Oral administration of zein-based nanoparticles reduces glycemia and improves glucose tolerance in rats

The aim was to evaluate the effect of zein-based nanoparticles on the glucose homeostasis, following oral administration to Wistar rats. For this purpose, bare nanoparticles (NP, with tropism for the upper intestinal regions) and poly(ethylene glycol)-coated nanoparticles (NP-PEG), with the capability to reach the ileum and cecum of animals, were evaluated. Both formulations were spherical in shape, displaying sizes around 200 nm and a negative surface zeta potential. The oral administration of a single dose of these nanoparticles to animals (50 mg/kg) induced a significant decrease of the glycemia, compared control rats and in animals treated with the free protein (p < 0.001). Moreover, these nanoparticles improved the glycemic control against an intraperitoneal glucose tolerance test; particularly NP-PEG. These findings would be due to an increased release of glucagon-like peptide-1 (GLP-1) by L-cells, which are more abundant in distal regions of the intestine. In fact, the GLP-1 blood levels of animals treated with nanoparticles were significantly higher than controls (about 40 % and 60 % for NP and NP-PEG groups, respectively). This higher capability of NP-PEG, with respect to NP, to increase the release of GLP-1 and control glycemia would be related to its ability to reach the distal areas of the small intestine

Improved Performance of an Epoxy Matrix as a Result of Combining Graphene Oxide and Reduced Graphene

We present an easy and effective way to improve the mechanical properties of an epoxy matrix by reinforcing it with a combination of graphene oxide (GO) and reduced graphene oxide (RGO). These nanocomposites were prepared with different load of nanofillers: 0.1, 0.4, 0.7, 1.0 wt% and a neat epoxy. Ratios of graphene oxide and reduced graphene (GO : RGO) employed were: 0 : 1, 0.25 : 0.75, 0.5 : 0.5, 0.75 : 0.25, and 1 : 0. Results show that with only 0.4 wt% and a ratio 0.2 : 0.75 of GO : RGO, tensile strength and tensile toughness are 52% and 152% higher than neat epoxy while modulus of elasticity was improved ~20%. The obtained results suggest that it is possible achieve advantageous properties by combining graphene in oxidized and reduced conditions as it shows a synergic effect by the presence of both nanofillers

Preparation and evaluation of PEG-coated zein nanoparticles for oral drug delivery purposes

The aim was to produce PEG-coated nanoparticles (NP-PEG), with mucus-permeating properties, for oral drug delivery purposes by using simple procedures and regulatory-approved compounds in order to facilitate a po- tential clinical development. For this purpose, zein nanoparticles were prepared by desolvation and, then, coated by incubation with PEG 35,000. The resulting nanocarriers displayed a mean size of about 200 nm and a negative zeta potential. The presence of PEG on the surface of nanoparticles was evidenced by electron microscopy and confirmed by FTIR analysis. Likely, the hydrophobic surface of zein nanoparticles (NP) was significantly reduce by their coating with PEG. This increase of the hydrophilicity of PEG-coated nanoparticles was associated with an important increase of their mobility in pig intestinal mucus. In laboratory animals, NP-PEG (fluorescently labelled with Lumogen® Red 305) displayed a different behavior when compared with bare nanoparticles. After oral administration, NP appeared to be trapped in the mucus mesh, whereas NP-PEG were capable of crossing the protective mucus layer and reach the epithelium. Finally, PEG-coated zein nanoparticles, prepared by a simple and reproducible method without employing reactive reagents, may be adequate carriers for promoting the oral bioavailability of biomacromolecules and other biologically active compounds with low permeability propertie

Use of time-of-flight mass spectrometry for large screening of organic pollutants in surface waters and soils from a rice production area in Colombia

The irrigate district of Usosaldaña, an important agricultural area in Colombia mainly devoted to rice crop production, is subjected to an intensive use of pesticides. Monitoring these compounds is necessary to know the impact of phytosanitary products in the different environmental compartments. In this work, surface water and soil samples from different sites of this area have been analyzed by applying an analytical methodology for large screening based on the use of time-of-flight mass spectrometry (TOF MS) hyphenated to liquid chromatography (LC) and gas chromatography (GC). Several pesticides were detected and unequivocally identified, such as the herbicides atrazine, diuron or clomazone. Some of their main metabolites and/or transformation products (TPs) like deethylatrazine (DEA), deisopropylatrazine (DIA) and 3,4-dichloroaniline were also identified in the samples. Among fungicides, carbendazim, azoxystrobin, propiconazole and epoxiconazole were the most frequently detected. Insecticides such as thiacloprid, or p,p′-DDT metabolites (p,p′-DDD and p,p′-DDE) were also found. Thanks to the accurate-mass full-spectrum acquisition in TOF MS it was feasible to widen the number of compounds to be investigated to other families of contaminants. This allowed the detection of emerging contaminants, such as the antioxidant 3,5-di-tertbutyl-4-hydroxy-toluene (BHT), its metabolite 3,5-di-tert-butyl-4-hydroxy-benzaldehyde (BHT-CHO), or the solar filter benzophenone, among other

Clinical factors associated with high glycemic variability defined by coefficient of variation in patients with type 2 diabetes

Antecedentes: La Variabilidad Glucémica Alta (VHG) ha convertirse en un predictor más fuerte de hipoglucemia. Sin embargo, aún se desconocen los factores clínicos asociados con el VHG. Objetivo:Determinar las variables clínicas que se asociaron con un coeficiente de variación (CV) superior al 36% evaluado mediante monitorización continua de glucosa (MCG) en un grupo de pacientes con diabetes mellitus. Métodos: Se evaluó una cohorte de pacientes con diabetes tipo 2 (T2D). Se evaluaron variables demográficas, HbA1c, tasa de filtración glomerular (TFG) y régimen de tratamiento. Se realizó un análisis bivariado, para evaluar la asociación entre la variable resultado (CV > 36%) y cada una de las variables independientes. Se construyó un modelo multivariado para evaluar las asociaciones después de controlar las variables de confusión. Resultados:Se analizaron los datos de MCG de 274 pacientes. CV> 36% estuvo presente en 56 pacientes (20,4%). En el análisis bivariado se incluyeron variables demográficas y clínicas, como tiempo desde el diagnóstico, antecedente de hipoglucemia, A1c, FG y tratamiento instaurado. En el análisis multivariante, FG 9% (OR 2,81; IC 1,05,7,51; p:0,04) y antecedentes de hipoglucemia (OR 2,09; IC 1,02, 4,32; p: 0,04) se asociaron con VHG. El tratamiento con iDPP4 (OR 0,39; IC 0,19, 0,82; p: 0,01) y AGLP1 (OR 0,08; IC 0,01, 0,68; p: 0,02) se asoció inversamente con la VG. Conclusión:Variables clínicas como FG 9% y antecedentes de hipoglucemia se asocian a un VG alto. Nuestros datos sugieren que el uso de tecnología y tratamientos capaces de reducir la variabilidad glucémica podría ser útil en esta población para reducir el riesgo de hipoglucemia y mejorar el control glucémico.Q3Background: High glycemic Variability (HGV) has become a stronger predictor of hypoglycemia. However, clinical factors associate with HGV still are unknown. Objective: To determine clinical variables that were associated with a coefficient of variation (CV) above 36% evaluated by continuous glucose monitoring (CGM) in a group of patients with diabetes mellitus. Methods: A cohort of patients with type 2 diabetes (T2D) was evaluated. Demographic variables, HbA1c, glomerular filtration rate (GFR) and treatment regimen were assessed. A bivariate analysis was performed, to evaluate the association between the outcome variable (CV> 36%) and each of the independent variables. A multivariate model was constructed to evaluate associations after controlling for confounding variables. Results: CGM data from 274 patients were analyzed. CV> 36% was present in 56 patients (20.4%). In the bivariate analysis, demographic and clinical variables were included, such as time since diagnosis, hypoglycemia history, A1c, GFR and treatment established. In the multivariate analysis, GFR 9% (OR 2.81; CI 1.05,7.51; p:0.04) and hypoglycemia history (OR 2.09; CI 1.02,4.32; p:0.04) were associated with HGV. Treatment with iDPP4 (OR 0.39; CI 0.19,0.82; p:0.01) and AGLP1 (OR 0.08; CI 0.01,0.68; p:0.02) was inversely associated with GV. Conclusion: Clinical variables such as GFR 9% and a history of hypoglycemia are associated with a high GV. Our data suggest that the use of technology and treatments able to reduce glycemic variability could be useful in this population to reduce the risk of hypoglycemia and to improve glycemic control.Revista Internacional - Indexad

Transcriptome Profiling of the Intoxication Response of Tenebrio molitor Larvae to Bacillus thuringiensis Cry3Aa Protoxin

Bacillus thuringiensis (Bt) crystal (Cry) proteins are effective against a select number of insect pests, but improvements are needed to increase efficacy and decrease time to mortality for coleopteran pests. To gain insight into the Bt intoxication process in Coleoptera, we performed RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that consumed either a control diet or a diet containing Cry3Aa protoxin. Approximately 134,090 and 124,287 sequence reads from the control and Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated with mitochondrial respiration, signalling, maintenance of cell structure, membrane integrity, protein recycling/synthesis, and glycosyl hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid synthesis. Microarray analysis was used to evaluate temporal changes in gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of the RNA-Seq data. Of the three intoxication intervals, larvae demonstrated more differential expression of transcripts after 12 h exposure to Cry3Aa. Gene expression examined by three different methods in control vs. Cry3Aa-treated larvae at the 24 h time point indicated that transcripts encoding proteins with chitin-binding domain 3 were the most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the data suggest that T. molitor larvae mount a complex response to Cry3Aa during the initial 24 h of intoxication. Data from this study represent the largest genetic sequence dataset for T. molitor to date. Furthermore, the methods in this study are useful for comparative analyses in organisms lacking a sequenced genome

Pathogenesis of Intradermal Staphylococcal Infections Rabbit Experimental Approach to Natural Staphylococcus aureus Skin Infections

[EN] Despite the enormous efforts made to achieve effective tools that fight against Staphylococcus aureus, the results have not been successful. This failure may be due to the absence of truly representative experimental models. To overcome this deficiency, the present work describes and immunologically characterizes the infection for 28 days, in an experimental low-dose (300 colony-forming units) intradermal model of infection in rabbits, which reproduces the characteristic staphylococcal abscess. Surprisingly, when mutant strains in the genes involved in virulence (J Delta agr, J Delta coa Delta vwb, J Delta hla, and J Delta psm alpha) were inoculated, no strong effect on the severity of lesions was observed, unlike other models that use high doses of bacteria. The inoculation of a human rabbitized (FdltB(r)) strain demonstrated its capacity to generate a similar inflammatory response to a wild-type rabbit strain and, therefore, validated this model for conducting these experimental studies with human strains. To conclude, this model proved reproducible and may be an option of choice to check both wild-type and mutant strains of different origins.Supported by the Spanish Ministry of Economy and Competitiveness (MINECO) grant AGL2014-53405-C2-2-P, the Universidad CEU Cardenal Herrera, and European Union Development Fund (FEDER) Programme PO FEDER 2007-2013. A.M.-S., A.G.-Q., and E.M.-G. receive fellowship support from the Universidad CEU Cardenal Herrera; S.P.-F. receives fellowship support from the Generalitat Valenciana ACIF/2016/085; and M.P. and E.M.-G. receive fellowship support from the Spanish Ministry of Education, Culture, and Sport AP2010-3907 and FPU17/02708, respectively.Muñoz-Silvestre, A.; Penadés, M.; Selva, L.; Pérez-Fuentes, S.; Moreno Grua, E.; García-Quirós, A.; Pascual Amorós, JJ.... (2020). Pathogenesis of Intradermal Staphylococcal Infections Rabbit Experimental Approach to Natural Staphylococcus aureus Skin Infections. The American Journal of Pathology. 190(6):1188-1210. https://doi.org/10.1016/j.ajpath.2020.01.019S118812101906Kobayashi, S. D., Malachowa, N., & DeLeo, F. R. (2015). Pathogenesis of Staphylococcus aureus Abscesses. The American Journal of Pathology, 185(6), 1518-1527. doi:10.1016/j.ajpath.2014.11.030Lowy, F. D. (2011). HowStaphylococcus aureusAdapts to Its Host. New England Journal of Medicine, 364(21), 1987-1990. doi:10.1056/nejmp1100251Peschel, A., & Otto, M. (2013). Phenol-soluble modulins and staphylococcal infection. Nature Reviews Microbiology, 11(10), 667-673. doi:10.1038/nrmicro3110Von Eiff, C., Becker, K., Machka, K., Stammer, H., & Peters, G. (2001). Nasal Carriage as a Source ofStaphylococcus aureusBacteremia. New England Journal of Medicine, 344(1), 11-16. doi:10.1056/nejm200101043440102Saïd-Salim, B., Dunman, P. M., McAleese, F. M., Macapagal, D., Murphy, E., McNamara, P. J., … Kreiswirth, B. N. (2003). Global Regulation of Staphylococcus aureus Genes by Rot. Journal of Bacteriology, 185(2), 610-619. doi:10.1128/jb.185.2.610-619.2003Gao, J., & Stewart, G. C. (2004). Regulatory Elements of the Staphylococcus aureus Protein A (Spa) Promoter. Journal of Bacteriology, 186(12), 3738-3748. doi:10.1128/jb.186.12.3738-3748.2004Fridkin, S. K., Hageman, J. C., Morrison, M., Sanza, L. T., Como-Sabetti, K., Jernigan, J. A., … Farley, M. M. (2005). Methicillin-ResistantStaphylococcus aureusDisease in Three Communities. New England Journal of Medicine, 352(14), 1436-1444. doi:10.1056/nejmoa043252DeLeo, F. R., Otto, M., Kreiswirth, B. N., & Chambers, H. F. (2010). Community-associated meticillin-resistant Staphylococcus aureus. The Lancet, 375(9725), 1557-1568. doi:10.1016/s0140-6736(09)61999-1Talan, D. A., Krishnadasan, A., Gorwitz, R. J., Fosheim, G. E., Limbago, B., … Albrecht, V. (2011). Comparison of Staphylococcus aureus From Skin and Soft-Tissue Infections in US Emergency Department Patients, 2004 and 2008. Clinical Infectious Diseases, 53(2), 144-149. doi:10.1093/cid/cir308Bae, I.-G., Tonthat, G. T., Stryjewski, M. E., Rude, T. H., Reilly, L. F., Barriere, S. L., … Fowler, V. G. (2009). Presence of Genes Encoding the Panton-Valentine Leukocidin Exotoxin Is Not the Primary Determinant of Outcome in Patients with Complicated Skin and Skin Structure Infections Due to Methicillin-Resistant Staphylococcus aureus  : Results of a Multinational Trial. Journal of Clinical Microbiology, 47(12), 3952-3957. doi:10.1128/jcm.01643-09Kennedy, A. D., Wardenburg, J. B., Gardner, D. J., Long, D., Whitney, A. R., Braughton, K. R., … DeLeo, F. R. (2010). Targeting of Alpha‐Hemolysin by Active or Passive Immunization Decreases Severity of USA300 Skin Infection in a Mouse Model. The Journal of Infectious Diseases, 202(7), 1050-1058. doi:10.1086/656043Viana, D., Selva, L., Segura, P., Penadés, J. R., & Corpa, J. M. (2007). Genotypic characterization of Staphylococcus aureus strains isolated from rabbit lesions. Veterinary Microbiology, 121(3-4), 288-298. doi:10.1016/j.vetmic.2006.12.003Viana, D., Comos, M., McAdam, P. R., Ward, M. J., Selva, L., Guinane, C. M., … Penadés, J. R. (2015). A single natural nucleotide mutation alters bacterial pathogen host tropism. Nature Genetics, 47(4), 361-366. doi:10.1038/ng.3219Jung, E. C., & Maibach, H. I. (2014). Animal models for percutaneous absorption. Journal of Applied Toxicology, 35(1), 1-10. doi:10.1002/jat.3004Malachowa, N., Kobayashi, S. D., Porter, A. R., Braughton, K. R., Scott, D. P., Gardner, D. J., … DeLeo, F. R. (2016). Contribution of Staphylococcus aureus Coagulases and Clumping Factor A to Abscess Formation in a Rabbit Model of Skin and Soft Tissue Infection. PLOS ONE, 11(6), e0158293. doi:10.1371/journal.pone.0158293Le, V. T. M., Tkaczyk, C., Chau, S., Rao, R. L., Dip, E. C., Pereira-Franchi, E. P., … Diep, B. A. (2016). Critical Role of Alpha-Toxin and Protective Effects of Its Neutralization by a Human Antibody in Acute Bacterial Skin and Skin Structure Infections. Antimicrobial Agents and Chemotherapy, 60(10), 5640-5648. doi:10.1128/aac.00710-16Otto, M. (2014). Staphylococcus aureus toxins. Current Opinion in Microbiology, 17, 32-37. doi:10.1016/j.mib.2013.11.004Collins, L. V., Kristian, S. A., Weidenmaier, C., Faigle, M., van Kessel, K. P. M., van Strijp, J. A. G., … Peschel, A. (2002). Staphylococcus aureusStrains Lackingd‐Alanine Modifications of Teichoic Acids Are Highly Susceptible to Human Neutrophil Killing and Are Virulence Attenuated in Mice. The Journal of Infectious Diseases, 186(2), 214-219. doi:10.1086/341454Novick, R. P. (1991). [27] Genetic systems in Staphylococci. Bacterial Genetic Systems, 587-636. doi:10.1016/0076-6879(91)04029-nLindsay, J. A., Ruzin, A., Ross, H. F., Kurepina, N., & Novick, R. P. (1998). The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands inStaphylococcus aureus. Molecular Microbiology, 29(2), 527-543. doi:10.1046/j.1365-2958.1998.00947.xArnaud, M., Chastanet, A., & Débarbouillé, M. (2004). New Vector for Efficient Allelic Replacement in Naturally Nontransformable, Low-GC-Content, Gram-Positive Bacteria. Applied and Environmental Microbiology, 70(11), 6887-6891. doi:10.1128/aem.70.11.6887-6891.2004Úbeda, C., Maiques, E., Knecht, E., Lasa, Í., Novick, R. P., & Penadés, J. R. (2005). Antibiotic-induced SOS response promotes horizontal dissemination of pathogenicity island-encoded virulence factors in staphylococci. Molecular Microbiology, 56(3), 836-844. doi:10.1111/j.1365-2958.2005.04584.xLi, M., Cheung, G. Y. C., Hu, J., Wang, D., Joo, H., DeLeo, F. R., & Otto, M. (2010). Comparative Analysis of Virulence and Toxin Expression of Global Community‐Associated Methicillin‐ResistantStaphylococcus aureusStrains. The Journal of Infectious Diseases, 202(12), 1866-1876. doi:10.1086/657419Bunce, C., Wheeler, L., Reed, G., Musser, J., & Barg, N. (1992). Murine model of cutaneous infection with gram-positive cocci. Infection and Immunity, 60(7), 2636-2640. doi:10.1128/iai.60.7.2636-2640.1992Voyich, J. M., Otto, M., Mathema, B., Braughton, K. R., Whitney, A. R., Welty, D., … DeLeo, F. R. (2006). Is Panton‐Valentine Leukocidin the Major Virulence Determinant in Community‐Associated Methicillin‐ResistantStaphylococcus aureusDisease? The Journal of Infectious Diseases, 194(12), 1761-1770. doi:10.1086/509506Jeklova, E., Leva, L., & Faldyna, M. (2007). Lymphoid organ development in rabbits: Major lymphocyte subsets. Developmental & Comparative Immunology, 31(6), 632-644. doi:10.1016/j.dci.2006.10.002Guerrero, I., Ferrian, S., Blas, E., Pascual, J. J., Cano, J. L., & Corpa, J. M. (2011). Evolution of the peripheral blood lymphocyte populations in multiparous rabbit does with two reproductive management rhythms. Veterinary Immunology and Immunopathology, 140(1-2), 75-81. doi:10.1016/j.vetimm.2010.11.017Hulstaert, F., Hannet, I., Deneys, V., Munhyeshuli, V., Reichert, T., De Bruyere, M., & Strauss, K. (1994). Age-Related Changes in Human Blood Lymphocyte Subpopulations. Clinical Immunology and Immunopathology, 70(2), 152-158. doi:10.1006/clin.1994.1023Armand-Lefevre, L., Ruimy, R., & Andremont, A. (2005). Clonal Comparison ofStaphylococcus aureusIsolates from Healthy Pig Farmers, Human Controls, and Pigs. Emerging Infectious Diseases, 11(5), 711-714. doi:10.3201/eid1105.040866Graveland, H., Duim, B., van Duijkeren, E., Heederik, D., & Wagenaar, J. A. (2011). Livestock-associated methicillin-resistant Staphylococcus aureus in animals and humans. International Journal of Medical Microbiology, 301(8), 630-634. doi:10.1016/j.ijmm.2011.09.004Aires-de-Sousa, M. (2017). Methicillin-resistant Staphylococcus aureus among animals: current overview. Clinical Microbiology and Infection, 23(6), 373-380. doi:10.1016/j.cmi.2016.11.002Moreno-Grúa, E., Pérez-Fuentes, S., Muñoz-Silvestre, A., Viana, D., Fernández-Ros, A. B., Sanz-Tejero, C., … Selva, L. (2018). Characterization of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Isolates Obtained From Commercial Rabbitries Located in the Iberian Peninsula. Frontiers in Microbiology, 9. doi:10.3389/fmicb.2018.01812Viana, D., Selva, L., Callanan, J. J., Guerrero, I., Ferrian, S., & Corpa, J. M. (2011). Strains of Staphylococcus aureus and pathology associated with chronic suppurative mastitis in rabbits. The Veterinary Journal, 190(3), 403-407. doi:10.1016/j.tvjl.2010.11.022Cheng, A. G., DeDent, A. C., Schneewind, O., & Missiakas, D. (2011). A play in four acts: Staphylococcus aureus abscess formation. Trends in Microbiology, 19(5), 225-232. doi:10.1016/j.tim.2011.01.007Chen, X., Du, Y., Lin, X., Qian, Y., Zhou, T., & Huang, Z. (2016). CD4 + CD25 + regulatory T cells in tumor immunity. International Immunopharmacology, 34, 244-249. doi:10.1016/j.intimp.2016.03.009Bekeredjian-Ding, I. (2017). Deciphering the significance of the T-cell response to Staphylococcus aureus. Future Microbiology, 12(12), 1023-1026. doi:10.2217/fmb-2017-0138Krishna, S., & Miller, L. S. (2011). Innate and adaptive immune responses against Staphylococcus aureus skin infections. Seminars in Immunopathology, 34(2), 261-280. doi:10.1007/s00281-011-0292-6Liu, Q., Mazhar, M., & Miller, L. S. (2018). Immune and Inflammatory Reponses to Staphylococcus aureus Skin Infections. Current Dermatology Reports, 7(4), 338-349. doi:10.1007/s13671-018-0235-8Miller, L. S., & Cho, J. S. (2011). Immunity against Staphylococcus aureus cutaneous infections. Nature Reviews Immunology, 11(8), 505-518. doi:10.1038/nri3010Terada, M., Tsutsui, H., Imai, Y., Yasuda, K., Mizutani, H., Yamanishi, K., … Nakanishi, K. (2006). Contribution of IL-18 to atopic-dermatitis-like skin inflammation induced by Staphylococcus aureus product in mice. Proceedings of the National Academy of Sciences, 103(23), 8816-8821. doi:10.1073/pnas.0602900103Syed, A. K., Reed, T. J., Clark, K. L., Boles, B. R., & Kahlenberg, J. M. (2015). Staphlyococcus aureus Phenol-Soluble Modulins Stimulate the Release of Proinflammatory Cytokines from Keratinocytes and Are Required for Induction of Skin Inflammation. Infection and Immunity, 83(9), 3428-3437. doi:10.1128/iai.00401-15Laouini, D., Kawamoto, S., Yalcindag, A., Bryce, P., Mizoguchi, E., Oettgen, H., & Geha, R. S. (2003). Epicutaneous sensitization with superantigen induces allergic skin inflammation. Journal of Allergy and Clinical Immunology, 112(5), 981-987. doi:10.1016/j.jaci.2003.07.007Holtfreter, S., Radcliff, F. J., Grumann, D., Read, H., Johnson, S., Monecke, S., … Wiles, S. (2013). Characterization of a Mouse-Adapted Staphylococcus aureus Strain. PLoS ONE, 8(9), e71142. doi:10.1371/journal.pone.0071142Kobayashi, S. D., Malachowa, N., Whitney, A. R., Braughton, K. R., Gardner, D. J., Long, D., … DeLeo, F. R. (2011). Comparative Analysis of USA300 Virulence Determinants in a Rabbit Model of Skin and Soft Tissue Infection. 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Regulation of the transcriptional program by DNA methylation during human αβ T-cell development

© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. Thymocyte differentiation is a complex process involving well-defined sequential developmental stages that ultimately result in the generation of mature T-cells. In this study, we analyzed DNA methylation and gene expression profiles at successive human thymus developmental stages. Gain and loss of methylation occurred during thymocyte differentiation, but DNA demethylation was much more frequent than de novo methylation and more strongly correlated with gene expression. These changes took place in CpG-poor regions and were closely associated with T-cell differentiation and TCR function. Up to 88 genes that encode transcriptional regulators, some of whose functions in T-cell development are as yet unknown, were differentially methylated during differentiation. Interestingly, no reversion of accumulated DNA methylation changes was observed as differentiation progressed, except in a very small subset of key genes (RAG1, RAG2, CD8A, PTCRA, etc.), indicating that methylation changes are mostly unique and irreversible events. Our study explores the contribution of DNA methylation to T-cell lymphopoiesis and provides a fine-scale map of differentially methylated regions associated with gene expression changes. These can lay the molecular foundations for a better interpretation of the regulatory networks driving human thymopoiesis.Plan Nacional de [I+D+I 2008–2011]; Instituto de Salud Carlos III [grant number PI12/02587]; Red Española de Investigación Renal (REDinREN) [grant number RD12/0021/0018 and RD12/0021/0021]; Spanish Ministry of Science and Innovation [grant number SAF2010- 15106 and PLE2009-0110]; European Union [Fondos FEDER]Peer Reviewe

Direct Polyphenol Attachment on the Surfaces of Magnetite Nanoparticles, Using Vitis vinifera, Vaccinium corymbosum, or Punica granatum

This study presents an alternative approach to directly synthesizing magnetite nanoparticles (MNPs) in the presence of Vitis vinifera, Vaccinium corymbosum, and Punica granatum derived from natural sources (grapes, blueberries, and pomegranates, respectively). A modified co-precipitation method that combines phytochemical techniques was developed to produce semispherical MNPs that range in size from 7.7 to 8.8 nm and are coated with a ~1.5 nm thick layer of polyphenols. The observed structure, composition, and surface properties of the MNPs@polyphenols demonstrated the dual functionality of the phenolic groups as both reducing agents and capping molecules that are bonding with Fe ions on the surfaces of the MNPs via –OH groups. Magnetic force microscopy images revealed the uniaxial orientation of single magnetic domains (SMDs) associated with the inverse spinel structure of the magnetite (Fe3O4). The samples’ inductive heating (H0 = 28.9 kA/m, f = 764 kHz), measured via the specific loss power (SLP) of the samples, yielded values of up to 187.2 W/g and showed the influence of the average particle size. A cell viability assessment was conducted via the MTT and NRu tests to estimate the metabolic and lysosomal activities of the MNPs@polyphenols in K562 (chronic myelogenous leukemia, ATCC) cells

Complete Closed Genome Sequence of Nontoxigenic Invasive Corynebacterium diphtheriae bv. mitis Strain ISS 3319

The genome sequence of the human pathogen Corynebacterium diphtheriae bv. mitis strain ISS 3319 was determined and closed in this study. The genome is estimated to have 2,404,936 bp encoding 2,257 proteins. This strain also possesses a plasmid of 1,960 bp