The Role of β7 Integrins in CD8 T Cell Trafficking During an Antiviral Immune Response

The requirement of β7 integrins for lymphocyte migration was examined during an ongoing immune response in vivo. Transgenic mice (OT-I) expressing an ovalbumin-specific major histocompatibility complex class I–restricted T cell receptor for antigen were rendered deficient in expression of all β7 integrins or only the αEβ7 integrin. To quantitate the relative use of β7 integrins in migration in vivo, equal numbers of OT-I and OT-I-β7−/− or OT-I-αE−/− lymph node (LN) cells were adoptively transferred to normal mice. Although OT-I-β7−/− LN cells migrated to mesenteric LN and peripheral LN as well as wild-type cells, β7 integrins were required for naive CD8 T cell and B cell migration to Peyer's patch. After infection with a recombinant virus (vesicular stomatitis virus) encoding ovalbumin, β7 integrins became critical for migration of activated CD8 T cells to the mesenteric LN and Peyer's patch. Naive CD8 T cells did not enter the lamina propria or the intestinal epithelium, and the majority of migration of activated CD8 T cells to the small and large intestinal mucosa, including the epithelium, was β7 integrin–mediated. The αEβ7 integrin appeared to play no role in migration during a primary CD8 T cell immune response in vivo. Furthermore, despite dramatic upregulation of αEβ7 by CD8 T cells after entry into the epithelium, long-term retention of intestinal intraepithelial lymphocytes was also αEβ7 independent

Continuity or change in business representation in Britain? An assessment of the Heseltine initiatives of the 1990s

Britain has a fragmented, overlapping, and underresourced system of business representation. Attempts at reform, however, have proved difficult and largely unsuccessful. A coherent and logical system is relevant, in terms of both an effective dialogue between government and business, and the promotion of competitiveness and productivity. Through interviews and archival evidence, I look at how government has attempted to reform business associations. The main focus is the Heseltine initiatives of the 1990s: I outline the various initiatives taken, reveal the extent to which policy represented continuity or change, and consider whether the initiatives were effective. I show that they had a degree of success but that they would have made greater impact if they had been sustained over a longer period of time. A consideration of the historical context, moreover, suggests there may be limits to the role of government intervention in business association reform

London equation studies of thin-film superconductors with a triangular antidot lattice

We report on a study of vortex pinning in nanoscale antidot defect arrays in the context of the London Theory. Using a wire network model, we discretize the array with a fine mesh, thereby providing a detailed treatment of pinning phenomena. The use of a fine grid has enabled us to examine both circular and elongated defects, patterned in the form of a rhombus. The latter display pinning characteristics superior to circular defects constructed with the similar area. We calculate pinning potentials for defects containing zero and single quanta, and we obtain a pinning phase diagram for the second matching field, $H = 2 \Phi_{o}$.Comment: 10 pages and 14 figure

A Longitudinal Study of Pediatricians Early in their Careers: PLACES

The American Academy of Pediatrics (AAP) launched the Pediatrician Life and Career Experience Study (PLACES), a longitudinal study that tracks the personal and professional experiences of early career pediatricians, in 2012. We used a multipronged approach to develop the study methodology and survey domains and items, including review of existing literature and qualitative research with the target population. We chose to include 2 cohorts of US pediatricians on the basis of residency graduation dates, including 1 group who were several years out of residency (2002–2004 Residency Graduates Cohort) and a second group who recently graduated from residency at study launch (2009–2011 Residency Graduates Cohort). Recruitment into PLACES was a 2-stage process: (1) random sample recruitment from the target population and completion of an initial intake survey and (2) completion of the first Annual Survey by pediatricians who responded positively to stage 1. Overall, 41.2% of pediatricians randomly selected to participate in PLACES indicated positive interest in the study by completing intake surveys; of this group, 1804 (93.7%) completed the first Annual Survey and were considered enrolled in PLACES. Participants were more likely to be female, AAP members, and graduates of US medical schools compared with the target sample; weights were calculated to adjust for these differences. We will survey PLACES pediatricians 2 times per year. PLACES data will allow the AAP to examine career and life choices and transitions experienced by early-career pediatricians

Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583

The alternative sigma factor σ54 has been shown to regulate the expression of a wide array of virulence-associated genes, as well as central metabolism, in bacterial pathogens. In Gram-positive organisms, the σ54 is commonly associated with carbon metabolism. In this study, we show that the Enterococcus faecalis alternative sigma factor σ54 (RpoN) and its cognate enhancer binding protein MptR are essential for mannose utilization and are primary contributors to glucose uptake through the Mpt phosphotransferase system. To gain further insight into how RpoN contributes to global transcriptional changes, we performed microarray transcriptional analysis of strain V583 and an isogenic rpoN mutant grown in a chemically defined medium with glucose as the sole carbon source. Transcripts of 340 genes were differentially affected in the rpoN mutant; the predicted functions of these genes mainly related to nutrient acquisition. These differentially expressed genes included those with predicted catabolite-responsive element (cre) sites, consistent with loss of repression by the major carbon catabolite repressor CcpA. To determine if the inability to efficiently metabolize glucose/mannose affected infection outcome, we utilized two distinct infection models. We found that the rpoN mutant is significantly attenuated in both rabbit endocarditis and murine catheter-associated urinary tract infection (CAUTI). Here, we examined a ccpA mutant in the CAUTI model and showed that the absence of carbon catabolite control also significantly attenuates bacterial tissue burden in this model. Our data highlight the contribution of central carbon metabolism to growth of E. faecalis at various sites of infection

Predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome

Few data exist regarding predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome (MFS). To identify independent predictors of the rate of aortic root (AoR) dilation and referral for aortic surgery, we investigated the data from the Pediatric Heart Network randomized trial of atenolol versus losartan in young patients with MFS. Data were analyzed from the echocardiograms at 0, 12, 24, and 36months read in the core laboratory of 608 trial subjects, aged 6months to 25 years, who met original Ghent criteria and had an AoR z-score (AoRz)>3. Repeated measures linear and logistic regressions were used to determine multivariable predictors of AoR dilation. Receiver operator characteristic curves were used to determine cut-points in AoR dilation predicting referral for aortic surgery. Multivariable analysis showed rapid AoR dilation as defined by change in AoRz/year>90th percentile was associated with older age, higher sinotubular junction z-score, and atenolol use (R-2=0.01) or by change in AoR diameter (AoRd)/year>90th percentile with higher sinotubular junction z-score and non-white race (R-2=0.02). Referral for aortic root surgery was associated with higher AoRd, higher ascending aorta z-score, and higher sinotubular junction diameter:ascending aorta diameter ratio (R-2=0.17). Change in AoRz of 0.72 SD units/year had 42% sensitivity and 92% specificity and change in AoRd of 0.34cm/year had 38% sensitivity and 95% specificity for predicting referral for aortic surgery. In this cohort of young patients with MFS, no new robust predictors of rapid AoR dilation or referral for aortic root surgery were identified. Further investigation may determine whether generalized proximal aortic dilation and effacement of the sinotubular junction will allow for better risk stratification. Rate of AoR dilation cut-points had high specificity, but low sensitivity for predicting referral for aortic surgery, limiting their clinical use. Clinical Trial Number ClinicalTrials.gov number, NCT00429364

Disappearance of back-to-back high pTp_T hadron correlations in central Au+Au collisions at sNN\sqrt{s_{NN}} = 200 GeV

Azimuthal correlations for large transverse momentum charged hadrons have been measured over a wide pseudo-rapidity range and full azimuth in Au+Au and p+p collisions at $\sqrt{s_{NN}}$ = 200 GeV. The small-angle correlations observed in p+p collisions and at all centralities of Au+Au collisions are characteristic of hard-scattering processes already observed in elementary collisions. A strong back-to-back correlation exists for p+p and peripheral Au + Au. In contrast, the back-to-back correlations are reduced considerably in the most central Au+Au collisions, indicating substantial interaction as the hard-scattered partons or their fragmentation products traverse the medium.Comment: submitted to Phys. Rev. Let

Azimuthal anisotropy and correlations in the hard scattering regime at RHIC

Azimuthal anisotropy ($v_2$) and two-particle angular correlations of high $p_T$ charged hadrons have been measured in Au+Au collisions at $\sqrt{s_{NN}}$=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high $p_T$ partons. The monotonic rise of $v_2(p_T)$ for $p_T<2$ GeV/c is consistent with collective hydrodynamical flow calculations. At \pT>3 GeV/c a saturation of $v_2$ is observed which persists up to $p_T=6$ GeV/c.Comment: As publishe

Biology and Impacts of Pacific Island Invasive Species: 8. Eleutherodactylus planirostris, the Greenhouse Frog (Anura: Eleutherodactylidae)

The greenhouse frog, Eleutherodactylus planirostris, is a direct-developing (i.e., no aquatic stage) frog native to Cuba and the Bahamas. It was introduced to Hawaii via nursery plants in the early 1990s and then subsequently from Hawaii to Guam in 2003. The greenhouse frog is now widespread on five Hawaiian Islands and Guam. Infestations are often overlooked due to the frog’s quiet calls, small size, and cryptic behavior, and this likely contributes to its spread. Because the greenhouse frog is an insectivore, introductions may reduce invertebrates. In Hawaii, the greenhouse frog primarily consumes ants, mites, and springtails, and obtains densities of up to 12,500 frogs ha-1. At this density, it is estimated that they can consume up to 129,000 invertebrates ha-1 night-1. They are a food source for the non-native brown tree snake in Guam and may be a food source for other non-native species. They may also compete with other insectivores for available prey. The greatest direct economic impacts of the invasions are to the nursery trade that must treat infested shipments. Although various control methods have been developed to control frogs in Hawaii, and citric acid, in particular, is effective in reducing greenhouse frogs, the frog’s inconspicuous nature often prevents populations from being identified and managed