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Background: The JOURNEY II Bi-Cruciate Stabilizing Total Knee System (BLINDED) is a second-generation guided-motion knee implant that has been used in over 100,000 primary total knee arthroplasties (TKAs) worldwide. However, performance information is limited.Methods: Data for 2059 primary TKAs were abstracted at 7 US and 3 European sites. Estimates of cumulative incidence of revision were compared with registry data for cemented posterior-stabilized implants.Results: Average age was 64.3 years (range, 18-91); 58.5% were females; and 12.3% TKAs were in subjects younger than 55 years. Patellae were resurfaced in 95.9%. Median time since primary TKA was 4.2 years; longest was 6.1 years; and 78.9% were 3 years or more since primary TKA. Of 67 revisions (3.2%), 20 (30%) involved femoral or tibial component removal compared to 42% in the Australian Joint Registry (Australian Orthopedic Association National Joint Replacement Registry). All-component revisions accounted for 15 of 67, femoral component only for 2 of 67, tibial component only for 3 of 67, patellar component with/without tibial insert exchange for 17 of 67, and isolated tibial insert exchange for 30 of 67. In addition, there were 18 reoperations without component exchange. Component revision indications were infection (33%), mechanical loosening (21%), fracture of bone around the joint (16%), and instability (15%). Kaplan-Meier revision estimate was 3.1 and 3.6 per 100 TKAs at 3 and 5 years, respectively, compared to Australian Orthopedic Association National Joint Replacement Registry estimates of 3.1 and 4.1 per 100 TKAs.Conclusion: The revision rate for the second-generation implant was similar to cemented posterior-stabilized registry controls. [ABSTRACT FROM AUTHOR]

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The introduction in modern breweries of tall cylindroconical fermentors, replacing the traditional open fermentation vats, unexpectedly revealed strong inhibition of flavor production by the high CO 2 pressure in the fermentors. We have screened our collection of Saccharomyces cerevisiae strains for strains displaying elevated tolerance to inhibition of flavor production by +0.65 bar CO 2 , using a laboratory scale CO 2 pressurized fermentation system. We focused on the production of isoamyl acetate, a highly desirable flavor compound conferring fruity banana flavor in beer and other alcoholic beverages, from its precursor isoamyl alcohol (IAAc/Alc ratio). We selected the most tolerant Saccharomyces cerevisiae strain, saké yeast Kyokai no. 1, isolated a stable haploid segregant seg63 with the same high IAAc/Alc ratio under CO 2 pressure, crossed seg63 with the unrelated inferior strain ER7A and phenotyped 185 haploid segregants, of which 28 displaying a high IAAc/Alc ratio were pooled. Mapping of Quantitative Trait Loci (QTLs) by whole-genome sequence analysis based on SNP variant frequency revealed two QTLs. In the major QTL, reciprocal hemizygosity analysis identified MDS3 as the causative mutant gene, a putative member of the TOR signaling pathway. The MDS3 Seg.63 allele was dominant and contained a single causative point mutation, T2171C, resulting in the F274S substitution. Introduction of MDS3 Seg.63 in an industrial tetraploid lager yeast with CRISPR/Cas9 enhanced isoamyl acetate production by 145% under CO 2 pressure. This work shows the strong potential of polygenic analysis and targeted genetic modification for creation of cisgenic industrial brewer's yeast strains with specifically improved traits. IMPORTANCE The upscaling of fermentation to very tall cylindroconical tanks is known to negatively impact beer flavor. Most notably, the increased CO 2 pressure in such tanks compromises production by the yeast of the desirable fruity "banana" flavor (isoamyl acetate). The cause of the CO 2 inhibition of yeast flavor production has always remained enigmatic. Our work has brought the first insight into its molecular-genetic basis and provides a specific gene tool for yeast strain improvement. We first identified a yeast strain with superior tolerance to CO 2 inhibition of flavor production, and applied polygenic analysis to identify the responsible gene. We narrowed down the causative element to a single nucleotide difference, MDS3 T2171C , and showed that it can be engineered into brewing yeast to obtain strains with superior flavor production in high CO 2 pressure conditions, apparently without affecting other traits relevant for beer brewing. Alternatively, such a strain could be obtained through marker-assisted breeding.

Ever since the introduction of controlled fermentation processes, alcoholic fermentations and Saccharomyces cerevisiae starter cultures proved to be a match made in heaven. The ability of S. cerevisiae to produce and withstand high ethanol concentrations, its pleasant flavour profile and the absence of health-threatening toxin production are only a few of the features that make it the ideal alcoholic fermentation organism. However, in certain conditions or for certain specific fermentation processes, the physiological boundaries of this species limit its applicability. Therefore, there is currently a strong interest in non-Saccharomyces (or non-conventional) yeasts with peculiar features able to replace or accompany S. cerevisiae in specific industrial fermentations. Brettanomyces (teleomorph: Dekkera), with Brettanomyces bruxellensis as the most commonly encountered representative, is such a yeast. Whilst currently mainly considered a spoilage organism responsible for off-flavour production in wine, cider or dairy products, an increasing number of authors report that in some cases, these yeasts can add beneficial (or at least interesting) aromas that increase the flavour complexity of fermented beverages, such as specialty beers. Moreover, its intriguing physiology, with its exceptional stress tolerance and peculiar carbon- and nitrogen metabolism, holds great potential for the production of bioethanol in continuous fermentors. This review summarizes the most notable metabolic features of Brettanomyces, briefly highlights recent insights in its genetic and genomic characteristics and discusses its applications in industrial fermentation processes, such as the production of beer, wine and bioethanol., (Copyright © 2015. Published by Elsevier B.V.)

Yeast cells often encounter a mixture of different carbohydrates in industrial processes. However, glucose and sucrose are always consumed first. The presence of these sugars causes repression of gluconeogenesis, the glyoxylate cycle, respiration and the uptake of less-preferred carbohydrates. Glucose and sucrose also trigger unexpected, hormone-like effects, including the activation of cellular growth, the mobilization of storage compounds and the diminution of cellular stress resistance. In an industrial context, these effects lead to several yeast-related problems, such as slow or incomplete fermentation, 'off flavors' and poor maintenance of yeast vitality. Recent studies indicate that the use of mutants with altered responses to carbohydrates can significantly increase productivity. Alternatively, avoiding unnecessary exposure to glucose and sucrose could also improve the performance of industrial yeasts.

In the yeast Saccharomyces cerevisiae, the enzymes which catalyse the synthesis of ethyl acetate, ethyl n-hexanoate and isoamyl acetate were partly resolved from a fraction containing slowly sedimenting lipoproteins released during cell disruption with glass beads. Solubilization with detergents and fractionation by affinity chromatography have demonstrated the presence of at least three, and probably four, ester synthases which differ in their catalytic properties. Isoamyl-acetate synthase was solubilized and extensively purified to apparent homogeneity by successive chromatographies on various columns. On the basis of its specific activity in cell-free extracts, the enzyme was purified 19,000-fold with a 5% activity yield. As judged by SDS/PAGE, it consists of a single polypeptide chain with a molecular mass of 57 +/- 3 kDa and its apparent pI is 5.5. The enzyme acetylates isoamyl alcohol, ethanol and 12-DL-hydroxystearic acid from acetyl-CoA but is unable to use n-hexanoyl-CoA as a cosubstrate. This enzyme, defined as an acetyl-CoA: O-alcohol acetyltransferase, could be the product of one of the anaerobically induced genes in S. cerevisiae.