Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia

Aims/hypothesis Recent evidence suggests that a particular gut microbial community may favour occurrence of the metabolic diseases. Recently, we reported that high-fat (HF) feeding was associated with higher endotoxaemia and lower Bifidobacterium species (spp.) caecal content in mice. We therefore tested whether restoration of the quantity of caecal Bifidobacterium spp. could modulate metabolic endotoxaemia, the inflammatory tone and the development of diabetes. Methods Since bifidobacteria have been reported to reduce intestinal endotoxin levels and improve mucosal barrier function, we specifically increased the gut bifidobacterial content of HF-diet-fed mice through the use of a prebiotic (oligofructose [OFS]). Results Compared with normal chow-fed control mice, HF feeding significantly reduced intestinal Gram-negative and Gram-positive bacteria including levels of bifidobacteria, a dominant member of the intestinal microbiota, which is seen as physiologically positive. As expected, HF-OFS-fed mice had totally restored quantities of bifidobacteria. HF-feeding significantly increased endotoxaemia, which was normalised to control levels in HF-OFS-treated mice. Multiple-correlation analyses showed that endotoxaemia significantly and negatively correlated with Bifidobacterium spp., but no relationship was seen between endotoxaemia and any other bacterial group. Finally, in HF-OFS-treated-mice, Bifidobacterium spp. significantly and positively correlated with improved glucose tolerance, glucose-induced insulin secretion and normalised inflammatory tone (decreased endotoxaemia, plasma and adipose tissue proinflammatory cytokines). Conclusions/interpretation Together, these findings suggest that the gut microbiota contribute towards the pathophysiological regulation of endotoxaemia and set the tone of inflammation for occurrence of diabetes and/or obesity. Thus, it would be useful to develop specific strategies for modifying gut microbiota in favour of bifidobacteria to prevent the deleterious effect of HF-diet-induced metabolic diseases.

Agonist-selective, receptor-specific interaction of human P-2Y receptors with beta-arrestin-1 and-2

Interaction of G-protein-coupled receptors with beta-arrestins is an important step in receptor desensitization and in triggering "alternative" signals. By means of confocal microscopy and fluorescence resonance energy transfer, we have investigated the internalization of the human P2Y receptors 1, 2, 4, 6, 11, and 12 and their interaction with beta-arrestin-1 and -2. Co-transfection of each individual P2Y receptor with beta-arrestin-1-GFP or beta-arrestin-2-YFP into HEK-293 cells and stimulation with the corresponding agonists resulted in a receptor-specific interaction pattern. The P2Y(1) receptor stimulated with ADP strongly translocated beta-arrestin-2-YFP, whereas only a slight translocation was observed for beta-arrestin-1-GFP. The P2Y(4) receptor exhibited equally strong translocation for beta-arrestin-1-GFP and beta-arrestin-2YFP when stimulated with UTP. The P2Y(6), P2Y(11), and P2Y(12) receptor internalized only when GRK2 was additionally cotransfected, but beta-arrestin translocation was only visible for the P2Y(6) and P2Y(11) receptor. The P2Y(2) receptor showed a beta-arrestin translocation pattern that was dependent on the agonist used for stimulation. UTP translocated beta-arrestin-1-GFP and beta-arrestin-2-YFP equally well, whereas ATP translocated beta-arrestin-1-GFP to a much lower extent than beta-arrestin2- YFP. The same agonist-dependent pattern was seen in fluorescence resonance energy transfer experiments between the fluorescently labeled P2Y(2) receptor and beta-arrestins. Thus, the P2Y(2) receptor would be classified as a class A receptor when stimulated with ATP or as a class B receptor when stimulated with UTP. The ligand-specific recruitment of beta-arrestins by ATP and UTP stimulation of P2Y(2) receptors was further found to result in differential stimulation of ERK phosphorylation. This suggests that the two different agonists induce distinct active states of this receptor that show differential interactions with beta-arrestins.

Characterisation of cyclin D1 down-regulation in coronavirus infected cells

The positive strand RNA coronavirus, infectious bronchitis virus (IBV), induces a G2/M phase arrest and reduction in the G1 and G1/S phase transition regulator cyclin D1. Quantitative real-time RT-PCR and Western blot analysis demonstrated that cyclin D1 was reduced post-transcriptionally within infected cells independently of the cell-cycle stage at the time of infection. Confocal microscopy revealed that cyclin D1 decreased in IBV-infected cells as infection progressed and inhibition studies indicated that a population of cyclin D1 could be targeted for degradation by a virus mediated pathway. In contrast to the SARS-coronavirus, IBV nucleocapsid protein did not interact with cyclin D1. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Huntington's disease patients have selective problems with insight

The objective of this study was to determine insight in patients with Huntington's disease (HD) by contrasting patients' ability to rate their own behavior with their ability to rate a person other than themselves. HD patients and carers completed the Dysexecutive Questionnaire (DEX), rating themselves and each other at two time points. The temporal stability of these ratings was initially examined using these two time points since there is no published test-retest reliability of the DEX with this Population to date. This was followed by a comparison of patients' self-ratings and carer's independent ratings of patients by performing correlations with patients' disease variables, and in exploratory factor analysis was conducted on both sets of ratings. The DEX showed good test-retest reliability, with patients consistently and persistently underestimating the degree of their dysexecutive behavior, but not that of their carers. Patients' self-ratings and caters' ratings of patients both showed that dysexecutive behavior in HD can be fractionated into three underlying components (Cognition, Self-regulation, Insight), and the relative ranking of these factors was similar for both data sets. HD patients consistently underestimated the extent of only their own dysexecutive behaviors relative to carers' ratings by 26%, but were similar in ascribing ranks to the components of dysexecutive behavior. (c) 2005 Movement Disorder Society.

Divided attention, selective attention and drawing: processing preferences in Williams syndrome are dependent on the task administered

The visuo-spatial abilities of individuals with Williams syndrome (WS) have consistently been shown to be generally weak. These poor visuo-spatial abilities have been ascribed to a local processing bias by some [R. Rossen, E.S. Klima, U. Bellugi, A. Bihrle, W. Jones, Interaction between language and cognition: evidence from Williams syndrome, in: J. Beitchman, N. Cohen, M. Konstantareas, R. Tannock (Eds.), Language, Learning and Behaviour disorders: Developmental, Behavioural and Clinical Perspectives, Cambridge University Press, New York, 1996, pp. 367-392] and conversely, to a global processing bias by others [Psychol. Sci. 10 (1999) 453]. In this study, two identification versions and one drawing version of the Navon hierarchical processing task, a non-verbal task, were employed to investigate this apparent contradiction. The two identification tasks were administered to 21 individuals with WS, 21 typically developing individuals, matched by non-verbal ability, and 21 adult participants matched to the WS group by mean chronological age (CA). The third, drawing task was administered to the WS group and the typically developing (TD) controls only. It was hypothesised that the WS group would show differential processing biases depending on the type of processing the task was measuring. Results from two identification versions of the Navon task measuring divided and selective attention showed that the WS group experienced equal interference from global to local as from local to global levels, and did not show an advantage of one level over another. This pattern of performance was broadly comparable to that of the control groups. The third task, a drawing version of the Navon task, revealed that individuals with WS were significantly better at drawing the local form in comparison to the global figure, whereas the typically developing control group did not show a bias towards either level. In summary, this study demonstrates that individuals with WS do not have a local or a global processing bias when asked to identify stimuli, but do show a local bias in their drawing abilities. This contrast may explain the apparently contrasting findings from previous studies. (C) 2002 Elsevier Science Ltd. All rights reserved.

The role of spectral- and temporal-envelope room-acoustic cues in auditory selective attention

Listeners can attend to one of several simultaneous messages by tracking one speaker’s voice characteristics. Using differences in the location of sounds in a room, we ask how well cues arising from spatial position compete with these characteristics. Listeners decided which of two simultaneous target words belonged in an attended “context” phrase when it was played simultaneously with a different “distracter” context. Talker difference was in competition with position difference, so the response indicates which cue‐type the listener was tracking. Spatial position was found to override talker difference in dichotic conditions when the talkers are similar (male). The salience of cues associated with differences in sounds, bearings decreased with distance between listener and sources. These cues are more effective binaurally. However, there appear to be other cues that increase in salience with distance between sounds. This increase is more prominent in diotic conditions, indicating that these cues are largely monaural. Distances between spectra calculated using a gammatone filterbank (with ERB‐spaced CFs) of the room’s impulse responses at different locations were computed, and comparison with listeners’ responses suggested some slight monaural loudness cues, but also monaural “timbre” cues arising from the temporal‐ and spectral‐envelope differences in the speech from different locations.

Selective biodegradation of keratin matrix in feather rachis reveals classic bioengineering

Flight necessitates that the feather rachis is extremely tough and light. Yet, the crucial filamentous hierarchy of the rachis is unknown—study hindered by the tight chemical bonding between the filaments and matrix. We used novel microbial biodegradation to delineate the fibres of the rachidial cortex in situ. It revealed the thickest keratin filaments known to date (factor >10), approximately 6 µm thick, extending predominantly axially but with a small outer circumferential component. Near-periodic thickened nodes of the fibres are staggered with those in adjacent fibres in two- and three-dimensional planes, creating a fibre–matrix texture with high attributes for crack stopping and resistance to transverse cutting. Close association of the fibre layer with the underlying ‘spongy’ medulloid pith indicates the potential for higher buckling loads and greater elastic recoil. Strikingly, the fibres are similar in dimensions and form to the free filaments of the feather vane and plumulaceous and embryonic down, the syncitial barbules, but, identified for the first time in 140+ years of study in a new location—as a major structural component of the rachis. Early in feather evolution, syncitial barbules were consolidated in a robust central rachis, definitively characterizing the avian lineage of keratin.

Signal detection for orthogonal space-time block coding over time-selective fading channels: the H(i) systems

One major assumption in all orthogonal space-time block coding (O-STBC) schemes is that the channel remains static over the length of the code word. However, time-selective fading channels do exist, and in such case conventional O-STBC detectors can suffer from a large error floor in the high signal-to-noise ratio (SNR) cases. As a sequel to the authors' previous papers on this subject, this paper aims to eliminate the error floor of the H(i)-coded O-STBC system (i = 3 and 4) by employing the techniques of: 1) zero forcing (ZF) and 2) parallel interference cancellation (PIC). It is. shown that for an H(i)-coded system the PIC is a much better choice than the ZF in terms of both performance and computational complexity. Compared with the, conventional H(i) detector, the PIC detector incurs a moderately higher computational complexity, but this can well be justified by the enormous improvement.

Signal detection for orthogonal space-time block coding over time-selective fading channels: a PIC approach for the Gi Systems

One major assumption in all orthogonal space-time block coding (O-STBC) schemes is that the channel remains static over the entire length of the codeword. However, time selective fading channels do exist, and in such case the conventional O-STBC detectors can suffer from a large error floor in the high signal-to-noise ratio (SNR) cases. This paper addresses such an issue by introducing a parallel interference cancellation (PIC) based detector for the Gi coded systems (i=3 and 4).

Orthogonal space-time block coding over time-selective fading channels: a PIC detector for the Gi systems

All the orthogonal space-time block coding (O-STBC) schemes are based on the following assumption: the channel remains static over the entire length of the codeword. However, time selective fading channels do exist, and in many cases the conventional O-STBC detectors can suffer from a large error floor in the high signal-to-noise ratio (SNR) cases. This paper addresses such an issue by introducing a parallel interference cancellation (PIC) based detector for the Gi coded systems (i=3 and 4).

Space-time block coding for four transmit antennas over time-selective fading channels: orthogonal or non-orthogonal design?

The paper deals with an issue in space time block coding (STBC) design. It considers whether, over a time-selective channel, orthogonal STBC (O-STBC) or non-orthogonal STBC (NO-STBC) performs better. It is shown that, under time-selectiveness, once vehicle speed has risen above a certain value, NO-STBC always outperforms O-STBC across the whole SNR range. Also, considering that all existing NO-STBC schemes have been investigated under quasi-static channels only, a new simple receiver is derived for the NO-STBC system under time-selective channels.