Trends in the Discovery of New Marine Natural Products from Invertebrates over the Last Two Decades – Where and What Are We Bioprospecting?

It is acknowledged that marine invertebrates produce bioactive natural products that may be useful for developing new drugs. By exploring untapped geographical sources and/or novel groups of organisms one can maximize the search for new marine drugs to treat human diseases. The goal of this paper is to analyse the trends associated with the discovery of new marine natural products from invertebrates (NMNPI) over the last two decades. The analysis considers different taxonomical levels and geographical approaches of bioprospected species. Additionally, this research is also directed to provide new insights into less bioprospected taxa and world regions. In order to gather the information available on NMNPI, the yearly-published reviews of Marine Natural Products covering 1990–2009 were surveyed. Information on source organisms, specifically taxonomical information and collection sites, was assembled together with additional geographical information collected from the articles originally describing the new natural product. Almost 10000 NMNPI were discovered since 1990, with a pronounced increase between decades. Porifera and Cnidaria were the two dominant sources of NMNPI worldwide. The exception was polar regions where Echinodermata dominated. The majority of species that yielded the new natural products belong to only one class of each Porifera and Cnidaria phyla (Demospongiae and Anthozoa, respectively). Increased bioprospecting efforts were observed in the Pacific Ocean, particularly in Asian countries that are associated with the Japan Biodiversity Hotspot and the Kuroshio Current. Although results show comparably less NMNPI from polar regions, the number of new natural products per species is similar to that recorded for other regions. The present study provides information to future bioprospecting efforts addressing previously unexplored taxonomic groups and/or regions. We also highlight how marine invertebrates, which in some cases have no commercial value, may become highly valuable in the ongoing search for new drugs from the sea

Holographic Wilsonian flows and emergent fermions in extremal charged black holes

We study holographic Wilsonian RG in a general class of asymptotically AdS backgrounds with a U(1) gauge field. We consider free charged Dirac fermions in such a background, and integrate them up to an intermediate radial distance, yielding an equivalent low energy dual field theory. The new ingredient, compared to scalars, involves a `generalized' basis of coherent states which labels a particular half of the fermion components as coordinates or momenta, depending on the choice of quantization (standard or alternative). We apply this technology to explicitly compute RG flows of charged fermionic operators and their composites (double trace operators) in field theories dual to (a) pure AdS and (b) extremal charged black hole geometries. The flow diagrams and fixed points are determined explicitly. In the case of the extremal black hole, the RG flows connect two fixed points at the UV AdS boundary to two fixed points at the IR AdS_2 region. The double trace flow is shown, both numerically and analytically, to develop a pole singularity in the AdS_2 region at low frequency and near the Fermi momentum, which can be traced to the appearance of massless fermion modes on the low energy cut-off surface. The low energy field theory action we derive exactly agrees with the semi-holographic action proposed by Faulkner and Polchinski in arXiv:1001.5049 [hep-th]. In terms of field theory, the holographic version of Wilsonian RG leads to a quantum theory with random sources. In the extremal black hole background the random sources become `light' in the AdS_2 region near the Fermi surface and emerge as new dynamical degrees of freedom.Comment: 37 pages (including 8 pages of appendix), 10 figures and 2 table

The two-hour orbit of a binary millisecond X-ray pulsar

Typical radio pulsars are magnetized neutron stars that are born rapidly rotating and slow down as they age on time scales of 10 to 100 million years. However, millisecond radio pulsars spin very rapidly even though many are billions of years old. The most compelling explanation is that they have been "spun up" by the transfer of angular momentum during accretion of material from a companion star in so-called low-mass X-ray binary systems, LMXBs. (LMXBs consist of a neutron star or black hole accreting from a companion less than one solar mass.) The recent detection of coherent X-ray pulsations with a millisecond period from a suspected LMXB system appears to confirm this link. Here we report observations showing that the orbital period of this binary system is two hours, which establishes it as an LMXB. We also find an apparent modulation of the X-ray flux at the orbital period (at the two per cent level), with a broad minimum when the pulsar is behind this low-mass companion star. This system seems closely related to the "black widow" millisecond radio pulsars, which are evaporating their companions through irradiation. It may appear as an eclipsing radio pulsar during periods of X-ray quiescence.Comment: 4 pages with 1 figure. Style files included. Fig. 2 deleted and text revised. To appear in Nature. Press embargo until 18:00 GMT on 1998 July 2

ミャンマー産植物Premna serratifoliaとJatropha multifida及び海綿Clathria proliferaに含まれるメラニン産生制御成分に関する研究

富山大学・富医薬博甲第305号・禹 昭年・2019/03/26当該博士論文は以下の項評論文で構成されています。①Woo, SY., Win, N.N., Wong, C.P. et al. Two new pyrrolo-2-aminoimidazoles from a Myanmarese marine sponge, Clathria prolifera, J Nat Med (2018) 72: 803-807. https://doi.org/10.1007/s11418-018-1205-y This is a pre-print of an article published in Journal of Natural Medicines. The final authenticated version is available online at: https://doi.org/10.1007/s11418-018-1205-y”.②So-Yeun Woo et al. Lignans with melanogenesis effects from Premna serratifolia wood, Fitoterapia (2019) 133:35-42. https://doi.org/10.1016/j.fitote.2018.12.008③So-Yeun Woo et al. A New Tetrahydrofuran Lignan from Premna serratifolia Wood, Natural Product Communications (2019) 14:113-116. https://doi.org/10.1177/1934578X1901400130富山大

Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The three sub-species of &lt;i&gt;Trypanosoma brucei&lt;/i&gt; are important pathogens of sub-Saharan Africa. &lt;i&gt;T. b. brucei&lt;/i&gt; is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. &lt;i&gt;T. b. rhodesiense&lt;/i&gt; and &lt;i&gt;T. b. gambiense&lt;/i&gt; are able to resist lysis by TLF. There are two distinct sub-groups of &lt;i&gt;T. b. gambiense&lt;/i&gt; that differ genetically and by human serum resistance phenotypes. Group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (&lt;i&gt;HpHbR&lt;/i&gt;)) gene. Here we investigate if this is also true in group 2 parasites.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology:&lt;/b&gt; Isogenic resistant and sensitive group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the &lt;i&gt;HpHbR&lt;/i&gt; gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to &lt;i&gt;T. b. brucei&lt;/i&gt;. Both resistant and sensitive group 2, as well as group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt;, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data indicate that, despite group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of &lt;i&gt;HpHbR&lt;/i&gt;. Thus there are differences in the mechanism of human serum resistance between &lt;i&gt;T. b. gambiense&lt;/i&gt; groups 1 and 2.&lt;/p&gt

Exploring the impact of providing evidence-based medicine training to service users

© 2015 Gibson et al. Background Within the UK, health services research in the 1990s was marked by growing interest in evidence-based medicine (EBM) and in the potential of patient and public involvement (PPI) in research. However, there has been relatively little discussion of how these two developments might relate to each other, despite their common concern to improve the quality and transparency of clinical decision making. Indeed, some in the user involvement movement have expressed doubts about the implications of EBM for PPI. The purpose of this paper is to examine the potential for EBM and PPI to complement one another. Methods We used a case study design. Fifteen EBM workshops, involving PPI members, were conducted between June 2010 and December 2014. All 13 lay participants, who attended the first five workshops, were asked to fill in a standard feedback proforma designed by a member of the NIHR Collaboration for Leadership in Applied Health Research and Care for the South West Peninsula (PenCLAHRC) Public Involvement Group (PenPIG). Ten responses were received, and these were analysed thematically. Results Four themes emerged from the thematic analysis: research knowledge, research skills, shared clinical decision making and learning environment. Participation in the workshops appears to have increased the ability and confidence of members of the public to actively participate as both producers and consumers of research evidence. Conclusions There is an untapped potential for EBM and PPI to complement one another in their shared desire to improve the quality and transparency of clinical decision making

Corner contributions to holographic entanglement entropy

The entanglement entropy of three-dimensional conformal field theories contains a universal contribution coming from corners in the entangling surface. We study these contributions in a holographic framework and, in particular, we consider the effects of higher curvature interactions in the bulk gravity theory. We find that for all of our holographic models, the corner contribution is only modified by an overall factor but the functional dependence on the opening angle is not modified by the new gravitational interactions. We also compare the dependence of the corner term on the new gravitational couplings to that for a number of other physical quantities, and we show that the ratio of the corner contribution over the central charge appearing in the two-point function of the stress tensor is a universal function for all of the holographic theories studied here. Comparing this holographic result to the analogous functions for free CFT's, we find fairly good agreement across the full range of the opening angle. However, there is a precise match in the limit where the entangling surface becomes smooth, i.e., the angle approaches $\pi$, and we conjecture the corresponding ratio is a universal constant for all three-dimensional conformal field theories. In this paper, we expand on the holographic calculations in our previous letter arXiv:1505.04804, where this conjecture was first introduced.Comment: 62 pages, 6 figures, 1 table; v2: minor modifications to match published version, typos fixe

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie