Meal ingestion provokes entry of lipoproteins containing fat from the previous meal: possible metabolic implications

Background: Prolonged and exaggerated postprandial plasma triacylglycerol (TAG) concentrations are considered as an independent risk factor for coronary artery disease. Western populations eat many meals at regular intervals, and can be in a postprandial state for at least 17h of a 24h period. After consuming 2 meals an early plasma TAG peak has been observed after the second meal, the origin of which is unclear. Aim of the study: To test the hypothesis that the early TAG peak observed following sequential meals was of intestinal origin and represented fat derived from the previous meal. Methods: Postprandial plasma lipaemic responses of 17 healthy postmenopausal women were studied by giving a test breakfast followed by a lunch. Watermiscible retinyl palmitate (RP) was added to the breakfast, but not the lunch test meal. Plasma TAG, retinyl esters (RE) and apo B-48 were determined for a 10h period following breakfast. Results: In response to the test meals, RE, apo B-48 and TAG showed multiple peaks. Despite omission of RP from the lunch, RE showed an early peak response after ingestion of lunch in 15 of 17 subjects. The peak response after lunch of all three markers appeared significantly earlier compared with their respective peak responses after the breakfast (P < 0.0001). The area of RE response after lunch was significantly correlated with the RE lipaemic response to the breakfast (r = 0.67; P < 0.004) and to the fasting TAG concentration (r = 0.48; P < 0.05). Conclusions: Since the lunch did not contain RP, the distinctive second influx of RE after lunch was believed to have originated from the breakfast. This, together with the fact that all three markers showed an earlier response to the lunch than the breakfast, supports the view that ingestion of a second meal provokes entry of fat from the previous meal, from an as yet unidentified site (gut, enterocytes, lymph). The results indicate that the degree of TAG "storage" from previous meals might be a function of TAG tolerance and provide a possible site of regulation of the entry of fat into the systemic circulation.

Localization to the nucleolus is a common feature of coronavirus nucleoproteins and the protein may disrupt host cell division

The subcellular localization of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) (group I and group II coronaviruses, respectively) nucleoproteins (N proteins) were examined by confocal microscopy. The proteins were shown to localize either to the cytoplasm alone or to the cytoplasm and a structure in the nucleus. This feature was confirmed to be the nucleolus by using specific antibodies to nucleolin, a major component of the nucleolus, and by confocal microscopy to image sections through a cell expressing N protein. These findings are consistent with our previous report for infectious bronchitis virus (group III coronavirus) (J. A. Hiscox et al., J. Virol. 75:506-512, 2001), indicating that nucleolar localization of the N protein is a common feature of the coronavirus family and is possibly of functional significance. Nucleolar localization signals were identified in the domain III region of the N protein from all three coronavirus groups, and this suggested that transport of N protein to the nucleus might be an active process. In addition, our results suggest that the N protein might function to disrupt cell division. Thus, we observed that approximately 30% of cells transfected with the N protein appeared to be undergoing cell division. The most likely explanation for this is that the N protein induced a cell cycle delay or arrest, most likely in the G2/M phase. In a fraction of transfected cells expressing coronavirus N proteins, we observed multinucleate cells and dividing cells with nucleoli (which are only present during interphase). These findings are consistent with the possible inhibition of cytokinesis in these cells.

Spatio-temporal variation in predation by urban domestic cats (Felis catus) and the acceptability of possible management actions in the UK

Urban domestic cat (Felis catus) populations can attain exceedingly high densities and are not limited by natural prey availability. This has generated concerns that they may negatively affect prey populations, leading to calls for management. We enlisted cat-owners to record prey returned home to estimate patterns of predation by free-roaming pets in different localities within the town of Reading, UK and questionnaire surveys were used to quantify attitudes to different possible management strategies. Prey return rates were highly variable: only 20% of cats returned ≥4 dead prey annually. Consequently, approximately 65% of owners received no prey in a given season, but this declined to 22% after eight seasons. The estimated mean predation rate was 18.3 prey cat−1 year−1 but this varied markedly both spatially and temporally: per capita predation rates declined with increasing cat density. Comparisons with estimates of the density of six common bird prey species indicated that cats killed numbers equivalent to adult density on c. 39% of occasions. Population modeling studies suggest that such predation rates could significantly reduce the size of local bird populations for common urban species. Conversely, most urban residents did not consider cat predation to be a significant problem. Collar-mounted anti-predation devices were the only management action acceptable to the majority of urban residents (65%), but were less acceptable to cat-owners because of perceived risks to their pets; only 24% of cats were fitted with such devices. Overall, cat predation did appear to be of sufficient magnitude to affect some prey populations, although further investigation of some key aspects of cat predation is warranted. Management of the predation behavior of urban cat populations in the UK is likely to be challenging and achieving this would require considerable engagement with cat owners.

The mysterious presence of a 5-methylcytosine oxidase in the Drosophila genome: Possible explanations

5-methylcytosine is an important epigenetic modification involved in gene control in vertebrates and many other complex living organisms. Its presence in Drosophila has been a matter of debate and recent bisulfite sequencing studies of early-stage fly embryos have concluded that the genome of Drosophila is essentially unmethylated. However, as we outline here, the Drosophila genome harbors a well-conserved homolog of the TET protein family. The mammalian orthologs TET1/2/3 are known to convert 5-methylcytosine into 5-hydroxymethylcytosine. We discuss several possible explanations for these seemingly contradictory findings. One possibility is that the 2 modified cytosine bases are generated in Drosophila only at certain developmental stages and in a cell type-specific manner during neurogenesis. Alternatively, Drosophila Tet and its mammalian homologs may carry out catalytic activity-independent functions, and the possibility that these proteins may oxidize 5-methylcytosine in RNA created by the methyltransferase Dnmt2 should also be strongly considered.

Obesity, diabetes and longevity in the Gulf: is there a Gulf Metabolic Syndrome?

The Gulf is experiencing a pandemic of lifestyle-induced obesity and type 2 diabetes mellitus (T2DM), with rates exceeding 50 and 30%, respectively. It is likely that T2DM represents the tip of a very large metabolic syndrome iceberg, which precedes T2DM by many years and is associated with abnormal/ectopic fat distribution, pathological systemic oxidative stress and inflammation. However, the definitions are still evolving with the role of different fat depots being critical. Hormetic stimuli, which include exercise, calorie restriction, temperature extremes, dehydration and even some dietary components (such as plant polyphenols), may well modulate fat deposition. All induce physiological levels of oxidative stress, which results in mitochondrial biogenesis and increased anti-oxidant capacity, improving metabolic flexibility and the ability to deal with lipids. We propose that the Gulf Metabolic Syndrome results from an unusually rapid loss of hormetic stimuli within an epigenetically important time frame of 2-3 generations. Epigenetics indicates that thriftiness can be programmed by the environment and passed down through several generations. Thus this loss of hormesis can result in continuation of metabolic inflexibility, with mothers exposing the foetus to a milieu that perpetuates a stressed epigenotype. As the metabolic syndrome increases oxidative stress and reduces life expectancy, a better descriptor may therefore be the Lifestyle-Induced Metabolic Inflexibility and accelerated AGEing syndrome – LIMIT-AGE. As life expectancy in the Gulf begins to fall, with perhaps a third of this life being unhealthy – including premature loss of sexual function, it is vital to detect evidence of this condition as early in life as possible. One effective way to do this is by detecting evidence of metabolic inflexibility by studying body fat content and distribution by magnetic resonance (MR). The Gulf Metabolic Syndrome thus represents an accelerated form of the metabolic syndrome induced by the unprecedented rapidity of lifestyle change in the region, the stress of which is being passed from generation to generation and may be accumulative. The fundamental cause is probably due to a rapid increase in countrywide wealth. This has benefited most socioeconomic groups, resulting in the development of an obesogenic environment as the result of the rapid adoption of Western labour saving and stress relieving devices (e.g. cars and air conditioning), as well as the associated high calorie diet.

Long-term variations in the magnetic field of the Sun and possible implications for terrestrial climate

Recent studies of the variation of geomagnetic activity over the past 140 years have quantified the "coronal source" or "open" magnetic flux F-s that leaves the solar atmosphere and enters the heliosphere and have shown that it has risen, on average, by 34% since 1963 and by 140% since 1900. This variation is reflected in studies of the heliospheric field using isotopes deposited in ice sheets and meteorites by the action of galactic comic rays. The variation has also been reproduced using a model that demonstrates how the open flux accumulates and decays, depending on the rate of flux emergence in active regions and on the length of the solar cycle. The cosmic ray flux at energies > 3 GeV is found to have decayed by about 15% during the 20(th) century (and by about 4% at > 13 GeV). We show that the changes in the open flux do reflect changes in the photospheric and sub-surface field which offers an explanation of why open flux appears to be a good proxy for solar irradiance extrapolation. Correlations between F-s, solar cycle length, L, and 11-year smoothed sunspot number, R-11, explain why the various irradiance reconstructions for the last 150 years are similar in form. Possible implications of the inferred changes in cosmic ray flux and irradiance for global temperatures on Earth are discussed.

"The past is still right here in the present": second-generation Bajan-Brit transnational migrants' views on issues relating to race and colour class

This paper deals with second-generation Barbadians or 'Bajan-Brits', who have decided to,return' to the birthplace of their parents, focusing on their reactions to matters relating to race relations and racialised identities. The importance of race and the operation of the 'colour-class' system in the Caribbean are established at the outset. Based on fifty-two qualitative in-depth interviews, the paper initially considers the positive things that the second-generation migrants report about living in a majority black country and the salience of such racial affirmation as part of their migration process. The paper then presents an analysis of the narratives provided by the Bajan-Brits concerning their reactions to issues relating to race relations in Barbadian society. The impressions of the young returnees provide clear commentaries on what are regarded as (i) the 'acceptance of white hegemony' within Barbadian society, (ii) the occurrence of de facto 'racial segregation, (iii) perceptions of the 'existence of apartheid, and (iv) 'the continuation of slavery'. The account then turns to the contemporary operation of the colour-class system. It is concluded that, despite academic arguments that the colour-class dimension has to be put to one side as the principal dimension of social stratification in the contemporary Caribbean, the second-generation migrants are acutely aware of the continued existence and salience of such gradations within society. Thus, the analysis not only serves to emphasise the continued importance of racial-based stratification in the contemporary Caribbean, but also speaks of the 'hybrid' and 'in-between' racialised identities of the second-generation migrants.

Empirical Orthogonal Functions: The Medium is the Message

Empirical orthogonal function (EOF) analysis is a powerful tool for data compression and dimensionality reduction used broadly in meteorology and oceanography. Often in the literature, EOF modes are interpreted individually, independent of other modes. In fact, it can be shown that no such attribution can generally be made. This review demonstrates that in general individual EOF modes (i) will not correspond to individual dynamical modes, (ii) will not correspond to individual kinematic degrees of freedom, (iii) will not be statistically independent of other EOF modes, and (iv) will be strongly influenced by the nonlocal requirement that modes maximize variance over the entire domain. The goal of this review is not to argue against the use of EOF analysis in meteorology and oceanography; rather, it is to demonstrate the care that must be taken in the interpretation of individual modes in order to distinguish the medium from the message.

Choosing the number of doses and the cohort size for phase I dose-escalation studies

This paper reviews Bayesian procedures for phase 1 dose-escalation studies and compares different dose schedules and cohort sizes. The methodology described is motivated by the situation of phase 1 dose-escalation studiesin oncology, that is, a single dose administered to each patient, with a single binary response ("toxicity"' or "no toxicity") observed. It is likely that a wider range of applications of the methodology is possible. In this paper, results from 10000-fold simulation runs conducted using the software package Bayesian ADEPT are presented. Four designs were compared under six scenarios. The simulation results indicate that there are slight advantages of having more dose levels and smaller cohort sizes.

The placenta is simply a neuroendocrine parasite

This paper will document the early scientific observations that kindled my neuroendocrinological interest in pre-eclampsia, a life-threatening disease that affects both mother and baby. My interest in this subject started with the placental origin of melanotrophin activity, moving on, through corticotrophin-releasing factor and its binding protein, to a tachykinin modified specifically in the placenta by phosphocholine, a post-translational moiety normally used by parasites to avoid immune surveillance and rejection. This work may finally have led to an understanding of the identity of the elusive placental factor that, whilst attempting to compensate for the poor implantation of the placenta, causes the many symptoms seen in the mother during pre-eclampsia.

The use of dead-end and cross-flow nanofiltration to purify prebiotic oligosaccharides from reaction mixtures

Nanofiltration (NF) of model sugar solutions and commercial oligosaccharide mixtures were studied in both dead-end and cross-flow modes. Preliminary trials, with a dead-end filtration cell, demonstrated the feasibility of fractionating monosaccharides from disaccharides and oligosaccharides in mixtures, using loose nanofiltration (NF-CA-50, NF-TFC-50) membranes. During the nanofiltration purification of a commercial oligosaccharide mixture, yields of 19% (w w-1) for the monosaccharides and 88% (w w-1) for di, and oligosaccharides were obtained for the NF-TFC-50 membrane after four filtration steps, indicating that removal of the monosaccharides is possible, with only minor losses of the oligosaccharide content of the mixture. The effects of pressure, feed concentration, and filtration temperature were studied in similar experiments carried out in a cross-flow system, in full recycle mode of operation. The rejection rates of the sugar components increased with increasing pressure, and decreased with both increasing total sugar concentration in the feed and increasing temperature. Continuous diafiltration (CD) purification of model sugar solutions and commercial oligosaccharide mixtures using NF-CA-50 (at 25oC) and DS-5-DL (at 60oC) membranes, gave yield values of 14 to 18% for the monosaccharide, 59 to 89% for the disaccharide and 81 to 98% for the trisaccharide present in the feed. The study clearly demonstrates the potential of cross flow nanofiltration in the purification of oligosaccharide mixtures from the contaminant monosaccharides.