Cystine-mediated oxidative defence in Lactobacillus reuteri BR11

Lactobacillus reuteri BR11 possesses an abundant cystine uptake (Cyu) ABC-transporter that was previously found to be involved in a novel mechanism of oxidative defence mediated by cystine. The current study aimed to elucidate this mechanism with a focus on the role of the co-transcribed cystathionine ã-lyase (Cgl). Growth studies of wild-type L. reuteri BR11 and mutants inactivated in cgl and the cystine-binding protein encoding gene cyuC showed that in contrast to the Cyu transporter, whose inactivation led to growth arrest in aerated cultures, Cgl is not crucial for oxidative defence. However, the role of Cgl in oxidative defence became apparent in the presence of severe oxidative damage and cysteine deprivation. Cysteine was found to be protective against oxidative stress, and the action of Cgl in both cysteine biosynthesis and degradation poses a seemingly futile pathway that deprives the intracellular cysteine pool. To further characterise the relationship between Cgl activity and cysteine and their roles in oxidative defence, enzymatic assays were performed on purified Cgl, and intracellular concentrations of cysteine, cystathionine and methionine were determined. Cgl was highly active towards cystine and cystathionine and less active towards cysteine in vitro, suggesting the main function of Cgl to be cysteine biosynthesis. Cysteine was found at high concentrations in the cell, but the levels were not significantly affected by inactivation of cgl or growth under aerobic conditions. It was concluded that both anabolic and catabolic activities of Cgl towards cysteine contribute to oxidative defence, the former by maintaining an intracellular reservoir of thiol analogous to glutathione, and the latter by producing H2S which is readily secreted, thus creating a reducing extracellular environment. The significance of the Cyu transporter to the physiology of L. reuteri BR11 prompted a phylogenetic study to determine its presence in bacteria. Orthologs of the Cyu transporter that are closest matches to the Cyu transporter are only limited to several species of Lactobacillus and Leuconostoc. Outside the Lactobacillales order, the closest matching orthologs belong to Proteobacteria, and there are more orthologs in Proteobacteria than non-Lactobacillales Firmicutes, suggesting that the Cyu transporter locus was present in the ancestor of the Proteobacteria and Firmicutes, and over evolutionary time has been lost or diverged in many Firmicutes. The clustering of the Cyu transporter locus with a gene encoding a Cgl family protein is even rarer. It was only found in L. reuteri, Lactobacillus vaginalis, Weissella paramesenteroides, the Lactobacillus casei group, and several Campylobacter sp. An accompanying phylogenetic study of L. reuteri BR11 using multi-locus sequence analysis showed that L. reuteri BR11 had diverged from more than 100 strains of L. reuteri isolated from various hosts and geographical locations. However, comparison with other Lactobacillus species supported the current classification of BR11 as L. reuteri. The most closely related species to L. reuteri is L. vaginalis or Lactobacillus antri, depending on the housekeeping gene used for analysis. The close evolutionary relationship of L. vaginalis to L. reuteri and the high degree of sequence identity between the cgl-cyuABC loci in both species suggest that the Cyu system is highly likely to perform similar functions in L. vaginalis. In search of other genes that function in oxidative defence, a number of mutants which were inactivated in genes that confer increased resistance to oxidative stress in other bacteria were constructed. The genes targeted were ahpC (peroxidase component of the alkyl hydroperoxide reductase system), tpx (thiol peroxidase), osmC (osmotically induced protein C), mntH (Mn2+/Fe2+ transporter), gshA (ã-glutamylcysteine synthetase) and msrA (methionine sulfoxide reductase). The ahpC and mntH mutants had slightly lower minimum inhibitory concentrations of organic peroxides, suggesting these genes might be involved in resistance to organic peroxides in L. reuteri. However, none of the mutants exhibited growth defects in aerated cultures, in stark contrast to the cyuC mutant. This may be due to compensatory functions of other genes, a hypothesis which cannot be tested until a robust protocol for constructing markerless multiple gene deletion mutants in L. reuteri is developed. These results highlight the importance of the Cyu transporter in oxidative defence and provide a foundation for extending the research of this system in other bacteria.

Availability of advance visual information constrains association-football goalkeeping performance during penalty kicks

A pressing concern within the literature on anticipatory perceptual-motor behaviour is the lack of clarity on the applicability of data, observed under video-simulation task constraints, to actual performance in which actions are coupled to perception, as captured during in-situ experimental conditions. We developed an in-situ experimental paradigm which manipulated the duration of anticipatory visual information from a penalty taker’s actions to examine experienced goalkeepers’ vulnerability to deception for the penalty kick in association football. Irrespective of the penalty taker’s kick strategy, goalkeepers initiated movement responses earlier across consecutively earlier presentation points. Overall goalkeeping performance was better in non-deception trials than in deception conditions. In deception trials, the kinematic information presented up until the penalty taker initiated his/her kicking action had a negative effect on goalkeepers’ performance. It is concluded that goalkeepers are likely to benefit from not anticipating a penalty taker’s performance outcome based on information from the run-up, in preference to later information that emerges just before the initiation of the penalty taker’s kicking action.

Physical function and health-related quality of life of older adults undergoing hospital rehabilitation : how strong is the association?

The purpose of this research is to report preliminary empirical evidence regarding the association between common physical performance measures and health-related quality of life (HRQoL) of hospitalized older adults recovering from illness and injury. Frequently, these patients do not return to premorbid levels of independence and physical ability. Rehabilitation for this population often focuses on improving physical functioning and mobility with the intention of maximizing their HRQoL for discharge and thereafter. For this reason, longitudinal use of physical performance measures as an indicator of improvement in physical functioning (and thus HRQoL) is common. Although this is a logical approach, there have been mixed results from previous investigations into the association between common measures of physical function and HRQoL amongst other adult patient populations.1,2 There has been no previous investigation reporting the association between HRQoL and a variety of common physical performance measures in hospitalized older adults.

Using Association Rules to Solve the Cold-Start Problem in Recommender Systems

Recommender systems are widely used online to help users find other products, items etc that they may be interested in based on what is known about that user in their profile. Often however user profiles may be short on information and thus it is difficult for a recommender system to make quality recommendations. This problem is known as the cold-start problem. Here we investigate using association rules as a source of information to expand a user profile and thus avoid this problem. Our experiments show that it is possible to use association rules to noticeably improve the performance of a recommender system under the cold-start situation. Furthermore, we also show that the improvement in performance obtained can be achieved while using non-redundant rule sets. This shows that non-redundant rules do not cause a loss of information and are just as informative as a set of association rules that contain redundancy.

HapMap tag-SNP analysis confirms a role for COMT in schizophrenia risk and reveals a novel association

Catechol-O-methyl transferase (COMT) encodes an enzyme involved in the metabolism of dopamine and maps to a commonly deleted region that increases schizophrenia risk. A non-synonymous polymorphism (rs4680) in COMT has been previously found to be associated with schizophrenia and results in altered activity levels of COMT. Using a haplotype block-based gene-tagging approach we conducted an association study of seven COMT single nucleotide polymorphisms (SNPs) in 160 patients with a DSM-IV diagnosis of schizophrenia and 250 controls in an Australian population. Two polymorphisms including rs4680 and rs165774 were found to be significantly associated with schizophrenia. The rs4680 results in a Val/Met substitution but the strongest association was shown by the novel SNP, rs165774, which may still be functional even though it is located in intron five. Individuals with schizophrenia were more than twice as likely to carry the GG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. This association was slightly improved when males were analysed separately possibly indicating a degree of sexual dimorphism. Our results confirm that COMT is a good candidate for schizophrenia risk, by replicating the association with rs4680 and identifying a novel SNP association.

Analysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia

Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated.

Individual differences in the visual control of intercepting a penalty kick in association football

Recent perceptual-motor studies have revealed variations in learning trajectories of novices. Despite such observation, relatively little attention has been paid to studying individual differences in experienced performers’ perceptual-motor behaviors. The present study examined individual differences for a visual anticipation task. Experienced association football goalkeepers attempted to intercept penalty kicks taken with deceptive and non-deceptive kicking actions. Data revealed that differences in the action capabilities of goalkeepers affected the timing and accuracy of movement response behaviors. Faster goalkeepers tended to wait until later before initiating movement in comparison with slower goalkeepers. The study of affordances in sport environments offers a theoretical framework with which to overcome some of the reported methodological limitations in the visual anticipation literature.

The ecological dynamics of 1v1 sub-phases in association football

This paper analyzes effects of different practice task constraints on heart rate (HR) variability during 4v4 smallsided football games. Participants were sixteen football players divided into two age groups (U13, Mean age: 12.4±0.5 yrs; U15: 14.6±0.5). The task consisted of a 4v4 sub-phase without goalkeepers, on a 25x15 m field, of 15 minutes duration with an active recovery period of 6 minutes between each condition. We recorded players’ heart rates using heart rate monitors (Polar Team System, Polar Electro, Kempele, Finland) as scoring mode was manipulated (line goal: scoring by dribbling past an extended line; double goal: scoring in either of two lateral goals; and central goal: scoring only in one goal). Subsequently, %HR reserve was calculated with the Karvonen formula. We performed a time-series analysis of HR for each individual in each condition. Mean data for intra-participant variability showed that autocorrelation function was associated with more short-range dependence processes in the “line goal” condition, compared to other conditions, demonstrating that the “line goal” constraint induced more randomness in HR response. Relative to inter-individual variability, line goal constraints demonstrated lower %CV and %RMSD (U13: 9% and 19%; U15: 10% and 19%) compared with double goal (U13: 12% and 21%; U15: 12% and 21%) and central goal (U13: 14% and 24%; U15: 13% and 24%) task constraints, respectively. Results suggested that line goal constraints imposed more randomness on cardiovascular stimulation of each individual and lower inter-individual variability than double goal and central goal constraints.

Reliable representations for association rules

Association rule mining has contributed to many advances in the area of knowledge discovery. However, the quality of the discovered association rules is a big concern and has drawn more and more attention recently. One problem with the quality of the discovered association rules is the huge size of the extracted rule set. Often for a dataset, a huge number of rules can be extracted, but many of them can be redundant to other rules and thus useless in practice. Mining non-redundant rules is a promising approach to solve this problem. In this paper, we first propose a definition for redundancy, then propose a concise representation, called a Reliable basis, for representing non-redundant association rules. The Reliable basis contains a set of non-redundant rules which are derived using frequent closed itemsets and their generators instead of using frequent itemsets that are usually used by traditional association rule mining approaches. An important contribution of this paper is that we propose to use the certainty factor as the criterion to measure the strength of the discovered association rules. Using this criterion, we can ensure the elimination of as many redundant rules as possible without reducing the inference capacity of the remaining extracted non-redundant rules. We prove that the redundancy elimination, based on the proposed Reliable basis, does not reduce the strength of belief in the extracted rules. We also prove that all association rules, their supports and confidences, can be retrieved from the Reliable basis without accessing the dataset. Therefore the Reliable basis is a lossless representation of association rules. Experimental results show that the proposed Reliable basis can significantly reduce the number of extracted rules. We also conduct experiments on the application of association rules to the area of product recommendation. The experimental results show that the non-redundant association rules extracted using the proposed method retain the same inference capacity as the entire rule set. This result indicates that using non-redundant rules only is sufficient to solve real problems needless using the entire rule set.

Risk of falls, injurious falls, and other injuries resulting from visual impairment among older adults with age-related macular degeneration

Purpose: Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment among older adults. This study explored the relationship between AMD, falls risk and other injuries and identified visual risk factors for these adverse events. Methods: Participants included 76 community-dwelling individuals with a range of severity of AMD (mean age, 77.0±6.9 years). Baseline assessment included binocular visual acuity, contrast sensitivity and merged visual fields. Participants completed monthly falls and injury diaries for one year following the baseline assessment. Results: Overall, 74% of participants reported having either a fall, injurious fall or other injury. Fifty-four percent of participants reported a fall and 30% reported more than one fall; of the 102 falls reported, 63% resulted in an injury. Most occurred outdoors (52%), between late morning and late afternoon (61%) and when navigating on level ground (62%). The most common non-fall injuries were lacerations (36%) and collisions with an object (35%). Reduced contrast sensitivity and visual acuity were associated with increased fall rate, after controlling for age, gender, cognitive function, cataract severity and self-reported physical function. Reduced contrast sensitivity was the only significant predictor of falls and other injuries. Conclusion: Among older adults with AMD, increased visual impairment was significantly associated with an increased incidence of falls and other injuries. Reduced contrast sensitivity was significantly associated with increased rates of falls, injurious falls and injuries, while reduced visual acuity was only associated with increased falls risk. These findings have important implications for the assessment of visually impaired older adults.

Genetic and gene expression analyses of the polycystic ovary syndrome candidate gene fibrillin-3 and other fibrillin family members in human ovaries

Several studies have demonstrated an association between polycystic ovary syndrome (PCOS) and the dinucleotide repeat microsatellite marker D19S884, which is located in intron 55 of the fibrillin-3 (FBN3) gene. Fibrillins, including FBN1 and 2, interact with latent transforming growth factor (TGF)-β-binding proteins (LTBP) and thereby control the bioactivity of TGFβs. TGFβs stimulate fibroblast replication and collagen production. The PCOS ovarian phenotype includes increased stromal collagen and expansion of the ovarian cortex, features feasibly influenced by abnormal fibrillin expression. To examine a possible role of fibrillins in PCOS, particularly FBN3, we undertook tagging and functional single nucleotide polymorphism (SNP) analysis (32 SNPs including 10 that generate non-synonymous amino acid changes) using DNA from 173 PCOS patients and 194 controls. No SNP showed a significant association with PCOS and alleles of most SNPs showed almost identical population frequencies between PCOS and control subjects. No significant differences were observed for microsatellite D19S884. In human PCO stroma/cortex (n = 4) and non-PCO ovarian stroma (n = 9), follicles (n = 3) and corpora lutea (n = 3) and in human ovarian cancer cell lines (KGN, SKOV-3, OVCAR-3, OVCAR-5), FBN1 mRNA levels were approximately 100 times greater than FBN2 and 200–1000-fold greater than FBN3. Expression of LTBP-1 mRNA was 3-fold greater than LTBP-2. We conclude that FBN3 appears to have little involvement in PCOS but cannot rule out that other markers in the region of chromosome 19p13.2 are associated with PCOS or that FBN3 expression occurs in other organs and that this may be influencing the PCOS phenotype.

Women's labor force participation and marriage : the case of Korea

In this paper, we examine the relationship between marital status and female labor force participation in Korea, and argue that marriage remains a major obstacle to young Korean women's employment. We find that an average married woman is much less likely (by 40–60%) to participate in the labor force than a single woman in urban Korea. Further investigation into the participation patterns among married women reveals that labor force participation rate (LFPR) varies with husband's occupation and her own age. Lower LFPR among the young married women is explained by demand-side factors, while relatively higher LFPR among the middle-aged married women is mostly explained by the supply-side factors.