1,792 research outputs found

    A Novel Mitigation Mechanism for Photo-Induced Trapping in an Anthradithiophene Derivative Using Additives

    Get PDF
    © 2020 Wiley-VCH GmbH A novel trap mitigation mechanism using molecular additives, which relieves a characteristic early turn-on voltage in a high-mobility p-type acene-based small-molecule organic semiconductor, when processed from hydrous solvents, is reported. The early turn-on voltage is attributed to photo-induced trapping, and additive incorporation is found to be very effective in suppressing this effect. Remarkably, the molecular additive does not disturb the charge transport properties of the small-molecule semiconductor, but rather intercalates in the crystal structure. This novel technique allows for the solution-processing of small molecular semiconductors from hydrous solvents, greatly simplifying manufacturing processes for large-area electronics. Along with various electric and spectroscopic characterization techniques, simulations have given a deeper insight into the trap mitigation effect induced by the additive

    Stem Cell Expansion and Fate Decision on Liquid Substrates Are Regulated by Self-Assembled Nanosheets

    Get PDF
    S.D.C. thanks the Institute of Bioengineering for a studentship. L.P. thanks the China Scholarship Council for a studentship (201708060335). J.E.G. and D.K. thank the Leverhulme Trust Foundation for financial support (RPG-2017-229, Grant 69241)

    Foot orthoses: how much customisation is necessary?

    Get PDF
    The relative merit of customised versus prefabricated foot orthoses continues to be the subject of passionate debate among foot health professionals. Although there is currently insufficient evidence to reach definitive conclusions, a growing body of research literature suggests that prefabricated foot orthoses may produce equivalent clinical outcomes to customised foot orthoses for some conditions. Consensus guidelines for the prescription of customised foot orthoses need to be developed so that the hypothesised benefits of these devices can be thoroughly evaluated

    Yeast axial-element protein, Red1, binds SUMO chains to promote meiotic interhomologue recombination and chromosome synapsis

    Get PDF
    The synaptonemal complex (SC) is a tripartite protein structure consisting of two parallel axial elements (AEs) and a central region. During meiosis, the SC connects paired homologous chromosomes, promoting interhomologue (IH) recombination. Here, we report that, like the CE component Zip1, Saccharomyces cerevisiae axial-element structural protein, Red1, can bind small ubiquitin-like modifier (SUMO) polymeric chains. The Red1–SUMO chain interaction is dispensable for the initiation of meiotic DNA recombination, but it is essential for Tel1- and Mec1-dependent Hop1 phosphorylation, which ensures IH recombination by preventing the inter-sister chromatid DNA repair pathway. Our results also indicate that Red1 and Zip1 may directly sandwich the SUMO chains to mediate SC assembly. We suggest that Red1 and SUMO chains function together to couple homologous recombination and Mec1–Tel1 kinase activation with chromosome synapsis during yeast meiosis

    Selective killing of Burkitt's lymphoma cells by mBAFF-targeted delivery of PinX1

    Get PDF
    Increased expression of BAFF (B cell-activating factor belonging to the TNF family) and its receptors has been identified in numerous B-cell malignancies. A soluble human BAFF mutant (mBAFF), binding to BAFF receptors but failing to activate B-lymphocyte proliferation, may function as a competitive inhibitor of BAFF and may serve as a novel ligand for targeted therapy of BAFF receptor-positive malignancies. Pin2/TRF1-interacting protein X1 (PinX1), a nucleolar protein, potently inhibits telomerase activity and affects tumorigenicity. In this study, we generated novel recombinant proteins containing mBAFF, a polyarginine tract 9R and PinX1 (or its C/N terminal), to target lymphoma cells. The fusion proteins PinX1/C–G4S–9R–G4S–mBAFF and PinX1/C–9R–mBAFF specifically bind and internalize into BAFF receptor-positive cells, and subsequently induce growth inhibition and apoptosis. The selective cytotoxicity of the fusion proteins is a BAFF receptor-mediated process and depends on mBAFF, PinX1/C and 9R. Moreover, the fusion proteins specifically kill BAFF receptor-expressing Burkitt's lymphoma (BL) cells by inhibiting telomerase activity and the consequent shortening of telomeres. Therapeutic experiments using PinX1C–G4S–9R–G4S–mBAFF in severe combined immunodeficient (SCID) mice implanted with Raji cells showed significantly prolonged survival times, indicating the in vivo antitumor activity of the fusion protein. These results suggest the potential of PinX1/C–G4S–9R–G4S–mBAFF in targeted therapy of BL

    Interplay between NS3 protease and human La protein regulates translation-replication switch of Hepatitis C virus

    Get PDF
    HCV NS3 protein plays a central role in viral polyprotein processing and RNA replication. We demonstrate that the NS3 protease (NS3pro) domain alone can specifically bind to HCV-IRES RNA, predominantly in the SLIV region. The cleavage activity of the NS3 protease domain is reduced upon HCV-RNA binding. More importantly, NS3pro binding to the SLIV hinders the interaction of La protein, a cellular IRES-trans acting factor required for HCV IRES-mediated translation, resulting in inhibition of HCV-IRES activity. Although overexpression of both NS3pro as well as the full length NS3 protein decreased the level of HCV IRES mediated translation, replication of HCV replicon RNA was enhanced significantly. These observations suggest that the NS3pro binding to HCV IRES reduces translation in favor of RNA replication. The competition between the host factor (La) and the viral protein (NS3) for binding to HCV IRES might regulate the molecular switch from translation to replication of HCV

    Platy limestones. 10 case studies in the Classical Karst

    Get PDF
    Il progetto RoofOfRock, finanziato nell’ambito del 2° bando di cooperazione transfrontaliera dell’Adriatico IPA 2007-2013 è iniziato nell’ottobre 2012, si concluderà a fine settembre del 2015 e coinvolge 10 partner di 4 nazioni: Slovenia, Italia, Croazia e Bosnia Erzegovina. In qualità di partner associato e stakeholder partecipano le regioni Friuli Venezia Giulia e Veneto. Il progetto RoofOfRock ha tra le sue finalità quelle di proporre un utilizzo del calcare tabulare compatibile con l’ambiente, di favorirne la protezione e la promozione nonché di elaborare delle linee guida utili per una sua valorizzazione come patrimonio naturale e culturale.Pri projektu RoofOfRock, ki je bil izbran za sofinanciranje v okviru 2. poziva Jadranskega čezmejnega programa IPA 2007–2013, sodeluje deset projektnih partnerjev iz štirih držav, in sicer iz Slovenije, Italije, s Hrvaške ter iz Bosne in Hercegovine. Projekt se je začel izvajati oktobra 2012 in se bo zaključil konec septembra 2015. Pri projektu sodelujeta tudi italijanski pokrajini Furlanija - Julijska krajina kot deležnik in Benečija kot pridruženi partner. Namen projekta RoofOfRock je vzpostaviti skupni temelj za trajnostno rabo, zaščito in promocijo ploščastih apnencev ter oblikovati uporabne smernice za trajnostno upravljanje ploščastih apnencev kot skupne naravne in kulturne vrednote na celotnem projektnem prostoru.The RoofOfRock Project is being implemented under 2nd call for ordinary projects of Adriatic IPA CBC Programme 2007, joining 10 partners from 4 countries Slovenia, Italy, Croatia and Bosnia and Herzegovina. It started in October 2012 and is going to be implemented until the end of September 2015. Two Italian Regions Friuli Venezia Giulia and Veneto are participating as stakeholder and associate partner . The RoofOfRock intention is to establish joint platform for platy limestone sustainable use, preservation and promotion, to create the relevant guidelines and to upgrade both individual and joint capacities in preserving such common natural and cultural heritage

    Transcriptional Regulation Is a Major Controller of Cell Cycle Transition Dynamics

    Get PDF
    DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries in various organisms showed the importance of positive feedbacks in other transitions as well. Here we investigate if a universal control system with transcriptional regulation(s) and post-translational positive feedback(s) can be proposed for the regulation of all cell cycle transitions. Through computational modeling, we analyze the transition dynamics in all possible combinations of transcriptional and post-translational regulations. We find that some combinations lead to ‘sloppy’ transitions, while others give very precise control. The periodic transcriptional regulation through the activator or the inhibitor leads to radically different dynamics. Experimental evidence shows that in cell cycle transitions of organisms investigated for cell cycle dependent periodic transcription, only the inhibitor OR the activator is under cyclic control and never both of them. Based on these observations, we propose two transcriptional control modes of cell cycle regulation that either STOP or let the cycle GO in case of a transcriptional failure. We discuss the biological relevance of such differences

    Dose-Response Aligned Circuits in Signaling Systems

    Get PDF
    Cells use biological signal transduction pathways to respond to environmental stimuli and the behavior of many cell types depends on precise sensing and transmission of external information. A notable property of signal transduction that was characterized in the Saccharomyces cerevisiae yeast cell and many mammalian cells is the alignment of dose-response curves. It was found that the dose response of the receptor matches closely the dose responses of the downstream. This dose-response alignment (DoRA) renders equal sensitivities and concordant responses in different parts of signaling system and guarantees a faithful information transmission. The experimental observations raise interesting questions about the nature of the information transmission through DoRA signaling networks and design principles of signaling systems with this function. Here, we performed an exhaustive computational analysis on network architectures that underlie the DoRA function in simple regulatory networks composed of two and three enzymes. The minimal circuits capable of DoRA were examined with Michaelis-Menten kinetics. Several motifs that are essential for the dynamical function of DoRA were identified. Systematic analysis of the topology space of robust DoRA circuits revealed that, rather than fine-tuning the network's parameters, the function is primarily realized by enzymatic regulations on the controlled node that are constrained in limiting regions of saturation or linearity
    corecore