Nutritional biology: a neglected basic discipline of nutritional science

On the basis of a scientific-philosophical analysis, this paper tries to show that the approaches in current nutritional science—including its subdisciplines which focus on molecular aspects—are predominantly application-oriented. This becomes particularly evident through a number of conceptual problems characterized by the triad of ‘dearth of theoretical foundation,’ ‘particularist research questions,’ and ‘reductionist understanding of nutrition.’ The thesis presented here is that an interpretive framework based on nutritional biology is able to shed constructive light on the fundamental problems of nutritional science. In this context, the establishment of ‘nutritional biology’ as a basic discipline in research and education would be a first step toward recognizing the phenomenon of ‘nutrition’ as an oecic process as a special case of an organism–environment interaction. Modern nutritional science should be substantively grounded on ecological—and therefore systems biology as well as organismic—principles. The aim of nutritional biology, then, should be to develop near-universal ‘law statements’ in nutritional science—a task which presents a major challenge for the current science system.     

Conformational Preference of ‘CαNN’ Short Peptide Motif towards Recognition of Anions

Among several ‘anion binding motifs’, the recently described ‘C^αNN’ motif occurring in the loop regions preceding a helix, is conserved through evolution both in sequence and its conformation. To establish the significance of the conserved sequence and their intrinsic affinity for anions, a series of peptides containing the naturally occurring ‘C^αNN’ motif at the N-terminus of a designed helix, have been modeled and studied in a context free system using computational techniques. Appearance of a single interacting site with negative binding free-energy for both the sulfate and phosphate ions, as evidenced in docking experiments, establishes that the ‘C^αNN’ segment has an intrinsic affinity for anions. Molecular Dynamics (MD) simulation studies reveal that interaction with anion triggers a conformational switch from non-helical to helical state at the ‘C^αNN’ segment, which extends the length of the anchoring-helix by one turn at the N-terminus. Computational experiments substantiate the significance of sequence/structural context and justify the conserved nature of the ‘C^αNN’ sequence for anion recognition through “local” interaction.     

Ecological fitness, genomic islands and bacterial pathogenicity. A Darwinian view of the evolution of microbes

The compositions of bacterial genomes can be changed rapidly and dramatically through a variety of processes including horizontal gene transfer. This form of change is key to bacterial evolution, as it leads to ‘evolution in quantum leaps’. Horizontal gene transfer entails the incorporation of genetic elements transferred from another organism—perhaps in an earlier generation—directly into the genome, where they form ‘genomic islands’, i.e. blocks of DNA with signatures of mobile genetic elements. Genomic islands whose functions increase bacterial fitness, either directly or indirectly, have most likely been positively selected and can be termed ‘fitness islands’. Fitness islands can be divided into several subtypes: ‘ecological islands’ in environmental bacteria and ‘saprophytic islands’, ‘symbiosis islands’ or ‘pathogenicity islands’ (PAIs) in microorganisms that interact with living hosts. Here we discuss ways in which PAIs contribute to the pathogenic potency of bacteria, and the idea that genetic entities similar to genomic islands may also be present in the genomes of eukaryotes.     

Plastid Proteomic Analysis in Tomato Fruit Development

To better understand the mechanism of plastid differentiation from chloroplast to chromoplast, we examined proteome and plastid changes over four distinct developmental stages of ‘Micro-Tom’ fruit. Additionally, to discover more about the relationship between fruit color and plastid differentiation, we also analyzed and compared ‘Micro-Tom’ results with those from two other varieties, ‘Black’ and ‘White Beauty’. We confirmed that proteins related to photosynthesis remain through the orange maturity stage of ‘Micro-Tom’, and also learned that thylakoids no longer exist at this stage. These results suggest that at a minimum there are changes in plastid morphology occurring before all related proteins change. We also compared ‘Micro-Tom’ fruits with ‘Black’ and ‘White Beauty’ using two-dimensional gel electrophoresis. We found a decrease of CHRC (plastid-lipid-associated protein) and HrBP1 (harpin binding protein-1) in the ‘Black’ and ‘White Beauty’ varieties. CHRC is involved in carotenoid accumulation and stabilization. HrBP1 in Arabidopsis has a sequence similar to proteins in the PAP/fibrillin family. These proteins have characteristics and functions similar to lipocalin, an example of which is the transport of hydrophobic molecules. We detected spots of TIL (temperature-induced lipocalin) in 2D-PAGE results, however the number of spots and their isoelectric points differed between ‘Micro-Tom’ and ‘Black’/‘White Beauty’. Lipocalin has various functions including those related to environmental stress response, apoptosis induction, membrane formation and fixation, regulation of immune response, cell growth, and metabolism adjustment. Lipocalin related proteins such as TIL and HrBP1 could be related to the accumulation of carotenoids, fruit color and the differentiation of chromoplast.     

Odour boosts visual object approach in flies

Multisensory integration is synergistic—input from one sensory modality might modulate the behavioural response to another. Work in flies has shown that a small visual object presented in the periphery elicits innate aversive steering responses in flight, likely representing an approaching threat. Object aversion is switched to approach when paired with a plume of food odour. The ‘open-loop’ design of prior work facilitated the observation of changing valence. How does odour influence visual object responses when an animal has naturally active control over its visual experience? In this study, we use closed-loop feedback conditions, in which a fly''s steering effort is coupled to the angular velocity of the visual stimulus, to confirm that flies steer toward or ‘fixate’ a long vertical stripe on the visual midline. They tend either to steer away from or ‘antifixate’ a small object or to disengage active visual control, which manifests as uncontrolled object ‘spinning’ within this experimental paradigm. Adding a plume of apple cider vinegar decreases the probability of both antifixation and spinning, while increasing the probability of frontal fixation for objects of any size, including a normally typically aversive small object.     

Pulse and Entrainment to Non-Isochronous Auditory Stimuli: The Case of North Indian Alap

Pulse is often understood as a feature of a (quasi-) isochronous event sequence that is picked up by an entrained subject. However, entrainment does not only occur between quasi-periodic rhythms. This paper demonstrates the expression of pulse by subjects listening to non-periodic musical stimuli and investigates the processes behind this behaviour. The stimuli are extracts from the introductory sections of North Indian (Hindustani) classical music performances (alap, jor and jhala). The first of three experiments demonstrates regular motor responses to both irregular alap and more regular jor sections: responses to alap appear related to individual spontaneous tempi, while for jor they relate to the stimulus event rate. A second experiment investigated whether subjects respond to average periodicities of the alap section, and whether their responses show phase alignment to the musical events. In the third experiment we investigated responses to a broader sample of performances, testing their relationship to spontaneous tempo, and the effect of prior experience with this music. Our results suggest an entrainment model in which pulse is understood as the experience of one’s internal periodicity: it is not necessarily linked to temporally regular, structured sensory input streams; it can arise spontaneously through the performance of repetitive motor actions, or on exposure to event sequences with rather irregular temporal structures. Greater regularity in the external event sequence leads to entrainment between motor responses and stimulus sequence, modifying subjects’ internal periodicities in such a way that they are either identical or harmonically related to each other. This can be considered as the basis for shared (rhythmic) experience and may be an important process supporting ‘social’ effects of temporally regular music.     

Long-term potentiation in the anterior cingulate cortex and chronic pain

Glutamate is the primary excitatory transmitter of sensory transmission and perception in the central nervous system. Painful or noxious stimuli from the periphery ‘teach’ humans and animals to avoid potentially dangerous objects or environments, whereas tissue injury itself causes unnecessary chronic pain that can even last for long periods of time. Conventional pain medicines often fail to control chronic pain. Recent neurobiological studies suggest that synaptic plasticity taking place in sensory pathways, from spinal dorsal horn to cortical areas, contributes to chronic pain. Injuries trigger long-term potentiation of synaptic transmission in the spinal cord dorsal horn and anterior cingulate cortex, and such persistent potentiation does not require continuous neuronal activity from the periphery. At the synaptic level, potentiation of excitatory transmission caused by injuries may be mediated by the enhancement of glutamate release from presynaptic terminals and potentiated postsynaptic responses of AMPA receptors. Preventing, ‘erasing’ or reducing such potentiation may serve as a new mechanism to inhibit chronic pain in patients in the future.     

The Neural Dynamics of Conflict Adaptation within a Look-to-Do Transition

Background

For optimal performance in conflict situations, conflict adaptation (conflict detection and adjustment) is necessary. However, the neural dynamics of conflict adaptation is still unclear.

Methods

In the present study, behavioral and electroencephalography (EEG) data were recorded from seventeen healthy participants during performance of a color-word Stroop task with a novel look-to-do transition. Within this transition, participants looked at the Stroop stimuli but no responses were required in the ‘look’ trials; or made manual responses to the Stroop stimuli in the ‘do’ trials.

Results

In the ‘look’ trials, the amplitude modulation of N450 occurred exclusively in the right-frontal region. Subsequently, the amplitude modulation of sustained potential (SP) emerged in the posterior parietal and right-frontal regions. A significantly positive correlation between the modulation of reconfiguration in the ‘look’ trials and the behavioral conflict adaptation in the ‘do’ trials was observed. Specially, a stronger information flow from right-frontal region to posterior parietal region in the beta band was observed for incongruent condition than for congruent condition. In the ‘do’ trials, the conflict of ‘look’ trials enhanced the amplitude modulations of N450 in the right-frontal and posterior parietal regions, but decreased the amplitude modulations of SP in these regions. Uniquely, a stronger information flow from centro-parietal region to right-frontal region in the theta band was observed for iI condition than for cI condition.

Conclusion

All these findings showed that top-down conflict adaptation is implemented by: (1) enhancing the sensitivity to conflict detection and the adaptation to conflict resolution; (2) modulating the effective connectivity between parietal region and right-frontal region.     

Maximum likelihood parentage assignment using quantitative genotypes

The cost of parentage assignment precludes its application in many selective breeding programmes and molecular ecology studies, and/or limits the circumstances or number of individuals to which it is applied. Pooling samples from more than one individual, and using appropriate genetic markers and algorithms to determine parental contributions to pools, is one means of reducing the cost of parentage assignment. This paper describes and validates a novel maximum likelihood (ML) parentage-assignment method, that can be used to accurately assign parentage to pooled samples of multiple individuals—previously published ML methods are applicable to samples of single individuals only—using low-density single nucleotide polymorphism (SNP) ‘quantitative’ (also referred to as ‘continuous’) genotype data. It is demonstrated with simulated data that, when applied to pools, this ‘quantitative maximum likelihood’ method assigns parentage with greater accuracy than established maximum likelihood parentage-assignment approaches, which rely on accurate discrete genotype calls; exclusion methods; and estimating parental contributions to pools by solving the weighted least squares problem. Quantitative maximum likelihood can be applied to pools generated using either a ‘pooling-for-individual-parentage-assignment’ approach, whereby each individual in a pool is tagged or traceable and from a known and mutually exclusive set of possible parents; or a ‘pooling-by-phenotype’ approach, whereby individuals of the same, or similar, phenotype/s are pooled. Although computationally intensive when applied to large pools, quantitative maximum likelihood has the potential to substantially reduce the cost of parentage assignment, even if applied to pools comprised of few individuals.Subject terms: Plant breeding, Agricultural genetics, Animal breeding, Genetic markers     

When the Sun Prickles Your Nose: An EEG Study Identifying Neural Bases of Photic Sneezing

Background

Exposure to bright light such as sunlight elicits a sneeze or prickling sensation in about one of every four individuals. This study presents the first scientific examination of this phenomenon, called ‘the photic sneeze reflex’.

Methodology and Principal Findings

In the present experiment, ‘photic sneezers’ and controls were exposed to a standard checkerboard stimulus (block 1) and bright flashing lights (block 2) while their EEG (electro-encephalogram) was recorded. Remarkably, we found a generally enhanced excitability of the visual cortex (mainly in the cuneus) to visual stimuli in ‘photic sneezers’ compared with control subjects. In addition, a stronger prickling sensation in the nose of photic sneezers was found to be associated with activation in the insula and stronger activation in the secondary somatosensory cortex.

Conclusion

We propose that the photic sneeze phenomenon might be the consequence of higher sensitivity to visual stimuli in the visual cortex and of co-activation of somatosensory areas. The ‘photic sneeze reflex’ is therefore not a classical reflex that occurs only at a brainstem or spinal cord level but, in stark contrast to many theories, involves also specific cortical areas.     

The Obesogenic Quality of the Home Environment: Associations with Diet,Physical Activity,TV Viewing,and BMI in Preschool Children

Objectives

The home environment is thought to play a key role in early weight trajectories, although direct evidence is limited. There is general agreement that multiple factors exert small individual effects on weight-related outcomes, so use of composite measures could demonstrate stronger effects. This study therefore examined whether composite measures reflecting the ‘obesogenic’ home environment are associated with diet, physical activity, TV viewing, and BMI in preschool children.

Methods

Families from the Gemini cohort (n = 1096) completed a telephone interview (Home Environment Interview; HEI) when their children were 4 years old. Diet, physical activity, and TV viewing were reported at interview. Child height and weight measurements were taken by the parents (using standard scales and height charts) and reported at interview. Responses to the HEI were standardized and summed to create four composite scores representing the food (sum of 21 variables), activity (sum of 6 variables), media (sum of 5 variables), and overall (food composite/21 + activity composite/6 + media composite/5) home environments. These were categorized into ‘obesogenic risk’ tertiles.

Results

Children in ‘higher-risk’ food environments consumed less fruit (OR; 95% CI = 0.39; 0.27–0.57) and vegetables (0.47; 0.34–0.64), and more energy-dense snacks (3.48; 2.16–5.62) and sweetened drinks (3.49; 2.10–5.81) than children in ‘lower-risk’ food environments. Children in ‘higher-risk’ activity environments were less physically active (0.43; 0.32–0.59) than children in ‘lower-risk’ activity environments. Children in ‘higher-risk’ media environments watched more TV (3.51; 2.48–4.96) than children in ‘lower-risk’ media environments. Neither the individual nor the overall composite measures were associated with BMI.

Conclusions

Composite measures of the obesogenic home environment were associated as expected with diet, physical activity, and TV viewing. Associations with BMI were not apparent at this age.     

Running backwards: soft landing–hard takeoff,a less efficient rebound

Human running at low and intermediate speeds is characterized by a greater average force exerted after ‘landing’, when muscle–tendon units are stretched (‘hard landing’), and a lower average force exerted before ‘takeoff’, when muscle–tendon units shorten (‘soft takeoff’). This landing–takeoff asymmetry is consistent with the force–velocity relation of the ‘motor’ (i.e. with the basic property of muscle to resist stretching with a force greater than that developed during shortening), but it may also be due to the ‘machine’ (e.g. to the asymmetric lever system of the foot operating during stance). Hard landing and soft takeoff—never the reverse—were found in running, hopping and trotting animals using diverse lever systems, suggesting that the different machines evolved to comply with the basic force–velocity relation of the motor. Here we measure the mechanical energy of the centre of mass of the body in backward running, an exercise where the normal coupling between motor and machine is voluntarily disrupted, in order to see the relevance of the motor–machine interplay in human running. We find that the landing–takeoff asymmetry is reversed. The resulting ‘soft landing’ and ‘hard takeoff’ are associated with a reduced efficiency of positive work production. We conclude that the landing–takeoff asymmetry found in running, hopping and trotting is the expression of a convenient interplay between motor and machine. More metabolic energy must be spent in the opposite case when muscle is forced to work against its basic property (i.e. when it must exert a greater force during shortening and a lower force during stretching).     

Does Subjective Rating Reflect Behavioural Coding? Personality in 2 Month-Old Dog Puppies: An Open-Field Test and Adjective-Based Questionnaire

A number of studies have recently investigated personality traits in non-human species, with the dog gaining popularity as a subject species for research in this area. Recent research has shown the consistency of personality traits across both context and time for adult dogs, both when using questionnaire based methods of investigation and behavioural analyses of the dogs’ behaviour. However, only a few studies have assessed the correspondence between these two methods, with results varying considerably across studies. Furthermore, most studies have focused on adult dogs, despite the fact that an understanding of personality traits in young puppies may be important for research focusing on the genetic basis of personality traits. In the current study, we sought to evaluate the correspondence between a questionnaire based method and the in depth analyses of the behaviour of 2-month old puppies in an open-field test in which a number of both social and non-social stimuli were presented to the subjects. We further evaluated consistency of traits over time by re-testing a subset of puppies. The correspondence between methods was high and test- retest consistency (for the main trait) was also good using both evaluation methods. Results showed clear factors referring to the two main personality traits ‘extroversion,’ (i.e. the enthusiastic, exuberant approach to the stimuli) and ‘neuroticism,’ (i.e. the more cautious and fearful approach to the stimuli), potentially similar to the shyness-boldness dimension found in previous studies. Furthermore, both methods identified an ‘amicability’ dimension, expressing the positive interactions the pups directed at the humans stranger, and a ‘reservedness’ dimension which identified pups who largely chose not to interact with the stimuli, and were defined as quiet and not nosey in the questionnaire.     

Development of a New Method to Track Multiple Honey Bees with Complex Behaviors on a Flat Laboratory Arena

A computer program that tracks animal behavior, thereby revealing various features and mechanisms of social animals, is a powerful tool in ethological research. Because honeybee colonies are populated by thousands of bees, individuals co-exist in high physical densities and are difficult to track unless specifically tagged, which can affect behavior. In addition, honeybees react to light and recordings must be made under special red-light conditions, which the eyes of bees perceive as darkness. The resulting video images are scarcely distinguishable. We have developed a new algorithm, K-Track, for tracking numerous bees in a flat laboratory arena. Our program implements three main processes: (A) The object (bee''s) region is detected by simple threshold processing on gray scale images, (B) Individuals are identified by size, shape and spatiotemporal positional changes, and (C) Centers of mass of identified individuals are connected through all movie frames to yield individual behavioral trajectories. The tracking performance of our software was evaluated on movies of mobile multi-artificial agents and of 16 bees walking around a circular arena. K-Track accurately traced the trajectories of both artificial agents and bees. In the latter case, K-track outperformed Ctrax, well-known software for tracking multiple animals. To investigate interaction events in detail, we manually identified five interaction categories; ‘crossing’, ‘touching’, ‘passing’, ‘overlapping’ and ‘waiting’, and examined the extent to which the models accurately identified these categories from bee''s interactions. All 7 identified failures occurred near a wall at the outer edge of the arena. Finally, K-Track and Ctrax successfully tracked 77 and 60 of 84 recorded interactive events, respectively. K-Track identified multiple bees on a flat surface and tracked their speed changes and encounters with other bees, with good performance.     

Experimental evidence for limited vocal recognition in a wild primate: implications for the social complexity hypothesis

Although monitoring social information is a key aspect of the social complexity hypothesis, surprisingly little work has compared social knowledge across different species of wild animals. In the present study, I use playback experiments to test for individual recognition in wild male geladas (Theropithecus gelada) to compare with published accounts of social knowledge in chacma baboons (Papio ursinus). Geladas and baboons are closely related primates living in socially complex groups that differ dramatically in group size—geladas routinely associate with more than 10 times the number of conspecifics than do baboons. Using grunts from non-rival males to simulate approaches, I examined the strength of a subject male''s response when the ‘approach’ was from the direction of (i) non-rival males (control), or (ii) rival males (a more salient stimulus if playback grunts are not recognized by the subject). I compared responses separately based on the degree of social overlap between the caller and the subject. Responses indicate that male geladas, unlike baboons, do not use vocalizations to recognize all of the individuals they regularly encounter. This represents, to my knowledge, the first documented evidence of ‘missing’ social knowledge in a natural primate population. The sharp distinction between baboons and geladas suggests that geladas are either unable or unmotivated to keep track of the individual identity of other males in their multi-level society—even males with whom they have a large degree of social overlap. Thus, these results are consistent with the central assumption of the social complexity hypothesis that social cognition is costly.     

Tuning of Human Modulation Filters Is Carrier-Frequency Dependent

Recent studies employing speech stimuli to investigate ‘cocktail-party’ listening have focused on entrainment of cortical activity to modulations at syllabic (5 Hz) and phonemic (20 Hz) rates. The data suggest that cortical modulation filters (CMFs) are dependent on the sound-frequency channel in which modulations are conveyed, potentially underpinning a strategy for separating speech from background noise. Here, we characterize modulation filters in human listeners using a novel behavioral method. Within an ‘inverted’ adaptive forced-choice increment detection task, listening level was varied whilst contrast was held constant for ramped increments with effective modulation rates between 0.5 and 33 Hz. Our data suggest that modulation filters are tonotopically organized (i.e., vary along the primary, frequency-organized, dimension). This suggests that the human auditory system is optimized to track rapid (phonemic) modulations at high sound-frequencies and slow (prosodic/syllabic) modulations at low frequencies.     

Structural Adaptation and Heterogeneity of Normal and Tumor Microvascular Networks

Relative to normal tissues, tumor microcirculation exhibits high structural and functional heterogeneity leading to hypoxic regions and impairing treatment efficacy. Here, computational simulations of blood vessel structural adaptation are used to explore the hypothesis that abnormal adaptive responses to local hemodynamic and metabolic stimuli contribute to aberrant morphological and hemodynamic characteristics of tumor microcirculation. Topology, vascular diameter, length, and red blood cell velocity of normal mesenteric and tumor vascular networks were recorded by intravital microscopy. Computational models were used to estimate hemodynamics and oxygen distribution and to simulate vascular diameter adaptation in response to hemodynamic, metabolic and conducted stimuli. The assumed sensitivity to hemodynamic and conducted signals, the vascular growth tendency, and the random variability of vascular responses were altered to simulate ‘normal’ and ‘tumor’ adaptation modes. The heterogeneous properties of vascular networks were characterized by diameter mismatch at vascular branch points (d³_var) and deficit of oxygen delivery relative to demand (O_2def). In the tumor, d³_var and O_2def were higher (0.404 and 0.182) than in normal networks (0.278 and 0.099). Simulated remodeling of the tumor network with ‘normal’ parameters gave low values (0.288 and 0.099). Conversely, normal networks attained tumor-like characteristics (0.41 and 0.179) upon adaptation with ‘tumor’ parameters, including low conducted sensitivity, increased growth tendency, and elevated random biological variability. It is concluded that the deviant properties of tumor microcirculation may result largely from defective structural adaptation, including strongly reduced responses to conducted stimuli.     

How (and why) the visual control of action differs from visual perception

Vision not only provides us with detailed knowledge of the world beyond our bodies, but it also guides our actions with respect to objects and events in that world. The computations required for vision-for-perception are quite different from those required for vision-for-action. The former uses relational metrics and scene-based frames of reference while the latter uses absolute metrics and effector-based frames of reference. These competing demands on vision have shaped the organization of the visual pathways in the primate brain, particularly within the visual areas of the cerebral cortex. The ventral ‘perceptual’ stream, projecting from early visual areas to inferior temporal cortex, helps to construct the rich and detailed visual representations of the world that allow us to identify objects and events, attach meaning and significance to them and establish their causal relations. By contrast, the dorsal ‘action’ stream, projecting from early visual areas to the posterior parietal cortex, plays a critical role in the real-time control of action, transforming information about the location and disposition of goal objects into the coordinate frames of the effectors being used to perform the action. The idea of two visual systems in a single brain might seem initially counterintuitive. Our visual experience of the world is so compelling that it is hard to believe that some other quite independent visual signal—one that we are unaware of—is guiding our movements. But evidence from a broad range of studies from neuropsychology to neuroimaging has shown that the visual signals that give us our experience of objects and events in the world are not the same ones that control our actions.