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1.
Mol Cell ; 83(21): 3852-3868.e6, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37852256

RESUMO

The Chaperonin Containing Tailless polypeptide 1 (CCT) complex is an essential protein folding machine with a diverse clientele of substrates, including many proteins with ß-propeller domains. Here, we determine the structures of human CCT in complex with its accessory co-chaperone, phosducin-like protein 1 (PhLP1), in the process of folding Gß5, a component of Regulator of G protein Signaling (RGS) complexes. Cryoelectron microscopy (cryo-EM) and image processing reveal an ensemble of distinct snapshots that represent the folding trajectory of Gß5 from an unfolded molten globule to a fully folded ß-propeller. These structures reveal the mechanism by which CCT directs Gß5 folding through initiating specific intermolecular contacts that facilitate the sequential folding of individual ß sheets until the propeller closes into its native structure. This work directly visualizes chaperone-mediated protein folding and establishes that CCT orchestrates folding by stabilizing intermediates through interactions with surface residues that permit the hydrophobic core to coalesce into its folded state.


Assuntos
Proteínas de Ligação ao GTP , Chaperonas Moleculares , Humanos , Microscopia Crioeletrônica , Chaperonas Moleculares/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Dobramento de Proteína , Transdução de Sinais , Chaperoninas
2.
J Biol Chem ; 299(1): 102782, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36502920

RESUMO

Lactones are prevalent in biological and industrial settings, yet there is a lack of information regarding enzymes used to metabolize these compounds. One compound, γ-valerolactone (GVL), is used as a solvent to dissolve plant cell walls into sugars and aromatic molecules for subsequent microbial conversion to fuels and chemicals. Despite the promise of GVL as a renewable solvent for biomass deconstruction, residual GVL can be toxic to microbial fermentation. Here, we identified a Ca2+-dependent enzyme from Rhodopseudomonas palustris (Rpa3624) and showed that it can hydrolyze aliphatic and aromatic lactones and esters, including GVL. Maximum-likelihood phylogenetic analysis of other related lactonases with experimentally determined substrate preferences shows that Rpa3624 separates by sequence motifs into a subclade with preference for hydrophobic substrates. Additionally, we solved crystal structures of this ß-propeller enzyme separately with either phosphate, an inhibitor, or a mixture of GVL and products to define an active site where calcium-bound water and calcium-bound aspartic and glutamic acid residues make close contact with substrate and product. Our kinetic characterization of WT and mutant enzymes combined with structural insights inform a reaction mechanism that centers around activation of a calcium-bound water molecule promoted by general base catalysis and close contacts with substrate and a potential intermediate. Similarity of Rpa3624 with other ß-propeller lactonases suggests this mechanism may be relevant for other members of this emerging class of versatile catalysts.


Assuntos
Lactonas , Rodopseudomonas , Cálcio , Catálise , Lactonas/química , Filogenia , Solventes/química , Especificidade por Substrato , Água/química
3.
BMC Genomics ; 25(1): 269, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468205

RESUMO

BACKGROUND: Polymorphisms of Plasmodium falciparum chloroquine resistance transporter (pfcrt), Plasmodium falciparum multi-drug resistance 1 (pfmdr1) and Plasmodium falciparum kelch 13-propeller (pfk13) genes are accepted as valid molecular markers of quinoline antimalarials and artemisinins. This study investigated the distribution patterns of these genes in P. falciparum isolates from the areas along the Thai-Myanmar border during the two different periods of antimalarial usage in Thailand. RESULTS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to detect pfcrt mutations at codons 76, 220, 271, 326, 356, and 371 as well as pfmdr1 mutation at codon 86. The prevalence of pfcrt mutations was markedly high (96.4-99.7%) in samples collected during both periods. The proportions of mutant genotypes (number of mutant/total isolate) at codons 76, 220, 271, 326, 356 and 371 in the isolates collected during 1993-1998 (period 1) compared with 2002-2008 (period 2) were 97.9% (137/140) vs. 97.1% (401/413), 97.9% (140/143) vs. 98.8% (171/173), 97.2% (139/143) vs. 97.1% (333/343), 98.6% (140/142) vs. 99.7% (385/386), 96.4% (134/139) vs. 98.2% (378/385) and 97.8% (136/139) vs. 98.9% (375/379), respectively. Most isolates carried pfmdr1 wild-type at codon 86, with a significant difference in proportions genotypes (number of wild type/total sample) in samples collected during period 1 [92.9% (130/140)] compared with period 2 [96.9% (379/391)]. Investigation of pfmdr1 copy number was performed by real-time PCR. The proportions of isolates carried 1, 2, 3 and 4 or more than 4 copies of pfmdr1 (number of isolates carried correspondent copy number/total isolate) were significantly different between the two sample collecting periods (65.7% (90/137) vs. 87.8% (390/444), 18.2% (25/137) vs. 6.3%(28/444), 5.1% (7/137) vs. 1.4% (6/444) and 11.0% (15/137) vs. 4.5% (20/444), for period 1 vs. period 2, respectively). No pfk13 mutation was detected by nested PCR and nucleotide sequencing in all samples with successful analysis (n = 68). CONCLUSIONS: The persistence of pfcrt mutations and pfmdr1 wild-types at codon 86, along with gene amplification in P. falciparum, contributes to the continued resistance of chloroquine and mefloquine in P. falciparum isolates in the study area. Regular surveillance of antimalarial drug resistance in P. falciparum, incorporating relevant molecular markers and treatment efficacy assessments, should be conducted.


Assuntos
Antimaláricos , Malária Falciparum , Humanos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Plasmodium falciparum , Tailândia , Mianmar , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Falciparum/genética , Resistência a Medicamentos/genética , Reação em Cadeia da Polimerase em Tempo Real , Biomarcadores , Proteínas de Protozoários/genética , Códon
4.
Magn Reson Med ; 91(6): 2546-2558, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38376096

RESUMO

PURPOSE: We aimed to develop a free-breathing (FB) cardiac DTI (cDTI) method based on short-axis PROPELLER (SAP) and M2 motion compensated spin-echo EPI (SAP-M2-EPI) to mitigate geometric distortion and eliminate aliasing in acquired diffusion-weighted (DW) images, particularly in patients with a higher body mass index (BMI). THEORY AND METHODS: The study involved 10 healthy volunteers whose BMI values fell into specific categories: BMI <25 (4 volunteers), 25< BMI <28 (5 volunteers), and BMI >30 (1 volunteer). We compared DTI parameters, including fractional anisotropy (FA), mean diffusivity (MD), and helix angle transmurality (HAT), between SAP-M2-EPI and M2-ssEPI. To evaluate the performance of SAP-M2-EPI in reducing geometric distortions in the left ventricle (LV) compared to CINE and M2-ssEPI, we utilized the DICE similarity coefficient (DSC) and assessed misregistration area. RESULTS: In all volunteers, SAP-M2-EPI yielded high-quality LV DWIs without aliasing, demonstrating significantly reduced geometric distortion (with an average DSC of 0.92 and average misregistration area of 90 mm2) and diminished signal loss due to bulk motion when compared to M2-ssEPI. DTI parameter maps exhibited consistent patterns across slices without motion related artifacts. CONCLUSION: SAP-M2-EPI facilitates free-breathing cDTI of the entire LV, effectively eliminating aliasing and minimizing geometric distortion compared to M2-ssEPI. Furthermore, it preserves accurate quantification of myocardial microstructure.


Assuntos
Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Humanos , Estudos de Viabilidade , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Imagem Ecoplanar/métodos
5.
J Fluoresc ; 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38198012

RESUMO

Synthesis-oriented design led us to the construction of a propeller-like dye, containing the triangle terthiophene and triphenylamine units. It reveals typical photochromic properties with alternated UV (390 nm) and visible light (˃ 440 nm) irradiation and the dye solution (in THF) color was also toggled between yellow-green and colorless. A new absorption band was observed in visible region (415-600 nm). Additionally, the photochromic dye was highly emissive with the absolute quantum yield being 0.27. After UV light irradiation, the emission was quenched significantly (Φ = 0.08) at photo-stationary state, and thus establishing a switchable emission "on-off" system by alternated UV/visible light irradiation cycle. Detailed structural analysis was carried out based on the optimized dye structure. Both the antiparallel conformation and the distance of reactive carbon atoms (< 4.2 Å) led to the smoothly photochromic behavior.

6.
BMC Musculoskelet Disord ; 25(1): 297, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627691

RESUMO

BACKGROUND: The efficacy and safety of perforator-based propeller flaps (PPF) versus free flaps (FF) in traumatic lower leg and foot reconstructions are debated. PPFs are perceived as simpler due to advantages like avoiding microsurgery, but concerns about complications, such as flap congestion and necrosis, persist. This study aimed to compare outcomes of PPF and FF in trauma-related distal lower extremity soft tissue reconstruction. METHODS: We retrospectively studied 38 flaps in 33 patients who underwent lower leg and foot soft tissue reconstruction due to trauma at our hospital from 2015 until 2022. Flap-related outcomes and complications were compared between the PPF group (18 flaps in 15 patients) and the FF group (20 flaps in 18 patients). These included complete and partial flap necrosis, venous congestion, delayed osteomyelitis, and the coverage failure rate, defined as the need for secondary flaps due to flap necrosis. RESULTS: The coverage failure rate was 22% in the PPF group and 5% in the FF group, with complete necrosis observed in 11% of the PPF group and 5% of the FF group, and partial necrosis in 39% of the PPF group and 10% of the FF group, indicating no significant difference between the two groups. However, venous congestion was significantly higher in 72% of the PPF group compared to 10% of the FF group. Four PPFs and one FF required FF reconstruction due to implant/fracture exposure from necrosis. Additionally, four PPFs developed delayed osteomyelitis post-healing, requiring reconstruction using free vascularized bone graft in three out of four cases. CONCLUSIONS: Flap necrosis in traumatic lower-leg defects can lead to reconstructive failure, exposing implants or fractures and potentially causing catastrophic outcomes like osteomyelitis, jeopardizing limb salvage. Surgeons should be cautious about deeming PPFs as straightforward and microsurgery-free procedures, given the increased complication rates compared to FFs in traumatic reconstruction. DATA ACCESS STATEMENT: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.


Assuntos
Traumatismos do Pé , Fraturas Ósseas , Retalhos de Tecido Biológico , Hiperemia , Osteomielite , Lesões dos Tecidos Moles , Humanos , Perna (Membro) , Estudos Retrospectivos , Retalhos de Tecido Biológico/efeitos adversos , Hiperemia/complicações , Extremidade Inferior/cirurgia , Fraturas Ósseas/cirurgia , Fraturas Ósseas/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Lesões dos Tecidos Moles/cirurgia , Lesões dos Tecidos Moles/complicações , Osteomielite/cirurgia , Osteomielite/complicações , Necrose/etiologia , Necrose/cirurgia , Resultado do Tratamento
7.
Ann Chir Plast Esthet ; 69(4): 320-325, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38866679

RESUMO

INTRODUCTION: Fournier's gangrene, a rare infectious condition affecting the external genitalia, often requires aggressive medical-surgical interventions, resulting in variable scrotal tissue loss. Despite numerous proposed reconstruction techniques, achieving a consensus on the most effective approach that balances aesthetics and function remains elusive. This case report presents a one-year follow-up on scrotal reconstruction using a pedicled Superficial Circumflex Iliac Artery Perforator (SCIP) propeller flap. CASE REPORT: A 56-year-old patient with significant scrotal tissue loss due to Fournier's gangrene underwent scrotal reconstruction using a pedicled SCIP propeller flap. Optimal placement was ensured through a subcutaneous tunnel, with a thin thigh skin graft applied to cover the penile skin defect. DISCUSSION: The SCIP flap is distinguished by its thin and pliable characteristics, rapid harvesting and featuring a discreet donor site. It stands as a compelling alternative to skin grafts, providing advantages in sensory restoration, color congruence, and resilience against tension. Considering the thickness of the reconstruction helps both in recovering testicular function and improving the appearance by restoring the natural contour. CONCLUSION: The utilization of the pedicled SCIP propeller flap for scrotal tissue loss resulting from Fournier's gangrene has demonstrated both aesthetic and functional success, underscoring its potential as an effective reconstructive option.


Assuntos
Gangrena de Fournier , Artéria Ilíaca , Retalho Perfurante , Escroto , Humanos , Masculino , Gangrena de Fournier/cirurgia , Escroto/cirurgia , Pessoa de Meia-Idade , Retalho Perfurante/irrigação sanguínea , Artéria Ilíaca/cirurgia , Procedimentos de Cirurgia Plástica/métodos
8.
Ann Chir Plast Esthet ; 69(4): 286-293, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38897881

RESUMO

BACKGROUND: The advent of propeller flaps has permitted new and less invasive coverage solutions for thoracic defects compared to conventional flaps. Through a retrospective analysis of our cases, we would like to show the advantages of the internal mammary artery perforator (IMAP) flap for anterior chest wall reconstruction. METHODS: We included patients who underwent anterior chest wall reconstruction with an IMAP propeller flap in the Toulouse University Hospital's plastic surgery department from January 2019 to December 2022. The data were collected on patient data, skin defects, and flap characteristics. RESULTS: Twenty-three IMAP flaps were realized to cover locoregional defects. The skin paddle size of the IMAP flap averaged 15.6cm long (12-20)×6.7cm wide (4-10). The average arc of rotation of the flap was 113.5° (range 70-140°). In 3 cases, the IMAP flap was performed with a superior epigastric artery perforator flap (SEAP). In 3 cases out of 23, the flap partially necrotized, requiring surgical revision. In 1 case, the flap was fully necrotized and had to be removed. DISCUSSION AND CONCLUSION: Our series of 23 IMAP flaps on thoracic reconstruction is one of the largest published to date. Our series shows that the IMAP flap offers a simple and reliable solution with minor donor site morbidity for reconstructing small to medium-sized defects in the medial and paramedian regions of the chest wall.


Assuntos
Artéria Torácica Interna , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Parede Torácica , Humanos , Retalho Perfurante/irrigação sanguínea , Parede Torácica/cirurgia , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Masculino , Artéria Torácica Interna/cirurgia , Idoso , Procedimentos de Cirurgia Plástica/métodos , Adulto
9.
J Cell Biochem ; 124(7): 989-1001, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37210732

RESUMO

Mutations in the αIIb ß-propeller domain have long been known to disrupt heterodimerization and intracellular trafficking of αIIbß3 complexes leading to diminished surface expression and/or function, resulting in Glanzmann thrombasthenia. Our previous study on three ß-propeller mutations, namely G128S, S287L, and G357S, showed variable defects in protein transport correlated with the patient's clinical phenotypes. Pulse-chase experiments revealed differences in αIIbß3 complex maturation among the three mutations. Hence, the current study aims to correlate conformational changes caused by each one of them. Evolutionary conservation analysis, stability analysis, and molecular dynamics simulations of the three mutant structures were carried out. Stability analysis revealed that, while G128S and G357S mutations destabilized the ß-propeller structure, S287L retained the stability. Wild-type and mutant ß-propeller structures, when subjected to molecular dynamics simulations, confirmed that G128S and G357S were both destabilizing in nature when compared with the wild-type and S287L based on several parameters studied, like RMSD, RMSF, Rg, FEL, PCA, secondary structure, and hydrogen bonds. In our previous study, we demonstrated that mutant S287L αIIbß3 complexes were more stable than the wild-type αIIbß3 complexes, as evidenced in pulse-chase experiments. These findings corroborate variable intracellular fates of mutant αIIbß3 complexes as a result of these ß-propeller mutations.


Assuntos
Integrina alfa2 , Integrina beta3 , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Trombastenia , Humanos , Integrina beta3/genética , Simulação de Dinâmica Molecular , Mutação , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/genética , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Estrutura Secundária de Proteína , Trombastenia/genética , Trombastenia/metabolismo , Integrina alfa2/genética , Integrina alfa2/metabolismo
10.
Magn Reson Med ; 90(6): 2454-2471, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37486854

RESUMO

PURPOSE: To develop a distortion-free motion-resolved four-dimensional diffusion-weighted PROPELLER EPI (4D-DW-PROPELLER-EPI) technique for benefiting clinical abdominal radiotherapy (RT). METHODS: An improved abdominal 4D-DWI technique based on 2D diffusion-weighted PROPELLER-EPI (2D-DW-PROPELLER-EPI), termed 4D-DW-PROPELLER-EPI, was proposed to improve the frame rate of repeated data acquisition and produce distortion-free 4D-DWI images. Since the radial or PROPELLER sampling with golden-angle rotation can achieve an efficient k-space coverage with a flexible time-resolved acquisition, the golden-angle multi-blade acquisition was used in the proposed 4D-DW-PROPELLER-EPI to improve the performance of data sorting. A new k-space and blade (K-B) amplitude binning method was developed for the proposed 4D-DW-PROPELLER-EPI to optimize the number of blades and the k-space uniformity before performing conventional PROPELLER-EPI reconstruction, by using two metrics to evaluate the adequacy of the acquired data. The proposed 4D-DW-PROPELLER-EPI was preliminarily evaluated in both simulation experiments and in vivo experiments with varying frame rates and different numbers of repeated acquisition. RESULTS: The feasibility of achieving distortion-free 4D-DWI images by using the proposed 4D-DW-PROPELLER-EPI technique was demonstrated in both digital phantom and healthy subjects. Evaluation of the 4D completeness metrics shows that the K-B amplitude binning method could simultaneously improve the acquisition efficiency and data reconstruction performance for 4D-DW-PROPELLER-EPI. CONCLUSION: 4D-DW-PROPELLER-EPI with K-B amplitude binning is an advanced technique that can provide distortion-free 4D-DWI images for resolving respiratory motion, and may benefit the application of image-guided abdominal RT.


Assuntos
Abdome , Imagem de Difusão por Ressonância Magnética , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Abdome/diagnóstico por imagem , Rotação , Simulação por Computador , Imagens de Fantasmas , Imagem Ecoplanar/métodos
11.
Am J Med Genet A ; 191(5): 1384-1387, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36750760

RESUMO

Beta-propeller protein-associated neurodegeneration (BPAN), a subgroup of neurodegeneration with brain iron accumulation, is typically characterized by non-progressive global developmental delay and seizures in childhood, followed by progressive neurological decline with parkinsonism and dementia in adolescence or early adulthood. It is difficult to clinically identify a patient with BPAN in childhood. Recent studies reported that serum levels of neuron-specific enolase (NSE) were elevated in children with BPAN. We reviewed the time course of serum NSE levels in a 21-year-old female patient genetically diagnosed (a de novo WDR45 variant c.268A > T) with BPAN, which was suspected based on prolonged elevation of serum NSE. There was an overall tendency for serum NSE levels to decrease in a stepwise fashion. The peak serum NSE level was observed during the first 2 years of age and then decreased rapidly in 1 year. High serum NSE levels persisted between 3 and 11 years of age. Subsequently, serum NSE levels decreased and plateaued after 13 years of age. There were tendencies for both blood AST and LDH levels to decrease over time in parallel with serum NSE levels. Serum NSE levels may be a diagnostic biomarker of BPAN in children but becomes of less value in identifying a patient with BPAN after childhood.


Assuntos
Distúrbios do Metabolismo do Ferro , Distrofias Neuroaxonais , Criança , Adolescente , Humanos , Feminino , Lactente , Adulto , Adulto Jovem , Proteínas de Transporte , Distrofias Neuroaxonais/diagnóstico , Distrofias Neuroaxonais/genética , Fosfopiruvato Hidratase/genética , Convulsões
12.
Malar J ; 22(1): 87, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36894982

RESUMO

BACKGROUND: Currently, chemotherapy stands out as the major malaria intervention strategy, however, anti-malarial resistance may hamper global elimination programs. Artemisinin-based combination therapy (ACT) stands as the drug of choice for the treatment of Plasmodium falciparum malaria. Plasmodium falciparum kelch13 gene mutations are associated with artemisinin resistance. Thus, this study was aimed at evaluating the circulation of P. falciparum k13 gene polymorphisms from Kisii County, Kenya during an era of ACT deployment. METHODS: Participants suspected to have malaria were recruited. Plasmodium falciparum was confirmed using the microscopy method. Malaria-positive patients were treated with artemether-lumefantrine (AL). Blood from participants who tested positive for parasites after day 3 was kept on filter papers. DNA was extracted using chelex-suspension method. A nested polymerase chain reaction (PCR) was conducted and the second-round products were sequenced using the Sanger method. Sequenced products were analysed using DNAsp 5.10.01 software and then blasted on the NCBI for k13 propeller gene sequence identity using the Basic Local Alignment Search Tool (BLAST). To assess the selection pressure in P. falciparum parasite population, Tajima' D statistic and Fu & Li's D test in DnaSP software 5.10.01 was used. RESULTS: Out of 275 enrolled participants, 231 completed the follow-up schedule. 13 (5.6%) had parasites on day 28 hence characterized for recrudescence. Out of the 13 samples suspected of recrudescence, 5 (38%) samples were positively amplified as P. falciparum, with polymorphisms in the k13-propeller gene detected. Polymorphisms detected in this study includes R539T, N458T, R561H, N431S and A671V, respectively. The sequences have been deposited in NCBI with bio-project number PRJNA885380 and accession numbers SAMN31087434, SAMN31087433, SAMN31087432, SAMN31087431 and SAMN31087430 respectively. CONCLUSIONS: WHO validated polymorphisms in the k13-propeller gene previously reported to be associated with ACT resistance were not detected in the P. falciparum isolates from Kisii County, Kenya. However, some previously reported un-validated k13 resistant single nucleotide polymorphisms were reported in this study but with limited occurrences. The study has also reported new SNPs. More studies need to be carried out in the entire country to understand the association of reported mutations if any, with ACT resistance.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Humanos , Plasmodium falciparum , Antimaláricos/uso terapêutico , Antimaláricos/farmacologia , Artemisininas/uso terapêutico , Quênia , Combinação Arteméter e Lumefantrina/uso terapêutico , Proteínas de Protozoários/genética , Proteínas de Protozoários/uso terapêutico , Artemeter/uso terapêutico , Malária Falciparum/epidemiologia , Polimorfismo de Nucleotídeo Único , Resistência a Medicamentos/genética
13.
BMC Infect Dis ; 23(1): 801, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974079

RESUMO

Malaria is a significant global health concern, with a majority of cases in Sub-Saharan African nations. Numerous antimalarial drugs have been developed to counter the rampant prevalence of Plasmodium falciparum malaria. Artemisinin-based Combination Therapy (ACT) has served as the primary treatment of uncomplicated malaria in Ghana since 2005. However, a growing concern has emerged due to the escalating reports of ACT resistance, particularly in Southeast Asia, and its encroachment into Africa. Specifically, mutations in the Kelch propeller domain on chromosome 13 (Pfk13) have been linked to ACT resistance. Yet, our understanding of mutation prevalence in Africa remains largely uncharted. In this study, we compared Pfk13 sequences obtained from 172 P. falciparum samples across three ecological and transmission zones in Ghana. We identified 27 non-synonymous mutations among these sequences, of which two of the mutations, C580Y (found in two samples from the central region) and Y493H (found in one sample from the north), had previously been validated for their association with artemisinin resistance, a phenomenon widespread in Southeast Asia. The Pfk13 gene diversity was most pronounced in the northern savannah than the central forest and south coastal regions, where transmission rates are lower. The observed mutations were not significantly associated with geographical regions, suggesting a frequent spread of mutations across the country. The ongoing global surveillance of artemisinin resistance remains pivotal, and our findings provides insights into the potential spread of resistant parasites in West Africa. Furthermore, the identification of novel codon mutations in this study raises their potential association to ACT resistance, warranting further investigation through in vitro assays to ascertain their functional significance.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Humanos , Plasmodium falciparum/genética , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Gana/epidemiologia , Resistência a Medicamentos/genética , Proteínas de Protozoários/genética , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Polimorfismo Genético , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Mutação
14.
Sensors (Basel) ; 23(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36617131

RESUMO

Grass cutting is necessary to prevent grass from diverting essential nutrients and water from crops. Usually, in hilly and mountainous areas, grass cutting is performed on steep slopes with an inclination angle of up to 60° (inclination gradient of 173%). However, such grass cutting tasks are dangerous owing to the unstable positioning of workers. For robots to perform these grass cutting tasks, slipping and falling must be prevented on inclined surfaces. In this study, a robot based on stable propeller control and four-wheel steering was developed to provide stable locomotion during grass cutting tasks. The robot was evaluated in terms of locomotion for different steering methods, straight motion on steep slopes, climbing ability, and coverage area. The results revealed that the robot was capable of navigating uneven terrains with steep slope angles. Moreover, no slipping actions that could have affected the grass cutting operations were observed. We confirmed that the proposed robot is able to cover 99.95% and 98.45% of an area on a rubber and grass slope, respectively. Finally, the robot was tested on different slopes with different angles in hilly and mountainous areas. The developed robot was able to perform the grass cutting task as expected.


Assuntos
Robótica , Humanos , Poaceae , Locomoção , Água , Movimento (Física)
15.
Sensors (Basel) ; 23(21)2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37960655

RESUMO

Vessels frequently encounter challenging marine conditions that expose the propeller-hull to corrosive water and marine fouling. These challenges necessitate innovative approaches to optimize propeller-hull performance. This study aims to assess a method for predicting propeller-hull degradation. The proposed solution revolves around an innovative Key Performance Indicator (KPI) based on Artificial Neural Networks (ANNs). Our objective is to validate the findings; thus, a thorough comparison is conducted between the proposed method and the baseline solution derived from the ISO-19030. Emphasis is placed on determining the optimal parameters for computing the KPI, which involves applying various features, filters, and pre-processing techniques. The proposed method is tested on real data collected by an Internet of Things (IoT) system installed in different types of vessels. Four distinct experiments with ANNs are conducted. Results demonstrate that the ANN-based indicator offers greater accuracy in predicting propeller-hull degradation compared to the baseline method. Additionally, it is demonstrated that selecting a diverse set of features and implementing consistent filtering and preprocessing techniques enhance the performance of the traditional indicator. The utilization of Deep Learning (DL) in the maritime industry is of great significance, as it enables a comprehensive and dynamic assessment of predictive maintenance of the propeller-hull. The DL index method holds potential for diverse maintenance applications, providing a holistic platform with anticipated environmental and financial benefits.

16.
Sensors (Basel) ; 23(12)2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37420900

RESUMO

Lubricated tribosystems such as main-shaft bearings in gas turbines have been successfully diagnosed by oil sampling for many years. In practice, the interpretation of wear debris analysis results can pose a challenge due to the intricate structure of power transmission systems and the varying degrees of sensitivity among test methods. In this work, oil samples acquired from the fleet of M601T turboprop engines were tested with optical emission spectrometry and analyzed with a correlative model. Customized alarm limits were determined for iron by binning aluminum and zinc concentration into four levels. Two-way analysis of variance (ANOVA) with interaction analysis and post hoc tests was carried out to study the impact of aluminum and zinc concentration on iron concentration. A strong correlation between iron and aluminum, as well as a weaker but still statistically significant correlation between iron and zinc, was observed. When the model was applied to evaluate a selected engine, deviations of iron concentration from the established limits indicated accelerated wear long before the occurrence of critical damage. Thanks to ANOVA, the assessment of engine health was based on a statistically proven correlation between the values of the dependent variable and the classifying factors.


Assuntos
Alumínio , Zinco
17.
Molecules ; 28(3)2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36770913

RESUMO

A series of OLED-relevant compounds, consisting of 1,3,5-triazine core linked to various aromatic arms by amino group, has been synthesized and characterized. The studied compounds exist in solution as a mixture of two conformers, a symmetric propeller and asymmetric conformer, in which one of the aromatic arms is rotated around the C-N bond. At temperatures below -40 °C, the VT NMR spectra in DMF-d7 are in a slow exchange regime, and the signals of two conformers can be elucidated. At temperatures above 100 °C, the VT NMR spectra in DMSO-d6 are in a fast exchange regime, and the averaged spectra can be measured. The ratio of symmetric and asymmetric conformers in DMF-d7 varies from 14:86 to 50:50 depending on the substituents. The rotational barriers of symmetric and asymmetric conformers in DMF-d7 were measured for all compounds and are in the interval from 11.7 to 14.7 kcal/mol. The ground-state energy landscapes of the studied compounds, obtained by DFT calculations, show good agreement with the experimental rotational barriers. The DFT calculations reveal that the observed chemical exchange occurs by the rotation around the C(1,3,5-triazine)-N bond. Although some of the compounds are potentially tautomeric, the measured absorption and emission spectra do not indicate proton transfer neither in the ground nor in the excited state.

18.
Acta Chir Plast ; 65(1): 20-27, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37211420

RESUMO

INTRODUCTION: Lower extremity wounds have always been a challenge for the reconstructive surgeons. Free perforator flaps are considered to be the best option for this problem but require the complexity of microsurgery. So, pedicled perforator flaps have emerged as an alternative option. PATIENTS AND METHODS: Prospective study was conducted in 40 patients with traumatic soft tissue defects in the leg and foot. The free flaps included the anterolateral thigh flap (ALT) and medial sural artery perforator flap (MSAP). In pedicled perforator flaps group, 10 cases were designed as propeller flaps while the other 10 flaps were designed as perforator plus flaps. RESULTS: Free flaps were mainly used for large-sized defects; we had one case of partial flap loss and one case of complete flap necrosis.  MSAP flap was the first option for coverage of large-sized defects on foot and ankle as it is a thin and pliable flap, while ALT flap was used for coverage of larger defects on the leg. Pedicled perforator flaps were used mainly for small to medium-sized defects, especially in the lower third of the leg; we had three cases of flap loss in propeller flap design while we had no cases of flap loss in perforator plus flap. CONCLUSION: Perforator flaps have become a reasonable solution for soft tissue defects of the lower extremity. Careful assessment of the dimensions, location, patient comorbidities, availability of surrounding soft tissue and presence of adequate perforators are mandatory for proper perforator flap selection.


Assuntos
Retalho Perfurante , Lesões dos Tecidos Moles , Humanos , Retalho Perfurante/irrigação sanguínea , Perna (Membro)/irrigação sanguínea , Perna (Membro)/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Extremidade Inferior , Complicações Pós-Operatórias , Lesões dos Tecidos Moles/cirurgia
19.
Indian J Plast Surg ; 56(4): 373-377, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37705822

RESUMO

Propeller flaps are effective reconstructive tools for small-to-medium sized defects of the lower limb and a reasonable alternative to free flaps. A major vessel of the lower limb remains undisturbed while raising the flap and the flap donor and recipient areas are addressed in the same operative field. Perforator-based propeller flaps are based on single perforator arising from a major vessel and during rotation of the larger paddle there is a possibility of kink in the venous component leading to congestion of flap. In our modification, one superficial vein of the lower limb namely the great saphenous or short saphenous vein was included in the flap territory to enhance the retrograde or antegrade venous drainage of the flap. We observed, no flap congestion or necrosis in the postoperative period. Also, the patency of the incorporated vein was confirmed using handheld and color Doppler.

20.
Angew Chem Int Ed Engl ; 62(33): e202305404, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37221132

RESUMO

Organic circularly polarized luminescence (CPL)-active molecular emitters featuring dynamic propeller-like luminophores were prepared in one step from cyclic(alkyl)(amino) carbenes (CAACs). These molecules exhibit through-space arene-arene π-delocalization and rapid intramolecular inter-system crossing (ISC) in line with their helical character.

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