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1.
Sci Rep ; 14(1): 20445, 2024 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227667

RESUMEN

With the rapid advancement of drone technology and the growing applications in the field of drone engineering, the demand for precise and efficient path planning in complex and dynamic environments has become increasingly important. Traditional algorithms struggle with complex terrain, obstacles, and weather changes, often falling into local optima. This study introduces an Improved Crown Porcupine Optimizer (ICPO) for drone path planning, which enables drones to better avoid obstacles, optimize flight paths, and reduce energy consumption. Inspired by porcupines' defense mechanisms, a visuo-auditory synergy perspective is adopted, improving early convergence by balancing visual and auditory defenses. The study also employs a good point set population initialization strategy to enhance diversity and eliminates the traditional population reduction mechanism. To avoid local optima in later stages, a novel periodic retreat strategy inspired by porcupines' precise defenses is introduced for better position updates. Analysis on the IEEE CEC2022 test set shows that ICPO almost reaches the optimal value, demonstrating robustness and stability. In complex mountainous terrain, ICPO achieved optimal values of 778.1775 and 954.0118; in urban terrain, 366.2789 and 910.1682 and ranked first among the compared algorithms, proving its effectiveness and reliability in drone delivery path planning. Looking ahead, the ICPO will provide greater efficiency and safety for drone path planning in navigating complex environments.


Asunto(s)
Algoritmos , Puercoespines , Animales , Robótica/métodos , Ambiente
2.
Micromachines (Basel) ; 15(7)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39064430

RESUMEN

The morphology size of laser cladding is a crucial parameter that significantly impacts the quality and performance of the cladding layer. This study proposes a predictive model for the cladding morphology size based on the Least Squares Support Vector Regression (LSSVR) and the Crowned Porcupine Optimization (CPO) algorithm. Specifically, the proposed model takes three key parameters as inputs: laser power, scanning speed, and powder feeding rate, with the width and height of the cladding layer as outputs. To further enhance the predictive accuracy of the LSSVR model, a CPO-based optimization strategy is applied to adjust the penalty factor and kernel parameters. Consequently, the CPO-LSSVR model is established and evaluated against the LSSVR model and the Genetic Algorithm-optimized Backpropagation Neural Network (GA-BP) model in terms of relative error metrics. The experimental results demonstrate that the CPO-LSSVR model can achieve a significantly improved relative error of no more than 2.5%, indicating a substantial enhancement in predictive accuracy compared to other methods and showcasing its superior predictive performance. The high accuracy of the CPO-LSSVR model can effectively guide the selection of laser cladding process parameters and thereby enhance the quality and efficiency of the cladding process.

3.
Materials (Basel) ; 17(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38730756

RESUMEN

The mechanical properties of porcupine quills have attracted the interest of researchers due to their unique structure and composition. However, there is still a knowledge gap in understanding how these properties can be utilized to design biomimetic structures with enhanced performance. This study delves into the nanomechanical and macro-mechanical properties of porcupine quills, unveiling varied elastic moduli across different regions and cross sections. The results indicated that the elastic moduli of the upper and lower epidermis were higher at 8.13 ± 0.05 GPa and 7.71 ± 0.14 GPa, respectively, compared to other regions. In contrast, the elastic modulus of the mid-dermis of the quill mid-section was measured to be 7.16 ± 0.10 GPa. Based on the micro- and macro-structural analysis of porcupine quills, which revealed distinct variations in elastic moduli across different regions and cross sections, various biomimetic porous structures (BPSs) were designed. These BPSs were inspired by the unique properties of the quills and aimed to replicate and enhance their mechanical characteristics in engineering applications. Compression, torsion, and impact tests illustrated the efficacy of structures with filled hexagons and circles in improving performance. This study showed enhancements in maximum torsional load and crashworthiness with an increase in filled structures. Particularly noteworthy was the biomimetic porous circular structure 3 (BPCS_3), which displayed exceptional achievements in average energy absorption (28.37 J) and specific energy absorption (919.82 J/kg). Finally, a response surface-based optimization method is proposed to enhance the design of the structure under combined compression-torsion loads, with the goal of reducing mass and deformation. This research contributes to the field of biomimetics by exploring the potential applications of porcupine quill-inspired structures in fields such as robotics, drive shafts, and aerospace engineering.

4.
Bioinspir Biomim ; 19(4)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38631361

RESUMEN

This paper presents a novel approach for designing a freeform bending-resistant structure from the combination of explicit discrete component-based topology optimization (TO) and the porcupine quill-inspired features. To embed the porcupine quill's features into the TO formulations, the method involves constructing discrete components at various scales to imitate features including solid shell, stochastically distributed pores, and graded stiffeners. The components are iteratively updated, and the optimization process allows for the grading of quill-inspired features while achieving optimal structural compliance under bending loads. The proposed approach is demonstrated to be effective through the resolution of Messershmitt-Bolkow-Blohm (MBB) beam designs, parameterized studies of geometric parameters, and numerical validation of long-span and short-span quill-inspired beam designs. By examining the von Mises stress distribution, the study highlights the mitigation of material yielding at the shell region brought by the geometric features of porcupine quills, leading to the potential theory support for the bending resistance. The optimized MBB beams are manufactured using the material extrusion technique, and three-point bending tests are conducted to explore the failure mitigation capability of the quill-inspired beam under large deformation. Consequently, the study concludes that the proposed quill-inspired component-based TO approach can design a structure with excellent bending resistance according to the improved energy absorption as well as increased deformation after reaching 75% peak load.


Asunto(s)
Puercoespines , Porosidad , Puercoespines/fisiología , Puercoespines/anatomía & histología , Animales , Estrés Mecánico , Materiales Biomiméticos/química , Biomimética/métodos , Simulación por Computador
5.
J Fish Biol ; 104(6): 2086-2089, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38477062

RESUMEN

The occurrence of a small specimen of Brosme brosme (Gadiformes: Lotidae) from the Porcupine Bank is reported. A single specimen with a total length of 73.2 mm was caught with bottom trawl at a depth of 322 m depth in 2017. The specimen was identified morphologically and confirmed by molecular taxonomy using DNA barcoding. Based on the size and ontogenetic characters found, the specimen was identified as a post-larval individual, and a pelagic habitat of the specimen seems more likely.


Asunto(s)
Gadiformes , Animales , Gadiformes/anatomía & histología , Gadiformes/genética , Gadiformes/clasificación , Código de Barras del ADN Taxonómico , Irlanda , Ecosistema
6.
J Sci Food Agric ; 104(3): 1741-1755, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37862230

RESUMEN

BACKGROUND: Porcupine quills, a by-product of porcupine pork, are rich in keratin, which is an excellent source of bioactive peptides. The objective of this study was to investigate the underlying mechanism of anti-proliferation effect of porcupine quills keratin peptides (PQKPs) on MCF-7 cells. RESULTS: Results showed that PQKPs induced MCF-7 cells apoptosis by significantly decreasing the secretion level of anti-apoptosis protein Bcl-2 and increasing the secretion levels of pro-apoptosis proteins Bax, cytochrome c, caspase 9, caspase 3 and PARP. PQKPs also arrested the cell cycle at G0/G1 phase via remarkably reducing the protein levels of CDK4 and enhancing the protein levels of p53 and p21. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis identified nine peptides with molecular weights less than 1000 Da in PQKPs. Molecular docking results showed that TPGPPT and KGPAC identified from PQKPs could bind with p53 mutant and Bcl-2 protein by conventional hydrogen bonds, carbon hydrogen bonds and van der Waals force. Furthermore, the anti-proliferation impact of synthesized peptides (TPGPPT and KGPAC) was shown in MCF-7 cells. CONCLUSION: These findings indicated that PQKPs suppressed the proliferation of MCF-7 breast cancer cells by triggering apoptosis and G0/G1 cell cycle arrest. Moreover, the outcome of this study will bring fresh insights into the production and application of animal byproducts. © 2023 Society of Chemical Industry.


Asunto(s)
Neoplasias de la Mama , Puercoespines , Humanos , Animales , Femenino , Células MCF-7 , Caspasas/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Puercoespines/metabolismo , Puntos de Control de la Fase G1 del Ciclo Celular , Queratinas/metabolismo , Simulación del Acoplamiento Molecular , Espectrometría de Masas en Tándem , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/farmacología , Ciclo Celular , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Proliferación Celular , Línea Celular Tumoral
7.
Cell ; 186(23): 5028-5040.e14, 2023 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-37852257

RESUMEN

Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility Wnts from the ER to the extracellular space remain unclear. Through structural and functional analyses of Wnt7a, a crucial Wnt involved in central nervous system angiogenesis and blood-brain barrier maintenance, we have elucidated the principles of Wnt biogenesis and Wnt7-specific signaling. The Wnt7a-WLS complex binds to calreticulin (CALR), revealing that CALR functions as a chaperone to facilitate Wnt transfer from PORCN to WLS during Wnt biogenesis. Our structures, functional analyses, and molecular dynamics simulations demonstrate that a phospholipid in the core of Wnt-bound WLS regulates the association and dissociation between Wnt and WLS, suggesting a lipid-mediated Wnt secretion mechanism. Finally, the structure of Wnt7a bound to RECK, a cell-surface Wnt7 co-receptor, reveals how RECKCC4 engages the N-terminal domain of Wnt7a to activate Wnt7-specific signaling.


Asunto(s)
Receptores Acoplados a Proteínas G , Proteínas Wnt , Vía de Señalización Wnt , Barrera Hematoencefálica/metabolismo , Unión Proteica , Receptores Acoplados a Proteínas G/metabolismo , Humanos , Proteínas Wnt/química , Proteínas Wnt/metabolismo
8.
Animals (Basel) ; 13(16)2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37627342

RESUMEN

This paper aimed to describe an atlas of the crested porcupine (Hystrix cristata) head by applying advanced imaging techniques such as MRI. Furthermore, by combining the images acquired through these techniques with anatomical sections, we obtained an adequate description of the structures that form the CNS and associated structures of this species. This anatomical information could serve as a valuable diagnostic tool for the clinical evaluation of different pathological processes in porcupines, such as abscesses, skull malformations, fractures, and neoplasia.

9.
Transl Cancer Res ; 12(7): 1703-1714, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37588740

RESUMEN

Background: Porcupine O-acyltransferase (PORCN), a membrane-bound O-acyltransferase, is crucial in Wnt ligand palmitoylation. However, the roles of PORCN in the development of hepatocellular carcinoma (HCC) remain unknown. Methods: Western blot, real-time quantitative polymerase chain reaction (RT-qPCR) assays, and The Cancer Genome Atlas (TCGA) database were used to study the expression and prognostic values of PORCN in patients with HCC. Following this, Cell Counting Kit-8 (CCK-8), wound-healing tests, Transwell assay, and a xenograft mouse model were employed to examine the effect of PORCN on HCC cells. Finally, the underlying molecular mechanisms involved in cell proliferation and migration caused by PORCN were identified. Results: The protein and messenger RNA (mRNA) levels of PORCN in HCC tissues were higher than those of adjacent normal tissues. The analysis of TCGA database indicated that patients with higher PORCN expression had a lower overall survival (OS) rate. Overexpression of PORCN could promote the proliferation and migration abilities of HCC cells both in vitro and in vivo. Gene set enrichment analysis (GSEA) showed that the effect of PORCN on the biological characteristics of HCC cells mainly centered on the Wnt-ß-catenin signaling pathway. Mechanically, immunofluorescence staining and subcellular protein fraction assays showed that PORCN could induce epithelial-mesenchymal transition (EMT) by promoting the translocation of ß-catenin from the cytoplasm to nucleus, ultimately promoting the progression of HCC. Conclusions: The findings of this study suggest that PORCN can promote HCC cell proliferation and migration by stimulating the Wnt-ß-catenin signaling pathway. Therefore, PORCN may be a promising therapeutic target for HCC.

10.
PeerJ ; 11: e15653, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37609437

RESUMEN

A structural protein called keratin is often employed in the medical industry to create medication carriers. Process improvement, antioxidant, antibacterial, and adjuvant drug studies of synthetic bioactive keratin microparticles made from lipids and keratin derived from porcupine (Hystrix indica) quills are the main objectives of this study. After coating the keratin microparticles with lipids which were obtained from the same porcupine quills, the bioactive keratin microparticles were produced. The response surface technique was applied to optimize the conditions for extraction of the keratin protein and sizing of the keratin microparticles. An infrared spectroscopy was used to analyze the chemical shifts in compositions of keratin microparticles while the optical microscopy was used to measure the size of the keratin microparticles. The results of this work revealed that a yield 27.36 to 42.25% of the keratin protein could be obtained from porcupine quills. The keratin microparticles were sized between 60.65 and 118.87 µm. Through response surface optimization, mercaptoethanol and urea were shown to be the main variables which positively affected the yield and the size of the keratin protein. The lipid stacking on the keratin microparticles' surface was confirmed by infrared spectroscopy. The 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonate) assay confirmed the keratin microparticle's antioxidant activity of 29.83%. Compared to lipid alone, the antibacterial properties of the keratin microparticles against Escherichia coli-a gram-negative-and Staphylococcus aureus-a gram-positive-bacteria enhanced by up to 55% following the coating of the microparticles with the lipids. The pharmacological action against these bacterial species was further improved by the lipid-loaded erythromycin that was carried on the surface of keratin microparticles. This work has demonstrated the design and uses of the keratin microparticles obtained from porcupine quills for clinical applications.


Asunto(s)
Queratinas , Puercoespines , Animales , Antioxidantes/farmacología , Adyuvantes Farmacéuticos , Antibacterianos/farmacología , Escherichia coli , Lípidos
11.
Vet Pathol ; 60(6): 898-904, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37264637

RESUMEN

Erethizon dorsatum papillomavirus 1 (EdPV1) and Erethizon dorsatum papillomavirus 2 (EdPV2) are associated with cutaneous papillomas in North American porcupines (Erethizon dorsatum). This study defined gross, histopathologic, and molecular characteristics of viral papillomas in 10 North American porcupines submitted to the New York State Animal Health Diagnostic Center. Investigation for the presence of EdPV1 and EdPV2 DNA via polymerase chain reaction (PCR) was performed in 9 of the 10 (90.0%) porcupines, and all porcupines were investigated for the detection and localization of EdPV1 and EdPV2 E6 and E7 nucleic acid via chromogenic in situ hybridization (CISH). Next-generation sequencing (NGS) was performed in 2 porcupines. Papillomas were diagnosed on the muzzle (n = 4), caudal dorsum (n = 1), upper lip (n = 1), chin (n = 1), gingiva (n = 2), and nasal planum (n = 1). Histologically, the lesions consisted of hyperplastic epidermis or epithelium with orthokeratotic keratin, prominent keratohyalin granules, and intranuclear inclusion bodies. PCR identified EdPV1 in 6 of 9 samples and EdPV2 in the remaining 3 samples. NGS resulted in 100% genome coverage of EdPV1 and 76.20% genome coverage of EdPV2 compared with GenBank reference sequences, with 99.8% sequence identity to the complete EdPV2 L1 gene of a novel subtype recently identified in France. Hybridization patterns in 9 of the 10 (90.0%) porcupines were characterized by strong nuclear signals in the superficial epidermis, with strong nuclear and punctate cytoplasmic signals in the stratum spinosum and basale. In one animal, CISH suggested dual EdPV1 and EdPV2 infection.


Asunto(s)
Papiloma , Puercoespines , Enfermedades de los Roedores , Animales , Papillomaviridae/genética , América del Norte , Papiloma/veterinaria , Francia
12.
Bioinspir Biomim ; 18(4)2023 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-37158291

RESUMEN

This paper presents the bending behaviour of the porcupine quill and bioinspired Voronoi sandwich panels, aiming to explore the effect of geometrical design on the bending performance of the inspired structures. Through the x-ray micro-computed tomography, the internal morphology of the quill is explored. The longitudinal cross-section of the porcupine quill revealed a functionally graded design in the foam structure. Based on this observation, Voronoi sandwich panels are designed by incorporating the Voronoi seed distribution strategy and gradient transition design configurations. Porcupine-inspired sandwich panels with various core designs are fabricated via material jetting technique and tested under three-point bending condition. Results show that the sample failed at the bottom face panels for uniform sandwich panels, whereas graded samples failed in the core panel. The bending behaviour developed via simulation software shows a good agreement with the experimental results. The parametric study provides insights into structural designs for engineering applications, particularly in the aerospace and automobile industries.


Asunto(s)
Resistencia Flexional , Microtomografía por Rayos X
13.
Int J Mol Sci ; 24(7)2023 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37047705

RESUMEN

In a continuous search for the improvement of antitumor therapies, the inhibition of the Wnt signaling pathway has been recognized as a promising target. The altered functioning of the Wnt signaling in human tumors points to the strategy of the inhibition of its activity that would impact the clinical outcomes and survival of patients. Because the Wnt pathway is often mutated or epigenetically altered in tumors, which promotes its activation, inhibitors of Wnt signaling are being intensively investigated. It has been shown that knocking down specific components of the Wnt pathway has inhibitory effects on tumor growth in vivo and in vitro. Thus, similar effects are expected from the application of Wnt inhibitors. In the last decades, molecules acting as inhibitors on the pathway's specific molecular levels have been identified and characterized. This review will discuss the inhibitors of the canonical Wnt pathway, summarize knowledge on their effectiveness as therapeutics, and debate their side effects. The role of the components frequently mutated in various tumors that are principal targets for Wnt inhibitors is also going to be brought to the reader's attention. Some of the molecules identified as Wnt pathway inhibitors have reached early stages of clinical trials, and some have only just been discovered. All things considered, inhibition of the Wnt signaling pathway shows potential for the development of future therapies.


Asunto(s)
Neoplasias , Vía de Señalización Wnt , Humanos , Neoplasias/tratamiento farmacológico , beta Catenina/metabolismo
14.
Curr Top Dev Biol ; 153: 1-60, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36967191

RESUMEN

Wnts are secreted proteins that control stem cell maintenance, cell fate decisions, and growth during development and adult homeostasis. Wnts carry a post-translational modification not seen in any other secreted protein: during biosynthesis, they are appended with a palmitoleoyl moiety that is required for signaling but also impairs solubility and hence diffusion in the extracellular space. In some contexts, Wnts act only in a juxtacrine manner but there are also instances of long range action. Several proteins and processes ensure that active Wnts reach the appropriate target cells. Some, like Porcupine, Wntless, and Notum are dedicated to Wnt function; we describe their activities in molecular detail. We also outline how the cell infrastructure (secretory, endocytic, and retromer pathways) contribute to the progression of Wnts from production to delivery. We then address how Wnts spread in the extracellular space and form a signaling gradient despite carrying a hydrophobic moiety. We highlight particularly the role of lipid-binding Wnt interactors and heparan sulfate proteoglycans. Finally, we briefly discuss how evolution might have led to the emergence of this unusual signaling pathway.


Asunto(s)
Transducción de Señal , Proteínas Wnt , Proteínas Wnt/metabolismo , Procesamiento Proteico-Postraduccional , Vía de Señalización Wnt
15.
Acta Trop ; 242: 106915, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36997011

RESUMEN

We investigated the occurrence and genotypic diversity of E. bieneusi in farmed Asiatic brush-tailed porcupines and bamboo rats from Hainan Province, China. Four hundred and sixty-seven fresh feces were collected from 164 Asiatic brush-tailed porcupines and 303 bamboo rats. DNA extraction from the feces and genotyping of E. bieneusi were performed by the amplification of the internal transcribed spacer (ITS) region of rDNA of E. bieneusi using PCR. A neighbor-joining tree was constructed based on the sequences obtained here and other sequences of E. bieneusi genotypes stored in Genbank. The total rate of infection with E. bieneusi was 32.5% (152/467), with 14.6% (24/164) in Asiatic brush-tailed porcupines and 42.2% (128/303) in bamboo rats infected. Seventeen genotypes of E. bieneusi were identified including 12 known genotypes, i.e., D (n = 78), Henan-III (n = 21), SHW7 (n = 19), KIN-1 (n = 11), ETMK5 (n = 7), TypeIV (n = 4), EbpD (n = 2), EbpA (n = 1), EbpC (n = 1), S7 (n = 1), HNPL-III (n = 1), HNR-VII (n = 1), and five novel genotypes named as HNZS-I (n = 1) and HNHZ-I to HNHZ-IV (n = 1 per genotype). Phylogenetic analysis revealed that all the genotypes found here except genotype S7 fell into Group 1. The present study demonstrated a relatively high prevalence of E. bieneusi infection (32.5%) and a large genetic variation of E. bieneusi (seventeen genotypes) in farmed Asiatic brush-tailed porcupines and bamboo rats in Hainan, China. The high proportion (78.3%) of zoonotic genotypes identified in the animals investigated here suggests that there is the potential for zoonotic or cross-species transmission which may pose a serious public health threat in the area. Public education on the management of Asiatic brush-tailed porcupines and bamboo rats should be implemented in the investigated areas.


Asunto(s)
Enterocytozoon , Microsporidiosis , Puercoespines , Animales , Zoonosis/epidemiología , Enterocytozoon/genética , Filogenia , Microsporidiosis/epidemiología , Microsporidiosis/veterinaria , Microsporidiosis/genética , China/epidemiología , Genotipo , Prevalencia , Heces , Variación Genética
16.
Development ; 150(3)2023 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36763105

RESUMEN

Intercellular communication by Wnt proteins governs many essential processes during development, tissue homeostasis and disease in all metazoans. Many context-dependent effects are initiated in the Wnt-producing cells and depend on the export of lipidated Wnt proteins. Although much focus has been on understanding intracellular Wnt signal transduction, the cellular machinery responsible for Wnt secretion became better understood only recently. After lipid modification by the acyl-transferase Porcupine, Wnt proteins bind their dedicated cargo protein Evi/Wntless for transport and secretion. Evi/Wntless and Porcupine are conserved transmembrane proteins, and their 3D structures were recently determined. In this Review, we summarise studies and structural data highlighting how Wnts are transported from the ER to the plasma membrane, and the role of SNX3-retromer during the recycling of its cargo receptor Evi/Wntless. We also describe the regulation of Wnt export through a post-translational mechanism and review the importance of Wnt secretion for organ development and cancer, and as a future biomarker.


Asunto(s)
Proteínas de la Membrana , Proteínas Wnt , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Proteínas de la Membrana/metabolismo , Membrana Celular/metabolismo , Vía de Señalización Wnt/genética , Proteínas Portadoras/metabolismo
17.
Virol J ; 20(1): 12, 2023 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-36658615

RESUMEN

BACKGROUND: Only two cases of papillomavirus infections in North American porcupines (Erethizon dorsatum) have been described thus far, and molecular investigation linked these cases to two distinct papillomavirus species. METHODS: In this report, we present the clinical, histological and molecular investigation of a third case of a porcupine papillomavirus infection. Papillomatous lesions occurred on the upper and lower lip of an otherwise healthy three-year old female that was kept in captivity. Within one month, the lesions progressed into exophytic black nodules, followed by a temporary stabilization and ultimately spontaneous regression within seven months of their initial observation. PCR-based screening using specific primers for Erethizon dorsatum papillomavirus 1 and 2 revealed the presence of both these virus types, after which nanopore sequencing was used to determine the complete sequences of the two virus genomes. RESULTS: One of the genomes shares 99.9% similarity with the only known sequence for Erethizon dorsatum papillomavirus 1, while the second represents a distinct lineage of Erethizon dorsatum papillomavirus 2, sharing only 93.3% similarity with the previously discovered strain. CONCLUSIONS: This report marks the first observation of a papillomavirus co-infection in a North American porcupine, although the individual contribution of the two virus types to the clinical presentation was not assessed.


Asunto(s)
Coinfección , Puercoespines , Animales , Femenino , Humanos , Preescolar , Coinfección/veterinaria , Técnicas de Amplificación de Ácido Nucleico , América del Norte
18.
Acta Pharmacol Sin ; 44(6): 1149-1160, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36473990

RESUMEN

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent, and lacks effective treatment. The aberration of WNT pathway underlies many pathological processes including cardiac fibrosis and hypertrophy, while porcupine is an acyltransferase essential for the secretion of WNT ligands. In this study we investigated the role of WNT signaling pathway in HFpEF as well as whether blocking WNT signaling by a novel porcupine inhibitor CGX1321 alleviated HFpEF. We established two experimental HFpEF mouse models, namely the UNX/DOCA model and high fat diet/L-NAME ("two-hit") model. The UNX/DOCA and "two-hit" mice were treated with CGX1321 (3 mg·kg-1·d-1) for 4 and 10 weeks, respectively. We showed that CGX1321 treatment significantly alleviated cardiac hypertrophy and fibrosis, thereby improving cardiac diastolic function and exercise performance in both models. Furthermore, both canonical and non-canonical WNT signaling pathways were activated, and most WNT proteins, especially WNT3a and WNT5a, were upregulated during the development of HEpEF in mice. CGX1321 treatment inhibited the secretion of WNT ligands and repressed both canonical and non-canonical WNT pathways, evidenced by the reduced phosphorylation of c-Jun and the nuclear translocation of ß-catenin and NFATc3. In an in vitro HFpEF model, MCM and ISO-treated cardiomyocytes, knockdown of porcupine by siRNA leads to a similar inhibitory effect on WNT pathways, cardiomyocyte hypertrophy and cardiac fibroblast activation as CGX1321 did, whereas supplementation of WNT3a and WNT5a reversed the anti-hypertrophy and anti-fibrosis effect of CGX1321. We conclude that WNT signaling activation plays an essential role in the pathogenesis of HFpEF, and porcupine inhibitor CGX1321 exerts a therapeutic effect on HFpEF in mice by attenuating cardiac hypertrophy, alleviating cardiac fibrosis and improving cardiac diastolic function.


Asunto(s)
Cardiomiopatías , Acetato de Desoxicorticosterona , Insuficiencia Cardíaca , Animales , Ratones , Cardiomegalia/patología , Cardiomiopatías/patología , Acetato de Desoxicorticosterona/farmacología , Acetato de Desoxicorticosterona/uso terapéutico , Fibrosis , Insuficiencia Cardíaca/metabolismo , Miocitos Cardíacos , Volumen Sistólico/fisiología , Vía de Señalización Wnt
19.
J Biomol Struct Dyn ; 41(13): 6413-6421, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35930335

RESUMEN

Vancomycin and daptomycin are commonly used glycopeptide antibiotics to cure Gram-positive staphylococcal infections. The clinical isolates of mutant Staphylococcus aureus strains, Methicillin-Resistant (MRSA) and Vancomycin-Resistant (VRSA), have developed resistance against these antibiotics. A recently discovered Serine/threonine phosphatase (Stp1) is an Mn+2 containing protein at the active site with a flap sub-domain that participates in the phospho-signaling system of bacterial cell wall formation. The flap sub-domain probably regulates substrates recruitment and release with an extra Mn+2, possibly highly flexible as in the other homologous family of proteins. In this study, the flap sub-domain has been sampled with conventional and accelerated molecular dynamics (cMD and aMD) simulations to get other sub-optimal conformational states of the protein that are nearly impossible to observe through experimental methods. Trajectory analysis has shown that protein remained static in cMD while dynamic in aMD with RMSD of ∼2Å and ∼3Å, respectively. Accelerated MD has shown greater flexibility of ∼4 Å in the flap sub-domain, while cMD only captured a deviation of ∼ 2 Å. Later, the dynamic cross-correlation map (DCCM) confirmed that the flap sub-domain is significantly more flexible than the other part of the structure, indicating its role in substrate regulation. Secondary structure transition in the flap sub-domain, i.e. 3-10 helix and turn (PRO159 - ILE163) region of the flap sub-domain shifted into α-helix, which is a more stable structure. Further, the trajectory has been clustered, and conformational states extracted, which may be exploited in structure-based antibiotics discovery.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Infecciones Estafilocócicas , Staphylococcus aureus , Humanos , Vancomicina , Simulación de Dinámica Molecular , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/microbiología , Antibacterianos/farmacología , Fosfoproteínas Fosfatasas/química , Fosfoproteínas Fosfatasas/metabolismo
20.
Braz. j. biol ; 83: 1-12, 2023. graf, map, tab
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1468929

RESUMEN

The Indian crested porcupine (Hystrix indica) is a vertebrate pest of agricultural lands and forest. The study was aimed to report the damage to local crops by the Indian crested porcupine (Hystrix indica) in the Muzaffarabad District. A survey was conducted to identify the porcupine-affected areas and assess the crop damage to the local farmers in district Muzaffarabad Azad Jammu and Kashmir (AJK) from May 2017 to October 2017. Around 19 villages were surveyed, and a sum of 191 semi-structured questionnaires was distributed among farmers. Crop damage was found highest in village Dhanni where a porcupine destroyed 175 Kg/Kanal of the crops. Regarding the total magnitude of crop loss, village Danna and Koomi kot were the most affected areas. More than half (51.8%) of the respondents in the study area suffered the economic loss within the range of 101-200$, and (29.8%) of the people suffered losses in the range of 201-300$ annually. Among all crops, maize (Zea mays) was found to be the most damaged crop ranging between 1-300 Kg annually. In the study area, porcupine also inflicted a lot of damages to some important vegetables, including spinach (Spinacia oleracea), potato (Solanum tuberosum) and onion (Allium cepa). It was estimated that, on average, 511Kg of vegetables are destroyed by porcupine every year in the agricultural land of Muzaffarabad. It was concluded that the Indian crested porcupine has a devastating effect on agriculture which is an important source of income and food for the local community. Developing an effective pest control strategy with the help of the local government and the Wildlife department could help the farmers to overcome this problem.


O porco-espinho de crista indiano (Hystrix indica) é uma praga vertebrada de terras agrícolas e florestais. No estudo atual, o dano às plantações locais pelo porco-espinho de crista indiano (Hystrix indica) foi relatado pela primeira vez no distrito de Muzaffarabad. O estudo foi projetado para investigar a perda econômica causada pelo porco espinho de crista indiano (Hystrix indica) nos distritos de Muzaffarabad, Azad Jammu e Caxemira (AJK) de maio de 2017 a outubro de 2017. Um estudo baseado em pesquisa foi conduzido para identificar as áreas afetadas por porcos-espinhos e avaliar os danos às colheitas para os agricultores locais. Cerca de 19 aldeias foram pesquisadas e um total de 191 questionários semiestruturados foi distribuído entre os agricultores. Os danos às colheitas foram encontrados mais intensamente na aldeia Dhanni, onde um porco-espinho destruiu 175 kg / Kanal das colheitas. Em relação à magnitude total da perda de safra, as aldeias Danna e Koomi Kot foram as áreas mais afetadas. Mais da metade (51,8%) dos entrevistados na área de estudo sofreu perdas econômicas na faixa de 101-200 $, e 29,8% das pessoas sofreram perdas na faixa de 201-300 $ anualmente. Entre todas as culturas, o milho (Zea mays) foi considerado a cultura mais danificada, variando entre 1-300 kg anualmente. Na área de estudo, o porco-espinho também causou muitos danos a alguns vegetais importantes, incluindo espinafre (Spinacia oleracea), batata (Solanum tuberosum) e cebola (Allium cepa). Estimou-se que, em média, 511 kg de vegetais são destruídos pelo porco-espinho todos os anos nas terras agrícolas de Muzaffarabad. Concluiu-se que o porco-espinho de crista indiano tem um efeito devastador na agricultura, que é importante fonte de renda e alimento para a comunidade local. O desenvolvimento de uma estratégia eficaz de controle de pragas com a ajuda do governo local e do Departamento de Vida Selvagem pode ajudar os agricultores a superar esse problema.


Asunto(s)
Control de Plagas/economía , Puercoespines , Plagas Agrícolas
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