Our aim was to quantify microplastic ingestion by fish assemblages in two tropical Brazilian estuaries and to evaluate whether biological and ecological factors influence the ingestion of ...microplastics by fish species. Of 2233 fish from both estuaries (from 69 species) examined in this study, 9% of the individuals (24 species) had microplastics in their gut contents. Microplastic ingestion occurred irrespective of fish size and functional group. The diet of fish species was analyzed based on prey items identified in the fish's full stomach contents and five feeding guilds were defined. Microplastics were common throughout all feeding guilds. Low (average ingestion values 1.06±0.30 items/total fish) but widespread occurrence among estuaries also indicates proliferation of microplastic pollution. Our findings highlight the need to focus on assemblage level studies to understand the real magnitude of the problem and emphasize the urgency of mitigation measures directed at microplastic pollution in estuarine ecosystems.
•We analyzed microplastic ingestion in 69 fish species collected along two estuaries.•Microplastic ingestion was widespread in fish assemblages in two tropical estuaries.•Microplastic ingestion was independent of fish size and fish functional groups.•Microplastics were observed in fish from five different feeding guilds.•The level of anthropogenic pressures did not influence microplastic ingestion.
•Venetoclax resistance is mediated by methylation and silencing of PUMA.•Treatment algorithms should consider the PUMA, MCL1, and BAX status.
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The BCL2 inhibitor venetoclax has been ...approved to treat different hematological malignancies. Because there is no common genetic alteration causing resistance to venetoclax in chronic lymphocytic leukemia (CLL) and B-cell lymphoma, we asked if epigenetic events might be involved in venetoclax resistance. Therefore, we employed whole-exome sequencing, methylated DNA immunoprecipitation sequencing, and genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 screening to investigate venetoclax resistance in aggressive lymphoma and high-risk CLL patients. We identified a regulatory CpG island within the PUMA promoter that is methylated upon venetoclax treatment, mediating PUMA downregulation on transcript and protein level. PUMA expression and sensitivity toward venetoclax can be restored by inhibition of methyltransferases. We can demonstrate that loss of PUMA results in metabolic reprogramming with higher oxidative phosphorylation and adenosine triphosphate production, resembling the metabolic phenotype that is seen upon venetoclax resistance. Although PUMA loss is specific for acquired venetoclax resistance but not for acquired MCL1 resistance and is not seen in CLL patients after chemotherapy-resistance, BAX is essential for sensitivity toward both venetoclax and MCL1 inhibition. As we found loss of BAX in Richter’s syndrome patients after venetoclax failure, we defined BAX-mediated apoptosis to be critical for drug resistance but not for disease progression of CLL into aggressive diffuse large B-cell lymphoma in vivo. A compound screen revealed TRAIL-mediated apoptosis as a target to overcome BAX deficiency. Furthermore, antibody or CAR T cells eliminated venetoclax resistant lymphoma cells, paving a clinically applicable way to overcome venetoclax resistance.
Two complementary articles shed new light on resistance to venetoclax in lymphoid malignancies. Thijssen et al use single-cell studies to reveal the multilayered nature of the mechanisms underpinning the recurrence of chronic lymphocytic leukemia in patients on long-term venetoclax, identifying a range of recurring genetic and epigenetic changes in apoptotic regulators. Overlying this heterogeneity, heightened expression of MCL1 driven by NF-κB is ubiquitous but reversible upon drug discontinuation. Thomalla and colleagues use B-lineage cell lines and patient samples to elegantly demonstrate how methylation and silencing of PUMA, a pro-apoptotic, causes failure of venetoclax. Both articles provide clinically applicable suggestions for circumventing emergent resistance to venetoclax.
To report on the safety of the first 5 cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt dystrophy due to ...mutations in ABCA4.
Nonrandomized multicenter phase I/IIa clinical trial.
Patients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at 3 dose levels and were followed for 3 years after treatment.
The primary end point was ocular and systemic adverse events. The secondary end points were best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, multifocal ERG, color fundus photography, short-wavelength fundus autofluorescence, and spectral domain optical coherence tomography.
The subretinal injections were well tolerated by all 22 patients across 3 dose levels. There was 1 case of a treatment-related ophthalmic serious adverse event in the form of chronic ocular hypertension. The most common adverse events were associated with the surgical procedure. In 1 patient treated with the highest dose, there was a significant decline in the number of macular flecks as compared with the untreated eye. However, in 6 patients, hypoautofluorescent changes were worse in the treated eye than in the untreated eye. Of these, 1 patient had retinal pigment epithelium atrophy that was characteristic of tissue damage likely associated with bleb induction. No patients had any clinically significant changes in best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, or multifocal ERG attributable to the treatment.
Subretinal treatment with EIAV-ABCA4 was well tolerated with only 1 case of ocular hypertension. No clinically significant changes in visual function tests were found to be attributable to the treatment. However, 27% of treated eyes showed exacerbation of retinal pigment epithelium atrophy on fundus autofluorescence. There was a significant reduction in macular flecks in 1 treated eye from the highest dose cohort. Additional follow-up and continued investigation in more patients will be required to fully characterize the safety and efficacy of EIAV-ABCA4.
The aim of this study was to investigate functional and morphological alterations caused by oxidative stress in streptozotocin (STZ)-induced diabetic rats and to evaluate the antioxidant effect of ...quercetin (QUE) in this disease. One hundred and thirty male Wistar rats, it were randomly distributed in 10 different experimental groups, with ten animals per group: Control Saline (CS), Control Ethanol (CE), Control QUE 5mg/kg (CQ5), Control QUE 25mg/kg (CQ25), Control QUE 50mg/kg (CQ50), Diabetic Saline (DS), Diabetic Ethanol (DE), Diabetic QUE 5mg/kg (DQ5), Diabetic QUE25mg/kg (DQ25), Diabetic QUE 50mg/kg (DQ50). Therefore, hyperglycemia is directly involved in oxidative stress production, as well as in functional and morphological alterations caused by the excess of free radicals. QUE, specially at the dosage of 50mg/kg, can act as an antioxidant and anti-inflammatory agent, becoming a promising adjuvant in the treatment of diabetes mellitus.
CERRADO SMALL MAMMALS Mendonça, André; Percequillo, Alexandre R.; Camargo, Nicholas F. ...
Ecology (Durham),
08/2018, Letnik:
99, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Patterns in distribution and local abundance of species within a biome are central concerns in ecology and allow the understanding of the effects of habitat loss on rates of species extinction; ...provide support for the creation and management of reserves; and contribute to the identification and quantification of the processes that allow niche partitioning by species. However, despite the importance in the conservation and management of the ecosystems, most systematized information on the abundance and distribution of small mammals is restricted to the northern hemisphere or forest ecosystems. For tropical biomes, an important part of this information remains dispersed and difficult to access in the form of theses, technical reports, or unpublished data sets. Here we present a comprehensive data set of abundance and richness of small mammals in the Cerrado, the largest Neotropical savanna. This data set includes 2,599 records of 446 sites from 96 studies. More than 50% of references in this data set are peer-reviewed journal articles, but 45.78% of communities were compiled from theses. The data set comprises 24,283 individuals of 55 genera and at least 118 species of small mammals including 29 marsupials, two lagomorphs (one exotic), and 87 rodents (three exotic). Local species richness ranged from 1 to 26 species (5.82 ± 3.55, average species richness ± SD). We observed hyperdominance of a few species; the 10 most abundant species in this data set represented 60.19% of all recorded individuals. The hairy-tailed bolo mouse (Necromys lasiurus) represented over than 20% of all individuals and occurred at more than 50% of sites. Furthermore, we identified 18 environments, 16 native vegetation types, and 2 anthropic environments. Typical savanna and gallery forest were the most frequently sampled vegetation types (comprising 46.94% of all sampled sites) and the most speciose ones (57 species for typical savanna and 53 species for gallery forest). The information contained in this data set can be used to analyze ecological questions such as the relationship between local abundance and regional distribution, the relevance of local and regional factors to community structuring, and the role of phylogenetic mechanisms in community assemblage. It can also be useful in conservation efforts in this biodiversity hotspot. No copyright, proprietary, or cost restrictions apply. Please cite this paper when the data are used in publications. We also request that researchers and teachers inform us of how they are using the data.
The aim of the present study was to test whether different degrees of human activity affect the diet of the Brazilian silverside Atherinella brasiliensis in two tropical estuaries. Fish were ...collected along the salinity gradient of two Brazilian estuaries, the heavily impacted Paraiba Estuary and the less impacted Mamanguape Estuary, in the dry and wet seasons. The findings confirm that A. brasiliensis has generalist feeding habits and is able to change its diet under different environmental conditions. The results indicate clear spatial (i.e. along the estuarine gradient) changes in diet composition in both estuaries, but diet was also influenced by the degree of anthropogenic disturbance. During the wet season in the nutrient enriched Paraiba Estuary, when human activity was higher, the diet of A. brasiliensis was poorer and dominated by few dietary items, reflecting the potential impoverishment of prey items in this heavily disturbed system. The specimens collected in the most affected estuary also had a greater frequency of micro‐plastics and parasites in their stomachs, reflecting the greater degree of human disturbance in the estuary. The present findings suggest that the diet of A. brasiliensis could be a useful indicator of changes in the ecological quality of these and other tropical estuaries of the western Atlantic Ocean.
The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) regulates metabolic genes in skeletal muscle and contributes to the response of muscle to ...exercise. Muscle PGC-1α transgenic expression and exercise both increase the expression of thermogenic genes within white adipose. How the PGC-1α-mediated response to exercise in muscle conveys signals to other tissues remains incompletely defined. We employed a metabolomic approach to examine metabolites secreted from myocytes with forced expression of PGC-1α, and identified β-aminoisobutyric acid (BAIBA) as a small molecule myokine. BAIBA increases the expression of brown adipocyte-specific genes in white adipocytes and β-oxidation in hepatocytes both in vitro and in vivo through a PPARα-mediated mechanism, induces a brown adipose-like phenotype in human pluripotent stem cells, and improves glucose homeostasis in mice. In humans, plasma BAIBA concentrations are increased with exercise and inversely associated with metabolic risk factors. BAIBA may thus contribute to exercise-induced protection from metabolic diseases.
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•β-aminoisobutyric acid (BAIBA) is secreted from PGC-1α-expressing myocytes•BAIBA activates the thermogenic program in white adipocytes via PPARα•Circulating BAIBA levels in mice and humans are increased with exercise•BAIBA is inversely correlated with cardiometabolic risk factors in humans
Roberts et al. use metabolic profiling to identify β-aminoisobutyric acid (BAIBA) as a PGC-1α-responsive small molecule myokine that induces β-oxidation in hepatocytes and the browning of white adipose tissue. In humans, plasma BAIBA concentrations are increased with exercise and inversely associated with metabolic risk factors.
The Barkhausen noise method has long been applied to measure time degradation of engineering materials. In this paper, fatigue damage evolution of an engineering structural AISI 8620 steel is studied ...by using Barkhausen noise measurements. The influence of applied alternating stresses and number of cycles on a Barkhausen noise parameter was evaluated. For stress range between fatigue and yield limit of the material, it was found that the Barkhausen noise increase with increasing applied stress. The Barkhausen noise increases rapidly at the begin of test, in the early stage of fatigue life. When the applied maximum stress is above yield limit of the material, plastic strain has to be accounted for, and no equivalence between fatigue damage and Barkhausen noise can be stated.
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