α,γ-Peptide nanotube templating of one-dimensional parallel fullerene arrangements

(Figure Presented) The formation and full characterization of single self-assembling α,γ-peptide nanotubes (α,γ-SPNs) is described. The introduction of C60 into cyclic peptides allows the preparation of supramolecular 1D fullerene arrangements induced by peptide nanotube formation under appropriate conditions. © 2009 American Chemical Society.This work was supported by the Spanish Ministry of Education and Science and the ERDF [SAF2007-61015 and Consolider Ingenio 2010 (CSD2007-00006)] and the Xunta de Galicia (GRC2006/ 132, PGIDIT06PXIB209018PR, PGIDIT08CSA047209PR, and R2006/ 124). The work by J.M.V. and J.L.C. was supported by Grants BFU2007- 62382/BMC from the Spanish MEC (J.M.V.) and S-0505/MAT/0283 from the Madrid Regional Government (J.M.V. and J.L.C.). C.R. and R.J.B. thank the Spanish MEC for their FPU Fellowships. We also thank Dr. Carmen Serra (Nanotechnology and Surface Analysis Service at C.A.C.T.I., University of Vigo) for her help with STM. We also thank Dowpharma for their kind gift of ENZA enzymes used in the preparation of D-Boc-γ-Acp-OH.Peer reviewe

Revelando la geometría en profundidad de las fallas activas que limitan el valle del Guadalentín mediante sísmica de reflexión de alta resolución: resultados preliminares

[EN]: To produce seismic hazard assessments to the current state-of-the-art, it is essential to characterize the active faults in terms of geometry, interrelation and seismotectonic status. The Guadalentin Depression is the main basin within the Eastern Betic Shear Zone, which corresponds to a NE-SW tectonic corridor bounded by the Carrascoy, Alhama de Murcia and Palomares faults, from north to south. Although a number of active tectonics and paleoseismological studies have been carried out in these faults, almost nothing is known about their geometry at depth. To unveil the deep structure, geometry and upper Neogene deformation history of these faults we have carried out a high-resolution seismic reflection survey. The acquired seismic profiles will allow to improve our understanding of the deep geometry of the known active faults (up to 2 km depth), as well as to identify potential buried branches and will help to reduce the uncertainties in seismic hazard assessment.[ES]: Para producir evaluaciones del peligro sísmico actualizadas al estado del arte actual, es esencial caracterizar las fallas activas de una región en términos de geometría, interrelación y estado sismotectónico. La depresión del Guadalentín es la principal cuenca cuaternaria dentro de la Zona de Cizalla de las Béticas Orientales, la cual corresponde a un corredor tectónico con dirección NE-SW delimitado por las fallas de Carrascoy, Alhama de Murcia y Palomares, de norte a sur. Aunque varios estudios de tectónica activa y paleosismología se han centrado en estas fallas, su geometría en profundidad es bastante incierta. Para revelar la estructura profunda, la geometría y el historial de deformación desde el Neógeno superior de estas fallas, hemos llevado a cabo un estudio de sísmica de reflexión de alta resolución. Los perfiles sísmicos adquiridos permitirán mejorar nuestra comprensión de la geometría profunda de las fallas activas conocidas (hasta 2 km de profundidad), así como identificar posibles ramas ciegas, y ayudarán a reducir las incertidumbres en los cálculos de peligrosidad sísmicaHector Perea es un investigador postdoctoral del programa "Atracción de Talento" en la Universidad Complutense de Madrid financiado por la Comunidad de Madrid (2018-T1/AMB-11039). Paula Herrero y Júlia Molins han estado contratadas por el proyecto UNrIDDLE (2018-T1/AMB-11039). Juan Alcalde ha recibido financiación de las ayudas IJC2018-036074-I financiadas por MCIN/AEI/10.13039/501100011033.Peer reviewe

Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.Instituto Multidisciplinario de Biología Celula

Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.Instituto Multidisciplinario de Biología Celula

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation

To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice

Effect of Organochloride Guest Molecules on the Stability of Homo/Hetero Self-Assembled α,γ-Cyclic Peptide Structures: A Computational Study Toward the Control of Nanotube Length

We present here a molecular dynamics study on peptide nanotubes composed of <i>cis-</i>3-aminocyclohexanecarboxylic acid-(γ-Ach) or <i>cis-</i>3-aminocyclopentanecarboxylic acid (γ-Acp)-based α,γ-cyclohexapeptides and also on those formed by heterodimeric pairs from a combination of the two aforementioned peptides (γ-Ach/Acp), which is the first time that a self-assembling cyclic peptide nanotube composed of heteromeric units is investigated. The main advantage of these types of nanotube is that they have a partially hydrophobic inner cavity, a property that makes them very exciting alternatives to classical nanotubes. In an effort to analyze the fine details of these ensembles, we investigated the dynamical behavior of model dimeric structures that mimic the fundamental repeating structural motif of longer nanotubes. Despite the structural analogy of the β-sheet interaction, our results suggest that extrapolation of the information obtained from those “capped” dimers to nanotube properties has some limitations because several significant differences have been found between the two systems. This finding is not only relevant for α,γ-cyclic peptide nanotubes but also shows that special care should also be taken when considering other related peptide nanotubes in which N-methylated dimers are used to obtain information about the stability and formation of the nanotubes. The structural and dynamical behavior of dimers and nanotubes in nonpolar (chloroform) and polar protic solvents (water) has been analyzed using state-of-the-art theoretical methods. A marked destabilizing effect on the structure was observed in aqueous solution for all systems studied, suggesting that most of the water molecules that compete for the hydrogen bonds are those that occupy the internal cavity. We show that the introduction of organochloride molecules within the dimers and nanotubes is stabilized in water, and this property opens the door to a large number of possible future applications that are an important challenge in the field of molecular self-assembly, such as in drug delivery processes to control nanotube length by means of appropriate guests. A precise control of the nanotube length can be envisaged from the MD simulations of the encapsulation of 1,2-bis­[2-(2,2,2-trichloroethoxy)­ethoxy]­ethane inside its inner cavity, opening a very interesting possibility in this area