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1.
Dalton Trans ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958025

RESUMO

Currently, there are many uses of metal complexes, especially in the fields of medicinal chemistry and catalysis. Thus, fabrication of new complexes which perform as a catalyst and chemotherapeutic drug is always a beneficial addition to the literature. Herein, we report three heterocyclic thiosemicarbazone-based Pd(II) complexes [Pd(HL1)Cl] (C1), [Pd(L2)(PPh3)] (C2) and [Pd(L3)(PPh3)]Cl (C3) having coligands Cl and PPh3. Thiosemicarbazone ligands (H2L1, H2L2 and HL3) and the complexes (C1-C3) were characterized methodically using several spectroscopic techniques. Single-crystal X-ray diffraction methods reveal that the structural environment around the metal center of C2 is square planar, while for C1 and C3 it is a slighty distorted square plane. The supramolecular network of compounds was built via hydrogen bonds, C-H⋯π and π⋯π interactions. Density functional theory (DFT) study of the structure of the complexes supports experimental findings. The application of these complexes as catalysts toward Suzuki-Miyaura coupling reactions has been examined with various aryl halides and phenyl boronic acid in PEG 400 solvent. The complexes displayed good biomolecular interactions with DNA/protein, with a binding constant value of the order of 105 M-1. C3 showed greater binding efficacy toward these biomolecules than the other complexes, which might be due to the cationic nature of C3. Furthermore, antitumor activity of the complexes was studied against the human triple-negative breast cancer (TNBC) cell line MDA-MB-231. It was found that C3 was more toxic (IC50 = 10 ± 2.90 µM) toward MDA-MB-231 cells than the other complexes. A known chemotherapeutic drug, 5-fluorouracil, was included as positive control. The programmed cell death mechanism of C3 was confirmed. Additionally, complex-induced apoptosis was confirmed and occurred via a mitochondria-dependent (intrinsic) pathway.

2.
J Biosci ; 492024.
Artigo em Inglês | MEDLINE | ID: mdl-38726827

RESUMO

Metabolism is the key cellular process of plant physiology. Understanding metabolism and its dynamical behavior under different conditions may help plant biotechnologists to design new cultivars with desired goals. Computational systems biochemistry and incorporation of different omics data unravelled active metabolism and its variations in plants. In this review, we mainly focus on the basics of flux balance analysis (FBA), elementary flux mode analysis (EFMA), and some advanced computational tools. We describe some important results that were obtained using these tools. Limitations and challenges are also discussed.


Assuntos
Plantas , Biologia de Sistemas , Plantas/metabolismo , Plantas/genética , Redes e Vias Metabólicas/genética , Análise do Fluxo Metabólico , Modelos Biológicos , Fenômenos Fisiológicos Vegetais
3.
Comput Biol Chem ; 108: 107978, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37956471

RESUMO

Interactions between distantly placed amino acids in the primary chain (long-range) play a very crucial role in the formation and stabilization of the tertiary structure of a protein, while interactions between closely placed amino acids in the primary chain (short-range) mostly stabilize the secondary structures. Every protein needs to maintain marginal stability in order to perform its physiological functions in its native environment. The requirements for this stability in mesophilic and thermophilic proteins are different. Thermophilic proteins need to form more interactions as well as more stable interactions to survive in the extreme environment, they live in. Here, we aim to find out how the interacting amino acids in three-dimensional space are positioned in the primary chains in thermophilic and mesophilic. How does this arrangement help thermophiles to maintain their structural integrity at high temperatures? Working on a dataset of 1560 orthologous pairs we perceive that thermophiles are not only enriched with long-range interactions, they feature bigger connected clusters and higher network densities compared to their mesophilic orthologs, at higher interaction strengths between the amino acids. Moreover, we have observed the enrichment of different types of interactions at different secondary structural regions.


Assuntos
Aminoácidos , Proteínas , Temperatura , Proteínas/química , Aminoácidos/química , Estrutura Secundária de Proteína , Proteínas de Bactérias/química
4.
Cancer Sci ; 114(12): 4732-4746, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37792582

RESUMO

Oral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) is the most common cancer among men in India, and is associated with poor prognosis and frequent recurrence. Cellular heterogeneity in OSCC-GB was investigated by single-cell RNA sequencing of tumors derived from the oral cavity of 12 OSCC-GB patients, 3 of whom had concomitant presence of a precancerous lesion (oral submucous fibrosis [OSMF]). Unique malignant cell types, features, and phenotypic shifts in the stromal cell population were identified in oral tumors with associated submucous fibrosis. Expression levels of FOS, ATP1A, and DUSP1 provided robust discrimination between tumors with or without the concomitant presence of OSMF. Malignant cell populations shared between tumors with and without OSMF were enriched with the expression of partial epithelial-mesenchymal transition (pEMT) or fetal cell type signatures indicative of two dominant cellular programs in OSCC-GB-pEMT and fetal cellular reprogramming. Malignant cells exhibiting fetal cellular and pEMT programs were enriched with the expression of immune-related pathway genes known to be involved in antitumor immune response. In the tumor microenvironment, higher infiltration of immune cells than the stromal cells was observed. The T cell population was large in tumors and diverse subtypes of T cells with varying levels of infiltration were found. We also detected double-negative PLCG2+ T cells and cells with intermediate M1-M2 macrophage polarization. Our findings shed light on unique aspects of cellular heterogeneity and cell states in OSCC-GB.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Fibrose Oral Submucosa , Masculino , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Fibrose Oral Submucosa/patologia , Perfilação da Expressão Gênica , Microambiente Tumoral/genética
5.
J Biosci ; 482023.
Artigo em Inglês | MEDLINE | ID: mdl-37539551

RESUMO

As in most plants, during their growth from immature to mature stages, the leaves of Setaria viridis, a model C4 bioenergy plant, have differential growth rates from the base (immature or growing) to the tip (most mature). In this study, we constructed a multi-segment C4 leaf metabolic model of S. viridis with two cell types (bundle sheath and mesophyll cells) across four leaf segments (base to tip). We incorporated differential growth rates for each leaf segment as constraints and integrated transcriptomic data as the objective function for our model simulation using flux balance analysis. The model was able to predict the exchanges of metabolites between immature and mature segments of the leaf and the distribution of the activities of biomass synthesis across those segments. Our model demonstrated the use of a modelling approach in studying the source-sink relationship within an organ and provided insights into the metabolic interactions across different parts of a leaf.


Assuntos
Setaria (Planta) , Setaria (Planta)/genética , Setaria (Planta)/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Células do Mesofilo/metabolismo , Fotossíntese/genética , Biomassa
6.
J Mater Chem B ; 11(28): 6646-6663, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37366114

RESUMO

Quercetin (Qu), a potential bioflavonoid has gained considerable interest as a promising chemotherapeutic drug which can inhibit the proliferation of triple-negative breast cancer (TNBC) cells due to its regulation of the expression of tumor-suppressor gene metastasis and antioxidant property. Notably, Qu exhibits a very negligible cytotoxic effect on normal cells, even with high-dose treatment, while it is shows high affinity to TNBC. However, the efficiency of Qu is limited clinically due to its poor bioavailability, caused by its low aqueous solubility (2.15 µg mL-1 at 25 °C), rapid gastrointestinal digestion and chemical instability in alkaline and neutral media. Herein, polydopamine (PDA)-coated, NH2-PEG-NH2 and hyaluronic acid (HA)-functionalized Gd3+-doped Prussian blue nanocubes (GPBNC) are reported as a multifunctional platform for the codelivery of Qu as a chemotherapeutic agent and GPBNC as a photodynamic (PDT) and photothermal (PTT) agent with improved therapeutic efficiency to overcome theses barriers. PDA, NH2-PEG-NH2 and HA stabilize GPBNC@Qu and facilitate bioavailability and active-targeting, while absorption of near infrared (NIR) (808 nm; 1 W cm-2) induces PDT and PTT activities and dual T1-T2-weighted magnetic resonance imaging (MRI) with high relaxometric parameters (r1 10.06 mM-1 s-1 and r2 24.96 mM-1 s-1 at a magnetic field of 3 T). The designed platform shows a pH-responsive Qu release profile and NIR-induced therapeutic efficiency of ∼79% in 20 minutes of irradiation, wherein N-terminal gardermin D (N-GSDMD) and a P2X7-receptor-mediated pyroptosis pathway induces cell death, corroborating the up-regulation of NLRP3, caspase-1, caspase-5, N-GSDMD, IL-1ß, cleaved Pannexin-1 and P2X7 proteins. More interestingly, the increasing relaxivity values of Prussian blue nanocubes with Gd3+ doping have been explained on the basis of Solomon-Bloembergen-Morgan theory, considering inner- and outer-sphere relaxivity, wherein crystal defects, coordinated water molecules, tumbling rate, metal to water proton distance, correlation time, magnetisation value etc. play a significant role. In summary, our study suggests that GPBNC could be a beneficial nanocarrier for theranostic purposes against TNBC, while our conceptual study clearly demonstrates the role of various factors in increasing relaxometric parameters.


Assuntos
Quercetina , Neoplasias de Mama Triplo Negativas , Humanos , Quercetina/farmacologia , Células MDA-MB-231 , Neoplasias de Mama Triplo Negativas/patologia , Imageamento por Ressonância Magnética/métodos , Água , Caspases
7.
ACS Omega ; 8(5): 4566-4577, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36777585

RESUMO

Carbon dots (CQDs) have been widely investigated as prime candidates for developing a tumor theranostic platform due to their tunable fluorescence emission and excitation, high water solubility, good photostability, and biocompatibility. Among the CQDs, natural CQDs are an emerging class of nanomaterials in the carbon family. Herein, highly fluorescent carbon quantum dots (CQDs) were synthesized from orange juice using a one-step hydrothermal method and characterized by different techniques. After that, CQD/Ag heterostructures were synthesized by the reduction of silver salt, in particular silver nitrate (AgNO3) solution using sodium borohydride (NaBH4) in different ratios. The photostability and characterization of CQD/Ag heterostructures were investigated. At last, a comparative cellular toxicity measurement was done to select the superior CQD/Ag heterostructure in the human colorectal carcinoma (HCT 116) cell line along with the imaging property. The detailed cell death signaling was also observed in the HCT 116 cell line via the ROS-dependent mitochondrial-mediated pathway, where Akt (RAC-α serine/threonine-protein kinase) played a important role.

8.
J Biomol Struct Dyn ; 41(5): 1745-1752, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-34996344

RESUMO

Proteins from thermophilic organisms are a matter of immense interest for decades because of its application in fields like de-novo protein design, thermostable variants of biocatalysts etc. Previous studies have found several sequence and structural adaptations related to thermal stability, while charge reversal study remains ignored. Here we address whether charge reversal mutations naturally occur in mesophilic-thermophilic/hyperthermophilic orthologous proteins. Do they contribute to thermal stability? Our systematic study on 1550 mesophilic-thermophilic/hyperthermophilic orthologous protein pairs with remarkable structural and topological similarity, shows gain in coulombic interaction energy in thermophilic/hyperthermophilic proteins at short range associated with partially exposed and buried charge reversal mutations, which may enhance thermostability. Our findings call forth its application in future protein engineering studies. Communicated by Ramaswamy H. Sarma.


Assuntos
Engenharia de Proteínas , Proteínas , Proteínas/genética , Proteínas/química , Archaea , Mutação
9.
RSC Adv ; 12(38): 24555-24570, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36128364

RESUMO

A targeted multimodal strategy on a single nanoplatform is attractive in the field of nanotheranostics for the complete ablation of cancer. Herein, we have designed mesoporous silica (m-SiO2)-coated Prussian blue nanocubes (PBNCs), functionalized with hyaluronic acid (HA) to construct a multifunctional PBNC@m-SiO2@HA nanoplatform that exhibited good biocompatibility, excellent photodynamic activity, and in vitro T 1-weighted magnetic resonance imaging ability (r 1 ∼ 3.91 mM-1 s-1). After loading doxorubicin into the as-prepared PBNC@m-SiO2@HA, the developed PBNC@m-SiO2@HA@DOX displayed excellent pH-responsive drug release characteristics. Upon irradiation with 808 nm (1.0 W cm-2) laser light, PBNC@m-SiO2@HA@DOX exhibited synergistic photodynamic and chemotherapeutic efficacy (∼78% in 20 minutes) for human colorectal carcinoma (HCT 116) cell line compared to solo photodynamic or chemotherapy. Herein, the chemo-photodynamic therapeutic process was found to follow the apoptotic pathway via ROS-mediated mitochondrion-dependent DNA damage with a very low cellular uptake of PBNC@m-SiO2@HA@DOX for the human embryonic kidney (HEK 293) cell line, illustrating its safety. Hence, it may be stated that the developed nanoplatform can be a potential theranostic agent for future applications. Most interestingly, we have noted variation in r 1 at each step of the functionalization along with size variation that has been the first time modelled on the basis of the Solomon-Bloembergen-Morgan theory considering changes in the defect crystal structure, correlation time, water diffusion rate, etc., due to varied interactions between PBNC and water molecules.

10.
BJOG ; 129(12): 2052-2061, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35596694

RESUMO

OBJECTIVE: To assess the diagnostic performance of preoperative application of the Enzian classification (cEnzian) using surgical findings as reference standard. DESIGN: A prospective international non-interventional study. SETTING: Twelve endometriosis centres in four European countries (Austria, Germany, Switzerland and Czech Republic). POPULATION: 1062 women with endometriosis surgery. METHODS: Extent of endometriosis was preoperatively classified using the cEnzian classification based on gynaecological examination and/or transvaginal ultrasound (TVS) and/or magnetic resonance imaging (MRI). After subsequent surgery, the surgeon classified the intraoperative findings using the Enzian classification. MAIN OUTCOME MEASURES: Sensitivity, specificity, PPV, NPV, LR+ , LR- and accuracy were calculated. Conditional frequencies of intraoperative Enzian codings and the corresponding 95% confidence intervals were computed for each preoperative coding and visualised in plots. RESULTS: Although overall consistency of cEnzian and Enzian was poor (35.14%, 95% confidence interval 32.26-38.03), high specificities and negative predictive values (NPVs) of the cEnzian compartments could be demonstrated. Looking at the individual parts of the Enzian classification, the poorest diagnostic performance was detected for compartment B and the highest PPVs were found for category 3 lesions (>3 cm), independent of the compartment. CONCLUSIONS: Using the Enzian classification in a non-invasive setting is a useful tool providing us with an 'at a glance' summary of the diagnostic workup regarding deep endometriosis with high specificities and NPVs. An attempt to merge the two new endometriosis classification systems (#Enzian and AAGL 2021) seems reasonable taking into consideration the respective advantages of each other.


Assuntos
Endometriose , Áustria , Endometriose/diagnóstico por imagem , Endometriose/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia
11.
Materials (Basel) ; 14(16)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34442974

RESUMO

This paper summarises the findings of an investigation into the durability of cold spray repairs, also known as supersonic particle deposition or SPD repairs, to simulated corrosion damage in AA7075-T7351 aluminium alloy specimens. A feature of this paper is that it is the first to show how to perform the mandatory durability analysis of repaired corroded structures, where the corroded material is first removed by machining and then repaired using cold spray, in a fashion consistent with the requirements delineated in USAF Structures Bulletin EZ-19-01, MIL-STD-1530D, and the US Joint Services Structural Guidelines JSSG2006.

12.
Front Microbiol ; 12: 613067, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679637

RESUMO

Klebsiella pneumoniae is a leading cause of pneumonia and septicemia across the world. The rapid emergence of multidrug-resistant K. pneumoniae strains necessitates the discovery of effective drugs against this notorious pathogen. However, there is a dearth of knowledge on the mechanisms by which this deadly pathogen subverts host cellular machinery. To fill this knowledge gap, our study attempts to identify the potential mechanisms of host cell subversion by building a K. pneumoniae-human interactome based on rigorous computational methodology. The putative host targets inferred from the predicted interactome were found to be functionally enriched in the host's immune surveillance system and allied functions like apoptosis, hypoxia, etc. A multifunctionality-based scoring system revealed P53 as the most multifunctional protein among host targets accompanied by HIF1A and STAT1. Moreover, mining of host protein-protein interaction (PPI) network revealed that host targets interact among themselves to form a network (TTPPI), where P53 and CDC5L occupy a central position. The TTPPI is composed of several inter complex interactions which indicate that K. pneumoniae might disrupt functional coordination between these protein complexes through targeting of P53 and CDC5L. Furthermore, we identified four pivotal K. pneumoniae-targeted transcription factors (TTFs) that are part of TTPPI and are involved in generating host's transcriptional response to K. pneumoniae-mediated sepsis. In a nutshell, our study identifies some of the pivotal molecular targets of K. pneumoniae which primarily correlate to the physiological response of host during K. pneumoniae-mediated sepsis.

13.
FEBS J ; 288(11): 3428-3447, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33319437

RESUMO

Precise control of protein and messenger RNA (mRNA) degradation is essential for cellular metabolism and homeostasis. Controlled and specific degradation of both molecular species necessitates their engagements with the respective degradation machineries; this engagement involves a disordered/unstructured segment of the substrate traversing the degradation tunnel of the machinery and accessing the catalytic sites. However, while molecular factors influencing protein degradation have been extensively explored on a genome scale, and in multiple organisms, such a comprehensive understanding remains missing for mRNAs. Here, we analyzed multiple genome-scale experimental yeast mRNA half-life data in light of experimentally derived mRNA secondary structures and protein binding data, along with high-resolution X-ray crystallographic structures of the RNase machines. Results unraveled a consistent genome-scale trend that mRNAs comprising longer terminal and/or internal unstructured segments have significantly shorter half-lives; the lengths of the 5'-terminal, 3'-terminal, and internal unstructured segments that affect mRNA half-life are compatible with molecular structures of the 5' exo-, 3' exo-, and endoribonuclease machineries. Sequestration into ribonucleoprotein complexes elongates mRNA half-life, presumably by burying ribonuclease engagement sites under oligomeric interfaces. After gene duplication, differences in terminal unstructured lengths, proportions of internal unstructured segments, and oligomerization modes result in significantly altered half-lives of paralogous mRNAs. Side-by-side comparison of molecular principles underlying controlled protein and mRNA degradation in yeast unravels their remarkable mechanistic similarities and suggests how the intrinsic structural features of the two molecular species, at two different levels of the central dogma, regulate their half-lives on genome scale.


Assuntos
Endorribonucleases/genética , Conformação de Ácido Nucleico , Estabilidade de RNA/genética , RNA Mensageiro/ultraestrutura , Endorribonucleases/ultraestrutura , Genoma Fúngico/genética , Meia-Vida , Estrutura Secundária de Proteína/genética , RNA Mensageiro/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/ultraestrutura
14.
Curr Res Environ Sustain ; 3: 100086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34977607

RESUMO

Monitoring frameworks under a non-disaster scenario can be helpful to identify the various socio-technical constraints of local and regional origin which influence the economics and resources management of marine fisheries. However, local-scale manifestations of regional/global changes due to the rapid onset of a disaster scenario may lead to unprecedented distortion of the market demand-supply value chains for the fisheries sector at shorter temporal scales. The global pandemic of COronaVIrus Disease (COVID-19) provided a unique short, temporal window to study the evolution of socio-economic challenges to sustainable fishing in the Bay of Bengal (BoB), India. The present study provides a detailed multi-source assessment of the factors that lead to massive complications of market disruption beginning with a public curfew on 22nd March 2020, followed by a nationwide complete lockdown of 54 days beginning from 25th March 2020, indicating an "all-pain no-gain" scenario for the fishers. Aggravating factors as a cessation of food services, and the restriction of exports of perishable commodities indicated negative spin-offs for allied activities sectors such as food processing due to low or negligible demand. The present investigation also indicated that as part of rehabilitation, policies related to overfishing are necessary to promote sustainable fishing practices in the BoB region in a post-pandemic period. New policy frameworks must consider the community-centric factors which facilitated the alleviation of the impacts of anthropogenic activities related to fishing and the slow restoration of the demand-supply chain, with long-term benefits for natural resources sustenance and to aid marine conservation efforts.

15.
BMC Womens Health ; 20(1): 144, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660473

RESUMO

BACKGROUND: Endometriosis can be associated with considerable pain and sterility. After surgical excision of moderate or severe endometriosis lesions, the rate of recurrence reaches up to 67%. The objective of this retrospective study was to establish the recurrence and pregnancy rates following surgical resection of stage III/IV endometriosis lesions. Indications for operation were endometriosis symptoms, sonographic findings and/or infertility. METHODS: A total of 456 patients who underwent stage III/IV endometriosis surgery between 2004 and 2014 were sent a questionnaire relating to their postoperative medical treatment, pregnancies, relief of symptoms and recurrence. Responses of 206 patients (45.2%) and their clinical data were analysed for this study. RESULTS: A total of 66.5% (N = 137) of patients had stage III disease, and 33.5% (N = 69) had stage IV disease. The average age was 37 years (17-59). A total of 63.1% (N = 130) of surgeries were performed by laparoscopy, 21.8% (N = 45) were performed by laparotomy and 15% (N = 31) were performed by conversion. Complete resection of endometriosis lesions was achieved in 90.8% of patients (N = 187). After surgery, 48.5% (N = 100) of the women did not receive hormonal treatment; the main reason was the desire for children in 53%. Complete or partial relief in complaints was achieved in 93.2% (N = 192). The rate of recurrence was 21.8% (N = 45). The statistically significant factors that was associated with a higher risk to develop recurrence was an age < 35 (p < 0.005). After surgery, 65.8% (79/120) of patients who wished to have children became pregnant. There was a statistically significant association among a higher postoperative pregnancy rate and age < 35 (p < 0.003) in multivariate logistic regression analysis and laparoscopic surgical access in univariate logistic regression analysis (p < 0.01). CONCLUSION: We assessed the high percentage of complete or partial relief of symptoms of 93.2%, the high postoperative pregnancy rate of 65.8% and the low rate of recurrence of 21.8% compared to international literature to be very encouraging for women suffering from moderate and severe endometriosis. Though laparoscopy is considered the 'gold standard'of endometriosis surgery, laparotomy still may be indicated in patients with extensive endometriosis especially to preserve reproductive function.


Assuntos
Endometriose/cirurgia , Infertilidade Feminina/etiologia , Laparoscopia , Taxa de Gravidez , Adolescente , Adulto , Endometriose/complicações , Feminino , Fertilidade/fisiologia , Humanos , Infertilidade Feminina/cirurgia , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Recidiva , Reprodução , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
16.
RNA Biol ; 17(9): 1331-1341, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32476560

RESUMO

Regulation of protein synthesis is an essential step of gene expression. This process is under the control of cis-acting RNA elements and trans-acting factors. Gemin5 is a multifunctional RNA-binding protein organized in distinct domains. The protein bears a non-canonical RNA-binding site, designated RBS1, at the C-terminal end. Among other cellular RNAs, the RBS1 region recognizes a sequence located within the coding region of Gemin5 mRNA, termed H12. Expression of RBS1 stimulates translation of RNA reporters carrying the H12 sequence, counteracting the negative effect of Gemin5 on global protein synthesis. A computational analysis of RBS1 protein and H12 RNA variability across the evolutionary scale predicts coevolving pairs of amino acids and nucleotides. RBS1 footprint and gel-shift assays indicated a positive correlation between the identified coevolving pairs and RNA-protein interaction. The coevolving residues of RBS1 contribute to the recognition of stem-loop SL1, an RNA structural element of H12 that contains the coevolving nucleotides. Indeed, RBS1 proteins carrying substitutions on the coevolving residues P1297 or S1299S1300, drastically reduced SL1-binding. Unlike the wild type RBS1 protein, expression of these mutant proteins in cells failed to enhance translation stimulation of mRNA reporters carrying the H12 sequence. Therefore, the PXSS motif within the RBS1 domain of Gemin5 and the RNA structural motif SL1 of its mRNA appears to play a key role in fine-tuning the expression level of this essential protein.


Assuntos
Sítios de Ligação , Motivos de Ligação ao RNA , Proteínas de Ligação a RNA/química , RNA/química , Proteínas do Complexo SMN/química , Sequência de Aminoácidos , Evolução Biológica , Sequência Conservada , Conformação de Ácido Nucleico , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , RNA/genética , RNA/metabolismo , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas do Complexo SMN/metabolismo
17.
Materials (Basel) ; 13(6)2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32183483

RESUMO

The USAF requirements for the durability and damage tolerance certification for additively manufactured (AM) aircraft structural parts, which are detailed in Structures Bulletin EZ-19-01, raise a number of new and, as yet, unanswered questions. The present paper attempts to address three questions: How to perform a fracture mechanics-based analysis of crack growth in an AM part so as to account for the residual stresses, how to perform a fracture mechanics-based durability analysis of a cold spray repair so as to account for both the induced residual stresses and the presence of multiple co-located cracks, and how to perform a fracture mechanics-based durability analysis of an AM part so as to account for the presence of multiple collocated surface braking cracks. In this context, the present paper reveals the potential of the Hartman-Schijve variant of the NASGRO crack growth equation to accurately predict the growth of each of the individual (collocated) cracks that arose in a cold spray-repaired specimen and in a specimen from a crack that nucleated and grew from a rough surface.

18.
Proteins ; 88(6): 788-808, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31872464

RESUMO

Are there any generalized molecular principles of thermal adaptation? Here, integrating the concepts of structural bioinformatics, sequence analysis, and classical knot theory, we develop a robust computational framework that seeks for mechanisms of thermal adaptation by comparing orthologous mesophilic-thermophilic and mesophilic-hyperthermophilic proteins of remarkable structural and topological similarities, and still leads us to context-independent results. A comprehensive analysis of 4741 high-resolution, non-redundant X-ray crystallographic structures collected from 11 hyperthermophilic, 32 thermophilic and 53 mesophilic prokaryotes unravels at least five "nearly universal" signatures of thermal adaptation, irrespective of the enormous sequence, structure, and functional diversity of the proteins compared. A careful investigation further extracts a set of amino acid changes that can potentially enhance protein thermal stability, and remarkably, these mutations are overrepresented in protein crystallization experiments, in disorder-to-order transitions and in engineered thermostable variants of existing mesophilic proteins. These results could be helpful to find a precise, global picture of thermal adaptation.


Assuntos
Adaptação Fisiológica/genética , Archaea/química , Proteínas Arqueais/química , Bactérias/química , Proteínas de Bactérias/química , Archaea/fisiologia , Proteínas Arqueais/genética , Proteínas Arqueais/metabolismo , Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cristalografia por Raios X , Mineração de Dados , Conjuntos de Dados como Assunto , Temperatura Alta , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Mutação , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Dobramento de Proteína , Domínios e Motivos de Interação entre Proteínas , Estabilidade Proteica , Estrutura Terciária de Proteína , Eletricidade Estática , Relação Estrutura-Atividade , Termodinâmica
19.
Sensors (Basel) ; 19(13)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31266148

RESUMO

The paper highlights some of the significant works done in the field of medical and biomedical sensing using silicon-based technology. The use of silicon sensors is one of the pivotal and prolonged techniques employed in a range of healthcare, industrial and environmental applications by virtue of its distinct advantages over other counterparts in Microelectromechanical systems (MEMS) technology. Among them, the sensors for biomedical applications are one of the most significant ones, which not only assist in improving the quality of human life but also help in the field of microfabrication by imparting knowledge about how to develop enhanced multifunctional sensing prototypes. The paper emphasises the use of silicon, in different forms, to fabricate electrodes and substrates for the sensors that are to be used for biomedical sensing. The electrical conductivity and the mechanical flexibility of silicon vary to a large extent depending on its use in developing prototypes. The article also explains some of the bottlenecks that need to be dealt with in the current scenario, along with some possible remedies. Finally, a brief market survey is given to estimate a probable increase in the usage of silicon in developing a variety of biomedical prototypes in the upcoming years.


Assuntos
Técnicas Biossensoriais , Nanofios/química , Silício/química , Pesquisa Biomédica/métodos , Eletrodos , Humanos , Microtecnologia
20.
Sensors (Basel) ; 19(7)2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974757

RESUMO

This paper showcases a substantial review on some of the significant work done on 3D printing of sensors for biomedical applications. The importance of 3D printing techniques has bloomed in the sensing world due to their essential advantages of quick fabrication, easy accessibility, processing of varied materials and sustainability. Along with the introduction of the necessity and influence of 3D printing techniques for the fabrication of sensors for different healthcare applications, the paper explains the individual methodologies used to develop sensing prototypes. Six different 3D printing techniques have been explained in the manuscript, followed by drawing a comparison between them in terms of their advantages, disadvantages, materials being processed, resolution, repeatability, accuracy and applications. Finally, a conclusion of the paper is provided with some of the challenges of the current 3D printing techniques about the developed sensing prototypes, their corresponding remedial solutions and a market survey determining the expenditure on 3D printing for biomedical sensing prototypes.


Assuntos
Pesquisa Biomédica/tendências , Técnicas Biossensoriais/tendências , Impressão Tridimensional/tendências , Humanos
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