Search results for "init"
showing 10 items of 6629 documents
Discovery of Retinoic Acid-Related Orphan Receptor γt Inverse Agonists via Docking and Negative Image-Based Screening
2018
Retinoic acid-related orphan receptor γt (RORγt) has a vital role in the differentiation of T-helper 17 (TH17) cells. Potent and specific RORγt inverse agonists are sought for treating TH17-related diseases such as psoriasis, rheumatoid arthritis, and type 1 diabetes. Here, the aim was to discover novel RORγt ligands using both standard molecular docking and negative image-based screening. Interestingly, both of these in silico techniques put forward mostly the same compounds for experimental testing. In total, 11 of the 34 molecules purchased for testing were verified as RORγt inverse agonists, thus making the effective hit rate 32%. The pIC50 values for the compounds varied from 4.9 (11 μ…
IGF2BP3 Associates with Proliferative Phenotype and Prognostic Features in B-Cell Acute Lymphoblastic Leukemia
2021
Simple Summary Although the prognosis of acute lymphoblastic leukemia (ALL) has improved significantly during the past decades, ALL remains a major cause of pediatric cancer mortality, and more accurate risk-stratification is required. We investigated IGF2BP3, which has previously been associated with aggressive cancers, and found high and subtype-specific expression of IGF2BP3 in B-cell ALL, that was associated with good outcome in high-risk patients. Results suggest that IGF2BP3 could be useful to improve stratification and prognosis of B-ALL. Abstract The oncofetal protein insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) belongs to a family of RNA-binding proteins involved i…
Small things matter : of phages and antibiotic resistance conferring plasmids
2016
Viruses and plasmids are small units of genetic material dependent on cells either transiently or continuously. Intriguingly, stories of these small entities intertwine in antibiotic resistance crisis. Horizontal gene transfer enables bacteria to respond rapidly to chances in their environment. Anthropogenic consumption of antibiotics induces the travel of resistance encoding genes mainly as passengers of conjugative plasmids. In this thesis, I demonstrate that clinically important resistance plasmids could evolutionarily rescue susceptible bacteria under lethal antibiotic concentrations. If mobile resistance genes are available in surrounding community, administration of high doses of anti…
Species and genetic diversity relationships in benthic macroinvertebrate communities along a salinity gradient
2022
Background Species- and genetic diversity can change in parallel, resulting in a species-genetic diversity correlation (SGDC) and raising the question if the same drivers influence both biological levels of diversity. The SGDC can be either positive or negative, depending on whether the species diversity and the genetic diversity of the measured species respond in the same or opposite way to drivers. Using a traditional species diversity approach together with ultra-conserved elements and high throughput sequencing, we evaluated the SGDCs in benthic macrofauna communities in the Baltic Sea, a geologically young brackish water sea characterised by its steep salinity gradient and low species …
The Interaction Mechanism of Intrinsically Disordered PP2A Inhibitor Proteins ARPP-16 and ARPP-19 With PP2A
2021
Protein phosphatase 2A (PP2A) activity is critical for maintaining normal physiological cellular functions. PP2A is inhibited by endogenous inhibitor proteins in several pathological conditions including cancer. A PP2A inhibitor protein, ARPP-19, has recently been connected to several human cancer types. Accordingly, the knowledge about ARPP-19—PP2A inhibition mechanism is crucial for the understanding the disease development and the therapeutic targeting of ARPP-19—PP2A. Here, we show the first structural characterization of ARPP-19, and its splice variant ARPP-16 using NMR spectroscopy, and SAXS. The results reveal that both ARPP proteins are intrinsically disordered but contain transient…
Magneto-Structural Properties and Theoretical Studies of a Family of Simple Heterodinuclear Phenoxide/Alkoxide Bridged MnIIILnIII Complexes : On the …
2018
A family of MnIIILnIII strictly dinuclear complexes of general formula [MnIII(μ-L)(μ-OMe)(NO3)LnIII(NO3)2(MeOH)] (LnIII = Gd, Dy, Er, Ho) has been assembled in a one pot synthesis from a polydentate, multipocket aminobis(phenol)ligand [6,6'-{(2-(1-morpholyl)ethylazanediyl)bis(methylene)}bis(2-methoxy-4-methylphenol)], Mn(NO3)2·4H2O, Ln(NO3)3· nH2O, and NEt3 in MeOH. These compounds represent the first examples of fully structurally and magnetically characterized dinuclear MnIIILnIII complexes. Single X-ray diffraction studies reveal that all complexes are isostructural, consisting of neutral dinuclear molecules where the MnIII and LnIII metal ions, which exhibit distorted octahedral MnN2O4 …
Analysis of the effects of magnetic field on the induced stress in drilled plates
2013
Abstract A drilled plate of ferromagnetic material suitably coupled by coils of enameled copper wire fed by a DC power supply to 30 V is considered in this paper. It is analyzed with finite element and later experiments are performed to validate the obtained results. After polishing the plate, two strain gauges for measuring the deformation along the x axis and along the z axis are installed. The values of strain are 5 μm/m in z direction and −2 μm/m in x direction. The experimental–numerical comparison shows that the laboratory results are lower than numerical, while signs and orders of magnitude are the same. It is concluded that the results of the FEM analysis can be considered acceptabl…
Maschilità "sacrificate", maschilità "esibite" e maschilità "revansciste" nel sex work di strada
2022
Il presente articolo, approfondendo dei dati etnografici sul sex work maschile di strada raccolti dall'autore tra il 2011 e il 2018, intende evidenziare i significati attribuiti allo scambio sessuo-economico e delineare le relazioni gerarchiche che si definiscono per via della costruzione egemonica di genere e sessuale ma anche, inevitabilmente, per la corresponsione di una paga a seguito di una prestazione con l'obiettivo di identificare le modalità attraverso le quali si costruiscono modelli di maschilità situazionali e negoziate. L'analisi prova che la reputazione maschile deve essere costantemente preservata e dal momento che determina una sorta di rendita da posizionamento, essa è cost…
Male Sex Working and Masculinity: Finding ‘Check and Balance’ Between Stigmatisation and Homosexualisation
2021
Abstract in conference proceedings
Best Practices in Constant pH MD Simulations: Accuracy and Sampling
2022
Various approaches have been proposed to include the effect of pH in molecular dynamics (MD) simulations. Among these, the λ-dynamics approach proposed by Brooks and co-workers [Kong, X.; Brooks III, C. L. J. Chem. Phys.1996, 105, 2414−2423] can be performed with little computational overhead and hfor each typeence be used to routinely perform MD simulations at microsecond time scales, as shown in the accompanying paper [Aho, N. et al. J. Chem. Theory Comput.2022, DOI: 10.1021/acs.jctc.2c00516]. At such time scales, however, the accuracy of the molecular mechanics force field and the parametrization becomes critical. Here, we address these issues and provide the community with guidelines on…