Seasonality Modifies Methylation Profiles in Healthy People

DNA methylation is a well-characterized epigenetic modification that plays an important role in the regulation of gene expression. There is growing evidence on the involvement of epigenetic mechanisms in disease onset, including cancer. Environmental factors seem to induce changes in DNA methylation affecting human health. However, little is known about basal methylation levels in healthy people and about the correlation between environmental factors and different methylation profiles. We investigated the effect of seasonality on basal methylation by testing methylation levels in the long interspersed nucleotide element-1 (LINE-1) and in two cancer-related genes (RASSF1A and MGMT) of 88 healthy male heavy smokers involved in an Italian randomized study; at enrolment the subjects donated a blood sample collected in different months. Methylation analyses were performed by pyrosequencing. Mean methylation percentage was higher in spring and summer for the LINE1, RASSF1A and MGMT genes (68.26%, 2.35%, and 9.52% respectively) compared with autumn and winter (67.43%, 2.17%, and 8.60% respectively). In particular, LINE-1 was significantly hypomethylated (p = 0.04 or 0.05 depending on the CpG island involved) in autumn and winter compared with spring and summer. Seasonality seems to be a modifier of methylation levels and this observation should be taken into account in future analyses.     

Genetic analysis of durable resistance against leaf rust in durum wheat

The Italian durum wheat cultivar Creso possesses a high level of durable resistance to leaf rust based on both hypersensitive and non-hypersensitive components. In order to investigate the genetic basis of this resistance, a segregating population composed of 123 recombinant inbred lines (RILs) derived from the cross Creso × Pedroso, was evaluated for disease severity in adult plants under field conditions. Furthermore, the resistance of parents and RILs was evaluated by assessing macroscopically the latency period and microscopically the number and type of pathogen colonies formed following artificial inoculation with a specific isolate. This experiment was performed at controlled conditions at two developmental stages. Besides some minor QTLs, one major QTL explaining both reduction of disease severity in the field and increased latency period was found on the long arm of chromosome 7B, and closely associated PCR-based and DArT markers were identified. Daniela Marone and Ana I. Del Olmo contributed equally to the work.     

Regulation of cell-matrix adhesion by OLA1, the Obg-like ATPase 1

Attachment of cells to the extracellular matrix induces clustering of membrane receptor integrins which in turn triggers the formation of focal adhesions (FAs). The adaptor/scaffold proteins in FAs provide linkage to actin cytoskeleton, whereas focal adhesion kinase (FAK) and other FA-associated kinases and phosphatases transduce integrin-mediated signaling cascades, promoting actin polymerization and progression of cell spreading. In this study, we explored the role of OLA1, a newly identified member of Obg-like ATPases, in regulating cell adhesion processes. We showed that in multiple human cell lines RNAi-mediated downregulation of OLA1 significantly accelerated cell adhesion and spreading, and conversely overexpression of OLA1 by gene transfection resulted in delayed cell adhesion and spreading. We further found that OLA1-deficient cells had elevated levels of FAK protein and decreased Ser3 phosphorylation of cofilin, an actin-binding protein and key regulator of actin filament dynamics, while OLA1-overexpressing cells exhibited the opposite molecular alterations in FAK and cofilin. These findings suggest that OLA1 plays an important negative role in cell adhesion and spreading, in part through the regulation of FAK expression and cofilin phosphorylation, and manipulation of OLA1 may lead to significant changes in cell adhesion and the associated phenotypes.     

Immunomodulatory mediators from pollen enhance the migratory capacity of dendritic cells and license them for Th2 attraction

The immune response of atopic individuals against allergens is characterized by increased levels of Th2 cytokines and chemokines. However, the way in which the cytokine/chemokine profile is matched to the type of invading allergen, and why these profiles sometimes derail and lead to disease, is not well understood. We recently demonstrated that pollen modulates dendritic cell (DC) function in a way that results in an enhanced capacity to initiate Th2 responses in vitro. Here, we examined the effects of aqueous birch pollen extracts (Bet.-APE) on chemokine receptor expression and chemokine production by human monocyte-derived DCs. Bet.-APE strongly induced expression and function of CXCR4 and reduced CCR1 and CCR5 expression on immature DCs. In addition, DC treatment with Bet.-APE significantly reduced LPS-induced production of CXCL10/IP-10, CCL5/RANTES; induced CCL22/macrophage-derived chemokine; and did not significantly change release of CCL17/thymus and activation-regulated chemokine. At a functional level, Bet.-APE increased the capacity of LPS-stimulated DCs to attract Th2 cells, whereas the capacity to recruit Th1 cells was reduced. Bet.-APE significantly and dose-dependently enhanced intracellular cAMP, suggesting that water-soluble factors from pollen grains bind a G(alphas)-protein-coupled receptor. E(1)-Phytoprostanes were identified to be one player in the Th2-polarizing potential of aqueous pollen extracts. In summary, our results demonstrate that pollen itself releases regulatory mediators which generate a Th2-promoting micromilieu with preferential recruitment of Th2 cells to the site of pollen exposure.     

3,4-Dihydroquinazoline derivatives inhibit the activities of cholinesterase enzymes

A series of 3,4-dihydroquinazoline derivatives consisting of the selected compounds from our chemical library on the diversity basis and the new synthetic compounds were in vitro tested for their inhibitory activities for both acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum) enzymes. It was discovered that most of the compounds displayed weak AChE and strong BuChE inhibitory activities. In particular, compound 8b and 8d were the most active compounds in the series against BChE with IC₅₀ values of 45 nM and 62 nM, as well as 146- and 161-fold higher affinity to BChE, respectively. To understand the excellent activity of these compounds, molecular docking simulations were performed to get better insights into the mechanism of binding of 3,4-dihydroquinazoline derivatives. As expected, compound 8b and 8d bind to both catalytic anionic site (CAS) and peripheral site (PS) of BChE with better interaction energy values than AChE, in agreement with our experimental data. Furthermore, the non-competitive/mixed-type inhibitions of both compounds further confirmed their dual binding nature in kinetic studies.     

Heating systems LCA: comparison of biomass-based appliances

Purpose

Biomass provides an attractive solution for residential heating systems based on renewable fuels, even though biomass-based domestic heating systems are recognized as significant particulate matter emitters; thus, a life cycle assessment (LCA) approach was used in the study to compare two different appliances: a wood stove and a pellet stove, both modeled according to the best available technologies definition.

Methods

System boundaries of each scenario refer to a cradle-to-grave approach, including production, use and disposal of the heating appliance, as well as the preparation of biomass feedstock. The assessment of environmental impacts was performed assuming 1 MJ of thermal energy as the reference flow, considering the categories of particulate matter formation, human toxicity, climate change, and fossil fuel depletion, according to the ReCiPe 1.07 method. Finally, the comparison was extended to certain innovative heating systems in order to qualitatively evaluate potential improvements in residential heating performances.

Results and discussion

The results show that the wood stove reaches the highest scores in the categories of particulate matter formation and negative effects for human toxicity, as a consequence of the stove’s lower combustion efficiency, which would lead to a preference for the pellet stove. However, when climate change affecting human health and the ecosystem, and fossil depletion are considered, the choice appears more uncertain due to the energy consumption from the pelletizing step. Alternative technologies (e.g., solar panels in combination with a gas boiler) show better scores related to fine particles emission reduction, even if a worsening in other categories is observed. The results were validated by a sensitivity analysis.

Conclusions

The study suggests that a LCA approach can support the choice of the best domestic heating system, helping to promote policy initiatives on a sound basis and to understand which are the main key levers to act for reducing the total environmental burdens of biomass-based heating appliances.     

Grasping Hand Verbs: Oscillatory Beta and Alpha Correlates of Action-Word Processing

The grounded cognition framework proposes that sensorimotor brain areas, which are typically involved in perception and action, also play a role in linguistic processing. We assessed oscillatory modulation during visual presentation of single verbs and localized cortical motor regions by means of isometric contraction of hand and foot muscles. Analogously to oscillatory activation patterns accompanying voluntary movements, we expected a somatotopically distributed suppression of beta and alpha frequencies in the motor cortex during processing of body-related action verbs. Magnetoencephalographic data were collected during presentation of verbs that express actions performed using the hands (H) or feet (F). Verbs denoting no bodily movement (N) were used as a control. Between 150 and 500 msec after visual word onset, beta rhythms were suppressed in H and F in comparison with N in the left hemisphere. Similarly, alpha oscillations showed left-lateralized power suppression in the H-N contrast, although at a later stage. The cortical oscillatory activity that typically occurs during voluntary movements is therefore found to somatotopically accompany the processing of body-related verbs. The combination of a localizer task with the oscillatory investigation applied to verb reading as in the present study provides further methodological possibilities of tracking language processing in the brain.     

Effectiveness of a microbial formula,as a bioaugmentation agent,tailored for bioremediation of diesel oil and heavy metal co-contaminated soil

The activation of natural bioremediation potentials is the challenge that research is currently addressing for overcoming bottlenecks still affecting bioremediation applications. Bioaugmentation is one possible way to activate such natural potentials, provided that the biodiversity introduced to increase catabolically relevant capacity is identified also considering the ecological context. The present work deals with bioaugmentation aimed at the remediation of a soil co-contaminated (spiked) with both diesel oil (1%, v/w), and heavy metals (Pb and Zn), using intact soil core microcosms in different experimental conditions. We supposed that both heavy metal resistance and active metabolism towards organic pollutants are essential metabolic traits to trap the energetic flux, which drives the microbial community towards biodegradation under the given experimental conditions. Consequently, the bioaugmentation was performed by introducing a tailor made microbial formula composed of 12 allochthonous strains. They belong to a stable population previously isolated from a chronic polluted site and are both hydrocarbon degraders and heavy metal resistant and, also, compatible with the autochthonous microbial community. The active role of the microbial formula in pushing the entire community towards an effective bioremediation of diesel oil close to 75%, in the presence of bioavailable metals, has been proven through hydrocarbons analysis, metabolic and molecular profiling at community level (Biolog system, DGGE).