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1.
Immunol Cell Biol ; 102(5): 381-395, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38629182

RESUMO

Resident macrophages of various mammalian organs are characterized by several distinctive features in their gene expression profile and phenotype, including involvement in the regulation of organ functions, as well as reduced sensitivity to proinflammatory activation factors. The reasons for the formation of such a specific phenotype remain the subject of intensive research. Some papers emphasize the role of the origin of organ macrophages. Other studies indicate that monocytes that develop in the red bone marrow are also able to form resident macrophages with a phenotype characteristic of a particular organ, but this requires appropriate microenvironmental conditions. In this article, we studied the possibility of differentiation of monocyte-derived macrophages into cells with a Kupffer-like phenotype under the influence of the main stromal components of Kupffer cells macrophage niche: Ito cells, liver sinusoid endotheliocytes and hepatocyte growth factor (HGF). It was found that Kupffer cells are characterized by several features, including increased expression of transcription factors Spic and Id3, as well as MUP family genes, Clusterin and Ngp genes. In addition, Kupffer cells were characterized by a higher proliferative activity. The expression of marker genes of Kupffer cells (i.e. Id3, Spic, Marco and Timd4) increased in monocyte-derived macrophages during coculture with Ito cells, liver sinusoid endothelial cells, macrophage colony-stimulating factor and HGF cells only by 3 days. However, the expression level of these genes was always higher in Kupffer cells. In addition, a complete coincidence of the expressed gene profile in monocyte-derived macrophages and Kupffer cells did not occur even after 3 days of culturing.


Assuntos
Diferenciação Celular , Microambiente Celular , Células de Kupffer , Macrófagos , Fenótipo , Células de Kupffer/metabolismo , Células de Kupffer/citologia , Macrófagos/metabolismo , Animais , Monócitos/metabolismo , Monócitos/citologia , Fator de Crescimento de Hepatócito/metabolismo , Células Endoteliais/metabolismo , Técnicas de Cocultura , Humanos , Proliferação de Células , Células Cultivadas , Fígado/citologia , Fígado/metabolismo , Camundongos
2.
Nano Lett ; 23(17): 8218-8224, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37647545

RESUMO

The tunability of the optical properties of lead halide perovskite nanocrystals makes them highly appealing for applications. Halide anion exchange and quantum confinement enable tailoring of the band gap. For spintronics, the Landé g-factors of electrons and holes are essential. Using empirical tight-binding and k·p methods, we calculate them for nanocrystals of all-inorganic lead halide perovskites CsPbX3 (X = I, Br, Cl). The hole g-factor band gap dependence follows the universal law found for bulk perovskites, while for electrons, a considerable modification is predicted. Based on the k·p analysis, we conclude that this difference arises from the interaction of the bottom conduction band with the spin-orbit split electron states. These predictions are confirmed experimentally for electron and hole g-factors in CsPbI3 nanocrystals in a glass matrix, measured by time-resolved Faraday ellipticity in a magnetic field at cryogenic temperatures.

3.
Cell Biol Int ; 47(2): 327-340, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36342241

RESUMO

The serious problems of conventional breast cancer therapy strategies such as drug resistance, severe side effects, and lack of selectivity prompted the development of various cold atmospheric plasma (CAP) devices. Due to its advanced technology, CAP can produce a unique environment rich in reactive oxygen and nitrogen species (RONS), photons, charged ions, and an electric field, making it a promising revolutionary platform for cancer therapy. Despite substantial technological successes, CAP-based therapeutic systems are encounter with distinct limitations, including low control of the generated RONS, poor knowledge about its anticancer mechanisms, and challenges concerning designing, manufacturing, clinical translation, and commercialization, which must be resolved. The latest developments in CAP-based therapeutic systems for breast cancer treatment are discussed in this review. More significantly, the integration of CAP-based medicine approaches with other breast cancer therapies, including chemo- and nanotherapy is thoroughly addressed.


Assuntos
Neoplasias da Mama , Gases em Plasma , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Gases em Plasma/uso terapêutico , Espécies Reativas de Oxigênio , Espécies Reativas de Nitrogênio , Oxigênio
4.
Org Biomol Chem ; 21(17): 3615-3622, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37057616

RESUMO

The introduction of thiocyano groups into organic molecules is important for the preparation of many active ingredients and synthetic intermediates. A commonly used and attractive strategy is the nucleophilic substitution of halogens with the SCN anion or oxidative thiocyanation using an excess amount of external oxidants. A sustainable alternative to stoichiometric reagents is electrochemistry based on anodic oxidation of the SCN anion and other intermediates. Electrochemical thiocyanation of various organic compounds, carried out in the usual non-acidic organic solvents, is well known. Here, we present an electrochemical thiocyanation of 1,3-dicarbonyl compounds in which high efficiency was only achieved using AcOH as the solvent. Electrolysis proceeds in an undivided cell under constant current conditions without any additional halogen-containing electrolytes. Ammonium thiocyanate was used as the source of the SCN group and the electrolyte. Electrochemical thiocyanation of 1,3-dicarbonyl compounds begins with the generation of (SCN)2 from the thiocyanate anion, followed by the addition of thiocyanogen to the double bond of the enol tautomer of 1,3-dicarbonyl compounds, which finally gives the products. A variety of thiocyanated 1,3-dicarbonyl compounds bearing different functional groups were obtained in 37-82% yields and were shown to exhibit high antifungal activity.

5.
Nano Lett ; 22(11): 4583-4588, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35621509

RESUMO

Lead halide perovskite nanocrystals in a glass matrix are a promising platform for optoelectronic applications due to their excellent optical properties combined with outstanding stability against the environment. We reveal the potential of this system for spintronics by studying the electron spin properties of CsPb(Cl,Br)3 nanocrystals in a fluorophosphate glass matrix. Using optical spin orientation and spin depolarization with a radio frequency field, we measure longitudinal spin relaxation time, T1, reaching several hundreds of microseconds at low temperatures. This time T1 corresponds to a spin state with a small g factor, which we attribute to a weakly exchange-coupled electron-hole pair with antiparallel spins.

6.
Int J Mol Sci ; 24(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36674987

RESUMO

There is accumulating evidence that mitochondria and mitochondrial STAT3 are involved in the activation of mast cells. The mitochondria-targeted curcuminoids Mitocur-1 and Mitocur-3 have been suggested to reduce antigen-dependent mast cell activation by inhibiting mitochondrial STAT3. The aim of the current work was to investigate the mechanisms of action of these mitocurcuminoids on mast cells and mitochondrial functions. The pretreatment of rat basophilic leukemia cells RBL-2H3 with Mitocur-1 and Mitocur-3 decreased antigen-dependent degranulation but did not affect spontaneous degranulation. Both compounds caused mitochondrial fragmentation and increased mitochondrial ROS. Inhibition of Drp1 prevented mitochondrial fragmentation induced by Mitocur-3 but not by Mitocur-1. The antioxidant N-acetylcysteine inhibited mitochondrial fission induced by Mitocur-1 but not Mitocur-3. Mitochondrial fragmentation caused by Mitocur-3 but not Mitocur-1 was accompanied by activation of Drp1 and AMPK. These data suggest a distinct mechanism of action of mitocurcuminoids on the mitochondria of RBL-2H3 cells: Mitocur-3 stimulated AMPK and caused Drp1-dependent mitochondrial fragmentation, while Mitocur-1-induced mitochondrial fission was ROS-dependent. This difference may contribute to the higher toxicity of Mitocur-3 compared to Mitocur-1. The findings contribute to further drug development for inflammatory and allergic diseases.


Assuntos
Degranulação Celular , Mastócitos , Ratos , Animais , Mastócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Antígenos/metabolismo , Mitocôndrias
7.
Int J Mol Sci ; 24(19)2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37834280

RESUMO

Potato virus Y, an important viral pathogen of potato, has several genetic variants and geographic distributions which could be affected by environmental factors, aphid vectors, and reservoir plants. PVY is transmitted to virus-free potato plants by aphids and passed on to the next vegetative generations through tubers, but the effects of tuber transmission in PVY is largely unknown. By using high-throughput sequencing, we investigated PVY populations transmitted to potato plants by aphids in different climate zones of Russia, namely the Moscow and Astrakhan regions. We analyzed sprouts from the tubers produced by field-infected plants to investigate the impact of tuber transmission on PVY genetics. We found a significantly higher diversity of PVY isolates in the Astrakhan region, where winters are shorter and milder and summers are warmer compared to the Moscow region. While five PVY types, NTNa, NTNb, N:O, N-Wi, and SYR-I, were present in both regions, SYRI-II, SYRI-III, and 261-4 were only found in the Astrakhan region. All these recombinants were composed of the genome sections derived from PVY types O and N, but no full-length sequences of such types were present. The composition of the PVY variants in the tuber sprouts was not always the same as in their parental plants, suggesting that tuber transmission impacts PVY genetics.


Assuntos
Afídeos , Potyvirus , Solanum tuberosum , Animais , Potyvirus/genética , Doenças das Plantas , Solanum tuberosum/genética , Federação Russa , Genoma Viral , Afídeos/genética
8.
Org Biomol Chem ; 20(17): 3629-3636, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35420113

RESUMO

The electrochemical thiocyanation of barbituric acids with NH4SCN was disclosed in an undivided cell under constant current conditions. The electrosynthesis is the most efficient at a record high current density (janode ≈50-70 mA cm-2). NH4SCN has a dual role as the source of the SCN group and as the electrolyte. Electrochemical thiocyanation of barbituric acids starts with the generation of (SCN)2 from the thiocyanate anion. The addition of thiocyanogen to the double bond of the enol tautomer of barbituric acid gives thiocyanated barbituric acid. A variety of thiocyanated barbituric acids bearing different functional groups were obtained in 18-95% yields and were shown to exhibit promising antifungal activity.


Assuntos
Barbitúricos , Barbitúricos/química , Barbitúricos/farmacologia
9.
J Cell Physiol ; 236(4): 2829-2839, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32926425

RESUMO

In the course of the coronavirus disease 2019 (COVID-19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID-19 patients compared with the control group. Forty COVID-19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR-related orphan receptor gamma [RORγt], IL-17, and IL-23), and the secretion levels of IL-17 and IL-23 cytokines in COVID-19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor-ß [TGF-ß], and IL-10), and cytokine secretion levels (TGF-ß and IL-10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL-17/IL-10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019-n-CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID-19-dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients.


Assuntos
COVID-19/imunologia , Inflamação/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Idoso , Citocinas/imunologia , Feminino , Humanos , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia
10.
BMC Cardiovasc Disord ; 21(1): 483, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620082

RESUMO

BACKGROUND: Early recurrences of atrial arrhythmias (ERAA) after atrial fibrillation (AF) catheter ablation do not predict procedural failure. A well-demarcated homogeneous lesion delivered by cryoballoon is less arrhythmogenic, and the recommended three-months blanking period may not refer to cryoballoon ablation (CBA). OBJECTIVE: We aimed to evaluate the predictive role of ERAA after second-generation CBA using an implantable loop recorder. METHODS: This prospective observational study enrolled 100 patients (58 males, median age 58) with paroxysmal/persistent AF undergoing pulmonary vein (PV) CBA using second-generation cryoballoon with simultaneous ECG loop recorder implantation. The duration of follow-up was 12 months, with scheduled visits at 3, 6 and 12 months. RESULTS: 99 patients from 100 completed the 12-month follow-up period. ERAA occurred in 31.3 % of patients. 83.9 % of patients with ERAA also developed late recurrences. The 12-month freedom from AF in patients with ERAA was significantly lower than in those without ERAA (p < 0.0001). Non-paroxysmal AF and longer arrhythmia history were associated with increased risk of both early (HR 3.27; 95 % CI 1.32-8.08; p = 0.010 and HR 1.0147; 95 % CI 1.008-1.086; p = 0.015, respectively) and late recurrences (HR 3.89; 95 % CI 1.67-9.04; p = 0.002 and HR 1.0142; 95 % CI 1.007-1.078; p = 0.019, respectively) of AF. ERAA were another predictor for procedural failure (HR 15.2; 95 % CI (6.42-35.99; p = 0.019). CONCLUSIONS: ERAA occurred in the third of the patients after PV second-generation CBA and are strongly associated with procedural failure. Longer duration of AF history and persistent AF are independent predictors of AF's early and late recurrence.


Assuntos
Fibrilação Atrial/cirurgia , Criocirurgia/efeitos adversos , Eletrocardiografia Ambulatorial , Veias Pulmonares/cirurgia , Tecnologia de Sensoriamento Remoto , Potenciais de Ação , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Eletrocardiografia Ambulatorial/instrumentação , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Veias Pulmonares/fisiopatologia , Recidiva , Tecnologia de Sensoriamento Remoto/instrumentação , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
11.
Space Weather ; 17(10): 1384-1403, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31894181

RESUMO

The Community Coordinated Modeling Center has been leading community-wide space science and space weather model validation projects for many years. These efforts have been broadened and extended via the newly launched International Forum for Space Weather Modeling Capabilities Assessment (https://ccmc.gsfc.nasa.gov/assessment/). Its objective is to track space weather models' progress and performance over time, a capability that is critically needed in space weather operations and different user communities in general. The Space Radiation and Plasma Effects Working Team of the aforementioned International Forum works on one of the many focused evaluation topics and deals with five different subtopics (https://ccmc.gsfc.nasa.gov/assessment/topics/radiation-all.php) and varieties of particle populations: Surface Charging from tens of eV to 50-keV electrons and internal charging due to energetic electrons from hundreds keV to several MeVs. Single-event effects from solar energetic particles and galactic cosmic rays (several MeV to TeV), total dose due to accumulation of doses from electrons (>100 keV) and protons (>1 MeV) in a broad energy range, and radiation effects from solar energetic particles and galactic cosmic rays at aviation altitudes. A unique aspect of the Space Radiation and Plasma Effects focus area is that it bridges the space environments, engineering, and user communities. The intent of the paper is to provide an overview of the current status and to suggest a guide for how to best validate space environment models for operational/engineering use, which includes selection of essential space environment and effect quantities and appropriate metrics.

12.
BMC Immunol ; 18(1): 31, 2017 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-28633645

RESUMO

BACKGROUND: Recent fundamental and clinical studies have confirmed the effectiveness of utilizing the potential of the immune system to remove tumor cells disseminated in a patient's body. Cytotoxic T lymphocytes (CTLs) are considered the main effectors in cell-mediated antitumor immunity. Approaches based on antigen presentation to CTLs by dendritic cells (DCs) are currently being intensively studied, because DCs are more efficient in tumor antigen presentation to T cells through their initiation of strong specific antitumor immune responses than other types of antigen-presenting cells. Today, it has become possible to isolate CTLs specific for certain antigenic determinants from heterogeneous populations of mononuclear cells. This enables direct and specific cell-mediated immune responses against cells carrying certain antigens. The aim of the present study was to develop an optimized protocol for generating CTL populations specific for epitopes of tumor-associated antigen HER2/neu, and to assess their cytotoxic effects against the HER2/neu-expressing MCF-7 tumor cell line. METHODS: The developed protocol included sequential stages of obtaining mature DCs from PBMCs from HLA A*02-positive healthy donors, magnet-assisted transfection of mature DCs with the pMax plasmid encoding immunogenic peptides HER2 p369-377 (E75 peptide) and HER2 p689-697 (E88 peptide), coculture of antigen-activated DCs with autologous lymphocytes, magnetic-activated sorting of CTLs specific to HER2 epitopes, and stimulation of isolated CTLs with cytokines (IL-2, IL-7, and IL-15). RESULTS: The resulting CTL populations were characterized by high contents of CD8+ cells (71.5% in cultures of E88-specific T cells and 90.2% in cultures of E75-specific T cells) and displayed strong cytotoxic effects against the MCF-7 cell line (percentages of damaged tumor cells in samples under investigation were 60.2 and 65.7% for E88- and E75-specific T cells, respectively; level of spontaneous death of target cells was 17.9%). CONCLUSIONS: The developed protocol improves the efficiency of obtaining HER2/neu-specific CTLs and can be further used to obtain cell-based vaccines for eradicating targeted tumor cells to prevent tumor recurrence after the major tumor burden has been eliminated and preventing metastasis in patients with HER2-overexpressing tumors.


Assuntos
Adenocarcinoma/imunologia , Neoplasias da Mama/imunologia , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Imunoterapia Adotiva/métodos , Receptor ErbB-2/metabolismo , Linfócitos T Citotóxicos/imunologia , Adenocarcinoma/terapia , Neoplasias da Mama/terapia , Epitopos/genética , Feminino , Antígeno HLA-A2/metabolismo , Humanos , Ativação Linfocitária , Células MCF-7 , Metástase Neoplásica , Fragmentos de Peptídeos/genética , Receptor ErbB-2/genética , Linfócitos T Citotóxicos/transplante
13.
BMC Plant Biol ; 17(1): 153, 2017 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-28899358

RESUMO

BACKGROUND: Most data concerning chromosome organization have been acquired from studies of a small number of model organisms, the majority of which are mammals. In plants with large genomes, the chromosomes are significantly larger than the animal chromosomes that have been studied to date, and it is possible that chromosome condensation in such plants was modified during evolution. Here, we analyzed chromosome condensation and decondensation processes in order to find structural mechanisms that allowed for an increase in chromosome size. RESULTS: We found that anaphase and telophase chromosomes of plants with large chromosomes (average 2C DNA content exceeded 0.8 pg per chromosome) contained chromatin-free cavities in their axial regions in contrast to well-characterized animal chromosomes, which have high chromatin density in the axial regions. Similar to animal chromosomes, two intermediates of chromatin folding were visible inside condensing (during prophase) and decondensing (during telophase) chromosomes of Nigella damascena: approximately 150 nm chromonemata and approximately 300 nm fibers. The spatial folding of the latter fibers occurs in a fundamentally different way than in animal chromosomes, which leads to the formation of chromosomes with axial chromatin-free cavities. CONCLUSION: Different compaction topology, but not the number of compaction levels, allowed for the evolution of increased chromosome size in plants.


Assuntos
Cromossomos de Plantas/ultraestrutura , Nigella damascena/genética , Nigella damascena/ultraestrutura , Cromatina/ultraestrutura , Montagem e Desmontagem da Cromatina , Estruturas Cromossômicas , Cromossomos de Plantas/fisiologia , DNA de Plantas , Tamanho do Genoma , Genoma de Planta , Mitose
14.
Cell Biol Int ; 40(11): 1140-1151, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27569720

RESUMO

The first description of intrachromosomal fibers was made by Baranetzky in 1880. Since that time, a plethora of fibrillar substructures have been described inside the mitotic chromosomes, and published data indicate that chromosomes may be formed as a result of the hierarchical folding of chromatin fibers. In this review, we examine the evolution and the current state of research on the morphological organization of mitotic chromosomes.


Assuntos
Cromatina/química , Cromatina/fisiologia , Animais , Humanos , Mitose/fisiologia , Nucleossomos/fisiologia
15.
Biochim Biophys Acta ; 1830(11): 5059-67, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23876295

RESUMO

BACKGROUND: Genetically encoded photosensitizers are a promising optogenetic instrument for light-induced production of reactive oxygen species in desired locations within cells in vitro or whole body in vivo. Only two such photosensitizers are currently known, GFP-like protein KillerRed and FMN-binding protein miniSOG. In this work we studied phototoxic effects of miniSOG in cancer cells. METHODS: HeLa Kyoto cell lines stably expressing miniSOG in different localizations, namely, plasma membrane, mitochondria or chromatin (fused with histone H2B) were created. Phototoxicity of miniSOG was tested on the cells in vitro and tumor xenografts in vivo. RESULTS: Blue light induced pronounced cell death in all three cell lines in a dose-dependent manner. Caspase 3 activation was characteristic of illuminated cells with mitochondria- and chromatin-localized miniSOG, but not with miniSOG in the plasma membrane. In addition, H2B-miniSOG-expressing cells demonstrated light-induced activation of DNA repair machinery, which indicates massive damage of genomic DNA. In contrast to these in vitro data, no detectable phototoxicity was observed on tumor xenografts with HeLa Kyoto cell lines expressing mitochondria- or chromatin-localized miniSOG. CONCLUSIONS: miniSOG is an excellent genetically encoded photosensitizer for mammalian cells in vitro, but it is inferior to KillerRed in the HeLa tumor. GENERAL SIGNIFICANCE: This is the first study to assess phototoxicity of miniSOG in cancer cells. The results suggest an effective ontogenetic tool and may be of interest for molecular and cell biology and biomedical applications.


Assuntos
Flavoproteínas/genética , Terapia Genética/métodos , Oxigênio/metabolismo , Fármacos Fotossensibilizantes/metabolismo , Animais , Caspase 3/genética , Caspase 3/metabolismo , Morte Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Membrana Celular/genética , Membrana Celular/metabolismo , Cromatina/genética , Cromatina/metabolismo , Dano ao DNA , Reparo do DNA , Dermatite Fototóxica/etiologia , Dermatite Fototóxica/genética , Dermatite Fototóxica/metabolismo , Feminino , Flavoproteínas/metabolismo , Células HEK293 , Células HeLa , Humanos , Luz/efeitos adversos , Camundongos , Camundongos Nus , Mitocôndrias/genética , Mitocôndrias/metabolismo , Riboflavina/genética , Riboflavina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
J Affect Disord ; 363: 520-531, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39043310

RESUMO

BACKGROUND: Compulsive- and anxiety-like behaviour can be efficiently modelled in SAPAP3 knockout (KO) mice, a preclinical model of relevance to obsessive-compulsive disorder (OCD). Although there is emerging evidence in the clinical literature of gastrointestinal dysfunction in OCD, no previous studies have investigated gut function in preclinical models of relevance to OCD. Similarly, the effects of voluntary exercise (EX) or environmental enrichment (EE) have not yet been explored in this context. METHOD: We comprehensively phenotyped the SAPAP3 KO mouse model, including the assessment of grooming microstructure, anxiety- and depressive-like behaviour, and gastrointestinal function. Mice were exposed to either standard housing (SH), exercise (EX, provided by giving mice access to running wheels), or environmental enrichment (EE) for 4 weeks to investigate the effects of enriched housing conditions in this animal model relevant to OCD. FINDINGS: Our study is the first to assess grooming microstructure, perseverative locomotor activity, and gastrointestinal function in SAPAP3 KO mice. We are also the first to report a sexually dimorphic effect of grooming in young-adult SAPAP3 KO mice; along with changes to grooming patterning and indicators of gut dysfunction, which occurred in the absence of gut dysbiosis in this model. Overall, we found no beneficial effects of voluntary exercise or environmental enrichment interventions in this mouse model; and unexpectedly, we revealed a deleterious effect of wheel-running exercise on grooming behaviour. We suspect that the detrimental effects of experimental housing in our study may be indicative of off-target effects of stress-a conclusion that warrants further investigation into the effects of chronic stress in this preclinical model of compulsive behaviour.

17.
Mar Pollut Bull ; 205: 116695, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38996758

RESUMO

Birds have been impacted by plastic pollution via entanglement, accidental ingestion, and exposure to chemical contaminants. However, plastics were also observed as a nesting material for several species. For the first time, we describe the occurrence and composition of plastics in 36 nests of the crested oropendola (Psarocolius decumanus) in three different sites on the Amazon coast. Plastics were present in 67 % of abandoned, fallen nests. At the mangrove site, all nests contained plastics, while at the grassy clearing and the fishermen's village, plastics were present at 35.3 and 90 % of the nests, respectively. Blue fibers and ropes were the main plastics observed, probably derived from discarded fishing gear. Of 79 analyzed fibers, 97.5 % were composed of Polyethylene, and 83.5 % contained Cobalt Phthalocyanine as an additive. Our results showed a widespread use of plastics by P. decumanus, which may increase the exposure of both juveniles and adults to potential contaminants.


Assuntos
Monitoramento Ambiental , Plásticos , Plásticos/análise , Brasil , Animais , Comportamento de Nidação , Aves
18.
HGG Adv ; : 100334, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033325

RESUMO

The effective implementation of WES and WGS-based diagnostics in the management of children affected with genetic diseases and the rapid decrease in the cost of NGS enables the expansion of this method to the newborn genetic screening programs. Such NGS-based screening greatly increases the number of diseases that can be detected compared to conventional newborn screening, as the latter being aimed at early detection of a limited number of inborn diseases. Moreover, genetic testing provides new possibilities for family members of the proband, as many variants responsible for adult-onset conditions are inherited from the parents. However, the idea of NGS-based screening in healthy children raises issues of medical and ethical integrity as well as technical questions including interpretation of the observed variants. Pilot studies have shown that both parents and medical professionals have moved forward and are enthused about these new possibilities. However, either the number of participants or the number of genes studied in previous investigations, so far has been limited to a few hundreds, restricting the scope of potential findings. Our current study (NCT05325749) includes 7,000 apparently healthy infants born at our center between February 2021 and May 2023, who were screened for pathogenic variants in 2,350 genes. Clinically significant variants associated with early-onset diseases that can be treated, prevented or where symptoms can be alleviated with the timely introduced symptomatic therapy, were observed in 0.9% of phenotypically normal infants, 2.1% of the screened newborns were found to carry variants associated with reduced penetrance or monogenic diseases of adult-onset and/or variable expressivity, and 0.3% had chromosomal abnormalities. Here, we report our results and address questions regarding interpretation of variants in newborns who were presumed to be healthy.

19.
Cell Rep ; 43(4): 114062, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38588339

RESUMO

The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4+ T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients. Single-cell RNA and TCR sequencing of VZV-specific T cells shows that T cell activation pathways are significantly decreased after stimulation with VZV peptides in convalescent HZ patients. TCR clustering indicates that TCRs from HZ patients co-cluster more often together than TCRs from controls. Collectively, our results suggest that not only lower VZV-specific TCR diversity but also reduced functional TCR affinity for VZV-specific proteins in HZ patients leads to lower T cell activation and consequently affects the susceptibility for viral reactivation.


Assuntos
Herpes Zoster , Herpesvirus Humano 3 , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T , Humanos , Herpes Zoster/imunologia , Herpes Zoster/virologia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/imunologia , Ativação Linfocitária/imunologia , Herpesvirus Humano 3/imunologia , Feminino , Pessoa de Meia-Idade , Masculino , Linfócitos T CD4-Positivos/imunologia , Idoso , Adulto , Epitopos de Linfócito T/imunologia
20.
Monogr Soc Res Child Dev ; 78(3): vii-viii, 1-129, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23782434

RESUMO

Children with incarcerated parents are at risk for a variety of problematic outcomes, yet research has rarely examined protective factors or resilience processes that might mitigate such risk in this population. In this volume, we present findings from five new studies that focus on child- or family-level resilience processes in children with parents currently or recently incarcerated in jail or prison. In the first study, empathic responding is examined as a protective factor against aggressive peer relations for 210 elementary school age children of incarcerated parents. The second study further examines socially aggressive behaviors with peers, with a focus on teasing and bullying, in a sample of 61 children of incarcerated mothers. Emotion regulation is examined as a possible protective factor. The third study contrasts children's placement with maternal grandmothers versus other caregivers in a sample of 138 mothers incarcerated in a medium security state prison. The relation between a history of positive attachments between mothers and grandmothers and the current cocaregiving alliance are of particular interest. The fourth study examines coparenting communication in depth on the basis of observations of 13 families with young children whose mothers were recently released from jail. Finally, in the fifth study, the proximal impacts of a parent management training intervention on individual functioning and family relationships are investigated in a diverse sample of 359 imprisoned mothers and fathers. Taken together, these studies further our understanding of resilience processes in children of incarcerated parents and their families and set the groundwork for further research on child development and family resilience within the context of parental involvement in the criminal justice system.


Assuntos
Filho de Pais com Deficiência/psicologia , Prisioneiros , Resiliência Psicológica , Bullying , Criança , Custódia da Criança , Emoções , Empatia , Feminino , Humanos , Relação entre Gerações , Masculino , Apego ao Objeto , Poder Familiar , Grupo Associado
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