25 research outputs found

    Redox-active and DNA-binding coordination complexes of clotrimazole

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    DNA interactions of anticancer mononuclear Cu2+, Co2+, Zn2+, and Ni2+ complexes with the biologically active ligand clotrimazole (clotri) are reported. To fully characterize DNA binding modes for these complexes of the formulae [M(clotri)2Cl2]·nH2O (1–4), [M(clotri)2Br2]·nH2O (5,6), [M(clotri)3NO3]NO3·nH2O (9), and [M(clotri)3(NO3)2] (10), circular dichroism (CD) and linear dichroism (LD) spectroscopy, UV melting experiments, atomic force microscopy (AFM) and ethidium bromide (EtBr) displacement methods were used. Results indicate mixed electrostatic interactions, possibly through groove binding, that result in accretion and coiling of DNA. Electrochemical studies indicate that the Cu2+ complex 9 readily reduces to the reactive-oxygen-species-generating Cu+, which oxidatively damages DNA. There is a subtle correlation between log P values, calculated electrostatic potentials, and cytotoxicity of the complexes. The extent of cell-nucleus DNA-metal adduct formation in the HeLa cervix-uterine carcinoma cell line does not necessarily correlate with cytotoxicity, indicating that the nature of DNA lesions may be crucial to activity

    Early Pleistocene faunivorous hominins were not kleptoparasitic, and this impacted the evolution of human anatomy and socio-ecology

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    Humans are unique in their diet, physiology and socio-reproductive behavior compared to other primates. They are also unique in the ubiquitous adaptation to all biomes and habitats. From an evolutionary perspective, these trends seem to have started about two million years ago, coinciding with the emergence of encephalization, the reduction of the dental apparatus, the adoption of a fully terrestrial lifestyle, resulting in the emergence of the modern anatomical bauplan, the focalization of certain activities in the landscape, the use of stone tools, and the exit from Africa. It is in this period that clear taphonomic evidence of a switch in diet with respect to Pliocene hominins occurred, with the adoption of carnivory. Until now, the degree of carnivorism in early humans remained controversial. A persistent hypothesis is that hominins acquired meat irregularly (potentially as fallback food) and opportunistically through klepto-foraging. Here, we test this hypothesis and show, in contrast, that the butchery practices of early Pleistocene hominins (unveiled through systematic study of the patterning and intensity of cut marks on their prey) could not have resulted from having frequent secondary access to carcasses. We provide evidence of hominin primary access to animal resources and emphasize the role that meat played in their diets, their ecology and their anatomical evolution, ultimately resulting in the ecologically unrestricted terrestrial adaptation of our species. This has major implications to the evolution of human physiology and potentially for the evolution of the human brain

    Los Batanes: A trap for the Pyrenean wild goat during the Late Pleistocene (Spain)

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    Los Batanes cave (1025 m.a.s.l.) is a karstic system formed by pressure ducts, near the locality of Biescas in the Upper Gallego Valley (Huesca, Spain). Many fossil remains were retrieved from the cave sediments. The minimum sediment calendar age was determined to be 12.770 ± 60 BP. This date indicates that the deposit was formed before the Late Pleistocene-Early Holocene transition at the Pyrenees. Here we analyze the faunal assemblage of the site that is only conformed by remains of Pyrenean wild goat (Capra pyrenaica pyrenaica), which is a recently extinct subspecies of Iberian wild goat (C. pyrenaica). In the site, 1079 remains of Iberian wild goat have been recovered being one of the most numerous both in minimum number of individuals (MNI) and number of identified specimens (NISP) recovered until now in a natural trap in the Spanish Pyrenees. The population of Los Batanes shows a wide range of ages between juvenile and senile individuals and the MNI estimated from the number of right metatarsus is nine. The taphonomic features indicate that the cave acted as a trap for the goats which inhabited the vicinity of the cave. These goats probably stumbled and fell to the bottom of the pit and they could not get out, dying inside. Due to the origin of the accumulation numerous complete bones have been recovered. These fossil allow us to perform a biometric analysis that indicates that population of Los Batanes is in the range size of other goats from Late Pleistocene of Iberian Peninsula

    Now, the part of intuition. Research, Art and Creation, 2018

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    Catálogo de Exposición del Máster en Investigación en Arte y Creación de la UCM. Muestra celebrada del 25 de septiembre al 10 de octubre de 2018 en la Sala de Exposiciones de la Facultad de Bellas Artes. C / Pintor el Greco 2, Ciudad Universitaria. 28040 Madrid. Comisariado de Javier Mañero Rodicio.Exhibition catalog of the Master in Art and Creation Research of the UCM. September 25 to October 10, 2018 in the Exhibition Hall of the Faculty of Fine Arts. C / Pintor El Greco 2, University City. 28040 Madrid. Curated by Javier Mañero Rodicio.Fac. de Bellas ArtesFALSEFacultad de Bellas Artes. Universidad Complutense de Madrid.pu

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
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