Intracellular pathways involved in bone regeneration triggered by recombinant silk-silica chimeras

Biomineralization at the organic-inorganic interface is critical to many biology material functions in vitro and in vivo. Recombinant silk-silica fusion peptides are organic-inorganic hybrid material systems that can be effectively used to study and control biologically-mediated mineralization due to the genetic basis of sequence control. However, to date, the mechanisms by which these functionalized silk-silica proteins trigger the differentiation of human mesenchymal stem cells (hMSCs) to osteoblasts remain unknown. To address this challenge, we analyzed silk-silica surfaces for silica-hMSC receptor binding and activation, and the intracellular pathways involved in the induction of osteogenesis on these bioengineered biomaterials. The induction of gene expression of αVβ3 integrin, all three Mitogen-activated Protein Kinsases (MAPKs) as well as c-Jun, Runt-related Transcription Factor 2 (Runx2) and osteoblast marker genes was demonstrated upon growth of the hMSCs on the silk-silica materials. This induction of key markers of osteogenesis correlated with the content of silica on the materials. Moreover, computational simulations were performed for silk/silica-integrin binding which showed activation of αVβ3 integrin in contact with silica. This integrated computational and experimental approach provides insight into interactions that regulate osteogenesis towards more efficient biomaterial designs

Seroprevalence of HCV and HIV infections by year of birth in Spain: impact of US CDC and USPSTF recommendations for HCV and HIV testing

Instituto de Salud Carlos III; CP08/00214Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM13/0032

Biomedical and therapeutic applications of biosurfactants

During the last years, several applications of biosurfactants with medical purposes have been reported. Biosurfactants are considered relevant molecules for applications in combating many diseases and as therapeutic agents due to their antibacterial, antifungal and antiviral activities. Furthermore, their role as anti-adhesive agents against several pathogens illustrate their utility as suitable anti-adhesive coating agents for medical insertional materials leading to a reduction of a large number of hospital infections without the use of synthetic drugs and chemicals. Biomedical and therapeutic perspectives of biosurfactants applications are presented and discussed in this chapter

Materialistic cues make us miserable: A meta‐analysis of the experimental evidence for the effects of materialism on individual and societal well‐being

open access articleConsumer‐oriented societies are awash with materialistic messages that link happiness and success to wealth and consumption. However, despite extensive research evidence that dispositional materialistic orientations are correlated with lower well‐being, the effects of materialistic cues on the well‐being of individuals and social groups have not been examined. The present research meta‐analytically reviews the experimental evidence for the causal effects of materialism on two dimensions of well‐being: (a) individual and (b) societal. We included 27 independent studies that met the inclusion criteria of priming materialism and measuring well‐being (N = 3,649), containing a total of 62 effect sizes. Multilevel modeling revealed that materialism has an effect on both individual (δ = −0.39) and societal well‐being (δ = −0.41), suggesting that materialistic cues cause lower well‐being. Moderation effects suggested that materialistic cues might have a higher effect on interpersonal well‐being than on self‐evaluation indicators. We discuss the limitations of the current evidence, highlight the research gaps and underdeveloped areas, and provide recommendations such as minimum sample size for future experimental work, since the advancement of this area will help us to gain a better understanding of the impact of consumer‐oriented societies on the well‐being of individuals and social groups

Novel CYP4F22 mutations associated with autosomal recessive congenital ichthyosis (ARCI). Study of the CYP4F22 c.1303C>T founder mutation

Mutations in CYP4F22 cause autosomal recessive congenital ichthyosis (ARCI). However, less than 10% of all ARCI patients carry a mutation in CYP4F22. In order to identify the molecular basis of ARCI among our patients (a cohort of ninety-two Spanish individuals) we performed a mutational analysis using direct Sanger sequencing in combination with a multigene targeted NGS panel. From these, eight ARCI families (three of them with Moroccan origin) were found to carry five different CYP4F22 mutations, of which two were novel. Computational analysis showed that the mutations found were present in highly conserved residues of the protein and may affect its structure and function. Seven of the eight families were carriers of a highly recurrent CYP4F22 variant, c.1303C>T; p.(His435Tyr). A 12Mb haplotype was reconstructed in all c.1303C>T carriers by genotyping ten microsatellite markers flanking the CYP4F22 gene. A prevalent 2.52Mb haplotype was observed among Spanish carrier patients suggesting a recent common ancestor. A smaller core haplotype of 1.2Mb was shared by Spanish and Moroccan families. Different approaches were applied to estimate the time to the most recent common ancestor (TMRCA) of carrier patients with Spanish origin. The age of the mutation was calculated by using DMLE and BDMC2. The algorithms estimated that the c.1303C>T variant arose approximately 2925 to 4925 years ago, while Spanish carrier families derived from a common ancestor who lived in the XIII century. The present study reports five CYP4F22 mutations, two of them novel, increasing the number of CYP4F22 mutations currently listed. Additionally, our results suggest that the recurrent c.1303C>T change has a founder effect in Spanish population and c.1303C>T carrier families originated from a single ancestor with probable African ancestry

Biogeographical origin and timing of the founder ichthyosis TGM1 c.1187G > A mutation in an isolated Ecuadorian population

An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabi. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in Ecuadorian patients and population matched controls, we were able to estimate the age of c.1187G > A and the time to their most recent common ancestor (TMRCA) of c.1187G > A Ecuadorian carriers. While the estimated mutation age is 41 generations ago (~1,025 years ago [ya]), the TMRCA of Ecuadorian c.1187G > A carrier haplotypes dates to just 17 generations (~425 ya). Probabilistic-based inferences of local ancestry allowed us to infer a most likely European origin of a few (16% to 30%) Ecuadorian haplotypes carrying this mutation. In addition, inferences on demographic historical changes based on c.1187G > A Ecuadorian carrier haplotypes estimated an exponential population growth starting ~20 generations, compatible with a recent founder effect occurring in Manabi. Two main hypotheses can be considered for the origin of c.1187G > A: (i) the mutation could have arisen in Spain >1,000 ya (being Galicia the possible homeland) and then carried to Ecuador by Spaniards in colonial times ~400 ya, and (ii) two independent mutational events originated this mutation in Ecuador and Galicia. The geographic and cultural characteristics of Manabi could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region

Impacto da adição de caulim nas propriedades físico-mecânicas do papel formado por sequências ECF

The paper industry is the main global consumer of kaolin. It is mostly used as paper filler, due to its lower cost as compared to pulp cost. Color removal process from pulp - chemical bleaching - determines final pulp's characteristics. Effort has been made to make possible to obtain less toxic bleaching processes. This study aims to evaluate the influence of three bleaching sequences, on kaolin retention and paper properties. Industrial eucalyptus kraft pulp, oxygen pre-delignified, was bleached by the sequences D(E+P)DP (reference), A HT(E+P)DP (ECF-A) and A HT D(E+P)P (ECF-Light). Kaolin was added to the pulps after its refining in PFI mill to 40°SR, corresponding to an amount of 20% weighted kaolin for each handsheet. The results showed the addition of 20% kaolin significantly presented lower retention for ECF-Light sample, remaining reference sequence equal to A-ECF sequence; the higher the fines content, the greater the retention load; the ECF-Light sequence showed higher cost, lower tear resistance and low internal resistance of fibers; smoothness and compression were not influenced by bleaching sequence or by adding kaolin.A indústria de papel é a principal consumidora de caulim. Sua maior utilização no papel é como enchimento, pelo fato de ser mais barato do que a polpa celulósica. O processo de remoção de cor da celulose conhecido como branqueamento é determinante nas características da polpa final. Muito esforço tem sido feito para que processos de branqueamento menos tóxicos sejam viabilizados. No presente trabalho, objetivou-se avaliar a influência de três sequências de branqueamento de polpa kraft de eucalipto na retenção de caulim e nas propriedades do papel formado. A polpa industrial de eucalipto pré-deslignificada com oxigênio foi branqueada pelas sequências D(E+P)DP (referência), A HT D(E+P)DP (A-ECF) e A HT D(E+P)P (ECF-Light). O caulim foi adicionado às polpas celulósicas após seu refino em moinho PFI para 40°SR, correspondendo a uma quantidade mássica de 20% de caulim para cada folha formada. Os resultados apontaram que a adição de 20% de caulim apresentou retenção significativamente menor para a amostra ECF-Light, permanecendo a sequência referência igual à A-ECF; quanto maior o teor de finos, maior foi a retenção da carga; a sequência ECF-Light apresentou maior custo, menor resistência ao rasgo e menor resistência interna das fibras; a lisura e a compressão não foram influenciadas pela escolha da sequência de branqueamento, tanto quanto pela adição de caulim.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Estadual PaulistaUniversidade Estadual Paulist

ACRATA: a novel electron transfer domain associated to apoptosis and cancer

BACKGROUND: Recently, several members of a vertebrate protein family containing a six trans-membrane (6TM) domain and involved in apoptosis and cancer (e.g. STEAP, STAMP1, TSAP6), have been identified in Golgi and cytoplasmic membranes. The exact function of these proteins remains unknown. METHODS: We related this 6TM domain to distant protein families using intermediate sequences and methods of iterative profile sequence similarity search. RESULTS: Here we show for the first time that this 6TM domain is homolog to the 6TM heme binding domain of both the NADPH oxidase (Nox) family and the YedZ family of bacterial oxidoreductases. CONCLUSIONS: This finding gives novel insights about the existence of a previously undetected electron transfer system involved in apoptosis and cancer, and suggests further steps in the experimental characterization of these evolutionarily related families

Influence of very low doses of mediators on fungal laccase activity - nonlinearity beyond imagination

Laccase, an enzyme responsible for aerobic transformations of natural phenolics, in industrial applications requires the presence of low-molecular substances known as mediators, which accelerate oxidation processes. However, the use of mediators is limited by their toxicity and the high costs of exploitation. The activation of extracellular laccase in growing fungal culture with highly diluted mediators, ABTS and HBT is described. Two high laccase-producing fungal strains, Trametes versicolor and Cerrena unicolor, were used in this study as a source of enzyme. Selected dilutions of the mediators significantly increased the activity of extracellular laccase during 14 days of cultivation what was distinctly visible in PAGE technique and in colorimetric tests. The same mediator dilutions increased demethylation properties of laccase, which was demonstrated during incubation of enzyme with veratric acid. It was established that the activation effect was assigned to specific dilutions of mediators. Our dose-response dilution process smoothly passes into the range of action of homeopathic dilutions and is of interest for homeopaths

The Nutritional Induction of COUP-TFII Gene Expression in Ventromedial Hypothalamic Neurons Is Mediated by the Melanocortin Pathway

BACKGROUND: The nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an important coordinator of glucose homeostasis. We report, for the first time, a unique differential regulation of its expression by the nutritional status in the mouse hypothalamus compared to peripheral tissues. METHODOLOGY/PRINCIPAL FINDINGS: Using hyperinsulinemic-euglycemic clamps and insulinopenic mice, we show that insulin upregulates its expression in the hypothalamus. Immunofluorescence studies demonstrate that COUP-TFII gene expression is restricted to a subpopulation of ventromedial hypothalamic neurons expressing the melanocortin receptor. In GT1-7 hypothalamic cells, the MC4-R agonist MTII leads to a dose dependant increase of COUP-TFII gene expression secondarily to a local increase in cAMP concentrations. Transfection experiments, using a COUP-TFII promoter containing a functional cAMP responsive element, suggest a direct transcriptional activation by cAMP. Finally, we show that the fed state or intracerebroventricular injections of MTII in mice induce an increased hypothalamic COUP-TFII expression associated with a decreased hepatic and pancreatic COUP-TFII expression. CONCLUSIONS/SIGNIFICANCE: These observations strongly suggest that hypothalamic COUP-TFII gene expression could be a central integrator of insulin and melanocortin signaling pathway within the ventromedial hypothalamus. COUP-TFII could play a crucial role in brain integration of circulating signal of hunger and satiety involved in energy balance regulation