Immunological cross-reactivity of mycobacterial topoisomerase I and divergence from other bacteria

Mycobacterium smegmatis topoisomerase I exhibits several distinctive characteristics among all topoisomerases. The enzyme is devoid of Zn2+fingers found typically in other bacterial type I topoisomerases and binds DNA in a site-specific manner. Using polyclonal antibodies, we demonstrate the high degree of relatedness of the enzyme across mycobacteria but not other bacteria. This absence of cross-reactivity from other bacteria indicates that mycobacterial topoisomerase I has diverged from Escherichia coli and other bacteria. We have investigated further the immunological properties of the enzyme by raising a panel of monoclonal antibodies that recognises different antigenically active regions of the enzyme and binds it with widely varied affinity. Inhibition of a C-terminal domain-specific antibody binding by enzyme-specific and non-specific oligonucleotides suggests the possibility of using these monoclonal antibodies to probe the structure, function and in vivo role of the enzyme.

Cross-sectional study of a microsatellite marker in the low density lipoprotein receptor gene in obese normotensives

1. The low density lipoprotein receptor is an important regulator of serum cholesterol which may have implications for the development of both hypertension and obesity. In this study, genotypes for a low density lipoprotein receptor gene (LDLR) dinucleotide polymorphism were determined in both lean and obese normotensive populations. 2. In previous cross-sectional association studies an ApaLI and a HincII polymorphism for LDLR were shown to be associated with obesity in essential hypertensives. However, these polymorphisms did not show an association with obesity in normotensives. 3. In contrast, this study reports that preliminary results for an LDLR microsatellite marker, located more towards the 3' end of the gene, show a significant association with obesity in the normotensive population studied. These results indicate that LDLR could play an important role in the development of obesity, which might be independent of hypertension.

Protein cross-linking with oxidative enzymes and transglutaminase : Effects in meat protein systems

The effects of tyrosinase, laccase and transglutaminase (TG) were studied in different meat protein systems. The study was focused on the effects of the enzymes on the gel formation properties of myofibrils, and on the textural and water-holding properties of the heated meat systems. The cross-linking efficiency of a novel Trichoderma reesei tyrosinase was compared to that of the commercial Agaricus bisporus tyrosinase. Trichoderma tyrosinase was found to be superior compared to the Agaricus enzyme in its protein cross-linking efficiency and in the incorporation of a small molecule into a complex proteinaceous substrate. Tyrosinase, laccase and TG all polymerised myofibrillar proteins, but laccase was also found to cause protein fragmentation. A positive connection between covalent cross-link and gel formation was observed with tyrosinase and TG. Laccase was able to increase the gel formation only slightly. With an excessive laccase dosage the gel formation declined due to protein fragmentation. Tyrosinase, laccase and TG had different effects on the texture and water-holding of the heated chicken breast meat homogenates. Tyrosinase improved the firmness of the homogenate gels free of phosphate and with a low amount of meat. TG improved the firmness of all studied homogenates. Laccase weakened the gel firmness of the low-meat, low-salt and low-salt/phosphate homogenates and maintained the firmness on the control level in the homogenate free of phosphate. Tyrosinase was the only enzyme capable of reducing the weight loss in the homogenates containing a low amount of meat and a low amount of NaCl. TG was the only enzyme that could positively affect the firmness of the homogenate gel containing both low NaCl and phosphate amounts. In pilot scale the test products were made of coarsely ground chicken breast fillet with a moderate amount of salt. Increasining the amount of meat, salt and TG contents favoured the development of firmness of the test products. The evaporation loss decreased slightly along with increasing TG and NaCl amounts in the experimental conditions used, indicating a positive interaction between these two factors. In this work it was shown that tyrosinase, laccase and TG affected the same myofibrillar proteins, i.e. myosin and troponin T. However, these enzymes had distinguishable effects on the gel formation of a myofibril system as well as on the textural and water-holding properties of the finely ground meat homogenates, reflecting distinctions at least in the reaction mechanisms and target amino acid availability in the protein substrates for these enzymes.

The impact of a streamlined funding application process on application time: Two cross-sectional surveys of Australian researchers

Objective: To examine if streamlining a medical research funding application process saved time for applicants. Design: Cross-sectional surveys before and after the streamlining. Setting: The National Health and Medical Research Council (NHMRC) of Australia. Participants: Researchers who submitted one or more NHMRC Project Grant applications in 2012 or 2014. Main outcome measures: Average researcher time spent preparing an application and the total time for all applications in working days. Results: The average time per application increased from 34 working days before streamlining (95% CI 33 to 35) to 38 working days after streamlining (95% CI 37 to 39; mean difference 4 days, bootstrap p value <0.001). The estimated total time spent by all researchers on applications after streamlining was 614 working years, a 67-year increase from before streamlining. Conclusions: Streamlined applications were shorter but took longer to prepare on average. Researchers may be allocating a fixed amount of time to preparing funding applications based on their expected return, or may be increasing their time in response to increased competition. Many potentially productive years of researcher time are still being lost to preparing failed applications.

Relations between chronic regulatory focus and future time perspective: Results of a cross-lagged structural equation model

Future time perspective - the way individuals perceive their remaining time in life - importantly influences socio-emotional goals and motivational outcomes. Recently, researchers have called for studies that investigate relationships between personality and future time perspective. Using a cross-lagged panel design, this study investigated effects of chronic regulatory focus dimensions (promotion and prevention orientation) on future time perspective dimensions (focus on opportunities and limitations). Survey data were collected two times, separated by a 3. month time lag, from 85 participants. Results of structural equation modeling showed that promotion orientation had a positive lagged effect on focus on opportunities, and prevention orientation had a positive lagged effect on focus on limitations.

Fatty acids, fibre, carotenoids and tocopherols in relation to glucose metabolism in subjects at high risk for type 2 diabetes : a cross-sectional analysis

Fatty acids, fibre, carotenoids and tocopherols in relation to glucose metabolism in subjects at high risk for type 2 diabetes a cross-sectional analysis Type 2 diabetes (T2D) is a heterogeneous disorder of carbohydrate, lipid and protein metabolism, resulting from genetics, environmental influences and interactions between these. The disease is characterized by insulin resistance, β-cell dysfunction, hepatic glucose overproduction and disordered fat mobilization and storage. The literature on associations between dietary factors and glucose metabolism is inconsistent. One factor behind the discrepant results may be genetic heterogeneity of study populations. Data on nutrient-gene interactions in relation to glucose metabolism are scarce. Thus, investigating high-risk populations and exploring nutrient-gene interactions are essential for improving the understanding of T2D aetiology. Ideally, this information could help to develop prevention programmes that take into account the genetic predisposition to the disease. In this study, associations between measures of glucose metabolism predicting T2D and fatty acids, antioxidative nutrients and fibre were examined in a high-risk population, i.e., in non-diabetic relatives of affected patients. Interactions between the PPARG Pro12Ala polymorphism and fatty acids on glucose metabolism were taken into consideration. This common polymorphism plays an important role in the regulation of glucose metabolism. The inverse associations observed between dietary fibre and insulin resistance are consistent with the prevailing recommendations urging increased intake of fibre to prevent T2D. Beneficial associations observed between the intake of carotenoids and glucose levels stress that a high consumption of vegetables, fruits and berries rich in carotenoids might also play a role in the prevention of T2D. Whether tocopherols have an independent association with glucose metabolism remains questionable. Observed interactions between fatty acids and glucose metabolism suggest that a high intake of palmitic acid is associated with high fasting glucose levels mainly in female Ala allele carriers. Furthermore, the PPARG Pro12Ala polymorphism may modify the metabolic response to dietary marine fat. The beneficial associations of high intake of marine n 3 fatty acids with insulin resistance and glucose levels may be restricted to carriers of the Ala allele. The findings pertain to subjects with a family history of T2D, and the cross-sectional nature of the study precludes inferences about causality. Results nevertheless show that associations of dietary factors with glucose metabolism may be modulated by the genetic makeup of an individual. Additional research is warranted to elucidate the role of probably numerous nutrient-gene interactions, some of which may be sex-specific, in the aetiology of T2D.

Defining Adequate Vitamin D Intake : Cross-sectional and Intervention Studies

D-vitamiini ylläpitää normaalia luun kasvua ja uudistumista koko elämän ajan. Suomessa, kuten monissa muissakin länsimaissa, väestön D-vitamiinitilanne on riittämätön – talvisin osalla jopa puutteellinen. Tässä väitöskirjassa on tutkittu, lisääkö D-vitamiini luumassan kertymistä kasvuiässä, ja ylläpitäkö D-vitamiini luuston tasapainoista aineenvaihduntaa aikuisiällä. Nämä vaikutukset saattavat ehkäisi osteoporoosin kehittymistä eri ikäkausina. Väitöskirjatyössä tutkittiin erisuuruisten D-vitamiinilisäysten vaikutuksia kolmessa eri ikäryhmässä, jotka olivat 11-12 -vuotiaat tytöt (N=228), 21-49 -vuotiaat miehet (N=54) ja 65-85 -vuotiaat naiset (N=52). Tutkittavat satunnaistettiin ryhmiin, jotka nauttivat joko lumevalmistetta tai 5-20 µg D3-vitamiinia vitamiinilisänä. Tutkimukset olivat kaksoissokkoutettuja. Tutkimuksen aikana tutkittavilta otettiin paastoveri- ja virtsanäytteitä. Lisäksi he täyttivät tutkimuslomakkeen taustatietojen kartoittamiseksi sekä frekvenssikyselylomakkeen kalsiumin ja D-vitamiinin saannin selvittämiseksi. Tyttöjen luunmineraalitiheys (BMD) mitattiin DXA–laitteella ja miesten volumetrinen luuntiheys pQCT-menetelmällä. Näytteistä määritettiin mm. seerumin 25-hydroksi-D-vitamiinin (=S-25-OHD), lisäkilpirauhashormonin (=S-PTH) ja luun aineenvaihduntaa kuvaavien merkkiaineiden pitoisuuksia. Murrosikäisten tyttöjen poikkileikkaustutkimuksessa S-25-OHD- ja luun muodostusmerkkiaineen pitoisuudet vaihtelivat kuukausien välillä; suurimmat pitoisuudet mitattiin syyskuussa ja pienimmät maaliskuussa, mikä kuvastaa vuodenaikaisvaihtelua. Vastaava vaihtelu havaittiin lannerangan ja reisiluun BMD:ssä. D-vitamiinilisäyksellä oli myönteinen vaikutus tyttöjen luumassan lisääntymiseen. Suurin D-vitamiinilisä (10 µg/vrk) lisäsi luumassaa 17.2% enemmän reisiluussa ja 12.5% enemmän lannerangassa verrattuna lumevalmistetta nauttivien tyttöjen vastaaviin tuloksiin, mutta tulos riippui hoitomyöntyvyydestä. D-vitamiinin vaikutus luustoon välittyi vähentyneen luun hajotuksen kautta. Tutkimustuloksiin perustuen riittävä D-vitamiinin saanti murrosikäisille tytöille on 15 µg/vrk. D-vitamiinilisän vaikutus 65-85 -vuotiaiden naisten S-25-OHD-pitoisuuteen vakioitui kuudessa viikossa annoksen ollessa 5-20 µg/vrk. Näillä D-vitamiiniannoksilla ei saavutettu tavoiteltavaa S-25-OHD-pitoisuutta, joka on 80 nmol/l. Arvioimme, että 60 nmol/l -pitoisuuden, jota esiintyy kesäisin tämän ikäryhmän suomalaisilla, tämän ikäryhmän naiset saavuttaisivat 24 µg:n päivittäisellä D-vitamiinin saannilla. Terveillä miehillä havaittiin vuodenaikaisvaihtelu S-25-OHD- ja S-PTH-pitoisuudessa sekä luun hajotusta kuvaavassa merkkiainepitoisuudessa. Toisaalta vaihtelua ei havaittu radiuksen volumetrisessä luuntiheydessä eikä luun muodostusmerkkiaineen pitoisuudessa. Vuodenaikaisvaihtelu estettiin 17 µg:n päivittäisellä D-vitamiinin saannilla, mutta tämän ei havaittu vaikuttavan radiuksen luuntiheyteen kuusi kuukautta kestävän tutkimuksen aikana. Yhteenvetona todetaan, että D-vitamiinin saanti on edelleenkin riittämätöntä tutkimusten kohderyhmillä. Tämä näkyy S-25-OHD- ja PTH-pitoisuuden sekä luunaineenvaihduntaa kuvaavien merkkiaineiden vuodenaikaisvaihteluna, mikä on haitallista luuston hyvinvoinnille. D-vitamiinin saantia tulisi lisätä, jotta vähintäänkin riittävä D-vitamiinitilanne (S-25-OHD>50 nmol/l) tai mahdollisesti jopa tavoiteltava D-vitaminitilanne (S-25-OHD≥80 nmol/l) saavutettaisiin. Jotta D-vitamiinin saannin lisääminen olisi kaikissa ikäryhmissä mahdollista, on suunniteltava nykyistä enemmän D-vitamiinilla täydennettyjä elintarvikkeita.

The UNCITRAL Model Law on Cross-border Insolvency and its Potential Role in Upholding the Rule of Law

The rule of law is understood to be a core aspect in achieving a stable economy and an ordered society. Without the elements that are inherent in this principle the possibilities of anarchy, unfairness and uncertainty are amplified, which in turn can result in an economy with dramatic fluctuations. In this regard, commentators do not always agree that the rule of law is strictly adhered to in the international legal context. Therefore, this paper will explore one aspect of international regulation and consider whether the UNCITRAL Model Law on Cross-border Insolvency (1997) (‘Model Law’) and its associated Guide to Enactment and Interpretation (2013) contribute to the promotion of the key elements of the rule of law.

Maternal and paternal support for physical activity and healthy eating in preschool children: A cross-sectional study

BACKGROUND Parental support is a key influence on children's health behaviours; however, no previous investigation has simultaneously explored the influence of mothers' and fathers' social support on eating and physical activity in preschool-aged children. This study evaluated the singular and combined effects of maternal and paternal support for physical activity (PA) and fruit and vegetable consumption (FV) on preschoolers' PA and FV. METHODS A random sample comprising 173 parent-child dyads completed validated scales assessing maternal and paternal instrumental support and child PA and FV behaviour. Pearson correlations, controlling for child age, parental age, and parental education, were used to evaluate relationships between maternal and paternal support and child PA and FV. K-means cluster analysis was used to identify families with distinct patterns of maternal and paternal support for PA and FV, and one-way ANOVA examined the impact of cluster membership on child PA and FV. RESULTS Maternal and paternal support for PA were positively associated with child PA (r = 0.37 and r = 0.36, respectively; P < 0.001). Maternal but not paternal support for FV was positively associated with child FV (r = 0.35; P < 0.001). Five clusters characterised groups of families with distinct configurations of maternal and paternal support for PA and FV: 1) above average maternal and paternal support for PA and FV, 2) below average maternal and paternal support for PA and FV, 3) above average maternal and paternal support for PA but below average maternal and paternal support for FV, 4) above average maternal and paternal support for FV but below average maternal and paternal support for PA, and 5) above average maternal support but below average paternal support for PA and FV. Children from families with above average maternal and paternal support for both health behaviours had higher PA and FV levels than children from families with above average support for just one health behaviour, or below average support for both behaviours. CONCLUSIONS The level and consistency of instrumental support from mothers and fathers for PA and FV may be an important target for obesity prevention in preschool-aged children.

Pulsatile flow in tubes of varying cross-sections

The pulsatile flow of an incompressible viscous fluid in a cylindrical tube of varying cross section is investigated for small Reynolds numbers. The solutions consist of a stedy and an oscillatory part. The shear stress distribution on the wall is evaluated and discussed in detail for special geometries like tapered tubes, locally constricted tubes and peristaltic tubes. The existence of separation in the flow field is noticed.

The non-pathogenic Australian rabbit calicivirus RCV-A1 provides temporal and partial cross protection to lethal Rabbit Haemorrhagic Disease Virus infection which is not dependent on antibody titres

The endemic non-pathogenic Australian rabbit calicivirus RCV-A1 is known to provide some cross protection to lethal infection with the closely related Rabbit Haemorrhagic Disease Virus (RHDV). Despite its obvious negative impacts on viral biocontrol of introduced European rabbits in Australia, little is known about the extent and mechanisms of this cross protection. In this study 46 rabbits from a colony naturally infected with RCV-A1 were exposed to RHDV. Survival rates and survival times did not correlate with titres of serum antibodies specific to RCV-A1 or cross reacting to RHDV, but were instead influenced by the time between infection with the two viruses, demonstrating for the first time that the cross protection to lethal RHDV infection is transient. These findings are an important step towards a better understanding of the complex interactions of co-occurring pathogenic and non-pathogenic lagoviruses.

Considering gambling involvement in the understanding of problem gambling: A large cross-sectional study of an Australian population

Instead of regarding a particular type of gambling activity (for example, electronic gambling machines, table games) as an isolated factor for problem gambling, recent research suggests that gambling involvement (for example, as measured by the number of different types of gambling activities played) should also be considered. Using a large sample of the Victorian adult population, this study found that the strength of association between problem gambling and the type of gambling reduced after adjusting for gambling involvement. This finding supports recent research that gambling involvement is an important factor in assessing the risk of problem gambling. The study also provides insights into the measurements of gambling involvement and provides alternative statistical modelling to analyse problem gambling.

Total photoproduction cross section at very high energy

In this paper we apply to the photoproduction total cross section a model we have proposed for purely hadronic processes and which is based on QCD mini-jets and soft gluon re-summation. We compare the predictions of our model with the HERA data as well as with other models. For cosmic rays, our model predicts substantially higher cross sections at TeV energies than models based on factorization, but lower than models based on mini-jets alone, without soft gluons. We discuss the origin of this difference.

Coordination and plasticity in leaf anatomical traits of invasive and native vine species

Premise of the study: Plant invasiveness can be promoted by higher values of adaptive traits (e.g., photosynthetic capacity, biomass accumulation), greater plasticity and coordination of these traits, and by higher and positive relative influence of these functionalities on fitness, such as increasing reproductive output. However, the data set for this premise rarely includes linkages between epidermal–stomatal traits, leaf internal anatomy, and physiological performance.• Methods: Three ecological pairs of invasive vs. noninvasive (native) woody vine species of South-East Queensland, Australia were investigated for trait differences in leaf morphology and anatomy under varying light intensity. The linkages of these traits with physiological performance (e.g., water-use efficiency, photosynthesis, and leaf construction cost) and plant adaptive traits of specific leaf area, biomass, and relative growth rates were also explored.• Key results: Except for stomatal size, mean leaf anatomical traits differed significantly between the two groups. Plasticity of traits and, to a very limited extent, their phenotypic integration were higher in the invasive relative to the native species. ANOVA, ordination, and analysis of similarity suggest that for leaf morphology and anatomy, the three functional strategies contribute to the differences between the two groups in the order phenotypic plasticity > trait means > phenotypic integration.• Conclusions: The linkages demonstrated in the study between stomatal complex/gross anatomy and physiology are scarce in the ecological literature of plant invasiveness, but the findings suggest that leaf anatomical traits need to be considered routinely as part of weed species assessment and in the worldwide leaf economic spectrum.