Nrt1 and Tna1-Independent Export of NAD+ Precursor Vitamins Promotes NAD+ Homeostasis and Allows Engineering of Vitamin Production

NAD+ is both a co-enzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD+ consuming enzymes. NAD+ biosynthesis is required for two different regimens that extend lifespan in yeast. NAD+ is synthesized from tryptophan and the three vitamin precursors of NAD+: nicotinic acid, nicotinamide and nicotinamide riboside. Supplementation of yeast cells with NAD+ precursors increases intracellular NAD+ levels and extends replicative lifespan. Here we show that both nicotinamide riboside and nicotinic acid are not only vitamins but are also exported metabolites. We found that the deletion of the nicotinamide riboside transporter, Nrt1, leads to increased export of nicotinamide riboside. This discovery was exploited to engineer a strain to produce high levels of extracellular nicotinamide riboside, which was recovered in purified form. We further demonstrate that extracellular nicotinamide is readily converted to extracellular nicotinic acid in a manner that requires intracellular nicotinamidase activity. Like nicotinamide riboside, export of nicotinic acid is elevated by the deletion of the nicotinic acid transporter, Tna1. The data indicate that NAD+ metabolism has a critical extracellular element in the yeast system and suggest that cells regulate intracellular NAD+ metabolism by balancing import and export of NAD+ precursor vitamins

Gell-Mann--Okubo Mass Formula for an SU(4) Meson Hexadecuplet

Using a linear mass spectrum of an $SU(4)$ meson hexadecuplet, we derive the Gell-Mann--Okubo mass formula for the charmed mesons, in good agreement with experiment. Possible generalization of this method to a higher symmetry group is briefly discussed.Comment: 11 pages, LaTe

A novel fluorescent probe for NAD-consuming enzymes

A novel, fluorescent NAD derivative is processed as substrate by three different NAD-consuming enzymes. The new probe has been used to monitor enzymatic activity in a continuous format by changes in fluorescence and, in one case, to directly visualize alternative reaction pathways

Клинико-морфологические аспекты изначально первичной гормональной резистентности рака предстательной железы

By using the routine studies, the authors have analyzed clinical and morphological data of 129 prostate cancer (PC) patients, 48-92 years old with different clinical stages. PC turned out to be initially heterogenic in the composition of tumor cells (cytotypic and immunophenotypic heterogenicity). Therefore combined PC treatment should take into account the presence of hormone-resistant tumor cells even when a neoplasm looks at the light microscopy as a usual low- or moderate-grade adenocarcinoma with a great number of adrenoceptors in the tumor cells.

Negotiating professional and social voices in research principles and practice

This paper draws on work conducted for a qualitative interview based study which explores the gendered racialised and professional identifications of health and social care professionals. Participants for the project were drawn from the professional executive committees of recently formed Primary Care Trusts. The paper discusses how the feminist psychosocial methodological approach developed for the project is theoretically, practically and ethically useful in exploring the voices of those in positions of relative power in relation to both health and social care services and the social relations of gender and ethnicity. The approach draws on psychodynamic accounts of (defended) subjectivity and the feminist work of Carol Gilligan on a voice-centred relational methodology. Coupling the feminist with the psychosocial facilitates an emphasis on voice and dialogic communication between participant and researcher not always captured in psychosocial approaches which tend towards favouring the interviewer as ‘good listener’. This emphasis on dialogue is important in research contexts where prior and ongoing relationships with professional participants make it difficult and indeed undesirable for researchers to maintain silence

Relativistic mass distribution in event-anti-event system and ``realistic'' equation of state for hot hadronic matter

We find the equation of state $p,\rho \propto T^6,$ which gives the value of the sound velocity $c^2=0.20,$ in agreement with the ``realistic'' equation of state for hot hadronic matter suggested by Shuryak, in the framework of a covariant relativistic statistical mechanics of an event--anti-event system with small chemical and mass potentials. The relativistic mass distribution for such a system is obtained and shown to be a good candidate for fitting hadronic resonances, in agreement with the phenomenological models of Hagedorn, Shuryak, {\it et al.} This distribution provides a correction to the value of specific heat 3/2, of the order of 5.5\%, at low temperatures.Comment: 19 pages, report TAUP-2161-9

The transformative potential of international service-learning at a university with a Christian foundation in the UK

This article draws upon the findings of a study at Liverpool Hope University (LHU) into the transformative nature of International Service-Learning (ISL) experiences for student participants. This research is concerned with the implications of these findings for professional practice, in particular how ISL is constructed in Higher Education policy and practice. Recognising the problematic nature of this endeavor, this article responds to a call for discussion around pedagogical approaches underpinning counter-cultural and critical service programmes aligned with the radical principles of the Catholic social teaching. This study is grounded in a holistic conceptualisation of transformative learning that demands looking beyond an epistemological process that involves shifts in worldview and habits of mind to an ontological process that accounts for changes to our being in the world. It investigated how LHU students describe their ongoing experience of ISL and explored the conditions for learning and the associated transformative processes and outcomes in this context. Data analysis involved phenomenological description, constant comparative thematic analysis followed by a critical, hermeneutical analysis. This article will explicate the themes of moral and spiritual learning that emerged as part of a broader framework. In particular, it was found that the development of authentic relationships between travelling companions, accompanying tutors and partners overseas is central to learning that is reciprocated and provides a model of the transformative process in this context. This article concludes that this presents a pedagogical approach grounded in social justice that enables ISL to reach its transformative potential

Very high upper critical fields in MgB2 produced by selective tuning of impurity scattering

We report a significant enhancement of the upper critical field $H_{c2}$ of different $MgB_2$ samples alloyed with nonmagnetic impurities. By studying films and bulk polycrystals with different resistivities $\rho$, we show a clear trend of $H_{c2}$ increase as $\rho$ increases. One particular high resistivity film had zero-temperature $H_{c2}(0)$ well above the $H_{c2}$ values of competing non-cuprate superconductors such as $Nb_3Sn$ and Nb-Ti. Our high-field transport measurements give record values $H_{c2}^\perp (0) \approx 34T$ and $H_{c2}\|(0) \approx 49 T$ for high resistivity films and $H_{c2}(0)\approx 29 T$ for untextured bulk polycrystals. The highest $H_{c2}$ film also exhibits a significant upward curvature of $H_{c2}(T)$, and temperature dependence of the anisotropy parameter $\gamma(T) = H_{c2}\|/ H_{c2}^\perp$ opposite to that of single crystals: $\gamma(T)$ decreases as the temperature decreases, from $\gamma(T_c) \approx 2$ to $\gamma(0) \approx 1.5$. This remarkable $H_{c2}$ enhancement and its anomalous temperature dependence are a consequence of the two-gap superconductivity in $MgB_2$, which offers special opportunities for further $H_{c2}$ increase by tuning of the impurity scattering by selective alloying on Mg and B sites. Our experimental results can be explained by a theory of two-gap superconductivity in the dirty limit. The very high values of $H_{c2}(T)$ observed suggest that $MgB_2$ can be made into a versatile, competitive high-field superconductor.Comment: An updated version of the paper (12/12/2002)that was placed on cond-mat on May 7 200

Towards resolution of the scalar meson nonet enigma

By the application of a linear mass spectrum to a composite system of both the pseudoscalar and scalar meson nonets, we find three mass relations for the masses of the scalar states which suggest the $q\bar{q}$ assignment for the scalar meson nonet: $a_0(1320),$ $K_0^\ast (1430),$ $f_0(1500),$ $f_0'(980).$Comment: 16 pages, LaTe