Conducting school-based research with newcomer immigrant adolescents: Challenges and solutions.

Newcomer immigrant adolescents (NIA) represent a particularly vulnerable group in the United States, facing numerous stressors placing them at risk for social-emotional and academic concerns. Schools play a critical role in supporting NIA in the United States. Despite this, insufficient research addressing the needs of this group within schools has been conducted. Considering the complexity of engaging in community-based research with marginalized populations, such as NIA, in this article, we elaborate on the challenges we faced during our research with NIA and propose solutions to these challenges. We do so with the goal of promoting continued engagement of such efforts within our field as to better address the needs of NIA within the United States. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

MLDSR, the transcriptional regulator of the major lipid droplets protein MLDS, is controlled by long-chain fatty acids and contributes to the lipid-accumulating phenotype in oleaginous Rhodococcus strains.

Microorganism lipid droplet small regulator (MLDSR) is a transcriptional regulator of the major lipid droplet (LD)-associated protein MLDS in Rhodococcus jostii RHA1 and Rhodococcus opacus PD630. In this study, we investigated the role of MLDSR on lipid metabolism and triacylglycerol (TAG) accumulation in R. jostii RHA1 at physiological and molecular levels. MLDSR gene deletion promoted a significant decrease of TAG accumulation, whereas inhibition of de novo fatty acid biosynthesis by the addition of cerulenin significantly repressed the expression of the mldsr-mlds cluster under nitrogen-limiting conditions. In vitro and in vivo approaches revealed that MLDSR-DNA binding is inhibited by fatty acids and acyl-CoA residues through changes in the oligomeric or conformational state of the protein. RNAseq analysis indicated that MLDSR not only controls the expression of its own gene cluster but also of several genes involved in central, lipid, and redox metabolism, among others. We also identified putative MLDSR-binding sites on the upstream regions of genes coding for lipid catabolic enzymes and validated them by EMSA assays. Overexpression of mldsr gene under nitrogen-rich conditions promoted an increase of TAG accumulation, and further cell lysis with TAG release to the culture medium. Our results suggested that MLDSR is a fatty acid-responsive regulator that plays a dual role in cells by repression or activation of several metabolic genes in R. jostii RHA1. MLDSR seems to play an important role in the fine-tuning regulation of TAG accumulation, LD formation, and cellular lipid homeostasis, contributing to the oleaginous phenotype of R. jostii RHA1 and R. opacus PD630.

Interfacial Hyperactivation of Candida rugosa Lipase onto Ca2Fe2O5 Nanoparticles: pH and Ionic Strength Fine-Tuning to Modulate Protein-Support Interactions.

The current study provides a comprehensive look of the adsorption process of Candida rugosa lipase (CRL) on Ca2Fe2O5 iron oxide nanoparticles (NPs). Protein-support interactions were identified across a broad range of pH and ionic strengths (mM) through a response surface methodology, surface charge determination, and spectroscopic and in silico analyses. The maximum quantity of immobilized protein was achieved at an ionic strength of 50 mM and pH 4. However, this condition did not allow for the greatest hydrolytic activity to be obtained. Indeed, it was recorded at acidic pH, but at 150 mM, where evaluation of the recovered activity revealed hyperactivation of the enzyme. These findings were supported by adsorption isotherms performed under different conditions. Based on zeta potential measurements, electrostatic interactions contributed differently to protein-support binding under the conditions tested, showing a strong correlation with experimentally determined immobilization parameters. Raman spectra revealed an increase in hydrophobicity around tryptophan residues, whereas the enzyme immobilization significantly reduced the phenylalanine signal in CRL. This suggests that this residue was involved in the interaction with Ca2Fe2O2 and molecular docking analysis confirmed these findings. Fluorescence spectroscopy showed distinct behaviors in the CRL emission patterns with the addition of Ca2Fe2O5 at pH 4 and 7. The calculated thermodynamic parameters indicated that the contact would be mediated by hydrophobic interactions at both pHs, as well as by ionic ones at pH 4. In this approach, this work adds to our understanding of the design of biocatalysts immobilized in iron oxide NPs.

Tuning surface interactions on MgFe2O4 nanoparticles to induce interfacial hyperactivation in Candida rugosa lipase immobilization.

Lipase adsorption on solid supports can be mediated by a precise balance of electrostatic and hydrophobic interactions. A suitable fine-tuning could allow the immobilized enzyme to display high catalytic activity. The objective of this work was to investigate how pH and ionic strength fluctuations affected protein-support interactions during immobilization via physical adsorption of a Candida rugosa lipase (CRL) on MgFe2O5. The highest amount of immobilized protein (IP) was measured at pH 4, and an ionic strength of 90 mM. However, these immobilization conditions did not register the highest hydrolytic activity (HA) in the biocatalyst (CRLa@MgFe2O4), finding the best values also at acidic pH but with a slight shift towards higher values of ionic strength around 110 mM. These findings were confirmed when the adsorption isotherms were examined under different immobilization conditions so that the maximum measurements of IP did not coincide with that of HA. Furthermore, when the recovered activity was examined, a strong interfacial hyperactivation of the lipase was detected towards acidic pH and highly charged surrounding environments. Spectroscopic studies, as well as in silico molecular docking analyses, revealed a considerable involvement of surface hydrophobic protein-carrier interactions, with aromatic aminoacids, especially phenylalanine residues, playing an important role. In light of these findings, this study significantly contributes to the body of knowledge and a better understanding of the factors that influence the lipase immobilization process on magnetic inorganic oxide nanoparticle surfaces.

Exploration of Anti-HIV Phytocompounds against SARS-CoV-2 Main Protease: Structure-Based Screening, Molecular Simulation, ADME Analysis and Conceptual DFT Studies.

The ever-expanding pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has gained attention as COVID-19 and caused an emergency in public health to an unmatched level to date. However, the treatments used are the only options; currently, no effective and licensed medications are available to combat disease transmission, necessitating further research. In the present study, an in silico-based virtual screening of anti-HIV bioactive compounds from medicinal plants was carried out through molecular docking against the main protease (Mpro) (PDB: 6LU7) of SARS-CoV-2, which is a key enzyme responsible for virus replication. A total of 16 anti-HIV compounds were found to have a binding affinity greater than -8.9 kcal/mol out of 150 compounds screened. Pseudohypericin had a high affinity with the energy of -10.2 kcal/mol, demonstrating amino acid residual interactions with LEU141, GLU166, ARG188, and GLN192, followed by Hypericin (-10.1 kcal/mol). Moreover, the ADME (Absorption, Distribution, Metabolism and Excretion) analysis of Pseudohypericin and Hypericin recorded a low bioavailability (BA) score of 0.17 and violated Lipinski's rule of drug-likeness. The docking and molecular simulations indicated that the quinone compound, Pseudohypericin, could be tested in vitro and in vivo as potent molecules against COVID-19 disease prior to clinical trials.This was also supported by the theoretical and computational studies conducted. The global and local descriptors, which are the underpinnings of Conceptual Density FunctionalTheory (CDFT) have beenpredicted through successful model chemistry, hoping that they could be of help in the comprehension of the chemical reactivity properties of the molecular systems considered in this study.

Características clínicas y evolución de la infección por SARS-CoV-2 en pacientes con lupus eritematoso sistémico en Argentina: datos del registro nacional SAR-COVID / Clinical characteristics and course of SARS-CoV-2 infection in patients with systemic lupus erythematosus in Argentina: data from the SAR-COVID national registry

Introducción: el lupus eritematoso sistémico (LES) es una enfermedad sistémica que se ha asociado a mayor severidad con la infección por SARS-CoV-2. Particularmente la alta actividad de la enfermedad y algunos inmunosupresores se han vinculado a peores desenlaces. Objetivos: describir las características por SARS-CoV-2 en pacientes con LES en Argentina del registro SAR-COVID y establecer los factores asociados a peor desenlace de la misma. Materiales y métodos: estudio observacional. Se incluyeron pacientes con diagnóstico de LES con infección confirmada por SARS-CoV-2 (RT-PCR y/o serología positiva) del registro SAR-COVID. Los datos se recolectaron desde agosto de 2020 hasta marzo de 2022. El desenlace de la infección se midió mediante la escala ordinal de la Organización Mundial de la Salud (EO-OMS). Se definió COVID-19 severo con un valor EO-OMS ≥5. Análisis descriptivo, test T de Student, test de Mann Whitney U, ANOVA, chi2 y Fisher. Regresión logística múltiple. Resultados: se incluyeron 399 pacientes, el 93% de sexo femenino, con una edad media de 40,9 años (DE 12,2). El 39,6% tenía al menos una comorbilidad. Al momento de la infección, el 54,9% recibía glucocorticoides, el 30,8% inmunosupresores y el 3,3% agentes biológicos. La infección por SARS-CoV-2 fue leve en la mayoría de los casos, mientras que un 4,6% tuvo curso severo y/o falleció. Estos últimos presentaban comorbilidades, usaban glucocorticoides y tenían síndrome antifosfolipídico (SAF) con mayor frecuencia y mayor actividad de la enfermedad al momento de la infección. En el análisis multivariado, la hipertensión arterial, el diagnóstico de SAF y el uso de glucocorticoides se asociaron a hospitalización severa y/o muerte por COVID-19 (EO-OMS ≥5). Conclusiones: en esta cohorte de pacientes con LES con infección por SARS-CoV-2 confirmada, la mayoría cursó de manera sintomática, un 22,1% fue hospitalizado y un 5% requirió ventilación mecánica. La mortalidad fue cercana al 3%. El diagnóstico de SAF, tener hipertensión arterial y el uso de glucocorticoides se asociaron significativamente con COVID-19 severo.

Introduction: systemic lupus erythematosus (SLE) is a systemic disease that has been associated with greater severity with SARS-CoV-2 infection. Particularly high disease activity and some immunosuppressants have been linked to worse outcomes. Objectives: to describe the characteristics due to SARS-CoV-2 in patients with SLE in Argentina from the SAR-COVID registry and to establish the factors associated with a worse outcome of the same. Materials and methods: observational study. Patients diagnosed with SLE with confirmed SARS-CoV-2 infection (RT-PCR and/or positive serology) from the SAR-COVID registry were included. Data was collected from August 2020 to March 2022. The outcome of the infection was measured using the World Health Organization - ordinal scale (WHO-OS). Severe COVID-19 was defined as an WHO-OS value ≥5. Descriptive analysis, Student's T test, Mann Whitney U, ANOVA, chi2 and Fisher. Multiple logistic regression. Results: a total of 399 patients were included, 93% female, with a mean age of 40.9 years (SD 12.2), 39.6% had at least one comorbidity. At the time of infection, 54.9% were receiving glucocorticoids, 30.8% immunosuppressants, and 3.3% biological agents. SARS-CoV-2 infection was mild in most cases, while 4.6% had a severe course and/or died. The latter had comorbidities, used glucocorticoids and had antiphospholipid syndrome (APS) more frequently and higher disease activity at the time of infection. In the multivariate analysis, high blood pressure, the diagnosis of APS, and the use of glucocorticoids were associated with severe hospitalization and/or death from COVID-19 (WHO-EO ≥5). Conclusions: in this cohort of SLE patients with confirmed SARS-CoV-2 infection, most had a symptomatic course, 22.1% were hospitalized, and 5% required mechanical ventilation. Mortality was close to 3%. The diagnosis of APS, having high blood pressure, and the use of glucocorticoids were significantly associated with severe COVID-19.

Repositioning Therapeutics for SARS-CoV-2: Virtual Screening of Plant-based Anti-HIV Compounds as Possible Inhibitors against COVID-19 Viral RdRp.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a global pandemic with a high mortality and morbidity rate worldwide. The COVID-19 vaccines that are currently in development or already approved are expected to provide at least some protection against the emerging variants of the virus, but the mutations may reduce the efficacy of the existing vaccines. Purified phytochemicals from medicinal plants provide a helpful framework for discovering new therapeutic leads as they have long been employed in traditional medicine to treat many disorders. OBJECTIVE: The objectives of the study are to exploit the anti-HIV bioactive compounds against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through molecular docking studies and to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of potential compounds. METHODS: Molecular docking was performed to study the interaction of ligands with the target sites of RdRp protein (PDB: 6M71) using AutoDock Vina. The ADMET properties of potential compounds were predicted using the pkCSM platform. RESULTS: A total of 151 phytochemicals derived from the medicinal plants with recognized antiviral activity and 18 anti-HIV drugs were virtually screened against COVID-19 viral RdRp to identify putative inhibitors that facilitate the development of potential anti-COVID-19 drug candidates. The computational studies identified 34 compounds and three drugs inhibiting viral RdRp with binding energies ranging from -10.2 to -8.5 kcal/mol. Among them, five compounds, namely Michellamine B, Quercetin 3-O-(2'',6''-digalloyl)-beta-Dgalactopyranoside, Corilagin, Hypericin, and 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose residues, bound efficiently with the binding site of RdRp. Besides, Lopinavir, Maraviroc, and Remdesivir drugs also inhibited SARS-CoV-2 polymerase. In addition, the ADMET properties of top potential compounds were also predicted in comparison to the drugs. CONCLUSION: The present study suggested that these potential drug candidates can be further subjected to in vitro and in vivo studies that may help develop effective anti-COVID-19 drugs.

Silver nanoparticles synthesized by the heavy metal resistant strain Amycolatopsis tucumanensis and its application in controlling red strip disease in sugarcane.

The production of bioethanol and sugar from sugarcane is an important economic activity in several countries. Sugarcane is susceptible to different phytopathogens. Over the last years, the red stripe disease caused by the bacterium Acidovorax avenae subsp. avenae produced significant losses in sugarcane crops. Bio-nanotechnology emerged as an eco-friendly alternative to the biosynthesis of antimicrobial molecules. The aims of this study were to (a) produce extracellular silver nanoparticles using the heavy metal resistant strain Amycolatopsis tucumanensis, (b) evaluate their antibacterial in vitro effect and (c) determine the potential of silver nanoparticles to protect sugarcane against red stripe disease. Amycolatopsis tucumanensis synthesized spherical silver nanoparticles with an average size of 35 nm. Nanoparticles were able to control the growth of A. avenae subsp. avenae in in vitro assays. In addition, in vivo assays in sugarcane showed a control upon the red stripe disease when silver nanoparticles were applied as preventive treatment. The Disease Severity Index was 28.94% when silver nanoparticles were applied 3 days before inoculation with A. avenae subsp. a venae. To our knowledge, this is the first report of silver nanoparticles extracellularly synthesized by an Amycolatopsis strain that were able to inhibited the growth of A. avenae subsp. avenae and control the red stripe disease in sugarcane.

Vitamin D status, proinflammatory cytokines and bone mineral density in Mexican people with multiple sclerosis.

BACKGROUND: Vitamin D (VD) has been classically associated with calcium homeostasis and bone mineral density since it has a key role on mineralization and resorption. Immunomodulatory effects have been attributable to VD; low concentrations of VD have been associated with elevation of inflammatory markers. Inflammatory autoimmune diseases, such as multiple sclerosis (MS), a chronic neurodegenerative suffering, whose etiology is still unknown, is directly related to an increase in pro-inflammatory cytokines such as interleukin 17 and interleukin 1ß who play an important role in this physiopathology. Nowadays, even though additional studies have linked MS's clinical signs with low VD concentration, there is scarce information of this association in people from regions with sufficient sun exposure. The aim of this study was to evaluate serum VD and cytokine concentrations, and bone density, in Mexican people with MS. METHODS: Vitamin D (25OHD), interleukin 1ß, interleukin 6 and interleukin 17 concentrations of twenty-five volunteers with MS were determined by enzyme-linked immunosorbent assay. Bone mineral density and body composition assessment was performed by dual energy X-Ray absorptiometry. RESULTS: A mean concentration of 17.3 ± 4.6 ng/ml of 25OHD was obtained, in a range of 5.15 to 25.71 ng/ml; when international advisory bodies thresholds were applied 76% of the participants exhibited some degree of VD inadequacy. Pro-inflammatory markers were detectable among the participants: interleukin 1ß in 100%, interleukin 6 in 64%, whereas interleukin 17 was found in 24% of the volunteers. Bone mineral density below the expected for the age was found in 8% of the participants, with lumbar spine as the most affected anatomic region. Non-significant correlations were found between VD and bone mineral density (Z-score) or pro-inflammatory markers. CONCLUSION: Although non-significant correlations were found between VD and bone mineral density or cytokines, it is important to highlight that an important percentage of our participants exhibited some degree of VD inadequacy, an unknown fact for them, since these are not included in routine clinical evaluations. The low concentrations of VD among this sample regardless of annual UVB sun exposure may suggest the involvement of endogenous and not environmental factors. Further works are needed in order to deepen the physiological causes and effects of VD deficiency in people with MS.

Characterization of substrate specificity and inhibitory mechanism of bile salt hydrolase from Lactobacillus reuteri CRL 1098 using molecular docking analysis.

OBJECTIVES: To elucidate the molecular mechanisms involved in the substrate interaction of the bile salt hydrolase of Lactobacillus reuteri CRL 1098 (LrBSH) with bile acids (BAs) and to evaluate potential enzyme inhibitors based on computer and in vitro modeling assays. RESULTS: Asp19, Asn79, and Asn171 participated in the LrBSH interaction with all BAs tested while Leu56 and Glu 222 played an important role in the interaction with glyco- and tauro-conjugated BAs, respectively. A great percentage of hydrophobic and polar interactions were responsible for the binding of LrBSH with glyco- and tauro-conjugated BAs, respectively. Remarkably, the four binding pocket loops participated in the substrate binding site of LrBSH unlike most of the reported BSHs. Inhibition assays showed that ascorbic acid, citric acid, penicillin G, and ciprofloxacin decreased LrBSH activity by 47.1%, 40.14%, 28.8%, and 9%, respectively. Docking analysis revealed that tetracycline and caffeic acid phenethyl ester had the low binding energy (-7.32 and -7.19 kcal/mol, respectively) and resembled the interaction pattern of GDCA (-6.88 kcal/mol) while penicillin (-6.25 kcal/mol) and ascorbic acid (-5.98 kcal/mol) interacted at a longer distance. CONCLUSION: This study helps to delve into the molecular mechanisms involved in the recognition of substrates and potential inhibitors of LrBSH.

Lipid profile: causal relationship on cognitive performance in multiple sclerosis?

Although cognitive impairment (CI) is classically associated with aging, it has been proposed that neurological pathologies may increase the risk to suffer CI. Despite the evidence of an elevated prevalence of CI in patients with multiple sclerosis (MS), it is not considered among standard clinical evaluations, due the lack of specialists and time required. The aim of this study was to evaluate if lipid profile is associated with cognitive performance in persons with MS. Twenty patients with MS were evaluated. Montreal Cognitive Assessment (MoCA) was employed to determine cognitive performance. CI was observed in 85% of patients, with memory recall and language as the most affected domains. Despite biomarkers were mostly found within reference values, several correlations were observed. MoCA total score was correlated with cholesterol (r = - 0.468, p = 0.037) and LDL (r = - 0.453, p = 0.045). Visuospatial domain was correlated with LDL (r = - 0.493, p = 0.027). Attention domain correlated with triglycerides (r = - 0.455, p = 0.044) and cholesterol (r = - 0.549, p = 0.012). When the person reaches borderline levels of triglycerides, LDL and cholesterol a decrease in cognitive performance can be observed. The mechanism underlying this association has not been established still, it has been proposed that it could be linked with neuroinflammation, alterations in synapses and in the metabolism of amyloid-ß protein. This study settles the potential importance that lipid profile could have on cognitive performance in MS. Further studies are needed to establish optimal levels and implication of lipid profile in the diagnosis and monitoring of cognitive performance in Mexican people with MS.

Impact of temperature changes and pH on aqueous solutions of TCAB, a derived propanil contaminant.

3,4,3',4'-tetrachloroazobenzene known as TCAB is an unwanted product derivate from the degradation of propanil herbicide. In this work UV-visible and infrared spectroscopies were used to experimentally explore the impact of pH and temperature changes of TCAB in aqueous and ethanol solutions. Two isomeric forms, cis and trans, are present in solution. The density functional theory (DFT) with PCM methodology was used to analyze the stability of each isomer in solution phase by the evaluation of solvation energy and frontier orbital energies of TCBA at 25 and 40 °C. This compound has been studied from room temperature to 50 °C, revealing the weakening of trans form with an increment of cis form in ethanol and high temperature. Interestingly, under acid conditions the protonated azo compound was evidenced in solution. We found that the cis form is predominant in aqueous solution at 40 °C and 30 min. Finally, FTIR studies show that the increasing of the temperature promote irreversible structural changes via a trans to cis interconversion process. The derivative results from this study may contributed to understanding of transformation of TCAB in aqueous solution by pH and temperature changes.

Biosynthesized ZnO-NPs from Morus indica Attenuates Methylglyoxal-Induced Protein Glycation and RBC Damage: In-Vitro, In-Vivo and Molecular Docking Study.

The development of advanced glycation end-products (AGEs) inhibitors is considered to have therapeutic potential in diabetic complications inhibiting the loss of the biomolecular function. In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized from aqueous leaf extract of Morus indica and were characterized by various techniques such as ultraviolet (UV)-Vis spectroscopy, Powder X-Ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FT-IR), Scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). Further, the inhibition of AGEs formation after exposure to ZnO-NPs was investigated by in-vitro, in-vivo, and molecular docking studies. Biochemical and histopathological changes after exposure to ZnO-NPs were also studied in streptozotocin-induced diabetic rats. ZnO-NPs showed an absorption peak at 359 nm with a purity of 92.62% and ~6-12 nm in size, which is characteristic of nanoparticles. The images of SEM showed agglomeration of smaller ZnO-NPs and EDS authenticating that the synthesized nanoparticles were without impurities. The biosynthesized ZnO-NPs showed significant inhibition in the formation of AGEs. The particles were effective against methylglyoxal (MGO) mediated glycation of bovine serum albumin (BSA) by inhibiting the formation of AGEs, which was dose-dependent. Further, the presence of MGO resulted in complete damage of biconcave red blood corpuscles (RBCs) to an irregular shape, whereas the morphological changes were prevented when they were treated with ZnO-NPs leading to the prevention of complications caused due to glycation. The administration of ZnO-NPs (100 mg Kg-1) in streptozotocin(STZ)-induced diabetic rats reversed hyperglycemia and significantly improved hepatic enzymes level and renal functionality, also the histopathological studies revealed restoration of kidney and liver damage nearer to normal conditions. Molecular docking of BSA with ZnO-NPs confirms that masking of lysine and arginine residues is one of the possible mechanisms responsible for the potent antiglycation activity of ZnO-NPs. The findings strongly suggest scope for exploring the therapeutic potential of diabetes-related complications.

Coping strategies and quality of life in Mexican multiple sclerosis patients: Physical, psychological and social factors relationship.

BACKGROUND: Multiple sclerosis (MS) is one of the principal causes of non-traumatic neurological disability among young adults. The unpredictable and progressive evolution of multiple sclerosis is associated with a decline in physical and psychological health, affecting quality of life, which may be influenced by additional physical and psycho-social factors. OBJECTIVE: The present investigation aims to evaluate the quality of life (QoL), use of coping strategies and their relationship with other physical and psycho-social factors among 26 Mexican persons with MS. METHODS: Eight questionnaires were administrated for evaluation of the additional psycho-social and physical factors, including quality of life, coping strategies, social support system, family functionality, depression and anxiety prevalence. RESULTS: Results showed that the use of positive coping strategies (84.6% of our population) improve QoL perception (r = 0.396, p = 0.045) and the following domains: physical health (r = 0.514, p = 0.009), psychological health (r = 0.516, p = 0.008), social relationships (r = 0.654, p = 0.000) and environment (r = 0.600, p = 0.002). Negative correlations were observed between QoL and the presence of symptoms of both depression (r = -0.557, p = 0.003) and anxiety (r = -0.517, p = 0.007). A multiple linear regression model showed that QoL can be explained by physical and psycho-social factor in 54.6% of the cases that were evaluated. CONCLUSION: The use of positive coping strategies in conjunction with a suitable psycho-social environment and good physical health result in a better perception of QoL in Mexican patients living with MS. Still, the negative factors are ineffectively diagnosed and hence generally under treated in medical MS monitoring. An interdisciplinary evaluation will provide the adequate tools to confront the diagnosis and the uncertainty of multiple sclerosis evolution, benefiting the QoL of Mexican patients with MS.

Effects of Lysozyme on the Activity of Ionic of Fluoroquinolone Species.

Fluoroquinolones (FQs) constitute an important class of biologically active broad-spectrum antibacterial drugs that are which are in contact with many biological fluids under different acidity conditions. We studied the reactivity of ciprofloxacin (Cpx) and levofloxacin (Lev) and their interaction with lysozyme (Lyz) at different pH values, using UV-visible absorption, fluorescence, infrared spectroscopies supported by DFT calculation and docking. In addition, by antimicrobial assays, the biological consequences of the interaction were evaluated. DFT calculation predicted that the FQ cationic species present at acid pH have lower stabilization energies, with an electric charge rearrangement because of their interactions with solvent molecules. NBO and frontier orbital calculations evidenced the role of two charged centers, NH2⁺ and COO-, for interactions by electronic delocalization effects. Both FQs bind to Lyz via a static quenching with a higher interaction in neutral medium. The interaction induces a structural rearrangement in ß-sheet content while in basic pH a protective effect against the denaturation of Lyz was inferred. The analysis of thermodynamic parameters and docking showed that hydrophobic, electrostatic forces and hydrogen bond are the responsible of Cpx-Lyz and Lev-Lyz associations. Antimicrobial assays evidenced an antagonist effect of Lyz in acid medium while in neutral medium the FQs' activities were not modified by Lyz.

An update on the comorbidity of ADHD and ASD: a focus on clinical management.

Attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) commonly co-occur. With the DSM-5, clinicians are permitted to make an ASD diagnosis in the context of ADHD. In earlier versions of the DSM, this was not acceptable. Both ASD and ADHD are reported to have had substantial increases in prevalence within the past 10 years. As a function of both the increased prevalence of both disorders as well as the ability to make an ASD diagnosis in ADHD, there has been a significant amount of research focusing on the comorbidity between ADHD and ASD in the past few years. Here, we provide an update on the biological, cognitive and behavioral overlap/distinctiveness between the two neurodevelopmental disorders with a focus on data published in the last four years. Treatment strategies for the comorbid condition as well as future areas of research and clinical need are discussed.

Oxidative stress and antioxidant response in fibroblasts from Werner and atypical Werner syndromes.

Werner Syndrome (WS, ICD-10 E34.8, ORPHA902) and Atypical Werner Syndrome (AWS, ICD-10 E34.8, ORPHA79474) are very rare inherited syndromes characterized by premature aging. While approximately 90% of WS individuals have any of a range of mutations in theWRN gene, there exists a clinical subgroup in which the mutation occurs in the LMNA/C gene in heterozygosity. Although both syndromes exhibit an age-related pleiotropic phenotype, AWS manifests the onset of the disease during childhood, while major symptoms in WS appear between the ages of 20 and 30. To study the molecular mechanisms of progeroid diseases provides a useful insight into the normal aging process. Main changes found were the decrease in Cu/Zn and Mn SOD activities in the three cell lines. In AWS, both mRNA SOD and protein levels were also decreased. Catalase and glutathione peroxidases decrease, mainly in AWS. Glutaredoxin (Grx) and thioredoxin (Trx) protein expression was lower in the three progeroid cell lines. Grx and Trx were subjected to post-transcriptional regulation, because protein expression was reduced although mRNA levels were not greatly affected in WS. Low antioxidant defense and oxidative stress occur simultaneously in these rare genetic instability disorders at the onset of progeroid disease.

Nupr1 deletion protects against glucose intolerance by increasing beta cell mass.

AIMS/HYPOTHESIS: The stress-activated nuclear protein transcription regulator 1 (NUPR1) is induced in response to glucose and TNF-α, both of which are elevated in type 2 diabetes, and Nupr1 has been implicated in cell proliferation and apoptosis cascades. We used Nupr1(-/-) mice to study the role of Nupr1 in glucose homeostasis under normal conditions and following maintenance on a high-fat diet (HFD). METHODS: Glucose homeostasis in vivo was determined by measuring glucose tolerance, insulin sensitivity and insulin secretion. Islet number, morphology and beta cell area were assessed by immunofluorescence and morphometric analysis, and islet cell proliferation was quantified by analysis of BrdU incorporation. Islet gene expression was measured by gene arrays and quantitative RT-PCR, and gene promoter activities were monitored by measuring luciferase activity. RESULTS: Nupr1(-/-) mice had increased beta cell mass as a consequence of enhanced islet cell proliferation. Nupr1-dependent suppression of beta cell Ccna2 and Tcf19 promoter activities was identified as a mechanism through which Nupr1 may regulate beta cell cycle progression. Nupr1(-/-) mice maintained on a normal diet were mildly insulin resistant, but were normoglycaemic with normal glucose tolerance because of compensatory increases in basal and glucose-induced insulin secretion. Nupr1 deletion was protective against HFD-induced obesity, insulin resistance and glucose intolerance. CONCLUSIONS/INTERPRETATION: Inhibition of NUPR1 expression or activity has the potential to protect against the metabolic defects associated with obesity and type 2 diabetes.

Histone carbonylation occurs in proliferating cells.

Chromatin is a dynamic structure formed mainly by DNA and histones, and chemical modifications on these elements regulate its compaction. Histone posttranslational modifications (PTMs) have a direct impact on chromatin conformation, controlling important cellular events such as cell proliferation and differentiation. Redox-related posttranslational modifications may have important effects on chromatin structure and function, offering a new intriguing area of research termed "redox epigenetics." Little is known about histone carbonylation, a PTM that may be related to modifications in the cellular redox environment. The aim of our study was to determine the carbonylation of the various histones during cell proliferation, a moment in cell life during which important redox changes take place. Here, we describe changes in histone carbonylation during cell proliferation in NIH3T3 fibroblasts. In addition, we have studied the variations of poly(ADP-ribosyl)ation and phospho-H2AX at the same time, because both modifications are related to DNA damage responses. High levels of carbonylation on specific histones (H1, H1(0), and H3.1 dimers) were found when cells were in an active phase of DNA synthesis. The modification decreased when nuclear proteasome activity was activated. However, these results did not correlate completely with poly(ADP-ribosyl)ation and phospho-H2AX levels. Therefore, histone carbonylation may represent a specific event during cell proliferation. We describe a new methodology named oxy-2D-TAU Western blot that allowed us to separate and analyze the carbonylation patterns of the histone variants. In addition we offer a new role for histone carbonylation and its implication in redox epigenetics. Our results suggest that histone carbonylation is involved in histone detoxification during DNA synthesis.

Mitochondrial DNA as a non-invasive biomarker: accurate quantification using real time quantitative PCR without co-amplification of pseudogenes and dilution bias.

Circulating mitochondrial DNA (MtDNA) is a potential non-invasive biomarker of cellular mitochondrial dysfunction, the latter known to be central to a wide range of human diseases. Changes in MtDNA are usually determined by quantification of MtDNA relative to nuclear DNA (Mt/N) using real time quantitative PCR. We propose that the methodology for measuring Mt/N needs to be improved and we have identified that current methods have at least one of the following three problems: (1) As much of the mitochondrial genome is duplicated in the nuclear genome, many commonly used MtDNA primers co-amplify homologous pseudogenes found in the nuclear genome; (2) use of regions from genes such as ß-actin and 18S rRNA which are repetitive and/or highly variable for qPCR of the nuclear genome leads to errors; and (3) the size difference of mitochondrial and nuclear genomes cause a "dilution bias" when template DNA is diluted. We describe a PCR-based method using unique regions in the human mitochondrial genome not duplicated in the nuclear genome; unique single copy region in the nuclear genome and template treatment to remove dilution bias, to accurately quantify MtDNA from human samples.