Modulation of Rab GTPase function by a protein phosphocholine transferase.

The intracellular pathogen Legionella pneumophila modulates the activity of host GTPases to direct the transport and assembly of the membrane-bound compartment in which it resides. In vitro studies have indicated that the Legionella protein DrrA post-translationally modifies the GTPase Rab1 by a process called AMPylation. Here we used mass spectrometry to investigate post-translational modifications to Rab1 that occur during infection of host cells by Legionella. Consistent with in vitro studies, DrrA-mediated AMPylation of a conserved tyrosine residue in the switch II region of Rab1 was detected during infection. In addition, a modification to an adjacent serine residue in Rab1 was discovered, which was independent of DrrA. The Legionella effector protein AnkX was required for this modification. Biochemical studies determined that AnkX directly mediates the covalent attachment of a phosphocholine moiety to Rab1. This phosphocholine transferase activity used CDP-choline as a substrate and required a conserved histidine residue located in the FIC domain of the AnkX protein. During infection, AnkX modified both Rab1 and Rab35, which explains how this protein modulates membrane transport through both the endocytic and exocytic pathways of the host cell. Thus, phosphocholination of Rab GTPases represents a mechanism by which bacterial FIC-domain-containing proteins can alter host-cell functions

Junior secondary students\u27 perceptions of influences on their engagement with schooling

Various explanations and solutions have been proposed over the last decade in relation to the implications of students’ apparent lack of engagement with middle years schooling in Australia. In this article we report on responses to a questionnaire by 333 Year 8 students (aged about 13, the second year of high school) on perceptions of factors relating to their engagement with the academic curriculum. We found that while the majority of students reported a strong sense of the importance of, and opportunities in, schooling, and saw English, mathematics and science connected to those opportunities, this orientation was not matched by corresponding positive engagement with these same subjects. We also found that there was diversity in the responses of students, and recommend that schools take steps to identify individual students’ perceptions of factors influencing their engagement, and where appropriate, address those perceptions

Effect of a Medical Student Emergency Ultrasound Clerkship on Number of Emergency Department Ultrasounds

Objective: To determine whether a medical student emergency ultrasound clerkship has an effect on the number of patients undergoing ultrasonography and the number of total scans in the emergency department.Methods: We conducted a prospective, single-blinded study of scanning by emergency medicine residents and attendings with and without medical students. Rotating ultrasound medical students were assigned to work equally on all days of the week. We collected the number of patients scanned and the number of scans, as well as participation of resident and faculty.Results: In seven months 2,186 scans were done on the 109 days with students and 707 scans on the 72 days without them. Data on 22 days was not recorded. A median of 13 patients per day were scanned with medical students (CI 12-15) versus seven (CI 6-9) when not. In addition, the median number of scans was 18 per day with medical students (CI 16-20) versus eight (CI 6-10) without them.Conclusion: There were significantly more patients scanned and scans done when ultrasound medical students were present. [West J Emerg Med. 2010; 11:31-34]

Accuracy of ED Bedside Ultrasound for Identification of gallstones: retrospective analysis of 575 studies

Study Objective: To determine the ability of emergency department (ED) physicians to diagnose cholelithiasis with bedside ultrasound. Methods: ED gallbladder ultrasounds recorded over 37 months were compared to radiology ultrasound interpretation. Results: Of 1,690 ED gallbladder ultrasound scans performed during this period, radiology ultrasound was performed in 575/1690 (34%) cases. ED physician bedside interpretation was 88% sensitive [95% CI, 84-91] and 87% specific [95% CI, 82-91], while positive predictive value (PPV) was 91% [88- 94%] and negative predictive value (NPV) was 83% [78-87%], using radiology interpretation as the criterion reference. Conclusion: ED physician ultrasound of the gallbladder for cholelithiasis is both sensitive and specific

Educational Assessment of Medical Student Rotation in Emergency Ultrasound

Background: Medical student ultrasound education is sparse. In 2002, we began the first medical student rotation in emergency ultrasound. Objective: To evaluate if medical students can learn and retain sonographic skills during a two- or four-week elective. Methods: We gave students an exam on the first and last days of the rotation. Six months later, students took the exam a third time. A control group was used for comparison. Results: Over a 19-month period, we enrolled 45 students (25 on the two-week and 20 on the four-week elective). The four-week student post-test score was significantly better than the two- week posttest score (81% vs. 72%, p=0.003). On the six-month exam, the four-week student post-test score was significantly better than the two-week post-test score (77% vs 69%, p=0.008). The control group did not statistically improve. Conclusion: Medical students can learn bedside ultrasound interpretation with clinical integration and retain the knowledge six months later

Sustainable Development and Its Discontents

Sustainable development (or sustainability) is a decision-making framework for maintaining and achieving human well-being, both in the present and into the future. The framework requires both consideration and achievement of environmental protection, social justice and economic development. In that framework, environmental protection must be integrated into decisions about social and economic development, and social justice and economic viability must be integrated into decisions about environmental quality. First endorsed by the world’s nations in 1992, this framework is intended to provide an effective response to the twin global challenges of growing environmental degradation and widespread extreme poverty. Sustainability provides a framework for humans to live in harmony with nature, rather than at nature’s expense. It may therefore be one of the most important ideas to come out of the 20th century. In the last two decades, the framework has become a touchstone in nearly every economic sector and at every level of government, unleashing an extraordinary range of creativity in all of those realms. Sustainable development is having a significant effect on the practice of law and on the way in which laws are written and implemented. Understanding the framework is increasingly important for law makers and lawyers. As sustainable development (or sustainability) has grown in prominence, its critics have become more numerous and more vocal. Three major lines of criticism are that the term is “too boring” to command public attention, “too vague” to provide guidance, and “too late” to address the world’s problems. Critics suggest goals such as abundance, environmental integrity, and resilience. Beginning with the international agreements that shaped the concept of sustainable development, this Article provides a functional and historical analysis of the meaning of sustainable development. It then analyzes and responds to each of these criticisms in turn. While the critics, understood constructively, suggest ways of strengthening this framework, they do not provide a compelling alternative. The challenge for lawyers, law makers, and others is to use and improve this framework to make better decisions

Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury

World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target

Inference on the Nature and the Mass of Earth's Late Veneer from Noble Metals and Gases

Noble metals and gases are very sensitive to the late accretion to the Earth of asteroids and comets. We present mass balance arguments based on these elements that indicate that 0.7E22-2.7E22 kg of extraterrestrial bodies struck the Earth after core formation and that comets comprised less than 1E-5 by mass of the impacting population. These results imply that the dynamics of asteroids and comets changed drastically with time and that biogenic elements and prebiotic molecules were not delivered to the Earth by comets but rather by carbonaceous asteroids.Comment: 10 pages, 2 figures, 1 table, submitted to JG