A convenient and efficient synthesis of (S)-lysine and (S)-arginine homologues via olefin cross-metathesis

A convenient five step synthesis of (S)-homolysine, incorporating a key olefin cross-metathesis step in the chain extension methodology, has been developed, together with a six step related synthesis of a new homologue of arginine, (S)-bishomoarginine

Capripoxvirus tissue tropism and shedding: A quantitative study in experimentally infected sheep and goats

AbstractSheeppox virus and goatpox virus cause systemic disease in sheep and goats that is often associated with high morbidity and high mortality. To increase understanding of the pathogenesis of these diseases, we undertook quantitative time-course studies in sheep and goats following intradermal inoculation of Nigerian sheeppox virus or Indian goatpox virus in their respective homologous hosts. Viremia, determined by virus isolation and real-time PCR, cleared within 2 to 3 weeks post inoculation. Peak shedding of viral DNA and infectious virus in nasal, conjunctival and oral secretions occurred between 10 and 14 days post inoculation, and persisted at low levels for up to an additional 3 to 6 weeks. Although gross lesions developed in multiple organ systems, highest viral titers were detected in skin and in discrete sites within oronasal tissues and gastrointestinal tract. The temporal distribution of infectious virus and viral DNA in tissues suggests an underlying pathogenesis that is similar to smallpox and monkeypox where greatest viral replication occurs in the skin. Our data demonstrate that capripoxvirus infections in sheep and goats provide additional and convenient models which are suitable not only for evaluation of poxvirus-specific vaccine concepts and therapeutics, but also study of poxvirus–host interactions

A Composite HST Spectrum of Quasars

We construct a composite quasar spectrum from 284 HST FOS spectra of 101 quasars with redshifts z > 0.33. The spectrum covers the wavelengths between 350 and 3000 A in the rest frame. There is a significant steepening of the continuum slope around 1050 A. The continuum between 1050 and 2200 A can be modeled as a power law with alpha = -0.99. For the full sample the power-law index in the extreme ultraviolet (EUV) between 350 and 1050 A is alpha = -1.96. The continuum flux in the wavelengths near the Lyman limit shows a depression of about 10 percent. The break in the power-law index and the slight depression of the continuum near the Lyman limit are features expected in Comptonized accretion-disk spectra.Comment: 10 figures To appear in the February 1, 1997, issue of the Ap.

Human Placental Syncytiotrophoblasts Restrict Toxoplasma gondii Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines

Toxoplasma gondii is a major source of congenital disease worldwide, but the cellular and molecular factors associated with its vertical transmission are largely unknown. In humans, the placenta forms the key interface between the maternal and fetal compartments and forms the primary barrier that restricts the hematogenous spread of microorganisms. Here, we utilized primary human trophoblast (PHT) cells isolated from full-term placentas and human midgestation chorionic villous explants to determine the mechanisms by which human trophoblasts restrict and respond to T. gondii infection. We show that placental syncytiotrophoblasts, multinucleated cells that are in direct contact with maternal blood, restrict T. gondii infection at two distinct stages of the parasite lytic cycle—at the time of attachment and also during intracellular replication. Utilizing comparative transcriptome sequencing (RNA-seq) transcriptional profiling, we also show that human placental trophoblasts from both the second and third trimesters respond uniquely to T. gondii infection compared to trophoblast cell lines, typified by the upregulation of several immunity-related genes. One of the most differentially induced genes was the chemokine CCL22, which relies on the secretion of a parasite effector(s) either during or after invasion for its induction. Collectively, our findings provide new insights into the mechanisms by which the human placenta restricts the vertical transmission of T. gondii at early and late stages of human pregnancy and demonstrate the existence of at least two interferon-independent pathways that restrict T. gondii access to the fetal compartment. IMPORTANCE Toxoplasma gondii is a major source of congenital disease worldwide and must breach the placental barrier to be transmitted from maternal blood to the developing fetus. The events associated with the vertical transmission of T. gondii are largely unknown. Here, we show that primary human syncytiotrophoblasts, the fetus-derived cells that comprise the primary placental barrier, restrict T. gondii infection at two distinct stages of the parasite life cycle and respond to infection by inducing a unique immunomodulatory transcriptional profile. Collectively, our findings provide important insights into the mechanisms by which human syncytiotrophoblasts restrict T. gondii infection at early and late stages of human pregnancy, identify both permissive and resistant human placental cell types, and identify the placenta-enriched signaling pathways induced in response to infection

Characterisation of a new VUV beamline at the Daresbury SRS using a dispersed fluorescence apparatus incorporating CCD detection

The design and performance of a new normal incidence monochromator at the Daresbury Synchrotron Radiation Source, optimised for experiments requiring high flux of vacuum-UV radiation, are described. The re-developed beamline 3.1, based on the Wadsworth design of monochromator, is the source of tunable vacuum-UV photons in the range 4 – 31 eV, providing over two orders of magnitude more flux than the vacuum-UV, Seya monochromator in its previous manifestation. The undispersed and dispersed fluorescence spectra resulting from photoexcitation of N$_2$, CO$_2$, CF$_4$ and C$_6$F$_6$ are presented. Emitting species observed were N$_2^+$ B$^2\Sigma_u^+$ - X$^2\Sigma_g^+$, CO$_2^+$ A$^2\Pi_u$ - X$^2\Pi_g$ and B$^2\Sigma_u^+$ - X$^2\Pi_g$, CF$_4$$^+$ C$^2$T$_2$ - X$^2$T$_1$ and C$^2$T$_2$ - A$^2$T$_2$, CF$_3$* $^2$A$^’_2$ - $^2$A$^”_2$, and C$_6$F$_6^+$ B$^2$A$_{2u}$ - X$^2$E$_{1g}$. A CCD multi-channel detector has significantly reduced the time period needed to record dispersed fluorescence spectra with a comparable signal-to-noise ratio

Adaptable data management for systems biology investigations

<p>Abstract</p> <p>Background</p> <p>Within research each experiment is different, the focus changes and the data is generated from a continually evolving barrage of technologies. There is a continual introduction of new techniques whose usage ranges from in-house protocols through to high-throughput instrumentation. To support these requirements data management systems are needed that can be rapidly built and readily adapted for new usage.</p> <p>Results</p> <p>The adaptable data management system discussed is designed to support the seamless mining and analysis of biological experiment data that is commonly used in systems biology (e.g. ChIP-chip, gene expression, proteomics, imaging, flow cytometry). We use different content graphs to represent different views upon the data. These views are designed for different roles: equipment specific views are used to gather instrumentation information; data processing oriented views are provided to enable the rapid development of analysis applications; and research project specific views are used to organize information for individual research experiments. This management system allows for both the rapid introduction of new types of information and the evolution of the knowledge it represents.</p> <p>Conclusion</p> <p>Data management is an important aspect of any research enterprise. It is the foundation on which most applications are built, and must be easily extended to serve new functionality for new scientific areas. We have found that adopting a three-tier architecture for data management, built around distributed standardized content repositories, allows us to rapidly develop new applications to support a diverse user community.</p