Examining the quality of adolescent–parent relationships among Chilean families

The purpose of this study was to examine if adolescents reports of warm and harsh parenting practices by their mothers and fathers varied as a function of demographic, youth and their mothers or mother figures' individual and family characteristics. Data are from 707 community-dwelling adolescents (mean age=14, SD=1.4) and their mothers or mother figures in Santiago, Chile. Having a warmer relationship with both parents was inversely associated with the adolescents' age and positively associated with adolescents' family involvement and parental monitoring. Both mothers' and fathers' harsh parenting were positively associated with adolescent externalizing behaviors and being male and inversely associated with youth autonomy and family involvement. These findings suggest that net of adolescent developmental emancipation and adolescent behavioral problems, positive relationships with parents, especially fathers, may be nurtured through parental monitoring and creation of an interactive family environment, and can help to foster positive developmental outcomes.http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC3839673&blobtype=pdfAccepted manuscrip

Preparation of human primary macrophages to study the polarization from monocyte-derived macrophages to pro- or anti-inflammatory macrophages at biomaterial interface in vitro

Background/purpose: Testing of dental materials when in contact with innate immune cells has been so far hindered by the lack of proper in vitro models. Human primary monocyte-derived macrophages (MDMs) would be an excellent option to this aim. However, the inability to detach them from the tissue culture plates contrast the possibility to culture them on biomaterials. The goal of the present work is to present and validate an innovative protocol to obtain MDMs from peripheral blood monocytes, and to reseed them in contact with biomaterials without altering their viability and phenotype. Materials and methods: We differentiated MDMs on ultra-low attachment tissue culture plastics and recovered them with specific detachment solution in order to be reseeded on a secondary substrate. Therefore, using biological assays (RT-PCR, Western blot, and immunofluorescence) we compared their phenotype to MDMs differentiated on standard culture plates. Results: Transferred MDMs keep their differentiated M0 resting state, as well as the ability to be polarized into M1 (pro-inflammatory) or M2 (anti-inflammatory) macrophages. Conclusion: These data provide the dental material research community the unprecedented possibility to investigate the immunomodulatory properties of biomaterials for dental application

A note on abscissas of Dirichlet series

[EN] We present an abstract approach to the abscissas of convergence of vector-valued Dirichlet series. As a consequence we deduce that the abscissas for Hardy spaces of Dirichlet series are all equal. We also introduce and study weak versions of the abscissas for scalar-valued Dirichlet series.A. Defant: Partially supported by MINECO and FEDER MTM2017-83262-C2-1-P. A. Pérez: Supported by La Caixa Foundation, MINECO and FEDER MTM2014-57838-C2-1-P and Fundación Séneca - Región de Murcia (CARM 19368/PI/14). P. Sevilla-Peris: Supported by MINECO and FEDER MTM2017-83262-C2-1-P.Defant, A.; Pérez, A.; Sevilla Peris, P. (2019). A note on abscissas of Dirichlet series. Revista de la Real Academia de Ciencias Exactas Físicas y Naturales Serie A Matemáticas. 113(3):2639-2653. https://doi.org/10.1007/s13398-019-00647-yS263926531133Bayart, F.: Hardy spaces of Dirichlet series and their composition operators. Mon. Math. 136(3), 203–236 (2002)Bohnenblust, H.F., Hille, E.: On the absolute convergence of Dirichlet series. Ann Math. 32(3), 600–622 (1931)Bohr, H.: Über die Bedeutung der Potenzreihen unendlich vieler Variablen in der Theorie der Dirichlet–schen Reihen $$\sum \,\frac{a_n}{n^s}$$ ∑ a n n s . Nachr. Ges. Wiss. Göttingen, Math. Phys. Kl., pp. 441–488 (1913)Bonet, J.: Abscissas of weak convergence of vector valued Dirichlet series. J. Funct. Anal. 269(12), 3914–3927 (2015)Carando, D., Defant, A., Sevilla-Peris, P.: Bohr’s absolute convergence problem for $$\cal{H}_p$$ H p -Dirichlet series in Banach spaces. Anal. PDE 7(2), 513–527 (2014)Carando, D., Defant, A., Sevilla-Peris, P.: Some polynomial versions of cotype and applications. J. Funct. Anal. 270(1), 68–87 (2016)Defant, A., García, D., Maestre, M., Pérez-García, D.: Bohr’s strip for vector valued Dirichlet series. Math. Ann. 342(3), 533–555 (2008)Defant, A., García, D., Maestre, M., Sevilla–Peris, P.: Dirichlet Series and Holomorphic Funcions in High Dimensions, vol. 37 of New Mathematical Monographs. Cambridge University Press, Cambridge (2019)Defant, A., Pérez, A.: Optimal comparison of the $$p$$ p -norms of Dirichlet polynomials. Israel J. Math. 221(2), 837–852 (2017)Defant, A., Pérez, A.: Hardy spaces of vector-valued Dirichlet series. Studia Math. 243(1), 53–78 (2018)Diestel, J., Jarchow, H., Tonge, A.: Absolutely summing operators, vol. 43 of Cambridge studies in advanced mathematics. Cambridge University Press, Cambridge (1995)Maurizi, B., Queffélec, H.: Some remarks on the algebra of bounded Dirichlet series. J. Fourier Anal. Appl. 16(5), 676–692 (2010)Queffélec, H., Queffélec, M.: Diophantine approximation and Dirichlet series, vol. 2 of Harish–Chandra research institute lecture notes. Hindustan Book Agency, New Delhi (2013

Effectiveness of hand washing on the removal of iron oxide nanoparticles from human skin ex vivo.

In this study, the effectiveness of washing with soap and water in removing nanoparticles from exposed skin was investigated. Dry, nanoscale hematite (α-Fe javax.xml.bind.JAXBElement@3059c7bd O javax.xml.bind.JAXBElement@2ae40c27 ) or maghemite (γ-Fe javax.xml.bind.JAXBElement@1b3855ef O javax.xml.bind.JAXBElement@384459af ) powder, with primary particle diameters between 20-30 nm, were applied to two samples each of fresh and frozen ex vivo human skin in two independent experiments. The permeation of nanoparticles through skin, and the removal of nanoparticles after washing with soap and water were investigated. Bare iron oxide nanoparticles remained primarily on the surface of the skin, without penetrating beyond the stratum corneum. Skin exposed to iron oxide nanoparticles for 1 and 20 hr resulted in removal of 85% and 90%, respectively, of the original dose after washing. In the event of dermal exposure to chemicals, removal is essential to avoid potential local irritation or permeation across skin. Although manufactured at an industrial scale and used extensively in laboratory experiments, limited data are available on the removal of engineered nanoparticles after skin contact. Our finding raises questions about the potential consequences of nanoparticles remaining on the skin and whether alternative washing methods should be proposed. Further studies on skin decontamination beyond use of soap and water are needed to improve the understanding of the potential health consequences of dermal exposure to nanoparticles

CRISPR/Cas9 DNA cleavage at SNP-derived PAM enables both in vitro and in vivo KRT12 mutation-specific targeting

CRISPR/Cas9-based therapeutics hold the possibility for permanent treatment of genetic disease. The potency and specificity of this system has been used to target dominantly inherited conditions caused by heterozygous missense mutations through inclusion of the mutated base in the short-guide RNA (sgRNA) sequence. This research evaluates a novel approach for targeting heterozygous single-nucleotide polymorphisms (SNPs) using CRISPR/Cas9. We determined that a mutation within KRT12, which causes Meesmann's epithelial corneal dystrophy (MECD), leads to the occurrence of a novel protospacer adjacent motif (PAM). We designed an sgRNA complementary to the sequence adjacent to this SNP-derived PAM and evaluated its potency and allele specificity both in vitro and in vivo. This sgRNA was found to be highly effective at reducing the expression of mutant KRT12 mRNA and protein in vitro. To assess its activity in vivo we injected a combined Cas9/sgRNA expression construct into the corneal stroma of a humanized MECD mouse model. Sequence analysis of corneal genomic DNA revealed non-homologous end-joining repair resulting in frame-shifting deletions within the mutant KRT12 allele. This study is the first to demonstrate in vivo gene editing of a heterozygous disease-causing SNP that results in a novel PAM, further highlighting the potential for CRISPR/Cas9-based therapeutics

A novel role for CRIM1 in the corneal response to UV and pterygium development

Pterygium is a pathological proliferative condition of the ocular surface, characterised by formation of a highly vascularised, fibrous tissue arising from the limbus that invades the central cornea leading to visual disturbance and, if untreated, blindness. Whilst chronic ultraviolet (UV) light exposure plays a major role in its pathogenesis, higher susceptibility to pterygium is observed in some families, suggesting a genetic component. In this study, a Northern Irish family affected by pterygium but reporting little direct exposure to UV was identified carrying a missense variant in CRIM1 NM_016441.2: c.1235 A > C (H412P) through whole-exome sequencing and subsequent analysis. CRIM1 is expressed in the developing eye, adult cornea and conjunctiva, having a role in cell differentiation and migration but also in angiogenesis, all processes involved in pterygium formation. We demonstrate elevated CRIM1 expression in pterygium tissue from additional individual Northern Irish patients compared to unaffected conjunctival controls. UV irradiation of HCE-S cells resulted in an increase in ERK phosphorylation and CRIM1 expression, the latter further elevated by the addition of the MEK1/2 inhibitor, U0126. Conversely, siRNA knockdown of CRIM1 led to decreased UV-induced ERK phosphorylation and increased BCL2 expression. Transient expression of the mutant H412P CRIM1 in corneal epithelial HCE-S cells showed that, unlike wild-type CRIM1, it was unable to reduce the cell proliferation, increased ERK phosphorylation and apoptosis induced through a decrease of BCL2 expression levels. We propose here a series of intracellular events where CRIM1 regulation of the ERK pathway prevents UV-induced cell proliferation and may play an important role in the in the pathogenesis of pterygium