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2.
ACS Nanosci Au ; 4(4): 235-242, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39184832

RESUMO

Although chemical promotion led to essential improvements in Cu-based catalysts for CO2 hydrogenation to methanol, surpassing structural limitations such as active phase aggregation under reaction conditions remains challenging. In this report, we improved the textural properties of Cu/In2O3/CeO2 and Cu/In2O3/ZrO2 catalysts by coating the nanoparticles with a mesoporous SiO2 shell. This strategy limited particle size up to 3.5 nm, increasing metal dispersion and widening the metal-metal oxide interface region. Chemometric analysis revealed that these structures could maintain high activity and selectivity in a wide range of reaction conditions, with methanol space-time yields up to 4 times higher than those of the uncoated catalysts.

3.
Genet Mol Biol ; 47(3): e20230350, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39158377

RESUMO

ATP-binding cassette (ABC) transporters, including P-glycoproteins (PGP), have been implicated in drug resistance in different organisms including Haemonchus contortus. This study confirmed the resistance status of H. contortus isolates selected for ivermectin (IVM) and oxfendazole (OXF) resistances using the fecal egg count reduction test and evaluated the gene expression of seven ABC transporters using RT-qPCR for two biological scenarios: the effect of selection for anthelmintic resistance and the effect of drug exposure on gene expression. Gene expression results showed that selection for IVM resistance led to the significant upregulation of Hco-pgp-9a (1.5-fold), Hco-pgp-11 (3-fold) and Hco-haf-9 (1.5-fold) (p < 0.05). Similarly, selection for OXF resistance led to the significant upregulation of Hco-pgp-9a (3-fold), Hco-pgp-11 (4-fold) and Hco-haf-9 (2-fold) when comparing with the unselected ISE isolate (p < 0.05). Exposure of selected isolates to anthelmintics lead to no significant upregulation of the studied transporter genes. We also observed instances where there was strong intragroup variation regarding samples originating from parasites obtained from different individual hosts pointing that the interactions of the animal host with the tested anthelmintics may also play a role in the expression of the studied nematode genes.

4.
Nat Biomed Eng ; 8(7): 842-853, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39085646

RESUMO

Many antimicrobial peptides directly disrupt bacterial membranes yet can also damage mammalian membranes. It is therefore central to their therapeutic use that rules governing the membrane selectivity of antimicrobial peptides be deciphered. However, this is difficult even for short peptides owing to the large combinatorial space of amino acid sequences. Here we describe a method for measuring the loss or maintenance of antimicrobial-peptide activity for thousands of peptide-sequence variants simultaneously, and its application to Protegrin-1, a potent yet toxic antimicrobial peptide, to determine the positional importance and flexibility of residues across its sequence while identifying variants with changes in membrane selectivity. More bacterially selective variants maintained a membrane-bound secondary structure while avoiding aromatic residues and cysteine pairs. A machine-learning model trained with our datasets accurately predicted membrane-specific activities for over 5.7 million Protegrin-1 variants, and identified one variant that showed substantially reduced toxicity and retention of activity in a mouse model of intraperitoneal infection. The high-throughput methodology may help elucidate sequence-structure-function relationships in antimicrobial peptides and inform the design of peptide-based synthetic drugs.


Assuntos
Peptídeos Catiônicos Antimicrobianos , Aprendizado de Máquina , Animais , Camundongos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/genética , Sequência de Aminoácidos , Mutação , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/química , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Feminino
5.
Rev Bras Ortop (Sao Paulo) ; 59(3): e409-e414, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38911877

RESUMO

Objective To identify the location of the Riché-Cannieu anastomosis (RCA) in relation to the Cardinal Kaplan Line (KCL) and the Y line. Methods A total of 20 hands of 10 recently-deceased adult male cadavers aged between 27 and 66 years were dissected for the investigation of the relationship of the most distal point of the RCA with the KCL and with the Y line, drawn from the axis of the third metacarpal head, following the longitudinal axis of the hand. Results In 20 limbs, the most distal point of the nerve communication was positioned distally in relation to the KCL. The Y line was positioned on the radial side in relation to the most distal point of the RCA in 14 limbs, and it was positioned on the ulnar side in relation to the Y line in 6 limbs. The crossing between the KCL and the Y line occurred proximal to the RCA in 18 limbs; in 1 hand, it was positioned distal to the intersection between these lines; and in another hand, the KCL was positioned exactly on the RCA. Conclusion Knowledge of these anatomical relationships can prevent damage to nerve branches and thus also prevent paralysis of intrinsic muscles in surgical procedures in the palm of the hand.

6.
Rev. bras. ortop ; 59(3): 409-414, May-June 2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1569751

RESUMO

Abstract Objective To identify the location of the Riché-Cannieu anastomosis (RCA) in relation to the Cardinal Kaplan Line (KCL) and the Y line. Methods A total of 20 hands of 10 recently-deceased adult male cadavers aged between 27 and 66 years were dissected for the investigation of the relationship of the most distal point of the RCA with the KCL and with the Y line, drawn from the axis of the third metacarpal head, following the longitudinal axis of the hand. Results In 20 limbs, the most distal point of the nerve communication was positioned distally in relation to the KCL. The Y line was positioned on the radial side in relation to the most distal point of the RCA in 14 limbs, and it was positioned on the ulnar side in relation to the Y line in 6 limbs. The crossing between the KCL and the Y line occurred proximal to the RCA in 18 limbs; in 1 hand, it was positioned distal to the intersection between these lines; and in another hand, the KCL was positioned exactly on the RCA. Conclusion Knowledge of these anatomical relationships can prevent damage to nerve branches and thus also prevent paralysis of intrinsic muscles in surgical procedures in the palm of the hand.


Resumo Objetivo Identificar a localização da anastomose de Riché-Cannieu (ARC) em relação à linha cardinal de Kaplan (LCK) e à linha Y. Métodos Ao todo, 20 mãos de 10 cadáveres adultos do sexo masculino com idades entre 27 e 66 anos, recentemente falecidos, foram dissecadas para a investigação da relação do ponto mais distal da ARC com a LCK e a linha Y traçada a partir do eixo da cabeça do terceiro metacarpo seguindo o eixo longitudinal da mão. Resultados Nos 20 membros, o ponto mais distal da comunicação nervosa era distal à LCK. A linha Y estava no lado radial em relação ao ponto mais distal da ARC em 14 membros, e no lado ulnar em relação à linha Y em 6 membros. O cruzamento entre a LCK e a linha Y foi proximal à ARC em 18 membros; em 1 mão, era distal à intersecção entre essas linhas e, em outra mão, a LCK estava exatamente na ARC. Conclusão O conhecimento dessas relações anatômicas pode prevenir danos aos ramos nervosos e, assim, também prevenir a paralisia dos músculos intrínsecos em procedimentos cirúrgicos na palma da mão.

7.
Int. j. morphol ; 42(3): 623-630, jun. 2024. ilus
Artigo em Inglês | LILACS | ID: biblio-1564600

RESUMO

SUMMARY: The objective of this study was to analyze the potential for compression of the median nerve (MN) caused by the bicipital aponeurosis (BA), the humeral and ulnar heads of the pronator teres muscle (PTM) and the arcade of the flexor digitorum superficialis muscle (FDS) in recently deceased cadavers. In this analysis 20 forearms of 10 recently deceased adult male cadavers were dissected. Dissections were performed in the institution's autopsy room or anatomy laboratory. The short and long heads of the biceps brachii muscle, as well as the BA were identified in all upper upper limbs. The BA received contribution from the short and long heads of the biceps brachii muscle. In 12 upper limbs the BA was wide and thickened and in 8 it was supported by the MN. In 5 upper limbs, the BA was wide but not very thick, and in 3 it was narrow and not very thick. We identified the existence of the FDS muscle arcade in all dissected upper limbs. A fibrous arcade was identified in 4 forearms, a muscular arcade in 14 and a transparent arcade in 2 upper limbs. In all of them, we recorded that the arcade was in contact with the MN. We recorded the humeral and ulnar heads of the PTM in all dissected upper limbs, with the presence of fibrous beams between them along their entire length. The MN was positioned between the humeral and ulnar heads of the PTM in all upper limbs. In eight upper limbs (40 %), we identified that the BA had thickness and contact with the MN with the potential to cause its compression. Compression between the humeral and ulnar heads of the PTM by the fibrous connections has the potential to cause nerve compression in all upper limbs (100 %). We did not identify that the anatomical structure of the FDS arcade had the potential to cause compression in the MN.


El objetivo de este estudio fue analizar la potencial compresión del nervio mediano (NM) causado por la aponeurosis bicipital (AB), las cabezas humeral y cubital del músculo pronador redondo (MPR) y la arcada del músculo flexor superficial de los dedos (MFS). En este análisis se diseccionaron 20 antebrazos de 10 cadáveres masculinos de individuos adultos fallecidos recientemente. Las disecciones se realizaron en la sala de autopsias o en el laboratorio de anatomía de la Institución. En todos los miembros superiores se identificaron las cabezas corta y larga del músculo bíceps braquial, así como la AB. La AB recibió contribución de las cabezas corta y larga del músculo bíceps braquial. En 12 miembros superiores la AB era ancha y engrosada y en 8 estaba sostenida por el NM. En 5 miembros superiores la AB era ancha pero poco gruesa, y en 3 era estrecha y de menor grosor. Identificamos la existencia de la arcada muscular MFS en todos los miembros superiores disecados. Se identificó una arcada fibrosa en 4 antebrazos, una arcada muscular en 14 y una arcada delgada y transparente en 2 miembros superiores. En todos ellos registramos que la arcada estaba en contacto con el NM. Registramos las cabezas humeral y cubital del MPR en todos los miembros superiores disecados, con presencia de haces fibrosos entre ellas en toda su longitud. El NM estaba situado entre las cabezas humeral y cubital del MPR en todos los miembros superiores. En ocho miembros superiores (40 %), identificamos que la AB era gruesa y tenía contacto con el NM con potencial para causar su compresión. La compresión entre las cabezas humeral y ulnar del MPR, por las conexiones fibrosas, tiene el potencial de causar compresión nerviosa en todos los miembros superiores (100 %). No identificamos que la estructura anatómica de la arcada MFS tuviera el potencial de causar compresión del NM.


Assuntos
Humanos , Masculino , Adulto , Antebraço , Nervo Mediano , Anormalidades Musculoesqueléticas , Síndromes de Compressão Nervosa/patologia , Cadáver , Dissecação , Cotovelo
8.
J Bone Miner Res ; 39(6): 753-764, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38619281

RESUMO

The bone-muscle unit refers to the reciprocal regulation between bone and muscle by mechanical interaction and tissue communication via soluble factors. The RANKL stimulation induces mitochondrial biogenesis and increases the oxidative capacity in osteoclasts and adipocytes. RANKL may bind to the membrane bound RANK or to osteoprotegerin (OPG), a decoy receptor that inhibits RANK-RANKL activation. RANK is highly expressed in skeletal muscle, but the contribution of RANKL to healthy skeletal muscle fiber remains elusive. Here we show that RANKL stimulation in C2C12-derived myotubes induced activation of mitochondrial biogenesis pathways as detected by RNA-seq and western blot. RANKL expanded the mitochondrial reticulum, as shown by mitochondrial DNA quantification and MitoTracker staining, and boosted the spare respiratory capacity. Using MEK and MAPK inhibitors, we found that RANKL signals via ERK and p38 to induce mitochondrial biogenesis. The soleus from OPG-/- and OPG+/- mice showed higher respiratory rates compared to C57BL6/J WT mice, which correlates with high serum RANKL levels. RANKL infusion using a mini-osmotic pump in WT mice increased the number of mitochondria, boosted the respiratory rate, increased succinate dehydrogenase activity in skeletal muscle, and improved the fatigue resistance of gastrocnemius. Therefore, our findings reveal a new role of RANKL as an osteokine-like protein that impacts muscle fiber metabolism.


Bone modeling and remodeling are processes intricately related to bone health regulated by the RANKL system. The RANKL is a protein essential for bone resorption. RANKL activates RANK in the cell membrane of osteoclasts and can also bind to osteoprotegerin (OPG), which acts as a soluble decoy receptor. Therefore, the levels of RANKL and OPG determine the degree of osteoclast activation and bone resorption. Bone and muscle mechanically interact for movement as bone is a lever for skeletal muscle to exert force. They also communicate via soluble factors that reciprocally regulate their function. Skeletal muscle fibers express RANK, but the role of RANKL signaling in healthy myotubes was still unknown. Here, we propose that RANKL regulates muscle metabolism by inducing mitochondrial biogenesis. We show that RANKL increases mitochondrial area in myotubes and the expression of mitochondrial markers, boosting the spare respiratory capacity. In mice knockout for OPG, which shows high levels of RANKL and unopposed RANK­RANKL stimulation, we found higher respiratory rates than in the wild-type mice. We also infused a low dose of RANKL in wild-type mice, which is around 10 times lower than the dose to induce osteoporosis, and found increased mitochondrial number and higher respiratory rates in soleus. In the gastrocnemius, we also observed increased phosphorylative respiration and improved resistance to fatigue compared to mice treated with the vehicle solution. Our findings indicate that RANKL regulates both bone and muscle under physiological conditions by inducing mitochondrial biogenesis and oxidative metabolism in skeletal muscle fibers.


Assuntos
Músculo Esquelético , Ligante RANK , Transdução de Sinais , Animais , Ligante RANK/metabolismo , Camundongos , Músculo Esquelético/metabolismo , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Osteoprotegerina/metabolismo , Oxirredução , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Camundongos Knockout , Linhagem Celular , Biogênese de Organelas , Respiração Celular/efeitos dos fármacos , Masculino , Mitocôndrias/metabolismo
9.
Biol Sport ; 41(2): 185-199, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38524823

RESUMO

This descriptive study aimed to investigate the current practices of Portuguese and Brazilian soccer coaches in the design and implementation of small-sided games (SSGs) in soccer. A total of 187 male coaches participated in the online survey, consisting of 82 Portuguese and 105 Brazilian individuals. These coaches held various positions within the technical staff, with 63 serving as head coaches, 38 as assistant coaches, 38 as physical trainers, and 48 in other roles related to the technical staff. Additionally, the participants represented both youth (n = 102) and adult competitive levels (n = 59), along with some who were not currently associated with a specific group. The survey consisted of 32 questions divided into three main sections: (i) the timing of SSG application, (ii) the methods used for applying SSGs, and (iii) the reasons for applying SSGs. The Chi-square test revealed a statistically significant association between nationality and the frequency of SSGs used in training sessions during the pre-season (p = 0.039) and in-season (p < 0.001). Moreover, significant association between nationality and the time allocated to employing SSGs for targeting aerobic training (p < 0.001) was found. There was a significant association between nationality and the weekly frequency of SSGs use for targeting sprint training (p = 0.019). The Chi-square test identified significant associations between nationality and the use of SSGs for targeting technical training (p = 0.002), as well as for tactical training (p = 0.002). In summary, this study underscores that SSGs are primarily employed to enhance aerobic fitness, change of direction, technical skills, and tactical behaviors. Coaches generally favor employing SSGs two to three times a week, with typical sessions lasting between 16 to 30 minutes. Notably, the major discrepancies between nationalities lie in the importance assigned to the use of SSGs. However, in practice, the formats and objectives for implementing SSGs remain relatively similar.

10.
J Imaging Inform Med ; 37(1): 145-150, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38343236

RESUMO

To assess the effect of digital enhancement on the image quality of radiographs obtained with photostimulable phosphor (PSP) plates partially damaged by ambient light. Radiographs of an aluminum step wedge were obtained using the VistaScan and Express systems. Half of the PSP plates was exposed to ambient light for 0, 10, 30, 60, or 90 s before being scanned. The resulting radiographs were exported with and without digital enhancement. Metrics for brightness, contrast, and contrast-to-noise ratio (CNR) were derived, and the ratio of each metric between the exposed-to-light and non-exposed-to-light halves of the radiographs was calculated. The resulting ratios of the radiographs with digital enhancement were subtracted from those without digital enhancement and compared among each other. For the VistaScan system, digital enhancement partially restored brightness, contrast, and CNR. For the Express system, digital enhancement only restored CNR and not the impact of ambient light on brightness and contrast. Specifically, digital enhancement restored 23.48% of brightness for the VistaScan, while percentages below 1% were observed for the Express. Digital enhancement restored 53.25% of image contrast for the VistaScan and 5.79% for the Express; 40.71% of CNR was restored for the VistaScan, and 35% for the Express. Digital enhancement can partially restore the damage caused by ambient light on the brightness and contrast of PSP-based radiographs obtained with the VistaScan, as well as on CNR for the VistaScan and Express systems. The exposure of PSP plates to light can lead to unnecessary retakes and increased patient exposure to X-rays.

11.
Microb Cell Fact ; 23(1): 22, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38229067

RESUMO

BACKGROUND: Trichoderma reesei is an organism extensively used in the bioethanol industry, owing to its capability to produce enzymes capable of breaking down holocellulose into simple sugars. The uptake of carbohydrates generated from cellulose breakdown is crucial to induce the signaling cascade that triggers cellulase production. However, the sugar transporters involved in this process in T. reesei remain poorly identified and characterized. RESULTS: To address this gap, this study used temporal membrane proteomics analysis to identify five known and nine putative sugar transporters that may be involved in cellulose degradation by T. reesei. Docking analysis pointed out potential ligands for the putative sugar transporter Tr44175. Further functional validation of this transporter was carried out in Saccharomyces cerevisiae. The results showed that Tr44175 transports a variety of sugar molecules, including cellobiose, cellotriose, cellotetraose, and sophorose. CONCLUSION: This study has unveiled a transporter Tr44175 capable of transporting cellobiose, cellotriose, cellotetraose, and sophorose. Our study represents the first inventory of T. reesei sugar transportome once exposed to cellulose, offering promising potential targets for strain engineering in the context of bioethanol production.


Assuntos
Celulase , Glucanos , Hypocreales , Trichoderma , Celobiose/metabolismo , Proteoma/metabolismo , Proteínas de Membrana/metabolismo , Celulose/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Saccharomyces cerevisiae/metabolismo , Celulase/metabolismo , Açúcares/metabolismo , Oligossacarídeos/metabolismo , Trichoderma/metabolismo
13.
Res Sq ; 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37790501

RESUMO

Antimicrobial peptides commonly act by disrupting bacterial membranes, but also frequently damage mammalian membranes. Deciphering the rules governing membrane selectivity is critical to understanding their function and enabling their therapeutic use. Past attempts to decipher these rules have failed because they cannot interrogate adequate peptide sequence variation. To overcome this problem, we develop deep mutational surface localized antimicrobial display (dmSLAY), which reveals comprehensive positional residue importance and flexibility across an antimicrobial peptide sequence. We apply dmSLAY to Protegrin-1, a potent yet toxic antimicrobial peptide, and identify thousands of sequence variants that positively or negatively influence its antibacterial activity. Further analysis reveals that avoiding large aromatic residues and eliminating disulfide bound cysteine pairs while maintaining membrane bound secondary structure greatly improves Protegrin-1 bacterial specificity. Moreover, dmSLAY datasets enable machine learning to expand our analysis to include over 5.7 million sequence variants and reveal full Protegrin-1 mutational profiles driving either bacterial or mammalian membrane specificity. Our results describe an innovative, high-throughput approach for elucidating antimicrobial peptide sequence-structure-function relationships which can inform synthetic peptide-based drug design.

14.
Dentomaxillofac Radiol ; 52(8): 20230321, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37870152

RESUMO

OBJECTIVES: To develop and validate a novel artificial intelligence (AI) tool for automated segmentation of mandibular incisive canal on cone beam computed tomography (CBCT) scans. METHODS: After ethical approval, a data set of 200 CBCT scans were selected and categorized into training (160), validation (20), and test (20) sets. CBCT scans were imported into Virtual Patient Creator and ground truth for training and validation were manually segmented by three oral radiologists in multiplanar reconstructions. Intra- and interobserver analysis for human segmentation variability was performed on 20% of the data set. Segmentations were imported into Mimics for standardization. Resulting files were imported to 3-Matic for analysis using surface- and voxel-based methods. Evaluation metrics involved time efficiency, analysis metrics including Dice Similarity Coefficient (DSC), Intersection over Union (IoU), Root mean square error (RMSE), precision, recall, accuracy, and consistency. These values were calculated considering AI-based segmentation and refined-AI segmentation compared to manual segmentation. RESULTS: Average time for AI-based segmentation, refined-AI segmentation and manual segmentation was 00:10, 08:09, and 47:18 (284-fold time reduction). AI-based segmentation showed mean values of DSC 0.873, IoU 0.775, RMSE 0.256 mm, precision 0.837 and recall 0.890 while refined-AI segmentation provided DSC 0.876, IoU 0.781, RMSE 0.267 mm, precision 0. 852 and recall 0.902 with the accuracy of 0.998 for both methods. The consistency was one for AI-based segmentation and 0.910 for manual segmentation. CONCLUSIONS: An innovative AI-tool for automated segmentation of mandibular incisive canal on CBCT scans was proofed to be accurate, time efficient, and highly consistent, serving pre-surgical planning.


Assuntos
Mandíbula , Tomografia Computadorizada de Feixe Cônico Espiral , Humanos , Mandíbula/diagnóstico por imagem , Inteligência Artificial , Tomografia Computadorizada de Feixe Cônico/métodos , Processamento de Imagem Assistida por Computador/métodos
15.
Virus Genes ; 59(6): 817-822, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37796410

RESUMO

Rabies is worldwide zoonosis caused by Lyssavirus rabies (RABV) a RNA negative sense virus with low level of fidelity during replication cycle. Nucleoprotein of RABV is the most conserved between all five proteins of the virus and is the most used gene for phylogenetic and phylogeographic studies. Despite of rabies been very important in Public Health concern, it demands continuous prophylactic care for herbivores with economic interest, such as cattle and horses. The main transmitter of RABV for these animals in Brazil is the hematophagous bats Desmodus rotundus. The aim of this study was to determine the dispersion over time and space of RABV transmitted by D. rotundus. Samples of RABV from the State of São Paulo (SP), Southeast Brazil isolated from the central nervous system (CNS) of cattle, were submitted to RNA extraction, RT-PCR, sequencing and phylogeographic analyzes with BEAST (Bayesian Evolutionary Analysis Sampling Trees) v 2.5 software. Was possible to identify high rate of diversification in starts sublineages of RABV what are correlated with a behavior of D. rotundus, the main transmitter of rabies to cattle. This study also highlights the importance of continuous monitoring of genetic lineages of RABV in Brazil.


Assuntos
Quirópteros , Lyssavirus , Vírus da Raiva , Raiva , Animais , Bovinos , Raiva/veterinária , Lyssavirus/genética , Filogenia , Teorema de Bayes , Brasil , RNA
16.
Acta Ortop Bras ; 31(spe3): e267572, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37720811

RESUMO

Objectives: Analyze the donor site morbidity of the dorsalis pedis neurovascular flap in traumatic injuries with hand tissue loss. Material and Methods: The study involved dorsalis pedis neurovascular flaps that were used to reconstruct the hands of eight male patients, between 1983 and 2003, aged between 21 and 53 years (mean 34.6, SD ± 10.5 years). The size of the lesions ranged from 35 to 78 cm2 (mean 53, SD ± 14.4 cm2). Surgical procedures were performed two to 21 days after the injuries had occurred. The patients were followed up for an average of 10.3 years (ranging 8-14, SD ± 2.1 years). Results: Regarding the donor site, in one case there was hematoma formation, which was drained; in another case, the skin graft needed to be reassessed. All patients experienced delayed healing, with complete healing from 2 to 12 months after the surgery (mean 4.3, SD ± 3.2 months). Conclusion: Despite the advantages of the dorsalis pedis neurovascular flap, we consider that the sequelae in the donor site is cosmetically unacceptable. Nowadays, this procedure is only indicated and justified when associated with the second toe transfer. Level of Evidence IV; Case series .


Objetivos: Analisar a morbidade da área doadora do retalho neurovascular do dorso do pé em lesões traumáticas com perda de tecido da mão. Material e métodos: O estudo envolveu retalhos neurovasculares do dorso do pé usados para reconstruir as mãos de oito pacientes do sexo masculino, entre 1983 e 2003, com idades entre 21 e53 anos (média de 34,6, DP ± 10,5 anos). O tamanho das lesões variou de 35 a 78 cm2 (média de 53, DP ± 14,4 cm2). Os procedimentos cirúrgicos foram realizados entre dois a 21 dias após a ocorrência das lesões. Os pacientes foram acompanhados por uma média de10,3 anos (variando de 8 a 14, DP ± 2,1 anos). Resultados: Quanto ao local doador, em um caso houve formação de hematoma, que foi drenado; em outro caso, o enxerto de pele precisou ser reavaliado. Todos os pacientes apresentaram retardo na cicatrização, com cicatrização completa de 2 a 12 meses após a cirurgia (média de 4,3, DP ± 3,2 meses). Conclusão: Apesar das vantagens do retalho neurovascular do dorso do pé, consideramos que as sequelas no local doador são cosmeticamente inaceitáveis. Atualmente, esse procedimento só é indicado e justificado quando associado à transferência do segundo dedo do pé. Nível de evidência IV; Série de casos .

17.
bioRxiv ; 2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37547010

RESUMO

Antimicrobial peptides commonly act by disrupting bacterial membranes, but also frequently damage mammalian membranes. Deciphering the rules governing membrane selectivity is critical to understanding their function and enabling their therapeutic use. Past attempts to decipher these rules have failed because they cannot interrogate adequate peptide sequence variation. To overcome this problem, we develop deep mutational surface localized antimicrobial display (dmSLAY), which reveals comprehensive positional residue importance and flexibility across an antimicrobial peptide sequence. We apply dmSLAY to Protegrin-1, a potent yet toxic antimicrobial peptide, and identify thousands of sequence variants that positively or negatively influence its antibacterial activity. Further analysis reveals that avoiding large aromatic residues and eliminating disulfide bound cysteine pairs while maintaining membrane bound secondary structure greatly improves Protegrin-1 bacterial specificity. Moreover, dmSLAY datasets enable machine learning to expand our analysis to include over 5.7 million sequence variants and reveal full Protegrin-1 mutational profiles driving either bacterial or mammalian membrane specificity. Our results describe an innovative, high-throughput approach for elucidating antimicrobial peptide sequence-structure-function relationships which can inform synthetic peptide-based drug design.

18.
Acta Ortop Bras ; 31(4): e265467, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547236

RESUMO

Objective: This study aims to present lines A1 and A2 in association with Kaplan's cardinal line (LCK), and relate them to the thenar motor branch of the median nerve (RMTNM) and to the deep branch of the ulnar nerve (RPNU). Methods: Ten hands of five adult cadavers were dissected. Results: The RMTNM origin was positioned proximal to the LCK in all limbs. In two, the RMTNM was positioned exactly on the A1 line; in seven, it was on the ulnar side in relation to A1. In one, it was on the radial side relative to the A1. The origin of the RPNU was identified between the pisiform and the LCK in nine limbs; in one, the RPNU was positioned from the ulnar nerve in relation to A2; and in two, the A2 passed exactly at the point of division of the ulnar nerve into superficial branches and deep. We did not identify the positioning of the RPNU on the radial side of the A2 line. Conclusion: The impact of this study was to identify the anatomical trajectory of these nerves by detaching A1 and A2 along with the KCL, avoiding iatrogenic lesions during surgical procedures. Level of Evidence IV, Case Series.


Objetivo: Apresentar as linhas A1 e A2 em associação com a linha cardinal de Kaplan (LCK) e relacioná-las ao ramo motor tenar do nervo mediano (RMTNM) e ao ramo profundo do nervo ulnar (RPNU). Métodos: Foram dissecadas dez mãos de 5 cadáveres adultos. Resultados: Em todos os membros, a origem do RMTNM posicionou proximal a LCK. Em dois, o RMTNM foi posicionado exatamente na linha A1, em sete foi no lado ulnar em relação à A1. Em um, foi no lado radial em relação à A1. A origem do RPNU foi identificada entre o pisiforme e o LCK em 9 membros, em um, o RPNU foi posicionado a partir do nervo ulnar em relação à A2, em dois, a A2 passou exatamente no ponto de divisão do nervo ulnar em ramos superficial e profundo. Não identificamos o posicionamento do RPNU no lado radial da linha A2. Conclusão: O impacto deste trabalho é que, ao destacar A1 e A2 juntamente com o LCK, conseguimos identificar a trajetória anatômica desses nervos e, evitar lesões iatrogênicas durante os procedimentos cirúrgicos. Nível de Evidência IV; Série de Casos.

19.
Chemosphere ; 340: 139894, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37607599

RESUMO

Tebuthiuron (TBU), a phenylurea herbicide, is widely applied in agricultural and non-agricultural soils. Because TBU resists degradation, it can contaminate water and reach the biota once it is released into the environment. However, the potential toxic effects of TBU on aquatic developing organisms have been poorly studied. By taking advantage of the early-life stages of zebrafish (Danio rerio), we have combined morphological, biochemical, behavioural, and molecular approaches to investigate the developmental toxicity triggered by environmentally relevant concentrations (from 0.1 to 1000 µg/L) of TBU. Exposure to TBU did not elicit morphological abnormalities but it significantly delayed hatching. In addition, TBU altered the frequency of tail coils in one-day post-fertilization (dpf) old embryos. Moreover, TBU exposure during four days significantly inhibited the whole body AChE activity of larvae. At the molecular level, TBU did not significantly affect the mRNA levels of four genes (elavl3, gfap, gap43, and shha) that play key roles during the neurodevelopment of zebrafish. By assessing the motor responses to repeated light-dark stimuli, 6 dpf larvae exposed to TBU displayed hyperactivity, showing greater travelling distance during the dark periods. Our categorization of swimming speed revealed an interesting finding - after the light was turned off, the exposed larvae abandoned the freezing mode (<2 mm/s) and travelled mainly at cruising speed (2-20 mm/s), showing that the larval hyperactivity did not translate into higher swimming velocity. Overall, our results offer new insights into the TBU toxicity to developing organisms, namely effects in AChE activity and hyperactivity, providing support data for future studies considering environmental risk assessment of this herbicide.


Assuntos
Herbicidas , Peixe-Zebra , Animais , Agricultura , Biota , Herbicidas/toxicidade , Larva
20.
Mol Biol Evol ; 40(9)2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37619989

RESUMO

The most highly expressed genes in microbial genomes tend to use a limited set of synonymous codons, often referred to as "preferred codons." The existence of preferred codons is commonly attributed to selection pressures on various aspects of protein translation including accuracy and/or speed. However, gene expression is condition-dependent and even within single-celled organisms transcript and protein abundances can vary depending on a variety of environmental and other factors. Here, we show that growth rate-dependent expression variation is an important constraint that significantly influences the evolution of gene sequences. Using large-scale transcriptomic and proteomic data sets in Escherichia coli and Saccharomyces cerevisiae, we confirm that codon usage biases are strongly associated with gene expression but highlight that this relationship is most pronounced when gene expression measurements are taken during rapid growth conditions. Specifically, genes whose relative expression increases during periods of rapid growth have stronger codon usage biases than comparably expressed genes whose expression decreases during rapid growth conditions. These findings highlight that gene expression measured in any particular condition tells only part of the story regarding the forces shaping the evolution of microbial gene sequences. More generally, our results imply that microbial physiology during rapid growth is critical for explaining long-term translational constraints.


Assuntos
Uso do Códon , Magnoliopsida , Proteômica , Escherichia coli/genética , Biossíntese de Proteínas , Saccharomyces cerevisiae/genética , Viés
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