Comportamiento de las genodermatosis en el municipio de San Juan y Martínez

Introduction: genetic diseases and congenital defects constitute the second cause of death only in the child of one year; these diseases can be of chromosomal, multifactorial and monogenetic origin. Genodermatoses are included in the last one, where the early diagnosis influences on the prognosis of life of the genetic carrier.Objective: to characterize the behavior of genodermatoses in San Juan y Martinez municipality in the period 2018-2019.Methods: a descriptive, cross-sectional research was conducted, with a target group comprising 476 patients with genetic diseases and a sample of 40 patients with genodermatoses; working with the variables of age, sex, color of skin, family history, type of genodermatosis and type of hereditary patterns, through the collection of data for the review of clinical histories.    Results: it was recorded that 83,3 % belonged to male sex, white skin color prevailed (78 %), 29 patients had no family history, ichthyosis (27,5 %) predominated, and autosomal dominant hereditary pattern was the most frequent (70 %). Conclusions: genetic diseases are gaining a greater position in society every day, as a result preventive actions must be taken, starting from the Primary Health Care in order to counteract its incidence and improve the quality of life of the patients. Introducción: las enfermedades genéticas y defectos congénitos constituyen la segunda causa de muerte en menores de un año, conociendo que estas enfermedades pueden ser de origen cromosómico, multifactorial y monogénicas. En esta última se incluyen las genodermatosis, donde el diagnóstico precoz influye en el pronóstico de vida del paciente que la contrae.Objetivo: caracterizar el comportamiento de las genodermatosis en el municipio de San Juan y Martínez en el período 2018-2019.Métodos: se realizó una investigación descriptiva y transversal, con un universo de 476 pacientes con enfermedades genéticas y una muestra de 40 pacientes con genodermatosis. Se trabajó con las variables: edad, sexo, color de la piel, antecedentes familiares, tipo de genodermatosis y tipo de patrones de herencia, mediante la obtención de datos por la revisión de historias clínicas.Resultados: se obtuvo que el 83,3 % pertenecían al sexo masculino, predominó el color de la piel blanca con un 78 %, 29 pacientes no tuvieron antecedentes patológicos familiares, predominaron las ictiosis con un 27,5 %, y el patrón de herencia más frecuente fue el autosómico dominante con un 70 %.Conclusiones: las enfermedades genéticas cada día ganan un lugar mayor en la sociedad, por lo que se deben intensificar las acciones preventivas desde la atención primaria de salud, para así contrarrestar su incidencia y mejorar la calidad de vida de los pacientes

Comportamiento de las genodermatosis en el municipio de San Juan y Martínez

Introduction: genetic diseases and congenital defects constitute the second cause of death only in the child of one year; these diseases can be of chromosomal, multifactorial and monogenetic origin. Genodermatoses are included in the last one, where the early diagnosis influences on the prognosis of life of the genetic carrier.Objective: to characterize the behavior of genodermatoses in San Juan y Martinez municipality in the period 2018-2019.Methods: a descriptive, cross-sectional research was conducted, with a target group comprising 476 patients with genetic diseases and a sample of 40 patients with genodermatoses; working with the variables of age, sex, color of skin, family history, type of genodermatosis and type of hereditary patterns, through the collection of data for the review of clinical histories.    Results: it was recorded that 83,3 % belonged to male sex, white skin color prevailed (78 %), 29 patients had no family history, ichthyosis (27,5 %) predominated, and autosomal dominant hereditary pattern was the most frequent (70 %). Conclusions: genetic diseases are gaining a greater position in society every day, as a result preventive actions must be taken, starting from the Primary Health Care in order to counteract its incidence and improve the quality of life of the patients. Introducción: las enfermedades genéticas y defectos congénitos constituyen la segunda causa de muerte en menores de un año, conociendo que estas enfermedades pueden ser de origen cromosómico, multifactorial y monogénicas. En esta última se incluyen las genodermatosis, donde el diagnóstico precoz influye en el pronóstico de vida del paciente que la contrae.Objetivo: caracterizar el comportamiento de las genodermatosis en el municipio de San Juan y Martínez en el período 2018-2019.Métodos: se realizó una investigación descriptiva y transversal, con un universo de 476 pacientes con enfermedades genéticas y una muestra de 40 pacientes con genodermatosis. Se trabajó con las variables: edad, sexo, color de la piel, antecedentes familiares, tipo de genodermatosis y tipo de patrones de herencia, mediante la obtención de datos por la revisión de historias clínicas.Resultados: se obtuvo que el 83,3 % pertenecían al sexo masculino, predominó el color de la piel blanca con un 78 %, 29 pacientes no tuvieron antecedentes patológicos familiares, predominaron las ictiosis con un 27,5 %, y el patrón de herencia más frecuente fue el autosómico dominante con un 70 %.Conclusiones: las enfermedades genéticas cada día ganan un lugar mayor en la sociedad, por lo que se deben intensificar las acciones preventivas desde la atención primaria de salud, para así contrarrestar su incidencia y mejorar la calidad de vida de los pacientes

Epigenetic modifiers as potential therapeutic targets in diabetic kidney disease

Diabetic kidney disease is one of the fastest growing causes of death worldwide. Epigenetic regulators control gene expression and are potential therapeutic targets. There is functional interventional evidence for a role of DNA methylation and the histone post-translational modifications—histone methylation, acetylation and crotonylation—in the pathogenesis of kidney disease, including diabetic kidney disease. Readers of epigenetic marks, such as bromodomain and extra terminal (BET) proteins, are also therapeutic targets. Thus, the BD2 selective BET inhibitor apabetalone was the first epigenetic regulator to undergo phase-3 clinical trials in diabetic kidney disease with an endpoint of kidney function. The direct therapeutic modulation of epigenetic features is possible through pharmacological modulators of the specific enzymes involved and through the therapeutic use of the required substrates. Of further interest is the characterization of potential indirect effects of nephroprotective drugs on epigenetic regulation. Thus, SGLT2 inhibitors increase the circulating and tissue levels of β-hydroxybutyrate, a molecule that generates a specific histone modification, β-hydroxybutyrylation, which has been associated with the beneficial health effects of fasting. To what extent this impact on epigenetic regulation may underlie or contribute to the so-far unclear molecular mechanisms of cardio-and nephroprotection offered by SGLT2 inhibitors merits further in-depth studies.This research was funded by FIS/FEDER funds (PI15/00298, CP14/00133, PI16/01900, PI18/01386, PI18/0133, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071), ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD- 3686 CIFRA2-CM. Salary support: ISCIII Miguel Servet to ABS and MDS-N, ISCIII Sara Borrell to JM-MM, REDinREN RD016/0009 to MF-B, and MICIU to JG-M

Self-assembly and surface behaviour of pure and mixed zwitterionic amphiphiles in a deep eutectic solvent

Recent investigations have shown that deep eutectic solvents provide a suitable environment for self-organisation of biomolecules, in particular phospholipids and proteins. However, the solvation of complex lyophilic moieties by deep eutectic solvents still remains unclear. Here we explore the behaviour of zwitterionic surfactants in choline chloride:glycerol eutectic mixture. Dodecyl-2-(trimethylammonio)ethylphosphate and N-alkyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (alkyl = dodecyl, tetradecyl) surfactants were investigated by means of surface tension, X-ray reflectivity and small-angle neutron scattering. These surfactants were found to remain surface active and form globular micelles in deep eutectic solvents. Still, the surface behaviour of these species was found to differ depending on the headgroup and tail structure. The morphology of the micelles also slightly varies between surfactants, demonstrating differences in the packing of individual monomers. The characteristics of mixtures of the dodecyl surfactants is also reported, showing a deviation from ideal mixing associated with attractive interactions between sulfobetaine and phosphocholine headgroups. Such non-ideality results in variation of the surface behaviour and self-assembly of these surfactant mixtures. The results presented here will potentially lead to the development of new alternatives for drug-delivery, protein solubilisation and biosensing through a better fundamental understanding of the behaviour of zwitterionic surfactants in deep eutectic solvents

Dual ifgMosaic: A Versatile Method for Multispectral and Combinatorial Mosaic Gene-Function Analysis

Improved methods for manipulating and analyzing gene function have provided a better understanding of how genes work during organ development and disease. Inducible functional genetic mosaics can be extraordinarily useful in the study of biological systems; however, this experimental approach is still rarely used in vertebrates. This is mainly due to technical difficulties in the assembly of large DNA constructs carrying multiple genes and regulatory elements and their targeting to the genome. In addition, mosaic phenotypic analysis, unlike classical single gene-function analysis, requires clear labeling and detection of multiple cell clones in the same tissue. Here, we describe several methods for the rapid generation of transgenic or gene-targeted mice and embryonic stem (ES) cell lines containing all the necessary elements for inducible, fluorescent, and functional genetic mosaic (ifgMosaic) analysis. This technology enables the interrogation of multiple and combinatorial gene function with high temporal and cellular resolution.This work was supported by grants to the PI R.B. from the Spanish Ministry of Economy, Industry and Competitiveness (SAF2013-44329-P, SAF2013-42359-ERC, and RYC-2013-13209) and European Research Council (ERC-2014-StG - 638028). S.P.-Q., M.F.-C., and I.G.-G. were supported by PhD fellowships from Fundacion La Caixa (CX-SO-2013-02, CX\_E-2015-01, and CX-SO-16-1, respectively). W.L. by a FP7-PEOPLE-2012-COFUND GA600396 postdoctoral contract. We thank Simon Bartlett for English editing, Ralf H. Adams for sharing the Cdh5(PAC)-CreERT2 mice, Jose Luis de La Pompa for comments throughout the project and for sharing the Tie2-Cre mice, Gonzalo Gancedo for the help with the mouse colony, Valeria Caiolfa for the help with the microscopy, and all the members of the CNIC gene targeting, transgenesis, cellomics, and microscopy units. The CNIC is supported by MEIC/MINECO and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Influence of two polymer-based superplasticizers (poly-naphthalene sulfonate, PNS, and lignosulfonate, LS) on compressive and flexural strength, freeze-thaw, and sulphate attack resistance of lime-metakaolin grouts

A new range of grouts prepared by air lime and metakaolin (MK) as a pozzolanic admixture has been obtained by using as dispersing agents two polymers, namely poly-naphthalene sulfonate (PNS) and lignosulfonate (LS), with the aim of improving the fluidity of the fresh grouts. Fluidity and setting times of the grouts were assessed. Differences in the molecular architecture and in the anionic charge density explained the different adsorption of the polymers and the different performance. The higher anionic charge of PNS and its linear shape explained its better adsorption and effectiveness. The pozzolanic reaction was favoured in grouts with PNS, achieving the highest values of compressive strength (4.8 MPa after 182 curing days). The addition of PNS on lime grouts slightly decreased the frost resistance of the grouts (from 24 freeze-thaw cycles for the polymer-free samples to 19 or 20 cycles with 0.5 or 1 wt % of PNS). After the magnesium sulphate attack, grouts were altered by decalcification of hydrated phases and by formation of hexahydrite and gypsum. A protective role of portlandite against magnesium sulphate attack was clearly identified. Accordingly, the polymer LS, which preserves a significant amount of Ca(OH)2, could be an alternative for the obtaining of grouts requiring high sulphate attack resistance

Hydrophobized lime grouts prepared with microsilica and superplasticizers

This work reports the obtaining of lime-based grouts as repairing materials. Microsilica was added as pozzolanic additive to enhance the compressive strength of the hardened grouts. Sodium oleate, as water repellent admixture, and different superplasticizers were also incorporated to reduce the water absorption and to enhance the injectability of the grouts. Polycarboxylate ether (PCE), polynaphthalene sulfonate (PNS), melamine sulfonate (MMS) and polyacrylic acid (PA) were tested as plasticizing agents. Regarding the fluidity of the grouts, PCE was seen to improve the injectability, followed by PNS, MMS and PA. However, PCE addition was also accompanied by a severe delay in the setting time. The other three superplasticizers did not provoke significant delays in the hardening of the samples. The water contact angle underwent an increase pointing to an effective hydrophobization of the surface as a consequence of the water repellent admixture. The combination with PCE was the most effective in keeping the water repellency in comparison with the control sample (lime grout + oleate). MMS yielded high compressive strengths and durability of the mortars, in the face of freezing-thawing cycles, was enhanced

Evolution of CRISPR-associated endonucleases as inferred from resurrected proteins

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 is an effector protein that targets invading DNA and plays a major role in the prokaryotic adaptive immune system. Although Streptococcus pyogenes CRISPR–Cas9 has been widely studied and repurposed for applications including genome editing, its origin and evolution are poorly understood. Here, we investigate the evolution of Cas9 from resurrected ancient nucleases (anCas) in extinct firmicutes species that last lived 2.6 billion years before the present. We demonstrate that these ancient forms were much more flexible in their guide RNA and protospacer-adjacent motif requirements compared with modern-day Cas9 enzymes. Furthermore, anCas portrays a gradual palaeoenzymatic adaptation from nickase to double-strand break activity, exhibits high levels of activity with both single-stranded DNA and single-stranded RNA targets and is capable of editing activity in human cells. Prediction and characterization of anCas with a resurrected protein approach uncovers an evolutionary trajectory leading to functionally flexible ancient enzymes.This work has been supported by grant nos. PID2019-109087RB-I00 (to R.P.-J.) and RTI2018-101223-B-I00 and PID2021-127644OB-I00 (to L.M.) from the Spanish Ministry of Science and Innovation. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 964764 (to R.P.-J.). The content presented in this document represents the views of the authors, and the European Commission has no liability in respect to the content. We acknowledge financial support from the Spanish Foundation for the Promotion of Research of Amyotrophic Lateral Sclerosis. A.F. acknowledges Spanish Center for Biomedical Network Research on Rare Diseases (CIBERE) intramural funds (no. ER19P5AC756/2021). F.J.M.M. acknowledges research support by Conselleria d’Educació, Investigació, Cultura i Esport from Generalitat Valenciana, research project nos. PROMETEO/2017/129 and PROMETEO/2021/057. M.M. acknowledges funding from CIBERER (grant no. ER19P5AC728/2021). The work has received funding from the Regional Government of Madrid (grant no. B2017/BMD3721 to M.A.M.-P.) and from Instituto de Salud Carlos III, cofounded with the European Regional Development Fund ‘A way to make Europe’ within the National Plans for Scientific and Technical Research and Innovation 2017–2020 and 2021–2024 (nos. PI17/1659, PI20/0429 and IMP/00009; to M.A.M.-P. B.P.K. was supported by an MGH ECOR Howard M. Goodman Award and NIH P01 HL142494

Intrinsically microporous polymer retains porosity in vacuum thermolysis to electroactive heterocarbon

Vacuum carbonization of organic precursors usually causes considerable structural damage and collapse of morphological features. However, for a polymer with intrinsic microporosity (PIM-EA-TB with a Brunauer–Emmet–Teller (BET) surface area of 1027 m2g–1), it is shown here that the rigidity of the molecular backbone is retained even during 500 °C vacuum carbonization, yielding a novel type of microporous heterocarbon (either as powder or as thin film membrane) with properties between those of a conducting polymer and those of a carbon. After carbonization, the scanning electron microscopy (SEM) morphology and the small-angle X-ray scattering (SAXS) Guinier radius remain largely unchanged as does the cumulative pore volume. However, the BET surface area is decreased to 242 m2g–1, but microporosity is considerably increased. The new material is shown to exhibit noticeable electrochemical features including two pH-dependent capacitance domains switching from ca. 33 Fg–1 (when oxidized) to ca. 147 Fg–1 (when reduced), a low electron transfer reactivity toward oxygen and hydrogen peroxide, and a four-point-probe resistivity (dry) of approximately 40 MΩ/square for a 1–2 μm thick film