Centrins, small calcium binding EF-hand proteins, function in the duplication of a variety of microtubule organizing centers. These include centrioles in humans, basal bodies in green algae, and spindle pole bodies in yeast. The ciliate Tetrahymena thermophila contains at least four centrin genes as determined by sequence homology, and these have distinct localization and expression patterns. CEN1's role at the basal body was examined more closely. The Cen1 protein localizes primarily to two locations: one is the site at the base of the basal body where duplication is initiated. The other is the transition zone between the basal body and axoneme. CEN1 is an essential gene, the deletion of which results in the loss of basal bodies, which is likely due to defects in both basal body duplication and basal body maintenance. Analysis of the three other centrins indicates that two of them function at microtubule-rich structures unique to ciliates, whereas the fourth is not expressed under conditions examined in this study, although when artificially expressed it localizes to basal bodies. This study provides evidence that in addition to its previously known function in the duplication of basal bodies, centrin is also important for the integrity of these organelles.

Entry of most primary human immunodeficiency virus, type 1 (HIV-1) isolates into their target cells requires the cellular receptor CD4 and the G proteincoupled chemokine coreceptor CCR5. An acidic, tyrosine-rich, and tyrosine-sulfated domain of the CCR5 amino terminus plays a critical role in the ability of CCR5 to serve as an HIV-1 coreceptor, and tyrosinesulfated peptides based on this region physically associate with the HIV-1 envelope glycoprotein gp120 and slow HIV-1 entry into CCR5-expressing cells. Here we show that the same tyrosine-sulfated peptides, but not their unsulfated analogs, can restore the HIV-1 coreceptor activity of a CCR5 variant lacking residues 2-17 of its amino terminus. Additionally, these sulfated peptides restored the ability of this CCR5 variant to mobilize calcium in response to the chemokines macrophage inflammatory factors 1␣ and 1␤. These observations show that a tyrosine-sulfated region of the CCR5 amino terminus can function independently to mediate association of chemokines and the HIV-1 envelope glycoprotein with the remaining domains of CCR5.

Ecthyma gangrenosum is classically a cutaneous manifestation of a pseudomonal septicemia that presents in a patient with an immunodeficiency or hematologic malignancy. We describe a previously healthy 8-month-old girl who developed transient neutropenia and characteristic ecthyma gangrenosum lesions secondary to methicillin-resistant Staphylococcus aureus. This unique presentation of methicillin-resistant Staphylococcus aureus ecthyma gangrenosum emphasizes the importance of broad empiric coverage and early culturing for microorganism and susceptibilities in any patient presenting with ecthyma gangrenosum.

QUESTIONS1. What data exist regarding an association between vascular disease and psoriasis?2. What methods were employed to evaluate the risk of stroke in patients with psoriasis? 3. What were the major findings of this study? 4. What are the limitations of this study? 5. How might the results of this study influence patient care?The past decade has been a roller-coaster ride for patients with psoriasis. Excitement surrounding the advent of biologic agents for the treatment of psoriasis has been displaced by sobering reports that patients with psoriasis are at increased risk for severe vascular disease (Shelling et al., 2008). This increased risk is imparted by both a predilection for patients with psoriasis to have traditional vascular disease risk factors (e.g., diabetes, hypertension, smoking, dyslipidemia) (Federman et al., 2009) and the recent recognition that psoriasis itself is an independent risk factor for vascular disease (Gelfand et al., 2006). The latter is probably mediated by systemic inflammation associated with psoriasis, similar to that observed in patients with rheumatoid arthritis. Patients whose psoriasis develops at a young age and those with more severe disease are at the greatest risk (Gelfand et al., 2006).Initial psoriasis comorbidity studies focused on cardiovascular disease, but atherosclerosis is a systemic disease (Prodanovich et al., 2009). It is reasonable to postulate that if the likelihood of myocardial infarction is increased in patients with psoriasis, other manifestations of atherosclerosis, such as stroke, might also be more common in these patients. Stroke is a leading cause of mortality, and many who survive experience functional disability, with up to 30% being permanently disabled and 20% requiring institutional care (Rosamond et al., 2008).Gelfand and colleagues returned to a large medical-records database in the United Kingdom that they had used previously for epidemiological research (Gelfand et al., 2009, this issue) to study the association between psoriasis and stroke. Nearly 133,000 patients with psoriasis included in this database were evaluated (129,143 with mild psoriasis, 3,603 with severe psoriasis) and compared with more than half a million matched control patients for the risk of stroke. Patients with psoriasis were more likely to have vascular disease risk factors than were controls. After adjusting for major risk factors for stroke, patients with psoriasis were found to be more likely to suffer a stroke. For mild psoriasis, a 6% increase in risk was identified (hazard ratio 1.06, 95% confidence interval 1.01-1.11); for severe psoriasis, the increased risk was determined to be 43% (1.43, 95% confidence interval 1.1-1.87).Through the following questions, we examine this paper in greater detail. For discussion and brief answers, please refer to the supplementary information linked to the online version of the paper at http://www.nature.com/jid. references