102,566 research outputs found
Yeast and yeast-like diversity in the southernmost glacier of Europe (Calderone Glacier, Apennines, Italy)
No full textThe present study reports the characterization of psychrophilic yeast and yeast-like diversity in cold habitats (superficial and deep sediments, ice cores and meltwaters)
of the Calderone Glacier (Italy), which is the southernmost glacier in
Europe. After incubation at 4 and 20°C, sediments contained about 10^2–10^3 CFU of yeasts g^(-1). The number of viable yeast cells in ice and meltwaters was several orders of magnitude lower. The concomitant presence of viable bacteria and filamentous fungi has also been observed. In all, 257 yeast strains were isolated and identified by 26S rRNA gene D1/D2 and internal transcribed spacers (1 and 2)
sequencing as belonging to 28 ascomycetous and basidiomycetous species of 11 genera (Candida, Cystofilobasidium, Cryptococcus, Dioszegia, Erythrobasidium, Guehomyces, Mastigobasidium, Mrakia, Mrakiella, Rhodotorula and Sporobolomyces).
Among them, the species Cryptococcus gastricus accounted for almost 40% of the total isolates. In addition, 12 strains were identified as belonging to the yeast-like species Aureobasidium pullulans and Exophiala dermatitidis, whereas 15 strains, presumably belonging to new species, yet to be described, were also isolated. Results herein reported indicate that the Calderone Glacier, although currently considered a vanishing ice body due to the ongoing global-warming phenomenon, still harbors viable psychrophilic yeast populations. Differences of
yeast and yeast-like diversity between the glacier under study and other worldwide cold habitats are also discussed
Study of expression and role of Metabotropic Glutamate Receptors in Human Acute Myeloid Leukemia cell lines and involvement of L1-CAM in migration of mGluR1+ mouse melanoma cell lines
No full textmGluRs are a family of G-coupled protein receptors with widespread expression in the central nervous system (CNS), some normal tissues, and in various cancers. The predominant functions of mGluRs in the CNS are modulating presynaptic neurotransmission but in cancers, mGluRs are involved in regulating cell proliferation.
Acute Myeloid Leukemia (AML) is a clonal, malignant disease of hematopoietic tissue and is the most common type of acute leukemia in adults and the elderly. Despite the wide number of drugs available to treat this disease, there are many unmet needs in AML therapy; relapsed or refractory patients or those unable to receive intensive chemotherapy display a poor prognosis.
Skin cancer is described as the abnormal multiplication of skin cells, which is frequently detected in sun-exposed regions. Basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, cutaneous lymphoma, Kaposi sarcoma, and melanoma are the six primary forms. Melanoma is the most severe form of skin cancer and is caused by melanocyte transformation. In the United States, invasive melanoma is expected to account for about 100,000 new cases and over 7,000 fatalities from skin cancer in 2022.
In this study, there are two distinct studies, in one, we evaluated metabotropic glutamate receptors (mGluRs) to assess if one or more of mGluRs may be a putative therapeutic target in AML. We have found a novel, previously unknown role of mGluRs in AML. The second study is to use mGluR1+ mouse melanoma cell lines to determine if the presence of L1-NCAM (CD171), a neural cell adhesion molecule 1 is involved in cell migration as shown previously in glioblastoma cell
Large-conductance, Ca2+-activated K+ channels: function, pharmacology and drugs
No full textBecause of the physiological role played by the hyperpolarisation process resulting from a K(+) outflow, it is not surprising that compounds able to activate outward K(+) channels are considered as promising drugs, with exciting perspectives for the treatment of several cardiovascular, respiratory, neurological and urological diseases. Among the different and numerous K(+) channel families, medicinal chemistry has focused its major interest onto two channel types: the ATP-sensitive channels (K(ATP)) and the large conductance subtype (BK), that belongs to the wide family of calcium-activated K(+) channels. BK channels are almost ubiquitous and exhibit single channel conductance of 100-300 pS, a property which justifies the potent role of these channels in the control of the membrane potential. BK channels have been investigated as potential therapeutic targets for different neuropathies, because of their profound influence on the neuronal activity. Moreover, BK channels are expected to have applications for the therapy of cardiovascular diseases. A potent feed-back control of the vascular and non-vascular smooth muscle tone is mediated by these channels, whose activation can be promoted by both a rise of the intracellular free calcium concentration as well as a membrane depolarisation. Additionally, BK channel activation can also be induced by other factors, such as cAMP-mediated phosphorylation, G-proteins, GMP and cGMP. The aim of this paper is to give a concise overview of the biological and pharmacological properties and potential therapeutic applications of activators of BK channels present at the vascular level. The "state of the art" in the pharmaceutical development of natural and synthetic BK-activators, with a description of the lead chemical structures, will be also described
mentha: a resource for browsing integrated protein-interaction networks
No full textAbout mentha
mentha archives evidence collected from different sources and presents these data in a complete and comprehensive way. Its data comes from manually curated protein-protein interaction databases that have adhered to the IMEx consortium. The aggregated data forms an interactome which includes many organisms. mentha is a resource that offers a series of tools to analyse selected proteins in the context of a network of interactions. Protein interaction databases archive protein-protein interaction (PPI) information from published articles. However, no database alone has sufficient literature coverage to offer a complete resource to investigate "the interactome".
mentha's approach generates every week a consistent interactome (graph). Most importantly, the procedure assigns to each interaction a reliability score that takes into account all the supporting evidence. mentha offers eight interactomes (Homo sapiens, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Escherichia coli K12, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae) plus a global netowrk that comprises every organism, including those not mentioned. The website and the graphical application are designed to make the data stored in mentha accessible and analysable to all users
High-resolution Structures of Retinol-Binding Protein in Complex with Retinol: pH-induced Protein Structural Changes in the Crystal State
No full textThe targeted delivery of non-polar ligands by binding proteins to membranes or membrane receptors involves the release of these ligands on or near the plasma membrane of target cells. Because these hydrophobic ligands are often bound inside a deep cavity of binding proteins, as shown previously for plasma retinol-binding protein (RBP), their release from these proteins might require the destabilization of the protein structure by partially denaturing conditions, such as those possibly present near plasma membranes. RBP is a plasma transport protein which delivers specifically retinol from its. store sites to target cells. Here, we report the high-resolution (1.1-1.4 Angstrom) crystal structures of bovine holo-RBP at five different pH values, ranging from 9 to 2. While unraveling details of the native protein structure and of the interactions with retinol at nearly atomic resolution at neutral pH, this study provides evidence for definite pH-induced modifications of several structural features of RBR The structure most representative of the changes that holo-RBP undergoes at different pH values is that of its flexible state at pH 2. At this pH, most significant are the alteration of the arrangement of salt bridges and of the network of water molecules/H-bonds that participates in the retinol-RBP interaction, an appreciable increase of the volume of the beta-barrel cavity, a considerably higher degree of mobility of the RBP-bound ligand and of several protein regions and the disorder of a large number of solvent molecules that are ordered at neutral pH. These changes are likely to be accompanied by a modification of the pattern of charge distribution on the protein surface. All these changes, which reveal a substantially lowered conformational stability of RBP, presumably occur at the initial stages of the acidic denaturation of RBP and are possibly associated with a facilitated release of the retinol molecule from its carrier protein
Computer-driven development of an in silico tool for finding selective histone deacetylase 1 inhibitors
No full textHistone deacetylases (HDACs) are a class of epigenetic modulators overexpressed in numerous types of cancers. Consequently, HDAC inhibitors (HDACIs) have emerged as promising antineoplastic agents. Unfortunately, the most developed HDACIs suffer from poor selectivity towards a specific isoform, limiting their clinical applicability. Among the isoforms, HDAC1 represents a crucial target for designing selective HDACIs, being aberrantly expressed in several malignancies. Accordingly, the development of a predictive in silico tool employing a large set of HDACIs (aminophenylbenzamide derivatives) is herein presented for the first time. Software Phase was used to derive a 3D-QSAR model, employing as alignment rule a common-features pharmacophore built on 20 highly active/selective HDAC1 inhibitors. The 3D-QSAR model was generated using 370 benzamide-based HDACIs, which yielded an excellent correlation coefficient value (R2 = 0.958) and a satisfactory predictive power (Q2 = 0.822; Q2F3 = 0.894). The model was validated (r2ext_ts = 0.794) using an external test set (113 compounds not used for generating the model), and by employing a decoys set and the receiver-operating characteristic (ROC) curve analysis, evaluating the Güner–Henry score (GH) and the enrichment factor (EF). The results confirmed a satisfactory predictive power of the 3D-QSAR model. This latter represents a useful filtering tool for screening large chemical databases, finding novel derivatives with improved HDAC1 inhibitory activity
VirusMentha: a new resource for virus-host protein interactions
No full textViral infections often cause diseases by perturbing several cellular processes in the infected host. Viral proteins target host proteins and either form new complexes or modulate the formation of functional host complexes. Describing and understanding the perturbation of the host interactome following viral infection is essential for basic virology and for the development of antiviral therapies. In order to provide a general overview of such interactions, a few years ago we developed VirusMINT. We have now extended the scope and coverage of VirusMINT and established VirusMentha, a new virus-virus and virus-host interaction resource build on the detailed curation protocols of the IMEx consortium and on the integration strategies developed for mentha. VirusMentha is regularly and automatically updated every week by capturing, via the PSICQUIC protocol, interactions curated by five different databases that are part of the IMEx consortium. VirusMentha can be freely browsed at http://virusmentha.uniroma2.it/ and its complete data set is available for download
Phonotactic probabilities in Italian simplex and complex words: a fragment priming study.
No full textt(11;22) in three cases of peripheral neuroepithelioma
No full textShort‐term cultures of three cases of peripheral neuroepitheliomas were studied using G‐banding technique. A t(11;22)(q24;q12) was recognized in all three tumors. The results strengthen the hypothesis of a common histogenesis for neuroepithelioma, Ewing's sarcoma, and the Askin tumor
- …
