Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a ...functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.
Genome-wide association studies (GWAS) have identified multiple loci associated with plasma lipid concentrations. Common variants at these loci together explain <10% of variation in each lipid trait. ...Rare variants with large individual effects may also contribute to the heritability of lipid traits; however, the extent to which rare variants affect lipid phenotypes remains to be determined. Here we show an accumulation of rare variants, or a mutation skew, in GWAS-identified genes in individuals with hypertriglyceridemia (HTG). Through GWAS, we identified common variants in APOA5, GCKR, LPL and APOB associated with HTG. Resequencing of these genes revealed a significant burden of 154 rare missense or nonsense variants in 438 individuals with HTG, compared to 53 variants in 327 controls (P = 6.2 × 10−8), corresponding to a carrier frequency of 28.1% of affected individuals and 15.3% of controls (P = 2.6 × 10−5). Considering rare variants in these genes incrementally increased the proportion of genetic variation contributing to HTG.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Despite orders of magnitude difference in atmospheric reactivity and great diversity in biological functioning, little is known about monoterpene speciation in tropical forests. Here we report ...vertically resolved ambient air mixing ratios for 12 monoterpenes in a central Amazon rainforest including observations of the highly reactive cis‐β‐ocimene (160 ppt), trans‐β‐ocimene (79 ppt), and terpinolene (32 ppt) which accounted for an estimated 21% of total monoterpene composition yet 55% of the upper canopy monoterpene ozonolysis rate. All 12 monoterpenes showed a mixing ratio peak in the upper canopy, with three demonstrating subcanopy peaks in 7 of 11 profiles. Leaf level emissions of highly reactive monoterpenes accounted for up to 1.9% of photosynthesis confirming light‐dependent emissions across several Amazon tree genera. These results suggest that highly reactive monoterpenes play important antioxidant roles during photosynthesis in plants and serve as near‐canopy sources of secondary organic aerosol precursors through atmospheric photooxidation via ozonolysis.
Key Points
Mixing ratios of 12 Amazon monoterpenes reflect vertical forest structure
Light‐dependent reactive monoterpene leaf emissions observed in ambient air
Monoterpene ozonolysis rates suggest important local aerosol precursor source
Introdução - a isquemia renal é causa de graves lesões nesse órgão, estando presente em diferentes situações como em cirurgias renais, vasculares e no transplante renal. Assim, a procura de ...substâncias protetoras da função renal tem amplo interesse clínico. Neste estudo o objetivo foi o de analisar o efeito da lovastatina na isquemia renal normotérmica seguida da reperfusão.
To evaluate the antibacterial, antibiofilm and antivirulence potential of the main diterpenes from Copaifera spp. oleoresins against multidrug-resistant (MDR) bacteria. Antimicrobial assays included ...determination of the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Minimum Inhibitory Concentration of Biofilm (MICB
), as well as synergistic and antivirulence assays for eight diterpenes against MDR. The tests revealed that two diterpenes (named 1 and 5) showed the best results, with MIC and MBC between 12.5 and 50 μg/mL against most MDR bacteria. These diterpenes exhibited promising MICB
in concentration between 3.12-25 μg/mL but showed no synergistic antimicrobial activity. In the assessment of antivirulence activity, diterpenes 1 and 5 inhibited only one of the virulence factors evaluated (Dnase) produced by some strains of S. aureus at subinhibitory concentration (6.25 μg/mL). Results obtained indicated that diterpenes isolated from Copaifera oleoresin plays an important part in the search of new antibacterial and antibiofilm agents that can act against MDR bacteria.
Photocrosslinkable surgical adhesives provide many advantages when compared with traditional methods used in wound closure. This work aimed to develop UV-curable biodegradable adhesives based on ...lactic acid and PCL oligomers. Both materials were functionalized with 2-isocyanatoethyl acrylate (AOI). Subsequently, the photoinitiator (Irgacure® 2959) was added to the blend and then, the final materials were irradiated under UV light for two different times: 30 s and 2 min. After production of adhesives, its physicochemical properties were evaluated through FTIR-ATR and TGA, as well as its rheology, dynamic water contact angle, swelling capacity and hydrolytic degradation. Furthermore, the biocompatibility of the produced adhesives was also characterized in contact with human dermal fibroblasts cells. The antimicrobial activity of the materials was assessed by using Staphylococcus aureus and Escherichia coli, as bacterial models.
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•Photocrosslinkable macromers were prepared by functionalization with AOI;•The macromers were photocrosslinked using Irgacure® 2959 as the photoinitiator;•Influence of UV irradiation time was accessed during materials’ characterization;•In vitro studies showed that fibroblasts adhered and proliferated for 7 days;•LA materials displayed higher antimicrobial effect against E.coli and S. aureus.
This study evaluated the antibacterial and antiproliferative activities of the essential oil of Psidium guajava leaves (PG-EO), traditionally used in folk medicine. The essential oil was obtained ...from fresh leaves by hydrodistillation, using a modified Clevenger apparatus. The major PG-EO chemical constituents were identified by GC-MS and GC-FID as being β-caryophyllene (16.1%), α-humulene (11.9%), aromadendrene oxide (14.7%), δ-selinene (13.6%), and selin-11-en-4α-ol (12.5%). The antibacterial activity of the essential oil of P. guajava leaves was determined in terms of its minimum inhibitory concentrations (MIC) using the broth microdilution method in 96-well microplates. PG-EO had moderate activity against Streptococcus mutans (MIC = 200 µg/mL), S. mitis (MIC = 200 µg/mL), S. sanguinis (MIC = 400 µg/mL), S. sobrinus (MIC = 100 µg/mL), and S. salivarius (MIC = 200 µg/mL). The antiproliferative activity was evaluated against different tumor cell lines: breast adenocarcinoma (MCF-7), human cervical adenocarcinoma (HeLa), and human gliobastoma (M059J). A normal human cell line (GM07492A, lung fibroblasts) was included. The antiproliferative activity was evaluated using the XTT assay and the results were expressed as IC50. The essential oil showed significantly lower IC50 values against MCF-7 and M059J lines than that obtained for the normal line, showing selectivity. Our results suggest that the essential oil of Psidium guajava L. has promising biological activities and can be considered a new source of bioactive compounds.
Taxometric and behavioral genetic studies suggest that attention deficit hyperactivity disorder (ADHD) is best modeled as a dimension rather than a category. We extended these analyses by testing for ...the existence of putative ADHD-related deficits in basic information processing (BIP) and inhibitory-based executive function (IB-EF) in individuals in the subclinical and full clinical ranges. Consistent with the dimensional model, we predicted that ADHD-related deficits would be expressed across the full spectrum, with the degree of deficit linearly related to the severity of the clinical presentation.
A total of 1547 children (aged 6-12 years) participated in the study. The Development and Well-Being Assessment (DAWBA) was used to classify children into groups according to levels of inattention and hyperactivity independently: (1) asymptomatic, (2) subthreshold minimal, (3) subthreshold moderate and (4) clinical ADHD. Neurocognitive performance was evaluated using a two-choice reaction time task (2C-RT) and a conflict control task (CCT). BIP and IB-EF measures were derived using a diffusion model (DM) for decomposition of reaction time (RT) and error data.
Deficient BIP was found in subjects with minimal, moderate and full ADHD defined in terms of inattention (in both tasks) and hyperactivity/impulsivity dimensions (in the 2C-RT). The size of the deficit increased in a linear manner across increasingly severe presentations of ADHD. IB-EF was unrelated to ADHD.
Deficits in BIP operate at subclinical and clinical levels of ADHD. The linear nature of this relationship provides support for a dimensional model of ADHD in which diagnostic thresholds are defined in terms of clinical and societal burden rather than representing discrete pathophysiological states.
Abstract Cowpea is a leguminous plant belonging to the fabaceae family cultivated in the North and Northeast regions of Brazil, with productive potential. Among the abiotic factors, water deficiency ...is one of the main environmental limitations that influence agricultural production in the world. The objective of this work was to study the relative water content and osmoregulators of cowpea plants subjected to water stress. The experiment was carried out in a greenhouse at the Universidade Federal Rural da Amazônia (UFRA, Belém, PA), cowpea plants BR-17 Gurguéia Vigna unguiculata (L.) Walp were used. The experimental design was completely randomized (DIC) in a 2 × 2 factorial scheme, two water conditions (control and water deficit) and two times of stress (four and six days of water suspension), with 7 replications, totaling 28 experimental units. The water deficit affected plants, causing a reduction in relative water content (69.98%), starch (12.84% in leaves and 23.48% in roots) and carbohydrates (84.34%), and an increase in glycine-betaine, sucrose (114.11% in leaves and 18.71% in roots) and proline (358.86%) at time 2. The relative water content was negatively affected by water conditions, with a decrease in relation to the interaction of the aerial part and the root system. Therefore, greater metabolic responses were noted in plants that were subjected to stress treatment at time 2 (6 days).
Resumo O feijão-caupi é uma planta leguminosa pertencente à família das Fabaceae cultivada nas regiões Norte e Nordeste do Brasil, com potencial produtivo. Entre os fatores abióticos, a deficiência hídrica é uma das principais limitações ambientais que influenciam a produção agrícola no mundo. O objetivo do trabalho foi estudar o conteúdo relativo de água e os osmorreguladores de plantas de feijão-caupi submetidas ao estresse hídrico. O experimento foi conduzido em casa de vegetação da Universidade Federal Rural da Amazônia (UFRA, Belém, PA), foram utilizadas plantas de feijão-caupi BR-17 Gurguéia Vigna unguiculata (L.) Walp. O delineamento experimental foi inteiramente casualizado (DIC) em esquema fatorial 2 × 2, duas condições hídricas (controle e déficit hídrico) e dois tempos de estresse (quatro e seis dias de suspensão hídrica), com 7 repetições, totalizando 28 unidades experimentais. O estresse hídrico afetou as plantas, provocando redução no conteúdo relativos de água (69,98%), amido (12,84% nas folhas e 23,48% nas raízes) e carboidratos (84,34%), e aumento na glicina-betaína, sacarose (114,11% nas folhas e 18,71% nas raízes) e prolina (358,86%) no tempo 2. O conteúdo relativo de água foi afetado negativamente pelas condições hídricas, com diminuição em relação à interação da parte aérea e do sistema radicular. Diante disso, notou-se maiores respostas metabólicas nas plantas que foram submetidas ao tratamento de estresse no tempo 2 (6 dias).
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