N6-methyladenosine in 5' UTR does not promote translation initiation.

The most abundant N6-methyladenosine (m6A) modification on mRNAs is installed non-stoichiometrically across transcripts, with 5' untranslated regions (5' UTRs) being the least conductive. 5' UTRs are essential for translation initiation, yet the molecular mechanisms orchestrated by m6A remain poorly understood. Here, we combined structural, biochemical, and single-molecule approaches and show that at the most common position, a single m6A does not affect translation yields, the kinetics of translation initiation complex assembly, or start codon recognition both under permissive growth and following exposure to oxidative stress. Cryoelectron microscopy (cryo-EM) structures of the late preinitiation complex reveal that m6A purine ring established stacking interactions with an arginine side chain of the initiation factor eIF2α, although with only a marginal energy contribution, as estimated computationally. These findings provide molecular insights into m6A interactions with the initiation complex and suggest that the subtle stabilization is unlikely to affect the translation dynamics under homeostatic conditions or stress.

Engineered tRNAs suppress nonsense mutations in cells and in vivo.

Nonsense mutations are the underlying cause of approximately 11% of all inherited genetic diseases1. Nonsense mutations convert a sense codon that is decoded by tRNA into a premature termination codon (PTC), resulting in an abrupt termination of translation. One strategy to suppress nonsense mutations is to use natural tRNAs with altered anticodons to base-pair to the newly emerged PTC and promote translation2-7. However, tRNA-based gene therapy has not yielded an optimal combination of clinical efficacy and safety and there is presently no treatment for individuals with nonsense mutations. Here we introduce a strategy based on altering native tRNAs into  efficient suppressor tRNAs (sup-tRNAs) by individually fine-tuning their sequence to the physico-chemical properties of the amino acid that they carry. Intravenous and intratracheal lipid nanoparticle (LNP) administration of sup-tRNA in mice restored the production of functional proteins with nonsense mutations. LNP-sup-tRNA formulations caused no discernible readthrough at endogenous native stop codons, as determined by ribosome profiling. At clinically important PTCs in the cystic fibrosis transmembrane conductance regulator gene (CFTR), the sup-tRNAs re-established expression and function in cell systems and patient-derived nasal epithelia and restored airway volume homeostasis. These results provide a framework for the development of tRNA-based therapies with a high molecular safety profile and high efficacy in targeted PTC suppression.

Early Release Science of the exoplanet WASP-39b with JWST NIRISS.

The Saturn-mass exoplanet WASP-39b has been the subject of extensive efforts to determine its atmospheric properties using transmission spectroscopy1-4. However, these efforts have been hampered by modelling degeneracies between composition and cloud properties that are caused by limited data quality5-9. Here we present the transmission spectrum of WASP-39b obtained using the Single-Object Slitless Spectroscopy (SOSS) mode of the Near Infrared Imager and Slitless Spectrograph (NIRISS) instrument on the JWST. This spectrum spans 0.6-2.8 µm in wavelength and shows several water-absorption bands, the potassium resonance doublet and signatures of clouds. The precision and broad wavelength coverage of NIRISS/SOSS allows us to break model degeneracies between cloud properties and the atmospheric composition of WASP-39b, favouring a heavy-element enhancement ('metallicity') of about 10-30 times the solar value, a sub-solar carbon-to-oxygen (C/O) ratio and a solar-to-super-solar potassium-to-oxygen (K/O) ratio. The observations are also best explained by wavelength-dependent, non-grey clouds with inhomogeneous coverageof the planet's terminator.

A broadband thermal emission spectrum of the ultra-hot Jupiter WASP-18b.

Close-in giant exoplanets with temperatures greater than 2,000 K ('ultra-hot Jupiters') have been the subject of extensive efforts to determine their atmospheric properties using thermal emission measurements from the Hubble Space Telescope (HST) and Spitzer Space Telescope1-3. However, previous studies have yielded inconsistent results because the small sizes of the spectral features and the limited information content of the data resulted in high sensitivity to the varying assumptions made in the treatment of instrument systematics and the atmospheric retrieval analysis3-12. Here we present a dayside thermal emission spectrum of the ultra-hot Jupiter WASP-18b obtained with the NIRISS13 instrument on the JWST. The data span 0.85 to 2.85 µm in wavelength at an average resolving power of 400 and exhibit minimal systematics. The spectrum shows three water emission features (at >6σ confidence) and evidence for optical opacity, possibly attributable to H-, TiO and VO (combined significance of 3.8σ). Models that fit the data require a thermal inversion, molecular dissociation as predicted by chemical equilibrium, a solar heavy-element abundance ('metallicity', [Formula: see text] times solar) and a carbon-to-oxygen (C/O) ratio less than unity. The data also yield a dayside brightness temperature map, which shows a peak in temperature near the substellar point that decreases steeply and symmetrically with longitude towards the terminators.

Coxiella co-opts the Glutathione Peroxidase 4 to protect the host cell from oxidative stress-induced cell death.

The causative agent of human Q fever, Coxiella burnetii, is highly adapted to infect alveolar macrophages by inhibiting a range of host responses to infection. Despite the clinical and biological importance of this pathogen, the challenges related to genetic manipulation of both C. burnetii and macrophages have limited our knowledge of the mechanisms by which C. burnetii subverts macrophages functions. Here, we used the related bacterium Legionella pneumophila to perform a comprehensive screen of C. burnetii effectors that interfere with innate immune responses and host death using the greater wax moth Galleria mellonella and mouse bone marrow-derived macrophages. We identified MceF (Mitochondrial Coxiella effector protein F), a C. burnetii effector protein that localizes to mitochondria and contributes to host cell survival. MceF was shown to enhance mitochondrial function, delay membrane damage, and decrease mitochondrial ROS production induced by rotenone. Mechanistically, MceF recruits the host antioxidant protein Glutathione Peroxidase 4 (GPX4) to the mitochondria. The protective functions of MceF were absent in primary macrophages lacking GPX4, while overexpression of MceF in human cells protected against oxidative stress-induced cell death. C. burnetii lacking MceF was replication competent in mammalian cells but induced higher mortality in G. mellonella, indicating that MceF modulates the host response to infection. This study reveals an important C. burnetii strategy to subvert macrophage cell death and host immunity and demonstrates that modulation of the host antioxidant system is a viable strategy to promote the success of intracellular bacteria.

Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion Syndrome.

22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with a broad and heterogeneous phenotype, even though most of the deletions present similar sizes, involving ∼3 Mb of DNA. In a relatively large population of a Brazilian 22q11.2DS cohort (60 patients), we investigated genetic variants that could act as genetic modifiers and contribute to the phenotypic heterogeneity, using a targeted NGS (Next Generation Sequencing) with a specific Ion AmpliSeq panel to sequence nine candidate genes (CRKL, MAPK1, HIRA, TANGO2, PI4KA, HDAC1, ZDHHC8, ZFPM2, and JAM3), mapped in and outside the 22q11.2 hemizygous deleted region. In silico prediction was performed, and the whole-genome sequencing annotation analysis package (WGSA) was used to predict the possible pathogenic effect of single nucleotide variants (SNVs). For the in silico prediction of the indels, we used the genomic variants filtered by a deep learning model in NGS (GARFIELD-NGS). We identified six variants, 4 SNVs and 2 indels, in MAPK1, JAM3, and ZFPM2 genes with possibly synergistic deleterious effects in the context of the 22q11.2 deletion. Our results provide the opportunity for the discovery of the co-occurrence of genetic variants with 22q11.2 deletions, which may influence the patients´ phenotype.

Air-Stable Cobalt(III) and Chromium(III) Complexes as Single-Component Catalysts for the Activation of Carbon Dioxide and Epoxides.

Cobalt(III) and chromium(III) salophen chloride complexes were synthesized and tested for the cycloaddition of carbon dioxide (CO2) with epoxides to obtain cyclic carbonates. The cat1, cat2, cat4, and cat5 complexes presented high catalytic activity without cocatalysts and are solvent-free at 100 °C, 8 bar, and 9 h. At these conditions, the terminal epoxides (1a-1k) were successfully converted into the corresponding cyclic carbonates with a maximum conversion of ∼99%. Moreover, cat5 was highlighted due to its capability of opening internal epoxides such as limonene oxide (1l) with a 36% conversion to limonene carbonate (2l), and from cyclohexene oxide (1m), cyclic trans-cyclohexene carbonate (2m) and poly(cyclohexene carbonate) were obtained with 15% and 85% selectivity, respectively. A study of the coupling reaction mechanism was proposed with the aid of electrospray ionization mass spectrometry (ESI-MS) analysis, confirming the single-component behavior of the complexes through their ionization due to epoxide coordination. In addition, crystallographic analysis of cat1 single crystals grown in a saturated solution of pyridine helped to demonstrate that the substitution of chloride ion by pyridine ligands to form an octahedral coordination occurs (Py-cat1), supporting the proposed mechanism. Also, a recyclability study was performed for cat5, and a total turnover number of 952 was obtained with only minor losses in catalytic activity after five cycles.

Positive epistasis between disease-causing missense mutations and silent polymorphism with effect on mRNA translation velocity.

Epistasis refers to the dependence of a mutation on other mutation(s) and the genetic context in general. In the context of human disorders, epistasis complicates the spectrum of disease symptoms and has been proposed as a major contributor to variations in disease outcome. The nonadditive relationship between mutations and the lack of complete understanding of the underlying physiological effects limit our ability to predict phenotypic outcome. Here, we report positive epistasis between intragenic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)-the gene responsible for cystic fibrosis (CF) pathology. We identified a synonymous single-nucleotide polymorphism (sSNP) that is invariant for the CFTR amino acid sequence but inverts translation speed at the affected codon. This sSNP in cis exhibits positive epistatic effects on some CF disease-causing missense mutations. Individually, both mutations alter CFTR structure and function, yet when combined, they lead to enhanced protein expression and activity. The most robust effect was observed when the sSNP was present in combination with missense mutations that, along with the primary amino acid change, also alter the speed of translation at the affected codon. Functional studies revealed that synergistic alteration in ribosomal velocity is the underlying mechanism; alteration of translation speed likely increases the time window for establishing crucial domain-domain interactions that are otherwise perturbed by each individual mutation.

Nonlinear hydrological time series modeling to forecast river level dynamics in the Rio Negro Uruguay basin.

Floods significantly impact the well-being and development of communities. Hence, understanding their causes and establishing methodologies for risk prevention is a critical challenge for effective warning systems. Complex systems such as hydrological basins are modeled through hydrological models that have been utilized to understand water recharge of aquifers, available volume of dams, and floods in diverse regions. Acquiring real-time hydrometeorological data from basins and rivers is vital for establishing data-driven-based models as tools for the prediction of river-level dynamics and for understanding its nonlinear behavior. This paper introduces a hydrological model based on a multilayer perceptron neural network as a useful tool for time series modeling and forecasting river levels in three stations of the Rio Negro basin in Uruguay. Daily time series of river levels and rainfall serve as the input data for the model. The assessment of the models is based on metrics such as the Nash-Sutcliffe coefficient, the root mean square error, percent bias, and volumetric efficiency. The outputs exhibit varying model performance and accuracy during the prediction period across different sub-basin scales, revealing the neural network's ability to learn river dynamics. Lagged time series analysis demonstrates the potential for chaos in river-level time series over extended time periods, mainly when predicting dam-related scenarios, which shows physical connections between the dynamical system and the data-based model such as the evolution of the system over time.

Scalable Generation and Detection of on-Demand W States in Nanophotonic Circuits.

Quantum physics phenomena, entanglement and coherence, are crucial for quantum information protocols, but understanding these in systems with more than two parts is challenging due to increasing complexity. The W state, a multipartite entangled state, is notable for its robustness and benefits in quantum communication. Here, we generate eight-mode on-demand single-photon W states, using nanowire quantum dots and a silicon nitride photonic chip. We demonstrate a reliable and scalable technique for reconstructing the W state in photonic circuits using Fourier and real-space imaging, supported by the Gerchberg-Saxton phase retrieval algorithm. Additionally, we utilize an entanglement witness to distinguish between mixed and entangled states, thereby affirming the entangled nature of our generated state. The study provides a new imaging approach of assessing multipartite entanglement in W states, paving the way for further progress in image processing and Fourier-space analysis techniques for complex quantum systems.

Nickel(II)-Catalyzed Formal [3+2] Cycloadditions between Indoles and Donor-Acceptor Cyclopropanes.

This article describes the development of a nickel-catalyzed regio- and diastereoselective formal [3+2] cycloaddition between N-substituted indoles and donor-acceptor cyclopropanes to synthesize cyclopenta[b]indoles. Optimized reaction conditions provide the desired nitrogen-containing cycloadducts in up to 93% yield and dr 8.6:1 with complete regioselectivity. The substrate scope showed high tolerance to various substituted indoles and cyclopropanes, resulting in the synthesis of six new cyclopenta[b]indoles and the isolation of five derivatives previously reported in the literature. In addition, a mechanistic proposal for the reaction was studied through online reaction monitoring by ESI-MS, allowing for the identification of the reactive intermediates in the Ni(II) catalyzed process. X-ray crystallography confirmed the structure and relative endo stereochemistry of the products. This method enables the fast and efficient construction of fused indolines from readily accessible starting materials.

The light intensity in the cultivation environment and the impact of glyphosate on plants of the Urochloa genus.

The variation in light within the environment triggers morphophysiological changes in plants and can lead to distinct responses in sun-exposed or shaded plants to glyphosate. The response of Urochloa genotypes subjected to desiccation with 2160, 1622.4, 1080, 524.4, 273.6, and 0.0 g ha-1 of glyphosate was evaluated in full sun and shade conditions. Cayana grass, mulato II grass, and sabiá grass - hybrids recently launched on the market, in addition to palisade grass and congo grass were evaluated. Under full sun, we achieved control of congo grass using 1080 g ha-1 of glyphosate, while the other grasses required 2160 g ha-1. In the low-light environment, sabiá grass was effectively controlled with 524.4 g ha-1 of glyphosate, but the other grasses needed 273.6 g ha-1. In shading, compared to full sun, the savings with glyphosate were 75 and 76% for the control of congo grass and sabiá grass, respectively, and 87% for palisade grass, mulato II grass and cayana grass. Increasing glyphosate doses leads to a decline in the quantum efficiency of photosystem II and in the electron transport rate, especially in the shade. Urochloa genotypes are more sensitive to glyphosate in the shade, which must be considered when determining the herbicide dose.

Using artificial intelligence for exercise prescription in personalised health promotion: A critical evaluation of OpenAI's GPT-4 model.

The rise of artificial intelligence (AI) applications in healthcare provides new possibilities for personalized health management. AI-based fitness applications are becoming more common, facilitating the opportunity for individualised exercise prescription. However, the use of AI carries the risk of inadequate expert supervision, and the efficacy and validity of such applications have not been thoroughly investigated, particularly in the context of diverse health conditions. The aim of the study was to critically assess the efficacy of exercise prescriptions generated by OpenAI's Generative Pre-Trained Transformer 4 (GPT-4) model for five example patient profiles with diverse health conditions and fitness goals. Our focus was to assess the model's ability to generate exercise prescriptions based on a singular, initial interaction, akin to a typical user experience. The evaluation was conducted by leading experts in the field of exercise prescription. Five distinct scenarios were formulated, each representing a hypothetical individual with a specific health condition and fitness objective. Upon receiving details of each individual, the GPT-4 model was tasked with generating a 30-day exercise program. These AI-derived exercise programs were subsequently subjected to a thorough evaluation by experts in exercise prescription. The evaluation encompassed adherence to established principles of frequency, intensity, time, and exercise type; integration of perceived exertion levels; consideration for medication intake and the respective medical condition; and the extent of program individualization tailored to each hypothetical profile. The AI model could create general safety-conscious exercise programs for various scenarios. However, the AI-generated exercise prescriptions lacked precision in addressing individual health conditions and goals, often prioritizing excessive safety over the effectiveness of training. The AI-based approach aimed to ensure patient improvement through gradual increases in training load and intensity, but the model's potential to fine-tune its recommendations through ongoing interaction was not fully satisfying. AI technologies, in their current state, can serve as supplemental tools in exercise prescription, particularly in enhancing accessibility for individuals unable to access, often costly, professional advice. However, AI technologies are not yet recommended as a substitute for personalized, progressive, and health condition-specific prescriptions provided by healthcare and fitness professionals. Further research is needed to explore more interactive use of AI models and integration of real-time physiological feedback.

Effects of dipeptidyl peptidase 4 inhibition on the endothelial control of the vascular tone.

Dipeptidyl peptidase 4 (DPP4) is a serine protease known to cleave incretin hormones, which stimulate insulin secretion after food intake, a fact that supported the development of its inhibitors (DPP4i or gliptins) for the treatment of type 2 diabetes mellitus. In addition to their glucose-lowering effects, DPP4i show benefits for the cardiovascular system that could be related, at least in part, to their protective action on vascular endothelium. DPP4i have been associated with the reversal of endothelial dysfunction, an important predictor of cardiovascular events and a hallmark of diseases such as atherosclerosis, diabetes mellitus, hypertension, and heart failure. In animal models of these diseases, DPP4i increase nitric oxide bioavailability and limits oxidative stress, thereby improving the endothelium-dependent relaxation. Similar effects on flow-mediated dilation and attenuation of endothelial dysfunction have also been noted in human studies, suggesting a value for gliptins in the clinical scenario, despite the variability of the results regarding the DPP4i used, treatment duration, and presence of comorbidities. In this mini-review, we discuss the advances in our comprehension of the DPP4i effects on endothelial regulation of vascular tone. Understanding the role of DPP4 and its involvement in the signaling mechanisms leading to endothelial dysfunction will pave the way for a broader use of DPP4i in conditions that endothelial dysfunction is a pivotal pathophysiological player.

SIRT6 stabilization and cytoplasmic localization in macrophages regulates acute and chronic inflammation in mice.

Acute and chronic inflammations are key homeostatic events in health and disease. Sirtuins (SIRTs), a family of NAD-dependent protein deacylases, play a pivotal role in the regulation of these inflammatory responses. Indeed, SIRTs have anti-inflammatory effects through a myriad of signaling cascades, including histone deacetylation and gene silencing, p65/RelA deacetylation and inactivation, and nucleotide­binding oligomerization domain, leucine rich repeat, and pyrin domain­containing protein 3 inflammasome inhibition. Nevertheless, recent findings show that SIRTs, specifically SIRT6, are also necessary for mounting an active inflammatory response in macrophages. SIRT6 has been shown to positively regulate tumor necrosis factor alpha (TNFα) secretion by demyristoylating pro-TNFα in the cytoplasm. However, how SIRT6, a nuclear chromatin-binding protein, fulfills this function in the cytoplasm is currently unknown. Herein, we show by Western blot and immunofluorescence that in macrophages and fibroblasts there is a subpopulation of SIRT6 that is highly unstable and quickly degraded via the proteasome. Upon lipopolysaccharide stimulation in Raw 264.7, bone marrow, and peritoneal macrophages, this population of SIRT6 is rapidly stabilized and localizes in the cytoplasm, specifically in the vicinity of the endoplasmic reticulum, promoting TNFα secretion. Furthermore, we also found that acute SIRT6 inhibition dampens TNFα secretion both in vitro and in vivo, decreasing lipopolysaccharide-induced septic shock. Finally, we tested SIRT6 relevance in systemic inflammation using an obesity-induced chronic inflammatory in vivo model, where TNFα plays a key role, and we show that short-term genetic deletion of SIRT6 in macrophages of obese mice ameliorated systemic inflammation and hyperglycemia, suggesting that SIRT6 plays an active role in inflammation-mediated glucose intolerance during obesity.

A building-block database of distributed polarizabilities and dipole moments to estimate optical properties of biomacromolecules in isolation or in an explicitly solvated medium.

Since atomic or functional-group properties in the bulk are generally not available from experimental methods, computational approaches based on partitioning schemes have emerged as a rapid yet accurate pathway to estimate the materials behavior from chemically meaningful building blocks. Among several applications, a comprehensive and systematically built database of atomic or group polarizabilities and related opto-electronic quantities would be very useful not only to envisage linear or non-linear optical properties of biomacromolecules but also to improve the accuracy of classical force fields devoted to simulate biochemical processes. In this work, we propose the first entries of such database that contains distributed polarizabilities and dipole moments extracted from fragments of peptides. Twenty three prototypical conformers of the dipeptides alanine-alanine and glycine-glycine were used to extract functional groups such as CH2 , CHCH3 , NH2 , COOH, CONH, thus allowing construction of a diversity of chemically relevant environments. To evaluate the accuracy of our database, reconstructed properties of larger peptides containing up to six residues of alanine and glycine were tested against density functional theory calculations at the M06-HF/aug-cc-pVDZ level of theory. The procedure is particularly accurate for the diagonal components of the polarizability tensor with errors up to 15%. In order to include solvent effects explicitly, the peptides were also surrounded by a box of water molecules whose distribution was optimized using the CHARMM force field. Solvent effects introduced by a classical dipole-dipole interaction model were compared to those obtained from polarizable-continuum model calculations.

Prevalence and risk factors of psychiatric symptoms and diagnoses before and during the COVID-19 pandemic: findings from the ELSA-Brasil COVID-19 mental health cohort.

BACKGROUND: There is mixed evidence on increasing rates of psychiatric disorders and symptoms during the coronavirus disease 2019 (COVID-19) pandemic in 2020. We evaluated pandemic-related psychopathology and psychiatry diagnoses and their determinants in the Brazilian Longitudinal Study of Health (ELSA-Brasil) São Paulo Research Center. METHODS: Between pre-pandemic ELSA-Brasil assessments in 2008-2010 (wave-1), 2012-2014 (wave-2), 2016-2018 (wave-3) and three pandemic assessments in 2020 (COVID-19 waves in May-July, July-September, and October-December), rates of common psychiatric symptoms, and depressive, anxiety, and common mental disorders (CMDs) were compared using the Clinical Interview Scheduled-Revised (CIS-R) and the Depression Anxiety Stress Scale-21 (DASS-21). Multivariable generalized linear models, adjusted by age, gender, educational level, and ethnicity identified variables associated with an elevated risk for mental disorders. RESULTS: In 2117 participants (mean age 62.3 years, 58.2% females), rates of CMDs and depressive disorders did not significantly change over time, oscillating from 23.5% to 21.1%, and 3.3% to 2.8%, respectively; whereas rate of anxiety disorders significantly decreased (2008-2010: 13.8%; 2016-2018: 9.8%; 2020: 8%). There was a decrease along three wave-COVID assessments for depression [ß = -0.37, 99.5% confidence interval (CI) -0.50 to -0.23], anxiety (ß = -0.37, 99.5% CI -0.48 to -0.26), and stress (ß = -0.48, 99.5% CI -0.64 to -0.33) symptoms (all ps < 0.001). Younger age, female sex, lower educational level, non-white ethnicity, and previous psychiatric disorders were associated with increased odds for psychiatric disorders, whereas self-evaluated good health and good quality of relationships with decreased risk. CONCLUSION: No consistent evidence of pandemic-related worsening psychopathology in our cohort was found. Indeed, psychiatric symptoms slightly decreased along 2020. Risk factors representing socioeconomic disadvantages were associated with increased odds of psychiatric disorders.

Chemical similarity of dialkyl carbonates and carbon dioxide opens an avenue for novel greenhouse gas scavengers: cheap recycling and low volatility via experiments and simulations.

Global warming linked to the industrial emissions of greenhouse gases may be the end of mankind unless it is adequately and timely handled. To prevent irreversible changes to the climate of the Earth, numerous research groups are striving to develop robust CO2 sorbents. Dialkyl carbonates (DACs) and CO2 exhibit obvious chemical similarities in their structure and properties. The degrees of oxidation of all atoms composing DACs and CO2 are identical resulting in very similar nucleophilicities and electrophilicities of all interaction centers. While both compounds possess relatively high partial atomic charges on their polar moieties, the molecular geometries prevent tight binding of the head groups. The computed DAC-DAC binding energies are ∼40 kJ mol-1, whereas the effect of the alkyl chain length is marginal. The phase transition points and shear viscosities of DACs are very low. We herein hypothesize and numerically rationalize that DACs represent noteworthy physical sorbents for CO2 thanks to the similar sorbent-CO2 and sorbent-sorbent interaction energies. By reporting in silico-derived sorption thermodynamics at various conditions, spectral and structural properties, and experimentally derived CO2 capacities and recyclabilities, we highlight the mutual affinity of DACs and CO2. Indeed, the experimentally determined CO2 sorption capacity of 0.88 mol% (diethyl carbonate) at 278.15 K and 30 bar is competitive. The unprecedentedly low DAC-CO2 binding energies, ∼14 kJ mol-1, suggest a low-cost desorption process and outstanding recyclability of the sorbent. We also note that DACs possessing long alkyl chains (butyl, hexyl, octyl) exhibit negligible volatilities, while preserving the liquid aggregate state over a practically important temperature range. The reported results may foster the development of a new class of CO2 scavengers with possibly quite peculiar characteristics.

Sarcopenia in Immune-Mediated Rheumatic Diseases-Review.

INTRODUCTION: Sarcopenia is a condition characterized by decreased muscle strength and muscle mass, which can impact physical function. Sarcopenia develops as a consequence of age-related decline (primary sarcopenia) and has a major impact on physical, social, and emotional well-being. In addition, patients with rheumatic diseases may suffer from sarcopenia independently of aging (secondary sarcopenia). Exercise, pharmacological treatments, and nutritional supplementation are some of the strategies used for the management of sarcopenia in the general population. The aim of this review is to summarize the evidence around the prevalence and impact of sarcopenia in patients with rheumatic diseases. CONCLUSIONS: From our review, we can state that sarcopenia is a common and prevalent condition among the rheumatic diseases. Furthermore, the impacts of sarcopenia are not well-appreciated, and the implementation of treatment strategies has not been widespread. Strategies such as exercise and some pharmacological treatments are effective in improving physical and functional impairment related to these conditions. FUTURE RESEARCH DIRECTIONS IN THE FIELD: New pharmacological treatments are being actively studied and may contribute in the future to the management of sarcopenia.

Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias.

CD38 enzymatic activity regulates NAD+ and cADPR levels in mammalian tissues, and therefore has a prominent role in cellular metabolism and calcium homeostasis. Consequently, it is reasonable to hypothesize about its involvement in cardiovascular physiology as well as in heart related pathological conditions. AIM: To investigate the role of CD38 in cardiovascular performance, and its involvement in cardiac electrophysiology and calcium-handling. METHODS AND RESULTS: When submitted to a treadmill exhaustion test, a way of evaluating cardiovascular performance, adult male CD38KO mice showed better exercise capacity. This benefit was also obtained in genetically modified mice with catalytically inactive (CI) CD38 and in WT mice treated with antibody 68 (Ab68) which blocks CD38 activity. Hearts from these 3 groups (CD38KO, CD38CI and Ab68) showed increased NAD+ levels. When CD38KO mice were treated with FK866 which inhibits NAD+ biosynthesis, exercise capacity as well as NAD+ in heart tissue decreased to WT levels. Electrocardiograms of conscious unrestrained CD38KO and CD38CI mice showed lower basal heart rates and higher heart rate variability than WT mice. Although inactivation of CD38 in mice resulted in increased SERCA2a expression in the heart, the frequency of spontaneous calcium release from the sarcoplasmic reticulum under stressful conditions (high extracellular calcium concentration) was lower in CD38KO ventricular myocytes. When mice were challenged with caffeine-epinephrine, CD38KO mice had a lower incidence of bidirectional ventricular tachycardia when compared to WT ones. CONCLUSION: CD38 inhibition improves exercise performance by regulating NAD+ homeostasis. CD38 is involved in cardiovascular function since its genetic ablation decreases basal heart rate, increases heart rate variability and alters calcium handling in a way that protects mice from developing catecholamine induced ventricular arrhythmias.