Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for ...these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.
Impacts of environmental complexity on affective states in slow-growing broiler chickens (Gallus gallus domesticus) are unknown. Chickens' performance in judgment bias tests (JBT) can be limited as ...they are tested individually, causing fear and anxiety. The objectives were to apply a social-pair JBT to assess the effect of environmental complexity on slow-growing broiler chickens` affective states, and assess the impact of fearfulness, anxiety, and chronic stress on JBT performance. Six-hundred Hubbard Redbro broilers were housed in six low-complexity (similar to commercial) or six high-complexity (permanent and temporary enrichments) pens. Twelve chicken pairs were trained (1 pair/pen, n = 24 chickens) using a multimodal approach (visual and spatial cues), with reward and neutral cues of opposing color and location. Three ambiguous cues were tested: near-positive, middle, and near-neutral cues. Approach and pecking behavior were recorded. Eighty-three percent of chickens (20/24) were successfully trained in 13 days. Fearfulness, anxiety, and chronic stress did not impact chickens' performance. Chickens successfully discriminated between cues. Low-complexity chickens approached the middle cue faster than high-complexity chickens, indicating that they were in a more positive affective state. The environmental complexity provided in this study did not improve affective states in slow-growing broiler chickens compared to a control. A social-pair JBT resulted in excellent learning and testing outcomes in slow-growing broilers.
Abstract
Chikungunya virus (CHIKV) is the causative agent of Chikungunya fever, an acute febrile and arthritogenic illness with no effective treatments available. The development of effective ...therapeutic strategies could be significantly accelerated with detailed knowledge of the molecular components behind CHIKV replication. However, drug discovery is hindered by our incomplete understanding of their main components. The RNA-dependent RNA-polymerase (nsP4-CHIKV) is considered the key enzyme of the CHIKV replication complex and a suitable target for antiviral therapy. Herein, the nsP4-CHIKV was extensively characterized through experimental and computational biophysical methods. In the search for new molecules against CHIKV, a compound designated LabMol-309 was identified as a strong ligand of the nsp4-CHIKV and mapped to bind to its active site. The antiviral activity of LabMol-309 was evaluated in cellular-based assays using a CHIKV replicon system and a reporter virus. In conclusion, this study highlights the biophysical features of nsP4-CHIKV and identifies a new compound as a promising antiviral agent against CHIKV infection.
Interleukin 33 (IL-33) is a new member of the IL-1 family of cytokines which signals via its receptor, ST2 (IL-33R), and has an important role in Th2 and mast cell responses. This study shows that ...IL-33 orchestrates neutrophil migration in arthritis.
Methylated bovine serum albumin (mBSA) challenge in the knee joint of mBSA-immunised mice induced local neutrophil migration accompanied by increased IL-33R and IL-33 mRNA expression. Cell migration was inhibited by systemic and local treatments with soluble (s)IL-33R, an IL-33 decoy receptor, and was not evident in IL-33R-deficient mice. IL-33 injection also induced IL-33R-dependent neutrophil migration. Antigen- and IL-33-induced neutrophil migration in the joint was dependent on CXCL1, CCL3, tumour necrosis factor alpha (TNFalpha) and IL-1beta synthesis. Synovial tissue, macrophages and activated neutrophils expressed IL-33R. IL-33 induces neutrophil migration by activating macrophages to produce chemokines and cytokines and by directly acting on neutrophils. Importantly, neutrophils from patients with rheumatoid arthritis successfully treated with anti-TNFalpha antibody (infliximab) expressed significantly lower levels of IL-33R than patients treated with methotrexate alone. Only neutrophils from patients treated with methotrexate alone or from normal donors stimulated with TNFalpha responded to IL-33 in chemotaxis.
These results suggest that suppression of IL-33R expression in neutrophils, preventing IL-33-induced neutrophil migration, may be an important mechanism of anti-TNFalpha therapy of inflammation.
Dengue virus (DENV) causes a major arthropod-borne viral disease, with 2.5 billion people living in risk areas. DENV consists in a 50 nm-diameter enveloped particle in which the surface proteins are ...arranged with icosahedral symmetry, while information about nucleocapsid (NC) structural organization is lacking. DENV NC is composed of the viral genome, a positive-sense single-stranded RNA, packaged by the capsid (C) protein. Here, we established the conditions for a reproducible in vitro assembly of DENV nucleocapsid-like particles (NCLPs) using recombinant DENVC. We analyzed NCLP formation in the absence or presence of oligonucleotides in solution using small angle X-ray scattering, Rayleigh light scattering as well as fluorescence anisotropy, and characterized particle structural properties using atomic force and transmission electron microscopy imaging. The experiments in solution comparing 2-, 5- and 25-mer oligonucleotides established that 2-mer is too small and 5-mer is sufficient for the formation of NCLPs. The assembly process was concentration-dependent and showed a saturation profile, with a stoichiometry of 1:1 (DENVC:oligonucleotide) molar ratio, suggesting an equilibrium involving DENVC dimer and an organized structure compatible with NCLPs. Imaging methods proved that the decrease in concentration to sub-nanomolar concentrations of DENVC allows the formation of regular spherical NCLPs after protein deposition on mica or carbon surfaces, in the presence as well as in the absence of oligonucleotides, in this latter case being surface driven. Altogether, the results suggest that in vitro assembly of DENV NCLPs depends on DENVC charge neutralization, which must be a very coordinated process to avoid unspecific aggregation. Our hypothesis is that a specific highly positive spot in DENVC α4-α4' is the main DENVC-RNA binding site, which is required to be firstly neutralized to allow NC formation.
The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian
species mosquitos highlights a need to monitor the risk of reestablishment of urban ...YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.
Anti-Müllerian hormone (AMH) is expressed by granulosa cells of developing follicles and plays an inhibiting role in the cyclic process of follicular recruitment by determining follicle-stimulating ...hormone threshold levels. Knowledge of AMH expression in the porcine ovary is important to understand the reproductive efficiency in female pigs.
In the present study we investigated the expression of AMH during follicular development in prepubertal and adult female pigs by immunohistochemistry, laser capture micro-dissection and RT-qPCR.
Although in many aspects the immunohistochemical localization of AMH in the porcine ovary does not differ from other species, there are also some striking differences. As in most species, AMH appears for the first time during porcine follicular development in the fusiform granulosa cells of recruited primordial follicles and continues to be present in granulosa cells up to the antral stage. By the time follicles reach the pre-ovulatory stage, AMH staining intensity increases significantly, and both protein and gene expression is not restricted to granulosa cells; theca cells now also express AMH. AMH continues to be expressed after ovulation in the luteal cells of the corpus luteum, a phenomenon unique to the porcine ovary. The physiological function of AMH in the corpus luteum is at present not clear. One can speculate that it may contribute to the regulation of the cyclic recruitment of small antral follicles. By avoiding premature exhaustion of the ovarian follicular reserve, AMH may contribute to optimization of reproductive performance in female pigs.
The world tilapia production faces seasonal variations. However, very few nutritional studies have addressed suboptimal temperature. We evaluated the effect of two temperatures (20 or 30 °C) and two ...vegetable oil blends (one rich in corn oil (COR) and one rich linseed oil (LIN)) on tilapia growth, body composition, and blood parameters using a 2×2 factorial design with the following treatments: COR-20; LIN-20; COR-30; LIN-30 (Trial 1). In addition, we also evaluated the effect of postingestive signals of dietary oils when the organoleptic properties of diets were isolated (Trial 2). In the Trial 1, 256 fish (15.36 ± 0.14 g) were placed in 16 aquariums and submitted during 30 days to the 2×2 factorial designs: COR-20; LIN-20; COR-30; LIN-30. The temperatures were established in two independent water recirculation systems. In the Trial 2, 96 fish (34.02 ± 0.79 g) were placed in 12 aquariums and subjected to the same experimental design of Trial 1, but to evaluate fish feeding behavior. They were allowed to select the encapsulated diets provided in different feeding halls to evaluate if diet preferences are influenced by postingestive signals. As the Trial 1 results show, diets had no significant effects on growth, dietary protein use, and body centesimal composition, but 30 °C induced the best performance and protein deposition (P < 0.05). LIN-20 showed lower very-low-density lipoprotein and cortisol, but higher high-density lipoprotein (HDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and triglycerides (TG) than COR-20 (P < 0.05). COR-30 presented higher HDL, AST, ALT, TG, and cortisol than LIN-30. The fish fed COR showed lower C20:5n-3 (EPA) and higher n-6 than fish fed LIN (P < 0.05). The fish fed LIN had high n-3 highly unsaturated fatty acid. ∑ polyunsaturated fatty acid was higher at 30 °C. Finally, the tilapia in Trial 2 showed clear diet intake regulation and preference for LIN (P < 0.05), regardless of temperature. In short, lipid sources had no influence on tilapia performance; however, temperature affects carcass lipid deposition as well as fatty acids profile. Notably, the preference for linseed oil can suggest nutritional metabolic issues, contributing to animal behavior knowledge.
The aim of the present study was to investigate the effects of concurrent strength and endurance training on neuromuscular and hormonal parameters in elderly men. 23 healthy men (65±4 years) were ...randomly assigned to 1 of 3 groups: concurrent (CG, n=8), strength (SG, n=8) or endurance group (EG, n=7). The programs consisted, of strength training, endurance training on a cycle ergometer or a combination of both in the same session 3 times per week over a duration of 12 weeks. Subjects were evaluated on parameters related to muscle strength, muscle activation and serum hormones. There were significant increases in lower-body strength in all groups (P<0.05), with higher increases in SG (67%) than CG (41%) and both were higher than EG (25%) (p<0.01). Only SG and CG increased upper-body strength (p<0.01), with no significant difference between the 2 groups. Furthermore, there were significant decreases in free testosterone in EG after training. Significant increases in isometric strength and maximal muscle activation (p<0.05) as well as decreases in the submaximal muscle activation to the same load, were only seen in SG (p<0.05). The present results suggest that the interference effect observed due to concurrent strength and endurance training could be related to impairment of neural adaptations.
Climate change and species invasions interact in nature, disrupting biological communities. Based on this knowledge, we simultaneously assessed the effects of climate change on the native ...distribution of the Amazonian fish Colossoma macropomum as well as on its invasiveness across river basins of South America, using ecological niche modeling. We used six niche models within the ensemble forecast context to predict the geographical distribution of C. macropomum for the present time, 2050 and 2080. Given that this species has been continuously introduced into non-native South American basins by fish farming activities, we added the locations of C. macropomum farms into the modeling process to obtain a more realistic scenario of its invasive potential. Based on modelling outputs we mapped climate refuge areas at different times. Our results showed that a plenty of climatically suitable areas for the occurrence of C. macropomum occurrence are located outside the original basins at the present time and that its invasive potential is greatly amplified by fish farms. Simulations of future geographic ranges revealed drastic range contraction in the native region, implying concerns not only with respect to the species conservation but also from a socio-economic perspective since the species is a cornerstone of artisanal and commercial fisheries in the Amazon. Although the invasive potential is projected to decrease in the face of climate change, climate refugia will concentrate in Paraná River, Southeast Atlantic and East Atlantic basins, putting intense, negative pressures on the native fish fauna these regions. Our findings show that short and long-term management actions are required for: i) the conservation of natural stocks of C. macropomum in the Amazon, and ii) protecting native fish fauna in the climate refuges of the invaded regions.
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