RESUMEN
Accurate processing and analysis of non-human primate (NHP) brain magnetic resonance imaging (MRI) serves an indispensable role in understanding brain evolution, development, aging, and diseases. Despite the accumulation of diverse NHP brain MRI datasets at various developmental stages and from various imaging sites/scanners, existing computational tools designed for human MRI typically perform poor on NHP data, due to huge differences in brain sizes, morphologies, and imaging appearances across species, sites, and ages, highlighting the imperative for NHP-specialized MRI processing tools. To address this issue, in this paper, we present a robust, generic, and fully automated computational pipeline, called non-human primates Brain Extraction and Segmentation Toolbox (nBEST), whose main functionality includes brain extraction, non-cerebrum removal, and tissue segmentation. Building on cutting-edge deep learning techniques by employing lifelong learning to flexibly integrate data from diverse NHP populations and innovatively constructing 3D U-NeXt architecture, nBEST can well handle structural NHP brain MR images from multi-species, multi-site, and multi-developmental-stage (from neonates to the elderly). We extensively validated nBEST based on, to our knowledge, the largest assemblage dataset in NHP brain studies, encompassing 1,469 scans with 11 species (e.g., rhesus macaques, cynomolgus macaques, chimpanzees, marmosets, squirrel monkeys, etc.) from 23 independent datasets. Compared to alternative tools, nBEST outperforms in precision, applicability, robustness, comprehensiveness, and generalizability, greatly benefiting downstream longitudinal, cross-sectional, and cross-species quantitative analyses. We have made nBEST an open-source toolbox (https://github.com/TaoZhong11/nBEST) and we are committed to its continual refinement through lifelong learning with incoming data to greatly contribute to the research field.
Asunto(s)
Encéfalo , Aprendizaje Profundo , Imagen por Resonancia Magnética , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/anatomía & histología , Imagen por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Macaca mulatta , Neuroimagen/métodos , Pan troglodytes/anatomía & histología , Envejecimiento/fisiologíaRESUMEN
Persisters are a form of dormancy in bacteria that provide temporary resistance to antibiotics. The following reports on the formation of Escherichia coli O157:H7 E318 type II persisters from a protracted (8 days) challenge with ampicillin. Escherichia coli O157:H7 followed a multiphasic die-off pattern with an initial rapid decline (Phase I) of susceptible cells that transitioned to a slower rate representing tolerant cells (Phase II). After 24 h post-antibiotic challenge, the E. coli O157:H7 levels remained relatively constant at 2 log CFU/mL (Phase III), but became non-culturable within 8-days (Phase IV). The revival of persisters in Phase III could be achieved by the removal of antibiotic stress, although those in Phase IV required an extended incubation period or application of acid-shock. The carbon utilization profile of persister cells was less diverse compared with non-persisters, with only methyl pyruvate being utilized from the range tested. Inclusion of methyl pyruvate in tryptic soy agar revived non-cultural persisters, presumably by stimulating metabolism. The results suggest that persisters could be subdivided into culturable or non-culturable cells, with the former representing a transition state to the latter. The study provided insights into how to revive cells from dormancy to aid enumeration and control.
Asunto(s)
Ácidos/farmacología , Antibacterianos/farmacología , Escherichia coli O157/efectos de los fármacos , Escherichia coli O157/crecimiento & desarrollo , Piruvatos/farmacología , Recuento de Colonia Microbiana , Escherichia coli O157/genéticaRESUMEN
Transgenerational effects of microcystin-LR (MC-LR) released by cyanobacterial blooms have become a hot topic. In the present study, adult zebrafish pairs were exposed to 0, 0.4, 2, and 10 µg/L MC-LR for 60 days and the embryos (F1 generation) were hatched without or with continued MC-LR exposures at the same concentrations until 5 days postfertilization (dpf). The results showed the existence of MC-LR both in F0 gonads and in F1 embryos and indicated that MC-LR could be transferred directly from the F0 adult fish to F1 offspring. The adverse effects on sex hormone levels, sexual development, and fecundity in F0 generation along with abnormal development in F1 offspring were observed. Furthermore, downregulation of antioxidant genes (cat, mn-sod, gpx1a) and upregulation of innate immune-related genes (tlr4a, myd88, tnfα, il1ß) as well as increased proinflammation cytokine contents (TNF-α, IL-1ß, IL-6) were noticed in F1 offspring without/with continued MC-LR exposures. In addition, significant differences between the two F1 embryo treatments demonstrated that continuous MC-LR exposure could result in a higher degree of inflammatory response compared to those without MC-LR exposure. Our findings revealed that MC-LR could exert cross-generational effects of immunotoxicity by inhibiting the antioxidant system and activating an inflammatory response.
Asunto(s)
Contaminantes Químicos del Agua , Pez Cebra , Animales , Inmunidad Innata , Toxinas Marinas , Microcistinas , OxidorreductasasRESUMEN
Magnetic Resonance Imaging (MRI) plays a pivotal role in the accurate measurement of brain subcortical structures in macaques, which is crucial for unraveling the complexities of brain structure and function, thereby enhancing our understanding of neurodegenerative diseases and brain development. However, due to significant differences in brain size, structure, and imaging characteristics between humans and macaques, computational tools developed for human neuroimaging studies often encounter obstacles when applied to macaques. In this context, we propose an Anatomy Attentional Fusion Network (AAF-Net), which integrates multimodal MRI data with anatomical constraints in a multi-scale framework to address the challenges posed by the dynamic development, regional heterogeneity, and age-related size variations of the juvenile macaque brain, thus achieving precise subcortical segmentation. Specifically, we generate a Signed Distance Map (SDM) based on the initial rough segmentation of the subcortical region by a network as an anatomical constraint, providing comprehensive information on positions, structures, and morphology. Then we construct AAF-Net to fully fuse the SDM anatomical constraints and multimodal images for refined segmentation. To thoroughly evaluate the performance of our proposed tool, over 700 macaque MRIs from 19 datasets were used in this study. Specifically, we employed two manually labeled longitudinal macaque datasets to develop the tool and complete four-fold cross-validations. Furthermore, we incorporated various external datasets to demonstrate the proposed tool's generalization capabilities and promise in brain development research. We have made this tool available as an open-source resource at https://github.com/TaoZhong11/Macaque_subcortical_segmentation for direct application.
Asunto(s)
Encéfalo , Macaca , Imagen por Resonancia Magnética , Animales , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/anatomía & histología , Neuroimagen/métodos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
This study aimed to explore how Wuchang bream (Megalobrama amblycephala) survive and defend against the toxicity of ambient total ammonia nitrogen (0, 5, 10, 20 and 30 mg/L TA-N) during 30-day exposure. As a result, hepatic malondialdehyde and protein carbonylation as well as histopathological alterations increased with increasing TA-N level, which suggested that chronic ammonia exposure caused oxidative stress and damage in the liver of fish. Meanwhile, the activities of hepatic total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glucose 6-phosphate dehydrogenase (G6PD) as well as the mRNA expression of Cu/Zn sod, cat, gpx and g6pd were elevated significantly along with significant reduction of glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) (P < 0.05). These results indicated that hepatic antioxidant responses were activated to alleviate oxidative damages induced by ammonia, in which lower-concentration ammonia only initiate SOD-CAT-GR-G6PDH defense and higher ammonia activated the SOD-CAT-GPx-GSH-GR-G6PDH antioxidant response. In addition, significant increases of serum urea and hepatic ammonia, urea, glutamine, arginase as well as glutamine synthetase were detected with the increase of TA-N (P < 0.05), while serum ammonia levels kept stable (P > 0.05). The present findings further revealed that ammonia could be detoxified directly into glutamine and urea in Wuchang bream to cope with ammonia exposure. In conclusion, under chronic ammonia exposure, enhanced hepatic antioxidant responses as well as increased urea and glutamine synthesis worked in combination to allow Megalobrama amblycephala to defend against environmental ammonia toxicity.
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Amoníaco , Cyprinidae/metabolismo , Proteínas de Peces/metabolismo , Glutamina/metabolismo , Hígado , Urea/metabolismo , Amoníaco/metabolismo , Amoníaco/toxicidad , Animales , Hígado/metabolismo , Hígado/patología , Estrés Oxidativo , Contaminantes Químicos del Agua/toxicidadRESUMEN
Waterborne microcystin-LR (MC-LR) released by cyanobacterial blooms in eutrophic water bodies have caused serious risk to aquatic animal and human health. In the present study, we for the first time conducted a comprehensive in vivo investigation on chronic inflammatory responses and its molecular pathways of different environmental relevant levels of MC-LR (0, 0.4, 2 and 10⯵g/L) in male zebrafish (Danio rerio). The results showed that chronic MC-LR exposure caused splenic inflammatory changes including the formation of melano-macrophage centers, remarkable elevation of serum tumor necrosis factor alpha (TNFα) and interleukin 1 beta (IL1ß) levels as well as significant upregulated expression of MyD88-dependent toll-like receptor (TLR/MyD88) signaling pathway genes (tlr4a, myd88, erk2, p38a, il1ß and tnfα). The immunohistochemical and western blot results further validated that higher MC-LR concentrations tended to enhance the MyD88 signal. Moreover, significant decreases of serum C3 levels along with splenic c3b expression in the 10⯵g/L exposure group proved that chronic MC-LR exposure could ultimately decrease the innate immunity of fish. Our findings revealed that chronic exposure of MC-LR could cause chronic inflammation through TLR/MyD88 signaling pathway and subsequently induce immune disorders in male zebrafish, which also urge us to pay more attention on the potential immunotoxicity of long-term exposure to low concentration of MC-LR.
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Microcistinas/toxicidad , Factor 88 de Diferenciación Mieloide/metabolismo , Contaminantes Químicos del Agua/toxicidad , Proteínas de Pez Cebra/metabolismo , Animales , Masculino , Toxinas Marinas , Pez CebraRESUMEN
In order to investigate protective roles of dietary selenium yeast (SY) and tea polyphenols (TPs) on growth of juvenile Wuchang bream (Megalobrama amblycephala) and its resistance under ammonia stress, juvenile Wuchang bream were randomly assigned into four groups: a control group fed basal diets and three treatment groups fed basal diets supplemented with 0.50 mg/kg SY, 50 mg/kg TPs and a combination of 0.50 mg/kg SY and 50 mg/kg TPs, respectively. After 60 days of feeding, growth parameters of Wuchang bream were measured along with serum hormones and the transcription of growth axis-related genes. Then fish were exposed to ammonia stress of 22.5 mg/L total ammonia nitrogen. Hepatic oxidative damage parameters, antioxidant responses and ultrastructure were evaluated before ammonia exposure (0 h) and at 3, 6, 12, 24, and 48 h after ammonia exposure. Results show that before ammonia exposure, the growth parameters, serum GH and IGF-1 levels as well as the growth axis-related gene expression (gh, ghr2 and igf-1) for the SY and combination groups were higher than those determined for the fish on the control diet. In contrast, the administration of TP alone didn't have significant effects on the growth parameters and growth-related hormones. After ammonia exposure, compared with the control, remarkable increases in the activity and mRNA expression of hepatic antioxidant enzymes (glutathione peroxidase and catalase superoxide dismutase) in three treatment groups were observed along with decreases of hepatic malondialdehyde and protein carbonylation levels, indicating that the single and combined supplementation of SY and TPs could enhance antioxidant capacity to alleviate oxidative stress and damage by ammonia. Consistent with this finding, alterations of the liver ultrastructure in three treatment groups were less severe and faster recovery than in the control group after ammonia exposure. In conclusion, a basal diet supplemented with the combination of 0.50 mg/kg SY and 50 mg/kg TPs could has very beneficial effects on the whole aspects of the growth and ammonia resistance in Wuchang bream juveniles.
RESUMEN
Hazardous contaminants, such as nitrite and microcystin-leucine arginine (MC-LR), are released into water bodies during cyanobacterial blooms and may adversely influence the normal physiological function of hydrobiontes. The combined effects of nitrite and MC-LR on the antioxidant defense and innate immunity were evaluated through an orthogonal experimental design (nitrite: 0, 29, 290 µM; MC-LR: 0, 3, 30 nM). Remarkable increases in malondialdehyde (MDA) levels have suggested that nitrite and/or MC-LR exposures induce oxidative stress in fish spleen, which were indirectly confirmed by significant downregulations of total antioxidant capacity (T-AOC), glutathione (GSH) contents, as well as transcriptional levels of antioxidant enzyme genes cat1, sod1 and gpx1a. Simultaneously, nitrite and MC-LR significantly decreased serum complement C3 levels as well as the transcriptional levels of splenic c3b, lyz, il1ß, ifnγ and tnfα, and indicated that they could jointly impact the innate immunity of fish. The severity and extent of splenic lesions were aggravated by increased concentration of nitrite or MC-LR and became more serious in combined groups. The damages of mitochondria and pseudopodia in splenic macrophages suggest that oxidative stress exerted by nitrite and MC-LR aimed at the membrane structure of immune cells and ultimately disrupted immune function. Our results clearly demonstrate that nitrite and MC-LR exert synergistic suppressive effects on fish innate immunity via interfering antioxidant responses, and their joint toxicity should not be underestimated in eutrophic lakes.
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Inmunidad Innata/efectos de los fármacos , Microcistinas/toxicidad , Nitritos/toxicidad , Bazo/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Animales , Complemento C3/análisis , Sinergismo Farmacológico , Eutrofización , Glutatión/metabolismo , Masculino , Malondialdehído/metabolismo , Toxinas Marinas , Oxidación-Reducción , Bazo/metabolismo , Bazo/patología , Pez CebraRESUMEN
Microcystin-LR (MC-LR) released by Microcystis blooms degradation usually co-exists with a chemical called nitrite, posing a serious harm to aquatic organisms. To assess the single and combined effects of MC-LR and nitrite on the reproductive endocrine system, a fully factorial experiment was designed and adult male zebrafish (Danio rerio) were exposed to 9 treatment combinations of MC-LR (0, 3, 30⯵g/L) and nitrite (0, 2, 20â¯mg/L) for 30â¯d. The results showed that both MC-LR and nitrite caused concentration-dependent effects including the growth inhibition, decreased gonad index as well as testicular injuries with widen intercellular spaces and seminiferous epithelium deteriorations. And testicular pathological changes in the co-exposure groups of MC-LR and nitrite were similar but more serious than those in single-factor exposure groups. Concurrently, exposure to MC-LR or nitrite alone could significantly decrease T levels by downregulating gene expressions (gnrh2, lhß, ar, lhr) in the hypothalamic-pituitary-gonadal-liver-axis (HPGL-axis), and there were significant interactions between MC-LR and nitrite on them. In contrast, E2 levels as well as transcriptional levels of cyp19a1b, cyp19a1a and vtg1 showed significant inductions with increasing MC-LR concentrations, indicating an estrogen-like effect of MC-LR. Our findings illustrated that co-exposure of MC-LR and nitrite synergistically cause reproductive dysfunction by interfering with the HPGL axis in male fish, which prompt us to focus more on the potential risks in fish reproduction and even population dynamics due to the wide occurrence of toxic cyanobacterial blooms.