Seismic analysis of the Roman Temple of Évora, Portugal

The Roman temple of Évora dates back to the 1st century AD and has undergone several changes throughout history, including various additions, which have been removed. Several archaeological studies have recently been carried out, but the structural safety of the temple is unknown. Of particular concern is the temple’s seismic resistance, as it is located in a region subjected to a moderate seismic hazard. The main purpose of this paper is to ascertain the temple’s behaviour under seismic excitation through limit analysis and discrete element analysis. Both analysis techniques will use the assumption that the structure is composed of rigid blocks connected with dry joints. Geometric information has been derived from a recent laser scanning surveying, while calibration undertaken using in-situ results from GPR and dynamic identification tests. The main results are presented and discussed in detail as well as the need for possible repair works within the framework of the ICARSAH guidelines

Genetic diversity of Huaya India (\u3ci\u3eMelicoccus oliviformis\u3c/i\u3e Kunth), a neglected Neotropical fruit crop

Currently, some species of Sapindaceae are important fruit crops worldwide. The Huaya India (Meliccocus oliviformis, Sapindaceae) is a neglected Neotropical fruit tree consumed locally in the Maya Lowlands of Mexico, where it exists in both wild and domesticated forms. Our objective was to evaluate the genetic diversity of the Huaya India in its possible domestication area and thus generate knowledge that serves as the basis for a commercial management. A total of 450 individuals collected from 15 natural vegetation sites and 15 Maya villages, were characterized using nine microsatellite loci and population genetics approaches were applied. STRUCTURE, Neighbor-Joining and PCoA analyses suggested the existence of three main groups: 1) one composed by 14 natural vegetation sites, 2) one integrated by 10 Maya villages plus one natural vegetation site, 3) one composed by five Maya villages. At the species level, genetic differentiation was high (FST = 0.562) and gene flow was low (Nm = 0.395); between genetic groups, differentiation was low and gene flow was high. Genetic diversity was low at the level species (HE = 0.19) and higher in the group composed for only natural vegetation sites. When we considered only two groups (natural vegetation sites vs Maya villages) to explore a possible bottleneck as a consequence of human management, the natural vegetation sites showed higher, and significant, genetic diversity (HE = 0.231) than the Maya villages (HE = 0.152). This study can serve as a basis to develop management strategies for Huaya India in the Maya Lowlands of Mexico, but without compromising its conservation

Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development

Multimodality of rich clusters from the SDSS DR8 within the supercluster-void network

We study the relations between the multimodality of galaxy clusters drawn from the SDSS DR8 and the environment where they reside. As cluster environment we consider the global luminosity density field, supercluster membership, and supercluster morphology. We use 3D normal mixture modelling, the Dressler-Shectman test, and the peculiar velocity of cluster main galaxies as signatures of multimodality of clusters. We calculate the luminosity density field to study the environmental densities around clusters, and to find superclusters where clusters reside. We determine the morphology of superclusters with the Minkowski functionals and compare the properties of clusters in superclusters of different morphology. We apply principal component analysis to study the relations between the multimodality parametres of clusters and their environment simultaneously. We find that multimodal clusters reside in higher density environment than unimodal clusters. Clusters in superclusters have higher probability to have substructure than isolated clusters. The superclusters can be divided into two main morphological types, spiders and filaments. Clusters in superclusters of spider morphology have higher probabilities to have substructure and larger peculiar velocities of their main galaxies than clusters in superclusters of filament morphology. The most luminous clusters are located in the high-density cores of rich superclusters. Five of seven most luminous clusters, and five of seven most multimodal clusters reside in spider-type superclusters; four of seven most unimodal clusters reside in filament-type superclusters. Our study shows the importance of the role of superclusters as high density environment which affects the properties of galaxy systems in them.Comment: 16 pages, 12 figures, 2 online tables, accepted for publication in Astronomy and Astrophysic

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

C17 Prevents Inflammatory Arthritis and Associated Joint Destruction in Mice

C17 was first described about ten years ago as a gene expressed in CD34+ cells. A more recent study has suggested a role for C17 in chondrogenesis and development of cartilage. However, based on sequence analysis, we believe that C17 has homology to IL-2 and hence we present the hypothesis that C17 is a cytokine possessing immune-regulatory properties. We provide evidence that C17 is a secreted protein preferentially expressed in chondrocytes, hence in cartilage-rich tissues. Systemic expression of C17 in vivo reduces disease in a collagen antibody-induced arthritis model in mice (CAIA). Joint protection is evident by delayed disease onset, minimal edema, bone protection and absence of diverse histological features of disease. Expression of genes typically associated with acute joint inflammation and erosion of cartilage or bone is blunted in the presence of C17. Consistent with the observed reduction in bone erosion, we demonstrate reduced levels of RANKL in the paws and sera of mice over-expressing C17. Administration of C17 at the peak of disease, however, had no effect on disease progression, indicating that C17's immune-regulatory activity must be most prominent prior to or at the onset of severe joint inflammation. Based on this data we propose C17 as a cytokine that s contributes to immune homeostasis systemically or in a tissue-specific manner in the joint

Using fMRI to investigate the potential cause of inverse oxygenation reported in fNIRS studies of motor imagery

© 2019 Elsevier B.V. Motor imagery (MI) is a commonly used cognitive task in brain–computer interface (BCI) applications because it produces reliable activity in motor-planning regions. However, a number of functional near-infrared spectroscopy (fNIRS) studies have reported the unexpected finding of inverse oxygenation: increased deoxyhemoglobin and decreased oxyhemoglobin during task periods. This finding questions the reliability of fNIRS for BCI applications given that MI activation should result in a focal increase in blood oxygenation. In an attempt to elucidate this phenomenon, fMRI and fNIRS data were acquired on 15 healthy participants performing a MI task. The fMRI data provided global coverage of brain activity, thus allowing visualization of all potential brain regions activated and deactivated during task periods. Indeed, fMRI results from seven subjects included activation in the primary motor cortex and/or the pre-supplementary motor area during the rest periods in addition to the expected activation in the supplementary motor and premotor areas. Of these seven subjects, two showed inverse oxygenation with fNIRS. The proximity of the regions showing inverse oxygenation to the motor planning regions suggests that inverse activation detected by fNIRS may likely be a consequence of partial volume errors due to the sensitivity of the optodes to both primary motor and motor planning regions

Transglutaminase 2 facilitates the distant hematogenous metastasis of breast cancer by modulating interleukin-6 in cancer cells

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Introduction Inflammation has been implicated in cancer aggressiveness. As transglutaminase 2 (TG2), which has been associated with inflammatory signaling, has been suggested to play a role in tumor behavior, we propose that TG2 may be an important linker inducing interleukin (IL)-6-mediated cancer-cell aggressiveness, including distant hematogenous metastasis. Methods To investigate the role for TG2 and IL-6, TG2-knocked-down and IL-6-knocked-down cancer cells were generated by using shRNA. Human breast cancer cell xenograft model in highly immunocompromised mice and human advanced breast cancer primary tumor tissue microarrays were used in this study. Results IL-6 production in human breast cancer cells was dependent on their TG2 expression level. In vitro tumor-sphere formation was dependent on TG2 and downstream IL-6 production from cancer cells. Primary tumor growth in the mammary fat pads and distant hematogenous metastasis into the lung was also dependent on TG2 and downstream IL-6 expression levels. The effect of TG2 expression on human breast cancer distant metastasis was investigated by analyzing a tissue microarray of primary tumors from 412 patients with their clinical data after 7 years. TG2 expression in primary tumor tissue was inversely correlated with recurrence-free survival (P = 0.019) and distant metastasis-free survival (DMFS) (P = 0.006) in patients with advanced breast cancer. Furthermore, by using public datasets that included a total of 684 breast cancer patients, we found that the combined high expression of TG2 and IL-6 was associated with shorter DMFS, compared with the high expression of IL-6 only (P = 0.013). Conclusions We provide evidence that TG2 is an important link in IL-6-mediated tumor aggressiveness, and that TG2 could be an important mediator of distant metastasis, both in a xenograft animal model and in patients with advanced breast cancer

High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.National Institutes of Health (U.S.) (MH095096)National Institutes of Health (U.S.) (R01 GM089652