From Metabolism to Genetics and Vice Versa: The Rising Role of Oncometabolites in Cancer Development and Therapy.
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ABSTRACT:
SUBMITTER: Di Gregorio E
PROVIDER: S-EPMC8197491 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Inflammation is an essential immune response for the maintenance of tissue homeostasis. In a general sense, acute and chronic inflammation are different types of adaptive response that are called into action when other homeostatic mechanisms are insufficient. Although considerable progress has been made in understanding the cellular and molecular events that are involved in the acute inflammatory response to infection and tissue injury, the causes and mechanisms of systemic chronic inflammation are much less known. The pathogenic capacity of this type of inflammation is puzzling and represents a common link of the multifactorial diseases, such as cardiovascular diseases and type 2 diabetes. In recent years, interest has been raised by the discovery of novel mediators of inflammation, such as microRNAs and adipokines, with different effects on target tissues. In the present review, we discuss the data emerged from research of leptin in obesity as an inflammatory mediator sustaining multifactorial diseases and how this knowledge could be instrumental in the design of leptin-based manipulation strategies to help restoration of abnormal immune responses. On the other direction, chronic inflammation, either from autoimmune or infectious diseases, or impaired microbiota (dysbiosis) may impair the leptin response inducing resistance to the weight control, and therefore it may be a cause of obesity. Thus, we are reviewing the published data regarding the role of leptin in inflammation, and the other way around, the role of inflammation on the development of leptin resistance and obesity.
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Project description:Even when speakers are not actively doing another task, they can be interfered in their speech planning by concurrent auditory stimuli. In this study, we used picture naming with passive hearing, or active listening, combined to high-density electroencephalographic (EEG) recordings to investigate the locus and origin of interference on speech production. Participants named pictures while ignoring (or paying attention to) auditory syllables presented at different intervals (+150 ms, +300 ms or +450 ms). Interference of passive hearing was observed at all positive stimulus onset asynchronies (SOA) including when distractors appeared 450 ms after picture onset. Analyses of ERPs and microstates revealed modulations appearing in a time-window close to verbal response onset likely relating to post-lexical planning processes. A shift of latency of the N1 auditory component for syllables displayed 450 ms after picture onset relative to hearing in isolation was also observed. Data from picture naming with active listening to auditory syllables also pointed to post-lexical interference. The present study suggests that, beyond the lexical stage, post-lexical processes can be interfered and that the reciprocal interference between utterance planning and hearing relies on attentional demand and possibly competing neural substrates.
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Project description:Previous studies suggest that humans are capable of coregulating the speed of decisions and movements if promoted by task incentives. It is unclear however whether such behavior is inherent to the process of translating decisional information into movements, beyond posing a valid strategy in some task contexts. Therefore, in a behavioral online study we imposed time constraints to either decision- or movement phases of a sensorimotor task, ensuring that coregulating decisions and movements was not promoted by task incentives. We found that participants indeed moved faster when fast decisions were promoted and decided faster when subsequent finger tapping movements had to be executed swiftly. These results were further supported by drift diffusion modelling and inspection of psychophysical kernels: Sensorimotor delays related to initiating the finger tapping sequence were shorter in fast-decision as compared to slow-decision blocks. Likewise, the decisional speed-accuracy tradeoff shifted in favor of faster decisions in fast-tapping as compared to slow-tapping blocks. These findings suggest that decisions not only impact movement characteristics, but that properties of movement impact the time taken to decide. We interpret these behavioral results in the context of embodied decision-making, whereby shared neural mechanisms may modulate decisions and movements in a joint fashion.
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Project description:The world is currently suffering from a pandemic which has claimed the lives of over 230,000 people to date. The responsible virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes the coronavirus disease 2019 (COVID-19), which is mainly characterized by fever, cough and shortness of breath. In severe cases, the disease can lead to respiratory distress syndrome and septic shock, which are mostly fatal for the patient. The severity of disease progression was hypothesized to be related to an overshooting immune response and was correlated with age and comorbidities, including cancer. A lot of research has lately been focused on the pathogenesis and acute consequences of COVID-19. However, the possibility of long-term consequences caused by viral infections which has been shown for other viruses are not to be neglected. In this regard, this opinion discusses the interplay of SARS-CoV-2 infection and cancer with special focus on the inflammatory immune response and tissue damage caused by infection. We summarize the available literature on COVID-19 suggesting an increased risk for severe disease progression in cancer patients, and we discuss the possibility that SARS-CoV-2 could contribute to cancer development. We offer lines of thought to provide ideas for urgently needed studies on the potential long-term effects of SARS-CoV-2 infection.
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Project description:An escaped radial director profile in a nematic liquid crystal cell can be transformed into a pair of strength m = +1/2 surface defects (and their associated disclination lines) at a threshold electric field. Analogously, a half-integer defect pair can be transformed at a threshold electric field into a director profile that escapes into the third dimension. These transitions were demonstrated experimentally and numerically, and are discussed in terms of topologically discontinuous and continuous pathways that connect the two states. Additionally, we note that the pair of disclination lines associated with the m = +1/2 surface defects were observed to co-rotate around a common point for a sufficiently large electric field at a sufficiently low frequency.
| S-EPMC8083252 | biostudies-literature
Project description:Holding a territory is often crucial in order to acquire key resources, including mating partners. However, few studies have investigated the role of animal personality in the context of territorial conflicts and how the contest outcome itself may influence personality traits. We studied personality in male Speckled wood butterflies, Pararge aegeria, before and after territorial contests for sunspot territories. Before interactions, boldness decreased with age, while activity and exploration were only influenced by ambient conditions. Neither age nor morphology did influence the probability to win contests, but winners were more active and more explorative than losers and, moreover, males that received a red wing mark were more likely to be winners. Butterflies that lost a contest showed pronounced behavioural changes. Mean boldness increased and its repeatability was disrupted, while no such change was detected in winners. The observed boldness increase in losers may be explained by a 'desperado effect', though its implication for successive contests remains unknown. Given that territoriality is expected to have important consequences for reproductive success, our results suggest that personality traits may indirectly contribute to individual fitness by influencing the ability to gain access to mate-location patches.
| S-EPMC6391398 | biostudies-literature
Project description:BackgroundAgent-based models (ABM) are believed to be a very powerful tool in the social sciences, sometimes even treated as a substitute for social experiments. When building an ABM we have to define the agents and the rules governing the artificial society. Given the complexity and our limited understanding of the human nature, we face the problem of assuming that either personal traits, the situation or both have impact on the social behavior of agents. However, as the long-standing person-situation debate in psychology shows, there is no consensus as to the underlying psychological mechanism and the important question that arises is whether the modeling assumptions we make will have a substantial influence on the simulated behavior of the system as a whole or not.Methodology/principal findingsStudying two variants of the same agent-based model of opinion formation, we show that the decision to choose either personal traits or the situation as the primary factor driving social interactions is of critical importance. Using Monte Carlo simulations (for Barabasi-Albert networks) and analytic calculations (for a complete graph) we provide evidence that assuming a person-specific response to social influence at the microscopic level generally leads to a completely different and less realistic aggregate or macroscopic behavior than an assumption of a situation-specific response; a result that has been reported by social psychologists for a range of experimental setups, but has been downplayed or ignored in the opinion dynamics literature.SignificanceThis sensitivity to modeling assumptions has far reaching consequences also beyond opinion dynamics, since agent-based models are becoming a popular tool among economists and policy makers and are often used as substitutes of real social experiments.
| S-EPMC4219838 | biostudies-literature
Project description:BackgroundCirculating tumor cells (CTC) in the peripheral blood in women with breast cancer has been found to be an indicator of prognosis before the start of systemic treatment. The aim of this study is the assessment of specific cytokine profiles as markers for CTC involvement that could act as independent prognostic markers in terms of survival outcome for breast cancer patients.MethodsPatients selected for this study were defined as women with breast cancer of the SUCCESS study. A total of 200 patients' sera were included in this study, 100 patients being positive for circulating tumor cells (CTC) and 100 patients being CTC negative. The matching criteria were histo-pathological grading, lymph node metastasis, hormone receptor status, TNM classification, and patient survival. Commercial ELISA with a multi cytokine/chemokine array was used to screen the sera for Interleukin 15 (IL-15) and eotaxin.ResultsStatistically significant concentrations were exposed for IL-15 levels regardless of the CTC-Status, lymph node involvement, or hormone receptor status. Significantly enhanced serum IL-15 concentrations were observed in those patients with worse overall survival (OS) and disease-free survival (DFS). Elevated serum concentrations of IL-15 significantly correlate with patients diagnosed with Grade 3 tumor and worse OS. In contrast, patients with a Grade 3 tumor with a favourable OS and DFS demonstrated significantly decreased IL-15 values. The CTC negative patient subgroup with a favourable OS and DFS, showed statistically significant elevated eotaxin values.ConclusionThese findings suggest a potential functional interaction of increased IL-15 concentrations in the peripheral blood of patients with a worse OS and DFS, regardless of prognostic factors at primary diagnosis. The increased levels of the chemokine eotaxin in CTC negative patients and a favourable OS and DFS, on the other hand, suggest that the overexpression inhibits CTCs entering the peripheral blood, thus emphasizing a significant inhibition of circulation specific metastasis. To sum up, IL-15 could be used as an independent prognostic marker in terms of survival outcome for breast cancer patients and used as an early indicator to highlight high-risk patients and consequently the adjustment of cancer therapy strategies.
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Project description:This study offers a new perspective on the evolutionary patterns of cities or urban agglomerations. Such developments can range from chaotic to fully ordered. We demonstrate that in a dynamic space of interactive human behaviour cities produce a wealth of gravitational attractors whose size and shape depend on the resistance of space emerging inter alia from transport friction costs. This finding offers original insights into the complex evolution of spatial systems and appears to be consistent with the principles of central place theory known from the spatial sciences and geography. Our approach is dynamic in nature and forms a generalisation of hierarchical principles in geographic space.
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Project description:Hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) can be life-threatening. Here, we investigate the role of the gut microbiome and TGR5 bile acid receptors in MDMA-mediated hyperthermia. Fourteen days prior to treatment with MDMA, male Sprague-Dawley rats were provided water or water treated with antibiotics. Animals that had received antibiotics displayed a reduction in gut bacteria and an attenuated hyperthermic response to MDMA. MDMA treated animals showed increased uncoupling protein 1 (UCP1) and TGR5 expression levels in brown adipose tissue and skeletal muscle while increased expression of UCP3 was observed only in skeletal muscle. Antibiotics prior to MDMA administration significantly blunted these increases in gene expression. Furthermore, inhibition of the TGR5 receptor with triamterene or of deiodinase II downstream of the TGR5 receptor with iopanoic acid also resulted in the attenuation of MDMA-induced hyperthermia. MDMA-treatment enriched the relative proportion of a Proteus mirabilis strain in the ceca of animals not pre-treated with antibiotics. These findings suggest a contributing role for the gut microbiota in MDMA-mediated hyperthermia and that MDMA treatment can trigger a rapid remodeling of the composition of the gut microbiome.
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