From the IBPP Research Associates. Canada. Ismael Sambra

This articles discusses a declaration - Joint Declaration by the Committee of Cuban Political Ex-Prisoners and Cuba Friends and Cuban Canadian National Foundation Against The Laws That Persecute and Condemn Freedom in Cuba. - provided by Mr. Ismael Sambra, president of the Cuban Canadian National Foundation and Writer in Residence at York University, Ontario, Canada. Of note: Mr. Sambra published A Dictator\u27s Errors in IBPP (Author: Ismael Sambra, Volume 4, Number 25, June 26, 1998.

Bridging networks with Hyperdata

Hyperdata A storage & network-agnostic data model and schema(s) for linking data across different networks and platforms

Human islets expressing HNF1A variant have defective beta cell transcriptional regulatory networks

Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found that donor islets contained beta cells without insulitis and lacked glucose-stimulated insulin secretion despite a normal insulin response to cAMP-evoked stimulation. With these unexpected findings for T1D, we sequenced the donor DNA and found a pathogenic heterozygous variant in the gene encoding hepatocyte nuclear factor-1alpha (HNF1A). In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction leads to insulin-insufficient diabetes reminiscent of T1D by impacting the regulatory processes critical for glucose-stimulated insulin secretion and suggest a rationale for a therapeutic alternative to current treatment

Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression

Chrysotile, like other types of asbestos, has been associated with mesothelioma, lung cancer and asbestosis. However, the cellular abnormalities induced by these fibers involved in cancer development have not been elucidated yet. Previous works show that chrysotile fibers induce features of cancer cells, such as aneuploidy, multinucleation and multipolar mitosis. In the present study, normal and cancer derived human cell lines were treated with chrysotile and the cellular and molecular mechanisms related to generation of aneuploid cells was elucidated. The first alteration observed was cytokinesis regression, the main cause of multinucleated cells formation and centrosome amplification. The multinucleated cells formed after cytokinesis regression were able to progress through cell cycle and generated aneuploid cells after abnormal mitosis. To understand the process of cytokinesis regression, localization of cytokinetic proteins was investigated. It was observed mislocalization of Anillin, Aurora B, Septin 9 and Alix in the intercellular bridge, and no determination of secondary constriction and abscission sites. Fiber treatment also led to overexpression of genes related to cancer, cytokinesis and cell cycle. The results show that chrysotile fibers induce cellular and molecular alterations in normal and tumor cells that have been related to cancer initiation and progression, and that tetraploidization and aneuploid cell formation are striking events after fiber internalization, which could generate a favorable context to cancer development

A Single Cysteine, Cys-64, Is Essential for Assembly of Tenascin-C Hexabrachions

Tenascin-C is a large, multimeric extracellular matrix protein that is found in a variety of tissues and can have profound effects on cell adhesion. It is secreted from cells as a hexamer of six identical chains called a hexabrachion. Disulfide bonding among tenascin subunits mediates intracellular assembly into hexamers. The amino-terminal assembly domain consists of heptad repeats and at least six cysteine residues (Cys-64, -111, -113, -140, -146, -147) that could be involved in multimerization. We have now determined the requirements for these cysteine residues during hexamer assembly. Our results show that only Cys-64 is required to form the hexameric structure. Mutation of Cys-64 to glycine resulted in release of trimer intermediates, which probably form via the heptad repeats, but no hexamers were secreted. In contrast, individual or pairs of mutations of each of the other cysteines had no effect on tenascin hexamer formation, and inclusion of any other cysteine mutations along with C64G did not further disrupt the multimer pattern. However, when all six cysteines were mutated, monomers were the major extracellular form. Together, these results show that trimers are an intermediate of tenascin-C assembly and that Cys-64 is essential for formation of hexabrachions

Linked Data Notifications: A Resource-Centric Communication Protocol

In this article we describe the Linked Data Notifications (LDN) protocol, which is a W3C Candidate Recommendation. Notifications are sent over the Web for a variety of purposes, for example, by social applications. The information contained within a notification is structured arbitrarily, and typically only usable by the application which generated it in the first place. In the spirit of Linked Data, we propose that notifications should be reusable by multiple authorised applications. Through separating the concepts of senders, receivers and consumers of notifications, and leveraging Linked Data principles of shared vocabularies and URIs, LDN provides a building block for decentralised Web applications. This permits end users more freedom to switch between the online tools they use, as well as generating greater value when notifications from different sources can be used in combination. We situate LDN alongside related initiatives, and discuss additional considerations such as security and abuse prevention measures. We evaluate the protocol’s effectiveness by analysing multiple, independent implementations, which pass a suite of formal tests and can be demonstrated interoperating with each other. To experience the described features please open this document in your Web browser under its canonical URI: http://csarven.ca/linked-data-notifications

End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data

RNA-seq protocols that focus on transcript termini are well suited for applications in which template quantity is limiting. Here we show that, when applied to end-sequencing data, analytical methods designed for global RNA-seq produce computational artifacts. To remedy this, we created the End Sequence Analysis Toolkit (ESAT). As a test, we first compared end-sequencing and bulk RNA-seq using RNA from dendritic cells stimulated with lipopolysaccharide (LPS). As predicted by the telescripting model for transcriptional bursts, ESAT detected an LPS-stimulated shift to shorter 3\u27-isoforms that was not evident by conventional computational methods. Then, droplet-based microfluidics was used to generate 1000 cDNA libraries, each from an individual pancreatic islet cell. ESAT identified nine distinct cell types, three distinct beta-cell types, and a complex interplay between hormone secretion and vascularization. ESAT, then, offers a much-needed and generally applicable computational pipeline for either bulk or single-cell RNA end-sequencing

Proteomic and Transcriptional Profiles of Human Stem Cell-Derived beta Cells Following Enteroviral Challenge

Enteroviral infections are implicated in islet autoimmunity and type 1 diabetes (T1D) pathogenesis. Significant beta-cell stress and damage occur with viral infection, leading to cells that are dysfunctional and vulnerable to destruction. Human stem cell-derived beta (SC-beta) cells are insulin-producing cell clusters that closely resemble native beta cells. To better understand the events precipitated by enteroviral infection of beta cells, we investigated transcriptional and proteomic changes in SC-beta cells challenged with coxsackie B virus (CVB). We confirmed infection by demonstrating that viral protein colocalized with insulin-positive SC-beta cells by immunostaining. Transcriptome analysis showed a decrease in insulin gene expression following infection, and combined transcriptional and proteomic analysis revealed activation of innate immune pathways, including type I interferon (IFN), IFN-stimulated genes, nuclear factor-kappa B (NF-kappaB) and downstream inflammatory cytokines, and major histocompatibility complex (MHC) class I. Finally, insulin release by CVB4-infected SC-beta cells was impaired. These transcriptional, proteomic, and functional findings are in agreement with responses in primary human islets infected with CVB ex vivo. Human SC-beta cells may serve as a surrogate for primary human islets in virus-induced diabetes models. Because human SC-beta cells are more genetically tractable and accessible than primary islets, they may provide a preferred platform for investigating T1D pathogenesis and developing new treatments