Eicosapentaenoic acid induces DNA demethylation in carcinoma cells through a TET1-dependent mechanism

In cancer cells, global genomic hypomethylation is found together with localized hypermethylation of CpG islands within the promoters and regulatory regions of silenced tumor suppressor genes. Demethylating agents may reverse hypermethylation, thus promoting gene re-expression. Unfortunately, demethylating strategies are not efficient in solid tumor cells. DNA demethylation is mediated by ten-eleven translocation enzymes (TETs). They sequentially convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which is associated with active transcription; 5-formylcytosine; and finally, 5-carboxylcytosine. Although α-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid, the major n-3 polyunsaturated fatty acids, have anti-cancer effects, their action, as DNA-demethylating agents, has never been investigated in solid tumor cells. Here, we report that EPA demethylates DNA in hepatocarcinoma cells. EPA rapidly increases 5hmC on DNA, inducing p21Waf1/Cip1 gene expression, which slows cancer cell-cycle progression. We show that the underlying molecular mechanism involves TET1. EPA simultaneously binds peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RXRα), thus promoting their heterodimer and inducing a PPARγ-TET1 interaction. They generate a TET1-PPARγ-RXRα protein complex, which binds to a hypermethylated CpG island on the p21 gene, where TET1 converts 5mC to 5hmC. In an apparent shuttling motion, PPARγ and RXRα leave the DNA, whereas TET1 associates stably. Overall, EPA directly regulates DNA methylation levels, permitting TET1 to exert its anti-tumoral function.-Ceccarelli, V., Valentini, V., Ronchetti, S., Cannarile, L., Billi, M., Riccardi, C., Ottini, L., Talesa, V. N., Grignani, F., Vecchini, A., Eicosapentaenoic acid induces DNA demethylation in carcinoma cells through a TET1-dependent mechanism

New tree monitoring systems: from Industry 4.0 to Nature 4.0

Recently, Internet of Things (IoT) technologies have grown rapidly and represent now a unique opportunity to improve our environmental monitoring capabilities at extremely low costs. IoT is a new system of thinking in which objects, animals or people are equipped with unique identifiers and transfer data a network without requiring human-to-human or human-to-computer interaction. IoT has evolved from the convergence of wireless technologies, microelectromechanical systems (MEMS) and the Internet. The development of these technologies in environmental monitoring domains allows real-time data transmission and numerous low-cost monitoring points. We have designed a new device, the TreeTalker©, which is capable of measuring water transport in trees, diametrical growth, spectral characteristics of the leaves and microclimatic parameters and transmit data in semi-real time. Here we introduce the device’s features, provide an example of monitored data from a field test site and discuss the application of this new technology to tree monitoring in various contexts, from forest to urban green infrastructures management and ecological research

Relative echogenicity of tendons and ligaments of the palmar metacarpal region in foals from birth to 4 months of age: A longitudinal study

The objective of this study was to evaluate relative echogenicity of superficial and deep digital flexor tendons, the accessory ligament of the deep digital flexor tendon and interosseous muscle of the metacarpal region in foals ages 1 week to 4 months; and assess the association between echogenicity and sex or side/laterality. Seven Standardbred trotter foals were examined. Right and left metacarpal regions (palmar surface) were ultrasonographically investigated, and four regions of interest were assessed. A significant increase in echogenicity was seen in superficial and deep digital flexor tendons, accessory ligament of deep digital flexor tendon, and interosseous muscle during growth from 1 week to 4 months of age. Echogenicity of examined tendons and ligaments was not influenced by gender nor laterality. Reference values for tendon and ligament echogenicity could function as a tool to discriminate between physiological and abnormal conditions such as congenital contractural conditions

Is the star formation rate in z∼6z\sim 6 quasars overestimated?

The large total infrared (TIR) luminosities ($L_{\rm TIR} \gtrsim 10^{12}~L_\odot$) observed in $z \sim 6$ quasars are generally converted into high star formation rates ($SFR \gtrsim 10^2~M_\odot$ yr$^{-1}$) of their host galaxies. However, these estimates rely on the assumption that dust heating is dominated by stellar radiation, neglecting the contribution from the central Active Galactic Nuclei (AGN). We test the validity of this assumption by combining cosmological hydrodynamic simulations with radiative transfer calculations. We find that, when AGN radiation is included in the simulations, the mass (luminosity)-weighted dust temperature in the host galaxies increases from $T\approx 50$ K ($T \approx 70$ K) to $T\approx 80$ K ($T\approx 200$ K), suggesting that AGN effectively heat the bulk of dust in the host galaxy. We compute the AGN-host galaxy $SFR$ from the synthetic spectral energy distribution by using standard $SFR - L_{\rm TIR}$ relations, and compare the results with the "true" values in the simulations. We find that the $SFR$ is overestimated by a factor of $\approx 3$ ($\gtrsim 10$) for AGN bolometric luminosities of $L_{\rm bol} \approx 10^{12}~L_\odot$ ($\gtrsim 10^{13}~ L_\odot$), implying that the star formation rates of $z\sim 6$ quasars can be overestimated by over an order of magnitude.Comment: 9 pages, 6 figures. Accepted for publication by MNRA

SBI is uncommon in the absence of paediatricians' gut feeling and abnormal respiratory pattern

According to the Italian national statistical institute, severe bacterial infections (SBI) in Italy are responsible for 1.7% of mortality under five years of age and their recognition is often challenging, especially in the first stages of the disease. We tried to estimate the prevalence of SBI in our target population and to identify signs and symptoms that could guide in the initial evaluation of a child with a possible SBI

Balance between Regulatory T and Th17 Cells in Systemic Lupus Erythematosus: The Old and the New

Pathogenic mechanisms underlying the development of systemic lupus erythematosus (SLE) are very complex and not yet entirely clarified. However, the pivotal role of T lymphocytes in the induction and perpetuation of aberrant immune response is well established. Among T cells, IL-17 producing T helper (Th17) cells and regulatory T (Treg) cells represent an intriguing issue to be addressed in SLE pathogenesis, since an imbalance between the two subsets has been observed in the course of the disease. Treg cells appear to be impaired and therefore unable to counteract autoreactive T lymphocytes. Conversely, Th17 cells accumulate in target organs contributing to local IL-17 production and eventually tissue damage. In this setting, targeting Treg/Th17 balance for therapeutic purposes may represent an intriguing and useful tool for SLE treatment in the next future. In this paper, the current knowledge about Treg and Th17 cells interplay in SLE will be discussed

Long tree-ring chronologies provide evidence of recent tree growth decrease in a central african tropical forest

It is still unclear whether the exponential rise of atmospheric CO2 concentration has produced a fertilization effect on tropical forests, thus incrementing their growth rate, in the last two centuries. As many factors affect tree growth patterns, short -term studies might be influenced by the confounding effect of several interacting environmental variables on plant growth. Long-term analyses of tree growth can elucidate long-term trends of plant growth response to dominant drivers. The study of annual rings, applied to long tree-ring chronologies in tropical forest trees enables such analysis. Long-term tree-ring chronologies of three widespread African species were measured in Central Africa to analyze the growth of trees over the last two centuries. Growth trends were correlated to changes in global atmospheric CO2 concentration and local variations in the main climatic drivers, temperature and rainfall. Our results provided no evidence for a fertilization effect of CO2 on tree growth. On the contrary, an overall growth decline was observed for all three species in the last century, which appears to be significantly correlated to the increase in local temperature. These findings provide additional support to the global observations of a slowing down of C sequestration in the trunks of forest trees in recent decades. Data indicate that the CO2 increase alone has not been sufficient to obtain a tree growth increase in tropical trees. The effect of other changing environmental factors, like temperature, may have overridden the fertilization effect of CO2.It is still unclear whether the exponential rise of atmospheric CO2 concentration has produced a fertilization effect on tropical forests, thus incrementing their growth rate, in the last two centuries. As many factors affect tree growth patterns, short -term studies might be influenced by the confounding effect of several interacting environmental variables on plant growth. Long-term analyses of tree growth can elucidate long-term trends of plant growth response to dominant drivers. The study of annual rings, applied to long tree-ring chronologies in tropical forest trees enables such analysis. Long-term tree-ring chronologies of three widespread African species were measured in Central Africa to analyze the growth of trees over the last two centuries. Growth trends were correlated to changes in global atmospheric CO2 concentration and local variations in the main climatic drivers, temperature and rainfall. Our results provided no evidence for a fertilization effect of CO2 on tree growth. On the contrary, an overall growth decline was observed for all three species in the last century, which appears to be significantly correlated to the increase in local temperature. These findings provide additional support to the global observations of a slowing down of C sequestration in the trunks of forest trees in recent decades. Data indicate that the CO2 increase alone has not been sufficient to obtain a tree growth increase in tropical trees. The effect of other changing environmental factors, like temperature, may have overridden the fertilization effect of CO2

Selectivity of the CUBAN domain in the recognition of ubiquitin and NEDD8

Among the members of the Ubiquitin‐like (Ubl) protein family, Neural precursor cell expressed developmentally down‐regulated protein 8 (NEDD8) is the closest in sequence to ubiquitin (57% identity). The two modification mechanisms and their functions, however, are highly distinct and the two Ubls are not interchangeable. A complex network of interactions between modifying enzymes and adaptors, most of which are specific while others are promiscuous, ensures selectivity. Many domains that bind the ubiquitin hydrophobic patch also bind NEDD8 while no domain that specifically binds NEDD8 has yet been described. Here we report an unbiased selection of domains that bind ubiquitin and/or NEDD8 and we characterize their specificity/promiscuity. Many ubiquitin binding domains bind ubiquitin preferentially and, to a lesser extent, NEDD8. In a few cases, the affinity of these domains for NEDD8 can be increased by substituting the alanine at position 72 with arginine, as in ubiquitin. We have also identified a unique domain, mapping to the carboxyl‐end of the protein KHNYN, which has a starkly preference for NEDD8. Given its ability to bind neddylated cullins we have named this domain CUBAN (Cullin Binding domain Associating with NEDD8). We present here the solution structure of the CUBAN domain both in the isolated form and in complex with NEDD8. The results contribute to the understanding of the discrimination mechanism between ubiquitin and the Ubl. They also provide new insights on the biological role of a ill‐defined protein, whose function is hitherto only predicted

A novel approach for the purification and proteomic analysis of pathogenic immunglobulin free light chains from serum

An excess of circulating monoclonal free immunoglobulin light chains (FLC) is common in plasma cell disorders. A subset of FLC, as amyloidogenic ones, possess intrinsic pathogenicity. Because of their complex purification, little is known on the biochemical features of serum FLC, possibly related to their pathogenic spectrum. We developed an immunopurification approach to isolate serum FLC from patients with monoclonal gammopathies, followed by proteomic characterization. Serum monoclonal FLC were detected and quantified by immunofixation and immunonephelometry. Immunoprecipitation was performed by serum incubation with agarose beads covalently linked to polyclonal anti-κ or λ FLC antibodies. Isolated FLC were analyzed by SDS-PAGE, 2D-PAGE, immunoblotting, mass spectrometry (MS). Serum FLC were immunoprecipitated from 15 patients with ALλ amyloidosis (serum λ FLC range: 98-2350mg/L), 5 with ALκ amyloidosis and 1 with κ light chain (LC) myeloma (κ FLC range: 266-2660mg/L), and 3 controls. Monoclonal FLC were the prevalent eluted species in patients. On 2D-PAGE, both λ and κ FLC originated discrete spots with multiple pI isoforms. The nature of eluted FLC and coincidence with the LC sequence from the bone marrow clone was confirmed by MS, which also detected post-translational modifications, including truncation, tryptophan oxidation, cysteinylation, peptide dimerization. Serum FLC were purified in soluble form and adequate amounts for proteomics, which allowed studying primary sequence and detecting post-translational modifications. This method is a novel instrument for studying the molecular bases of FLC pathogenicity, allowing for the first time the punctual biochemical description of the circulating forms