Parity effect in a mesoscopic Fermi gas

We develop a quantitative analytic theory that accurately describes the odd-even effect observed experimentally in a one-dimensional, trapped Fermi gas with a small number of particles [G. Z\"urn et al., Phys. Rev. Lett. 111, 175302 (2013)]. We find that the underlying physics is similar to the parity effect known to exist in ultrasmall mesoscopic superconducting grains and atomic nuclei. However, in contrast to superconducting nanograins, the density (Hartree) correction dominates over the superconducting pairing fluctuations and leads to a much more pronounced odd-even effect in the mesoscopic, trapped Fermi gas. We calculate the corresponding parity parameter and separation energy using both perturbation theory and a path integral framework in the mesoscopic limit, generalized to account for the effects of the trap, pairing fluctuations, and Hartree corrections. Our results are in an excellent quantitative agreement with experimental data and exact diagonalization. Finally, we discuss a few-to-many particle crossover between the perturbative mesoscopic regime and non-perturbative many-body physics that the system approaches in the thermodynamic limit.Comment: 7 pages, 1 figur

Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair

Hereditary mutations in polynucleotide kinase-phosphatase (PNKP) result in a spectrum of neurological pathologies ranging from neurodevelopmental dysfunction in microcephaly with early onset seizures (MCSZ) to neurodegeneration in ataxia oculomotor apraxia-4 (AOA4) and Charcot-Marie-Tooth disease (CMT2B2). Consistent with this, PNKP is implicated in the repair of both DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs); lesions that can trigger neurodegeneration and neurodevelopmental dysfunction, respectively. Surprisingly, however, we did not detect a significant defect in DSB repair (DSBR) in primary fibroblasts from PNKP patients spanning the spectrum of PNKP-mutated pathologies. In contrast, the rate of SSB repair (SSBR) is markedly reduced. Moreover, we show that the restoration of SSBR in patient fibroblasts collectively requires both the DNA kinase and DNA phosphatase activities of PNKP, and the fork-head associated (FHA) domain that interacts with the SSBR protein, XRCC1. Notably, however, the two enzymatic activities of PNKP appear to affect different aspects of disease pathology, with reduced DNA phosphatase activity correlating with neurodevelopmental dysfunction and reduced DNA kinase activity correlating with neurodegeneration. In summary, these data implicate reduced rates of SSBR, not DSBR, as the source of both neurodevelopmental and neurodegenerative pathology in PNKP-mutated disease, and the extent and nature of this reduction as the primary determinant of disease severity

State of knowledge regarding the potential of macroalgae cultivation in providing climate-related and other ecosystem services

Macroalgae (or seaweed) aquaculture can potentially provide many ecosystem services, including climate change mitigation, coastal protection, preservation of biodiversity and improvement of water quality. Nevertheless, there are still many constraints and knowledge gaps that need to be overcome, as well as potential negative impacts or scale-dependent effects that need to be considered, before macroalgae cultivation in Europe can be scaled up successfully and sustainably. To investigate these uncertainties, the Expert Working Group (EWG) on Macroalgae was established. Its role was to determine the state of knowledge regarding the potential of macroalgae culture in providing climate-related and other ecosystem services (ES) and to identify specific knowledge gaps that must be addressed before harvesting this potential. The methodological framework combined a multiple expert consultation with Delphi process and a Quick Scoping Review (QSR). To analyse the outcome of both approaches, the EWG classified the findings under the categories Political, Environmental, Social, Technical, Economic and Legal (PESTEL approach) and categorised the ES based on the CICES 5.1 classification. Although representative stakeholders from many different disciplines were contacted, the majority of responses to the Delphi process were from representatives of academia or research. While the results of each method differed in many ways, both methods identified the following top six ecosystem services provided by seaweed cultivation: i) provisioning food, ii) provisioning hydrocolloids and feed, iii) regulating water quality, iv) provisioning habitats, v) provisioning of nurseries and vi) regulating climate. Diverse technological knowledge gaps were identified by both methods at all scales of the macroalgae cultivation process, followed by economic and environmental knowledge gaps depending on the method used. Based on suggestions from the expert respondents in the Delphi process, there is a clear need for an European-wide strategy for reducing risks for seaweed producers, providing clear standards and guidelines for obtaining permits, and providing financial support to improve technological innovation, that will ensure consistent quality. Legal (e.g., safety regulations), economic (e.g., lack of demand for seaweeds in many countries) and technological (e.g., production at large scale) constraints represented almost 70% of the total responses in the Delphi process, whereas environmental and technical constraints were more dominant in the literature. The most commonly identified potential negative impacts of macroalgae cultivation both among the expert responses and the reviewed articles were unknown environmental impacts, e.g. to deep sea, benthic and pelagic ecosystems. The present study provides an assessment of the state of knowledge regarding ES provided by seaweed cultivation and identifies the associated knowledge gaps, constraints and potential negative impacts. One of the main hurdles recognised by the EWG was the understanding of ES themselves by the different stakeholders, as well as the issue of scale. Studies providing clear evidence of ES provided by seaweed cultivation and/or valorisation of these services were lacking in the literature, and some aspects, like cultural impact etc. were missing in the responses to the questionnaires during the Delphi process. The issue of scale and scaling-up was omnipresent both in assessing the ES provided by seaweed cultivation and in identifying knowledge gaps, constraints and potential negative impacts. For example, the ES provided will depend on the scale of cultivation, the main technological knowledge gaps were often related to scale of cultivation. Likewise at a large scale of operations, there could be multiple associated potential side effects, which need to be further investigated. Based on the outcomes of this investigation, we provide an outlook with open questions that need to be answered to support the sustainable scaling-up of seaweed cultivation in Europe

A tectonic carpet of Variscan flysch at the base of a rootless accretionary prism in northwestern Iberia: U–Pb zircon age constrains from sediments and volcanic olistoliths

The allochthonous complexes of Galicia–Trás-os-Montes Zone (NW Iberia) are part of a rootless tectonic stack which preserves part of a Variscan accretionary prism. They are formed by individual tectonic slices marked by specific tectonometamorphic evolutions, which were piled up in a piggy-back mode onto its relative autochthon, the Central Iberian Zone (CIZ). Allochthony decreases from the structurally upper thrust sheets towards the lower ones. The lowermost unit of the stack is known as the Parautochthon or Schistose Domain. It is characterized by a low metamorphic grade in contrast with higher temperatures and/or pressures estimated for the overlying allochthonous units and shares the stratigraphic sequence with the underlying autochthon. The Parautochthon is divided in two structural and stratigraphic sub-units: (i) the Lower Parautochthon (LPa) is made of synorogenic flysch-type sediments with varied turbiditic units and olistostrome bodies, showing Upper Devonian–lower Carboniferous age according to the youngest zircon populations and fossiliferous content; (ii) the Upper Parautochthon (UPa) is composed of highly deformed preorogenic upper Cambrian–Silurian volcano-sedimentary sequence comparable with the nearby autochthon and to some extent, also with the high-P and low-T Lower Allochthon laying structurally above. The UPa was emplaced onto the LPa along the Main-Trás-os-Montes Thrust, and the LPa became detached from the CIZ relative autochthon by a regional-scale structure, the Basal Lower Parautochthon Detachment, which follows a weak horizon of Silurian carbonaceous slates. A review on the detrital zircon studies on the synorogenic LPa complemented by zircon dating of 17 new samples is presented here. The results support the extension of the LPa underneath the NW Iberian allochthonous complexes, from Cabo Ortegal, to Bragança and Morais massifs. Its current exposure follows the lowermost tectonic boundary between the Galicia–Trás-os-Montes (allochthon) and Central Iberian (autochthon) zones. The youngest zircon age populations point to a maximum sedimentation age for the LPa formations ranging from Famennian to Serpukhovian and supports the piggy-back mode of emplacement of the Galicia–Trás-os-Montes Zone, of which it represents the latest imbricate. The zircon age populations in the LPa allow the sedimentary provenance areas to be constrained, showing the intervention of nearby sources (mostly the UPa) and/or multiply recycled and long-transport sediments with a typically north-central Gondwana age fingerprint, also found in the Lower Allochthon, UPa and Autochthon. Complementary geochronology of volcanic olistoliths trapped in the LPa sediments and of late Cambrian to Upper Ordovician rhyolites from the UPa is also presented. It shows a direct relationship between the major blocks source area (UPa) and the setting place (LPa). Old zircon age patterns show that the LPa sedimentary rocks were recycled from detrital rocks of the allochthon (advancing wedge) and the nearby autochthon (peripheral bulge).info:eu-repo/semantics/publishedVersio

Prenatal treatment with rosiglitazone attenuates vascular remodeling and pulmonary monocyte influx in experimental congenital diaphragmatic hernia

Publication history: Accepted - 23 October 2018; Published online - 12 November 2018.Introduction Extensive vascular remodeling causing pulmonary hypertension (PH) represents a major cause of mortality in patients with congenital diaphragmatic hernia (CDH). The chemokine monocyte chemoattractant protein-1 (MCP-1) is a biomarker for the severity of PH and its activation is accompanied by pulmonary influx of monocytes and extensive vascular remodeling. MCP-1 activation can be reversed by application of rosiglitazone (thiazolidinedione). We performed this study to evaluate the role of MCP-1 for the pathogenesis of PH in experimental CDH. We hypothesized that vascular remodeling and MCP-1 activation is accompanied by pulmonary influx of fetal monocytes and can be attenuated by prenatal treatment with rosiglitazone. Methods In a first set of experiments pregnant rats were treated with either nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were harvested on D21 and divided into CDH and control. Quantitative real-time polymerase chain reaction, Western blot (WB), and immunohistochemistry (IHC) were used to evaluate MCP-1 expression, activation, and localization. Quantification and localization of pulmonary monocytes/macrophages were carried out by IHC. In a second set of experiments nitrofen-exposed dams were randomly assigned to prenatal treatment with rosiglitazone or placebo on D18+D19. Fetal lungs were harvested on D21, divided into control, CDH+rosiglitazone, and CDH+placebo and evaluated by WB as well as IHC. Results Increased thickness of pulmonary arteries of CDH fetuses was accompanied by increased systemic and perivascular MCP-1 protein expression and significantly higher amounts of pulmonary monocytes/macrophages compared to controls (p<0.01). These effects were reversed by prenatal treatment with rosiglitazone (p<0.01 vs. CDH+P; control). Conclusion Prenatal treatment with rosiglitazone has the potential to attenuate activation of pulmonary MCP-1, pulmonary monocyte influx, and vascular remodeling in experimental CDH. These results provide a basis for future research on prenatal immunomodulation as a novel treatment strategy to decrease secondary effects of PH in CDH.This work was supported by Children’s Medical & Research Foundation, Dublin, Ireland, https://cmrf.org/, Senior Research Fellowship JG, awarded to JG; German Research Foundation and Leipzig University within the program of Open Access Publishing, awarded to JG, https://www.ub.uni-leipzig.de/open-science/publikationsfonds/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

LEM-3 – A LEM Domain Containing Nuclease Involved in the DNA Damage Response in C. elegans

The small nematode Caenorhabditis elegans displays a spectrum of DNA damage responses similar to humans. In order to identify new DNA damage response genes, we isolated in a forward genetic screen 14 new mutations conferring hypersensitivity to ionizing radiation. We present here our characterization of lem-3, one of the genes identified in this screen. LEM-3 contains a LEM domain and a GIY nuclease domain. We confirm that LEM-3 has DNase activity in vitro. lem-3(lf) mutants are hypersensitive to various types of DNA damage, including ionizing radiation, UV-C light and crosslinking agents. Embryos from irradiated lem-3 hermaphrodites displayed severe defects during cell division, including chromosome mis-segregation and anaphase bridges. The mitotic defects observed in irradiated lem-3 mutant embryos are similar to those found in baf-1 (barrier-to-autointegration factor) mutants. The baf-1 gene codes for an essential and highly conserved protein known to interact with the other two C. elegans LEM domain proteins, LEM-2 and EMR-1. We show that baf-1, lem-2, and emr-1 mutants are also hypersensitive to DNA damage and that loss of lem-3 sensitizes baf-1 mutants even in the absence of DNA damage. Our data suggest that BAF-1, together with the LEM domain proteins, plays an important role following DNA damage – possibly by promoting the reorganization of damaged chromatin

Full-Exon Pyrosequencing Screening of BRCA Germline Mutations in Mexican Women with Inherited Breast and Ovarian Cancer

Hereditary breast cancer comprises 10% of all breast cancers. The most prevalent genes causing this pathology are BRCA1 and BRCA2 (breast cancer early onset 1 and 2), which also predispose to other cancers. Despite the outstanding relevance of genetic screening of BRCA deleterious variants in patients with a history of familial cancer, this practice is not common in Latin American public institutions. In this work we assessed mutations in the entire exonic and splice-site regions of BRCA in 39 patients with breast and ovarian cancer and with familial history of breast cancer or with clinical features suggestive for BRCA mutations by massive parallel pyrosequencing. First we evaluated the method with controls and found 41–485 reads per sequence in BRCA pathogenic mutations. Negative controls did not show deleterious variants, confirming the suitability of the approach. In patients diagnosed with cancer we found 4 novel deleterious mutations (c.2805_2808delAGAT and c.3124_3133delAGCAATATTA in BRCA1; c.2639_2640delTG and c.5114_5117delTAAA in BRCA2). The prevalence of BRCA mutations in these patients was 10.2%. Moreover, we discovered 16 variants with unknown clinical significance (11 in exons and 5 in introns); 4 were predicted as possibly pathogenic by in silico analyses, and 3 have not been described previously. This study illustrates how massive pyrosequencing technology can be applied to screen for BRCA mutations in the whole exonic and splice regions in patients with suspected BRCA-related cancers. This is the first effort to analyse the mutational status of BRCA genes on a Mexican-mestizo population by means of pyrosequencing

Friedrich Hayek and his visits to Chile

F. A. Hayek took two trips to Chile, the first in 1977, the second in 1981. The visits were controversial. On the first trip he met with General Augusto Pinochet, who had led a coup that overthrew Salvador Allende in 1973. During his 1981 visit, Hayek gave interviews that were published in the Chilean newspaper El Mercurio and in which he discussed authoritarian regimes and the problem of unlimited democracy. After each trip, he complained that the western press had painted an unfair picture of the economic situation under the Pinochet regime. Drawing on archival material, interviews, and past research, we provide a full account of this controversial episode in Hayek’s life

Nucleolar Proteins Suppress Caenorhabditis elegans Innate Immunity by Inhibiting p53/CEP-1

The tumor suppressor p53 has been implicated in multiple functions that play key roles in health and disease, including ribosome biogenesis, control of aging, and cell cycle regulation. A genetic screen for negative regulators of innate immunity in Caenorhabditis elegans led to the identification of a mutation in NOL-6, a nucleolar RNA-associated protein (NRAP), which is involved in ribosome biogenesis and conserved across eukaryotic organisms. Mutation or silencing of NOL-6 and other nucleolar proteins results in an enhanced resistance to bacterial infections. A full-genome microarray analysis on animals with altered immune function due to mutation in nol-6 shows increased transcriptional levels of genes regulated by a p53 homologue, CEP-1. Further studies indicate that the activation of innate immunity by inhibition of nucleolar proteins requires p53/CEP-1 and its transcriptional target SYM-1. Since nucleoli and p53/CEP-1 are conserved, our results reveal an ancient immune mechanism by which the nucleolus may regulate immune responses against bacterial pathogens