797 research outputs found
Tomato ionomic approach for food fortification and safety.
Food fortification is an issue of paramount of importance for people living both in developed
and in developing countries. Among substances listed as "nutriceuticals", essential minerals have
been recognised for their involvement in several healthy issues, involving all ages. In this frame,
food plants are playing a pivotal role since their capability to compartmentalise ions and proteinmetal
complexes in edible organs. Conversely, the accumulation of high metal levels in those
organs may lead to safety problems. In the recent years, thanks to the availability of new and
improved analytical apparatus in both ionic and genomic/transcrittomics areas, it is became feasible
to couple data coming from plant physiology and genetics. Ionomics is the discipline that studies
the cross-analysis of both data sets. Our group, in the frame of GenoPom project granted by MiUR,
is interested to study the ionomics of tomatoes cultivars derived by breeding programmes in which
wild relatives have been used to transfer several useful traits, such as resistance to biotic or abiotic
stresses, fruit composition and textiture, etc. The introgression of the wild genome into the
cultivated one produces new gene combinations. They might lead to the expression of some traits,
such as increased or reduced adsorption of some metals and their exclusion or loading into edible
organs, thus strongly involving the nutritional food value. Our final goal is to put together data
coming from ions homeostasis and gene expression analyses, thus obtaining an ionomic tomato
map related to ions absorption, translocation and accumulation in various plant organs, fruits
included. To follow our hypothesis, we are studying the ionome of Solanum lycopersicum cv. M82
along with 76 Introgression Lines (ILs) produced by interspecific crosses between this cultivar and
the wild species S. pennellii. These ILs are homozygous for small portions of the wild species
genome introgressed into the domesticated M82 one. They are used as a useful tool for mapping
QTL associated with many traits of interest. It is worthy to note that, until now, little information is
available on QTL for ions accumulation in tomato. Moreover, as our knowledge, effects of new
gene combinations in introgressed lines on ions uptake related to food safety have not been
extensively studied. In this presentation we show results coming from the ionome analysis, carried
out on S . lycopersicum M82 and several ILs. Plants were grown in pots in a greenhouse and
watered with deionised water Thirty day-old plants were left to grow for 15 days in the presence of
non-toxic concentration of Cd, Pb, As, Cr and Zn given combined. Leaves of all plants were then
harvested and stored at -80°C for ionome and gene expression analyses. Preliminary results of
ionome analysis of S. lycopersicum M82 and several ILs, carried out using an ICP-MS, showed that
traits correlated to toxic metals and micronutrients accumulation in apical leaves were significantly
modified in response to specific genetic backgrounds. Those results are perhaps due to the
introgression of traits linked to uptake, translocation and accumulation of useful and/or toxic metal
into plant apical leaves and to interactions of the wild type introgressed genomic regions with the
cultivated genome. Also, data are shown on the identification and isolation of Solanum gene
sequences related to ions uptake, translocation and accumulation, useful for further real-time gene
expression evaluation in both cultivated and ILs during the treatments with the above-mentioned
metals
The Interplay between Antibiotics and the Host Immune Response in Sepsis: From Basic Mechanisms to Clinical Considerations: A Comprehensive Narrative Review
Sepsis poses a significant global health challenge due to immune system dysregulation. This narrative review explores the complex relationship between antibiotics and the immune system, aiming to clarify the involved mechanisms and their clinical impacts. From pre-clinical studies, antibiotics exhibit various immunomodulatory effects, including the regulation of pro-inflammatory cytokine production, interaction with Toll-Like Receptors, modulation of the P38/Pmk-1 Pathway, inhibition of Matrix Metalloproteinases, blockade of nitric oxide synthase, and regulation of caspase-induced apoptosis. Additionally, antibiotic-induced alterations to the microbiome are associated with changes in systemic immunity, affecting cellular and humoral responses. The adjunctive use of antibiotics in sepsis patients, particularly macrolides, has attracted attention due to their immune-regulatory effects. However, there are limited data comparing different types of macrolides. More robust evidence comes from studies on community-acquired pneumonia, especially in severe cases with a hyper-inflammatory response. While studies on septic shock have shown mixed results regarding mortality rates and immune response modulation, conflicting findings are also observed with macrolides in acute respiratory distress syndrome. In conclusion, there is a pressing need to tailor antibiotic therapy based on the patient's immune profile to optimize outcomes in sepsis management
Glutamate and substance P coexist in primary afferent terminals in the superficial laminae of spinal cord.
By light microscopic immunocytochemistry it has been previously shown that approximately equal to 70% of the neurons in rat dorsal root ganglia are labeled with an antiserum for glutamate conjugated to hemocyanin; the smaller among these neurons are also positive for substance P. By using a postembedding ImmunoGold method and electron microscopy, it is shown here that synaptic terminals in the superficial laminae of the spinal cord of rats selectively stain for the same glutamate antiserum. Immunolabeling is in small dome-shaped and in large scalloped synaptic terminals. Scalloped terminals are of two types. One type consists of dark terminals with many agranular vesicles of different size and a few large granular vesicles; these are probably endings of unmyelinated and small myelinated primary afferent fibers. The other type consists of light terminals with small agranular vesicles homogeneous in size with neurofilaments and many mitochondria; these are probably endings of larger myelinated primary afferent fibers. By means of double-labeling electron microscopic immunocytochemistry with colloidal gold particles of two different sizes, it is also shown here that substance P is present in only the dark type of glutamate-labeled scalloped terminals. The primary afferent origin of the terminals labeled by the antisera for glutamate and for substance P is demonstrated by a triple-labeling strategy: immunocytochemistry for both antisera on sections from rats in which dorsal rhizotomy or dorsal root ganglion injection of horseradish peroxidase conjugated to wheat germ agglutinin was performed. It is proposed that glutamate is the neurotransmitter in primary afferents mediating input from different peripheral receptor classes, including nociceptors. Effects of glutamate and substance P on spinal dorsal horn neurons may result from co-release of these two mediators from the same dorsal root afferent terminal
Approach combining the Rietveld method and pairs distribution function analysis to study crystalline materials under high-pressure and/or temperature: Application to rhombohedral Bi2Te3 phase
An approach combining the Rietveld method and pairs distribution function
analysis to study crystalline materials under high pressure or temperature was
early proposed by us, and in this study, it was applied to investigate de
effect of high pressure on the rhombohedral Bi2Te3 phase. The refined
structural parameters obtained from the Rietveld refinement of the XRD patterns
measured for pressures up to 9.1 GPa were used as input data to simulate the
partial and total structure factors SBiBi, SBiTe, STeTe, and SBi2Te3. Fourier
transformation of the Sij factors permitted to obtain the partial and total
pairs distribution functions GBiBi, GBiTe, GTeTe, and GBi2Te3. The first
coordination shells of these Gij functions are formed by subshells and, with
increasing pressure in the 1.1 to 6.3 GPa range, occur a partial separation of
subshells. Also, the increase of pressure in this range promotes a drastic
reduction in the values of the intralayer angles TeBiTe, and consequently, in
the intralayer distance TeTe. A drastic reduction in the interlayers distance
Te-Te was also observed. Several studies are reported in the literature,
including one carried out by us, show the presence of an ETT in this pressure
range. The obtained results suggest that the ETT is related with the decrease
of the intralayer angles TeBiTe, and intra- and interlayer distance TeTe.
Experimental results describing the pressure dependence the thermoelectric
power, electrical resistivity, and power fator for rhombohedral Bi2Te3 are
reported, and an enhancement of the power factor in the 1.1 to 6.3 GPa range is
observed. The results obtained in this study give evidence that this
enhancement in the power factor is related with the decrease of the intralayer
angles TeBiTe, and with the decrease of intralayer- and interlayers homopolar
TeTe bonds
Synthesis and anticancer activity of CDDO and CDDO-me, two derivatives of natural triterpenoids
Triterpenoids are natural compounds synthesized by plants through cyclization of squalene, known for their weak anti-inflammatory activity. 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), and its C28 modified derivative, methyl-ester (CDDO-Me, also known as bardoxolone methyl), are two synthetic derivatives of oleanolic acid, synthesized more than 20 years ago, in an attempt to enhance the anti-inflammatory behavior of the natural compound. These molecules have been extensively investigated for their strong ability to exert antiproliferative, antiangiogenic, and antimetastatic activities, and to induce apoptosis and differentiation in cancer cells. Here, we discuss the chemical properties of natural triterpenoids, the pathways of synthesis and the biological effects of CDDO and its derivative CDDO-Me. At nanomolar doses, CDDO and CDDO-Me have been shown to protect cells and tissues from oxidative stress by increasing the transcriptional activity of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2). At doses higher than 100 nM, CDDO and CDDO-Me are able to modulate the differentiation of a variety of cell types, both tumor cell lines or primary culture cell, while at micromolar doses these compounds exert an anticancer effect in multiple manners; by inducing extrinsic or intrinsic apoptotic pathways, or autophagic cell death, by inhibiting telomerase activity, by disrupting mitochondrial functions through Lon protease inhibition, and by blocking the deubiquitylating enzyme USP7. CDDO-Me demonstrated its efficacy as anticancer drugs in different mouse models, and versus several types of cancer. Several clinical trials have been started in humans for evaluating CDDO-Me efficacy as anticancer and anti-inflammatory drug; despite promising results, significant increase in heart failure events represented an obstacle for the clinical use of CDDO-Me
DNA Topoisomerase I differentially modulates R-loops across the human genome
Background: Co-transcriptional R-loops are abundant non-B DNA structures in mammalian genomes. DNA Topoisomerase I (Top1) is often thought to regulate R-loop formation owing to its ability to resolve both positive and negative supercoils. How Top1 regulates R-loop structures at a global level is unknown. Results: Here, we perform high-resolution strand-specific R-loop mapping in human cells depleted for Top1 and find that Top1 depletion results in both R-loop gains and losses at thousands of transcribed loci, delineating two distinct gene classes. R-loop gains are characteristic for long, highly transcribed, genes located in gene-poor regions anchored to Lamin B1 domains and in proximity to H3K9me3-marked heterochromatic patches. R-loop losses, by contrast, occur in gene-rich regions overlapping H3K27me3-marked active replication initiation regions. Interestingly, Top1 depletion coincides with a block of the cell cycle in G0/G1 phase and a trend towards replication delay. Conclusions: Our findings reveal new properties of Top1 in regulating R-loop homeostasis in a context-dependent manner and suggest a potential role for Top1 in modulating the replication process via R-loop formation
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