Separable Crossover-Promoting and Crossover-Constraining Aspects of Zip1 Activity during Budding Yeast Meiosis.

Accurate chromosome segregation during meiosis relies on the presence of crossover events distributed among all chromosomes. MutSγ and MutLγ homologs (Msh4/5 and Mlh1/3) facilitate the formation of a prominent group of meiotic crossovers that mature within the context of an elaborate chromosomal structure called the synaptonemal complex (SC). SC proteins are required for intermediate steps in the formation of MutSγ-MutLγ crossovers, but whether the assembled SC structure per se is required for MutSγ-MutLγ-dependent crossover recombination events is unknown. Here we describe an interspecies complementation experiment that reveals that the mature SC is dispensable for the formation of Mlh3-dependent crossovers in budding yeast. Zip1 forms a major structural component of the budding yeast SC, and is also required for MutSγ and MutLγ-dependent crossover formation. Kluyveromyces lactis ZIP1 expressed in place of Saccharomyces cerevisiae ZIP1 in S. cerevisiae cells fails to support SC assembly (synapsis) but promotes wild-type crossover levels in those nuclei that progress to form spores. While stable, full-length SC does not assemble in S. cerevisiae cells expressing K. lactis ZIP1, aggregates of K. lactis Zip1 displayed by S. cerevisiae meiotic nuclei are decorated with SC-associated proteins, and K. lactis Zip1 promotes the SUMOylation of the SC central element protein Ecm11, suggesting that K. lactis Zip1 functionally interfaces with components of the S. cerevisiae synapsis machinery. Moreover, K. lactis Zip1-mediated crossovers rely on S. cerevisiae synapsis initiation proteins Zip3, Zip4, Spo16, as well as the Mlh3 protein, as do the crossovers mediated by S. cerevisiae Zip1. Surprisingly, however, K. lactis Zip1-mediated crossovers are largely Msh4/Msh5 (MutSγ)-independent. This separation-of-function version of Zip1 thus reveals that neither assembled SC nor MutSγ is required for Mlh3-dependent crossover formation per se in budding yeast. Our data suggest that features of S. cerevisiae Zip1 or of the assembled SC in S. cerevisiae normally constrain MutLγ to preferentially promote resolution of MutSγ-associated recombination intermediates.

Assessing and complying with regulatory oversight on utility performance.

This paper emphasises the importance of - and the complexity inherent in - the navigation of regulatory oversight and legal requirements in the area of electric utility performance. With a particular focus on utility companies in New York State, it discusses recent measures taken to adapt to the changing demands of regulatory compliance.

A public health response to a newly diagnosed case of hepatitis C associated with lapse in Infection Prevention and Control practices in a dental setting in Ontario, Canada.

BACKGROUND: Haliburton, Kawartha, Pine Ridge District Health Unit (HKPRDHU) investigated an exposure in an Ontario operatory dental facility related to a newly diagnosed hepatitis C virus (HCV) infection caused by a virus with an uncommon hepatitis C genotype. Lapses in Infection Prevention and Control (IPAC) and a second epidemiologically-linked case (with the same uncommon hepatitis C genotype) were identified, prompting a broader public health response and outbreak investigation. OBJECTIVES: a) To describe the investigation of a newly diagnosed case of hepatitis C; b) to describe the broader public health response, and c) to address a paucity in the literature related to the risk of disease transmission in dental settings due to IPAC lapses. METHODS: A collaborative approach with two dental practices, public health partners and regulatory bodies was used. An IPAC inspection was completed to determine and mitigate the risk of blood borne infection transmission within the facilities. Appropriate protocols were followed for the IPAC investigation and public health response. RESULTS: The investigation identified a risk of potential HCV transmission between two cases linked to the same dental facility. There were no other epi-linked cases of HCV identified. Challenges included a lack of adherence to IPAC standards in one of the dental settings and awareness in the dental community regarding HCV transmission, coordination with regulatory bodies and public health experts and low uptake of laboratory testing by patients. CONCLUSION: Despite the unique challenges associated with the investigation, HKPRDHU conducted a successful IPAC lapse investigation and public health response. Public health units need to maintain collaborative approaches with regulated health professionals, their regulatory bodies and public health experts.

Investigation of a community cluster of cutaneous Mycobacterium marinum infection, an emerging zoonotic pathogen in aquaculture industry, Haliburton, Kawartha, Pine Ridge District Health Unit, Ontario, Canada, July-August 2015.

In July 2015, a cluster of five suspect cases of clinically diagnosed Mycobacterium marinum (M. marinum) skin infections were reported to the Haliburton, Kawartha, Pine Ridge District Health Unit (HKPRDHU), Ontario, Canada, with two additional cases subsequently identified through case finding. All seven cases presented with cutaneous lesions located on the finger, hand and/or elbow regions typical of M. marinum infection. Specimens were collected by skin biopsy for two of the seven cases; both cases tested positive for M. marinum by molecular detection (hsp65 gene amplification and sequencing), and one was confirmed positive for M. marinum by culture. All seven cases reported handling raw shrimp from an aquaculture facility in the Health Unit's jurisdiction. M. marinum is not a reportable disease in Ontario, and there are no known previous reports of a cluster of M. marinum reported in Ontario, Canada. A cluster investigation working group was struck that included representation from various agencies including Public Health Ontario (PHO), Public Health Ontario Laboratories (PHOL), Ontario Ministry of Agriculture and Rural Affairs (OMAFRA) and the two health units involved in case investigations. Several public health and aquaculture farming recommendations were made to mitigate further risks associated with handling of raw shrimp from the facility. Several challenges were faced during the investigation process. The paper discusses these challenges and public health recommendations made in order to mitigate occupational and public health risks related to the hazard identified.