13C MRS: An outstanding tool for metabolic studies

We provide an overview of 13C magnetic resonance spectroscopy methods and their applications as an established metabolic tool with an emphasis on the use of high-resolution 13C magnetic resonance spectroscopy and 13C isotopomer analysis. Topics addressed include general properties of the 13C magnetic resonance spectroscopy spectrum; different 13C magnetic resonance spectroscopy acquisition protocols; determination of fractional 13C enrichment, kinetic, or steady state measurements of metabolic flux; 13C isotopomer analysis approaches; 13C(2H) magnetic resonance spectroscopy methodologies; and in vivo 13C magnetic resonance spectroscopy. Some illustrative applications are described. © 2005 Wiley Periodicals, Inc. Concepts Magn Reson Part A 27A: 1-16, 2005

Astrocytic–Neuronal–Astrocytic Pathway Selection for Formation and Degradation of Glutamate/GABA

Endocrinological research early recognized the importance of intercellular interactions and realized the importance of glutamatergic and GABAergic signaling. In turn this signalling depends on elaborate interactions between astrocytes and neurons, without which neurons would be unable to produce, reuse and metabolize transmitter glutamate and GABA. Details of these subjects are described in this Research Topic by key investigators in this field. It focuses on the intricate and extremely swift pathway producing these amino acid transmitters from glucose in brain but also discusses difficulties in determining expression of some of the necessary genes in astrocytes and related processes in pancreatic islets. However, it does not discuss how closely associated astrocytes and neurons are anatomically, enabling these interactions. This is elegantly shown in this cover image, kindly provided by Professor Andreas Reichenbach (University of Leipzig, Germany)

Quantitation of absolute 2H enrichment of plasma glucose by 2H NMR analysis of its monoacetone derivative

A simple 2H NMR method for quantifying absolute 2H-enrichments in all seven aliphatic positions of glucose following its derivatization to monoacetone glucose is presented. The method is based on the addition of a small quantity of 2H-enriched formate to the NMR sample. When the method was applied to [2-2H]monoacetone glucose samples prepared from [2-2H]glucose standards of known enrichments in the range of 0.2-2.5%, enrichment estimates derived by the NMR method were in good agreement with the real enrichment values of the [2-2H]glucose precursors. The measurement was also applied to monoacetone glucose derived from human plasma glucose samples following administration of 2H2O and attainment of isotopic steady state, where glucose H2 and body water enrichment are equivalent. In these studies, the absolute H2 enrichment of plasma glucose estimated by the formate method was in good agreement with the 2H-enrichment of body water measured by an independent method. Magn Reson Med 48:535-539, 2002. © 2002 Wiley-Liss, Inc

Machine learning for next-generation nanotechnology in healthcare

Funding: The authors acknowledge financial support from FCT Portugal in the framework of PhD grant 2020.06638.BD (to D.P.S.), and the European Research Council grant agreement 848325 (J. Conde for the ERC Starting Grant). T.R. is an Investigador Auxiliar supported by FCT Portugal (CEECIND/ 00684/2018).Nanotechnology for healthcare is coming of age, but automating the design of composite materials poses unique challenges. Although machine learning is supporting groundbreaking discoveries in materials science, new initiatives leveraging learned patterns are required to fully realize the promise of nanodelivery systems and accelerate development pipelines.publishersversionpublishe

Hypothyroidism decreases the biogenesis in free mitochondria and neuronal oxygen consumption in the cerebral cortex of developing rats

Thyroid hormone plays a critical role in mitochondrial biogenesis in two areas of the developing brain, the cerebral cortex and the striatum. Here we analyzed, in the cerebral cortex of neonatal rats, the effect of hypothyroidism on the biogenesis in free and synaptosomal mitochondria by analyzing, in isolated mitochondria, the activity of respiratory complex I, oxidative phosphorylation, oxygen consumption, and the expression of mitochondrial genome. In addition, we studied the effect of thyroid hormone in oxygen consumption in vivo by determining metabolic flow through C-13 nuclear magnetic resonance spectroscopy. Our results clearly show that in vivo, hypothyroidism markedly reduces oxygen consumption in the neural population of the cerebral cortex. This effect correlates with decreased free mitochondria biogenesis. In contrast, no effect was observed in the biogenesis in synaptosomal mitochondria. The parameters analyzed were markedly improved after T-3 administration. These results suggest that a reduced biogenesis and the subsequent reduction of respiratory capacity in free mitochondria could be the underlying cause of decreased oxygen consumption in the neurons of the cerebral cortex of hypothyroid neonates.This work was supported by Ministerio de Educaciín y Ciencia Grants SAF2004-06263-CO2-02 (to A.S.), SAF2004-06263-CO2-01, and SAF2007-62811 and Comunidad de Madrid Grant GR/SAL/0033/2004 (to A.P.-C.). Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas is funded by the Instituto de Salud Carlos III. T.B.R. is a recipient of a fellowship from the Fundaçâo para a Ciência e Tecnologia, Portugal (SFRH/BPD/26881/2006).Peer reviewe

Synthesis, characterization and cytotoxicity of S-nitrosomercaptosuccinic acid-containing alginate/chitosan nanoparticles

Nitric oxide (NO) is an endogenous free radical, which plays key roles in several biological processes including vasodilation, neurotransmission, inhibition of platelet adhesion, cytotoxicity against pathogens, wound healing, and defense against cancer. Due to the relative instability of NO in vivo (half-life of ca. 0.5 seconds), there is an increasing interest in the development of low molecular weight NO donors, such as S-nitrosothiols (RSNOs), which are able to prolong and preserve the biological activities of NO in vivo. In order to enhance the sustained NO release in several biomedical applications, RSNOs have been successfully allied to nanomaterials. In this context, this work describes the synthesis and characterization of the NO donor S-nitroso-mercaptosuccinic acid (S-nitroso-MSA), which belongs to the class of RSNOs, and its incorporation in polymeric biodegradable nanoparticles composed by alginate/chitosan. First, chitosan nanoparticles were obtained by gelation process with sodium tripolyphosphate (TPP), followed by the addition of the alginate layer, to enhance the nanoparticle protection. The obtained nanoparticles presented a hydrodynamic diameter of 343 +/- 38 nm, polydispersity index (PDI) of 0.36 +/- 0.1, and zeta potential of -30.3 +/- 0.4 mV, indicating their thermal stability in aqueous suspension. The negative zeta potential value was assigned to the presence of alginate chains on the surface of chitosan/TPP nanoparticles. The encapsulation efficiency of the NO donor into the polymeric nanoparticles was found to be 98 +/- 0.2%. The high encapsulation efficiency value was attributed to the positive interactions between the NO donor and the polymeric content of the nanoparticles. Kinetics of NO release from the nanoparticles revealed a spontaneous and sustained release of therapeutic amounts of NO, for several hours under physiological temperature. The incubation of NO-releasing alginate/chitosan nanoparticles with human hepatocellular carcinoma (HepG2) cell line revealed a concentration-dependent toxicity. These results point to the promising uses of NO-releasing alginate/chitosan nanoparticles for anti-cancer chemotherapy.Brazilian Network on NanotoxicologyLaboratory of Nanostructure Synthesis and Biosystem Interactions-NANOBIOSS (MCTI)Newton Advanced Fellowship (The Royal Society)Univ Fed ABC, Ctr Nat & Human Sci, Av Estados 5001, BR-09210580 Santo Andre, SP, BrazilUniv Fed Sao Paulo, Exact & Earth Sci Dept, Rua Sao Nicolau 210, BR-09913030 Diadema, SP, BrazilUniv Fed Sao Paulo, Exact & Earth Sci Dept, Rua Sao Nicolau 210, BR-09913030 Diadema, SP, BrazilBrazilian Network on Nanotoxicology: 52120/2011-1Laboratory of Nanostructure Synthesis and Biosystem Interactions-NANOBIOSS (MCTI): 402280-2013Newton Advanced Fellowship (The Royal Society): NA140046Web of Scienc

Placebo response in chronic peripheral neuropathic pain trials: systematic review and meta-analysis

Objective: To estimate the magnitude of the placebo and nocebo responses in chronic peripheral neuropathic pain (CNP) and explore possible associations with trial characteristics. // Methods: We searched CENTRAL, MEDLINE, and Embase for randomized controlled trials (RCTs) from inception to May 2020. We included placebo-controlled RCTs of ≥8 weeks investigating first-line pharmacological interventions for CNP. Primary endpoints were the placebo response, the proportion of patients receiving placebo with pain intensity reduction (PIR) ≥30% from baseline, and the nocebo response, the proportion of patients receiving placebo experiencing adverse events (AEs). Screening, data extraction, and bias assessment (with the Cochrane risk of bias tool) were conducted by independent reviewers. We pooled data using a random-effects model. // Results: We included 50 trials, with a combined 5,693 participants allocated to placebo, conducted between 1998 and 2020. Overall, 38% of patients receiving placebo reported PIR≥30% (95% CI 34 to 42, I2=86%); 23% reported PIR≥50% (95% CI 20 to 26; I2=81%). 50% of patients receiving placebo reported AEs (95% CI 0.43 to 0.58; I2=97%); 2% reported serious AEs (95% CI 2 to 3; I2=58%). In patients receiving active interventions, the placebo response accounts for 75% of the treatment effect on PIR≥30%, and the nocebo response accounts for 75% of the AEs. Interpreted inversely, only 25% of responses and 25% of adverse events can be attributed to the intervention. Publication year positively correlated with PIR≥30% and negatively correlated with AEs. Female sex negatively correlated with AEs. // Conclusions: The placebo and nocebo responses in parallel-designed RCTs in CNP are substantial and should be considered in trial interpretation and in the design of future trials

A network approach to emotion regulation and symptom activation in depression and anxiety

Background: Emotions can be regulated through several regulatory strategies that are involved in the development of psychopathological symptoms. Despite the well-established association between psychopathology and emotion dysregulation, little is known about the relationship between individual symptoms of depression and anxiety and emotion regulation strategies (ERS), as well as between ERS themselves. Method: We conducted a cross-sectional study and examined the interactions between six ERS (reappraisal, engagement, rumination, suppression, arousal control, and distraction) and assessed their distinctive association with the activation of specific symptoms of depression and anxiety in a community sample of 376 adults (80.4% female; Mage = 32.70; SDage = 11.80). The Regulation Emotion Systems Survey (RESS) was used to measure ERS. The Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) were used to assess psychological symptoms. An exploratory graph analysis was performed to examine the structural properties of the network of interactions between these behaviors. Additionally, to test the association of ERS with the activation of the depression symptoms network, an expected symptoms activity (ESA) was conducted. Results: Six communities were found that correspond to the six ERS. Rumination and suppression have a significant association with symptom activation (particularly low self-esteem), whereas reappraisal reduces symptomatic activation. The effect of arousal control, engagement, and distraction appears to depend on the remaining ERS rather than having much influence on their own. Conclusion: This study provides insight into how ERS interact with each other and with individual symptoms of depression and anxiety. Understanding the effects of these interactions on symptom activation and comorbidity can improve our understanding of psychopathology.info:eu-repo/semantics/publishedVersio

Room-temperature emitters in wafer-scale few-layer hBN by atmospheric pressure CVD

Hexagonal boron nitride (hBN) is a two-dimensional, wide band gap semiconductor material suitable for several technologies. 2D hBN appeared as a viable platform to produce bright and optically stable single photon emitters (SPEs) at room temperature, which are in demand for quantum technologies. In this context, one main challenge concerns the upscaling of 2D hBN with uniform spatial and spectral distribution of SPE sources. In this work we optimized the atmospheric-pressure chemical vapor deposition (APCVD) growth and obtained large-area 2D hBN with uniform fluorescence emission properties. We characterized the hBN films by a combination of electron microscopy, Raman and X-ray photoelectron spectroscopy techniques. The extensive characterization revealed few-layer, polycrystalline hBN films (∼3 nm thickness) with balanced stoichiometry and uniformity over 2″ wafer scale. We studied the fluorescence emission properties of the hBN films by multidimensional hyperspectral fluorescence microscopy. We measured simultaneously the spatial position, intensity, and spectral properties of the emitters, which were exposed to continuous illumination over minutes. Three main emission peaks (at 538, 582, and 617 nm) were observed, with associated replica peaks red-shifted by ∼53 nm. A surface emitter density of ∼0.1 emitters/μm2 was found. A comparative test with pristine hBN nanosheets produced by liquid-phase exfoliation (LPE) was performed, finding that CVD and LPE hBN possess analogous spectral emitter categories in terms of peak position/intensity and density. Overall, the line-shape and wavelength of the emission peaks, as well as the other measured features, are consistent with single-photon emission from hBN. The results indicate that APCVD hBN might proficiently serve as a SPE platform for quantum technologies.We acknowledge the financial support of i) the project “GEMIS – Graphene-enhanced Electro Magnetic Interference Shielding,” with the reference POCI-01-0247-FEDER-045939, co-funded by COMPETE 2020 – Operational Programme for Competitiveness and Internationalization and FCT –Science and Technology Foundation, under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); ii) the project "Graphene and novel thin films for super-resolution microscopy and bio-sensing" (PTDC/NAN-OPT/29417/2017) financed by ERDF, through the Competitiveness and Internationalization Operational Program (POCI) by Portugal 2020 and by the Portuguese Foundation for Science and Technology (FCT) with references POCI-01-0145-FEDER-029417 and PTDC/NAN-OPT/29417/2017; iii) the FCT in the framework of the Strategic Funding UIDB/04650/2020. One of the authors (T.Q.) acknowledges the FCT financial support under the Quantum Portugal Initiative Ph.D. scholarship SFRH/BD/150646/2020. We acknowledge the support by the INL AEMIS, Micro- and Nanofabrication, and Nanophotonics and Bioimaging research core facilities