The genetic diversity of bottom-fermenting yeast classified as Saccharomyces pastorianus is poor because strains are restricted to a few genetically distinct groups. Crossbreeding is an effective approach to construct novel yeast strains, but it is difficult because of inefficiency to obtain mating-competent cells (MCCs) of bottom-fermenting yeast. By using mating pheromone-supersensitive mutants, we previously isolated several mating-competent meiotic segregants from two bottom-fermenting yeast strains high isoamyl acetate-producing KY1247, and low diacetyl-producing KY2645. #link# Here, we constructed novel non-GM hybrids carrying preferable characteristics from both parents by crossbreeding these bottom-fermenting strains for the first time. Sixteen a/a-type meiotic segregants from KY2645 and 12 α/α-type meiotic segregants from KY1247 were mixed, and cells resembling zygotes were isolated via micromanipulation. In total, 149 hybrids were obtained and verified by examining known single-nucleotide polymorphisms (SNPs) between the parental strains. A sporulation test showed that some of the hybrids were able to sporulate. Moreover, fermentation tests on a test-tube and pilot-plant scale identified two hybrids with production levels of isoamyl acetate and diacetyl that were almost the same as KY1247 and KY2645, respectively. Both of these hybrids produced satisfactory beer in terms of taste, flavor, and overall quality, comparable to that produced by the parental strains. Collectively, our results suggest that crossbreeding between bottom-fermenting yeast strains has the potential to increase the diversity of yeast strains available for brewing, and our method of isolating MCCs provides a huge advance for crossbreeding of bottom-fermenting yeast without using DNA recombination techniques.An emerging approach toward repair of connective tissues applies exogenous crosslinkers to mechanically augment injured structures in vivo. One crosslinker that has been explored for this purpose is the plant-derived small molecule genipin. However, genipin’s high reactivity to primary amines in proteins, small size, and high diffusion coefficient necessitate localizing and controlling its delivery to avoid off-target or adverse effects. In this study, genipin-loaded polymers were evaluated for sustained local administration. Insoluble polymers comprising subunits of α-, β-, or γ-cyclodextrin, cyclic oligosaccharides possessing increasing cavity sizes, were compared to polymers comprising subunits of the non-cyclic polysaccharide dextran. Polymers made from β-cyclodextrin showed prolonged genipin release for over ten times longer than polymers made from α- or γ-cyclodextrins or dextran, indicating that genipin possesses molecular affinity for the β-cyclodextrin cavity. Modeling of complexation between genipin and cyclodextrin hosts supported this finding. Varespladib released from all polymers was confirmed to be functional by exogenous collagen crosslinking through fluorometric and mechanical readouts. Co-incubation of genipin-loaded polymers with bovine tendon explants showed genipin crosslink-mediated coloration that was confined to the sites of exposure. Altogether, results indicate that host-guest interactions within a polymeric delivery vehicle can help to control and confine genipin release.Microglia, the resident immune cells of the brain, have recently emerged as key players in Alzheimer Disease (AD) pathogenesis, but their roles in AD remain largely elusive and require further investigation. Microglia functions are readily altered when isolated from their brain environment, and microglia reporter mice thus represent valuable tools to study the contribution of these cells to neurodegenerative diseases such as AD. The CX3CR1+/eGFP mice is one of the most popular microglia reporter mice, and has been used in numerous studies to investigate in vivo microglial functions, including in the context of AD research. However, until now, the impact of CX3CR1 haplodeficiency on the typical features of Alzheimer Disease has not been studied in depth. To fill this gap, we generated APPswe/PSEN1dE9CX3CR1+/eGFP mice and analyzed these mice for Alzheimer’s like pathology and neuroinflammation hallmarks. More specifically, using robust multifactorial statistical and multivariate analyses, we investigated the impact of CX3CR1 deficiency in both males and females, at three typical stages of the pathology progression at early stage when Amyloid-β (Aβ) deposition just starts, at intermediate stage during Aβ accumulation phase and at more advanced stages when Aβ plaque number stabilizes. We found that CX3CR1 haplodeficiency had little impact on the progression of the pathology in the APPswe/PSEN1dE9 model and demonstrated that the APPswe/PSEN1dE9CX3CR1+/eGFP line is a relevant and useful model to study the role of microglia in Alzheimer Disease. In addition, although Aβ plaques density is higher in females compared to age-matched males, we show that their glial reaction, inflammation status and memory deficits are not different.

This study compared traumatic brain injury (TBI) outcomes from 2 cohorts the National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems (TBIMS) in the United States and Longitudinal Head Injury Outcome Study conducted in Victoria, Australia, by the Monash Epworth Rehabilitation Research Centre (MERRC).

Cohort study with 1- and 2-year follow-up.

Acute trauma care and inpatient rehabilitation with follow-up.

Patients (N=1056) with moderate-severe TBI admitted in 2000-2012 to inpatient rehabilitation after motor vehicle-related collisions, who completed follow-up, were matched using 12 matching algorithm based on age at injury, days of posttraumatic amnesia, and years education, resulting in groups of 352 (MERRC) and 704 patients (TBIMS).

The cohorts had received acute trauma care and inpatient rehabilitation for a median 38 (MERRC) or 33 days (TBIMS). The MERRC group also had routine access to community-based support and rehabilitation for resion of community-based supports could confer benefits for long-term TBI outcomes. Further studies documenting rehabilitation services are needed to explore this.