Household composition after resettlement and emotional health in adolescent migrants.

Background: Migration during adolescence constitutes an important stressor that particularly impacts unaccompanied minors (UAM). Adolescent UAM in the United States (U.S.) are relatively understudied, especially regarding their resilience and emotional well-being after resettlement. Small school-based studies have documented the mental health status of UAM who resettled reuniting with their parents. However, many do not resettle with parents and less is known about the degree to which post-resettlement household composition impacts resilience and emotional well-being. Methods: Our goal was to examine how migration characteristics, supports, resilience, and emotional well-being vary by UAM resettlement household composition (reunification with parents, reunification with a non-parental family member, or living in a household not containing any family members). Using a mixed-methods (quantitative-qualitative) cross-sectional approach, we assessed 46 Latin American adolescent UAM to the U.S. who resettled into these three household types. Results: Youth experienced support differently by household type, influencing their strategies for adapting and coping post-resettlement, impacting their resilience (Kruskal Wallis-H 4.8; p<0.09) and emotional well-being (Kruskal Wallis 5.3; p<0.07). Youth living in households without relatives (n = 9) had lower resilience (Fisher's exact test p<0.002) and positive affect (Fisher's exact test p<0.003) and needed to expend greater efforts to mobilize social supports than youth living with parents (n = 22) or with non-parental family members (n = 15). Conclusion: The needs and coping abilities of UAM migrants vary with the composition of their immediate receiving environment, their post-resettlement household. Understanding differences associated with these household characteristics can guide interventions to maximize emotional health and resilience.

Secondary Ion Mass Spectrometry Imaging Reveals Changes in the Lipid Structure of the Plasma Membranes of Hippocampal Neurons following Drugs Affecting Neuronal Activity.

The cellular functions of lipids in the neuronal plasma membranes have been increasingly acknowledged, particularly their association to neuronal processes and synaptic plasticity. However, the knowledge of their regulatory mechanisms in neuronal cells remains sparse. To address this, we investigated the lipid organization of the plasma membranes of hippocampal neurons in relation to neuronal activity using secondary ion mass spectrometry imaging. The neurons were treated with drugs, particularly tetrodotoxin (TTX) and bicuculline (BIC), to induce chronic activation and silencing. Distinct lipid organization was found in the plasma membrane of the cell body and the neurites. Moreover, significant alterations of the levels of the membrane lipids, especially ceramides, phosphatidylserines, phosphatidic acids, and triacylglycerols, were observed under the TTX and BIC treatments. We suggest that many types of membrane lipids are affected by, and may be involved in, the regulation of neuronal function.

CuA-based chimeric T1 copper sites allow for independent modulation of reorganization energy and reduction potential.

Attaining rational modulation of thermodynamic and kinetic redox parameters of metalloproteins is a key milestone towards the (re)design of proteins with new or improved redox functions. Here we report that implantation of ligand loops from natural T1 proteins into the scaffold of a CuA protein leads to a series of distorted T1-like sites that allow for independent modulation of reduction potentials (E°') and electron transfer reorganization energies (λ). On the one hand E°' values could be fine-tuned over 120 mV without affecting λ. On the other, λ values could be modulated by more than a factor of two while affecting E°' only by a few millivolts. These results are in sharp contrast to previous studies that used T1 cupredoxin folds, thus highlighting the importance of the protein scaffold in determining such parameters.

Citrus reticulata peel oil as an antiatherogenic agent: Hypolipogenic effect in hepatic cells, lipid storage decrease in foam cells, and prevention of LDL oxidation.

BACKGROUND AND AIMS: Hypercholesterolemia and oxidative stress are two of the most important risk factors for atherosclerosis. The aim of the present work was to evaluate mandarin (Citrus reticulata) peel oil (MPO) in cholesterol metabolism and lipid synthesis, and its antioxidant capacity. METHODS AND RESULTS: Incubation of hepatic HepG2 cells with MPO (15-60 µL/L) reduced cholesterogenesis and saponifiable lipid synthesis, demonstrated by [14C]acetate radioactivity assays. These effects were associated with a decrease in a post-squalene reaction of the mevalonate pathway. Molecular docking analyses were carried out using three different scoring functions to examine the cholesterol-lowering property of all the components of MPO against lanosterol synthase. Docking simulations proposed that minor components of MPO monoterpenes, like alpha-farnesene and neryl acetate, as well the major component, limonene and its metabolites, could be partly responsible for the inhibitory effects observed in culture assays. MPO also decreased RAW 264.7 foam cell lipid storage and its CD36 expression, and prevented low-density lipoprotein (LDL) lipid peroxidation. CONCLUSION: These results may imply a potential role of MPO in preventing atherosclerosis by a mechanism involving inhibition of lipid synthesis and storage and the decrease of LDL lipid peroxidation.

Lesiones dentales no cariosas: etiología y diagnóstico clínico. Revisión de literatura / Non-carious dental lesions: etiology and clinical diagnosis. Literatura reviews

Las lesiones dentales no cariosas comprenden un conjunto de procesos que se caracterizan por la pérdida o el desgaste patológico de los tejidos duros del diente, como ser el esmalte y la dentina. En la etapa inicial es difícil el diagnóstico, cuando la lesión va en aumento y si no es tratada a tiempo ni se modifican los factores de riesgo pueden llegar afectar de manera progresiva la pulpa dental. Estas lesiones han aumentado en los últimos años, debido al mayor tiempo de dientes en boca, acompañado de hábitos parafuncionales y dietas altamente acidas, a esto se le agrega el estrés que también provoca perdida de estructura dental. Por lo que no toda perdida de tejido mineralizado de los diente es provocada por una carga bacteriana. Estas lesionesno cariosas difieren en su etiología, se debe ser muy minucioso en su evaluación clínica y descripción, ya que muchas características clínicas pueden generar un diagnóstico erróneo y por ende un tratamiento no predecible, se debe tomar en consideración la existencia de combinaciones entre lesiones. Objetivo: Conocer la etiología y características clínicas propias de cada lesión, para poder realizar un diagnóstico oportuno y seguro. La revisión se realizó por medio de una búsqueda en internet en los buscadores de Hinari, Science Direct, Google académico, revisando artículos originales y revisiones bibliográficas entre los años de 2014-2019. Conclusiones: Las lesiones dentales no cariosas tienen etiologías multi factoriales, características clínicas diferenciales y puede haber una combinación de varias patologías...(AU)

Induction of oxidative stress as a possible mechanism by which geraniol affects the proliferation of human A549 and HepG2 tumor cells.

Geraniol (GOH), like other plant-derived natural bioactive compounds, has been found to possess antiproliferative properties that are essential to cope with malignant tumors. However, the mechanisms of molecular action of GOH are not fully elucidated. The aim of this study was to evaluate the effect of GOH on some oxidative parameters in human tumor cell lines (HepG2 and A549). Cytotoxicity evaluated in cell lines by the MTT assay, genotoxicity by the comet assay, and lipid peroxidation by the TBARS. The activities of antioxidant the enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST), were also analyzed. Additionally, intracellular reactive oxygen species (ROS), nitric oxide, and lactate production were determined in HepG2 cells. Both tumor cell lines showed a clear concentration-dependent response to GOH in several of the parameters evaluated. Lipids turned out to be more sensitive than DNA to oxidative damage induced by GOH. TBARS levels increased with respect to control (p < 0.05) by 33% and 122% in HepG2 and A549 cells, respectively treated with 200 µM GOH. However, GOH caused a statistically significant decrease in SOD and CAT activities in HepG2 cells only. GST was not affected in any cell lines. GOH induced the production of ROS but not nitric oxide in HepG2, which shows that ROS were mainly responsible for oxidative damage. Lactate release increased statistically significantly compared to control (p < 0.001), by 41% and 86% at 200 and 800 µM GOH respectively, showing that this monoterpene also affected the glycolytic pathway in HepG2 cells. These results suggest that oxidative stress could mediate the anti-proliferative effects of GOH in HepG2 and A549 cells.

Electron transfer and conformational transitions of cytochrome c are modulated by the same dynamical features.

Cytochrome c is a prototypical multifunctional protein that is implicated in a variety of processes that are essential both for sustaining and for terminating cellular life. Typically, alternative functions other than canonical electron transport in the respiratory chain are associated to alternative conformations. In this work we apply a combined experimental and computational study of Cyt c variants to assess whether the parameters that regulate the canonical electron transport function of Cyt c are correlated with those that determine the transition to alternative conformations, using the alkaline transition as a model conformational change. The results show that pKa values of the alkaline transition correlate with the activation energies of the frictionally-controlled electron transfer reaction, and that both parameters are mainly modulated by the flexibility of the Ω-loop 70-85. Reduction potentials and non-adiabatic ET reorganization energies, on the other hand, are both modulated by the flexibilities of the Ω-loops 40-57 and 70-85. Finally, all the measured thermodynamic and kinetic parameters that characterize both types of processes exhibit systematic variations with the dynamics of the hydrogen bond between the axial ligand Met80 and the second sphere ligand Tyr67, thus highlighting the critical role of Tyr67 in controlling canonical and alternative functions of Cyt c.

Fortification of bakery and corn masa-based foods in Mexico and dietary intake of folic acid and folate in Mexican national survey data.

BACKGROUND: In Mexico, wheat and corn flour fortification with folic acid (FA) was implemented in 2001 and mandated in 2008, but without direct enforcement. Current Mexican nutrient-content tables do not account for FA contained in bakery bread and corn masa-based foods, which are dietary staples in Mexico. OBJECTIVE: The objective of this study was to examine the impact of FA fortification of dietary staples on the proportion of the population consuming below the Estimated Average Requirement (EAR) for folate or above the Tolerable Upper Intake Level (UL) for FA. METHODS: We measured FA and folate content in dietary staples (bakery bread and tortillas) using microbial assays and MS, and we recalculated FA intake from 24-h recall dietary intake data collected in the 2012 Mexican National Health and Nutrition Survey (Encuesta Nacional de Salud y Nutrición) utilizing estimates from our food measurements, using nutrient concentrations from tortillas to approximate nutrient content of other corn masa-derived foods. The revised FA intake estimates were used to examine population-level intake of FA and dietary folate equivalent (DFE) accounting for geographic differences in FA content with statistical models. RESULTS: FA content in dietary staples was variable, whereas use of FA-fortified flour in corn masa tortillas increased with population size in place of residence. Accounting for dietary staples' FA fortification increased population estimates for FA and DFE intake, resulting in a lower proportion with intake below the EAR and a higher proportion with intake above the UL. Despite accounting for FA-fortified staple foods, 9-33% of women of childbearing age still have intake below the EAR, whereas up to 12% of younger children have intake above the UL. CONCLUSIONS: Unregulated FA fortification of dietary staples leads to unpredictable total folate intake without adequately impacting the intended target. Our findings suggest that monitoring, evaluation, and enforcement of mandatory fortification policies are needed. Without these, alternate strategies may be needed in order to reach women of childbearing age while avoiding overexposing children.

The alkaline transition of cytochrome c revisited: Effects of electrostatic interactions and tyrosine nitration on the reaction dynamics.

Here we investigated the effect of electrostatic interactions and of protein tyrosine nitration of mammalian cytochrome c on the dynamics of the so-called alkaline transition, a pH- and redox-triggered conformational change that implies replacement of the axial ligand Met80 by a Lys residue. Using a combination of electrochemical, time-resolved SERR spectroelectrochemical experiments and molecular dynamics simulations we showed that in all cases the reaction can be described in terms of a two steps minimal reaction mechanism consisting of deprotonation of a triggering group followed by ligand exchange. The pKaalk values of the transition are strongly modulated by these perturbations, with a drastic downshift upon nitration and an important upshift upon establishing electrostatic interactions with a negatively charged model surface. The value of pKaalk is determined by the interplay between the acidity of a triggering group and the kinetic constants for the forward and backward ligand exchange processes. Nitration of Tyr74 results in a change of the triggering group from Lys73 in WT Cyt to Tyr74 in the nitrated protein, which dominates the pKaalk downshift towards physiological values. Electrostatic interactions, on the other hand, result in strong acceleration of the backward ligand exchange reaction, which dominates the pKaalk upshift. The different physicochemical conditions found here to influence pKaalk are expected to vary depending on cellular conditions and subcellular localization of the protein, thus determining the existence of alternative conformations of Cyt in vivo.

Multifunctional Cytochrome c: Learning New Tricks from an Old Dog.

Cytochrome c (cyt c) is a small soluble heme protein characterized by a relatively flexible structure, particularly in the ferric form, such that it is able to sample a broad conformational space. Depending on the specific conditions, interactions, and cellular localization, different conformations may be stabilized, which differ in structure, redox properties, binding affinities, and enzymatic activity. The primary function is electron shuttling in oxidative phosphorylation, and is exerted by the so-called native cyt c in the intermembrane mitochondrial space of healthy cells. Under pro-apoptotic conditions, however, cyt c gains cardiolipin peroxidase activity, translocates into the cytosol to engage in the intrinsic apoptotic pathway, and enters the nucleus where it impedes nucleosome assembly. Other reported functions include cytosolic redox sensing and involvement in the mitochondrial oxidative folding machinery. Moreover, post-translational modifications such as nitration, phosphorylation, and sulfoxidation of specific amino acids induce alternative conformations with differential properties, at least in vitro. Similar structural and functional alterations are elicited by biologically significant electric fields and by naturally occurring mutations of human cyt c that, along with mutations at the level of the maturation system, are associated with specific diseases. Here, we summarize current knowledge and recent advances in understanding the different structural, dynamic, and thermodynamic factors that regulate the primary electron transfer function, as well as alternative functions and conformations of cyt c. Finally, we present recent technological applications of this moonlighting protein.

High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4.

BACKGROUND AND AIMS: Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype (GT)-1 and GT-4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. METHODS: This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed. RESULTS: Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109 /L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%-91.9%) than patients with less advanced liver disease (93.8%-95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE-associated discontinuation events occurred in 5.9% and 2.6%. CONCLUSIONS: In this large cohort of cirrhotic patients managed in the real-world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations.

Leaf venation pattern to recognize austral South American medicinal species of "cow's hoof" (Bauhinia L., Fabaceae)

ABSTRACT The leaves extracts of some species of Bauhinia L. s.l. are consumed to treat diabetes, inflammation, pains and several disorders in traditional medicine in austral South America. Despite its wide use and commercialization, sale is not controlled, and botanical quality of samples is not always adequate because of plant misidentification and adulteration. Here, we characterized leaf vein pattern in nineteen taxa to contribute to the recognition and commercial quality control of plant material commercially available. The vein characters intercostal tertiary and quinternary vein fabric, areole development and shape, free ending veinlet branching and marginal ultimate venation allowed to distinguish the main medicinal species in the region.

Structure, electrocatalysis and dynamics of immobilized cytochrome PccH and its microperoxidase.

Geobacter sulfurreducens cells have the ability to exchange electrons with conductive materials, and the periplasmic cytochrome PccH plays an essential role in the direct electrode-to-cell electron transfer in this bacterium. It has atypically low redox potential and unique structural features that differ from those observed in other c-type cytochromes. We report surface enhanced resonance Raman spectroscopic and electrochemical characterization of the immobilized PccH, together with molecular dynamics simulations that allow for the rationalization of experimental observations. Upon attachment to electrodes functionalized with partially or fully hydrophobic self-assembled monolayers, PccH displays a distribution of native and non-native heme spin configurations, similar to those observed in horse heart cytochrome c. The native structural and thermodynamic features of PccH are preserved upon attachment mixed hydrophobic (-CH3/-NH2) surfaces, while pure -OH, -NH2 and -COOH surfaces do not provide suitable platforms for its adsorption, indicating that its still unknown physiological redox partner might be membrane integrated. Neither of the employed immobilization strategies results in electrocatalytically active PccH capable of the reduction of hydrogen peroxide. Pseudoperoxidase activity is observed in immobilized microperoxidase, which is enzymatically produced from PccH and spectroscopically characterized. Further improvement of PccH microperoxidase stability is required for its application in electrochemical biosensing of hydrogen peroxide.

Stability, redox parameters and electrocatalytic activity of a cytochrome domain from a new subfamily.

We report a spectroscopic, electrochemical and spectroelectrochemical characterization of the soluble cytochrome c domain (Cyt-D) from the Rhodothermus marinus caa3 terminal oxygen reductase and its putative electron donor, a high potential [4Fe-4S] protein (HiPIP). Cyt-D exhibits superior stability, particularly at the level of the heme pocket, compared to archetypical cytochromes in terms of thermal and chemical denaturation, alkaline transition and oxidative bleaching of the heme, which is further increased upon adsorption on biomimetic electrodes. Therefore, this protein is proposed as a suitable building block for electrochemical biosensing. As a proof of concept, we show that the immobilized Cyt-D exhibits good electrocatalytic activity towards H2O2 reduction. Relevant thermodynamic and kinetic electron transfer parameters for Cyt-D and HiPIP are also reported, including reorganization energies of 0.33 eV and 0.42 eV, respectively.

Coupling of tyrosine deprotonation and axial ligand exchange in nitrocytochrome c.

Here we report a spectroscopic, electrochemical and computational study of cytochrome c showing that nitration of Tyr74 induces Tyr deprotonation, which is coupled to Met/Lys axial ligand exchange, and results in concomitant gain of peroxidatic activity at physiological pH.

Synthesis and evaluation as antitumor agents of 1,4-naphthohydroquinone derivatives conjugated with amino acids and purines.

We report on the synthesis of two series of 1,4-naphthohydroquinone derivatives conjugated with amino acids (Gly, Ala, Phe, and Glu) and with substituted purines linked by an aliphatic chain. The compounds were obtained through Diels-Alder cycloaddition between myrcene and 1,4-benzoquinone and evaluated in vitro for their cytotoxicity (GI50 ) against cultured human cancer cells of A-549 lung carcinoma, HT-29 colon adenocarcinoma, and MCF-7 breast carcinoma. The GI50 values found for some hydroquinone-amino acid and hydroquinone-purine hybrids against MCF-7 are in an activity range comparable to that of the reference drug doxorubicin.

Electrostatically driven second-sphere ligand switch between high and low reorganization energy forms of native cytochrome c.

We have employed a combination of protein film voltammetry, time-resolved vibrational spectroelectrochemistry and molecular dynamics simulations to evaluate the electron-transfer reorganization free energy (λ) of cytochrome c (Cyt) in electrostatic complexes that mimic some basic features of protein-protein and protein-lipid interactions. The results reveal the existence of two native-like conformations of Cyt that present significantly different λ values. Conversion from the high to the low λ forms is triggered by electrostatic interactions, and involves the rupture of a weak H-bond between first- (M80) and second-sphere (Y67) ligands of the heme iron, as a distinctive feature of the conformational switch. The two flexible Ω loops operate as transducers of the electrostatic signal. This fine-tuning effect is abolished in the Y67F Cyt mutant, which presents a λ value similar to the WT protein in electrostatic complexes. We propose that interactions of Cyt with the natural redox partner proteins activate a similar mechanism to minimize the reorganization energy of interprotein electron transfer.