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1.
J Mater Chem B ; 12(34): 8212-8234, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39058026

RESUMO

Aging, marked by dysregulated cellular systems, gives rise to a spectrum of age-related disorders, including neurodegeneration, atherosclerosis, immunosenescence, and musculoskeletal issues. These conditions contribute significantly to the global disease burden, posing challenges to health span and economic resources. Current therapeutic approaches, although diverse in mechanism, often fall short in targeting the underlying cellular pathologies. They fail to address the issues compounded by altered pharmacokinetics in the elderly. Nanotechnology emerges as a transformative solution, offering tissue-specific targeted therapies through nanoparticles. Functional nanomaterials (FNMs) respond to internal or external stimuli, with light-responsive nanomaterials gaining prominence. Harnessing the benefits of deep tissue penetration and ease of manipulation particularly in the near-infrared spectrum, light-responsive FNMs present innovative strategies for age-related comorbidities. This review comprehensively summarizes the potential of light-responsive FNM-based approaches for targeting cellular environments in age-related disorders, and also emphasizes the advantages over traditional treatment modalities. Specifically, it focuses on the development of various classes of light-responsive functional nanomaterials including plasmonic nanomaterials, nanomaterials as carriers, upconversion nanomaterials, 2D nanomaterials, transition metal oxide and dichalcogenide nanomaterials and carbon-based nanomaterials against age related diseases. We foresee that such advanced developments in the field of nanotechnology could provide a new hope for clinical diagnosis and treatment of age-related disorders.


Assuntos
Nanoestruturas , Humanos , Nanoestruturas/química , Envelhecimento/efeitos dos fármacos , Animais , Luz
2.
Genes Cells ; 29(9): 710-721, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38923083

RESUMO

The second messenger guanosine 3',5'-bis(diphosphate)/guanosine tetraphosphate (ppGpp) and guanosine 3'-diphosphate 5'-triphosphate/guanosine pentaphosphate (pppGpp) ((p)ppGpp) has been shown to be crucial for the survival of mycobacteria under hostile conditions. Unexpectedly, deletion of primary (p)ppGpp synthetase-Rel did not completely diminish (p)ppGpp levels leading to the discovery of novel bifunctional enzyme-RelZ, which displayed guanosine 5'-monophosphate,3'-diphosphate (pGpp), ppGpp, and pppGpp ((pp)pGpp) synthesis and RNAseHII activity. What conditions does it express itself under, and does it work in concert with Rel? The regulation of its transcription and whether the Rel enzyme plays a role in such regulation remain unclear. In this article, we have studied relZ promoter and compared its activity with rel promoter in different growth conditions. We observed that the promoter activity of relZ was constitutive; it is weaker than rel promoter, lies within 200 bp upstream of translation-start site, and it increased under carbon starvation. Furthermore, the promoter activity of relZ was compromised in the rel-knockout strain in the stationary phase. Our study unveils the dynamic regulation of relZ promoter activity by SigA and SigB sigma factors in different growth phases in mycobacteria. Importantly, elucidating the regulatory network of RelZ would enable the development of the targeted interventions for treating mycobacterial infections.


Assuntos
Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Ligases , Regiões Promotoras Genéticas , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Ligases/metabolismo , Ligases/genética , Guanosina Pentafosfato/metabolismo , Guanosina Tetrafosfato/metabolismo , Mycobacterium/genética , Mycobacterium/metabolismo
3.
Appl Environ Microbiol ; 90(7): e0031024, 2024 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-38934615

RESUMO

Integration of metabolites into the overall metabolic network of a cell requires careful coordination dependent upon the ultimate usage of the metabolite. Different stoichiometric needs, and thus pathway fluxes, must exist for compounds destined for diverse uses, such as carbon sources, nitrogen sources, or stress-protective agents. Herein, we expand upon our previous work that highlighted the nature of glycine betaine (GB) metabolism in Methylobacteria to examine the utilization of GB-derivative compounds dimethylglycine (DMG) and sarcosine into Methylorubrum extorquens in different metabolic capacities, including as sole nitrogen and/or carbon sources. We isolated gain-of-function mutations that allowed M. extorquens PA1 to utilize dimethylglycine as a carbon source and dimethylglycine and sarcosine as nitrogen source. Characterization of mutants demonstrated selection for variants of the AraC-like regulator Mext_3735 that confer constitutive expression of the GB metabolic gene cluster, allowing direct utilization of the downstream GB derivatives. Finally, among the distinct isolates examined, we found that catabolism of the osmoprotectant used for selection (GB or dimethylglycine) enhanced osmotic stress resistance provided in the presence of that particular osmolyte. Thus, access to the carbon and nitrogen and osmoprotective effects of GB and DMG are made readily accessible through adaptive mutations. In M. extorquens PA1, the limitations to exploiting this group of compounds appear to exist predominantly at the levels of gene regulation and functional activity, rather than being constrained by transport or toxicity.IMPORTANCEOsmotic stress is a common challenge for bacteria colonizing the phyllosphere, where glycine betaine (GB) can be found as a prevalent osmoprotectant. Though Methylorubrum extorquens PA1 cannot use GB or its demethylation products, dimethylglycine (DMG) and sarcosine, as a sole carbon source, utilization is highly selectable via single nucleotide changes for both GB and DMG growth. The innate inability to use these compounds is due to limited flux through steps in the pathway and regulatory constraints. Herein, the characterization of the transcriptional regulator, Mext_3735 (GbdR), expands our understanding of the various roles in which GB derivatives can be used in M. extorquens PA1. Interestingly, increased catabolism of GB and derivatives does not interfere with, but rather improves, the ability of cells to thrive under increased salt stress conditions, suggesting that metabolic flux improves stress tolerance rather than providing a distinct tension between uses.


Assuntos
Betaína , Pressão Osmótica , Sarcosina , Betaína/metabolismo , Sarcosina/análogos & derivados , Sarcosina/metabolismo , Methylobacterium extorquens/metabolismo , Methylobacterium extorquens/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Carbono/metabolismo
4.
Inflamm Res ; 73(8): 1333-1348, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38836870

RESUMO

OBJECTIVE: Systemic inflammation is associated with improper localization of hyperactive neutrophils and monocytes in visceral organs. Previously, a C-terminal fragment of adhesion protein Fibulin7 (Fbln7-C) was shown to regulate innate immune functionality during inflammation. Recently, a shorter bioactive peptide of Fbln7-C, FC-10, via integrin binding was shown to reduce ocular angiogenesis. However, the role of FC-10 in regulating the neutrophils and monocyte functionality during systemic inflammatory conditions is unknown. The study sought to explore the role of FC-10 peptide on the functionality of innate immune cells during inflammation and endotoxemic mice. METHODS: Neutrophils and monocytes were isolated from healthy donors and septic patient clinical samples and Cell adhesion assay was performed using a UV spectrophotometer. Gene expression studies were performed using qPCR. Protein level expression was measured using ELISA and flow cytometry. ROS assay, and activation markers analysis in vitro, and in vivo were done using flow cytometry. TREATMENT: Cells were stimulated with LPS (100 ng/mL) and studied in the presence of peptides (10 µg, and 20 µg/mL) in vitro. In an in vivo study, mice were administered with LPS (36.8 mg/kg bw) and peptide (20 µg). RESULTS: This study demonstrates that human neutrophils and monocytes adhere to FC-10 via integrin ß1, inhibit spreading, ROS, surface activation markers (CD44, CD69), phosphorylated Src kinase, pro-inflammatory genes, and protein expression, compared to scrambled peptide in cells isolated from healthy donors and clinical sample. In line with the in vitro data, FC-10 (20 µg) administration significantly decreases innate cell infiltration at inflammatory sites, improves survival in endotoxemia animals & reduces the inflammatory properties of neutrophils and monocytes isolated from septic patients. CONCLUSION: FC-10 peptide can regulate neutrophils and monocyte functions and has potential to be used as an immunomodulatory therapeutic in inflammatory diseases.


Assuntos
Imunidade Inata , Inflamação , Lipopolissacarídeos , Monócitos , Neutrófilos , Animais , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Imunidade Inata/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Masculino , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/induzido quimicamente , Camundongos Endogâmicos C57BL , Endotoxemia/imunologia , Endotoxemia/tratamento farmacológico , Endotoxemia/induzido quimicamente , Adesão Celular/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Feminino , Peptídeos/farmacologia , Células Cultivadas
5.
Small ; : e2402204, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778727

RESUMO

Potassium-ion batteries (KIBs) can offer high energy density, cyclability, and operational safety while being economical due to the natural abundance of potassium. Utilizing graphite as an anode, suitable cathodes can realize full cells. Searching for potential cathodes, this work introduces P3-type K0.5Ni1/3Mn2/3O2 layered oxide as a potential candidate synthesized by a simple solid-state method. The material works as a 3.2 V cathode combining Ni redox at high voltage and Mn redox at low voltage and exhibits highly reversible K+ ion (de)insertion at ambient and elevated (40-50 °C) temperatures. First-principles calculations suggest the ground state in-plane Mn-Ni ordering in the MO2 sheets is strongly correlated to the K-content in the framework, leading to an interwoven and alternative row ordering of Ni-Mn in K0.5Ni1/3Mn2/3O2. Postmortem and electrochemical titration reveal the occurrence of a solid solution mechanism during K+ (de)insertion. The findings suggest that the Ni addition can effectively tune the electronic and structural properties of the cathode, leading to improved electrochemical performance. This work provides new insights in the quest to develop potential low-cost Co-free KIB cathodes for practical applications in stationary energy storage.

6.
Cureus ; 16(2): e53739, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38465071

RESUMO

Background One of the main risks associated with percutaneous nephrolithotomy (PCNL) is bleeding. In the present study, efforts are made to evaluate the pre-operative predictive factors contributing to bleeding due to the procedure of PCNL. Materials and methods From December 2019 to November 2021, data were collected prospectively from 193 patients undergoing PCNL procedures at Indira Gandhi Institute of Medical Sciences, Patna, India. Following PCNL, to check for hematuria and the extent of blood loss, the urethral catheter's and nephrostomy tube's outputs were evaluated. Multivariate regression analysis was used to evaluate the relationship between blood loss and a variety of patient-related demographic and clinical characteristics. Results Included in the study were 193 patients who underwent PCNL. Male patients made up the majority. The average age of study participants was 33.5 years. No statistically significant difference was reported in the mean hemoglobin level drop in the age groups of up to 25 years (2.211 ± 1.540 g/dL), 26-50 years (2.023 ± 1.882 g/dL), and > 50 years (1.855 ± 0.986 g/dL) with P = 0.64. The mean hemoglobin level drop in patients with stone burden > 30 mm2 was reported to be higher, 2.359 ± 1.822 g/dL, compared to 1.859 ± 1.540 g/dL in patients with lower stone burden, reaching a statistically significant difference (P =0.0408). By univariate regression analysis, the presence of a horseshoe-shaped kidney (odds ratio = -0.158, 95% confidence interval (CI): -0.911, -0.059; P = 0.026) was associated with a higher risk for a drop in mean hemoglobin level. By multivariate regression analysis, the presence of a horseshoe-shaped kidney (odds ratio = 0.071, 95% CI: 0.006, 0.839; P = 0.036) remained significantly and independently associated with a higher risk of a drop in mean hemoglobin level. Conclusion In conclusion, the patients' burden of stones and the presence of a horseshoe-shaped kidney may be associated with a higher risk of bleeding following PCNL.

7.
Nat Commun ; 15(1): 1428, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365898

RESUMO

Lead-free, silicon compatible materials showing large electromechanical responses comparable to, or better than conventional relaxor ferroelectrics, are desirable for various nanoelectromechanical devices and applications. Defect-engineered electrostriction has recently been gaining popularity to obtain enhanced electromechanical responses at sub 100 Hz frequencies. Here, we report record values of electrostrictive strain coefficients (M31) at frequencies as large as 5 kHz (1.04×10-14 m2/V2 at 1 kHz, and 3.87×10-15 m2/V2 at 5 kHz) using A-site and oxygen-deficient barium titanate thin-films, epitaxially integrated onto Si. The effect is robust and retained upon cycling upto 6 million times. Our perovskite films are non-ferroelectric, exhibit a different symmetry compared to stoichiometric BaTiO3 and are characterized by twin boundaries and nano polar-like regions. We show that the dielectric relaxation arising from the defect-induced features correlates well with the observed giant electrostriction-like response. These films show large coefficient of thermal expansion (2.36 × 10-5/K), which along with the giant M31 implies a considerable increase in the lattice anharmonicity induced by the defects. Our work provides a crucial step forward towards formulating guidelines to engineer large electromechanical responses even at higher frequencies in lead-free thin films.

8.
Sci Rep ; 14(1): 3642, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351036

RESUMO

Artificial intelligence (AI)-generated media is used in entertainment, art, education, and marketing. AI-generated faces or facial expressions using deepfake-based technologies might also contribute to nonverbal behavior studies. As a proof of concept, in this research, we test the replicability of past results regarding the positive effects of facial expressiveness (e.g., gazing, nodding, and smiling) on social outcomes. Because the facial expressions when listening to someone (i.e., nonverbal immediacy) encompass several behaviors that are typically related (i.e., smiling while nodding), the effect of combinations of these behaviors is challenging to study. We thus test the effect of facial expressiveness (gazing, nodding, and smiling vs. none) on first impression judgements in a job interview setting using AI-generated experimental video material. We measure how competent, warm, and favorably independent observers (n = 823) perceive the targets (n = 159) showing AI-generated facial expressions. Our results replicate past research showing that the more targets are facially expressive, the more they are perceived favorably. Apart from supporting evidence of the importance of facial expressiveness for conveying a positive impression, we show the benefits of relying on AI-generated experimental video material for the study of nonverbal behavior.


Assuntos
Inteligência Artificial , Expressão Facial , Sorriso
9.
J Microsc ; 292(2): 90-102, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37698414

RESUMO

Scanning acoustic microscopy (SAM) is a potent and nondestructive technique capable of producing three-dimensional topographic and tomographic images of specimens. This is achieved by measuring the differences in time of flight (ToF) of acoustic signals emitted from various regions of the sample. The measurement accuracy of SAM strongly depends on the ToF measurement, which is affected by tilt in either the scanning stage or the sample stage. Hence, compensating for the ToF shift resulting from sample tilt is imperative for obtaining precise topographic and tomographic profiles of the samples in a SAM. In the present work, we propose an automated tilt compensation in ToF of acoustic signal based on proposed curve fitting method. Unlike the conventional method, the proposed approach does not demand manually choosing three separate coordinate points from SAM's time domain data. The effectiveness of the proposed curve fitting method is demonstrated by compensating time shifts in ToF data of a coin due to the presence of tilt. The method is implemented for the correction of different amounts of tilt in the coin corresponding to angles 6.67°, 12.65° and 15.95°. It is observed that the present method can perform time offset correction in the time domain data of SAM with an accuracy of 45 arcsec. The experimental results confirm the effectiveness of the suggested tilt compensation technique in SAM, indicating its potential for future applications.

10.
ACS Omega ; 8(36): 32258-32270, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37720788

RESUMO

M. tuberculosis, an etiological agent of tuberculosis, requires a long treatment regimen due to its ability to respond to stress and persist inside the host. The second messenger (p)ppGpp-mediated stress response plays a critical role in such long-term survival, persistence, and antibiotic tolerance which may also lead to the emergence of multiple drug resistance. In mycobacteria, (pp)pGpp molecules are synthesized predominantly by two bifunctional enzymes-long RSH-Rel and short SAS-RelZ. The long RSH-Rel is a major (p)ppGpp synthetase and hydrolase. How it switches its activity from synthesis to hydrolysis remains unclear. RelMtb mutant has been reported to be defective in biofilm formation, cell wall function, and persister cell formation. The survival of such mutants has also been observed to be compromised in infection models. In M. smegmatis, short SAS-RelZ has RNase HII activity in addition to (pp)Gpp synthesis activity. The RNase HII function of RelZ has been implicated in resolving replication-transcription conflicts by degrading R-loops. However, the mechanism and regulatory aspects of such a regulation remain elusive. In this article, we have discussed (p)ppGpp metabolism and its role in managing the stress response network of mycobacteria, which is responsible for long-term survival inside the host, making it an important therapeutic target.

11.
Sci Rep ; 13(1): 13212, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37580411

RESUMO

Scanning acoustic microscopy (SAM) is a label-free imaging technique used in biomedical imaging, non-destructive testing, and material research to visualize surface and sub-surface structures. In ultrasonic imaging, noises in images can reduce contrast, edge and texture details, and resolution, negatively impacting post-processing algorithms. To reduce the noises in the scanned image, we have employed a 4D block-matching (BM4D) filter that can be used to denoise acoustic volumetric signals. BM4D filter utilizes the transform domain filtering technique with hard thresholding and Wiener filtering stages. The proposed algorithm produces the most suitable denoised output compared to other conventional filtering methods (Gaussian filter, median filter, and Wiener filter) when applied to noisy images. The output from the BM4D-filtered images was compared to the noise level with different conventional filters. Filtered images were qualitatively analyzed using metrics such as structural similarity index matrix (SSIM) and peak signal-to-noise ratio (PSNR). The combined qualitative and quantitative analysis demonstrates that the BM4D technique is the most suitable method for denoising acoustic imaging from the SAM. The proposed block matching filter opens a new avenue in the field of acoustic or photoacoustic image denoising, particularly in scenarios with poor signal-to-noise ratios.

12.
Chem Commun (Camb) ; 59(57): 8818-8821, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37357798

RESUMO

Herein, we have demonstrated a rhodium-catalyzed carboamination of olefin with the double bond intact. For the first time, deacylative carboamination of the maleimide has been achieved wherein phenoxyacetamide has behaved as the aminating source. In addition to carboamination, we have also disclosed the C-H olefination protocol where the maleimide group has been installed successfully in the ortho-position of phenoxyacetamide. In this protocol, phenoxyacetamide behaved as a traceless directing group with the in situ release of acetamide. The base-assisted E2-elimination is the key to the success of the olefination reaction.


Assuntos
Ródio , Catálise , Estrutura Molecular , Ródio/química , Alcenos/química
13.
Eur Phys J Spec Top ; : 1-11, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37359185

RESUMO

This study focuses on the short-run wealth of listed firms' shareholders. Currently, all of the resulting organizations offer competitive pricing tactics to create a superior environment for our ongoing establishment. Some time ago, it was noted that a merger occurred, although some functions and technology integration remained with the previous structure. In this paper, it has been discovered that merger and acquisition deals have an impact on the firm's value; in other words, we can view it as shareholders' wealth or unit depending on the stock price after the announcement of merger and acquisition deals in the short term. Furthermore, we focused on influencing variables on stock prices after the announcement of merger and acquisition transactions, which is measured as a percentage change in the stock prices of the listed resulting firms. Furthermore, this research is based on secondary data sources from reputable organizations. It primarily uses the NSE database and website to evaluate announcements and stock prices of the twenty-nine publicly traded companies. Markets respond to investors' emotions and market expertise. When acquirers have a strong market position, market capitalization rises in other segments. However, it is declining due to a lack of supportive finances. To determine the impact of merger and acquisition announcement deals on stock price changes, average abnormal return and cumulative average abnormal return with the capital asset pricing model (CAPM) (CAPM reaction to changes) were used to identify the acquiring company's stock price reaction. We investigated its impact on the fluctuation of share prices posted on stock exchanges using fractal interpolation functions. This is due to greater investment by acquirer businesses in target companies as well as investor expectations for specific stock market strongholds.

14.
Inflamm Res ; 72(7): 1453-1463, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37378671

RESUMO

BACKGROUND: RhoG is a multifaceted member of the Rho family of small GTPases, sharing the highest sequence identity with the Rac subfamily members. It acts as a molecular switch, when activated, plays a central role in regulating the fundamental processes in immune cells, such as actin-cytoskeleton dynamics, transendothelial migration, survival, and proliferation, including immunological functions (e.g., phagocytosis and trogocytosis) during inflammatory responses. METHOD: We have performed a literature review based on published original and review articles encompassing the significant effect of RhoG on immune cell functions from central databases, including PubMed and Google Scholar. RESULTS AND CONCLUSIONS: Recently published data shows that the dynamic expression of different transcription factors, non-coding RNAs, and the spatiotemporal coordination of different GEFs with their downstream effector molecules regulates the cascade of Rho signaling in immune cells. Additionally, alterations in RhoG-specific signaling can lead to physiological, pathological, and developmental adversities. Several mutations and RhoG-modulating factors are also known to pre-dispose the downstream signaling with abnormal gene expression linked to multiple diseases. This review focuses on the cellular functions of RhoG, interconnecting different signaling pathways, and speculates the importance of this small GTPase as a prospective target against several pathological conditions.


Assuntos
Transdução de Sinais , Proteínas rho de Ligação ao GTP , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo , Transdução de Sinais/fisiologia , Fagocitose , Fatores de Transcrição/metabolismo
15.
Biomater Sci ; 11(12): 4200-4209, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37161699

RESUMO

Amyloid formation due to altered protein folding and aggregation has gained significant attention due to its association with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and systemic lysozyme amyloidosis. Amyloids are characterized by parallel and anti-parallel cross-ß-strands arranged to form stacks of sheets that provide stability and rigidity to the amyloid core. The prototypic protein Hen Egg White Lysozyme (HEWL) has been extensively used to understand protein hydrolysis, fragmentation, folding, misfolding, and amyloid formation. In the present study, we have examined the efficacy of plasmonic gold nanorods (GNRs) as an anti-amyloid agent against HEWL amyloids. Our results reveal that (i) the amyloid inhibition by plasmonic GNRs is dependent on their aspect ratio, (ii) the large aspect ratio GNRs ameliorate amyloid assembly completely, and (iii) GNRs interfere at several stages along the lysozyme fibril-formation pathway and block the conversion of monomeric and oligomeric intermediates into mature fibrils. Using a multi-parametric approach, we demonstrate that GNRs drive HEWL into off-pathway and amyloid-incompetent forms. To establish GNRs as generic amyloid inhibitors, we extended our studies to another archetypal protein, Bovine Serum Albumin (BSA), and observed similar results of GNRs inhibiting BSA aggregation. We believe that our results will pave the way for the potential use of GNRs with current therapeutics to reduce the burden of amyloid-related diseases.


Assuntos
Muramidase , Nanotubos , Muramidase/metabolismo , Ouro , Amiloide/metabolismo
16.
Adv Virol ; 2023: 2995443, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37065904

RESUMO

SARS-CoV-2 is a novel coronavirus that causes a potentially fatal respiratory disease known as coronavirus disease (COVID-19) and is responsible for the ongoing pandemic with increasing mortality. Understanding the host-virus interaction involved in SARS-CoV-2 pathophysiology will enhance our understanding of the mechanistic basis of COVID-19 infection. The characterization of post-transcriptional gene regulatory networks, particularly pre-mRNA splicing, and the identification and characterization of host proteins interacting with the 5' and 3'UTRs of SARS-CoV-2 will improve our understanding of post-transcriptional gene regulation during SARS-CoV-2 pathogenesis. Here, we demonstrate that either SARS-CoV-2 infection or exogenous overexpression of the 5' and 3'UTRs of the viral genomic RNAs, results in reduced mRNA levels possibly due to modulation of host cell pre-mRNA splicing. Further, we have investigated the potential RNA-binding proteins interacting with the 5' and 3'UTRs, using in-silico approaches. Our results suggest that 5' and 3'UTRs indeed interact with many RNA-binding proteins. Our results provide a primer for further investigations into the UTR-mediated regulation of splicing and related molecular mechanisms in host cells.

17.
Avicenna J Med ; 13(1): 56-59, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36969354

RESUMO

Idiopathic isolated right ventricular cardiomyopathy is an extremely rare cause of right ventricular failure. Here, we report a case of 65-year-old male presented with chief complaints of dyspnea, fatigue, and bilateral pedal edema for the last 6 months. On clinical evaluation, grade II/III pansystolic murmur was present in left parasternal area. Investigations and imaging revealed dilated right atrium and ventricle with normal pulmonary artery pressure without any etiology. Magnetic resonance imaging ruled out other common causes of right ventricular cardiomyopathy; thus, the patient was diagnosed as a case of idiopathic isolated right ventricular cardiomyopathy that is a diagnosis of exclusion.

18.
Front Plant Sci ; 14: 1087070, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36890890

RESUMO

Chlamydomonas reinhardtii is a eukaryotic, unicellular photosynthetic organism and a potential algal platform for producing biomass and recombinant proteins for industrial use. Ionizing radiation is a potent genotoxic and mutagenic agent used for algal mutation breeding that induces various DNA damage and repair responses. In this study, however, we explored the counterintuitive bioeffects of ionizing radiation, such as X- and γ-rays, and its potential as an elicitor to facilitate batch or fed-batch cultivation of Chlamydomonas cells. A certain dose range of X- and γ-rays was shown to stimulate the growth and metabolite production of Chlamydomonas cells. X- or γ-irradiation with relatively low doses below 10 Gy substantially increased chlorophyll, protein, starch, and lipid content as well as growth and photosynthetic activity in Chlamydomonas cells without inducing apoptotic cell death. Transcriptome analysis demonstrated the radiation-induced changes in DNA damage response (DDR) and various metabolic pathways with the dose-dependent expression of some DDR genes, such as CrRPA30, CrFEN1, CrKU, CrRAD51, CrOASTL2, CrGST2, and CrRPA70A. However, the overall transcriptomic changes were not causally associated with growth stimulation and/or enhanced metabolic activities. Nevertheless, the radiation-induced growth stimulation was strongly enhanced by repetitive X-irradiation and/or subsequent cultivation with an inorganic carbon source, i.e., NaHCO3, but was significantly inhibited by treatment of ascorbic acid, a scavenger of reactive oxygen species (ROS). The optimal dose range of X-irradiation for growth stimulation differed by genotype and radiation sensitivity. Here, we suggest that ionizing radiation within a certain dose range determined by genotype-dependent radiation sensitivity could induce growth stimulation and enhance metabolic activities, including photosynthesis, chlorophyll, protein, starch, and lipid synthesis in Chlamydomonas cells via ROS signaling. The counterintuitive benefits of a genotoxic and abiotic stress factor, i.e., ionizing radiation, in a unicellular algal organism, i.e., Chlamydomonas, may be explained by epigenetic stress memory or priming effects associated with ROS-mediated metabolic remodeling.

19.
Wiley Interdiscip Rev RNA ; 14(3): e1763, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36131558

RESUMO

Splicing of pre-mRNA is an essential part of eukaryotic gene expression. Serine-/arginine-rich (SR) proteins are highly conserved RNA-binding proteins present in all metazoans and plants. SR proteins are involved in constitutive and alternative splicing, thereby regulating the transcriptome and proteome diversity in the organism. In addition to their role in splicing, SR proteins are also involved in mRNA export, nonsense-mediated mRNA decay, mRNA stability, and translation. Due to their pivotal roles in mRNA metabolism, SR proteins play essential roles in normal growth and development. Hence, any misregulation of this set of proteins causes developmental defects in both plants and animals. SR proteins from the animal kingdom are extensively studied for their canonical and noncanonical functions. Compared with the animal kingdom, plant genomes harbor more SR protein-encoding genes and greater diversity of SR proteins, which are probably evolved for plant-specific functions. Evidence from both plants and animals confirms the essential role of SR proteins as regulators of gene expression influencing cellular processes, developmental stages, and disease conditions. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing.


Assuntos
Processamento Alternativo , Splicing de RNA , Animais , Precursores de RNA/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , RNA Mensageiro/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo
20.
Ann Afr Med ; 22(4): 554-556, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38358161

RESUMO

Mitral valve aneurysm is defined as outpouching of the mitral valve which expands in systole and collapse in diastole. It was first reported in 1729 by Morand. Most of the cases have been described in the African population. It is rare in the Indian population. Its chief presentations are congestive heart failure, palpitations, arrhythmia, or in rare cases an embolic phenomenon. It can be diagnosed either by echocardiography or cardiac imaging (magnetic resonance imaging/computed tomography). It can either occur as an isolated defect or with other associated valvular abnormalities. Here, we present a case of a 40-year-old male who was referred for the evaluation of palpitation who on the investigation was found to have a bicuspid aortic valve with severe Aortic Regurgitation (AR) along with aneurysm in the anterior mitral leaflet causing severe mitral regurgitation. This case highlights the importance of keeping a submitral aneurysm as a differential diagnosis for mitral regurgitation and searching for other associated valvular defects which may affect the management and treatment outcomes.


Résumé L'anévrisme de la valve mitrale est défini comme un gonflement de la valve mitrale qui se dilate en systole et s'effondre en diastole. Il a été signalé pour la première fois en. 1729 par Morand. La plupart des cas ont été décrits dans la population africaine. Il est rare dans la population indienne. Ses principales présentations sont insuffisance cardiaque congestive, palpitations, arythmie, ou dans de rares cas un phénomène embolique. Elle peut être diagnostiquée soit par échocardiographie, soit imagerie cardiaque (imagerie par résonance magnétique/tomodensitométrie). Il peut se produire soit comme un défaut isolé, soit avec d'autres défauts valvulaires associés. anomalies. Nous présentons ici le cas d'un homme de 40 ans qui a été référé pour l'évaluation de palpitations et qui, à l'examen, a été s'est avéré avoir une valve aortique bicuspide avec une insuffisance aortique sévère ainsi qu'un anévrisme dans le feuillet mitral antérieur provoquant une insuffisance mitrale sévère. Ce cas met en évidence l'importance de garder un anévrysme subsectoriel comme diagnostic différentiel d'une insuffisance mitrale et de rechercher d'autres défauts valvulaires associés pouvant affecter la prise en charge et les résultats du traitement. Mots-clés: Insuffisance aortique, valve aortique bicuspide, insuffisance mitrale, anévrisme submitral.


Assuntos
Aneurisma , Doença da Válvula Aórtica Bicúspide , Insuficiência da Valva Mitral , Masculino , Humanos , Adulto , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Doença da Válvula Aórtica Bicúspide/complicações , Aneurisma/complicações , Ecocardiografia/efeitos adversos , Ecocardiografia/métodos
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