Rapid Targeted Gene Disruption in Bacillus Anthracis

Anthrax is a zoonotic disease recognized to affect herbivores since Biblical times and has the widest range of susceptible host species of any known pathogen. The ease with which the bacterium can be weaponized and its recent deliberate use as an agent of terror, have highlighted the importance of gaining a deeper understanding and effective countermeasures for this important pathogen. High quality sequence data has opened the possibility of systematic dissection of how genes distributed on both the bacterial chromosome and associated plasmids have made it such a successful pathogen. However, low transformation efficiency and relatively few genetic tools for chromosomal manipulation have hampered full interrogation of its genome. Results: Group II introns have been developed into an efficient tool for site-specific gene inactivation in several organisms. We have adapted group II intron targeting technology for application in Bacillus anthracis and generated vectors that permit gene inactivation through group II intron insertion. The vectors developed permit screening for the desired insertion through PCR or direct selection of intron insertions using a selection scheme that activates a kanamycin resistance marker upon successful intron insertion. Conclusions: The design and vector construction described here provides a useful tool for high throughput experimental interrogation of the Bacillus anthracis genome and will benefit efforts to develop improved vaccines and therapeutics.Chem-Bio Diagnostics program from the Department of Defense Chemical and Biological Defense program through the Defense Threat Reduction Agency (DTRA) B102387MNIH GM037949Welch Foundation F-1607Cellular and Molecular Biolog

Out-of-Print and Antiquarian Books: Guides for Reference Librarians

Abstract: The issue of evaluating old books is one that, on a functional level, has been removed from the provenance of librarians by Internal Revenue Service regulations. But the question in public, academic, and special libraries persists as does the assumption on the part of the general public that librarians know something about old books and the antiquarian book trade. This article reviews the issues involved and discusses the sources of pricing information most useful for general libraries in the United States and Canada. Article: The technical areas of acquisitions are unfamiliar ground to most reference librarians who usually do not venture into the territory beyond directing patron inquiries about price and availability of books to local bookstores or to Books in Print. If the book in question is still available from the publisher, this response is undoubtedly sufficient for the immediate needs of the patron. When a book is out of print and no longer available from the publisher, a question of a different order is created, a question that many librarians feel illprepared to attempt to answer. The antiquarian book market is an unknown arena for most librarians and one in which there are no clear answers. Because these questions represent the junction between knowledge and information, which both have undefined value, and physical objects for which value is defined, the questions themselves seem to raise their own problems in the moral and ethical realm with which many librarians are uncomfortable. The ethical boundaries of reference service have been debated in the library community from the beginnings of American librarianship. Edmund Lester Pearson provided the librarian with this adjuration: "Question each Applicant closely. See that he be a Person of good Reputation, scholarly Habits, sober and courteous Demeanour. Any mere Trifler, a person that would Dally with Books, or seek in them shallow Amusement, may be Dismiss' d without Delay. 1 Though not made seriously, his words struck a chord among American librarians who, in 1909, were fully prepared to accept this injunction as a basic doctrine of eighteenth-century librarianship. 2 As guardians of a public trust committed to education, knowledge, and culture, librarians have, it seems, an ambivalent perspective on the motives that spur people to seek their services. In the past, this perspective has manifested itself in debate over newspaper reading rooms, popular fiction in library collections, and even in the provision of business information and other specialized reference services. The acceptance by American librarians of policy statements by the American Library Association insisting on freedom of access to information and on the right of library users to courteous and able responses to their queries has, to some extent, reduced the ambiguity inherent in librarians' tasks but has not eliminated it. Though the ethics of reference service dictate that each question asked by a library user is validated by that question's importance to the person asking it and that challenging the legitimacy of information needs is beyond the proper domain of librarians, it is evident that there are types of questions that are regarded as improper subjects of inquiry as well as groups of users who are seen as pariahs in the information world. Librarians have, in some sense, come to terms with the homeless and the latch-key children. They have pu

African trypanosome control in the insect vector and mammalian host

The life cycle of African trypanosomes involves adaptations to the defense mechanisms of two completely different hosts, the insect vector Glossina and the mammalian host. This interplay ultimately determines host resistance and/or tolerance to parasite infection. In the tsetse fly, the immune deficiency (IMD)-regulated pathway, the scavenger receptor peptidoglycan-recognition protein LB (PGRP-LB), and the reactive oxygen species (ROS)-mediated response modulate the insect's capacity to transmit the parasite. In experimental mice, control of parasite burden and tissue pathogenicity relies on timely regulated interactions between myeloid cells exhibiting distinct activation states (M1 versus M2 type). Tsetse fly saliva and various trypanosome components including adenylate cyclases, DNA, a kinesin heavy chain, and variant surface glycoprotein (VSG) interfere with resistance and tolerance to infection.SCOPUS: re.jinfo:eu-repo/semantics/publishe