A Flavonoid, Luteolin, Cripples HIV-1 by Abrogation of Tat Function

Despite the effectiveness of combination antiretroviral treatment (cART) against HIV-1, evidence indicates that residual infection persists in different cell types. Intensification of cART does not decrease the residual viral load or immune activation. cART restricts the synthesis of infectious virus but does not curtail HIV-1 transcription and translation from either the integrated or unintegrated viral genomes in infected cells. All treated patients with full viral suppression actually have low-level viremia. More than 60% of treated individuals also develop minor HIV-1 –associated neurocognitive deficits (HAND) due to residual virus and immune activation. Thus, new therapeutic agents are needed to curtail HIV-1 transcription and residual virus. In this study, luteolin, a dietary supplement, profoundly reduced HIV-1 infection in reporter cells and primary lymphocytes. HIV-1inhibition by luteolin was independent of viral entry, as shown by the fact that wild-type and VSV–pseudotyped HIV-1 infections were similarly inhibited. Luteolin was unable to inhibit viral reverse transcription. Luteolin had antiviral activity in a latent HIV-1 reactivation model and effectively ablated both clade-B- and -C -Tat-driven LTR transactivation in reporter assays but had no effect on Tat expression and its sub-cellular localization. We conclude that luteolin confers anti–HIV-1 activity at the Tat functional level. Given its biosafety profile and ability to cross the blood-brain barrier, luteolin may serve as a base flavonoid to develop potent anti–HIV-1 derivatives to complement cART

Brain architecture in the terrestrial hermit crab Coenobita clypeatus (Anomura, Coenobitidae), a crustacean with a good aerial sense of smell

<p>Abstract</p> <p>Background</p> <p>During the evolutionary radiation of Crustacea, several lineages in this taxon convergently succeeded in meeting the physiological challenges connected to establishing a fully terrestrial life style. These physiological adaptations include the need for sensory organs of terrestrial species to function in air rather than in water. Previous behavioral and neuroethological studies have provided solid evidence that the land hermit crabs (Coenobitidae, Anomura) are a group of crustaceans that have evolved a good sense of aerial olfaction during the conquest of land. We wanted to study the central olfactory processing areas in the brains of these organisms and to that end analyzed the brain of <it>Coenobita clypeatus </it>(Herbst, 1791; Anomura, Coenobitidae), a fully terrestrial tropical hermit crab, by immunohistochemistry against synaptic proteins, serotonin, FMRFamide-related peptides, and glutamine synthetase.</p> <p>Results</p> <p>The primary olfactory centers in this species dominate the brain and are composed of many elongate olfactory glomeruli. The secondary olfactory centers that receive an input from olfactory projection neurons are almost equally large as the olfactory lobes and are organized into parallel neuropil lamellae. The architecture of the optic neuropils and those areas associated with antenna two suggest that <it>C. clypeatus </it>has visual and mechanosensory skills that are comparable to those of marine Crustacea.</p> <p>Conclusion</p> <p>In parallel to previous behavioral findings of a good sense of aerial olfaction in C. clypeatus, our results indicate that in fact their central olfactory pathway is most prominent, indicating that olfaction is a major sensory modality that these brains process. Interestingly, the secondary olfactory neuropils of insects, the mushroom bodies, also display a layered structure (vertical and medial lobes), superficially similar to the lamellae in the secondary olfactory centers of <it>C. clypeatus</it>. More detailed analyses with additional markers will be necessary to explore the question if these similarities have evolved convergently with the establishment of superb aerial olfactory abilities or if this design goes back to a shared principle in the common ancestor of Crustacea and Hexapoda.</p

Kupplung von Amadori-Verbindungen mit Diazoniumsalzen Darstellung von Lactulose aus Lactose

1-Dezoxy-1-arylamino-ketosen kuppeln in Pyridin/Methanol mit Diazoniumsalzen zu schwer wasserlöslichen, kristallinen Diazoaminoverbindungen (Triazenen). Die Reaktion ist zur Abscheidung von Amadori-Verbindungen aus Gemischen mit N-Glykosiden und deren Zersetzungsprodukten geeignet. Es werden 14 Triazene von 7 verschiedenen Zuckern beschrieben. Salzsäure in Gegenwart von J-Ionen spaltet die Triazene in Aryljodid und Amadori-Verbindung. Katalytische Hydrierung der letzteren und Desaminierung der gebildeten 1-Desoxy-1-amino-ketosen führt zu den entsprechenden Ketosen. Aus Lactose erhält man auf diesem Wege in einer Gesamtausbeute von 17% d. Th. kristallisierte Lactulose

Zur Struktur der Amadori-Verbindungen

1-Desoxy-1-(p-toluidino)-D-fructose (I) kondensiert mit Benzaldehyd zu einem Oxazolidin-Derivat. Für dieses konnte durch Überführung in kristallisierte 1.3.4.5-Tetra-O-methyl-D-fructose (VII) die Pyranose-Struktur II bewiesen werden

High-performance dune modules for solving large-scale, strongly anisotropic elliptic problems with applications to aerospace composites

The key innovation in this paper is an open-source, high-performance iterative solver for high contrast, strongly anisotropic elliptic partial differential equations implemented within dune-pdelab. The iterative solver exploits a robust, scalable two-level additive Schwarz preconditioner, GenEO (Spillane et al., 2014). The development of this solver has been motivated by the need to overcome the limitations of commercially available modelling tools for solving structural analysis simulations in aerospace composite applications. Our software toolbox dune-composites encapsulates the mathematical complexities of the underlying packages within an efficient C++ framework, providing an application interface to our new high-performance solver. We illustrate its use on a range of industrially motivated examples, which should enable other scientists to build on and extend dune-composites and the GenEO preconditioner for use in their own applications. We demonstrate the scalability of the solver on more than 15,000 cores of the UK national supercomputer Archer, solving an aerospace composite problem with over 200 million degrees of freedom in a few minutes. This scale of computation brings composites problems that would otherwise be unthinkable into the feasible range. To demonstrate the wider applicability of the new solver, we also confirm the robustness and scalability of the solver on SPE10, a challenging benchmark in subsurface flow/reservoir simulation