Femto-chemometrics: the signal processing of fast pulse transients

Traditional chemometrics techniques are augmented with algorithms tailored specifically for the de-noising and analysis of femtosecond duration pulse datasets. The new algorithms provide additional insights on sample responses to broadband excitation and multi-moded propagation phenomena.

Beta event-related desynchronization as an index of individual differences in processing human facial expression: further investigations of autistic traits in typically developing adults

The human mirror neuron system (hMNS) has been associated with various forms of social cognition and affective processing including vicarious experience. It has also been proposed that a faulty hMNS may underlie some of the deficits seen in the autism spectrum disorders (ASDs). In the present study we set out to investigate whether emotional facial expressions could modulate a putative EEG index of hMNS activation (mu suppression) and if so, would this differ according to the individual level of autistic traits [high versus low Autism Spectrum Quotient (AQ) score]. Participants were presented with 3 s films of actors opening and closing their hands (classic hMNS mu-suppression protocol) while simultaneously wearing happy, angry, or neutral expressions. Mu-suppression was measured in the alpha and low beta bands. The low AQ group displayed greater low beta event-related desynchronization (ERD) to both angry and neutral expressions. The high AQ group displayed greater low beta ERD to angry than to happy expressions. There was also significantly more low beta ERD to happy faces for the low than for the high AQ group. In conclusion, an interesting interaction between AQ group and emotional expression revealed that hMNS activation can be modulated by emotional facial expressions and that this is differentiated according to individual differences in the level of autistic traits. The EEG index of hMNS activation (mu suppression) seems to be a sensitive measure of the variability in facial processing in typically developing individuals with high and low self-reported traits of autism.

Prefrontal inhibition of threat processing reduces working memory interference

Bottom-up processes can interrupt ongoing cognitive processing in order to adaptively respond to emotional stimuli of high potential significance, such as those that threaten wellbeing. However it is vital that this interference can be modulated in certain contexts to focus on current tasks. Deficits in the ability to maintain the appropriate balance between cognitive and emotional demands can severely impact on day-to-day activities. This fMRI study examined this interaction between threat processing and cognition; 18 adult participants performed a visuospatial working memory (WM) task with two load conditions, in the presence and absence of anxiety induction by threat of electric shock. Threat of shock interfered with performance in the low cognitive load condition; however interference was eradicated under high load, consistent with engagement of emotion regulation mechanisms. Under low load the amygdala showed significant activation to threat of shock that was modulated by high cognitive load. A directed top-down control contrast identified two regions associated with top-down control; ventrolateral PFC and dorsal ACC. Dynamic causal modeling provided further evidence that under high cognitive load, top-down inhibition is exerted on the amygdala and its outputs to prefrontal regions. Additionally, we hypothesized that individual differences in a separate, non-emotional top-down control task would predict the recruitment of dorsal ACC and ventrolateral PFC during top-down control of threat. Consistent with this, performance on a separate dichotic listening task predicted dorsal ACC and ventrolateral PFC activation during high WM load under threat of shock, though activation in these regions did not directly correlate with WM performance. Together, the findings suggest that under high cognitive load and threat, top-down control is exerted by dACC and vlPFC to inhibit threat processing, thus enabling WM performance without threat-related interference.

The case of tomato in Ghana: processing

Processing of highly perishable non-storable crops, such as tomato, is typically promoted for two reasons: as a way of absorbing excess supply, particularly during gluts that result from predominantly rainfed cultivation; and to enhance the value chain through a value-added process. For Ghana, improving domestic tomato processing would also reduce the country’s dependence on imported tomato paste and so improve foreign exchange reserves, as well as provide employment opportunities and development opportunities in what are poor rural areas of the country. Many reports simply repeat the mantra that processing offers a way of buying up the glut. Yet the reality is that the “tomato gluts,” an annual feature of the local press, occur only for a few weeks of the year, and are almost always a result of large volumes of rainfed local varieties unsuitable for processing entering the fresh market at the same time, not the improved varieties that could be used by the processors. For most of the year, the price of tomatoes suitable for processing is above the breakeven price for tomato processors, given the competition from imports. Improved varieties (such as Pectomech) that are suitable for processing are also preferred by consumers and achieve a premium price over the local varieties.

Increased neural processing of rewarding and aversive food stimuli in recovered anorexia nervosa

Background Recent evidence has shown that individuals with acute anorexia nervosa and those recovered have aberrant physiological responses to rewarding stimuli. We hypothesized that women recovered from anorexia nervosa would show aberrant neural responses to both rewarding and aversive disorder-relevant stimuli. Methods Using functional magnetic resonance imaging (fMRI), the neural response to the sight and flavor of chocolate, and their combination, in 15 women recovered from restricting-type anorexia nervosa and 16 healthy control subjects matched for age and body mass index was investigated. The neural response to a control aversive condition, consisting of the sight of moldy strawberries and a corresponding unpleasant taste, was also measured. Participants simultaneously recorded subjective ratings of “pleasantness,” “intensity,” and “wanting.” Results Despite no differences between the groups in subjective ratings, individuals recovered from anorexia nervosa showed increased neural response to the pleasant chocolate taste in the ventral striatum and pleasant chocolate sight in the occipital cortex. The recovered participants also showed increased neural response to the aversive strawberry taste in the insula and putamen and to the aversive strawberry sight in the anterior cingulate cortex and caudate. Conclusions Individuals recovered from anorexia nervosa have increased neural responses to both rewarding and aversive food stimuli. These findings suggest that even after recovery, women with anorexia nervosa have increased salience attribution to food stimuli. These results aid our neurobiological understanding and support the view that the neural response to reward may constitute a neural biomarker for anorexia nervosa.

Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment

Background Selective serotonin reuptake inhibitors (SSRIs) are popular medications for anxiety and depression, but their effectiveness, particularly in patients with prominent symptoms of loss of motivation and pleasure, has been questioned. There are few studies of the effect of SSRIs on neural reward mechanisms in humans. Methods We studied 45 healthy participants who were randomly allocated to receive the SSRI citalopram, the noradrenaline reuptake inhibitor reboxetine, or placebo for 7 days in a double-blind, parallel group design. We used functional magnetic resonance imaging to measure the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (sight of moldy strawberries and/or an unpleasant strawberry taste) on the final day of drug treatment. Results Citalopram reduced activation to the chocolate stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex. In contrast, reboxetine did not suppress ventral striatal activity and in fact increased neural responses within medial orbitofrontal cortex to reward. Citalopram also decreased neural responses to the aversive stimuli conditions in key “punishment” areas such as the lateral orbitofrontal cortex. Reboxetine produced a similar, although weaker effect. Conclusions Our findings are the first to show that treatment with SSRIs can diminish the neural processing of both rewarding and aversive stimuli. The ability of SSRIs to decrease neural responses to reward might underlie the questioned efficacy of SSRIs in depressive conditions characterized by decreased motivation and anhedonia and could also account for the experience of emotional blunting described by some patients during SSRI treatment.

Neural processing of reward and punishment in young people at increased familial risk of depression

Background Abnormalities in the neural representation of rewarding and aversive stimuli have been well-described in patients with acute depression, and we previously found abnormal neural responses to rewarding and aversive sight and taste stimuli in recovered depressed patients. The aim of the present study was to determine whether similar abnormalities might be present in young people at increased familial risk of depression but with no personal history of mood disorder. Methods We therefore used functional magnetic resonance imaging to examine the neural responses to pleasant and aversive sights and tastes in 25 young people (16–21 years of age) with a biological parent with depression and 25 age- and gender-matched control subjects. Results We found that, relative to the control subjects, participants with a parental history of depression showed diminished responses in the orbitofrontal cortex to rewarding stimuli, whereas activations to aversive stimuli were increased in the lateral orbitofrontal cortex and insula. In anterior cingulate cortex the at-risk group showed blunted neural responses to both rewarding and aversive stimuli. Conclusions Our findings suggest that young people at increased familial risk of depression have altered neural representation of reward and punishment, particularly in cortical regions linked to the use of positive and negative feedback to guide adaptive behavior.

The effect of processing on chlorogenic acid content of commercially available coffee

Chlorogenic acids (CGA) are a class of polyphenols noted for their health benefits. These compounds were identified and quantified, using LC–MS and HPLC, in commercially available coffees which varied in pro- cessing conditions. Analysis of ground and instant coffees indicated the presence of caffeoylquinic acids (CQA), feruloylquinic acids (FQA) and dicaffeoylquinic acids (diCQA) in all 18 samples tested. 5-CQA was present at the highest levels, between 25 and 30% of total CGA; subsequent relative quantities were: 4- CQA > 3-CQA > 5-FQA > 4-FQA > diCQA (sum of 3,4, 3,5 and 4,5-diCQA). CGA content varied greatly (27.33–121.25 mg/200 ml coffee brew), driven primarily by the degree of coffee bean roasting (a high amount of roasting had a detrimental effect on CGA content). These results highlight the broad range of CGA quantity in commercial coffee and demonstrate that coffee choice is important in delivering opti-mum CGA intake to consumers.

Does neural input or processing play a greater role in the magnitude of neuroimaging signals?

An important constraint on how hemodynamic neuroimaging signals such as fMRI can be interpreted in terms of the underlying evoked activity is an understanding of neurovascular coupling mechanisms that actually generate hemodynamic responses. The predominant view at present is that the hemodynamic response is most correlated with synaptic input and subsequent neural processing rather than spiking output. It is still not clear whether input or processing is more important in the generation of hemodynamics responses. In order to investigate this we measured the hemodynamic and neural responses to electrical whisker pad stimuli in rat whisker barrel somatosensory cortex both before and after the local cortical injections of the GABAA agonist muscimol. Muscimol would not be expected to affect the thalamocortical input into the cortex but would inhibit subsequent intra-cortical processing. Pre-muscimol infusion whisker stimuli elicited the expected neural and accompanying hemodynamic responses to that reported previously. Following infusion of muscimol, although the temporal profile of neural responses to each pulse of the stimulus train was similar, the average response was reduced in magnitude by ∼79% compared to that elicited pre-infusion. The whisker-evoked hemodynamic responses were reduced by a commensurate magnitude suggesting that, although the neurovascular coupling relationships were similar for synaptic input as well as for cortical processing, the magnitude of the overall response is dominated by processing rather than from that produced from the thalamocortical input alone.

Identification of micro-scale anthropogenic CO2, heat and moisture sources – processing eddy covariance fluxes for a dense urban environment

Anthropogenic emissions of heat and exhaust gases play an important role in the atmospheric boundary layer, altering air quality, greenhouse gas concentrations and the transport of heat and moisture at various scales. This is particularly evident in urban areas where emission sources are integrated in the highly heterogeneous urban canopy layer and directly linked to human activities which exhibit significant temporal variability. It is common practice to use eddy covariance observations to estimate turbulent surface fluxes of latent heat, sensible heat and carbon dioxide, which can be attributed to a local scale source area. This study provides a method to assess the influence of micro-scale anthropogenic emissions on heat, moisture and carbon dioxide exchange in a highly urbanized environment for two sites in central London, UK. A new algorithm for the Identification of Micro-scale Anthropogenic Sources (IMAS) is presented, with two aims. Firstly, IMAS filters out the influence of micro-scale emissions and allows for the analysis of the turbulent fluxes representative of the local scale source area. Secondly, it is used to give a first order estimate of anthropogenic heat flux and carbon dioxide flux representative of the building scale. The algorithm is evaluated using directional and temporal analysis. The algorithm is then used at a second site which was not incorporated in its development. The spatial and temporal local scale patterns, as well as micro-scale fluxes, appear physically reasonable and can be incorporated in the analysis of long-term eddy covariance measurements at the sites in central London. In addition to the new IMAS-technique, further steps in quality control and quality assurance used for the flux processing are presented. The methods and results have implications for urban flux measurements in dense urbanised settings with significant sources of heat and greenhouse gases.

Effect of provenance, plant part and processing on extract profiles from cultivated European Rhodiola rosea L. for medicinal use.

The demand for plant material of Rhodiola rosea L. (Crassulaceae) for medicinal use has increased recently, amid concerns about its quality and sustainability. We have analysed the content of phenylpropanoids (total rosavins) and salidroside in liquid extracts from 3-year old cultivated plants of European origin, and mapped the influence of plant part (rhizome versus root), genotype, drying, cutting, and extraction solvent to chemical composition. Rhizomes contained 1.5-4 times more salidroside (0.3-0.4% dry wt) and total rosavins (1.2-3.0%) than roots. The qualitative decisive phenylpropanoid content in the extracts was most influenced by plant part, solvent, and genotype, while drying temperature and cutting conditions were of less importance. We have shown that R. rosea from different boreal European provenances can be grown under temperate conditions and identified factors to obtain consistent high quality extracts provided that authentic germplasm is used and distinguished between rhizome, roots and their mixtures.

Human microbiota in health and disease

Each human body plays host to a microbial population which is both numerically vast (at around 1014 microbial cells) and phenomenally diverse (over 1,000 species). The majority of the microbial species in the gut have not been cultured but the application of culture-independent approaches for high throughput diversity and functionality analysis has allowed characterisation of the diverse microbial phylotypes present in health and disease. Studies in monozygotic twins, showing that these retain highly similar microbiota decades after birth and initial colonisation, are strongly indicative that diversity of the microbiome is host-specific and affected by the genotype. Microbial diversity in the human body is reflected in both richness and evenness. Diversity increases steeply from birth reaching its highest point in early adulthood, before declining in older age. However, in healthy subjects there appears to be a core of microbial phylotypes which remains relatively stable over time. Studies of individuals from diverse geopraphies suggest that clusters of intestinal bacterial groups tend to occur together, constituting ‘enterotypes’. So variation in intestinal microbiota is stratified rather than continuous and there may be a limited number of host/microbial states which respond differently to environmental influences. Exploration of enterotypes and functional groups may provide biomarkers for disease and insights into the potential for new treatments based on manipulation of the microbiome. In health, the microbiota interact with host defences and exist in harmonious homeostasis which can then be disturbed by invading organisms or when ‘carpet bombing’ by antibiotics occurs. In a portion of individuals with infections, the disease will resolve itself without the need for antibiotics and microbial homeostasis with the host’s defences is restored. The administration of probiotics (live microorganisms which when administered in adequate amounts confer a health benefit on the host) represents an artificial way to enhance or stimulate these natural processes. The study of innate mechanisms of antimicrobial defence on the skin, including the production of numerous antimicrobial peptides (AMPs), has shown an important role for skin commensal organisms. These organisms may produce AMPs, and also amplify the innate immune responses to pathogens by activating signalling pathways and processing host produced AMPs. Research continues into how to enhance and manipulate the role of commensal organisms on the skin. The challenges of skin infection (including diseases caused by multiply resistant organisms) and infestations remain considerable. The potential to re-colonise the skin to replace or reduce pathogens, and exploring the relationship between microbiota elsewhere and skin diseases are among a growing list of research targets. Lactobacillus species are among the best known ‘beneficial’ bacterial members of the human microbiota. Of the approximately 120 species known, about 15 are known to occur in the human vagina. These organisms have multiple properties, including the production of lactic acid, hydrogen peroxide and bacteriocins, which render the vagina inhospitable to potential pathogens. Depletion of the of the normal Lactobacillus population and overgrowth of vaginal anaerobes, accompanied by the loss of normal vaginal acidity can lead to bacterial vaginosis – the commonest cause of abnormal vaginal discharge in women. Some vaginal anaerobes are associated with the formation of vaginal biofilms which serve to act as a reservoir of organisms which persists after standard antibiotic therapy of bacterial vaginosis and may help to account for the characteristically high relapse rate in the condition. Administration of Lactobacillus species both vaginally and orally have shown beneficial effects in the treatment of bacterial vaginosis and such treatments have an excellent overall safety record. Candida albicans is a frequent coloniser of human skin and mucosal membranes, and is a normal part of the microbiota in the mouth, gut and vagina. Nevertheless Candida albicans is the most common fungal pathogen worldwide and is a leading cause of serious and often fatal nosocomial infections. What turns this organism from a commensal to a pathogen is a combination of increasing virulence in the organism and predisposing host factors that compromise immunity. There has been considerable research into the use of probiotic Lactobacillus spp. in vaginal candidiasis. Studies in reconstituted human epithelium and monolayer cell cultures have shown that L. rhamnosus GG can protect mucosa from damage caused by Candida albicans, and enhance the immune responses of mucosal surfaces. Such findings offer the promise that the use of such probiotic bacteria could provide new options for antifungal therapy. Studies of changes of the human intestinal microbiota in health and disease are complicated by its size and diversity. The Alimentary Pharmabiotic Centre in Cork (Republic of Ireland) has the mission to ‘mine microbes for mankind’ and its work illustrates the potential benefits of understanding the gut microbiota. Work undertaken at the centre includes: mapping changes in the microbiota with age; studies of the interaction between the microbiota and the gut; potential interactions between the gut microbiota and the central nervous system; the potential for probiotics to act as anti-infectives including through the production of bacteriocins; and the characterisation of interactions between gut microbiota and bile acids which have important roles as signalling molecules and in immunity. The important disease entity where the role of the gut microbiota appears to be central is the Irritable Bowel Syndrome (IBS). IBS patients show evidence of immune activation, impaired gut barrier function and abnormal gut microbiota. Studies with probiotics have shown that these organisms can exert anti-inflammatory effects in inflammatory bowel disease and may strengthen the gut barrier in IBS of the diarrhoea-predominant type. Formal randomised trials of probiotics in IBS show mixed results with limited benefit for some but not all. Studies confirm that administered probiotics can survive and temporarily colonise the gut. They can also stimulate the numbers of other lactic acid bacilli in the gut, and reduce the numbers of pathogens. However consuming live organisms is not the only way to influence gut microbiota. Dietary prebiotics are selectively fermented ingredients that can change the composition and/or activity of the gastrointestinal microbiota in beneficial ways. Dietary components that reach the colon, and are available to influence the microbiota include poorly digestible carbohydrates, such as non-starch polysaccharides, resistant starch, non-digestible oligosaccharides (NDOs) and polyphenols. Mixtures of probiotic and prebiotic ingredients that can selectively stimulate growth or activity of health promoting bacteria have been termed ‘synbiotics’. All of these approaches can influence gut microbial ecology, mainly to increase bifidobacteria and lactobacilli, but metagenomic approaches may reveal wider effects. Characterising how these changes produce physiological benefits may enable broader use of these tactics in health and disease in the future. The current status of probiotic products commercially available worldwide is less than ideal. Prevalent problems include misidentification of ingredient organisms and poor viability of probiotic microorganisms leading to inadequate shelf life. On occasions these problems mean that some commercially available products cannot be considered to meet the definition of a probiotic product. Given the potential benefits of manipulating the human microbiota for beneficial effects, there is a clear need for improved regulation of probiotics. The potential importance of the human microbiota cannot be overstated. ‘We feed our microbes, they talk to us and we benefit. We just have to understand and then exploit this.’ (Willem de Vos).

Error, reproducibility and sensitivity: a pipeline for data processing of Agilent oligonucleotide expression arrays

Background: Expression microarrays are increasingly used to obtain large scale transcriptomic information on a wide range of biological samples. Nevertheless, there is still much debate on the best ways to process data, to design experiments and analyse the output. Furthermore, many of the more sophisticated mathematical approaches to data analysis in the literature remain inaccessible to much of the biological research community. In this study we examine ways of extracting and analysing a large data set obtained using the Agilent long oligonucleotide transcriptomics platform, applied to a set of human macrophage and dendritic cell samples. Results: We describe and validate a series of data extraction, transformation and normalisation steps which are implemented via a new R function. Analysis of replicate normalised reference data demonstrate that intrarray variability is small (only around 2 of the mean log signal), while interarray variability from replicate array measurements has a standard deviation (SD) of around 0.5 log(2) units (6 of mean). The common practise of working with ratios of Cy5/Cy3 signal offers little further improvement in terms of reducing error. Comparison to expression data obtained using Arabidopsis samples demonstrates that the large number of genes in each sample showing a low level of transcription reflect the real complexity of the cellular transcriptome. Multidimensional scaling is used to show that the processed data identifies an underlying structure which reflect some of the key biological variables which define the data set. This structure is robust, allowing reliable comparison of samples collected over a number of years and collected by a variety of operators. Conclusions: This study outlines a robust and easily implemented pipeline for extracting, transforming normalising and visualising transcriptomic array data from Agilent expression platform. The analysis is used to obtain quantitative estimates of the SD arising from experimental (non biological) intra- and interarray variability, and for a lower threshold for determining whether an individual gene is expressed. The study provides a reliable basis for further more extensive studies of the systems biology of eukaryotic cells.

Sex differences in reward-related decision processing under stress

Recent research indicates gender differences in the impact of stress on decision behavior, but little is known about the brain mechanisms involved in these gender-specific stress effects. The current study used functional magnetic resonance imaging (fMRI) to determine whether induced stress resulted in gender-specific patterns of brain activation during a decision task involving monetary reward. Specifically, we manipulated physiological stress levels using a cold pressor task, prior to a risky decision making task. Healthy men (n = 24, 12 stressed) and women (n = 23, 11 stressed) completed the decision task after either cold pressor stress or a control task during the period of cortisol response to the cold pressor. Gender differences in behavior were present in stressed participants but not controls, such that stress led to greater reward collection and faster decision speed in males but less reward collection and slower decision speed in females. A gender-by-stress interaction was observed for the dorsal striatum and anterior insula. With cold stress, activation in these regions was increased in males but decreased in females. The findings of this study indicate that the impact of stress on reward-related decision processing differs depending on gender.

Pronoun processing in Broca's aphasia: discourse-syntax effects in ambiguous anaphora resolution

Background: The interpretation of ambiguous subject pronouns in a null subject language, like Greek, requires that one possesses grammatical knowledge of the two subject pronominal forms, i.e., null and overt, and that discourse constraints regulating the distribution of the two pronouns in context are respected. Aims: We investigated whether the topic-shift feature encoded in overt subject pronouns would exert similar interpretive effects in a group of seven participants with Broca’s aphasia and a group of language-unimpaired adults during online processing of null and overt subject pronouns in referentially ambiguous contexts. Method & Procedures: An offline picture–sentence matching task was initially administered to investigate whether the participants with Broca’s aphasia had access to the gender and number features of clitic pronouns. An online self-paced listening picture-verification task was subsequently administered to examine how the aphasic individuals resolve pronoun ambiguities in contexts with either null or overt subject pronouns and how their performance compares to that of language-unimpaired adults. Outcomes & Results: Results demonstrate that the Broca group, along with controls, had intact access to the morphosyntactic features of clitic pronouns. However, the aphasic individuals showed decreased preference for non-salient antecedents in object position during the online resolution of ambiguous overt subject pronouns and preferred to pick the subject antecedent instead. Conclusions: Broca’s aphasic participants’ parsing decisions in the online task reflect their difficulty with establishing topic-shifted interpretations of the ambiguous overt subject pronouns. The presence of a local topic-shift effect in the immediate temporal vicinity of the overt pronoun suggests that sensitivity to the marked informational status of overt pronouns is preserved in the aphasic individuals, yet, it is blocked under conditions of global sentential processing.