Impact of polymorphic transposable elements on transcription in lymphoblastoid cell lines from public data

Background: Transposable elements (TEs) are DNA sequences able to mobilize themselves and to increase their copy-number in the host genome. In the past, they have been considered mainly selfish DNA without evident functions. Nevertheless, currently they are believed to have been extensively involved in the evolution of primate genomes, especially from a regulatory perspective. Due to their recent activity they are also one of the primary sources of structural variants (SVs) in the human genome. By taking advantage of sequencing technologies and bioinformatics tools, recent surveys uncovered specific TE structural variants (TEVs) that gave rise to polymorphisms in human populations. When combined with RNA-seq data this information provides the opportunity to study the potential impact of TEs on gene expression in human. Results: In this work, we assessed the effects of the presence of specific TEs in cis on the expression of flanking genes by producing associations between polymorphic TEs and flanking gene expression levels in human lymphoblastoid cell lines. By using public data from the 1000 Genome Project and the Geuvadis consortium, we exploited an expression quantitative trait loci (eQTL) approach integrated with additional bioinformatics data mining analyses. We uncovered human loci enriched for common, less common and rare TEVs and identified 323 significant TEV-cis-eQTL associations. SINE-R/VNTR/Alus (SVAs) resulted the TE class with the strongest effects on gene expression. We also unveiled differential functional enrichments on genes associated to TEVs, genes associated to TEV-cis-eQTLs and genes associated to the genomic regions mostly enriched in TEV-cis-eQTLs highlighting, at multiple levels, the impact of TEVs on the host genome. Finally, we also identified polymorphic TEs putatively embedded in transcriptional units, proposing a novel mechanism in which TEVs may mediate individual-specific traits. Conclusion: We contributed to unveiling the effect of polymorphic TEs on transcription in lymphoblastoid cell lines

Solving variational inequalities and cone complementarity problems in nonsmooth dynamics using the alternating direction method of multipliers

This work presents a numerical method for the solution of variational inequalities arising in nonsmooth flexible multibody problems that involve set-valued forces. For the special case of hard frictional contacts, the method solves a second order cone complementarity problem. We ground our algorithm on the Alternating Direction Method of Multipliers (ADMM), an efficient and robust optimization method that draws on few computational primitives. In order to improve computational performance, we reformulated the original ADMM scheme in order to exploit the sparsity of constraint jacobians and we added optimizations such as warm starting and adaptive step scaling. The proposed method can be used in scenarios that pose major difficulties to other methods available in literature for complementarity in contact dynamics, namely when using very stiff finite elements and when simulating articulated mechanisms with odd mass ratios. The method can have applications in the fields of robotics, vehicle dynamics, virtual reality, and multiphysics simulation in general

Glioma Associated Stem Cells (GASCs) Isolation and Culture.

Glioma Associated Stem Cells (GASCs) represent a population of nontumorigenic multipotent stem cells hosted in the microenvironment of human gliomas. In vitro, these cells are able, through the release of exosomes, to increase the biological aggressiveness of glioma-initiating cells. The clinical importance of this finding is supported by the strong prognostic value associated with the GASCs surface immunophenotype thus suggesting that this patient-based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor strom

Induction of Isochromanones by Co-Cultivation of the Marine Fungus Cosmospora sp. and the Phytopathogen Magnaporthe oryzae

Microbial co-cultivation is a promising approach for the activation of biosynthetic gene clusters (BGCs) that remain transcriptionally silent under artificial culture conditions. As part of our project aiming at the discovery of marine-derived fungal agrochemicals, we previously used four phytopathogens as model competitors in the co-cultivation of 21 marine fungal strains. Based on comparative untargeted metabolomics analyses and anti-phytopathogenic activities of the co-cultures, we selected the co-culture of marine Cosmospora sp. with the phytopathogen Magnaporthe oryzae for in-depth chemical studies. UPLC-MS/MS-based molecular networking (MN) of the co-culture extract revealed an enhanced diversity of compounds in several molecular families, including isochromanones, specifically induced in the co-culture. Large scale co-cultivation of Cosmospora sp. and M. oryzae resulted in the isolation of five isochromanones from the whole co-culture extract, namely the known soudanones A, E, D (1-3) and their two new derivatives, soudanones H-I (4-5), the known isochromans, pseudoanguillosporins A and B (6, 7), naphtho-γ-pyrones, cephalochromin and ustilaginoidin G (8, 9), and ergosterol (10). Their structures were established by NMR, HR-ESIMS, FT-IR, electronic circular dichroism (ECD) spectroscopy, polarimetry ([α]D), and Mosher’s ester reaction. Bioactivity assays revealed antimicrobial activity of compounds 2 and 3 against the phytopathogens M. oryzae and Phytophthora infestans, while pseudoanguillosporin A (6) showed the broadest and strongest anti-phytopathogenic activity against Pseudomonas syringae, Xanthomonas campestris, M. oryzae and P. infestans. This is the first study assessing the anti-phytopathogenic activities of soudanones

Potential sources of particulate iron in surface and deep waters of the terra nova bay (Ross sea, antarctica)

The distribution of particulate Fe (pFe), suspended particulate matter (SPM), and other particulate trace metals were investigated in Terra Nova Bay as part of CDW Effects on glaciaL mElting and on Bulk of Fe in the Western Ross sea (CELEBeR) and Plankton biodiversity and functioning of the Ross Sea ecosystems in a changing Southern Ocean (P-ROSE) projects. Variable concentrations of SPM (0.09–97 mg L−1 ), pFe (0.51–8.70 nM) and other trace metals were found in the Antarctic Surface waters (AASW) layer, where the addition of meltwater contributed to the pool with both lithogenic and biogenic forms. The deeper layer of the water column was occupied by High Salinity Shelf Water (HSSW) and Terra Nova Bay Ice Shelf Water (TISW) encompassing glacial water as confirmed by the lightest δ18 O measured values. The concentration of pFe in TISW (11.7 ± 9.2 nM) was higher than in HSSW samples (5.55 ± 4.43 nM), suggesting that the drainage of material released from glaciers surrounding the area is relevant in terms of pFe contribution. Particulate Fe/Al and Mn/Al ratios were substantially in excess compared with the mean crustal ratios. Microscopic analyses confirmed that more labile Fe oxyhydroxides and authigenic MnO2 phases were present together with biogenic sinking material. Future expected increasing melt rates of these glaciers enlarge Fe input, thus having a greater role in supplying iron and counteracting the reductions in sea ice cover around Terra Nova Bay

Cholesterol derivatives make large part of the lipids from epidermal molts of the desert-adapted Gila monster lizard (Heloderma suspectum)

In order to understand the cutaneous water loss in the desert-adapted and venomous lizard Heloderma suspectum, the microscopic structure and lipid composition of epidermal molts have been examined using microscopic, spectroscopic and chemical analysis techniques. The molt is formed by a variably thick, superficial beta-layer, an extensive mesos-region and few alpha-cells in its lowermost layers. The beta-layer contains most corneous beta proteins while the mesos-region is much richer in lipids. The proteins in the mesos-region are more unstructured than those located in the beta-layer. Most interestingly, among other lipids, high contents of cholesteryl-β-glucoside and cholesteryl sulfate were detected, molecules absent or present in traces in other species of squamates. These cholesterol derivatives may be involved in the stabilization and compaction of the mesos-region, but present a limited permeability to water movements. The modest resistance to cutaneous water-loss of this species is compensated by adopting other physiological strategies to limit thermal damage and water transpiration as previous eco-physiological studies have indicated. The increase of steroid derivatives may also be implicated in the heat shock response, influencing the relative behavior in this desert-adapted lizard

Pyrenosetin D, a new pentacyclic decalinoyltetramic acid derivative from the algicolous fungus Pyrenochaetopsis sp. FVE-087

The fungal genus Pyrenochaetopsis is commonly found in soil, terrestrial, and marine environments, however, has received little attention as a source of bioactive secondary metabolites so far. In a recent work, we reported the isolation and characterization of three new anticancer decalinoyltetramic acid derivatives, pyrenosetins A–C, from the Baltic Fucus vesiculosus-derived endophytic fungus Pyrenochaetopsis sp. FVE-001. Herein we report a new pentacyclic decalinoylspirotetramic acid derivative, pyrenosetin D (1), along with two known decalin derivatives wakodecalines A (2) and B (3) from another endophytic strain Pyrenochaetopsis FVE-087 isolated from the same seaweed and showed anticancer activity in initial screenings. The chemical structures of the purified compounds were elucidated by comprehensive analysis of HR-ESIMS, FT-IR, [α]D, 1D and 2D NMR data coupled with DFT calculations of NMR parameters and optical rotation. Compounds 1–3 were evaluated for their anticancer and toxic potentials against the human malignant melanoma cell line (A-375) and the non-cancerous keratinocyte cell line (HaCaT). Pyrenosetin D (1) showed toxicity towards both A-375 and HaCaT cells with IC50 values of 77.5 and 39.3 µM, respectively, while 2 and 3 were inactive. This is the third chemical study performed on the fungal genus Pyrenochaetopsis and the first report of a pentacyclic decalin ring system from the fungal genus Pyrenochaetopsis

Analysis of LINE1 Retrotransposons in Huntington’s Disease

Transposable elements (TEs) are mobile genetic elements that made up about half the human genome. Among them, the autonomous non-LTR retrotransposon long interspersed nuclear element-1 (L1) is the only currently active TE in mammals and covers about 17% of the mammalian genome. L1s exert their function as structural elements in the genome, as transcribed RNAs to influence chromatin structure and as retrotransposed elements to shape genomic variation in somatic cells. L1s activity has been shown altered in several diseases of the nervous system. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expansion of a CAG repeat in the HTT gene which leads to a gradual loss of neurons most prominently in the striatum and, to a lesser extent, in cortical brain regions. The length of the expanded CAG tract is related to age at disease onset, with longer repeats leading to earlier onset. Here we carried out bioinformatic analysis of public RNA-seq data of a panel of HD mouse models showing that a decrease of L1 RNA expression recapitulates two hallmarks of the disease: it correlates to CAG repeat length and it occurs in the striatum, the site of neurodegeneration. Results were then experimentally validated in HttQ111 knock-in mice. The expression of L1-encoded proteins was independent from L1 RNA levels and differentially regulated in time and tissues. The pattern of expression L1 RNAs in human HD post-mortem brains showed similarity to mouse models of the disease. This work suggests the need for further study of L1s in HD and adds support to the current hypothesis that dysregulation of TEs may be involved in neurodegenerative diseases

Frog skin-derived peptides against corynebacterium jeikeium: correlation between antibacterial and cytotoxic activities

Corynebacterium jeikeium is a commensal bacterium that colonizes human skin, and it is part of the normal bacterial flora. In non-risk subjects, it can be the cause of bad body smell due to the generation of volatile odorous metabolites, especially in the wet parts of the body that this bacterium often colonizes (i.e., groin and axillary regions). Importantly, in the last few decades, there have been increasing cases of serious infections provoked by this bacterium, especially in immunocompromised or hospitalized patients who have undergone installation of prostheses or catheters. The ease in developing resistance to commonly-used antibiotics (i.e., glycopeptides) has made the search for new antimicrobial compounds of clinical importance. Here, for the first time, we characterize the antimicrobial activity of some selected frog skin-derived antimicrobial peptides (AMPs) against C. jeikeium by determining their minimum inhibitory and bactericidal concentrations (MIC and MBC) by a microdilution method. The results highlight esculentin-1b(1-18) [Esc(1-18)] and esculentin-1a(1-21) [Esc(1-21)] as the most active AMPs with MIC and MBC of 4–8 and 0.125–0.25 µM, respectively, along with a non-toxic profile after a short-and long-term (40 min and 24 h) treatment of mammalian cells. Overall, these findings indicate the high potentiality of Esc(1-18) and Esc(1-21) as (i) alternative antimicrobials against C. jeikeium infections and/or as (ii) additives in cosmetic products (creams, deodorants) to reduce the production of bad body odor

Switchable Solvent Selective Extraction of Hydrophobic Antioxidants from Synechococcus bigranulatus

Hydrophobic molecules, in particular, carotenoids, have been directly extracted from Synechococcus bigranulatus ACUF680 by means of secondary amine switchable solvent N-ethylbutylamine (EBA) without any other pretreatment. EBA was able to extract hydrophobic molecules from both fresh and frozen biomass at the same extent of the conventional procedure (about 20% of dry biomass). In particular, selective extraction of a zeaxanthin-enriched fraction (green fraction, GF) and a β-carotene-enriched fraction (orange fraction, OF) was obtained. The ratio between zeaxanthin and β-carotene was 4.4 ± 1.5 for GF, 0.07 ± 0.06 for OF, and about 1 for conventional extraction. These fractions showed in vitro antioxidant activity (IC50 values of 0.056 ± 0.013 and 0.024 ± 0.008 mg mL-1 for GF and OF, respectively) and biocompatibility on immortalized cells. Moreover, OF and GF were able to protect cells from oxidative stress, both before and after thermal treatment. Results clearly indicate that EBA is a good candidate to specifically extract β-carotene and zeaxanthin from the wet biomass of S. bigranulatus without affecting their biological activity. Skipping energy-intensive operations to break the cells and using either fresh or frozen biomass may be the driving factors to use EBA switchable solvent on an industrial scale