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An active environment is any atomic or molecular system changing a chromophore's nonadiabatic dynamics compared to the isolated molecule. The action of the environment on the chromophore occurs by changing the potential energy landscape and triggering new energy and charge flows unavailable in the vacuum. Surface hopping is a mixed quantum-classical approach whose extreme flexibility has made it the primary platform for implementing novel methodologies to investigate the nonadiabatic dynamics of a chromophore in active environments. This Perspective paper surveys the latest developments in the field, focusing on charge and energy transfer processes. ispartof: PHYSICAL CHEMISTRY CHEMICAL PHYSICS vol:25 issue:12 pages:8293-8316 ispartof: location:England status: published

Alcoholic hepatitis (AH) is a severe condition with poor short-term prognosis. Specific treatment with corticosteroids slightly improves short-term survival but is associated with infection and is not used in many centers. A reliable method to identify patients who will recover spontaneously will minimise the numbers of patients who experience side effects of available treatments.We analysed the trajectory of serum bilirubin concentration over the course of hospital admissions in patients with AH to predict spontaneous survival and the need for treatment.data from 426 patients were analysed. Based on bilirubin trajectory, patients were categorized into three groups: 'fast fallers' (bilirubin0.8 x admission value at day 7), 'static' (bilirubin of0.9 -1.2 x admission value) and 'rapid risers' (bilirubin of ≥1.2 x admission bilirubin). Fast fallers had significantly better 90-day survival compared to other groups (log rank p.001), and showed no benefit of corticosteroid therapy (OR for survival at 28 days of treatment, 0.94, 95% CI 0.06 - 8.41). These findings remained even amongst patients with severe disease based on initial DF, GAHS or MELD scores.We present an intuitive method of classifying patients with AH based on the trajectory of bilirubin over the first week of admission. It is complimentary to existing scores that identify candidates for corticosteroid treatment or assess response to treatment. This method identifies a group of patients with AH who recover spontaneously and can avoid corticosteroid therapy.

Parkinson’s disease, the second most prevalent neurodegenerative disorder worldwide, is characterized by a progressive loss of dopaminergic neurons in substantia nigra pars compacta, causing motor symptoms. This disorder’s main hallmark is the formation of intraneuronal protein inclusions, named Lewy bodies and neurites. The major component of these arrangements is α-synuclein, an intrinsically disordered and soluble protein that, in pathological conditions, can form toxic and cell-to-cell transmissible amyloid structures. Preventing α-synuclein aggregation has attracted significant effort in the search for a disease-modifying therapy for Parkinson’s disease. Small molecules like SynuClean-D, epigallocatechin gallate, trodusquemine, or anle138b exemplify this therapeutic potential. Here, we describe a subset of compounds containing a single aromatic ring, like dopamine, ZPDm, gallic acid, or entacapone, which act as molecular chaperones against α-synuclein aggregation. The simplicity of their structures contrasts with the complexity of the aggregation process, yet the block efficiently α-synuclein assembly into amyloid fibrils, in many cases, redirecting the reaction towards the formation of non-toxic off-pathway oligomers. Moreover, some of these compounds can disentangle mature α-synuclein amyloid fibrils. Their simple structures allow structure-activity relationship analysis to elucidate the role of different functional groups in the inhibition of α-synuclein aggregation and fibril dismantling, making them informative lead scaffolds for the rational development of efficient drugs.

BACKGROUND: Natural products are currently in the spotlight due to the increasing awareness of consumers. Among these products is phycocyanin (C-PC), a blue colorant that can be extracted from cyanobacteria – a poorly explored feedstock – and applied in several fields, due to its argued health benefits. Arthropira (previously called Spirulina) is the major source of C-PC nowadays, but within the scope of pursuing alternative sources, the cyanobacterium Anabaena cylindrica was used in the present study to extract this colorant. RESULTS: The biological activities of two types of extracts (raw and purified, both in fresh and in lyophilized forms) were analysed. The raw extracts produce better results than their pure counterparts by presenting a higher antioxidant activity and better biocompatibility and antitumor activity. However, when compared to literature records, C-PC extracts from A. cylindrica produced less impressive results. This leads to a new hypothesis and a simple comparison between the antioxidant activities of C-PC extracts from different biomass sources. These second-stage results showed that different cyanobacteria species produced different C-PC extracts with different antioxidant profiles; these results highlight that, even when the extracts are blue, they may present differential compositions and, therefore, different biological activities. CONCLUSION: This study proves that the direct link often made between biological activities and C-PC can be speculative, and thus, should be avoided. published

CD8+ T cells are key mediators of antiviral and antitumor immunity. The isolation and study of Ag-specific CD8+ T cells, as well as mapping of their MHC restriction, has practical importance to the study of disease and the development of therapeutics. Unfortunately, most experimental approaches are cumbersome, owing to the highly variable and donor-specific nature of MHC-bound peptide/TCR interactions. Here we present a novel system for rapid identification and characterization of Ag-specific CD8+ T cells, particularly well suited for samples with limited primary cells. Cells are stimulated ex vivo with Ag of interest, followed by live cell sorting based on surface-trapped TNF-α. We take advantage of major advances in single-cell sequencing to generate full-length sequence data from the paired TCR α- and β-chains from these Ag-specific cells. The paired TCR chains are cloned into retroviral vectors and used to transduce donor CD8+ T cells. These TCR transductants provide a virtually unlimited experimental reagent, which can be used for further characterization, such as minimal epitope mapping or identification of MHC restriction, without depleting primary cells. We validated this system using CMV-specific CD8+ T cells from rhesus macaques, characterizing an immunodominant Mamu-A1*002:01-restricted epitope. We further demonstrated the utility of this system by mapping a novel HLA-A*68:02-restricted HIV Gag epitope from an HIV-infected donor. Collectively, these data validate a new strategy to rapidly identify novel Ags and characterize Ag-specific CD8+ T cells, with applications ranging from the study of infectious disease to immunotherapeutics and precision medicine.

In the rapidly expanding field of peptide therapeutics, the short in vivo half-life of peptides represents a considerable limitation for drug action. D-peptides, consisting entirely of the dextrorotatory enantiomers of naturally occurring levorotatory amino acids (AAs), do not suffer from these shortcomings as they are intrinsically resistant to proteolytic degradation, resulting in a favourable pharmacokinetic profile. To experimentally identify D-peptide binders to interesting therapeutic targets, so-called mirror-image phage display is typically performed, whereby the target is synthesized in D-form and L-peptide binders are screened as in conventional phage display. This technique is extremely powerful, but it requires the synthesis of the target in D-form, which is challenging for large proteins. Here we present finDr, a novel web server for the computational identification and optimization of D-peptide ligands to any protein structure ( https://findr.biologie.uni-freiburg.de/ ). finDr performs molecular docking to virtually screen a library of helical 12-mer peptides extracted from the RCSB Protein Data Bank (PDB) for their ability to bind to the target. In a separate, heuristic approach to search the chemical space of 12-mer peptides, finDr executes a customizable evolutionary algorithm (EA) for the de novo identification or optimization of D-peptide ligands. As a proof of principle, we demonstrate the validity of our approach to predict optimal binders to the pharmacologically relevant target phenol soluble modulin alpha 3 (PSMα3), a toxin of methicillin-resistant Staphylococcus aureus (MRSA). We validate the predictions using in vitro binding assays, supporting the success of this approach. Compared to conventional methods, finDr provides a low cost and easy-to-use alternative for the identification of D-peptide ligands against protein targets of choice without size limitation. We believe finDr will facilitate D-peptide discovery with implications in biotechnology and biomedicine.

Objectives This study aimed to evaluate endophytic fungi isolated from Tocoyena bullata and Humiria balsamifera plant species for their antimycobacterial and anti-inflammatory activities, focusing on severe pulmonary tuberculosis cases which are often associated with exacerbated inflammation. Methods Mycobacterium suspensions were incubated with the samples for 5 days. RAW 264.7 macrophages stimulated with LPS were also incubated with them for 24 h to assess the inhibition of inflammatory mediator production and cytotoxicity. C57BL/6 mice were infected with Mtb M299 and treated for 15 days with lasiodiplodin (Lasio). Key findings Endophytic fungus Sordaria tamaensis, obtained from T. bullata, was the most promising. Its ethanolic extract impaired mycobacterial growth with MIC50 (µg/ml): 1.5 ± 0.6 (BCG), 66.8 ± 0.1 (H37Rv) and 80.0 ± 0.1 (M299). (R)-(+)-Lasio showed MIC50 92.2 ± 1.8 µg/ml (M299). In addition, Lasio was able to inhibit NO, IL-1β and TNF-α production and was not cytotoxic for macrophages. M. tuberculosis-infected C57BL/6 animals treated by Lasio reduced the number of acid-fast bacilli, lung pathology, leucocyte influx and proinflammatory cytokine production in the lungs. The class IIa fructose 1,6-bisphosphate aldolase was the predicted hypothetical target of Lasio. Conclusions (R)-(+)-Lasio stood out as a promising anti-TB compound, exhibiting anti-inflammatory and antimycobacterial effects, as well as low cytotoxicity.

Background & aims Upregulation of hepatic delta-aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta-aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria. Aims evaluate long-term efficacy and safety of givosiran in acute hepatic porphyria. Methods Interim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients with acute hepatic porphyria (≥12 years) with recurrent attacks received givosiran (2.5 mg/kg monthly) (n = 48) or placebo (n = 46) for 6 months (double-blind period); 93 received givosiran (2.5 mg or 1.25 mg/kg monthly) in the open-label extension (continuous givosiran, n = 47/48; placebo crossover, n = 46/46). Endpoints included annualized attack rate, urinary delta-aminolevulinic acid and porphobilinogen levels, hemin use, daily worst pain, quality of life, and adverse events. Results Patients receiving continuous givosiran had sustained annualized attack rate reduction (median 1.0 in double-blind period, 0.0 in open-label extension); in placebo crossover patients, median annualized attack rate decreased from 10.7 to 1.4. Median annualized days of hemin use were 0.0 (double-blind period) and 0.0 (open-label extension) for continuous givosiran patients and reduced from 14.98 to 0.71 for placebo crossover patients. Long-term givosiran led to sustained lowering of delta-aminolevulinic acid and porphobilinogen and improvements in daily worst pain and quality of life. Safety findings were consistent with the double-blind period. Conclusions Long-term givosiran has an acceptable safety profile and significantly benefits acute hepatic porphyria patients with recurrent attacks by reducing attack frequency, hemin use, and severity of daily worst pain while improving quality of life.

Composite materials based on CaO obtained from egg shells and k-carrageenan, an anionic sulfated linear polysaccharide obtained from red seaweeds was used as an efficient, environmentally friendly heterogeneous catalyst for the transesterification of soybean oil with methanol at 60 °C. The different composite samples were produced through the dissolution of the biopolymer in an ionic liquid (IL) derived from imidazolium ion and by further addition of CaO. The samples were characterized by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), Scanning Electron Microscopy (SEM) and Termogravimetry (TGA). The materials exhibit an internal structure consisting of meso and macropores which widen with the addition of small amounts of Hexamethylene diisocyanate (HMDI) that acts as a crosslinker. The composite materials present a similar thermal behaviour to k-carrageenan, without loss of stability. The catalytic activity of the prepared composite materials was evaluated in the transesterification reaction of soybean oil with methanol through catalytic runs in batch conditions. It was found that both CaO loading and polymer cross-linking affect the sorption capacity and the transport properties of the prepared catalytic materials, with best results obtained for the intermediate CaO concentration in membrane and a lower crosslinking degree.

COVID-19 is a worldwide health emergency, therapy for this disease is based on antiviral drugs and immunomodulators, however, there is no treatment to effectively reduce the COVID-19 mortality rate. Fucoidan is a polysaccharide obtained from marine brown algae, with anti-inflammatory, antiviral, and immune-enhancing properties, thus, fucoidan may be used as an alternative treatment (complementary to prescribed medical therapy) for the recovery of COVID-19. This work aimed to determine the effects of ex-vivo treatment with fucoidan on cytotoxicity, apoptosis, necrosis, and senescence, besides functional parameters of calcium flux and mitochondrial membrane potential (ΔΨm) on human peripheral blood mononuclear cells isolated from SARS-CoV-2 infected, recovered and healthy subjects. Data suggest that fucoidan does not exert cytotoxicity or senescence, however, it induces the increment of intracellular calcium flux. Additionally, fucoidan promotes recovery of ΔΨm in PBMCs from COVID-19 recovered females. Data suggest that fucoidan could ameliorate the immune response in COVID-19 patients.

Taro is a food source for many people in tropical countries. The use of biotechnological techniques for seed production is an alternative that allows obtaining propagation material of higher phytos...

The effect of water molecule on the excited states of CH3Cl(H2O), as compared to those of the isolated chloromethane, has been studied at the multireference configuration interaction with singles and doubles (MR-CISD), including extensivity corrections. Eight new Rydberg states are due to the water molecule but the common states of both systems are not severely altered. Potential energy curves of 23 singlet states along the C-Cl coordinate have also been computed at the MR-CISD level. The dissociation energy of the C-Cl bond decreases from ∼0.4 to 0.5 eV due to the water molecule. As for CH3Cl (de Medeiros, V. C., J. Am. Chem. Soc. 2016, 138, 272-280), a stable ion-pair has also been characterized. However, for CH3Cl(H2O), this ion-pair is better described as a solvent-shared semi-ion-pair, CH3+δ(H2O)Cl-δ. This species is connected with three ionic dissociation channels, with two being due to the water molecule. The presence of these new ionic channels, particularly the lowest energy one, [H3C-O]+ + Cl-, raises a very important question of atmospheric relevance: can the interaction of chloroalkanes with water decrease its deleterious effect on the ozone layer? Several potentially new competing dissociation channels are also studied. The latter results can help to set up the most important states to be included in nonadiabatic dynamic calculations to study how the yields of the ionic channels change due to the water molecule.

Background The AMP-activated protein kinase (AMPK) is a major regulator of cellular energetics which plays key role in acute metabolic response and in long-term adaptation to stress. Recent works have also suggested non-metabolic effects. Methods To decipher AMPK roles in the heart, we generated a cardio-specific inducible model of gene deletion of the main cardiac catalytic subunit of AMPK (Ampkα2) in mice. This allowed us to avoid the eventual impact of AMPK-KO in peripheral organs. Results Cardio-specific Ampkα2 deficiency led to a progressive left ventricular systolic dysfunction and the development of cardiac fibrosis in males. We observed a reduction in complex I-driven respiration without change in mitochondrial mass or in vitro complex I activity, associated with a rearrangement of the cardiolipins and reduced integration of complex I into the electron transport chain supercomplexes. Strikingly, none of these defects were present in females. Interestingly, suppression of estradiol signaling by ovariectomy partially mimicked the male sensitivity to AMPK loss, notably the cardiac fibrosis and the rearrangement of cardiolipins, but not the cardiac function that remained protected. Conclusion Our results confirm the close link between AMPK and cardiac mitochondrial function, but also highlight links with cardiac fibrosis. Importantly, we show that AMPK is differently involved in these processes in males and females, which may have clinical implications for the use of AMPK activators in the treatment of heart failure., Highlights AMPK is a metabolic sensor of cellular energy which regulates energy homeostasis.We generated a cardiac-specific inducible deletion of Ampkα2 and demonstrated that this deletion induces mild cardiac dysfunction in male only.Cardiac dysfunction observed in males was associated with cardiac fibrosis and cardiac cardiolipin remodeling that are not seen in females.Although no significant cardiac function alteration was noticed in ovariectomized female Ampkα2ciKO mice, these latter exhibited cardiac fibrosis and mild cardiolipins remodeling.Our results show a higher dependence on AMPK signaling fibrosis and cardiolipin biosynthesis/maturation in males, either due to the absence of female hormones protection or/and to the action of male hormones. This may contribute to the known difference in cardiovascular risk and outcome between sexes.

Altres ajuts: ICREA-Academia 2015 and 2020 Altres ajuts: acords transformatius de la UAB Nanostructures decorated with antibodies (Abs) are applied in bioimaging and therapeutics. However, most covalent conjugation strategies affect Abs functionality. In this study, we aimed to create protein-based nanoparticles to which intact Abs can be attached through tight, specific, and noncovalent interactions. Initially considered waste products, bacterial inclusion bodies (IBs) have been used in biotechnology and biomedicine. However, the amyloid-like nature of IBs limits their functionality and raises safety concerns. To bypass these obstacles, we have recently developed highly functional α-helix-rich IBs exploiting the natural self-assembly capacity of coiled-coil domains. We used this approach to create spherical, submicrometric, biocompatible and fluorescent protein nanoparticles capable of capturing Abs with high affinity. We showed that these IBs can be exploited for Ab-directed cell targeting. Simultaneous decoration of the nanoparticles with two different Abs in a controllable ratio enabled the construction of a bispecific antibody mimic that redirected T lymphocytes specifically to cancer cells. Overall, we describe an easy and cost-effective strategy to produce multivalent, traceable protein nanostructures with the potential to be used for biomedical applications. Statement of significance: Functional inclusion bodies (IBs) are promising platforms for biomedical and biotechnological applications. These nanoparticles are usually sustained by amyloid-like interactions, which imposes some limitations on their use. In this work, we exploit the natural coiled-coil self-assembly properties to create highly functional, nonamyloid, and fluorescent IBs capable of capturing antibodies. These protein-based nanoparticles are successfully used to specifically and simultaneously target two unrelated cell types and bring them close together, becoming a technology with potential application in bioimaging and immunotherapy.

Tetraphenylmethane appended with four pyridylpyridinium units works as a scaffold to self-assemble four ruthenium porphyrins in a tetrahedral shape-persistent giant architecture. The resulting supramolecular structure has been characterised in the solid state by X-ray single crystal analysis and in solution by various techniques. Multinuclear NMR spectroscopy confirms the 1 : 4 stoichiometry with the formation of a highly symmetric structure. The self-assembly process can be monitored by changes of the redox potentials, as well as by modifications in the visible absorption spectrum of the ruthenium porphyrin and by a complete quenching of both the bright fluorescence of the tetracationic scaffold and the weak phosphorescence of the ruthenium porphyrin. An ultrafast photoinduced electron transfer is responsible for this quenching process. The lifetime of the resulting charge separated state (800 ps) is about four times longer in the giant supramolecular structure compared to the model 1 : 1 complex formed by the ruthenium porphyrin and a single pyridylpyridinium unit. Electron delocalization over the tetrameric pyridinium structure is likely to be responsible for this effect.

Elucidation of the oxidation mechanism of naturally emitted reduced sulfur compounds, especially dimethyl sulfide, plays a central role in understanding background acid precipitation in the natural environment. Most frequently, theoretical studies of the addition and H-elimination reactions of dimethyl sulfide with hydroxyl radicals are studied considering the presence of oxygen that further reacts with the radicals formed in the initial steps. Although the reaction of intermediate species with additional hydroxyl radicals has been considered as part of the global mechanism of oxidation, few if any attention has been dedicated to the possibility of reactions of the initial radicals with a second •OH molecule. In this work we performed a computational study using quantum-chemical methods, of the mechanism of H-abstraction from dimethyl sulfide under normal atmospheric conditions and in reaction chambers at different O2 partial pressure, including complete absence of oxygen. Additionally, important rate coefficients were computed using canonical and variational transition state theory. The rate coefficient for abstraction affords a 4.72 x 10-12 cm3 molecule1 s-1 value, very close to the most recent experimental one (4.13 x 10-12 cm3 molecule-1 s-1). According to our best results, the initial methyl thiomethyl radical was obtained at -25.2 kcal/mol (experimentally -22.4 kcal/mol), and four important paths were identified on the potential energy surface. From the interplay of thermochemical and kinetic arguments, it was possible to demonstrate that the preferred product of the reaction of dimethyl sulfide with two hydroxyl radicals, is actually dimethyl sulfoxide.

Manganese oxides are important geomaterials, used in a large number of applications. For instance, as pigments in art works or in the treatment and removal of heavy metals from drinking water. Particularly, ramsdellite [Mn4+O2] and groutellite [(Mn0.54+,Mn0.53+)O1.5(OH)0.5], because of their 2 1 frameworks that enable proton diffusion, are very important cathode materials. Manganese oxides commonly occur as crypto-crystalline and very fine mixtures of different Mn-phases, iron oxides, silicates and carbonates. Thus, proper characterization can be a difficult task using XRPD. The lack of Raman data on groutellite and the little and conflicting data on ramsdellite do not allow their proper identification by Raman spectroscopy. In this work we characterize natural mixtures of ramsdellite and groutellite by combining SEM-EDS, XRPD, FT-IR and Raman spectroscopy, to provide reference Raman spectra. Our data show that they have a typical and unmistakable spectra, allowing clear recognition. Moreover, we have investigated their laser-induced degradation. Our data show that groutellite transforms into ramsdellite, by the loss of H+ and the oxidation of Mn3+ to Mn4+, already at a very low laser power. Further increasing the laser power the formation of hausmannite [Mn2+Mn2 3+O4] occurs via the reduction of Mn cations. Our data can be used to study the discharge mechanism in cathodic battery materials, by monitoring the Mn reduction from ramsdellite to groutellite, and finally to groutite [a-Mn3+OOH]. Moreover, Raman mapping allows the study of their distribution in all the investigated samples and, indirectly, those of H+ and Mn3+, which plays a key-role in electrochemical activity of these compounds.

The self-assembling of small peptides not only leads to the formation of intriguing nanoarchitectures, but also generates materials with unexpected functional properties. Oligopeptides can form amyloid-like cross-β assemblies that are able to emit intrinsic photoluminescence (PL), over the whole near-UV/visible range, whose origin is still largely debated. As proton transfer between the peptide chain termini within the assembly is one of the invoked interpretations of this phenomenon, we here evaluated the solid state PL properties of a series of self-assembled hexaphenalanine peptides characterized by a different terminal charge state. Overall, our data indicate that the charge state of these peptides has a marginal role in the PL emission as all systems exhibit very similar multicolour PL associated with a violation of the Kasha’s rule. On the other hand, charged/uncharged ends occasionally produce differences in the quantum yields. The generality of these observations has been proven by extending these analyses to the Aβ16−21 peptide. Collectively, the present findings provide useful information for deciphering the code that links the spectroscopic properties of these assemblies to their structural/electronic features.

The goal was to assess the effect of different substitution levels (SL) of wheat flour with germinated basul flour (GBF) on nutritional, physical, and sensory characteristics of bread. The previously soaked basul fruits were germinated, dried, and transformed into flour. This product substituted wheat flour in the following SL: 0 (control), 5, 10, 15, and 20% of GBF, respectively, for the processing of loaves of bread. Nutritional values were determined by AOAC method. The physical characteristics assessed were weight, volume, porosity, and colour. The Flash Profile technique was used for the sensory assessment. A significant increase in the content of protein and crude fibre (3.86 and 50.49%, respectively) and a decrease in the content of carbohydrates (2.57%) were observed in all loaves with SL of 20%. With this same SL, it was observed that the physical characteristics did not differ significantly, except for height. In the sensory characteristics, loaves made with 20% SL also had a sweet flavour and a spongy appearance, except for the colour (change to opaque colour), which gradually decreased with the increased SL. The inclusion of GBF in bread improved nutritional and sensory quality, without affecting physical quality, which is why it can be considered healthy food.

Suppressive myeloid cells inhibit antitumor immunity by preventing T-cell responses. Immunoglobulin-like transcript 3 (ILT3; also known as LILRB4) is highly expressed on tumor-associated myeloid cells and promotes their suppressive phenotype. However, the ligand that engages ILT3 within the tumor microenvironment and renders tumor-associated myeloid cells suppressive is unknown. Using a screening approach, we identified fibronectin as a functional ligand for ILT3. The interaction of fibronectin with ILT3 polarized myeloid cells toward a suppressive state, and these effects were reversed with an ILT3-specific antibody that blocked the interaction of ILT3 with fibronectin. Furthermore, ex vivo treatment of human tumor explants with anti-ILT3 reprogrammed tumor-associated myeloid cells toward a stimulatory phenotype. Thus, the ILT3–fibronectin interaction represents a “stromal checkpoint” through which the extracellular matrix actively suppresses myeloid cells. By blocking this interaction, tumor-associated myeloid cells may acquire a stimulatory phenotype, potentially resulting in increased antitumor T-cell responses.

Biofuels are a sustainable energy option that can contribute to solve some current environmental problems. For example, it seems imperative to find alternative energy sources; and among them adequate and sustainable raw materials to produce biofuels, such as bioethanol. This study, under the assumption that Maralfalfa grass would be a suitable substrate to produce biofuel, aimed at evaluating the biomass yield, chemical composition, and theoretical bioethanol production of Maralfalfa grass (C. purpureus Schumach.) Morrone harvested at three cutting frequencies (CF). Treatments were distributed in a randomized complete blocks design with split-plots arrangement and three replicates. Analysis of variance was done with GLM procedure and means were compared with Tukey test (p≤0.05). At 120 d, the lignocellulosic material content was the highest (p≤0.05) with 66% of holocellulose, 30% hemicellulose, 22% lignin, 1.8% acid soluble lignin, 20% acid insoluble lignin, 26% acid insoluble residue, and 6.2% ashes. The highest concentration of extractives compounds was found at 150 d harvest frequency (15.5%; p≤0.05), while the highest biomass production (32.6 Mg ha-1 y-1), calorific value (21.0 MJ kg-1), and bioethanol production (239.9 L Mg-1 MS-1) was obtained at the 180 d (p≤0.05). No significant changes were found for crude protein (p>0.05). Results showed that Maralfalfa grass (C. purpureus Schumach.) Morrone is an attractive alternative for bioethanol production due to high biomass yield and chemical composition at short harvesting times.

A controlled study evaluated the effect of condensed tannins (CT) from Gymnopodium floribundum leaf meal (GF), infection with Haemonchus contortus (I) and their interaction, on feed intake, diet digestibility and retention of N (NR) and energy (ER) in hair sheep lambs. Thirty-six, worm-free hair sheep lambs (14.9 ± 1.56 kg body weight) were housed in metabolic cages. Eighteen animals were infected with 6000 H. contortus L3, while other 18 lambs were kept non-infected. On day 28th post-infection (PI), infected lambs were assigned to three diet groups: a diet without GF (I-NONGF), a diet with GF (I + GF) and a diet with GF + polyethylene glycol (PEG) (I + GF + PEG). Non-infected (NI) lambs were assigned to similar diet groups: NI-NONGF, NI + GF and NI + GF + PEG. The packed cell volume (% PCV), ante-mortem faecal egg counts and post-mortem worm burdens were also evaluated. Infection did not affect digestibility, NR and ER. Meanwhile, CT intake from the GF diet reduced the digestibility of dry matter, organic matter and crude protein, as well as NR, compared to lambs consuming the NONGF and GF + PEG diets (P

Glucuronic acid containing diacylglycerols (3-(O-α-d-glucuronopyranosyl)-1,2-diacyl-sn-glycerols, GlcA-DAG) are glycolipids of plant membranes especially formed under phosphate-depletion conditions. An analytical approach for the structural characterization of GlcA-DAG in red ripe tomato (Solanum lycopersicum L.) extracts, based on reversed-phase liquid chromatography (RPLC) coupled with electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) using a linear ion trap, is described in this paper. At least 14 GlcA-DAG (R1/R2) species, including four regioisomers, containing three predominant fatty acyl chains C16:0, C18:2, and C18:3, were identified for the first time. Moreover, 29 GlcA-DAG acylated on the glucuronosyl ring (acyl-R3 GlcA-DAG) were discovered, alongside 15 acylated lyso-forms, i.e., acylated 3-(O-α-d-glucuronosyl)monoacylglycerols, abbreviated as acyl-R3 GlcA-MAG (R1/0) or (0/R2). Although many of these acylated lyso-forms were isomeric with GlcA-DAG (i.e., acyl chains with equivalent sum composition), they were successfully separated by reversed-phase liquid chromatography (RPLC) using a solid-core C18 column packed with 2.6 μm particle size. Tandem MS (and eventually MS3) data obtained from sodium adducts ([M + Na]+) and deprotonated molecules ([M - H]-) were fundamental to detect diagnostic product ions related to the glucuronosyl ring and then determine the identity of all investigated glycolipids, especially to recognize the acyl chain linked to the ring. A classification of GlcA-MAG, GlcA-DAG, and acylated GlcA-DAG and GlcA-MAG was generated by an in house-built database. The discovery of acylated derivatives emphasized the already surprising heterogeneity of glucuronic acid-containing mono- and diacylglycerols in tomato plants, stimulating interesting questions on the role played by these glycolipids.

Objective To analyse the antinociceptive interaction between quercetin (QUER) and diclofenac (DIC) in experimental arthritic gout-pain. Methods The antinociceptive effect of DIC and QUER alone and in combination were evaluated using an arthritic gout-pain model. Pain was induced through intra-articular administration of uric acid in the rats and the treatments were administered 2 h later. Additionally, the cyclooxygenase (COX) activity was determined in rats treated with DIC, QUER and their combination. Key findings DIC induced a maximal effect of 69.7 ± 2.7% with 3.1 mg/kg; whereas QUER only produced 17.6 ± 2.6% with the maximal dose (316 mg/kg). Ten of twelve DIC + QUER combinations showed a lesser antinociceptive effect than DIC alone did (P < 0.05). Moreover, DIC reduced total-COX (70.4 ± 1.3 versus 52.4 ± 1.8 and 77.4 ± 9.0 versus 56.1 ± 1.3, P < 0.05) and COX-2 (60.1 ± 1.0 versus 42.4 ± 1.8 and 58.1 ± 2.4 versus 48.7 ± 1.3, P < 0.05) activity after 1 and 3 h, respectively. Nevertheless, only the COX-2 activity induced by DIC was prevented in the presence of QUER (63.2 ± 3.0 versus 60.1 ± 1.0 and 56.6 ± 1.3 versus 58.1 ± 2.4 at 1 and 3 h, respectively). Conclusions All these data demonstrated that the simultaneous administration of QUER + DIC produces an unfavorable interaction on the antinociceptive effect of DIC. Therefore, this combination might not be recommendable to relieve arthritic gout-pain.

The annexin superfamily consists of 12 proteins with a highly structural homology that binds to phospholipids depending on the availability of Ca2+-dependent. Different studies of overexpression, inhibition, or using recombinant proteins have linked the main function of these proteins to their dynamic and reversible binding to membranes. Annexins are found in multiple cellular compartments, regulating different functions, such as membrane trafficking, anchoring to the cell cytoskeleton, ion channel regulation, as well as pro- or anti-inflammatory and anticoagulant activities. The use of animals deficient in any of these annexins has established their possible functions in vivo, demonstrating that annexins can participate in relevant functions independent of Ca2+ signalling. This review will focus mainly on the role of different annexins in the pathological vascular remodelling that underlies the formation of the atherosclerotic lesion, as well as in the control of cholesterol homeostasis.

Super sweet is classified as a special type of corn, due to the presence of genes which promote sugar accumulation in grains, significantly reducing starch content in the endosperm. This study aimed to evaluate the agronomic performance of experimental super sweet corn hybrids, carrying the gene shrunken-2, in order to identify and select promising genotypes for Southern Brazil. The experiments were carried out in two sowing seasons in 2017/18, in the experimental field of UNICENTRO, Guarapuava-PR, Brazil. Thirty-two experimental hybrids resulting from an 8x4 partial diallel among super sweet corn inbred lines from four distinct populations were evaluated along with two commercial hybrids (BRS Vivi and Tropical Plus) used as checks. Traits of agronomic and commercial interest were evaluated: male flowering (MF), husk covering index (HCI), yield of husked ears (YHE), grain yield (GY), commercial prolificacy (CPR), percentage of commercial ears (PCE), color (COL) and soluble solids (SS) of the grains. We verified significant differences among the experimental hybrids, except for COL. There was no significant effect of sowing season regarding to SS. Genotypes x seasons interaction was significant for YHE, GY, CPR, PCE and COL. There are promising experimental hybrids showing performances superior to commercial super sweet corn hybrids used in Brazil. The experimental hybrids D2-61 x D5-41 and D3-10 x D5-43 were superior to the other experimental genotypes. The experimental hybrid D2-61 x D5-41 shows potential to meet the demands of the current super sweet corn market.

Mandevilla pohliana is a species belonging to the Apocynaceae family found in Cerrado environments. The bjetive of this study was to evaluate the antifungal and antibacterial action of the floral ethanolic extract of M. pohliana. Flowers of M. pohliana were collected and the ethanolic extract produced by maceration. In different concentrations of extract, antifungal of the genus Candida were determined, and antibacterial activities on Escherichia, Salmonella, Enterococcus, Pseudomonas and Staphylococcus. Antibiosis activity was observed only for C. guilliermondii with 9-2 mm, for P. aeruginosa with 12-3 mm and for E. faecalis between 10-3 mm at the highest concentrations between 50-500 mg mL-1. The floral ethanolic extract of Mandevilla pohliana showed potential as a natural antifungal and antibacterial agent.

Brazilian traditional medicine has explored the antiviral properties of many plant extracts, including those from the Brazilian pepper tree, Schinus terebinthifolius. In the present study, we investigated the chemical composition and anti-mayaro virus (MAYV) activity of S. terebinthifolius fruit. Extensive virucidal activity (more than 95%) was detected for the ethyl acetate extract and the isolated biflavonoids. From the ethyl acetate extract of Schinus terebinthifolius fruits, two bioflavonoids were isolated ((2S, 2″S)-2,3,2″,3″-tetrahydroamentoflavone and agathisflavone), which showed strong virucidal activity against Mayaro virus. Furthermore, several other compounds like terpenes and phenolics were identified by hyphenated techniques (GC–MS, LC–MS and HPLC–UV), as well as by mass spectrometry. Immunofluorescence assay confirmed antiviral activity and transmission electron microscopy revealed damage in viral particles treated with biflavonoids. The data suggest the direct action of the extract and the biflavonoids on the virus particles. The biflavonoids tetrahydroamentoflavone and agathisflavone had strong virucidal activity and reduced MAYV infection.

Objective:To identify histopathological and immunophenotypical features with potential predictive or prognostic value in patients undergoing pulmonary metastasectomy from renal cell carcinoma (RCC).Methods:We retrospectively collected all consecutive patients undergoing pulmonary metastasectomy from RCC after prior nephrectomy. Paired samples of primary tumors and corresponding pulmonary metastases were analyzed, revising histopathological features and testing C-MET, mTOR, and PD-L1 by immunohistochemistry.Results:A total of 25 patients were included. Median overall survival (mOS) from metastasectomy was 5.5 years (95% CI = 1.9–9.1). The laterality of metastases had a significant predictive value, with median relapse-free survival (mRFS) from metastasectomy not reached (NR) at mean follow-up (FU) of 60.8 months for left lung involvement, mRFS of 52.9 months (95% CI = 0–145.5) for the right lung and 6.4 months (95% CI = 1.7–11) for bilateral metastases ( p = 0.028). Primary RCC with positive expression of mTOR had higher mOS after metastasectomy than negative cases ( p < 0.001), NR at mean FU of 4.3 years versus mOS of 2 years (95% CI = 0.7–3.3), respectively. PD-L1 positivity on intra-tumor (TILs) and peri-tumor (RILs) infiltrating lymphocytes of metastases was related to higher OS, NR versus 2 years (95% CI = 1.2–2.7, p = 0.003), and NR versus 1.4 years (95% CI = 0.2–2.6, p = 0.012), respectively. The shorter was the surgical interval, the more probably the metastases had high c-MET expression (>70%) ( p = 0.007) and PD-L1 expression >10% on TILs ( p = 0.024).Conclusions:mTOR positivity on primary RCC could be a favorable prognostic factor to select patients for pulmonary metastasectomy. The positive impact of PD-L1 expression on immune cells is opposite to the well-known negative prognostic value of PD-L1 on tumor cells in RCC.

As life expectancy increases, an increasing older population may require surgery with perioperative nutritional management. While little is known about the combined effect of age and stress on amino acid metabolism during enteral nutrition, we hypothesized that blood amino acid bioavailability may be influenced not only by the characteristics of the ingested protein but also by intestinal ageing and splanchnic sequestration of amino acids. Plasma amino acid kinetics were thus evaluated in aged and adult rats receiving continuous enteral nutrition before and after standardized surgical stress.Sixteen 5-month-old and sixteen 21-month-old male rats were used. After a gastrostomy, the insertion of a jugular vein catheter and a one-week recovery, the animals were enterally fed with commercially available formulas containing whole milk proteins or a whey hydrolysate for 24 h before (healthy state) and 18 h after a standardized laparotomy (surgical stress). Data were analyzed by 3-factor ANOVA.In all rats, enteral nutrition was associated with a marked increase in plasma alanine, threonine, lysine and proline (+50 to +150 μmol/L; p 0.001), and a decrease in glycine (≈-80 μmol/L; p 0.01). For most amino acids, their availability depended first on the amino acid composition of each protein and second on surgical stress. Aging was only associated with higher tyrosine and threonine availability (p 0.001). There was only limited statistical interaction between age and surgical stress.In rats, plasma amino acid availability during continuous enteral nutrition is determined by the nature of the protein source and the occurrence of stress. The effects of aging on plasma amino acid availability seem very limited. Commonly used formulas therefore appear to be as suitable for elderly patients as for adult patients.

International audience; Heart failure (HF) is a plague of the aging population in industrialized countries that continues to cause many deaths despite intensive research into more effective treatments. Although the therapeutic arsenal to face heart failure has been expanding, the relatively short life expectancy of HF patients is pushing towards novel therapeutic strategies. Heart failure is associated with drastic metabolic disorders, including severe myocardial mitochondrial dysfunction and systemic nutrient deprivation secondary to severe cardiac dysfunction. To date, no effective therapy has been developed to restore the cardiac energy metabolism of the failing myocardium, mainly due to the metabolic complexity and intertwining of the involved processes. Recent years have witnessed a growing scientific interest in natural molecules that play a pivotal role in energy metabolism with promising therapeutic effects against heart failure. Among these molecules, B vitamins are a class of water soluble vitamins that are directly involved in energy metabolism and are of particular interest since they are intimately linked to energy metabolism and HF patients are often B vitamin deficient. This review aims at assessing the value of B vitamin supplementation in the treatment of heart failure.

14 p.-7 fig.-2 tab., Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant disease characterized by the extracellular deposition of the transport protein transthyretin (TTR) as amyloid fibrils. Despite the progress achieved in recent years, understanding why different TTR residue substitutions lead to different clinical manifestations remains elusive. Here, we studied the molecular basis of disease-causing missense mutations affecting residues R34 and K35. R34G and K35T variants cause vitreous amyloidosis, whereas R34T and K35N mutations result in amyloid polyneuropathy and restrictive cardiomyopathy. All variants are more sensitive to pH-induced dissociation and amyloid formation than the wild-type (WT)-TTR counterpart, specifically in the variants deposited in the eyes amyloid formation occurs close to physiological pHs. Chemical denaturation experiments indicate that all the mutants are less stable than WT-TTR, with the vitreous amyloidosis variants, R34G and K35T, being highly destabilized. Sequence-induced stabilization of the dimer–dimer interface with T119M rendered tetramers containing R34G or K35T mutations resistant to pH-induced aggregation. Because R34 and K35 are among the residues more distant to the TTR interface, their impact in this region is therefore theorized to occur at long range. The crystal structures of double mutants, R34G/T119M and K35T/T119M, together with molecular dynamics simulations indicate that their strong destabilizing effect is initiated locally at the BC loop, increasing its flexibility in a mutation-dependent manner. Overall, the present findings help us to understand the sequence-dynamic-structural mechanistic details of TTR amyloid aggregation triggered by R34 and K35 variants and to link the degree of mutation-induced conformational flexibility to protein aggregation propensity., This work was funded by the Spanish Ministry of Science and Innovation PID2019-105017RB-100 to S. V., PID2019-104544GB-I00 to C. A., and by ICREA, ICREA-Academia 2020 to S. V. and Danmarks Grundforskningsfond (DNRF125) and Carlsbergfondet Distinguished Fellowship (CF18-0314) to E. P.

Purple phototrophic bacteria (PPB) showed an enormous potential for polyhydroxyalkanoates (PHA) production using the hydrolysate from lignocellulosic waste as feedstock. Thermal hydrolysis pretreatment was carried out at three different temperatures (120, 150 and 180 °C) aiming to improve the biodegradability of the lignocellulosic waste. After this pretreatment, two streams are collected: a solid and a liquid fraction. The anaerobic digestion process of the pretreated solid fraction at 180 °C increased its biodegradability extent by 31% compared to the untreated biomass, yielding 210 ± 10 LCH4 kgVS-1 even when the liquid fraction was removed. On the photo-heterotrophic of the liquid fraction, PPB was able to remove up to 55% of COD during batch operation, showing peaks of PHA production yield up to 21 wt. %. The treatment of the liquid fraction obtained at high temperatures (T˃120⁰C) reduce biomass growth and COD consumption efficiency, and thus potential productivity, with no effect over the specific activity This article is protected by copyright. All rights reservedand the biomass yield, indicating growth limitation by lack of nutrients (N and P). A preliminary economical assessment indicates suitable economic viability based on an energetic autarchy process. This study pioneered a PPB-based biorefinery for PHA production from lignocellulosic residues and aligned within the bioeconomy strategy of the European Union.

Background Metamizole is used to relieve the visceral pain but its adverse effects limit its use. An alternative to improve its efficacy with lower doses is to combine it with a natural product as hesperidin. Aim of the study. The aim of this study was to evaluate the antinociceptive interaction between metamizole and hesperidin in a visceral pain model using an isobolographic analysis. Methods Antinociception was evaluated in the writhing model using acetic acid (1%) to induce writhes in mice. Metamizole (1–316 mg/kg), hesperidin (3–300 mg/kg), or combinations with a fixed-dose ratio of 1:1 were administered intraperitoneally 30 min before the acetic acid and the number of writhes was counted for 30 min. Isobolographic analysis was employed to define the nature of the compound interaction. Results Metamizole and hesperidin in individual administration induced dose-dependent antinociceptive effects, reached an efficacy of 84.2 ± 5.9% and 66.3 ± 7.4%, respectively. The ED50 values calculated from their dose-response curves were 84.5 ± 22.7 and 108.9 ± 17.9 mg/kg, respectively. The analysis of DRC for the metamizole + hesperidin combination, in a ratio 1:1 showed a ED50 COMB value lower than the ED50 ADD estimated from the additivity line from the isobologram (46.7 ± 6.3 vs. 96.7 ± 11.9 mg/kg, respectively). In addition, the pharmacological interaction calculated was of 0.48. These results suggest a synergistic interaction for the antinociceptive activity of metamizole + hesperidin combination. Conclusion These data suggest that metamizole + hesperidin combination could be useful in treating visceral pain as it can interact synergistically using low dose of both drugs with the possibility of reducing the risk of adverse effects.

The two-spotted spider mite (TSSM) Tetranychus urticae is a polyphagous pest which infests several wild and cultivated species of plants worldwide. To date, this mite is the most deleterious pest attacking the strawberry plant under a protected environment. Exogenously applied salicylic acid (SA) has been found to induce resistance to biotic and abiotic stresses. Morpho-anatomical changes in strawberry leaflets and TSSM preference tests were investigated in response to SA treatment. Plants grown in a greenhouse were foliar sprayed with different concentrations of SA (0 mg · L−1, 25 mg · L−1, 50 mg · L−1, 75 mg · L−1 and 100 mg · L−1). After the third application, certain parameters including the number of glandular and non-glandular trichomes, thickness of leaflet, abaxial cell wall, adaxial cell wall, palisade and lacunous parenchyma and mesophyll were measured using scanning electronic microscopy (SEM). Two-choice and non-choice assays were employed to verify the TSSM preference. Exogenous treatment with SA promoted morpho-anatomical changes in the following parameters, namely: thickness of the leaflets, mesophyll, lacunous and palisade parenchyma, cell wall (abaxial and adaxial) and the number of glandular and non-glandular trichomes in strawberry leaflets. In general, TSSM preferred less leaflets treated with SA compared with the control in a two-choice assay. A lesser number of TSSM eggs and live females were also recorded in leaflets treated with SA compared with the control plants in no-choice assays. The values of the number of eggs and live females correlated negatively with those obtained for the morpho-anatomical traits induced by exogenous SA.

The primary motor symptoms of Parkinson's disease (PD) result from the degeneration of dopamine-producing neurons of the substantia nigra pars compacta (SNc), and often, the loss is asymmetrical, resulting in unilateral tremor presentation. Notably, age is the primary risk factor for PD, and it is likely that the disease ultimately stems from the impact of environmental factors, which interact with the aging process. Recent research has focused on the role of microglia and pro-oxidative responses in dopaminergic neuronal death. In this study, we sought to examine the neurodegenerative, inflammatory, and stress effects of exposure to the etiologically relevant pesticide, paraquat, over time (up to 6 months after injections). We also were interested in whether a high-resolution, 7-Tesla animal magnetic resonance imaging would be sensitive enough to detect the degenerative impact of paraquat. We found that paraquat induced a loss of dopaminergic SNc neurons and activation of microglia that surprisingly did not change over 6 months after the last injection. A long-lasting reduction was evident for body weight, and alterations in organ (lung and heart) weight were evident, which reflect the peripheral impact of the toxicant. The microglial proinflammatory actin-remodeling factor, WAVE2, along with the inflammatory transcription factor, nuclear factor kappa B were also elevated within the brain. Remarkably, the stress hormone, corticosterone, was still significantly elevated 1 month after paraquat, whereas the inflammasome factor, caspase-1, and antigen presentation factor, MFG-E8, both displayed delayed rises after the 6-month time. Using high-resolution magnetic resonance imaging, we detected no striatal changes but modest hemispheric differences in the SNc and time-dependent volumetric enlargement of the ventricles in paraquat-treated mice. These data suggest that paraquat induces long-term nigrostriatal pathology (possibly asymmetric) and inflammatory changes and stress and trophic/apoptotic effects that appear to either increase with the passage of time or are evident for at least 1 month. In brief, paraquat may be a useful nonspecific means to model widespread stress and inflammatory changes related to PD or age-related disease in general, but not the progressive nature of such diseases.

El objetivo de este estudio realizado en 2017 fue caracterizar el pasto mombaza (Megathyrsus maximus) para evaluar su potencial como materia prima para la producción de biocombustible líquido (bioetanol). La producción anual de biomasa, el poder calorífico, la composición química y el rendimiento teórico de bioetanol fueron determinadas en cuatro frecuencias de corte (30, 60, 90 y 120 d después del rebrote). Los datos se analizaron con el procedimiento GLM (SAS) y las medias de los tratamientos se compararon con la prueba de Tukey (p 0.05). La mayor producción de biomasa, poder calorífico, producción de energía, producción de bioetanol, FDN, LDA y hemicelulosa se obtuvieron en la frecuencia de corte de 120 d con 11 Mg ha-1 año-1; 16.1 MJ kg-1; 178.4 GJ ha-1 año-1; 238.2 L Mg-1 MS y 68.6, 6.5, 23.3%, respectivamente. No obstante, el mayor contenido de celulosa y FDA se encontraron en la frecuencia de corte de 90 d, con 41.2 y 47.4%, respectivamente. Los valores más altos de humedad, PC y cenizas se encontraron en la frecuencia de corte de 30 d con valores de 8.2, 10.4 y 12.1%, respectivamente, mientras que el contenido de EE fue mayor en la frecuencia de corte de 60 d (1.6%). De acuerdo con los resultados obtenidos en este estudio el pasto mombaza (Megathyrsus maximus) puede ser considerado como una materia prima atractiva para la producción de bioetanol en climas tropicales.

We exploit the unique characteristics of a sample of open clusters (OCs) and field stars for which high-precision 7Li abundances and stellar parameters are homogeneously derived by the Gaia-ESO Survey (GES). We derive possibly undepleted 7Li abundances for 26 OCs and star forming regions with ages from young to old spanning a large range of Galactocentric distances, which allows us to reconstruct the local late Galactic evolution of lithium as well as its current abundance gradient along the disc. Field stars are added to look further back in time and to constrain 7Li evolution in other Galactic components. The data are then compared to theoretical tracks from chemical evolution models that implement different 7Li forges. We find that the upper envelope of the 7Li abundances measured in field stars of nearly solar metallicities traces very well the level of lithium enrichment attained by the ISM as inferred from observations of cluster stars. We confirm previous findings that the abundance of 7Li in the solar neighbourhood does not decrease at supersolar metallicity. The comparison of the data with the chemical evolution model predictions favours a scenario in which the majority of the 7Li abundance in meteorites comes from novae. Current data also seem to suggest that the nova rate flattens out at later times. This requirement might have implications for the masses of the white dwarf nova progenitors and deserves further investigation. Neutrino-induced reactions taking place in core-collapse supernovae also produce some fresh lithium. This likely makes a negligible contribution to the meteoritic abundance, but could be responsible for a mild increase of the 7Li abundance in the ISM of low-metallicity systems that would counterbalance the astration processes., 17 pages, 10 figures, 3 tables (full tables 1 and 3 only available at the CDS), accepted for publication in Astronomy and Astrophysics. Version 2 includes corrections from language editor

To investigate the magnitude and time course of pseudorandom ffERG during light adaptation. Ten healthy subjects (26 ± 10.1 years) underwent 20 min of dark adaptation, and then the ffERG was evoked by pseudorandom flash sequences (4 ms per flash, 3 cd.s/m2) driven by m-sequences (210–1 stimulus steps) using Veris Science software and a Ganzfeld dome over a constant field of light adaptation (30 cd/m2). The base period of the m-sequence was 50 ms. Each stimulation sequence lasting 40 s was repeated at 0, 5, 10, 15 and 20 min of light adaptation. Relative amplitude and latency (corrected by values found at 0 min) of the three components (N1, P1, and N2) of first-order (K1) and first slice of the second-order (K2.1) kernel at 5 time points were evaluated. An exponential model was fitted to the mean amplitude and latency data as a function of the light adaptation duration to estimate the time course (τ) of the light adaptation for each component. Repeated one-way ANOVA followed by Tukey post-test was applied to the amplitude and latency data, considering significant values of p

Herein, a novel silver and chromium nanostructured N-doped carbonaceous material has been synthesized by a biomass-annealing approach using readily available chitosan as a raw material. The resulting catalyst AgCr@CN-800 has been applied for the dehydrogenative coupling reaction of various silanes with different alcohols to obtain the corresponding silyl ethers under aerobic and mild conditions. Besides excellent activity and selectivity, the as-prepared catalyst exhibits good stability and reusability. Characterization by X-ray diffraction, X-ray photoelectron spectroscopy, inductively coupled plasma mass spectrometry, and high-resolution transmission electron microscopy (TEM) in combination with careful examination of the structure with Cs-corrected high-angle annular dark-field scanning TEM revealed that the catalyst AgCr@CN-800 comprises Ag- and CrN-aggregated particles, as well as highly dispersed Ag–Nx and Cr–Nx sites embedded in N-doped graphitic structures. A comparative catalytic study using structure-related catalysts in combination with acid-leaching treatments has shown that the most active species are the Ag particles and that their activity is boosted by the presence of Cr-derived species. By in situ Raman spectroscopy experiments, it has been found that the dehydrogenative coupling of silanes with alcohols in the presence of catalyst AgCr@CN-800 takes place through an oxygen-assisted mechanism., The authors thank the financial support from MICIU/AEI/FEDER (PGC2018-094417-B-I00 and RTI2018-098237-B-C22) and Universitat Jaume I (UJI-A2019-16, UJI-B2019-30, and UJI-B2018-23). I.S. thanks the Spanish Ministerio de Economía, Industria y Competitividad (MINECO) for a postdoctoral “Juan de la Cierva-Incorporación” fellowship (IJCI-2016-30590), and the financial support from the “José Castillejo” Mobility Program (CAS19/00339) of the Ministerio de Ciencia, Innovación y Universidades (MICIU). S.M. acknowledges DGA/fondos FEDER (construyendo Europa desde Aragón) for funding the research group Platón (E31_17R). D.V.-E. thanks the MICIU for a FPU grant (FPU15/03011). E.L. and M.A. thank the financial support from FAPESP (2013/07296-2), CNPq (166281/2017-4), CAPES, and FINEP. The authors also thank the “Servei Central d’Instrumentació Científica (SCIC)” of the Universitat Jaume I, as well as Dr. G. Antorrena for technical support in XPS studies.

Gold nanoparticles (Au NPs) functionalized with N-heterocyclic carbene (NHC) ligands immobilized onto graphene are obtained via spontaneous decomposition of well-defined gold-NHC complexes by reduced graphene oxide (rGO) without reducing agents. NHC ligands are responsible for the formation of air-stable, crystalline and small (3.0–4-0 nm) Au NPs homogeneously distributed on the surface of graphene. The catalytic properties of three Au NPs functionalized with different ligands were tested in two benchmark reactions (hydration of alkynes and intramolecular hydroamination of alkynes). The results reveal a pronounced ligand effect on the stability of Au NPs on graphene, by acting as a bridge between them. The Au NPs functionalized with a NHC ligand lacking a polyaromatic group or having a naphthyl tag displayed limited stability and fast deactivation in the first run. On the contrary, the Au NPs functionalized with a NHC ligand containing a pyrenyl handle showed superior catalytic activity and can be recycled at least ten times. The particle size of the Au NPs is preserved after the recycling process indicating a high stability. These results illustrate the use of purposely designed ligands having affinity for both Au NPs and graphene to increase the stability of the hybrid catalyst., The authors thank the financial support from MICIU/AEI/FEDER (RTI2018-098237-B-C21, RTI2018-098237-B-C22 and PID2019-105881RB-I00) and Universitat Jaume I (UJI-B2018-23). S. M. acknowledges DGA/fondos FEDER (construyendo Europa desde Aragón) for funding the research group Platón (E31_17R). D. V-E. thanks the MINECO for the FPU grant (FPU15/03011).

Purpose To study the spatial retinal distribution of electroretinographic (ERG) responses that reflect signals in the L-/M-cone-opponent and luminance post-receptoral pathways. Methods ERG recordings to heterochromatic stimuli (sinusoidal counter-phase modulation of red and green LED light sources) were performed, while varying fractions of red and green modulation. Two temporal frequencies of the stimuli were employed: 12 Hz to record ERGs that reflect L-/M-cone-opponent signal and 36 Hz for recording ERG signals sensitive to stimulus luminance. Stimuli were about 20° in diameter and projected on various retinal locations: the fovea and four eccentricities (10°, 19°, 28° and 35°), each presented nasally, temporally, inferiorly and superiorly from the fovea. Results The 36 Hz stimuli elicited responses that strongly varied with red fraction and were minimal at iso-luminance. Moreover, response phases changed abruptly at the minimum by 180°. In contrast, the responses to the 12 Hz stimuli had amplitudes and phases that changed more gradually with red fraction. The 36 Hz response amplitudes were maximal close to the fovea and sharply decreased with increasing distance from the fovea. The responses to 12 Hz stimuli were more broadly distributed across the retina. Conclusions In the present study, it was found that retinal eccentricity and direction from the fovea have distinct effects on ERGs reflecting different post-receptoral mechanisms. The results are in accord with previous findings that ERGs to 12 Hz stimuli are predominantly determined by the red–green chromatic content of the stimuli, thus reflecting activation in the L-/M-cone-opponent pathway, while responses to 36 Hz stimuli manifest post-receptoral luminance-dependent activation. We found that the response in the cone-opponent pathway is broadly comparable across the retina; in comparison, response amplitude of the luminance pathway strongly depends on retinal stimulus position.

Based on the analysis of the ground surface, grinding forces, and energy, this paper brings a comprehensive approach to determine the effects of different process parameters (cutting and feed speeds, dressing feed speed, abrasive grain size, and grinding wheel bonding material) on the inducement of residual stresses in cemented tungsten carbide cutting inserts finished by plunge-face grinding. The obtained results demonstrated that compressive residual stresses of higher magnitude are mainly observed in the direction perpendicular to the abrasive grain path and can be achieved by the application of vitrified bonded grinding wheels with coarser abrasive grains.

Owing to their inferior hot hardness in comparison with alumina-based ceramics and polycrystalline cubic boron nitride, the performance of coated carbide tools when turning hardened steels strongly relies on proper chemical composition and carbide grain size, together with adequate cutting edge preparation. This work investigates the effect of geometric parameters on the performance of cutting tools applied to turning of AISI 4140 steel hardened to 40 and 50 HRC, in terms of the components of the turning force and temperature. Additionally to well-established geometric parameters, such as the projection of the hone radius on the rake face (Sγ), the projection of the hone radius on the clearance face (Sα), and the form factor K (ratio of Sγ to Sα), a novel parameter is proposed, namely perimeter ratio (P), which represents the ratio of the perimeter of the modified cutting edge to the circumference of the standard honed edge. Moreover, the experimental results were compared with analytical and numerical findings in order to assess their effectiveness in predicting the components of the turning force and chip temperature. The results indicated that analytical modeling was capable to satisfactorily predict the variation of the force components with edge preparation, using as input the value of the corresponding experimental forces for the standard honed cutting edge. On the other hand, the numerical modeling was successfully applied to predict the components of the resultant force at the expense of higher computational effort. The cutting force was not drastically affected by edge preparation, whereas the feed and passive forces increased with P and Sα and the form factor K was not capable to provide a consistent relationship with both the feed and passive forces. Both the experimental and numerical temperatures of the chip and the numerical temperature at the tool-chip interface did not present a straightforward trend with regard to edge preparation.

Developmental instability (DI) reflects an organism’s inability to develop an ideal phenotype when challenged by genetic and environmental insults. DI can be estimated via the proxy measure of fluctuating asymmetry (FA), i.e., the small random deviations from perfect bilateral symmetry observed in the morphology of paired traits. The mechanisms involved in the genesis of FA in human populations are relatively unknown, though animal research indicates that hormonal processes may be involved. As maternal stress during pregnancy is detrimental to various developmental processes, elevated prenatal cortisol may represent a causal factor in the subsequent emergence of an asymmetrical phenotype. The main purpose of this pre-registered meta-analysis based on three empirical studies was to investigate whether mid-trimester amniotic cortisol levels predict subsequent FA in finger lengths of infants from Germany, Portugal, and the UK. No statistically significant relationships were observed, and meta-analytic combination of the effect size estimates yielded a null result. We did, however, detect significant positive correlations between the cortisol present in the amniotic fluid and maternal plasma in the Portuguese cohort, and observed that FA in the German cohort was significantly lower at 70-months than at either 9- or 20-months. Taken together, the current findings run contrary to animal research showing that elevated prenatal corticosterone exposure leads to increased FA. However, this may be because a single cortisol assay obtained via amniocentesis is an inadequate proxy for average gestational exposure, and/or that prenatal cortisol levels at an earlier (i.e., first rather than second trimester) stage of pregnancy is what explains variance in subsequent FA.