Enteropathogenic E. coli, Salmonella, and Shigella: masters of host cell cytoskeletal exploitation.

Bacterial pathogens have evolved numerous strategies to exploit their host's cellular processes so that they can survive and persist. Often, a bacterium must adhere very tightly to the cells and mediate its effects extracellularly, or it must find a way to invade the host's cells and survive intracellularly. In either case, the pathogen hijacks the host's cytoskeleton. The cytoskeleton provides a flexible framework for the cell and is involved in mediating numerous cellular functions, from cell shape and structure to programmed cell death. Altering the host cytoskeleton is crucial for mediating pathogen adherence, invasion, and intracellular locomotion. We highlight recent advances in the pathogenesis of enteropathogenic Escherichia coli, Salmonella Typhimurium, and Shigella flexneri. Each illustrates how bacterial pathogens can exert dramatic effects on the host cytoskeleton

SPARC! Preparing First-Year Students for Information Overload

Presentation slides as presented at the Newfoundland and Labrador Library Association (NLLA) Conference, 2008. Outlines the SPARC (Summer Program in Academic Research & Communication) offered by Memorial University Libraries. Includes planning, marketing, delivery and assessment of the information literacy summer program designed for highschool students new to University

Status report on the Los Alamos National Laboratory Ion Beam Facility

The Ion Beam Facility operated for 6000 machine hours last year, ranging in energy from 300 Kev to 24 Mev. Improvements include cryopumps replacing diffusion pumps, a rebuilding of the tandem chopper electronics and the vertical's corona charging system. Methane molecules were successfully accelerated by the vertical in quantities of hundreds of nanoamperes. Two replacement magnet power supplies on the tandem and a completely new capacitor shell regulator on the vertical are soon to be installed

Making Memorial Student-Ready: Reflections on the First Year Success Experience

In eleven short chapters faculty, academic advising staff and student union representatives discuss aspects of Memorial’s First Year Success Program (piloted as a Teaching Learning Framework initiative 2012-2017). Teaching approaches, curriculum content and policy rationales are covered in a broad view of how and why students identified as least likely to succeed at university can be academically supported. Contributors identify the singular importance of the community that First Year Success provided them and its student participants

Nephrin Regulates Lamellipodia Formation by Assembling a Protein Complex That Includes Ship2, Filamin and Lamellipodin

Actin dynamics has emerged at the forefront of podocyte biology. Slit diaphragm junctional adhesion protein Nephrin is necessary for development of the podocyte morphology and transduces phosphorylation-dependent signals that regulate cytoskeletal dynamics. The present study extends our understanding of Nephrin function by showing in cultured podocytes that Nephrin activation induced actin dynamics is necessary for lamellipodia formation. Upon activation Nephrin recruits and regulates a protein complex that includes Ship2 (SH2 domain containing 5′ inositol phosphatase), Filamin and Lamellipodin, proteins important in regulation of actin and focal adhesion dynamics, as well as lamellipodia formation. Using the previously described CD16-Nephrin clustering system, Nephrin ligation or activation resulted in phosphorylation of the actin crosslinking protein Filamin in a p21 activated kinase dependent manner. Nephrin activation in cell culture results in formation of lamellipodia, a process that requires specialized actin dynamics at the leading edge of the cell along with focal adhesion turnover. In the CD16-Nephrin clustering model, Nephrin ligation resulted in abnormal morphology of actin tails in human podocytes when Ship2, Filamin or Lamellipodin were individually knocked down. We also observed decreased lamellipodia formation and cell migration in these knock down cells. These data provide evidence that Nephrin not only initiates actin polymerization but also assembles a protein complex that is necessary to regulate the architecture of the generated actin filament network and focal adhesion dynamics

The EHEC Type III Effector NleL Is an E3 Ubiquitin Ligase That Modulates Pedestal Formation

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and may result in potentially fatal hemolytic uremia syndrome in humans. EHEC colonize the intestinal mucosa and promote the formation of actin-rich pedestals via translocated type III effectors. Two EHEC type III secreted effectors, Tir and EspFu/TccP, are key players for pedestal formation. We discovered that an EHEC effector protein called Non-LEE-encoded Ligase (NleL) is an E3 ubiquitin ligase. In vitro, we showed that the NleL C753 residue is critical for its E3 ligase activity. Functionally, we demonstrated that NleL E3 ubiquitin ligase activity is involved in modulating Tir-mediated pedestal formation. Surprisingly, EHEC mutant strain deficient in the E3 ligase activity induced more pedestals than the wild-type strain. The canonical EPEC strain E2348/69 normally lacks the nleL gene, and the ectopic expression of the wild-type EHEC nleL, but not the catalytically-deficient nleL(C753A) mutant, in this strain resulted in fewer actin-rich pedestals. Furthermore, we showed that the C. rodentium NleL homolog is a E3 ubiquitin ligase and is required for efficient infection of murine colonic epithelial cells in vivo. In summary, our study demonstrated that EHEC utilizes NleL E3 ubiquitin ligase activity to modulate Tir-mediated pedestal formation.National Institutes of Health (U.S.) (grant AI078092)National Institutes of Health (U.S.) (grant AI068655

All blood, No stool: enterohemorrhagic Escherichia coli O157:H7 infection

Enterohemorrhagic Escherichia coli serotype O157:H7 is a pathotype of diarrheagenic E. coli that produces one or more Shiga toxins, forms a characteristic histopathology described as attaching and effacing lesions, and possesses the large virulence plasmid pO157. The bacterium is recognized worldwide, especially in developed countries, as an emerging food-borne bacterial pathogen, which causes disease in humans and in some animals. Healthy cattle are the principal and natural reservoir of E. coli O157:H7, and most disease outbreaks are, therefore, due to consumption of fecally contaminated bovine foods or dairy products. In this review, we provide a general overview of E. coli O157:H7 infection, especially focusing on the bacterial characteristics rather than on the host responses during infection

Evolution of a summer research/writing workshop for first-year university students

Purpose To describe a framework for a summer research/writing workshop for new university students, and its evolution over time and across institutions. Design/Methodology/Approach The University of Toronto at Scarborough (UTSC) has successfully offered its award-winning two-day Summer Learning Institute on Research, Writing and Presentation Skills for four years (2004-2007), to increasing enrollments. Memorial University of Newfoundland (Memorial) adapted the UTSC model and successfully piloted its four-day workshop, SPARC (Summer Program in Academic Research and Communication), in August 2006. Both programs were low-cost, non-credit summer workshops for new students to help them prepare for university-level research and writing. Memorial offered its program a second time in August 2007. This paper focuses on the Memorial experience. Findings The success of these programs is attributed to a common framework used in each case: program planning, marketing, and delivery and assessment. Practical implications The framework described in this paper could be adapted by other institutions wishing to implement such a program. In addition, the SPARC team will continually improve the program by reflecting on each part of the framework. Originality/value Much research has been done to identify and address the specific needs of first-year university students. For example, some institutions offer “first year experience” courses for credit, while others place first year students into Interest Groups. Most academic libraries offer information literacy sessions to groups of undergraduate students during the regular semester. This paper presents a model for reaching first year students before they take their first class at university. Keywords: information literacy, collaboration, marketing, writing skill