios Retrospectivos , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/complicaciones , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. However, there is a lack of comprehensive data from low- and middle-income countries (LMICs) regarding factors influencing COPD outcomes, particularly in regions where biomass exposure is prevalent. Objective: The Factors Affecting Survival in Severe and Very Severe COPD Patients Admitted to Tertiary Centers of India (FAST) study aims to address this gap by evaluating factors impacting survival and exacerbation rates among COPD patients in LMICs like India, with a specific focus on biomass exposure, clinical phenotypes, and nutritional status in patients admitted to the Intensive Care Unit (ICU). Methods: The FAST study is an observational cohort study conducted in university teaching hospitals across India. The study aims to enroll 1000 COPD patients admitted to the ICU meeting specific inclusion criteria, with follow-up assessments conducted every 6 months over a 2-year period. Data collection includes demographic information, clinical manifestations, laboratory investigations, pulmonary function tests, medications, nutritional status, mental health, and health-related quality of life. Adjudication of exacerbations and mortality will also be undertaken. The FAST study seeks to provide crucial insights into COPD outcomes in LMICs, informing more precise management strategies and mitigating the burden of COPD in these settings. By evaluating factors such as biomass exposure, clinical phenotypes, and nutritional status, the study aims to address key knowledge gaps in COPD research. How to cite this article: Arunachala S, Devapal S, Swamy DSN, Greeshma MV, Ul Hussain I, Siddaiah JB, et al. Factors Affecting Survival in Severe and Very Severe COPD after Admission in ICUs of Tertiary Care Centers of India (FAST COPD): Study Protocol for a Multicentric Cohort Study. Indian J Crit Care Med 2024;28(6):552-560.
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Engineering the utilization of non-native substrates, or synthetic heterotrophy, in proven industrial microbes such as Saccharomyces cerevisiae represents an opportunity to valorize plentiful and renewable sources of carbon and energy as inputs to bioprocesses. We previously demonstrated that activation of the galactose (GAL) regulon, a regulatory structure used by this yeast to coordinate substrate utilization with biomass formation during growth on galactose, during growth on the non-native substrate xylose results in a vastly altered gene expression profile and faster growth compared with constitutive overexpression of the same heterologous catabolic pathway. However, this effort involved the creation of a xylose-inducible variant of Gal3p (Gal3pSyn4.1), the sensor protein of the GAL regulon, preventing this semi-synthetic regulon approach from being easily adapted to additional non-native substrates. Here, we report the construction of a variant Gal3pMC (metabolic coordinator) that exhibits robust GAL regulon activation in the presence of structurally diverse substrates and recapitulates the dynamics of the native system. Multiple molecular modeling studies suggest that Gal3pMC occupies conformational states corresponding to galactose-bound Gal3p in an inducer-independent manner. Using Gal3pMC to test a regulon approach to the assimilation of the non-native lignocellulosic sugars xylose, arabinose, and cellobiose yields higher growth rates and final cell densities when compared with a constitutive overexpression of the same set of catabolic genes. The subsequent demonstration of rapid and complete co-utilization of all three non-native substrates suggests that Gal3pMC-mediated dynamic global gene expression changes by GAL regulon activation may be universally beneficial for engineering synthetic heterotrophy.
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Proteínas de Saccharomyces cerevisiae , Factores de Transcripción , Factores de Transcripción/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Procesos Heterotróficos , Galactosa/genética , Galactosa/metabolismo , Xilosa/genética , Xilosa/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMEN
Mycobacterium tuberculosis is a leading cause of human mortality worldwide, and the emergence of drug-resistant strains demands the discovery of new classes of antimycobacterial that can be employed in the therapeutic pipeline. Previously, a secondary metabolite, chrysomycin A, isolated from Streptomyces sp. OA161 displayed potent bactericidal activity against drug-resistant clinical isolates of M. tuberculosis and different species of mycobacteria. The antibiotic inhibits mycobacterial topoisomerase I and DNA gyrase, leading to bacterial death, but the mechanisms that could cause resistance to this antibiotic are currently unknown. To further understand the resistance mechanism, using M. smegmatis as a model, spontaneous resistance mutants were isolated and subjected to whole-genome sequencing. Mutation in a TetR family transcriptional regulator MSMEG_1380 was identified in the resistant isolates wherein the gene was adjacent to an operon encoding membrane proteins MSMEG_1381 and MSMEG_1382. Sequence analysis and modeling studies indicated that MSMEG_1381 and MSMEG_1382 are components of the Mmp family of efflux pumps and over-expression of either the operon or individual genes conferred resistance to chrysomycin A, isoniazid, and ethambutol. Our study highlights the role of membrane transporter proteins in conferring multiple drug resistance and the utility of recombinant strains overexpressing membrane transporters in the drug screening pipeline.
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Mycobacterium smegmatis , Mycobacterium tuberculosis , Humanos , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Antibacterianos/farmacología , Antibacterianos/metabolismo , Mycobacterium tuberculosis/genética , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Farmacorresistencia Bacteriana Múltiple/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
Electronically excited atoms or molecules in an environment are often subject to interatomic/intermolecular Coulombic decay (ICD) and/or electron transfer mediated decay (ETMD) mechanisms. A few of the numerous variables that can impact these non-radiative decay mechanisms include bond distance, the number of nearby atoms or molecules, and the polarisation effect. In this paper, we have studied the effect of protonation and deprotonation on the ionization potential (IP), double ionization potential (DIP), and lifetime (or decay width) of the temporary bound state in these non-radiative decay processes. We have chosen LiH-NH3 and LiH-H2 O as test systems. The equation of motion coupled cluster singles and doubles method augmented by complex absorbing potential (CAP-EOM-CCSD) has been used in calculating the energetic position of the decaying state and the system's decay rate. Deprotonation of LiH-NH3 /LiH-H2 O either from the metal center (LiH) or from ammonia/water lowers the IP and DIP compared to the neutral systems. In contrast, protonation increases these quantities compared to neutral systems. The protonation closes the inner valence state relaxation channels for ICD/ETMD. For example, the decay of the O-2s/N-2s state stops in protonated systems (LiH2 + -H2 O, LiH2 + -NH3 , and LiH-NH4 + ). Our study also shows that the efficiency, i. e., the rate of ICD/ETMD, can be altered by protonation and deprotonation. It is expected to have implications for chemical and biological systems.
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Electrones , Transporte de Electrón , Movimiento (Física)RESUMEN
BACKGROUND, OBJECTIVES AND DESIGN: Arachidonic acid 15-lipoxygenase (ALOX15) has been implicated in the pathogenesis of inflammatory diseases but since pro- and anti-inflammatory roles have been suggested, the precise function of this enzyme is still a matter of discussion. To contribute to this discussion, we created transgenic mice, which express human ALOX15 under the control of the activating protein 2 promoter (aP2-ALOX15 mice) and compared the sensitivity of these gain-of-function animals in two independent mouse inflammation models with Alox15-deficient mice (loss-of-function animals) and wildtype control animals. MATERIALS AND METHODS: Transgenic aP2-ALOX15 mice were tested in comparison with Alox15 knockout mice (Alox15-/-) and corresponding wildtype control animals (C57BL/6J) in the complete Freund's adjuvant induced hind-paw edema model and in the dextran sulfate sodium induced colitis (DSS-colitis) model. In the paw edema model, the degree of paw swelling and the sensitivity of the inflamed hind-paw for mechanic (von Frey test) and thermal (Hargreaves test) stimulation were quantified as clinical readout parameters. In the dextran sodium sulfate induced colitis model the loss of body weight, the colon lengths and the disease activity index were determined. RESULTS: In the hind-paw edema model, systemic inactivation of the endogenous Alox15 gene intensified the inflammatory symptoms, whereas overexpression of human ALOX15 reduced the degree of hind-paw inflammation. These data suggest anti-inflammatory roles for endogenous and transgenic ALOX15 in this particular inflammation model. As mechanistic reason for the protective effect downregulation of the pro-inflammatory ALOX5 pathways was suggested. However, in the dextran sodium sulfate colitis model, in which systemic inactivation of the Alox15 gene protected female mice from DSS-induced colitis, transgenic overexpression of human ALOX15 did hardly impact the intensity of the inflammatory symptoms. CONCLUSION: The biological role of ALOX15 in the pathogenesis of inflammation is variable and depends on the kind of the animal inflammation model.
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Araquidonato 15-Lipooxigenasa , Colitis , Humanos , Ratones , Femenino , Animales , Ratones Transgénicos , Adyuvante de Freund , Araquidonato 15-Lipooxigenasa/genética , Araquidonato 15-Lipooxigenasa/metabolismo , Araquidonato 15-Lipooxigenasa/uso terapéutico , Dextranos/efectos adversos , Dextranos/metabolismo , Ratones Endogámicos C57BL , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/tratamiento farmacológico , Colitis/metabolismo , Colon/metabolismo , Antiinflamatorios/farmacología , Ratones Noqueados , Edema/inducido químicamente , Edema/genética , Edema/metabolismo , Sulfato de Dextran/efectos adversos , Sulfato de Dextran/metabolismo , Modelos Animales de EnfermedadRESUMEN
PURPOSE: The clinical course of COVID-19 has been complicated by secondary infections, including bacterial and fungal infections. The rapid rise in the incidence of invasive mucormycosis in these patients is very much concerning. COVID-19-associated mucormycosis was detected in huge numbers during the second wave of the COVID-19 pandemic in India, with several predisposing factors indicated in its pathogenesis. This study aimed to evaluate the epidemiology, predisposing factor, cumulative mortality and factors affecting outcomes among the coronavirus disease COVID-19-associated mucormycosis (CAM). METHODS: A multicenter retrospective study across three tertiary health care centers in Southern part of India was conducted during April-June 2021. RESULTS: Among the 217 cases of CAM, mucormycosis affecting the nasal sinuses was the commonest, affecting 95 (44%) of the patients, orbital extension seen in 84 (38%), pulmonary (n = 25, 12%), gastrointestinal (n = 6, 3%), isolated cerebral (n = 2) and disseminated mucormycosis (n = 2). Diabetes mellitus, high-dose systemic steroids were the most common underlying disease among CAM patients. The mucormycosis-associated case-fatality at 6 weeks was 14%, cerebral or GI or disseminated mucormycosis had 9 times higher risk of death compared to other locations. Extensive surgical debridement along with sequential antifungal drug treatment improved the survival in mucormycosis patients. CONCLUSION: Judicious and appropriate management of the predisposing factor and factors affecting mortality associated with CAM with multi-disciplinary approach and timely surgical and medical management can be much helpful in achieving a successful outcome.
Asunto(s)
COVID-19 , Mucormicosis , Humanos , Mucormicosis/epidemiología , Mucormicosis/terapia , Estudios Retrospectivos , Pandemias , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/terapia , India/epidemiología , Causalidad , Antifúngicos/uso terapéuticoRESUMEN
The unintended impact of natural summer fire on soil is complicated and rather less studied than its above-ground impact. Recognising the impact of a fire on silvopastoral soils and their resilience can aid in improving the management of silvopastoral systems. We studied the immediate (after 1 week (W)) and short-term (after 3 months (M)) recovery of different soil biological and chemical properties after the natural fire, with specific emphasis on phosphorus (P) dynamics. Soil samples were collected from four different layers (0-15, 15-30, 30-45, and 45-60 cm) of Morus alba, Leucaena leucocephala, and Ficus infectoria based silvopastoral systems. In the 0-15 cm soil layer, soil organic carbon (SOC) declined by â¼37, 42, and 30% after the fire in Morus-, Leucaena-, and Ficus-based systems, respectively within 1W of fire. However, after 3M of fire, Morus and Leucaena regained â¼6 and 11.5% SOC as compared to their status after 1W in the 0-15 cm soil layer. After 1W of the fire, soil nitrogen (N), sulfur (S), and potassium availability declined significantly at 0-15 cm soil layer in all systems. Iron and manganese availability improved significantly after 1W of the fire. Saloid bound P and aluminium bound P declined significantly immediately after the fire, increasing availability in all systems. However, calcium bound P did not change significantly after the fire. Dehydrogenase and alkaline phosphatase activity declined significantly after the fire, however, phenol oxidase and peroxidase activity were unaltered. Resiliencies of these soil properties were significantly impacted by soil depth and time. Path analysis indicated microbial activity and cationic micronutrients majorly governed the resilience of soil P fractions and P availability. Pasture yield was not significantly improved after the fire, so natural summer fire must be prevented to avoid loss of SOC, N, and S.