Abstract
One of the major classes of pesticides is that of the organophosphates (OPs). Initial developments date back almost 2 centuries but it was only in the mid-1940s that OPs reached a prominent ...status as insecticides, a status that, albeit declining, is still ongoing. OPs are highly toxic to nontarget species including humans, the primary effects being an acute cholinergic toxicity (responsible for thousands of poisoning each year) and a delayed polyneuropathy. Several issues of current debate and investigation on the toxicology of OPs are discussed in this brief review. These include (1) possible additional targets of OPs, (2) OPs as developmental neurotoxicants, (3) OPs and neurodegenerative diseases, (4) OPs and the “aerotoxic syndrome,” (5) OPs and the microbiome, and (6) OPs and cancer. Some of these issues have been debated and studied for some time, while others are newer, suggesting that the study of the toxicology of OPs will remain an important scientific and public health issue for years to come.
Growing evidence suggests that the gut microbiota modulates the efficacy and toxicity of cancer therapy, most notably immunotherapy and its immune-related adverse effects. The poor response to ...immunotherapy in patients treated with antibiotics supports this influential role of the microbiota. Until recently, results pertaining to the identification of the microbial species responsible for these effects were incongruent, and relatively few studies analysed the underlying mechanisms. A better understanding of the taxonomy of the species involved and of the mechanisms of action has since been achieved. Defined bacterial species have been shown to promote an improved response to immune-checkpoint inhibitors by producing different products or metabolites. However, a suppressive effect of Gram-negative bacteria may be dominant in some unresponsive patients. Machine learning approaches trained on the microbiota composition of patients can predict the ability of patients to respond to immunotherapy with some accuracy. Thus, interest in modulating the microbiota composition to improve patient responsiveness to therapy has been mounting. Clinical proof-of-concept studies have demonstrated that faecal microbiota transplantation or dietary interventions might be utilized clinically to improve the success rate of immunotherapy in patients with cancer. Here, we review recent advances and discuss emerging strategies for microbiota-based cancer therapies.
Abstract
We present a second set of results from a wide-field photometric survey of the environs of Milky Way globular clusters. The clusters studied are NGC 1261, NGC 1851 and NGC 5824: all have ...data from the Dark Energy Camera on the Blanco 4 m telescope. NGC 5824 also has data from the Magellan Clay telescope with MegaCam. We confirm the existence of a large diffuse stellar envelope surrounding NGC 1851 of size at least 240 pc in radius. The radial density profile of the envelope follows a power-law decline with index γ = −1.5 ± 0.2 and the projected shape is slightly elliptical. For NGC 5824, there is no strong detection of a diffuse stellar envelope, but we find the cluster is remarkably extended and is similar in size (at least 230 pc in radius) to the envelope of NGC 1851. A stellar envelope is also revealed around NGC 1261. However, it is notably smaller in size with radius ∼105 pc. The radial density profile of the envelope is also much steeper with γ = −3.8 ± 0.2. We discuss the possible nature of the diffuse stellar envelopes, but are unable to draw definitive conclusions based on the current data. NGC 1851, and potentially NGC 5824, could be stripped dwarf galaxy nuclei, akin to the cases of ω Cen, M54 and M2. On the other hand, the different characteristics of the NGC 1261 envelope suggest that it may be the product of dynamical evolution of the cluster.
Decision Trees (DTs) are predictive models in supervised learning, known not only for their unquestionable utility in a wide range of applications but also for their interpretability and robustness. ...Research on the subject is still going strong after almost 60 years since its original inception, and in the last decade, several researchers have tackled key matters in the field. Although many great surveys have been published in the past, there is a gap since none covers the last decade of the field as a whole. This paper proposes a review of the main recent advances in DT research, focusing on three major goals of a predictive learner: issues regarding the fitting of training data, generalization, and interpretability. Moreover, by organizing several topics that have been previously analyzed in isolation, this survey attempts to provide an overview of the field, its key concerns, and future trends, serving as a good entry point for both researchers and newcomers to the machine learning community.
•Coffee silverskin is very rich in insoluble fibre (49%).•Potassium, magnesium and calcium are major macrominerals of silverskin.•The vitamin E profile of silverskin comprises seven ...vitamers.•Silverskin extracts protected erythrocytes from oxidative induced hemolysis,•At higher extract concentrations a pro-oxidant effect was observed.
Coffee silverskin (a coffee roasting by-product) contains high amounts of dietary fibre (49% insoluble and 7% soluble) and protein (19%). Potassium (∼5g/100g), magnesium (2g/100g) and calcium (0.6g/100g) are the major macrominerals. The vitamin E profile of silverskin comprises α-tocopherol, β-tocopherol, ɣ-tocopherol, δ-tocopherol, β-tocotrienol, ɣ-tocotrienol, and δ-tocotrienol. The fatty acid profile is mainly saturated (C16:0 and C22:0), but the total amount of fat is low (2.4%). Caffeine (1.25g/100g), chlorogenic acid (246mg/100g), and 5-hydroxymethylfurfural (5.68mg/100g) are also present in silverskin. Total phenolics and flavonoids are partially responsible for the in vitro antioxidant activity. Silverskin extracts protected erythrocytes from oxidative AAPH- and H2O2-induced hemolysis, but at high concentrations a pro-oxidant effect on erythrocyte morphology was observed.
Recent studies using Magnetic Resonance Imaging (MRI) have proposed that the brain's white matter is organized as a rich club, whereby the most highly connected regions of the brain are also highly ...connected to each other. Here we use both functional and diffusion-weighted MRI in the human brain to investigate whether the rich club phenomena is present with functional connectivity, and how this organization relates to the structural phenomena. We also examine whether rich club regions serve to integrate information between distinct brain systems, and conclude with a brief investigation of the developmental trajectory of rich-club phenomena. In agreement with prior work, both adults and children showed robust structural rich club organization, comprising regions of the superior medial frontal/dACC, medial parietal/PCC, insula, and inferior temporal cortex. We also show that these regions were highly integrated across the brain's major networks. Functional brain networks were found to have rich club phenomena in a similar spatial layout, but a high level of segregation between systems. While no significant differences between adults and children were found structurally, adults showed significantly greater functional rich club organization. This difference appeared to be driven by a specific set of connections between superior parietal, insula, and supramarginal cortex. In sum, this work highlights the existence of both a structural and functional rich club in adult and child populations with some functional changes over development. It also offers a potential target in examining atypical network organization in common developmental brain disorders, such as ADHD and Autism.
Transposase-Accessible Chromatin followed by sequencing (ATAC-seq) is a simple protocol for detection of open chromatin. Computational footprinting, the search for regions with depletion of cleavage ...events due to transcription factor binding, is poorly understood for ATAC-seq. We propose the first footprinting method considering ATAC-seq protocol artifacts. HINT-ATAC uses a position dependency model to learn the cleavage preferences of the transposase. We observe strand-specific cleavage patterns around transcription factor binding sites, which are determined by local nucleosome architecture. By incorporating all these biases, HINT-ATAC is able to significantly outperform competing methods in the prediction of transcription factor binding sites with footprints.
Nearly all the star clusters with ages of ∼1–2 Gyr in both Magellanic Clouds exhibit an extended main-sequence turn-off (eMSTO) whose origin is under debate. The main scenarios suggest that the eMSTO ...could be either due to multiple generations of stars with different ages or to coeval stellar populations with different rotation rates. In this paper we use Hubble Space Telescope images to investigate the ∼80-Myr old cluster NGC 1755 in the LMC. We find that the MS is split with the blue and the red MS hosting about the 25 per cent and the 75 per cent of the total number of MS stars, respectively. Moreover, the MSTO of NGC 1755 is broadened in close analogy with what is observed in the ∼300-Myr-old NGC 1856 and in most intermediate-age Magellanic-Cloud clusters. We demonstrate that both the split MS and the eMSTO are not due to photometric errors, field-stars contamination, differential reddening, or non-interacting binaries. These findings make NGC 1755 the youngest cluster with an eMSTO. We compare the observed CMD with isochrones and conclude that observations are not consistent with stellar populations with difference in age, helium, or metallicity only. On the contrary, the split MS is well reproduced by two stellar populations with different rotation, although the fit between the observed eMSTO and models with different rotation is not fully satisfactory. We speculate whether all stars in NGC 1755 were born rapidly rotating, and a fraction has slowed down on a rapid time-scale, or the dichotomy in rotation rate was present already at star formation. We discuss the implication of these findings on the interpretation of eMSTO in young and intermediate-age clusters.
Pesticides are substances widely used to control unwanted pests such as insects, weeds, fungi and rodents. Most pesticides are not highly selective, and are also toxic to nontarget species, including ...humans. A number of pesticides can cause neurotoxicity. Insecticides, which kill insects by targeting their nervous system, have neurotoxic effect in mammals as well. This family of chemicals comprises the organophosphates, the carbamates, the pyrethroids, the organochlorines, and other compounds. Insecticides interfere with chemical neurotransmission or ion channels, and usually cause reversible neurotoxic effects, that could nevertheless be lethal. Some herbicides and fungicides have also been shown to possess neurotoxic properties. The effects of pesticides on the nervous system may be involved in their acute toxicity, as in case of most insecticides, or may contribute to chronic neurodegenerative disorders, most notably Parkinson's disease. This brief review highlights some of the main neurotoxic pesticides, their effects, and mechanisms of action.
Traditional risk factors for obesity and the metabolic syndrome, such as excess energy intake and lack of physical activity, cannot fully explain the high prevalence of these conditions. Insufficient ...sleep and circadian misalignment predispose individuals to poor metabolic health and promote weight gain and have received increased research attention in the past 10 years. Insufficient sleep is defined as sleeping less than recommended for health benefits, whereas circadian misalignment is defined as wakefulness and food intake occurring when the internal circadian system is promoting sleep. This Review discusses the impact of insufficient sleep and circadian misalignment in humans on appetite hormones (focusing on ghrelin, leptin and peptide-YY), energy expenditure, food intake and choice, and risk of obesity. Some potential strategies to reduce the adverse effects of sleep disruption on metabolic health are provided and future research priorities are highlighted. Millions of individuals worldwide do not obtain sufficient sleep for healthy metabolic functions. Furthermore, modern working patterns, lifestyles and technologies are often not conducive to adequate sleep at times when the internal physiological clock is promoting it (for example, late-night screen time, shift work and nocturnal social activities). Efforts are needed to highlight the importance of optimal sleep and circadian health in the maintenance of metabolic health and body weight regulation.
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