scholarly journals Actinobacteriophages: Genomics, Dynamics, and Applications

2020 ◽  
Vol 7 (1) ◽  
pp. 37-61 ◽  
Author(s):  
Graham F. Hatfull
Keyword(s):  
Dna Sequences ◽  
Large Scale ◽  
Mycobacterium Abscessus ◽  
Genomic Diversity ◽  
Dynamic Interactions ◽  
Defense Proteins ◽  
Research Education ◽  
Defense Systems ◽  
Integrated Research

Actinobacteriophages are viruses that infect bacterial hosts in the phylum Actinobacteria. More than 17,000 actinobacteriophages have been described and over 3,000 complete genome sequences reported, resulting from large-scale, high-impact, integrated research-education initiatives such as the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Sciences (SEA-PHAGES) program. Their genomic diversity is enormous; actinobacteriophages comprise many architecturally mosaic genomes with distinct DNA sequences. Their genome diversity is driven by the highly dynamic interactions between phages and their hosts, and prophages can confer a variety of systems that defend against attack by genetically distinct phages; phages can neutralize these defense systems by coding for counter-defense proteins. These phages not only provide insights into diverse and dynamic phage populations but also have provided numerous tools for mycobacterial genetics. A case study using a three-phage cocktail to treat a patient with a drug-resistant Mycobacterium abscessus suggests that phages may have considerable potential for the therapeutic treatment of mycobacterial infections.

scholarly journals Mycobacteriophages: Diversity, Dynamics, and Therapy

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 55
Author(s):  
Graham F. Hatfull
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Biological Diversity ◽  
Mycobacterium Abscessus ◽  
Comparative Genomic ◽  
Research Education ◽  
Defense Systems ◽  
Dynamic Relationships ◽  
Susceptibility Profiles ◽  
Diversity Dynamics

Bacteriophages—viruses that infect bacteria—are the most numerous biological entities in the biosphere. The phage population is not only vast but dynamic and old, and perhaps not surprisingly, highly diverse genetically. We are exploring and defining this biological diversity by isolating and genomically characterizing individual phages, and through comparative genomic analyses. The development of large integrated research-education programs, such as the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) program, have established a large collection of 15,500 individual phages—all isolated on bacterial hosts within the phylum Actinobacteria—of which over 3000 are fully sequenced. These genomes are highly diverse genetically, even if isolated on the same bacterial strain, and are richly populated in genes of unknown function. We propose that many of these genes are involved in the dynamic relationships between bacteria and their viruses, either promoting or countering viral defense systems, or denying competing phages the opportunity to superinfect infected cells. Examples of these include prophage-mediated defense systems in which integrated prophages of temperate viruses lysogenically express genes that prevent attack by unrelated (heterotypic) phages. These systems are prevalent among temperate phages and can act with exquisite specificity in their defense profiles. Phages can also encode their own counter-defense systems to negate the functions of these prophage-mediated defenses. These contributions to microbial dynamics dictate the phage susceptibility profiles of individual strains of pathogenic bacteria, adding complexity to the prospects for the broad therapeutic use of phages against bacterial infections. However, we have shown that the administration of a three-phage cocktail engineered and personalized to a specific highly antibiotic-resistant strain of Mycobacterium abscessus contributes to substantial clinical improvement.

A Family With Autosomal-Dominant Progressive Sensorineural Hearing Loss

1996 ◽  
Vol 5 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Chris Halpin ◽  
Barbara Herrmann ◽  
Margaret Whearty
Keyword(s):  
Speech Production ◽  
Hearing Aids ◽  
Role Models ◽  
Speech Intelligibility ◽  
Large Scale ◽  
Speech Language Pathology ◽  
The Family ◽  
Patient Will ◽  
Language Pathology

The family described in this article provides an unusual opportunity to relate findings from genetic, histological, electrophysiological, psychophysical, and rehabilitative investigation. Although the total number evaluated is large (49), the known, living affected population is smaller (14), and these are spread from age 20 to age 59. As a result, the findings described above are those of a large-scale case study. Clearly, more data will be available through longitudinal study of the individuals documented in the course of this investigation but, given the slow nature of the progression in this disease, such studies will be undertaken after an interval of several years. The general picture presented to the audiologist who must rehabilitate these cases is that of a progressive cochlear degeneration that affects only thresholds at first, and then rapidly diminishes speech intelligibility. The expected result is that, after normal language development, the patient may accept hearing aids well, encouraged by the support of the family. Performance and satisfaction with the hearing aids is good, until the onset of the speech intelligibility loss, at which time the patient will encounter serious difficulties and may reject hearing aids as unhelpful. As the histological and electrophysiological results indicate, however, the eighth nerve remains viable, especially in the younger affected members, and success with cochlear implantation may be expected. Audiologic counseling efforts are aided by the presence of role models and support from the other affected members of the family. Speech-language pathology services were not considered important by the members of this family since their speech production developed normally and has remained very good. Self-correction of speech was supported by hearing aids and cochlear implants (Case 5’s speech production was documented in Perkell, Lane, Svirsky, & Webster, 1992). These patients received genetic counseling and, due to the high penetrance of the disease, exhibited serious concerns regarding future generations and the hope of a cure.

The Boeing 787 Dreamliner--A case study in large-scale design integration

2008 ◽  
Author(s):  
D. L. McMullin ◽  
A. R. Jacobsen ◽  
D. C. Carvan ◽  
R. J. Gardner ◽  
J. A. Goegan ◽  
...  
Keyword(s):  
Large Scale ◽  
Design Integration ◽  
Scale Design

Disruptive innovation and operationalization in local and sustainable food systems: Examining the University of Toronto-Local Food Plus partnership

2019 ◽  
Vol 6 (1) ◽  
pp. 120-139
Author(s):  
Lori Stahlbrand
Keyword(s):  
Food Systems ◽  
Large Scale ◽  
Food System ◽  
Local Food ◽  
Disruptive Innovation ◽  
Government Support ◽  
Sustainable Food ◽  
University Of Toronto ◽  
The University

This paper traces the partnership between the University of Toronto and the non-profit Local Food Plus (LFP) to bring local sustainable food to its St. George campus. At its launch, the partnership represented the largest purchase of local sustainable food at a Canadian university, as well as LFP’s first foray into supporting institutional procurement of local sustainable food. LFP was founded in 2005 with a vision to foster sustainable local food economies. To this end, LFP developed a certification system and a marketing program that matched certified farmers and processors to buyers. LFP emphasized large-scale purchases by public institutions. Using information from in-depth semi-structured key informant interviews, this paper argues that the LFP project was a disruptive innovation that posed a challenge to many dimensions of the established food system. The LFP case study reveals structural obstacles to operationalizing a local and sustainable food system. These include a lack of mid-sized infrastructure serving local farmers, the domination of a rebate system of purchasing controlled by an oligopolistic foodservice sector, and embedded government support of export agriculture. This case study is an example of praxis, as the author was the founder of LFP, as well as an academic researcher and analyst.

Algorithm of combining chromatography mass spectrometry-untargeted profiling and multivariate analysis for identification of marker-substances in samples of complex composition

2020 ◽  
Vol 86 (7) ◽  
pp. 12-19
Author(s):  
I. V. Plyushchenko ◽  
D. G. Shakhmatov ◽  
I. A. Rodin
Keyword(s):  
Mass Spectrometry ◽  
Multivariate Analysis ◽  
Large Scale ◽  
Complex Composition ◽  
Unified Protocol ◽  
Chromatography Mass Spectrometry ◽  
Marker Substances ◽  
Selection Testing ◽  
Untargeted Profiling

A viral development of statistical data processing, computing capabilities, chromatography-mass spectrometry, and omics technologies (technologies based on the achievements of genomics, transcriptomics, proteomics, metabolomics) in recent decades has not led to formation of a unified protocol for untargeted profiling. Systematic errors reduce the reproducibility and reliability of the obtained results, and at the same time hinder consolidation and analysis of data gained in large-scale multi-day experiments. We propose an algorithm for conducting omics profiling to identify potential markers in the samples of complex composition and present the case study of urine samples obtained from different clinical groups of patients. Profiling was carried out by the method of liquid chromatography mass spectrometry. The markers were selected using methods of multivariate analysis including machine learning and feature selection. Testing of the approach was performed using an independent dataset by clustering and projection on principal components.

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