Development of human single-chain antibodies against SARS-associated coronavirus.

The outbreak of severe acute respiratory syndrome (SARS), caused by a distinct coronavirus, in 2003 greatly threatened public health in China, Southeast Asia as well as North America. Over 1,000 patients died of the SARS virus, representing 10% of infected people. Like other coronaviruses, the SARS virus also utilizes a surface glycoprotein, namely the spike protein, to infect host cells. The spike protein of SARS virus consists of 1,255 amino acid residues and can be divided into two sub-domains, S1 and S2. The S1 domain mediates the binding of the virus to its receptor angiotensin-converting enzyme 2, which is abundantly distributed on the surface of human lung cells. The S2 domain mediates membrane fusion between the virus and the host cell. Hence two strategies can be used to block the infection of the SARS virus, either by interfering with the binding of the S1 domain to the receptor or by blocking the fusion of the virus with the cell membrane mediated by the S2 domain. Several antibodies against the S1 domain have been generated and all of them are able to neutralize the virus in vitro and in vivo using animal models. Unfortunately, point mutations have been identified in the S1 domain, so that the virus isolated in the future may not be recognized by these antibodies. As no mutation has been found in the S2 domain indicating that this region is more conserved than the S1 domain, it may be a better target for antibody binding. After predicting the immunogenicity of the epitopes of the S2 domain, we chemically synthesized two peptides and also expressed one of them using a recombinant DNA method. We screened a phage displaying library of human single-chain antibodies (ScFv) against the predicted epitopes and obtained a human ScFv which can recognize the SARS virus in vitro

Promoting contraceptive use among unmarried female migrants in one factory in Shanghai: a pilot workplace intervention

<p>Abstract</p> <p>Background</p> <p>In urban China, more single women are becoming pregnant and resorting to induced abortion, despite the wide availability of temporary methods of contraception. We developed and piloted a workplace-based intervention to promote contraceptive use in unmarried female migrants working in privately owned factories.</p> <p>Methods</p> <p>Quasi-experimental design. In consultation with clients, we developed a workplace based intervention to promote contraception use in unmarried female migrants in a privately owned factory. We then implemented this in one factory, using a controlled before-and-after design. The intervention included lectures, bespoke information leaflets, and support to the factory doctors in providing a contraceptive service.</p> <p>Results</p> <p>598 women participated: most were under 25, migrants to the city, with high school education. Twenty percent were lost when staff were made redundant, and implementation was logistically complicated. All women attended the initial lecture, and just over half the second lecture. Most reported reading the educational material provided (73%), but very few women reported using the free family planning services offered at the factory clinic (5%) or the Family Planning Institute (3%). At baseline, 90% (N = 539) stated that contraceptives were required if having sex before marriage; of those reporting sex in the last three months, the majority reporting using contraceptives (78%, 62/79) but condom use was low (44%, 35/79).</p> <p>Qualitative data showed that the reading material seemed to be popular and young women expressed a need for more specific reproductive health information, particularly on HIV/AIDS. Women wanted services with some privacy and anonymity, and views on the factory service were mixed.</p> <p>Conclusion</p> <p>Implementing a complex intervention with a hard to reach population through a factory in China, using a quasi-experimental design, is not easy. Further research should focus on the specific needs and service preferences of this population and these should be considered in any policy reform so that contraceptive use may be encouraged among young urban migrant workers.</p

Silencing COI1 in Rice Increases Susceptibility to Chewing Insects and Impairs Inducible Defense

The jasmonic acid (JA) pathway plays a key role in plant defense responses against herbivorous insects. CORONATINE INSENSITIVE1 (COI1) is an F-box protein essential for all jasmonate responses. However, the precise defense function of COI1 in monocotyledonous plants, especially in rice (Oryza sativa L.) is largely unknown. We silenced OsCOI1 in rice plants via RNA interference (RNAi) to determine the role of OsCOI1 in rice defense against rice leaf folder (LF) Cnaphalocrocis medinalis, a chewing insect, and brown planthopper (BPH) Nilaparvata lugens, a phloem-feeding insect. In wild-type rice plants (WT), the transcripts of OsCOI1 were strongly and continuously up-regulated by LF infestation and methyl jasmonate (MeJA) treatment, but not by BPH infestation. The abundance of trypsin protease inhibitor (TrypPI), and the enzymatic activities of polyphenol oxidase (PPO) and peroxidase (POD) were enhanced in response to both LF and BPH infestation, but the activity of lipoxygenase (LOX) was only induced by LF. The RNAi lines with repressed expression of OsCOI1 showed reduced resistance against LF, but no change against BPH. Silencing OsCOI1 did not alter LF-induced LOX activity and JA content, but it led to a reduction in the TrypPI content, POD and PPO activity by 62.3%, 48.5% and 27.2%, respectively. In addition, MeJA-induced TrypPI and POD activity were reduced by 57.2% and 48.2% in OsCOI1 RNAi plants. These results suggest that OsCOI1 is an indispensable signaling component, controlling JA-regulated defense against chewing insect (LF) in rice plants, and COI1 is also required for induction of TrypPI, POD and PPO in rice defense response to LF infestation

The Integrative Taxonomic Approach Reveals Host Specific Species in an Encyrtid Parasitoid Species Complex

Integrated taxonomy uses evidence from a number of different character types to delimit species and other natural groupings. While this approach has been advocated recently, and should be of particular utility in the case of diminutive insect parasitoids, there are relatively few examples of its application in these taxa. Here, we use an integrated framework to delimit independent lineages in Encyrtus sasakii (Hymenoptera: Chalcidoidea: Encyrtidae), a parasitoid morphospecies previously considered a host generalist. Sequence variation at the DNA barcode (cytochrome c oxidase I, COI) and nuclear 28S rDNA loci were compared to morphometric recordings and mating compatibility tests, among samples of this species complex collected from its four scale insect hosts, covering a broad geographic range of northern and central China. Our results reveal that Encyrtus sasakii comprises three lineages that, while sharing a similar morphology, are highly divergent at the molecular level. At the barcode locus, the median K2P molecular distance between individuals from three primary populations was found to be 11.3%, well outside the divergence usually observed between Chalcidoidea conspecifics (0.5%). Corroborative evidence that the genetic lineages represent independent species was found from mating tests, where compatibility was observed only within populations, and morphometric analysis, which found that despite apparent morphological homogeneity, populations clustered according to forewing shape. The independent lineages defined by the integrated analysis correspond to the three scale insect hosts, suggesting the presence of host specific cryptic species. The finding of hidden host specificity in this species complex demonstrates the critical role that DNA barcoding will increasingly play in revealing hidden biodiversity in taxa that present difficulties for traditional taxonomic approaches

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Search for B mesogenesis at BaBar

A new mechanism has been proposed to simultaneously explain the presence of dark matter and the matter-antimatter asymmetry in the Universe. This scenario predicts exotic B -meson decays into a baryon and a dark-sector antibaryon (ψ D ) with branching fractions accessible at B factories. We present a search for B→ΛψD decays using data collected by the BABAR experiment at SLAC. This reaction is identified by fully reconstructing the accompanying B meson and requiring the presence of a single Λ baryon in the remaining particles. No significant signal is observed, and bounds on the B → Λ ψ D branching fraction are derived in the range 0.13 – 5.2 × 10 − 5 for 1.0 < m ψ D < 4.2 GeV / c 2. These results set strong constraints on the parameter space allowed by the theory

Search for heavy neutral leptons using tau lepton decays at <i>BaBaR</i>

This article presents a model-independent search for an additional, mostly sterile, heavy neutral lepton (HNL), that is capable of mixing with the Standard Model τ neutrino with a mixing strength of |Uτ4|2, corresponding to the absolute square of the extended Pontecorvo-Maki-Nakagawa-Sakata matrix element. Data from the BABAR experiment, with a total integrated luminosity of 424 fb-1, are analyzed using a kinematic approach that makes no assumptions on the model behind the origins of the HNL, its lifetime or decay modes. No significant signal is found. Upper limits on |Uτ4|2 at the 95% confidence level, depend on the HNL mass hypothesis and vary from 2.31×10-2 to 5.04×10-6 (with all uncertainties considered), across the mass range 100<m4<1300 MeV/c2; the more stringent limits being placed at higher masses

Study of the reactions e plus e- ? K+K-,r0,r0,r0, e+ e-?K0SK?,r?,r0,r0, and e plus e-? K0SK?,r?,r+,r- at center-of-mass energies from threshold to 4.5 GeV using initial-state radiation

We study the processes e+e-→K+K-π0π0π0γ, KS0K±π?π0π0γ, and KS0K±π?π+π-γ in which an energetic photon is radiated from the initial state. The data were collected with the BABAR detector at the SLAC National Accelerator Laboratory. About 1200, 2600, and 6000 events, respectively, are selected from a data sample corresponding to an integrated luminosity of 469 fb-1. The invariant mass of the hadronic final state defines the effective e+e- center-of-mass energy. The center-of-mass energies range from threshold to 4.5 GeV. From the mass spectra, the first ever measurements of the e+e-→K+K-π0π0π0, e+e-→KS0K±π?π0π0, and e+e-→KS0K±π?π+π- cross sections are performed. The contributions from the intermediate states that include η, φ, ρ, K∗(892), and other resonances are presented. We observe the J/ψ and ψ(2S) in most of these final states and measure the corresponding branching fractions, many of them for the first time

Cytotoxic alkaloids from Boehmeria siamensis

Two new phenanthroquinolizidine alkaloids, boehmeriasins A and B, were isolated from the aqueous ethanolic extract of Boehmeria siamensis Craib (Urticaceae) by bioassay-guided fractionation. Their structures were elucidated on the basis of spectral evidence. Boehmeriasin A possesses cytotoxic activity against 12 cell lines from 6 panels of cancer including lung can-cer, colon cancer, breast cancer, prostate cancer, kidney cancer and leukemia with GI(50) between 0.2 and 100 ng/mL, whereas boehmeriasin B showed lower activity