Silyl-Modified Analogues of 2-Tritylpyrrolidine: Synthesis and Applications in Asymmetric Organocatalysis

Silicon-based organocatalysts: In an effort to study the effects of substituting carbon by silicon within the catalyst backbone, we developed an efficient synthesis of (S)-2-triphenylsilylpyrrolidine [(S)-2]. The evaluation of (S)-2 against its carbon analogue (S)-1 in two organocatalytic reactions is complemented by computational studies.

The influence of pomegranate by-product and punicalagins on selected groups of human intestinal microbiota.

We have examined the gut bacterial metabolism of pomegranate by-product (POMx) and major pomegranate polyphenols, punicalagins, using pH-controlled, stirred, batch culture fermentation systems reflective of the distal region of the human large intestine. Incubation of POMx or punicalagins with faecal bacteria resulted in formation of the dibenzopyranone-type urolithins. The time course profile confirmed the tetrahydroxylated urolithin D as the first product of microbial transformation, followed by compounds with decreasing number of phenolic hydroxy groups: the trihydroxy analogue urolithin C and dihydroxylated urolithin A. POMx exposure enhanced the growth of total bacteria, Bifidobacterium spp. and Lactobacillus spp., without influencing the Clostridium coccoides–Eubacterium rectale group and the C. histolyticum group. In addition, POMx increased concentrations of short chain fatty acids (SCFA) viz. acetate, propionate and butyrate in the fermentation medium. Punicalagins did not affect the growth of bacteria or production of SCFA. The results suggest that POMx oligomers, composed of gallic acid, ellagic acid and glucose units, may account for the enhanced growth of probiotic bacteria.

Gene expression profiling of human hibernating myocardium: Increased expression of B-type natriuretic peptide and proenkephalin in hypocontractile vs normally-contracting regions of the heart

A greater understanding of the molecular basis of hibernating myocardium may assist in identifying those patients who would most benefit from revascularization. Paired heart biopsies were taken from hypocontractile and normally-contracting myocardium (identified by cardiovascular magnetic resonance) from 6 patients with chronic stable angina scheduled for bypass grafting. Gene expression profiles of hypocontractile and normally-contracting samples were compared using Affymetrix microarrays. The data for patients with confirmed hibernating myocardium were analysed separately and a different, though overlapping, set (up to 380) of genes was identified which may constitute a molecular fingerprint for hibernating myocardium. The expression of B-type natriuretic peptide (BNP) was increased in hypocontractile relative to normally-contracting myocardium. The expression of BNP correlated most closely with the expression of proenkephalin and follistatin 3, which may constitute additional heart failure markers. Our data illustrate differential gene expression in hypocontractile and/hibernating myocardium relative to normally-contracting myocardium within individual human hearts. Changes in expression of these genes, including increased relative expression of natriuretic and other factors, may constitute a molecular signature for hypocontractile and/or hibernating myocardium.

The quantitation of lipoprotein lipase mRNA in biopsies of human adipose tissue, using the polymerase chain reaction, and the effect of increased consumption of n-3 polyunsaturated fatty acids

Objective: To examine the effects of the consumption of fish oils on the gene expression of lipoprotein lipase (LPL, EC 3.1.1.34) in human adipose tissue. In order to measure LPL mRNA in adipose tissue samples obtained by needle biopsy from human volunteers a competitive, reverse transcriptase PCR (RT-PCR) protocol was developed. Design: A randomised controlled, single blind cross over dietary study which compared the effects of a low level n-3 polyunsaturated fatty acids (PUFA) using normal foods enriched with eicosapentaenoic (EPA) and docosahexaenoic (DHA) (test diet), with non-enriched but otherwise identical foods (control). The diets were consumed for a period of 22 d with a wash out period of 5 months between the diets. Setting: Free-living individuals associated with the University of Surrey. Subjects: Six male subjects with a mean (±sd) age of 51.2±3.6 y were recruited. Major Outcome Measures: Pre-and postprandial blood samples were taken for the measurement of triacylglycerol (TAG), postheparin LPL activity and adipose tissue samples for the measurement of LPL mRNA levels. Results: Mean LPL expression values were 4.12´105 molecules of LPL mRNA per ng total RNA on the control diet and 4.60´105 molecules of LPL mRNA per ng total RNA on the n-3 PUFA enriched (test) diet. There was no significant difference between the levels of LPL expression following each diet, consistent with the lack of change in TAG levels in response to increased dietary n-3 PUFA intake. However, the change in LPL expression (Test-Control diet) correlated significantly with the change in fasting TAG levels (P=0.03, R=-0.87 and R2=0.75) and with the total area under the TAG-time response curve (P=0.003, R=-0.96 and R2=0.92) in individuals. Conclusions: These findings, although based on a small number of subjects, suggest that LPL expression may be a determinant of plasma TAG levels. The development of this methodology should allow further elucidation of the effects of dietary manipulation and disease processes on lipid clearance and regulation in human subjects.

Hardware development of the Yorick series of active vision systems

This paper presents a review of the design and development of the Yorick series of active stereo camera platforms and their integration into real-time closed loop active vision systems, whose applications span surveillance, navigation of autonomously guided vehicles (AGVs), and inspection tasks for teleoperation, including immersive visual telepresence. The mechatronic approach adopted for the design of the first system, including head/eye platform, local controller, vision engine, gaze controller and system integration, proved to be very successful. The design team comprised researchers with experience in parallel computing, robot control, mechanical design and machine vision. The success of the project has generated sufficient interest to sanction a number of revisions of the original head design, including the design of a lightweight compact head for use on a robot arm, and the further development of a robot head to look specifically at increasing visual resolution for visual telepresence. The controller and vision processing engines have also been upgraded, to include the control of robot heads on mobile platforms and control of vergence through tracking of an operator's eye movement. This paper details the hardware development of the different active vision/telepresence systems.

Adipose tissue metabolism in pregnancy: the lipolytic effect of human placental lactogen

In vitro adipose tissue lipolysis was investigated in pregnant and non-pregnant women. Basal and hormone-stimulated rates of lipolysis were significantly higher in the pregnant group. Human placental lactogen (HPL) was shown to be lipolytic on adipose tissue from both pregnant and non-pregnant women; the response being more marked in the pregnant group. We postulate that HPL is responsible for this increased lipolytic sensitivity in pregnancy, the result of which is the elevation in levels of plasma free fatty acids in the third trimester.

Intact automatic imitation of human and robot actions in autism spectrum disorders

The existence of a specialized imitation module in humans is hotly debated. Studies suggesting a specific imitation impairment in individuals with autism spectrum disorders (ASD) support a modular view. However, the voluntary imitation tasks used in these studies (which require socio-cognitive abilities in addition to imitation for successful performance) cannot support claims of a specific impairment. Accordingly, an automatic imitation paradigm (a ‘cleaner’ measure of imitative ability) was used to assess the imitative ability of 16 adults with ASD and 16 non-autistic matched control participants. Participants performed a prespecified hand action in response to observed hand actions performed either by a human or a robotic hand. On compatible trials the stimulus and response actions matched, while on incompatible trials the two actions did not match. Replicating previous findings, the Control group showed an automatic imitation effect: responses on compatible trials were faster than those on incompatible trials. This effect was greater when responses were made to human than to robotic actions (‘animacy bias’). The ASD group also showed an automatic imitation effect and a larger animacy bias than the Control group. We discuss these findings with reference to the literature on imitation in ASD and theories of imitation.