131,222 research outputs found
Insights into molecular mechanisms of metallodrugs using metallomic studies
No full textMetal ions are the center of an important class of therapeutics, i.e. metallodrugs for their unique coordination geometries and redox states. Many cellular functions depend on the interaction of metal ions with proteins, as well as the transport and uptake of metals into cells, storage and secretion which are regulated by peculiar control systems. The cellular redox homeostasis is regulated by a plethora of factors including metal ions that can produce reactive radicals and its dysregulation can lead to oxidative stress as observed in pathological conditions in many diseases as cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's, Parkinson's disease) and chronic inflammation. Omics approaches can provide in-depth insights into the mechanisms of action (MOAs) of metallo-therapeutic compounds and metallomics is a proteomic tool that allows to investigate MOAs of metallodrugs, including their physiological metabolism (e.g., cellular distribution and biotransformation) and their molecular targets. Herein, we review the most recent and significant metallomic studies concerning metallodrugs in pathological cellular conditions including oxidative stress
Mangrovivirga cuniculi Sefrji & Michoud & Marasco & Merlino & Daffonchio 2021, SP. NOV.
No full textDESCRIPTION OF MANGROVIVIRGA CUNICULI SP. NOV. Mangrovivirga cuniculi (cu.ni.cu′ li. L. gen. n. cuniculi of a burrow, named because the type species was isolated from a crab burrow). The cell morphology and chemotaxonomic characteristics are given in the genus description. Cells are 0.3–0.5 µm wide and 1–1.2µm long. Its colonies are circular with a diameter of 1–2mm and feature regular edges, a smooth and shiny surface, and an orange colour caused by the production of orange carotenoids. The permissive conditions for growth are a temperature of 20–40 °C (optimum, 37°C), pH 6–10 (optimum, pH 8) and 3%–11% NaCl for salinity (optimum, 7%–9% NaCl). The carbon sources used for growth are pectin, 2-deoxy-D-ribose,Dribose, 5-keto-D-gluconic acid,L-ornithine, dihydroxyacetone, thymidine, uridine and adenosine. The genome harbours genes responsible for protection against oxidative, osmotic and salinity stresses, and includes genes encoding proteins that produce osmoprotectants and carotenoids. The cells are negative for amylase, protease, lipase, cellulase, indole, siderophore production and phosphate solubilization, and are positive for auxin (IAA) and ammonia production. The strain is unable to reduce nitrate to nitrite. The type strain, R1DC9 T (=KCTC 72349 T =JCM 33609 T =NCCB 100698 T), was isolated from bioturbated mangrove sediment at the Ibn Sina Field Research Station and Nature Conservation Area in KAUST, Saudi Arabia. The genomic DNA G+C content and genome size of the type strain are 63.1 mol% and 4661901 bp, respectively.Published as part of Sefrji, Fatmah O., Michoud, Grégoire, Marasco, Ramona, Merlino, Giuseppe & Daffonchio, Daniele, 2021, MaNgROVIVIRga CUNICULI gen. nov., sp. nov., a moderately halophilic bacterium isolated from bioturbated Red Sea mangrove sediment, and proposal of the novel family MaNgROVIVIRgaCeae fam. nov., pp. 1-11 in International Journal of Systematic and Evolutionary Microbiology (004866) (004866) 71 (7) on page 9, DOI: 10.1099/ijsem.0.004866, http://zenodo.org/record/622410
Are peptidomimetics the compounds of choice for developing new modulators of the JAK-STAT pathway?
No full textProtein-protein interactions (PPIs) play critical roles in a wide range of biological processes including the dysregulation of cellular pathways leading to the loss of cell function, which in turn leads to diseases. The dysfunction of several signaling pathways is linked to the insurgence of pathological processes such as inflammation, cancer development and neurodegeneration. Thus, there is an urgent need for novel chemical modulators of dysregulated PPIs to drive progress in targeted therapies. Several PPIs have been targeted by bioactive compounds, and, often, to properly cover interacting protein regions and improve the biological activities of modulators, a particular focus concerns the employment of macrocycles as proteomimetics. Indeed, for their physicochemical properties, they occupy an intermediate space between small organic molecules and macromolecular proteins and are prominent in the drug discovery process. Peptide macrocycles can modulate fundamental biological mechanisms and here we will focus on peptidomimetics active on the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways
Identification of inhibitors of biological interactions involving intrinsically disordered proteins
No full textProtein-protein interactions involving disordered partners have unique features and represent prominent targets in drug discovery processes. Intrinsically Disordered Proteins (IDPs) are involved in cellular regulation, signaling and control: they bind to multiple partners and these high-specificity/low-affinity interactions play crucial roles in many human diseases. Disordered regions, terminal tails and flexible linkers are particularly abundant in DNA-binding proteins and play crucial roles in the affinity and specificity of DNA recognizing processes. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few "hot spots", thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Here, we propose a panoramic review of the structural features of IDPs and how they regulate molecular recognition mechanisms focusing attention on recently reported drug-design strategies in the field of IDPs
Utilization of cellobiose and other β-D-glucosides in Agrobacterium tumefaciens
No full textAgrobacterium tumefaciens strain C58 was able to utilize carbon from cellobiose and some other β-D-glucosides as efficiently as from glucose. β-D-glucoside utilization was partially inducible and the induction was subject to catabolite repression by glucose, independently of the presence of cyclic AMP in the medium. It was also independent of Ti plasmid-encoded functions. β-D-glucosides were hydrolysed by a single, cytoplasmic and constitutively expressed β-glucosidase, which was active on non-phosphorylated substrates and insensitive to glucose inhibition. © 1995
New mimetic peptides of Kinase Inhibitory Region (KIR) of SOCS1 through focused peptide libraries
No full textSOCS (suppressor of cytokine signalling) proteins are negative-feedback regulators of the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) pathway. Their expression levels are low under physiological conditions, but they are up-regulated in response to cytokine stimulation in many immune and inflammatory processes. Overexpression of SOCS1 in keratinocyte clones abrogates the IFNγ (interferon γ)-induced expression of many pro-inflammatory genes and the release of related chemokines by blocking the JAK/STAT pathway. SOCS1 inhibits JAK2 kinase activity by binding the catalytic site of JAK2, with its KIR (kinase-inhibitory region) acting as a pseudo-substrate of the enzyme. In the present study, we screened a focused combinatorial peptide library of KIR to identify new peptides able to mimic its function with an improved affinity towards the JAK2catalytic site.Using an alanine-scanning method, KIR residues that are crucial for the interaction with JAK2 were unveiled. In this way, the KIR sequence was restricted to a shorter segment and 'non-essential' residues were replaced by different amino acids following a simplified combinatorial approach. We selected a new unnatural sequence able to bind to JAK2 with K d values in the nanomolar range. This peptide was tested in human keratinocyte cultures and reduced the phosphorylation of STAT1 and the expression levels of IRF-1 (interferon regulatory factor-1). ©The Authors Journal compilation ©2012 Biochemical Society
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
'MORE CROP PER DROP': THE CONTRIBUTE OF PLANT GROWTH PROMOTING BACTERIA
No full textEnvironmental stresses are main factors limiting crop production worldwide. Water stress is a primary cause of crop losses, reducing average yields for most of the major crops by more than 50%, particularly in arid and semi-arid regions. Moreover, the increasing frequency of dry periods in many regions of the world, as a consequence of the global warming, frequently results in saline soils with low agricultural potential. Bacteria are among the first colonizers of soil habitats at different stages of development, largely contributing in determining soil structure and composition. In this context, understanding the diversity of soil- and plant-associated bacteria and their roles in soil structure maintenance, protection of plant health and development under harsh conditions is crucial, assuming that these associations could be manipulated to increase the productivity and sustainability of agro-ecosystems.
A new emerging approach to improve crop production without extending agriculture surfaces and agro-chemicals use, is the exploitation of the natural microbiota contribute in soil structure determination and of the association of plants with Plant Growth Promoting Bacteria (PGPB). During the last couple of decades, the use of PGPB for sustainable agriculture was increased in different parts of the world resulting in significant improvement in growth and yield of agronomical important crops, also in arid land. These beneficial bacteria can colonize the rhizosphere soil or the root system, and even thrive in the plant tissues as endophytic populations. Bacterial mechanisms of plant growth promotion include biological nitrogen fixation, synthesis of phytormones, stress reduction or protection from pathogens. In addition, plant-associated communities also increase availability of nutrients such as phosphorous, iron and other elements, playing key roles in ecosystem processes such as nutrient cycling and conservation of soil structure. To remove the erratic performance of microbial inoculation, the selection of native bacteria acclimatized to harsh environmental condition has been advocated. Recent reports documented the efficiency of PGP bacteria isolated from plants growing in arid and semi-arid regions.
This PhD thesis aimed to explore the microbial contribution in soil neogenesis in deglaciating environments where a soil fertility gradient can be envisaged. Besides, this thesis has the proposal to exploit the PGP properties of endophytes and rhizobacteria adapted to harsh conditions to develop an eco-friendly approach for the improvement of crop productivity in arid environments. For this purpose, a large collection of 5000 bacteria associated to plants grown in arid areas was established. Bacteria were isolated from the root tissues and soil fraction at increasing distance from the plant: the rhizosphere, the root surrounding soil and the bulk soil. The selected plants were Olea europea (olive tree), Vitis vinifera (grapevine) and Capsicum annuum (pepper) growing in arid and semi-arid regions of Tunisia, Egypt and Italy. These agricultural crops have a relevant economic interest in the Mediterranean basin and are known to be highly adapted to extreme stressful conditions of arid land, thus allowing to improve the chances to select drought resistant bacteria.
Analysis of the abundance and diversity of the cultivable bacterial fraction from root tissues and rhizosphere showed a difference in the spatial distribution of bacterial genera associated to the plants. In olive tree we observed higher bacterial densities in the rhizosphere compared to endophytic populations, due to the release of exudates in the rhizosphere from living roots.
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Besides, the low phylogenetic diversity observed in the endophyte fraction indicated that plant tissues may select specific bacterial colonizers. Particularly, the endophytes were dominated by the sporeformer Bacillales order represented by the genera Bacillus, Paenibacillus and Brevibacillus. The dominant order cultured from soil fractions was Actinobacteria, with dominant genera such as Arthrobacter and Streptomyces, frequently isolated from dry soils and desert crusts. Differently, in pepper plants sampled in Egypt and Italy the endophytic isolates were affiliated exclusively to the Bacilli class. Differently, isolates belonging to the gamma subgroup of the class Proteobacteria were predominant in rhizosphere, root surrounding soil and bulk soil of pepper plants from Egypt, with many of these isolates assigned to Enterobacteriaceae family, in particular to Klebsiella, Citrobacter, Raoultella genera and to the genus Pseudomonas. The family Enterobacteraceae comprises many species with enteric habitat, which origin could be attributable to the use of irrigation water of low hygienic quality.
The isolates from the different plant models were tested in vitro for their plant growth promotion (PGP) activities allowing to identify polyvalent isolates, i.e. those capable of expressing multiple activities against drought and salinity stresses. The results showed that 90% of the isolated bacteria presented multiple and differentiated PGP activities. All the isolates were osmotolerant, but a differential distribution of the PGP activities was observed among the different root system fractions sampled, with enhanced abilities for rhizobacteria in phosphate solubilisation, siderophore and ammonia production. Moreover, the results showed that bacteria belonging to the Bacillus genus often presented all the PGP activities tested and were able to tolerate harsh abiotic stresses, suggesting their possible use as inocula for sustaining agriculture in arid land.
Hence, the research was focused on bacteria endowed with 1-aminocyclopropane-1-carboxylate deaminase (ACCd) activity, able to hydrolyze ACC, the immediate biosynthetic precursor of ethylene. Ethylene is the stress hormone synthesized by plants as a direct consequence of stressful condition, causing a reduction of in plant growth. The expression of ACCd by plant associated bacteria could decrease the concentration of ethylene, releasing the plant from stress and preserving normal growth. The most active ACCd endophyte and rhizobacteria strains with multiple PGP activities isolated from herbaceous, Capsicum annuum L, and arboreal, Vitis vinifera cv. Barbera, plants were further assayed in a in vivo assay on the plants of origin. Experiments in microcosms subjected to different levels of water stress were performed using non sterilized soil in order to evaluate PGP inocula interaction with the autochthonous microbiota. The results showed different efficiency in plant growth promotion potential, nevertheless some strains displayed the distinctive attribute to sustain pepper and grapevine growth under drought. In pepper, strains PACC-R01, -R08 and -R10 increased both the fresh and dry root biomass by a 40-60% range, whereas two consortia of grapevine strains were able to improve the biomass of the aerial plant portion in grapevine plantlets.
To unravel the mechanism involved in plant growth promotion and the inner relationship between plant and bacteria, we focused our attention on endophytic bacteria isolated from pepper plant in arid Italian soils endowed with ACCd activity. Pepper plants grown hydroponically were inoculated with two strains, E1 and E3 belonging to Bacillus and Paenibacillus genera, respectively, in a nutrient solution with the addition of
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polyetilenglycole (PEG) to induce water stress. The strains were rhizo-competent and actively colonized different plant organs, as observed by microscopy analysis of gfp-cells and by re-isolation experiments. Gfp-E1 cells were able to tightly adhere on root surface and to envelop root hairs. Confocal microscopy showed the presence of gfp-cells in the outer cortex, confirming the bacteria ability to penetrate plant tissue. Re-isolation of rifampicin resistant (RifR) mutant strains revealed that endophytes were able to colonize the root system and also stems and leaves. The promotion of plant growth during drought was assessed at the leaf level by gas exchange measurements, determining net photosynthesis (Pn), evaporation/ transpiration (E) and stomatal conductance (Gs). After PEG addition, inoculated plants showed values of Pn, E and Gs parameters significantly higher than non inoculated plants. These data were reconfirmed also in a soil system in which plants experienced 12 days of water deprivation. At the root level, bacterial strains directly affected Na+ and K+ content: in the presence of PEG their concentration increased in inoculated plants respect to the control ones. The involvement of the vacuolar proton pumps H+-PPase and ATPase was investigated. An increase in H+-PPase expression in inoculated plants respect to control plants was observed both by Western Blot analysis and immuno-histochemical experiments. H+-PPase protein levels increased up to 51% in E1 and 96% in E3 inoculated plants. A similar increase in H+-PPase activity was observed. The proposed mechanism is that the increased expression and activity of the pump determines a decrease in the vacuolar potential, thus requiring an enhanced flux of water from the soil. The collected data suggest that the pump activation is mainly driven by the endophytes interaction.
The data obtained within this thesis project emphasize that PGP bacteria represent a potential eco-friendly solution to optimize soil stability, maximize plant survival and productivity under adverse environmental conditions. Besides, we provided a fine tuning of the experimental design to enhance the chances to select bacteria with the distinctive trait of stimulating plant growth during drought, using a combined approach based on the selection of site and plant of origin. A large microbial collection has been established and besides several strains showed (i) high levels of plant colonisation ability, (ii) plant growth promotion, and (iii) osmotic tolerance, that could be further exploited in field trials in the regions and countries suffering desertification
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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