Comparative composition of bacteria in the human intestinal microflora during remission and active ulcerative colitis

Ulcerative colitis is a severe, relapsing and remitting disease of the human large intestine characterised by inflammation of the mucosa and submucosa. The main site of disease is the sigmoid/rectal region of the large bowel but the aetiology remains unknown. There is considerable evidence to indicate that the components of the resident colonic microflora can play an important role in initiation of the disease. The present study was aimed at characterising the faecal microflora of ulcerative colitis patients in remission and active phases to determine profile differences. Faecal samples were obtained from 12 patients, 6 with active colitis and 6 in remission. The samples were analysed for populations of lactobacilli, bifidobacteria, clostridia, bacteroides, sulphate-reducing bacteria (SRB) and total bacteria using culture independent fluorescence in situ hybridisation (FISH). Lactobacillus-specific denaturing gradient gel electrophoresis (DGGE) was then performed to compare the species present. Numbers of lactobacilli were significantly lower (p<0.05) during the active phase of the disease but the other populations tested did not differ. DGGE analysis revealed that Lactobacillus salivarus, Lactobacillus manihotivorans and Pediococcus acidilactici were present in remission, but not during active inflammation. These results imply that a reduction in intestinal Lactobacillus species may be important in the initiation of ulcerative colitis.

How active gaze informs the hand in sequential pointing movements

Visual information is vital for fast and accurate hand movements. It has been demonstrated that allowing free eye movements results in greater accuracy than when the eyes maintain centrally fixed. Three explanations as to why free gaze improves accuracy are: shifting gaze to a target allows visual feedback in guiding the hand to the target (feedback loop), shifting gaze generates ocular-proprioception which can be used to update a movement (feedback-feedforward), or efference copy could be used to direct hand movements (feedforward). In this experiment we used a double-step task and manipulated the utility of ocular-proprioceptive feedback from eye to head position by removing the second target during the saccade. We confirm the advantage of free gaze for sequential movements with a double-step pointing task and document eye-hand lead times of approximately 200 ms for both initial movements and secondary movements. The observation that participants move gaze well ahead of the current hand target dismisses foveal feedback as a major contribution. We argue for a feedforward model based on eye movement efference as the major factor in enabling accurate hand movements. The results with the double-step target task also suggest the need for some buffering of efference and ocular-proprioceptive signals to cope with the situation where the eye has moved to a location ahead of the current target for the hand movement. We estimate that this buffer period may range between 120 and 200 ms without significant impact on hand movement accuracy.

Methylxanthines are the psycho-pharmacologically active constituents of chocolate

Rationale: Liking, cravings and addiction for chocolate ("chocoholism") are often explained through the presence of pharmacologically active compounds. However, mere "presence" does not guarantee psycho-activity. Objectives: Two double-blind, placebo-controlled studies measured the effects on cognitive performance and mood of the amounts of cocoa powder and methylxanthines found in a 50 g bar of dark chocolate. Methods: In study 1, participants (n=20) completed a test battery once before and twice after treatment administration. Treatments included 11.6 g cocoa powder and a caffeine and theobromine combination (19 and 250 mg, respectively). Study 2 (n=22) comprised three post-treatment test batteries and investigated the effects of "milk" and "dark" chocolate levels of these methylxanthines. The test battery consisted of a long duration simple reaction time task, a rapid visual information processing task, and a mood questionnaire. Results: Identical improvements on the mood construct "energetic arousal" and cognitive function were found for cocoa powder and the caffeine+theobromine combination versus placebo. In chocolate, both "milk chocolate" and "dark chocolate" methylxanthine doses improved cognitive function compared with "white chocolate". The effects of white chocolate did not differ significantly from those of water. Conclusion: A normal portion of chocolate exhibits psychopharmacological activity. The identical profile of effects exerted by cocoa powder and its methylxanthine constituents shows this activity to be confined to the combination of caffeine and theobromine. Methylxanthines may contribute to the popularity of chocolate; however, other attributes are probably much more important in determining chocolate's special appeal and in explaining related self-reports of chocolate cravings and "chocoholism".

Effects of active information processing on the understanding of risk information

Two experiments investigated effects of active processing of risk information on participants' understanding and judgments. It was hypothesized that more active processing would lead to better understanding and differences in affective judgments (e.g. increased satisfaction and reduced perceived risk to health). In both experiments participants were given a written scenario about their being prescribed a fictitious medication. This medication was said to cause side effects in 2% of people who took it. Before answering a series of written questions, participants in the active conditions of both experiments were asked to carry out a reflective task (portraying the size of risk on a bar chart in Experiment 1 and answering a reflective question in Experiment 2). The results showed that active participants rated the likelihood of experiencing possible side effects significantly lower than passive participants (Experiment 1), and that active participants were significantly more satisfied with the information and judged perceived risk to health from taking the medication significantly lower than passive participants (Experiment 2). In both experiments, active participants were significantly more correct in their probability and frequency estimates. The studies demonstrate that active processing of risk information leads to improved understanding of the information given. This has important implications for risk communication. In the context of health, better understanding should lead to improved decision-making and health outcomes. Copyright (C) 2004 John Wiley Sons, Ltd.

Semantic organization to enhance active learning based on distributed multimedia educational resources

In order to organize distributed educational resources efficiently, to provide active learners an integrated, extendible and cohesive interface to share the dynamically growing multimedia learning materials on the Internet, this paper proposes a generic resource organization model with semantic structures to improve expressiveness, scalability and cohesiveness. We developed an active learning system with semantic support for learners to access and navigate through efficient and flexible manner. We learning resources in an efficient and flexible manner. We provide facilities for instructors to manipulate the structured educational resources via a convenient visual interface. We also developed a resource discovering and gathering engine based on complex semantic associations for several specific topics.

Virtual reality Post Traumatic Stress Disorder (PTSD) exposure therapy results with active duty Iraq war combatants

Post Traumatic Stress Disorder (PTSD) is reported to be caused by traumatic events that are outside the range of usual human experience including (but not limited to) military combat, violent personal assault, being kidnapped or taken hostage and terrorist attacks. Initial data suggests that at least 1 out of 6 Iraq War veterans are exhibiting symptoms of depression, anxiety and PTSD. Virtual Reality (VR) delivered exposure therapy for PTSD has been used with reports of positive outcomes. The aim of the current paper is to present the rationale and brief description of a Virtual Iraq PTSD VR therapy application and present initial findings from its use with PTSD patients. Thus far, Virtual Iraq consists of a series of customizable virtual scenarios designed to represent relevant Middle Eastern VR contexts for exposure therapy, including a city and desert road convoy environment. User-centered design feedback needed to iteratively evolve the system was gathered from returning Iraq War veterans in the USA and from a system deployed in Iraq and tested by an Army Combat Stress Control Team. Results from an open clinical trial at San Diego Naval Medical Center of the first 18 treatment completers indicate that 14 no longer meet PTSD diagnostic criteria at post-treatment, with only one not maintaining treatment gains at 3 month follow-up. Clinical tests are also currently underway at Ft. Lewis, Emory University, Weill Cornell Medical College, Walter Reed Army Medical Center and 10 other sites. Other sites are preparing to use the application for a variety of PTSD and VR research purposes.

Effects of biologically active tumour-promoting and non-promoting phorbol esters on in vivo growth of melanocytic cells

Sapintoxin A (SAP A), a naturally occurring biologically active but non-promoting phorbol ester, acts as an effective in vitro mitogen for freshly derived human melanocytes. Seven days after addition of 50 nM SAP A there was a four to fivefold increase in melanocyte number over that observed in untreated control cultures comparable to that achieved with a 50 nM concentration of 12-0-tetradecanoylphorbol 13-acetate (TPA). The fluorescent stage 2 promoter sapintoxin D (SAP D) also supported the growth of these cells, with a 50 nM dose producing an increase in cell number comparable to that observed with 200 nM TPA. Similar results were obtained with an established, but non-tumorigenic, line of murine melanocytes. The same compounds exerted a potent anti-proliferative effect against transformed melanocyte lines of murine and human origin associated with morphological alterations and an increase in melanin production consistent with induced cytodifferentiation.

Extracts of tropical African spices are active against Plutella xylostella

Extracts from Piper guineense, Aframomum melegueta, Aframomum citratum and Afrostyrax kamerunensis were investigated for their antifeedant, lethal and developmental effects against Plutella xylostella larvae through laboratory dual-choice tests and topical application. Water and ethanol extracts of P. guineense were dose-dependent antifeedants at concentrations ≥300 and 500 ppm, respectively, whilst methanol extracts required ≥1,000 ppm. Methanol and hexane extracts of A. melegueta acted at ≥100 ppm and water extracts at ≥300 ppm, but ethanol extracts were deterring feeding only slightly at ≥1,000 ppm. Hexane and methanol extracts of A. citratum inhibited feeding at ≥300 ppm and water extracts did so at ≥500 ppm. None of the Afrostyrax kamerunensis extracts deterred feeding at any of the concentrations tested. No mortality was observed at any of the concentrations after topical application of the extracts on the larvae. However, the effects on larval development varied with extract concentration and larval age. Ingestion of the water and ethanol extracts of P. guineense caused 100% mortality of second instars at ≥100 ppm two to three days after infestation (DAI). Methanol and water extracts of A. melegueta and A. citratum, respectively, achieved ≥80% mortality of larvae at concentrations of ≥500 ppm and ≥1,000 ppm, respectively. With third instars, the mortalities were significantly lower; however, the P. guineense water or ethanol extracts caused 100% mortality two to four DAI. Larvae that survived till pupation had significantly longer larval periods compared with the control after application of A. melegueta extracts. We concluded that potent extracts from Aframomum melegueta, Aframomum citratum and especially P. guineense could be used as complementary measures in the management of P. xylostella by subsistence farmers.

Electronic transitions and bonding properties in a series of five-coordinate “16-electron” complexes [Mn(CO)3(L2)]− (L2=chelating redox-active π-donor ligand)

In this article we present for the first time accurate density functional theory (DFT) and time-dependent (TD) DFT data for a series of electronically unsaturated five-coordinate complexes [Mn(CO)(3)(L-2)](-), where L-2 stands for a chelating strong pi-donor ligand represented by catecholate, dithiolate, amidothiolate, reduced alpha-diimine (1,4-dialkyl-1,4-diazabutadiene (R-DAB), 2,2'-bipyridine) and reduced 2,2'-biphosphinine types. The single-crystal X-ray structure of the unusual compound [Na(BPY)][Mn(CO)(3)(BPY)]center dot Et2O and the electronic absorption spectrum of the anion [Mn(CO)(3)(BPY)](-) are new in the literature. The nature of the bidentate ligand determines the bonding in the complexes, which varies between two limiting forms: from completely pi-delocalized diamagnetic {(CO)(3)Mn-L-2}(-) for L-2 = alpha-diimine or biphosphinine, to largely valence-trapped {(CO)(3)Mn-1-L-2(2-)}(-) for L-2(2-) = catecholate, where the formal oxidation states of Mn and L-2 can be assigned. The variable degree of the pi-delocalization in the Mn(L-2) chelate ring is indicated by experimental resonance Raman spectra of [Mn(CO)(3)(L-2)](-) (L-2=3,5-di-tBu-catecholate and iPr-DAB), where accurate assignments of the diagnostically important Raman bands have been aided by vibrational analysis. The L-2 = catecholate type of complexes is known to react with Lewis bases (CO substitution, formation of six-coordinate adducts) while the strongly pi-delocalized complexes are inert. The five-coordinate complexes adopt usually a distorted square pyramidal geometry in the solid state, even though transitions to a trigonal bipyramid are also not rare. The experimental structural data and the corresponding DFT-computed values of bond lengths and angles are in a very good agreement. TD-DFT calculations of electronic absorption spectra of the studied Mn complexes and the strongly pi-delocalized reference compound [Fe(CO)(3)(Me-DAB)] have reproduced qualitatively well the experimental spectra. Analyses of the computed electronic transitions in the visible spectroscopic region show that the lowest-energy absorption band always contains a dominant (in some cases almost exclusive) contribution from a pi(HOMO) -> pi*(LUMO) transition within the MnL2 metallacycle. The character of this optical excitation depends strongly on the composition of the frontier orbitals, varying from a partial L-2 -> Mn charge transfer (LMCT) through a fully delocalized pi(MnL2) -> pi*(MnL2) situation to a mixed (CO)Mn -> L-2 charge transfer (LLCT/MLCT). The latter character is most apparent in the case of the reference complex [Fe(CO)(3)(Me-DAB)]. The higher-lying, usually strongly mixed electronic transitions in the visible absorption region originate in the three lower-lying occupied orbitals, HOMO - 1 to HOMO - 3, with significant metal-d contributions. Assignment of these optical excitations to electronic transitions of a specific type is difficult. A partial LLCT/MLCT character is encountered most frequently. The electronic absorption spectra become more complex when the chelating ligand L-2, such as 2,2'-bipyridine, features two or more closely spaced low-lying empty pi* orbitals.

Redox-active polymers based on nonbridged metal−metal bonds. Electrochemical formation of [Os(bpy)(CO)(L)]n(bpy = 2,2‘-bipyridine; L = CO, MeCN) and of their reduced forms: a spectroelectrochemical study

IR, UV-vis, and EPR spectroelectrochemistry at variable temperatures and in different solvents were applied to investigate in situ the formation of electroactive molecular chains with a nonbridged Os-Os backbone, in particular, the polymer [Os-0(bpy)(CO)(2)](n), (bpy = 2,2'-bipyridine), from a mononuclear Os(II) carbonyl precursor, [Os-II(bpy)(CO)(2)Cl-2]. The one-electron-reduced form, [Os-II(bpy(.-))(CO)(2)Cl-2](-), has been characterized spectroscopically at low temperatures. This radical anion is the key intermediate in the electrochemical propagation process responsible for the metal-metal bond formation. Unambiguous spectroscopic evidence has been gained also for the formation of [{Os-0(bpy(.-))(CO)(2)}(-)](n), the electron-rich electrocatalyst of CO2 reduction. The polymer species are fairly well soluble in butyronitrile, which is important for their potential utilization in nanoscience, for example, as conducting molecular wires. We have also shown that complete solubility is accomplished for the monocarbonyl-acetonitrile derivative of the polymer, [Os-0(bpy)(CO)(MeCN)(2)Cl](n).

Monophosphothreonyl extracellular signal-regulated kinases 1 and 2 (ERK1/2) are formed endogenously in intact cardiac myocytes and are enzymically active

ERK1 and ERK2 (ERK1/2) are central to the regulation of cell division, growth and survival. They are activated by phosphorylation of the Thr- and the Tyr- residues in their Thr-Glu-Tyr activation loops. The dogma is that dually-phosphorylated ERK1/2 constitute the principal activities in intact cells. We previously showed that, in neonatal rat cardiac myocytes, endothelin-1 and phorbol 12-myristate 13-acetate (PMA) powerfully and rapidly (maximal at ~ 5 min) activate ERK1/2. Here, we show that dually-phosphorylated ERK1/2 rapidly (< 2 min) appear in the nucleus following stimulation with endothelin-1. We characterized the active ERK1/2 species in myocytes exposed to endothelin-1 or PMA using MonoQ FPLC. Unexpectedly, two peaks of ERK1 and two peaks of ERK2 activity were resolved using in vitro kinase assays. One of each of these represented the dually-phosphorylated species. The other two represented activities for ERK1 or ERK2 which were phosphorylated solely on the Thr- residue. Monophosphothreonyl ERK1/2 represented maximally ~ 30% of total ERK1/2 activity after stimulation with endothelin-1 or PMA, and their kcat values were estimated to be minimally ~ 30% of the dually-phosphorylated species. Appearance of monophosphothreonyl ERK1/2 was rapid but delayed in comparison with dually-phosphorylated ERK1/2. Of 10 agonists studied, endothelin-1 and PMA were most effective in terms of ERK1/2 activation and in stimulating the appearance of monophosphothreonyl and dually-phosphorylated ERK1/2. Thus, enzymically active monophosphothreonyl ERK1/2 are formed endogenously following activation of the ERK1/2 cascade and we suggest that monophosphothreonyl ERK1/2 arise by protein tyrosine phosphatase-mediated dephosphorylation of dually-phosphorylated ERK1/2.

Speciation as an active force in promoting genetic evolution

There is a growing appreciation among evolutionary biologists that the rate and tempo of molecular evolution might often be altered at or near the time of speciation, i.e. that speciation is in some way a special time for genes. Molecular phylogenies frequently reveal increased rates of genetic evolution associated with speciation and other lines of investigation suggest that various types of abrupt genomic disruption can play an important role in promoting speciation via reproductive isolation. These phenomena are in conflict with the gradual view of molecular evolution that is implicit in much of our thinking about speciation and in the tools of modern biology. This raises the prospect of studying the molecular evolutionary consequences of speciation per se and studying the footprint of speciation as an active force in promoting genetic divergence. Here we discuss the reasons to believe that speciation can play such a role and elaborate on possible mechanisms for accelerated rates of evolution following speciation. We provide an example of how it is possible detect whether accelerated bursts of evolution occur in neutral and/or adaptive regions of genes and discuss the implications of rapid episodes of change for conventional models of molecular evolution. Speciation might often owe more to ephemeral and essentially arbitrary events that cause reproductive isolation than to the gradual and regular tug of natural selection that draws a species into a new niche.

Active micromachined integrated terahertz circuits

Schottky barrier diodes have been integrated into on-chip rectangular waveguides. Two novel techniques have been developed to fabricate diodes with posts suitable for integration into waveguides. One technique produces diodes with anode diameters of the order of microns with post heights from 90 to 125 microns and the second technique produces sub-micron anodes with post heights around 20 microns. A method has been developed to incorporate these structures into a rectangular waveguide and provide a top contact onto the anode which could be used as an I.F. output in a mixer circuit. Devices have been fabricated and D.C. characterized.