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Oxidative Stress and Inflammation, Key Targets of Atherosclerotic Plaque Progression and Vulnerability: Potential Impact of Physical Activity
Atherosclerosis, a complex cardiovascular disease, is a leading cause of mortality and morbidity worldwide. Oxidative stress and inflammation are both involved in the development of atherosclerotic plaque as they increase the biological processes associated with this pathology, such as endothelial dysfunction and macrophage recruitment and adhesion. Atherosclerotic plaque rupture leading to major ischemic events is the result of vulnerable plaque progression, which is a result of the detrimental effect of oxidative stress and inflammation on risk factors for atherosclerotic plaque rupture, such as intraplaque hemorrhage, neovascularization, and fibrous cap thickness. Thus, both are key targets for primary and secondary interventions. It is well recognized that chronic physical activity attenuates oxidative stress in healthy subjects via the improvement of antioxidant enzyme capacities and inflammation via the enhancement of anti-inflammatory molecules. Moreover, it was recently shown that chronic physical activity could decrease oxidative stress and inflammation in atherosclerotic patients. The aim of this review is to summarize the role of oxidative stress and inflammation in atherosclerosis and the results of therapeutic interventions targeting them in both preclinical and clinical studies. The effects of chronic physical activity on these two key processes are then reviewed in vulnerable atherosclerotic plaques in both coronary and carotid arteries.
Journal Article
Time-Delay Cosmography: Measuring the Hubble Constant and Other Cosmological Parameters with Strong Gravitational Lensing
Multiply lensed images of a same source experience a relative time delay in the arrival of photons due to the path length difference and the different gravitational potentials the photons travel through. This effect can be used to measure absolute distances and the Hubble constant (
H
0
) and is known as time-delay cosmography. The method is independent of the local distance ladder and early-universe physics and provides a precise and competitive measurement of
H
0
. With upcoming observatories, time-delay cosmography can provide a 1% precision measurement of
H
0
and can decisively shed light on the current reported ‘Hubble tension’. This manuscript details the general methodology developed over the past decades in time-delay cosmography, discusses recent advances and results, and, foremost, provides a foundation and outlook for the next decade in providing accurate and ever more precise measurements with increased sample size and improved observational techniques.
Journal Article
Quantitative Polymerase Chain Reaction Detection of Circulating DNA in Serum for Early Diagnosis of Mucormycosis in Immunocompromised Patients
The aim of our study was to assess the detection of circulating DNA from the most common species of Mucorales for early diagnosis of mucormycosis in at-risk patients.
We retrospectively evaluated a combination of 3 quantitative polymerase chain reaction (qPCR) assays using hydrolysis probes targeting Mucor/Rhizopus, Lichtheimia (formerly Absidia), and Rhizomucor for circulating Mucorales detection. Serial serum samples from 10 patients diagnosed with proven mucormycosis (2-9 samples per patient) were analyzed.
No cross-reactivity was detected in the 3 qPCR assays using 19 reference strains of opportunistic fungi, and the limit of detection ranged from 3.7 to 15 femtograms/10 µL, depending on the species. DNA from Mucorales was detected in the serum of 9 of 10 patients between 68 and 3 days before mucormycosis diagnosis was confirmed by histopathological examination and/or positive culture. All the qPCR results were concordant with culture and/or PCR-based identification of the causing agents in tissue (Lichtheimia species, Rhizomucor species, and Mucor/Rhizopus species in 4, 3, and 2 patients, respectively). Quantitative PCR was negative in only 1 patient with proven disseminated mucormycosis caused by Lichtheimia species.
Our study suggests that using specific qPCR targeting several species of Mucorales according to local ecology to screen at-risk patients could be useful in a clinical setting. The cost and efficacy of this strategy should be evaluated. However, given the human and economic cost of mucormycosis and the need for rapid diagnosis to initiate prompt directed antifungal therapy, this strategy could be highly attractive.
Journal Article
What Is a Personality Disorder?
The goal of this article is to describe, characterize, and differentiate personality disorders by connecting their conceptual features to their foundations in the natural sciences. What is proposed is akin to Freud's abandoned Project for a Scientific Psychology and Wilson's (1975) highly controversial Sociobiology. Both were worthy endeavors to advance our understanding of the styles and traits of human nature; this was to be done by exploring interconnections among the diverse disciplines of nature that evolved ostensibly unrelated bodies of research and manifestly dissimilar languages.
Journal Article
Evolutionary developmental transcriptomics reveals a gene network module regulating interspecific diversity in plant leaf shape
Despite a long-standing interest in the genetic basis of morphological diversity, the molecular mechanisms that give rise to developmental variation are incompletely understood. Here, we use comparative transcriptomics coupled with the construction of gene coexpression networks to predict a gene regulatory network (GRN) for leaf development in tomato and two related wild species with strikingly different leaf morphologies. The core network in the leaf developmental GRN contains regulators of leaf morphology that function in global cell proliferation with peripheral gene network modules (GNMs). The BLADE-ON-PETIOLE (BOP) transcription factor in one GNM controls the core network by altering effective concentration of the KNOTTED-like HOMEOBOX gene product. Comparative network analysis and experimental perturbations of BOP levels suggest that variation in BOP expression could explain the diversity in leaf complexity among these species through dynamic rewiring of interactions in the GRN. The peripheral location of the BOP -containing GNM in the leaf developmental GRN and the phenotypic mimics of evolutionary diversity caused by alteration in BOP levels identify a key role for this GNM in canalizing the leaf morphospace by modifying the maturation schedule of leaves to create morphological diversity.
Journal Article