Conventionally, evolution has always been described in terms of species. The Chemistry of Evolution takes a novel, not to say revolutionary, approach and examines the evolution of chemicals and the ...use and degradation of energy, coupled to the environment, as the drive behind it. The authors address the major changes of life from bacteria to man in a systematic and unavoidable sequence, reclassifying organisms as chemotypes. Written by the authors of the bestseller The Biological Chemistry of the Elements - The Inorganic Chemistry of Life (Oxford University Press, 1991), the clarity and precision of The Chemistry of Evolution plainly demonstrate that life is totally interactive with the environment. This exciting theory makes this work an essential addition to the academic and public library.* Provides a novel analysis of evolution in chemical terms * Stresses Systems Biology * Examines the connection between life and the environment, starting with the 'big bang' theory * Reorientates the chemistry of life by emphasising the need to analyse the functions of 20 chemical elements in all organisms
Swietenia macrophylla King is a plant commonly known as Brazilian mahogany. The wood from its stem is highly prized for its exceptional quality, while its leaves are valued for their high content of ...phragmalin-type limonoids, a subclass of compounds known for their significant biological activities, including antimalarial, antitumor, antiviral, and anti-inflammatory properties. In this context, twelve isolated limonoids from S. macrophylla leaves were employed as standards in mass spectrometry-based molecular networking to unveil new potential mass spectrometry signatures for phragmalin-type limonoids. Consequently, ultra-performance liquid chromatography coupled with high-resolution mass spectrometry was utilized for data acquisition. Subsequently, the obtained data were analyzed using the Global Natural Products Social Molecular Networking platform based on spectral similarity. In summary, this study identified 24 new putative phragmalin-type limonoids for the first time in S. macrophylla. These compounds may prove valuable in guiding future drug development efforts, leveraging the already established biological activities associated with limonoids.
The annotation of small molecules is one of the most challenging and important steps in untargeted mass spectrometry analysis, as most of our biological interpretations rely on structural ...annotations. Molecular networking has emerged as a structured way to organize and mine data from untargeted tandem mass spectrometry (MS/MS) experiments and has been widely applied to propagate annotations. However, propagation is done through manual inspection of MS/MS spectra connected in the spectral networks and is only possible when a reference library spectrum is available. One of the alternative approaches used to annotate an unknown fragmentation mass spectrum is through the use of in silico predictions. One of the challenges of in silico annotation is the uncertainty around the correct structure among the predicted candidate lists. Here we show how molecular networking can be used to improve the accuracy of in silico predictions through propagation of structural annotations, even when there is no match to a MS/MS spectrum in spectral libraries. This is accomplished through creating a network consensus of re-ranked structural candidates using the molecular network topology and structural similarity to improve in silico annotations. The Network Annotation Propagation (NAP) tool is accessible through the GNPS web-platform https://gnps.ucsd.edu/ProteoSAFe/static/gnps-theoretical.jsp.
The minimal geometric deformation (MGD), associated with the 4D Schwarzschild solution of the Einstein equations, is shown to be a solution of the pure 4D Ricci quadratic gravity theory, whose linear ...perturbations are then implemented by the Gregory–Laflamme eigentensors of the Lichnerowicz operator. The stability of MGD black strings is hence studied, through the correspondence between their Lichnerowicz eigenmodes and the ones associated with the 4D MGD solutions. It is shown that there exists a critical mass driving the MGD black strings stability, above which the MGD black string is precluded from any Gregory–Laflamme instability. The general-relativistic limit shows the MGD black string to be unstable, as expected, corresponding to the standard Gregory–Laflamme black string instability.
Public health concerns exist surrounding the epidemic of the Zika virus (ZIKV) and the rapid growth of transplantation in developing countries, including endemic zones of active arbovirus ...transmission, as well as travel to such regions by potential organ donors and recipients. Few data exist regarding the clinical characteristics of ZIKV infection in immunocompromised hosts. Laboratory screening protocols for transplantation to differentiate ZIKV infections from other endemic viral diseases and for the detection of possible donor‐derived infection have not been stated. The diagnosis of ZIKV infection remains a challenge, fueled by the lack of standardized commercially available diagnostic tests and validated reference diagnostic laboratories, as well as the limited duration of ZIKV viremia. In this small series, ZIKV infection in renal and liver recipients presented without rash, conjunctivitis, or neurological symptoms, and with abnormal graft function, thrombocytopenia, and bacterial superinfection. We report the first case series of ZIKV infection in solid organ recipients, with a description of clinical and laboratory features and therapeutic management.
In this study, the authors describe the features of Zika infection in solid organ transplant. See the editorial from Blumberg and Fishman on page 599.
Essential oils have shown promise as antiviral agents against several pathogenic viruses. In this work we hypothesized that essential oil components may interact with key protein targets of the 2019 ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A molecular docking analysis was carried out using 171 essential oil components with SARS-CoV-2 main protease (SARS-CoV-2 M
), SARS-CoV-2 endoribonucleoase (SARS-CoV-2 Nsp15/NendoU), SARS-CoV-2 ADP-ribose-1″-phosphatase (SARS-CoV-2 ADRP), SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp), the binding domain of the SARS-CoV-2 spike protein (SARS-CoV-2 rS), and human angiotensin-converting enzyme (hACE2). The compound with the best normalized docking score to SARS-CoV-2 M
was the sesquiterpene hydrocarbon (
)-β-farnesene. The best docking ligands for SARS-CoV Nsp15/NendoU were (
,
)-α-farnesene, (
)-β-farnesene, and (
,
)-farnesol. (
,
)-Farnesol showed the most exothermic docking to SARS-CoV-2 ADRP. Unfortunately, the docking energies of (
,
)-α-farnesene, (
)-β-farnesene, and (
,
)-farnesol with SARS-CoV-2 targets were relatively weak compared to docking energies with other proteins and are, therefore, unlikely to interact with the virus targets. However, essential oil components may act synergistically, essential oils may potentiate other antiviral agents, or they may provide some relief of COVID-19 symptoms.
Chronic exercise induces cardiac remodeling that promotes left ventricular hypertrophy and cardiac functional improvement, which are mediated by the mammalian or the mechanistic target of rapamycin ...(mTOR) as well as by the androgen and glucocorticoid receptors (GRs). However, pathological conditions (i.e., chronic heart failure, hypertension, and aortic stenosis, etc.) also induce cardiac hypertrophy, but with detrimental function, high levels of proinflammatory cytokines and myostatin, elevated fibrosis, reduced adenosine monophosphate‐activated protein kinase (AMPK) activation, and fetal gene reactivation. Furthermore, recent studies have evidenced that excessive training induced an inflammatory status in the serum, muscle, hypothalamus, and liver, suggesting a pathological condition that could also be detrimental to cardiac tissue. Here, we verified the effects of three running overtraining (OT) models on the molecular parameters related to physiological and pathological cardiac hypertrophy. C57BL/6 mice performed three different OT protocols and were evaluated for molecular parameters related to physiological and pathological cardiac hypertrophy, including immunoblotting, reverse transcription polymerase chain reaction, histology, and immunohistochemistry analyses. In summary, the three OT protocols induced left ventricle (LV) hypertrophy with signs of cardiac fibrosis and negative morphological adaptations. These maladaptations were accompanied by reductions in AMPKalpha (Thr172) phosphorylation, androgen receptor, and GR expressions, as well as by an increase in interleukin‐6 expression. Specifically, the downhill running–based OT model reduced the content of some proteins related to the mTOR signaling pathway and upregulated the β‐isoform of myosin heavy‐chain gene expression, presenting signs of LV pathological hypertrophy development.
(a) Overtraining protocols induced left ventricle hypertrophy with signs of cardiac fibrosis and negative morphological adaptations. (b) The downhill running–based overtraining model reduced the content of some proteins related to the mechanistic target of the rapamycin signaling pathway and upregulated the β‐myosin heavy‐chain gene expression.
Medicinal plants have long been used as an alternative to traditional drugs for the treatment of inflammatory conditions due to the classical side effects and restricted access of various ...commercially available drugs, such as steroids (GCs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Sambucus australis is a Brazilian herb that is commonly used to treat inflammatory diseases; however, few studies have examined the use of this species in the treatment of inflammatory conditions. The present study aims to evaluate the potential anti-inflammatory activity of S. australis in vitro. We established spleen cell cultures stimulated with pokeweed mitogen (PWM) to evaluate the production of proinflammatory cytokines, such as IL-4, IL-5, IFN-y, and IL-10 (by ELISA), and the expression of the transcription factor NF-kB (by RT-PCR). In addition, we evaluated the levels of nitric oxide in macrophage cultures and the membrane-stabilizing activity of S. australis methanolic extract (EMSA). Treatment with EMSA at concentrations of 100, 50, 25 and 12.5 µg/ml significantly decreased IL-4 (p<0.001) and IL-5 (p<0.001) levels. Treatment with 100 µg/ml EMSA reduced IFN-у (p<0.001) levels. Moreover, at 100 mg/ml, EMSA also increased IL-10 production and reduced NF-kB expression (p<0.01). In macrophage cultures stimulated with LPS, EMSA decreased nitric oxide levels (p<0.001) at all concentrations tested (100, 50, 25 and 12.5 µg/ml). Additionally, EMSA had a protective effect in the erythrocyte membrane stabilization assay. Taken together, these results suggest that S. australis has anti-inflammatory potential in vitro, characterized by the reduction of both inflammatory cytokines and the expression of NF-kB along with the up-regulation of IL-10.
This work aims to evaluate the chemical composition, in vitro antioxidant capacity, and in vivo antitumoral activity of S. guianensis essential oil against Ehrlich's ascitic carcinoma and the effects ...on oxidative stress. The animals (Mus musculus) received a daily dose of S. guianensis oil orally (100 mg/kg) for 9 days. The main constituents of essential oil were curzerenone (16.4±1.5 %), drimenol (13.7±0.2 %), and spathulenol (12.4±0.8 %). S. guianensis oil showed antioxidant activity, inhibiting 11.1 % of DPPH radicals (95.7 mgTE/g); and 15.5 % of the β‐carotene peroxidation. The group treated with S. guianensis showed a significant reduction in tumor cells (59.76±12.33) compared to the tumor group (96.88±19.15). Essential oil of S. guianensis decreased MDA levels and increased SOD levels in liver tissue. The essential oil of S. guianensis reduced oxidative stress, and showed antitumor and antioxidant activity, being characterized as a new chemical profile in the investigation of pathologies such as cancer.
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