Self-assembling peptide-enriched electrospun polycaprolactone scaffolds promote the h-osteoblast adhesion and modulate differentiation-associated gene expression

Electrospun polycaprolactone (PCL) is able to support the adhesion and growth of h-osteoblasts and to delay their degradation rate to a greater extent with respect to other polyesters. The drawbacks linked to its employment in regenerative medicine arise fromits hydrophobic nature and the lack of biochemical signals linked to it. This work reports on the attempt to add five different self-assembling (SA) peptides to PCL solutions before electrospinning. The hybrid scaffolds obtained had regular fibers (SEM analysis) whose diameters were similar to those of the extracellularmatrix, more stable hydrophilic (contact angle measurement) surfaces, and anamorphous phase constrained by peptides (DSC analysis). They appeared to have a notable capacity to promote the h-osteoblast adhesion and differentiation process by increasing the gene expression of alkaline phosphatase, bone sialoprotein, and osteopontin. Adding an Arg-Gly-Asp (RGD) motif to a self-assembling sequence was found to enhance cell adhesion, while the same motif condensed with a scrambled sequence did not, indicating that there is a cooperative effect between RGD and 3D architecture created by the self-assembling peptides. The study demonstrates that self-assembling peptide scaffolds are still able to promote beneficial effects on h-osteoblasts even after they have been included in electrospun polycaprolactone. The possibility of linking biochemical messages to self-assembling peptides could lead the way to a 3D decoration of fibrous scaffolds

Acute sensitivity of three Cladoceran species to different types of microplastics in combination with thermal stress

Microplastics (<5 mm, MP) are ubiquitously distributed in the environment, causing increasing concern regarding their potential toxicity to organisms. To date, most research has focussed on the impacts of MPs on marine and estuarine organisms, with fewer studies focussing on the effects of microplastics on freshwater ecosystems, especially under different environmental conditions. In the present study, the sensitivity of two temperate Cladoceran species, Daphnia magna and Daphnia pulex, and a smaller tropical species Ceriodaphnia dubia, to primary microplastics (PMP) and secondary (weathered) microplastics (SMP) was assessed. A prolonged acute toxicity assay (up to 72 or 96 h) was performed at 18°, 22°, and 26 °C, to determine the influence of temperature as an additional stressor and survival data were analysed using toxicokinetic-toxicodynamic (TK-TD) model. Acute sensitivity of D. magna and D. pulex to both PMP and SMP increased sharply with temperature, whereas that of C. dubia remained relatively stable across temperatures. C. dubia was the most sensitive species at 18 °C, followed by D. pulex and D. magna, which were of comparable sensitivity. However, this ranking was reversed at 26 °C as could be seen from the No Effect Concentration (NEC) estimates of the TK-TD model. In addition, SMP and PMP had a similar effect on D. magna and D. pulex, but PMP was more toxic to C. dubia. Effects on survival were strongly time-dependent and became substantially more severe after the standard 48 h test period. Our results indicate that sensitivity to microplastics may differ between species for different types of microplastics, and could be drastically influenced by temperature albeit at high exposure concentrations

Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models.

Continuous de novo fatty acid synthesis is a common feature of cancer that is required to meet the biosynthetic demands of a growing tumor. This process is controlled by the rate-limiting enzyme acetyl-CoA carboxylase (ACC), an attractive but traditionally intractable drug target. Here we provide genetic and pharmacological evidence that in preclinical models ACC is required to maintain the de novo fatty acid synthesis needed for growth and viability of non-small-cell lung cancer (NSCLC) cells. We describe the ability of ND-646-an allosteric inhibitor of the ACC enzymes ACC1 and ACC2 that prevents ACC subunit dimerization-to suppress fatty acid synthesis in vitro and in vivo. Chronic ND-646 treatment of xenograft and genetically engineered mouse models of NSCLC inhibited tumor growth. When administered as a single agent or in combination with the standard-of-care drug carboplatin, ND-646 markedly suppressed lung tumor growth in the Kras;Trp53-/- (also known as KRAS p53) and Kras;Stk11-/- (also known as KRAS Lkb1) mouse models of NSCLC. These findings demonstrate that ACC mediates a metabolic liability of NSCLC and that ACC inhibition by ND-646 is detrimental to NSCLC growth, supporting further examination of the use of ACC inhibitors in oncology

Microbially-mediated indirect effects of silver nanoparticles on aquatic invertebrates

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Aquatic Sciences 80 (2018): 44, doi:10.1007/s00027-018-0594-z.Complex natural systems are affected by multiple anthropogenic stressors, and therefore indirect effects within food webs are increasingly investigated. In this context, dead organic matter (OM) or detritus provides a food source sustaining detrital food webs that recycle the retained energy through microbial decomposition and invertebrate consumption. In aquatic environments, poorly water-soluble contaminants, including nanoparticles (NPs), quickly adsorb onto OM potentially modifying OM-associated microbial communities. Since invertebrates often depend on microbial conditioning to enhance OM quality, adverse effects on OM-associated microbial communities could potentially affect invertebrate performances. Therefore, this study assessed the effect of environmentally relevant concentrations of the model emerging contaminant, silver nanoparticles (AgNPs), on OM-associated microorganisms and subsequent indirect effects on growth of the invertebrate Asellus aquaticus. At low concentrations (0.8 ug/L), AgNPs inhibited activity and altered metabolic diversity of the OM-associated microbial community. This was observed to coincide with a negative effect on the growth of A. aquaticus due to antimicrobial properties, as a decreased growth was observed when offered AgNP-contaminated OM. When A. aquaticus were offered sterile OM in the absence of AgNPs, invertebrate growth was observed to be strongly retarded, illustrating the importance of microorganisms in the diet of this aquatic invertebrate. This outcome thus hints that environmentally relevant concentrations of AgNPs can indirectly affect the growth of aquatic invertebrates by affecting OM-associated microbial communities, and hence that microorganisms are an essential link in understanding bottom-up directed effects of chemical stressors in food webs.The Chinese Scholarship Council (CSC) is gratefully acknowledged for its financial support to Yujia Zhai [201506510003]. Martina G. Vijver is funded by NWO-VIDI [project number 864.13.010]

Cumprimento da sentença Gelman vs. Uruguai da Corte Interamericana dos Direitos Humanos. Especial referência à resolução número 11 e ao Poder Judiciário

More than eleven years after the judgement of the Inter-American Court of Human Rights (IACtHR) in the Gelman case, we proceed to study how this international ruling has influenced the national jurisprudence. Fluctuations can be observed in the jurisprudence until a kind of harmony is found between the national and the international jurisdiction.Luego de más de once años de dictada la sentencia de la Corte Interamericana de Derechos Humanos (Corte IDH) en el caso Gelman, se procede a estudiar cómo ha sido el cumplimiento de dicha sentencia frente al Poder Judicial y cómo ha influido dicho pronunciamiento internacional en la jurisprudencia nacional. Se aprecian vaivenes en la jurisprudencia hasta encontrar o aproximarse a una suerte de sintonía entre las jurisdicciones nacional e internacional.Depois de mais de onze anos de ditada a sentença da Corte Interamericana de Direitos Humanos (Corte IDH) no caso Gelman, procede-se a estudar como foi o cumprimento desta sentença mediante o Poder Judicial e como dito pronunciamento internacional influenciou na jurisprudência nacional. São observadas variações na jurisprudência até encontrar ou se aproximar a uma sorte de sintonia entre as jurisdições nacionais e internacionais

Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Brun, N. R., van Hage, P., Hunting, E. R., Haramis, A. G., Vink, S. C., Vijver, M. G., Schaaf, M. J. M., & Tudorache, C. Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish. Communications Biology, 2, (2019): 382, doi:10.1038/s42003-019-0629-6.Plastic nanoparticles originating from weathering plastic waste are emerging contaminants in aquatic environments, with unknown modes of action in aquatic organisms. Recent studies suggest that internalised nanoplastics may disrupt processes related to energy metabolism. Such disruption can be crucial for organisms during development and may ultimately lead to changes in behaviour. Here, we investigated the link between polystyrene nanoplastic (PSNP)-induced signalling events and behavioural changes. Larval zebrafish exhibited PSNP accumulation in the pancreas, which coincided with a decreased glucose level. By using hyperglycemic and glucocorticoid receptor (Gr) mutant larvae, we demonstrate that the PSNP-induced disruption in glucose homoeostasis coincided with increased cortisol secretion and hyperactivity in challenge phases. Our work sheds new light on a potential mechanism underlying nanoplastics toxicity in fish, suggesting that the adverse effect of PSNPs are at least in part mediated by Gr activation in response to disrupted glucose homeostasis, ultimately leading to aberrant locomotor activity.We thank Natalia Novik and Laurie Mans for technical assistance during glucose assay and in situ hybridisation, respectively, Rubén Marín-Juez for providing the ins riboprobe, and John J. Stegeman for his helpful comments on the manuscript. The research described in this work was supported by the Dutch research council NWO (MGV; 864.13.010)

Os amparos médicos na jurisprudência uruguaia recente

To complete two previous investigations about the writ of mandamus or injunction&nbsp;- excluding those writs to deliver medication or special medical treatments -, the jurisprudence of the last two years&nbsp;was reviewed from both the First Instance Courts of Montevideo and the Appeal Courts. It broke off with clearly discouraging results because Uruguayan courts have very restrictive criteria regarding de admissibility of this constitutional and international guarantee and a surprising situation was reached: just as most petitions for protection are rejected by the courts, the opposite happens when a petition for protection is filed for medical reasons. An attempt was made to find some causes for this difference in criteria.A los efectos de completar dos investigaciones anteriores referidas a acciones de amparo, pero excluyendo en aquellas oportunidades a los que tenían por objeto la obtención de medicamentos o tratamientos especiales, se relevó la jurisprudencia de primera y segunda instancia de Montevideo de los comúnmente llamados “amparos médicos” en los últimos dos años. Se partió de resultados claramente desalentadores respecto al funcionamiento de esta garantía constitucional e internacional, y se llegó a una situación sorprendente: así como las acciones de amparo son mayoritariamente rechazadas por los tribunales, con los amparos médicos ocurre lo contrario. Se intentó encontrar algunas causas de estas diferencias de criterios.Com o objetivo de complementar duas pesquisas anteriores referentes a ações de amparo, mas que excluíam naquelas ocasiões as que tinham como objetivo a obtenção de medicamentos ou tratamentos especiais, foi analisada a jurisprudência de primeira e segunda instância de Montevidéu dos comumente chamados “amparos médicos” nos últimos dois anos. Partiu-se de resultados claramente desanimadores sobre o funcionamento desta garantia constitucional e internacional, chegando-se a uma situação surpreendente: enquanto as ações de amparo são em sua maioria rejeitadas pelos tribunais, o contrário acontece com os amparos médicos. Buscou-se identificar algumas causas dessas diferenças de critérios

Palaeogenomics of Upper Palaeolithic to Neolithic European hunter-gatherers

Modern humans have populated Europe for more than 45,000 years1,2. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period3. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe4, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants

Palaeogenomics of Upper Palaeolithic to Neolithic European hunter-gatherers

Modern humans have populated Europe for more than 45,000 years. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants.Open access funding provided by Max Planck Society. This project has received funding by the European Research Council under the European Union’s Horizon 2020 research and innovation programme under grant agreements no. 803147-RESOLUTION (to S.T.), no. 771234-PALEoRIDER (to W.H.), no. 864358 (to K.M.), no. 724703 and no. 101019659 (to K.H.). K.H. is also supported by the Deutsche Forschungsgemeinschaft (DFG FOR 2237). E.A. has received funding from the Van de Kamp fonds. PACEA co-authors of this research benefited from the scientific framework of the University of Bordeaux’s IdEx Investments for the Future programme/GPR Human Past. A.G.-O. is supported by a Ramón y Cajal fellowship (RYC-2017-22558). L. Sineo, M.L. and D.C. have received funding from the Italian Ministry of University and Research (MUR) PRIN 2017 grants 20177PJ9XF and 20174BTC4R_002. H. Rougier received support from the College of Social and Behavioral Sciences of CSUN and the CSUN Competition for RSCA Awards. C.L.S. and T. Saupe received support from the European Union through the European Regional Development Fund (project no. 2014-2020.4.01.16-0030) and C.L.S. received support from the Estonian Research Council grant PUT (PRG243). S. Shnaider received support from the Russian Science Foundation (no. 19-78-10053).Peer reviewe

Warmth and competence perceptions of key protagonists are associated with containment measures during the COVID-19 pandemic: Evidence from 35 countries

It is crucial to understand why people comply with measures to contain viruses and their effects during pandemics. We provide evidence from 35 countries (Ntotal = 12,553) from 6 continents during the COVID-19 pandemic (between 2021 and 2022) obtained via cross-sectional surveys that the social perception of key protagonists on two basic dimensions—warmth and competence—plays a crucial role in shaping pandemic-related behaviors. Firstly, when asked in an open question format, heads of state, physicians, and protest movements were universally identified as key protagonists across countries. Secondly, multiple-group confirmatory factor analyses revealed that warmth and competence perceptions of these and other protagonists differed significantly within and between countries. Thirdly, internal meta-analyses showed that warmth and competence perceptions of heads of state, physicians, and protest movements were associated with support and opposition intentions, containment and prevention behaviors, as well as vaccination uptake. Our results have important implications for designing effective interventions to motivate desirable health outcomes and coping with future health crises and other global challenges.publishedVersio