Detection of Mycobacterium avium ss. Paratuberculosis in Blau Syndrome Tissues

Background and Aim of the Work. Blau syndrome is an inherited granulomatous inflammatory disorder with clinical findings of uveitis, arthritis, and dermatitis. Although rare, Blau syndrome shares features with the more common diseases sarcoidosis and Crohn's disease. The clinical findings of Blau syndrome are indistinguishable from juvenile sarcoidosis; the mutations of Blau syndrome are on the same gene of chromosome 16 (CARD15) that confers susceptibility to Crohn's disease. The product of this gene is part of the innate immune system. Mycobacterium avium ss. paratuberculosis (MAP) is the putative cause of Crohn's disease and has been implicated as a causative agent of sarcoidosis. Methods. Archival tissues of individuals with Blau syndrome were tested for the presence of MAP. Results. DNA evidence of MAP was detected in all of the tissues. Conclusions. This article finds that MAP is present in Blau syndrome tissue and postulates that it has a causal role. The presence of MAP in Blau syndrome—an autosomal dominant, systemic inflammatory disease—connects genetic and environmental aspects of “autoimmune” disease

Mapping of serotype-specific, immunodominant epitopes in the NS-4 region of hepatitis C virus (HCV):use of type-specific peptides to serologically differentiate infections with HCV types 1, 2, and 3

The effect of sequence variability between different types of hepatitis C virus (HCV) on the antigenicity of the NS-4 protein was investigated by epitope mapping and by enzyme-linked immunosorbent assay with branched oligopeptides. Epitope mapping of the region between amino acid residues 1679 and 1768 in the HCV polyprotein revealed two major antigenic regions (1961 to 1708 and 1710 to 1728) that were recognized by antibody elicited upon natural infection of HCV. The antigenic regions were highly variable between variants of HCV, with only 50 to 60% amino acid sequence similarity between types 1, 2, and 3. Although limited serological cross-reactivity between HCV types was detected between peptides, particularly in the first antigenic region of NS-4, type-specific reactivity formed the principal component of the natural humoral immune response to NS-4. Type-specific antibody to particular HCV types was detected in 89% of the samples from anti-HCV-positive blood donors and correlated almost exactly with genotypic analysis of HCV sequences amplified from the samples by polymerase chain reaction. Whereas almost all blood donors appeared to be infected with a single virus type (97%), a higher proportion of samples (40%) from hemophiliacs infected from transfusion of non-heat-inactivated clotting factor contained antibody to two or even all three HCV types, providing evidence that long-term exposure may lead to multiple infection with different variants of HCV

Cascades: A view from Audience

Cascades on online networks have been a popular subject of study in the past decade, and there is a considerable literature on phenomena such as diffusion mechanisms, virality, cascade prediction, and peer network effects. However, a basic question has received comparatively little attention: how desirable are cascades on a social media platform from the point of view of users? While versions of this question have been considered from the perspective of the producers of cascades, any answer to this question must also take into account the effect of cascades on their audience. In this work, we seek to fill this gap by providing a consumer perspective of cascade. Users on online networks play the dual role of producers and consumers. First, we perform an empirical study of the interaction of Twitter users with retweet cascades. We measure how often users observe retweets in their home timeline, and observe a phenomenon that we term the "Impressions Paradox": the share of impressions for cascades of size k decays much slower than frequency of cascades of size k. Thus, the audience for cascades can be quite large even for rare large cascades. We also measure audience engagement with retweet cascades in comparison to non-retweeted content. Our results show that cascades often rival or exceed organic content in engagement received per impression. This result is perhaps surprising in that consumers didn't opt in to see tweets from these authors. Furthermore, although cascading content is widely popular, one would expect it to eventually reach parts of the audience that may not be interested in the content. Motivated by our findings, we posit a theoretical model that focuses on the effect of cascades on the audience. Our results on this model highlight the balance between retweeting as a high-quality content selection mechanism and the role of network users in filtering irrelevant content

EpCAM (CD326) regulates intestinal epithelial integrity and stem cells via Rho-associated kinase

Humans with biallelic inactivating mutations in Epithelial Cell Adhesion Molecule (EpCAM) develop congenital tufting enteropathy (CTE). To gain mechanistic insights regarding EpCAM function in this disorder, we prepared intestinal epithelial cell (IEC) organoids and spheroids. IEC organoids and spheroids were generated fro

Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling

Activating mutations in genes of the Ras-mitogen-activated protein kinase (MAPK) pathway occur in approximately 30% of all human cancers; however, mutation of Ras alone is rarely sufficient to induce tumour development. Scribble is a polarity regulator recently isolated from a Drosophila screen for events that cooperate with Ras mutation to promote tumour progression and cell invasion. In mammals, Scribble regulates directed cell migration and wound healing in vivo; however, no role has been identified for mammalian Scribble in oncogenic transformation. Here we show that in human epithelial cells expressing oncogenic Ras or Raf, loss of Scribble promotes invasion of cells through extracellular matrix in an organotypic culture system. Further, we show that the mechanism by which this occurs is in the regulation of MAPK signalling by Scribble. The suppression of MAPK signalling is a highly conserved function of Scribble as it also prevents Raf-mediated defects in Drosophila wing development. Our data identify Scribble as an important mediator of MAPK signalling and provide a molecular basis for the observation that Scribble expression is decreased in many invasive human cancers. © 2008 Macmillan Publishers Limited All rights reserved

State-by-State Report on Permanent Public Access to Electronic Government Information

The purpose of this study was to research what, if anything, state governments are doing to meet the enormous challenges of ensuring permanent public access to state electronic government information. A comprehensive survey was created and distributed to AALL authors in each of the fifty states, the District of Columbia and Puerto Rico. State authors completed the survey by December 2002 and, in addition, submitted a short executive summary based on their survey results. The survey reveals that only one state—Colorado—has enacted legislation that explicitly addresses permanent public access (effective August 15, 2003). No state, including Colorado, comprehensively addresses the challenges of permanent public access to and preservation of electronic government information. State records boards, state archives and state libraries are often aware of permanent public access issues and have often taken steps to preserve electronic information. They have sometimes taken steps to provide continuous public access or have developed guidelines for state agencies to provide such access. These efforts of state records boards, state archives and state libraries are often ineffective, however, because they lack a solid statutory foundation. Without comprehensive statutes supporting a system to coordinate and centralize permanent public access, state agencies thwart the positive efforts of state records boards, state archives and state libraries. The agencies fail to appreciate the need to ensure the full lifecycle of electronic government information, particularly Web-based publications and records. And any guidelines for permanent public access that target them do not solve the problem of agencies’ lack the expertise, personnel and funding. We envisioned that this project would be the first step in the advocacy process necessary to enact state laws that will prevent the loss of important state government information in electronic format. Toward this end, we sought to create a document that could be provided to legislators and other policymakers to educate them about the responsibility of state governments to ensure permanent public access to electronic information. An additional objective was to strengthen the GRC and WAO’s ties to AALL members at the local level, thereby forming a base of activists who could advocate for improved laws mandating permanent public access to state government information. Because AALL and other library organizations lack the manpower to tackle the problem of disappearing electronic government information in all states simultaneously, the Grant Team has identified key states to target for legislative activity

Pten loss promotes MAPK pathway dependency in HER2/neu breast carcinomas

Loss of the tumor suppressor gene PTEN is implicated in breast cancer progression and resistance to targeted therapies, and is thought to promote tumorigenesis by activating PI3K signaling. In a transgenic model of breast cancer, Pten suppression using a tetracycline-regulatable short hairpin (sh)RNA cooperates with human epidermal growth factor receptor 2 (HER2/neu), leading to aggressive and metastatic disease with elevated signaling through PI3K and, surprisingly, the mitogen-activated protein kinase (MAPK) pathway. Restoring Pten function is sufficient to down-regulate both PI3K and MAPK signaling and triggers dramatic tumor regression. Pharmacologic inhibition of MAPK signaling produces similar effects to Pten restoration, suggesting that the MAPK pathway contributes to the maintenance of advanced breast cancers harboring Pten loss

Excitons in type-II quantum dots: Finite offsets

Quantum size effects for an exciton attached to a spherical quantum dot are calculated by a variational approach. The band line-ups are assumed to be type-II with finite offsets. The dependence of the exciton binding energy upon the dot radius and the offsets is studied for different sets of electron and hole effective masses

Eikonal analysis of Coulomb distortion in quasi-elastic electron scattering

An eikonal expansion is used to provide systematic corrections to the eikonal approximation through order $1/k^2$, where $k$ is the wave number. Electron wave functions are obtained for the Dirac equation with a Coulomb potential. They are used to investigate distorted-wave matrix elements for quasi-elastic electron scattering from a nucleus. A form of effective-momentum approximation is obtained using trajectory-dependent eikonal phases and focusing factors. Fixing the Coulomb distortion effects at the center of the nucleus, the often-used ema approximation is recovered. Comparisons of these approximations are made with full calculations using the electron eikonal wave functions. The ema results are found to agree well with the full calculations.Comment: 12 pages, 6 Postscript figure