Blockchain Technology as a Means for Brand Trust Repair – Empirical Evidence from a Digital Transgression

Though much discussion in the realm of blockchain revolves around the concept of trust, research examining blockchain technology as a means for brand trust repair is still at an initial stage. This study conducts an experiment that analyzes blockchain technology as a substantive response to a data breach within a global business-to-consumer information systems application. Thereby, the present study expands trust repair theories to the context of blockchain and branding. Research results indicate that the use of blockchain technology as a reaction to a digital transgression may be able to reinstate brand trust, having a superior impact compared to an approach that uses a centrally managed information systems platform to restore brand trust. Overall, study results suggest that the use of blockchain technology can be an effective component of brand trust repair strategies in the digital space

Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni

Background: Penetration of skin, migration through tissues and establishment of long-lived intravascular partners require Schistosoma parasites to successfully manipulate definitive host defences. While previous studies of larval schistosomula have postulated a function for excreted/secreted (E/S) products in initiating these host-modulatory events, the role of extracellular vesicles (EVs) has yet to be considered. Here, using preparatory ultracentrifugation as well as methodologies to globally analyse both proteins and small non-coding RNAs (sncRNAs), we conducted the first characterization of Schistosoma mansoni schistosomula EVs and their potential host-regulatory cargos. Results: Transmission electron microscopy analysis of EVs isolated from schistosomula in vitro cultures revealed the presence of numerous, 30–100 nm sized exosome-like vesicles. Proteomic analysis of these vesicles revealed a core set of 109 proteins, including homologs to those previously found enriched in other eukaryotic EVs, as well as hypothetical proteins of high abundance and currently unknown function. Characterization of E/S sncRNAs found within and outside of schistosomula EVs additionally identified the presence of potential gene-regulatory miRNAs (35 known and 170 potentially novel miRNAs) and tRNA-derived small RNAs (tsRNAs; nineteen 5′ tsRNAs and fourteen 3′ tsRNAs). Conclusions: The identification of S. mansoni EVs and the combinatorial protein/sncRNA characterization of their cargo signifies that an important new participant in the complex biology underpinning schistosome/host interactions has now been discovered. Further work defining the role of these schistosomula EVs and the function/stability of intra- and extra-vesicular sncRNA components presents tremendous opportunities for developing novel schistosomiasis diagnostics or interventions

Liberal market economies, business, and political finance: Britain under New Labour

The extent and nature of business financing of parties is an important feature of political finance. Britain’s transparent and permissive regulatory system provides an excellent opportunity to study business financing of parties. Business donations have been very important to the Conservative party over the last decade, and of only marginal importance to Labour. Unlike other Conservative contributors, business donors are more likely to contribute when the party is popular. In contrast to the previous period of Conservative government, the biggest British businesses tended to abstain from political finance under New Labour. However, their bias towards the Conservatives is affected by the party’s popularity and the closeness of an election. Britain shares the political importance of business financing of parties and its mixture of ideological and pragmatic motivations with other liberal market economies. However, in Britain the bias towards the right is much stronger and the role of big business more marginal

Sentinel lymph node biopsy for breast cancer: How many nodes are enough?

Introduction Sentinel lymph node (SLN) biopsy using blue dye and radioisotope often results in the removal of multiple SLNs. We sought to determine whether there is a point where the surgeon can terminate the procedure without sacrificing accuracy. Methods One thousand one hundred ninety-seven patients from University of Michigan and the Mayo Clinic undergoing SLN biopsy formed the study population. Surgeons removed all SLNs until counts within the axilla were less than 10% of the highest node ex vivo and recorded the order in which they were removed. Results The mean number of SLNs removed per patient was 2.5 (range 1–9). Approximately 42% of patients had three or more lymph nodes removed, while 19% had four or more lymph nodes removed. Eighteen percent of patients (132/725) at University of Michigan and 22% (103/472) at Mayo Clinic had a positive SLN. Ninety-eight percent (231/235) of patients with lymph node metastases were identified by the 3rd SLN while 100% were identified by the 4th SLN. Conclusion Among patients undergoing SLN biopsy for breast cancer, the only positive SLN is rarely identified in the 4th or higher node. Terminating the procedure at the 4th node may lower the cost of the procedure and reduce morbidity. J. Surg. Oncol. 2007;96:554–559. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57337/1/20878_ftp.pd

Hail Suppression: Impacts and Issues: Final Report Technology Assessment of the Suppression of Hail

published or submitted for publicationis peer reviewedOpe

Comparative analysis of small RNAs released by the filarial nematode Litomosoides sigmodontis in vitro and in vivo

Background: The release of small non-coding RNAs (sRNAs) has been reported in parasitic nematodes, trematodes and cestodes of medical and veterinary importance. However, little is known regarding the diversity and composition of sRNAs released by different lifecycle stages and the portion of sRNAs that persist in host tissues during filarial infection. This information is relevant to understanding potential roles of sRNAs in parasite-to-host communication, as well as to inform on the location within the host and time point at which they can be detected. Methodology and principal findings: We have used small RNA (sRNA) sequencing analysis to identify sRNAs in replicate samples of the excretory-secretory (ES) products of developmental stages of the filarial nematode Litomosoides sigmodontis in vitro and compare this to the parasite-derived sRNA detected in host tissues. We show that all L. sigmodontis developmental stages release RNAs in vitro, including ribosomal RNA fragments, 5’-derived tRNA fragments (5’-tRFs) and, to a lesser extent, microRNAs (miRNAs). The gravid adult females (gAF) produce the largest diversity and abundance of miRNAs in the ES compared to the adult males or microfilariae. Analysis of sRNAs detected in serum and macrophages from infected animals reveals that parasite miRNAs are preferentially detected in vivo, compared to their low levels in the ES products, and identifies miR-92-3p and miR-71-5p as L. sigmodontis miRNAs that are stably detected in host cells in vivo. Conclusions: Our results suggest that gravid adult female worms secrete the largest diversity of extracellular sRNAs compared to adult males or microfilariae. We further show differences in the parasite sRNA biotype distribution detected in vitro versus in vivo. We identify macrophages as one reservoir for parasite sRNA during infection, and confirm the presence of parasite miRNAs and tRNAs in host serum during patent infection

Macrophage migration inhibitory factor (MIF) is essential for Type 2 effector cell immunity to an intestinal helminth parasite

Immunity to intestinal helminths is known to require both innate and adaptive components of the immune system activated alongthe Type 2 IL-4R/STAT6-dependent pathway. We have found that macrophage migration inhibitory factor (MIF) is essential for thedevelopment of effective immunity to the intestinal helminth Heligmosomoides polygyrus, even following vaccination which inducessterile immunity in wild-type mice. A chemical inhibitor of MIF, 4-IPP, was similarly found to compromise anti-parasite immunity.Cellular analyses found that the adaptive arm of the immune response, including IgG1 antibody responses and Th2-derivedcytokines, was intact and that Foxp3+ T regulatory cell responses were unaltered in the absence of MIF. However, MIF was found tobe an essential cytokine for innate cells, with ablated eosinophilia and ILC2 responses, and delayed recruitment and activation ofmacrophages to the M2 phenotype (expressing Arginase 1, Chil3, and RΕLM‐alpha) upon infection of MIF‐deficient mice; amacrophage deficit was also seen in wild-type BALB/c mice exposed to 4-IPP. Gene expression analysis of intestinal and lymph nodetissues from MIF-deficient and -sufficient infected mice indicated significantly reduced levels of Arl2bp, encoding a factor involved innuclear localization of STAT3. We further found that STAT3-deficient macrophages expressed less Arginase-1, and that mice lackingSTAT3 in the myeloid compartment (LysMCrexSTAT3fl/fl) were unable to reject a secondary infection with H. polygyrus. We thusconclude that in the context of a Type 2 infection, MIF plays a critical role in polarizing macrophages into the protectivealternatively-activated phenotype, and that STAT3 signaling may make a previously unrecognized contribution to immunity tohelminths

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Kinetoplastid Phylogenomics Reveals the Evolutionary Innovations Associated with the Origins of Parasitism

The evolution of parasitism is a recurrent event in the history of life and a core problem in evolutionary biology. Trypanosomatids are important parasites and include the human pathogens Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp., which in humans cause African trypanosomiasis, Chagas disease, and leishmaniasis, respectively. Genome comparison between trypanosomatids reveals that these parasites have evolved specialized cell-surface protein families, overlaid on a well-conserved cell template. Understanding how these features evolved and which ones are specifically associated with parasitism requires comparison with related non-parasites. We have produced genome sequences for Bodo saltans, the closest known non-parasitic relative of trypanosomatids, and a second bodonid, Trypanoplasma borreli. Here we show how genomic reduction and innovation contributed to the character of trypanosomatid genomes. We show that gene loss has “streamlined” trypanosomatid genomes, particularly with respect to macromolecular degradation and ion transport, but consistent with a widespread loss of functional redundancy, while adaptive radiations of gene families involved in membrane function provide the principal innovations in trypanosomatid evolution. Gene gain and loss continued during trypanosomatid diversification, resulting in the asymmetric assortment of ancestral characters such as peptidases between Trypanosoma and Leishmania, genomic differences that were subsequently amplified by lineage-specific innovations after divergence. Finally, we show how species-specific, cell-surface gene families (DGF-1 and PSA) with no apparent structural similarity are independent derivations of a common ancestral form, which we call “bodonin.” This new evidence defines the parasitic innovations of trypanosomatid genomes, revealing how a free-living phagotroph became adapted to exploiting hostile host environments

Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes

Chromatin modification is important for virtually all aspects of DNA metabolism but little is known about the consequences of such modification in trypanosomatids, early branching protozoa of significant medical and veterinary importance. MYST-family histone acetyltransferases in other species function in transcription regulation, DNA replication, recombination and repair. Trypanosoma brucei HAT3 was recently shown to acetylate histone H4K4 and we now report characterization of all three T. brucei MYST acetyltransferases (HAT1–3). First, GFP-tagged HAT1–3 all localize to the trypanosome nucleus. While HAT3 is dispensable, both HAT1 and HAT2 are essential for growth. Strains with HAT1 knock-down display mitosis without nuclear DNA replication and also specific de-repression of a telomeric reporter gene, a rare example of transcription control in an organism with widespread and constitutive polycistronic transcription. Finally, we show that HAT2 is responsible for H4K10 acetylation. By analogy to the situation in Saccharomyces cerevisiae, we discuss low-level redundancy of acetyltransferase function in T. brucei and suggest that two MYST-family acetyltransferases are essential due to the absence of a Gcn5 homologue. The results are also consistent with the idea that HAT1 contributes to establishing boundaries between transcriptionally active and repressed telomeric domains in T. brucei