Cross‐Peaks in Simple Two‐Dimensional NMR Experiments from Chemical Exchange of Transverse Magnetisation

Two‐dimensional correlation measurements such as COSY, NOESY, HMQC, and HSQC experiments are central to small‐molecule and biomolecular NMR spectroscopy, and commonly form the basis of more complex experiments designed to study chemical exchange occurring during additional mixing periods. However, exchange occurring during chemical shift evolution periods can also influence the appearance of such spectra. While this is often exploited through one‐dimensional lineshape analysis (“dynamic NMR”), the analysis of exchange across multiple chemical shift evolution periods has received less attention. Here we report that chemical exchange‐induced cross‐peaks can arise in even the simplest two‐dimensional NMR experiments. These cross‐peaks can have highly distorted phases that contain rich information about the underlying exchange process. The quantitative analysis of such peaks, from a single 2D spectrum, can provide a highly accurate characterisation of underlying exchange processes

Protective Antiviral Immunity Conferred by a Nonintegrative Lentiviral Vector-Based Vaccine

Lentiviral vectors are under intense scrutiny as unique candidate viral vector vaccines against tumor and aggressive pathogens because of their ability to initiate potent and durable specific immune responses. Strategies that alleviate safety concerns will facilitate the clinical developments involving lentiviral vectors. In this respect, the development of integration deficient lentiviral vectors circumvents the safety concerns relative to insertional mutagenesis and might pave the way for clinical applications in which gene transfer is targeted to non-dividing cells. We thus evaluated the potential use of nonintegrative lentiviral vectors as vaccination tools since the main targeted cell in vaccination procedures is the non-dividing dendritic cell (DC). In this study, we demonstrated that a single administration of nonintegrative vectors encoding a secreted form of the envelope of a virulent strain of West Nile Virus (WNV) induces a robust B cell response. Remarkably, nonintegrative lentiviral vectors fully protected mice from a challenge with a lethal dose of WNV and a single immunization was sufficient to induce early and long-lasting protective immunity. Thus, nonintegrative lentiviral vectors might represent a safe and efficacious vaccination platform for the development of prophylactic vaccines against infectious agents

A Full Suite of Histone and Histone Modifying Genes Are Transcribed in the Dinoflagellate Lingulodinium

BACKGROUND: Dinoflagellates typically lack histones and nucleosomes are not observed in DNA spreads. However, recent studies have shown the presence of core histone mRNA sequences scattered among different dinoflagellate species. To date, the presence of all components required for manufacturing and modifying nucleosomes in a single dinoflagellate species has not been confirmed. METHODOLOGY AND RESULTS: Analysis of a Lingulodinium transcriptome obtained by Illumina sequencing of mRNA shows several different copies of each of the four core histones as well as a suite of histone modifying enzymes and histone chaperone proteins. Phylogenetic analysis shows one of each Lingulodinium histone copies belongs to the dinoflagellate clade while the second is more divergent and does not share a common ancestor. All histone mRNAs are in low abundance (roughly 25 times lower than higher plants) and transcript levels do not vary over the cell cycle. We also tested Lingulodinium extracts for histone proteins using immunoblotting and LC-MS/MS, but were unable to confirm histone expression at the protein level. CONCLUSION: We show that all core histone sequences are present in the Lingulodinium transcriptome. The conservation of these sequences, even though histone protein accumulation remains below currently detectable levels, strongly suggests dinoflagellates possess histones

Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection

BACKGROUND: Chikungunya (CHIK) virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK virus was associated with an unprecedented magnitude outbreak of CHIK disease in the Indian Ocean. Clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. Since the cellular targets of CHIK virus in humans are unknown, we studied the pathogenic events and targets of CHIK infection in skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistology on muscle biopsies from two CHIK virus-infected patients with myositic syndrome showed that viral antigens were found exclusively inside skeletal muscle progenitor cells (designed as satelllite cells), and not in muscle fibers. To evaluate the ability of CHIK virus to replicate in human satellite cells, we assessed virus infection on primary human muscle cells; viral growth was observed in CHIK virus-infected satellite cells with a cytopathic effect, whereas myotubes were essentially refractory to infection. CONCLUSIONS/SIGNIFICANCE: This report provides new insights into CHIK virus pathogenesis, since it is the first to identify a cellular target of CHIK virus in humans and to report a selective infection of muscle satellite cells by a viral agent in humans

On the evolutionary ecology of symbioses between chemosynthetic bacteria and bivalves

Mutualistic associations between bacteria and eukaryotes occur ubiquitously in nature, forming the basis for key ecological and evolutionary innovations. Some of the most prominent examples of these symbioses are chemosynthetic bacteria and marine invertebrates living in the absence of sunlight at deep-sea hydrothermal vents and in sediments rich in reduced sulfur compounds. Here, chemosynthetic bacteria living in close association with their hosts convert CO2 or CH4 into organic compounds and provide the host with necessary nutrients. The dominant macrofauna of hydrothermal vent and cold seep ecosystems all depend on the metabolic activity of chemosynthetic bacteria, which accounts for almost all primary production in these complex ecosystems. Many of these enigmatic mutualistic associations are found within the molluscan class Bivalvia. Currently, chemosynthetic symbioses have been reported from five distinct bivalve families (Lucinidae, Mytilidae, Solemyidae, Thyasiridae, and Vesicomyidae). This brief review aims to provide an overview of the diverse physiological and genetic adaptations of symbiotic chemosynthetic bacteria and their bivalve hosts

Search for Neutral Heavy Leptons Produced in Z Decays

Weak isosinglet Neutral Heavy Leptons ($\nu_m$) have been searched for using data collected by the DELPHI detector corresponding to $3.3\times 10^{6}$ hadronic~Z$^{0}$ decays at LEP1. Four separate searches have been performed, for short-lived $\nu_m$ production giving monojet or acollinear jet topologies, and for long-lived $\nu_m$ giving detectable secondary vertices or calorimeter clusters. No indication of the existence of these particles has been found, leading to an upper limit for the branching ratio $BR($Z$^0\rightarrow \nu_m \overline{\nu})$ of about $1.3\times10^{-6}$ at 95\% confidence level for $\nu_m$ masses between 3.5 and 50 GeV/$c^2$. Outside this range the limit weakens rapidly with the $\nu_m$ mass. %Special emphasis has been given to the search for monojet--like topologies. One event %has passed the selection, in agreement with the expectation from the reaction: %$e^+e^- \rightarrow\ell \bar\ell \nu\bar\nu$. The results are also interpreted in terms of limits for the single production of excited neutrinos

Measurement of inclusive π0\pi^{0} production in hadronic Z0Z^{0} decays

An analysis is presented of inclusive \pi^0 production in Z^0 decays measured with the DELPHI detector. At low energies, \pi^0 decays are reconstructed by \linebreak using pairs of converted photons and combinations of converted photons and photons reconstructed in the barrel electromagnetic calorimeter (HPC). At high energies (up to x_p = 2 \cdot p_{\pi}/\sqrt{s} = 0.75) the excellent granularity of the HPC is exploited to search for two-photon substructures in single showers. The inclusive differential cross section is measured as a function of energy for {q\overline q} and {b \bar b} events. The number of \pi^0's per hadronic Z^0 event is N(\pi^0)/ Z_{had}^0 = 9.2 \pm 0.2 \mbox{(stat)} \pm 1.0 \mbox{(syst)} and for {b \bar b}~events the number of \pi^0's is {\mathrm N(\pi^0)/ b \overline b} = 10.1 \pm 0.4 \mbox{(stat)} \pm 1.1 \mbox{(syst)} . The ratio of the number of \pi^0's in b \overline b events to hadronic Z^0 events is less affected by the systematic errors and is found to be 1.09 \pm 0.05 \pm 0.01. The measured \pi^0 cross sections are compared with the predictions of different parton shower models. For hadronic events, the peak position in the \mathrm \xi_p = \ln(1/x_p) distribution is \xi_p^{\star} = 3.90^{+0.24}_{-0.14}. The average number of \pi^0's from the decay of primary \mathrm B hadrons is found to be {\mathrm N} (B \rightarrow \pi^0 \, X)/\mbox{B hadron} = 2.78 \pm 0.15 \mbox{(stat)} \pm 0.60 \mbox{(syst)}