CRAMER: a lightweight, highly customizable web-based genome browser supporting multiple visualization instances.

SUMMARY: In recent years, the ability to generate genomic data has increased dramatically along with the demand for easily personalized and customizable genome browsers for effective visualization of diverse types of data. Despite the large number of web-based genome browsers available nowadays, none of the existing tools provides means for creating multiple visualization instances without manual set up on the deployment server side. The Cranfield Genome Browser (CRAMER) is an open-source, lightweight and highly customizable web application for interactive visualization of genomic data. Once deployed, CRAMER supports seamless creation of multiple visualization instances in parallel while allowing users to control and customize multiple tracks. The application is deployed on a Node.js server and is supported by a MongoDB database which stored all customizations made by the users allowing quick navigation between instances. Currently, the browser supports visualizing a large number of file formats for genome annotation, variant calling, reads coverage and gene expression. Additionally, the browser supports direct Javascript coding for personalized tracks, providing a whole new level of customization both functionally and visually. Tracks can be added via direct file upload or processed in real-time via links to files stored remotely on an FTP repository. Furthermore, additional tracks can be added by users via simple drag and drop to an existing visualization instance. AVAILABILITY AND IMPLEMENTATION: CRAMER is implemented in JavaScript and is publicly available on GitHub on https://github.com/FadyMohareb/cramer. The application is released under an MIT licence and can be deployed on any server running Linux or Mac OS. CONTACT: f.mohareb@cranfield.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Induction of Plasmodium falciparum sporozoite-neutralizing antibodies upon vaccination with recombinant Pfs16 vaccinia virus and/or recombinant Pfs16 protein produced in yeast.

Pfs16 is a sexual stage/sporozoite-specific antigen of Plasmodium falciparum and is a potential candidate for a sporozoite-neutralizing vaccine. To obtain more information on the function of Pfs16 and to investigate its role during transmission and hepatocyte invasion, immunization experiments were performed with both a Pfs16-specific recombinant vaccinia virus and virus-like particles produced in yeast composed of the hepatitis B surface antigen (HBsAg) and antigen Pfs16 fused to HBsAg. Upon transformation of yeast cells, harbouring a genomic copy of the HBsAg gene, with a plasmid carrying the fusion gene Pfs16-HBsAg (Pfs16-S) virus-like hybrid particles composed of HBsAg and Pfs16-S were formed of a size similar to those present in human sera after infection with the hepatitis B virus. Cells infected with recombinant Pfs16 vaccinia virus synthesized a polypeptide of approx. 16 kDa that reacted with a Pfs16-specific polyclonal antibody. Animals vaccinated with the yeast hybrid particles and/or recombinant vaccinia virus both produced Pfs16-specific antibodies. These antibodies showed no transmission-blocking activity, but they efficiently diminished or abolished in vitro invasion of sporozoites into human hepatoma cells (HepG2-A16) and primary human hepatocytes.

Nucleotide sequence of the gene encoding the active-site serine beta-lactamase from Actinomadura R39.

The gene encoding the extracellular, active-site serine beta-lactamase of Actinomadura R39, previously cloned into Streptomyces lividans, has the information for the synthesis of a 304 amino acid protein, the amino terminal region of which has the characteristic features of a signal peptide. The Actinomadura R39 beta-lactamase is another member of the class A beta-lactamases. In particular, it shows high homology with the beta-lactamase of Bacillus licheniformis.

Hand involvement in multiple hereditary exostosis.

In summary, patients with multiple hereditary exostosis often inherit hand involvement but rarely show hand deformity. The principal area of involvement appears to be around the MCP joint but the PIP joint is the most common area of deformity. Metacarpal shortening usually does not cause functional problems and need not be treated. Angular deformity, though rare, does cause problems and needs surgical treatment. Unfortunately, there is no evidence that prevention of deformity is possible by early excision of osteochondromas. Treatment, therefore, requires both osteochondroma excision and closing-wedge corrective osteotomy.

A clear catalyst effect.

PIP: A member of the International Council on Management of Population Programs (ICOMP) says that training women to manage and harbor employable skills has a very large multiplier effect. An international nongovernmental organization (NGO) based in Kuala Lumpur and established in 1973 to improve the performance of family planning programs in Asian developing countries through better management techniques, ICOMP boasts 35 developing countries as members. The organization's mandate has expanded over the years such that they now provide management and skills training programs through local NGOs in developing countries. The Asian Development Bank (ADB) has been assisting ICOMP's training programs in Bangladesh, Indonesia, Nepal, Pakistan, and the Philippines since 1989 with two technical assistance grants totalling $681,000. This is the first time that the Bank has supported training exclusively for women. Although the ADB planned to reach only 940 women under the first technical assistance, it eventually helped train more than 1200; an additional 1300 women have attended the courses offered under the Bank's second grant. Training courses are aimed at disadvantaged women who need training in employment skills, women engaged in community development or income-generating projects who need to develop basic management skills, and officials of the participating women NGOs who need training in organizing, developing, and implementing income-generating projects. The author discusses other elements of training aimed at improving the social and economic status of women, along with experiences of the Bangladesh Association for Community Education and the MELATI Foundation of Jakarta, Indonesia.^ieng

A better living. A small farmer development project benefits farmers and landless laborers.

PIP: Nepal suffers from massive poverty. The efforts of the Agricultural Development Bank (ADB) and the International Fund for Agricultural Development (AFAD) are directed to providing loans to small farmers for poverty alleviation. The 1st project between 1981 and 1987 and the 2nd project with closing loans in 1991 has assisted 88,000 rural poor in 41 districts, which is considerably more than the target of 58,000. A 3rd Loan Project funded just by ADB will benefit another 138,000 rural poor or 17% of eligible beneficiaries by 1995. Requirements for loans are income Rs2000, landless laborers, and farmers with .5 hectares of land. The credit limit is Rs30,000. An example of the improvement in standard of living of a mother and her 4 children is given; not only has her income increased form Rs2000/year to a potential Rs1800/month but her children are able to receive an education. She was 1 of 1550 participants in the subproject at Mahendra Nagar in the Dhanusa district. Another landless farmer joined an 8-person farmer group and the loan helped him establish a fishery which yields gross income of Rs7500/year. With an additional loan for expansion, he might be able to gross Rs15,000/year. The interest charge is 13% with repayment over 5 years compared with private moneylender charges of 60-100%. Support from the group organizer was needed, however, to encourage the fishery business, because the farmer's intentions were originally to buy a buffalo which other group members had done and then consumed, thus not providing for repayment of the loan. Organizers must not only direct farmers activities, but initially select suitable candidates, motivate them, and provide guidance. Organizers must have a certificate in science, social science, or agriculture. Loans can be obtained for agriculture, livestock and fish enterprises, cottage industries, and agricultural and retail trading. Group savings is encouraged through special meetings, as needed. 15% of the graduates have been women; the 3rd project included a special allocation just for women. The final example is of another woman who opened a tea stall and can now provide more than just subsistence for her 3 children.^ieng

Land of the thunder dragon is on the move. Bhutan.

PIP: A small and landlocked country in the Himalayas, the size of Switzerland, Bhutan or Druk Yul, Land of the Thunder Dragon, had for centuries been isolated from the outside world. Finally, its tradition-bound people are beginning to pick up new trades and vocations. Penjore Timber Industries & Exports Ltd. is one of the 1st modern wood-processing complexes in Bhutan still with a predominantly subsistence and barter agriculture economy. The company, set up with the financial support of the Asian Development Bank (ADB), is producing broomsticks, handles for tools, wooden doors, and window frames mainly for export. The industrial sector is small and accounts for only 4% of GDP. Most of the 125 private enterprises in the country are small. A development bank, the Bhutan Development Finance Corporation (BDFC), was established in 1988 with ADB support for the development of private industry. A general education system was established and schools were opened only in the early 1960s. The government had given the development of trained manpower high priority in its 5th Economic and Social Development Plan (FY 1981/82-FY 1986/87). The Royal Institute of Management (RIM) was established in 1986. About 40 trainees each in secretarial, accounting, and basic management training programs and 150 managerial personnel from public and private agencies are trained each year by RIM which the ADB supports under the Second Multiproject Loan to Bhutan with cofinancing by the Norwegian Development Agency. So far RIM has designed 12 different training courses, 92 students graduated in 1989, and by 1995 about 30 training courses are envisioned. According to 1987 data in a recent UN report Bhutan is the only one of the world's 42 least-developed countries with a more than 10% agricultural production growth rate where real GDP growth has outspaced population growth.^ieng

Becoming successful entrepreneurs. Bangladesh. ADB supports pioneering family-based approach to provide micro-credit and skills training.

PIP: The Thana Resource Development and Employment Project (TRDEP), built upon the successful experience of the Grameen Bank and other nongovernmental organizations, is a comprehensive poverty alleviation scheme implemented by the government of Bangladesh and targeted to the poorest segment of Bangladeshi society. The project provides soft loans to landless poor for income-generating activities involving non-crop livelihoods and trades. The loans are granted at an 18% interest rate including a 2% charge which goes into a risk fund. The poorest of poor are eligible to receive loans as long as each borrowing unit is a self-help group comprised of five members of one family and each member of the group assumes the responsibility of paying each other member's loan. Each member of a borrowing group may receive loans in the amount of Taka 3000-5000 (US$75-125). The loans are then repayable in 50 equal installments over the course of 1 year. One member's default disqualifies all other group members from receiving future credit until the default is cleared. TRDEP borrowers have started small, successful entrepreneurial activities with their loans as capital.^ieng

Hepatitis B virus-specific cytotoxic T lymphocyte responses in patients with acute and chronic hepatitis B virus infection.

An in vitro model was developed that allowed the analysis of hepatitis B virus-specific cytotoxic T lymphocyte responses in patients suffering from acute and chronic hepatitis B virus infections. Since virus-specific cytotoxic T lymphocytes recognize endogenously synthesized and processed antigen only when it is presented in the context of autologous HLA class I molecules and since hepatitis B virus does not infect human cells in vitro, a panel of recombinant vaccinia viruses was constructed to induce the expression of hepatitis B virus envelope and nucleocapsid proteins in cultured primary cells or cell lines derived from the patients to be studied. In order for a cytotoxic T lymphocyte response to be detectable with the currently available techniques, a sufficient number of activated cytotoxic T lymphocytes is required. To meet this requirement, lymphocytes freshly isolated from venous blood were stimulated in vitro with recombinant vaccinia-infected and formaldehyde-fixed autologous T lymphoblasts. The presence of hepatitis B virus-specific cytotoxic T lymphocytes, amplified and activated during this induction culture, was demonstrated in a microcytotoxicity assay using 51Cr-labeled, recombinant vaccinia-infected Epstein-Barr virus-immortalized, autologous B lymphocytes as target cells. Using this in vitro model, we were able to demonstrate the presence of hepatitis B virus envelope- and nucleocapsid-specific cytotoxic T lymphocytes in venous blood from one subject who had recently recovered from an acute hepatitis B virus infection and in three patients suffering from chronic hepatitis B virus infections. No hepatitis B virus-specific cytotoxic T lymphocytes activity was discernible in the venous blood from two vaccine recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cloning and amplified expression in Streptomyces lividans of the gene encoding the extracellular beta-lactamase of Actinomadura R39.

By using the promoter-probe plasmid pIJ424, genomic DNA fragments of Actinomadura R39 were shown to have promoter activity in Streptomyces lividans. The same 100-200-copy-number plasmid was used to clone in S. lividans TK24, the gene that encodes the Actinomadura R39 beta-lactamase. Gene cloning resulted in an amplified expression of the beta-lactamase when compared with the amounts of enzyme produced by the original strain (1 mg versus 0.008 mg.litre of culture-1).

Vaccination with recombinant vaccinia viruses expressing ICP27 induces protective immunity against herpes simplex virus through CD4+ Th1+ T cells.

This study was designed to evaluate the efficacy and mechanisms of protection mediated by recombinant vaccinia viruses encoding immediate-early (IE) proteins of herpes simplex virus type 2 (HSV-2). Three mouse strains were immunized against the IE proteins ICP27, ICP0, and ICP4, and mice were challenged intracutaneously in the zosteriform model with HSV-2 strain MS. Protection was observed only following immunization with the ICP27 construct and then only in the BALB/c mouse strain. Protection in BALB/c mice was ablated by CD4+ T-cell suppression but remained intact in animals depleted of CD8+ T cells. Moreover, protection could be afforded to SCID nude recipients with CD4+ but not CD8+ T cells from ICP27-immunized mice. Only BALB/c mice developed a delayed-type hypersensitivity reaction to HSV-2, and in vitro measurements of humoral and cell-mediated immunity revealed response patterns to ICP27 and HSV that differed between protected BALB/c and unprotected mouse strains. Accordingly, BALB/c responses showed antigen-induced cytokine profiles dominated by type 1 cytokines, whereas C57BL/6 and C3H/HeN mice generated cytokine responses mainly of the type 2 variety. Our results may indicate that protection against zosterification is mainly mediated by CD4+ T cells that express a type 1 cytokine profile and that protective vaccines against HSV which effectively induce such T-cell responses should be chosen.

Several antigenic determinants exposed on the gp120 moiety of HIV-1 gp160 are hidden on the mature gp120.

Mouse mAb reactive to the HIV-1 envelope glycoprotein precursor gp160 of the HTLVIII(B) isolate were characterized in radioimmunoprecipitation and immunoblot tests with the use of HTLVIII(B) isolate as Ag. The reactivities of these mAb were also measured in a capture enzyme immunoassay and in radioimmunoprecipitation assay by using gp160 and gp120 expressed as vaccinia recombinants. Striking differences in exposure of specific epitopes were noted between the gp120 component of the gp160 precursor and the fully processed gp120 in both tests. These conformational rearrangements affecting the gp120 moiety of the HIV-1 envelope glycoprotein might have important implications on its immunogenicity.