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Quantifying physiological data with Lempel-Ziv complexity--certain issues.

The oscillations observed in physiological data can be attributed largely to the presence of either a nonlinear deterministic or a nondeterministic component. The Lempel-Ziv complexity and its variants have been used successfully to quantify the regularity of these oscillations. The decrease in the complexity can be observed in the case of nontrivial deterministic patterns as well as correlated noise. Thus, any conclusion on the nature of the pattern based solely on the value of the Lempel-Ziv complexity is incomplete. In this paper, the use of the surrogate data technique is suggested to avoid spurious interpretation of this measure of complexity. The data sets considered include the uterine contraction obtained during active labor. The surrogates are generated using the amplitude adjusted fourier transform and the iterated amplitude adjusted fourier transform. The approximate entropy is used as an alternate measure to verify the results obtained.

Cluster Analysis↗

An antibody to recombinant crustacean hyperglycaemic hormone of Nephrops norvegicus cross-reacts with neuroendocrine organs of several taxa of malacostracan Crustacea.

The crustacean hyperglycaemic hormones (cHHs) are multifunctional neuropeptides that play a central role in the physiology of crustaceans. A partial cDNA coding for cHH of the Norway lobster, Nephrops norvegicus, was cloned; this cDNA was fused to glutathione- S-transferase (GST) to obtain a recombinant fusion protein that was used to raise a rabbit antiserum and to perform a biological assay. The specificity of the purified antibody was demonstrated by means of Western blotting. To validate the specificity of the purified antibody to the cHH of N. norvegicus and its cross-reactivity with other species, we performed standard immunocytochemistry of the eyestalk on: (1) paraffin sections of the decapod species N. norvegicus, Munida rugosa and Astacus leptodactylus and of the stomatopod Squilla mantis; (2) semithin resin sections of N. norvegicus and Palaemon elegans; (3) ultrathin sections of N. norvegicus sinus gland (transmission electron microscopy studies). The pattern of immunoreactivity shown by N. norvegicus eyestalk sections conforms to distribution, relative amount and ultrastructural features of cHH-containing neurons and nerve endings as reported in the previous literature. In all the crustacean species examined, the antibody marks precisely the X organ-sinus gland complex and unspecific staining is completely lacking. In addition, its specific cross-reaction by immunoprecipitation depletes shrimp eyestalk extract of hyperglycaemic activity in an in vivo bioassay. The results obtained show a cHH-specific molecular recognition despite the fact that the species tested belong to systematic groups increasingly remote in the phylogenetic tree. The antibody could be used for advancing our knowledge on cHH activity in a variety of crustacean species, e.g. for monitoring reproductive and stress conditions.

Animals↗

Elongated physiological summation pools in the human visual cortex.

The visibility of gratings improves with increasing stimulus area. This effect is usually interpreted as being due to probability summation between the outputs of linear, independent spatial filters, although non-linear spatial summation can have similar effects [1]. In order to distinguish between probabilistic and physiological summation models, we measured contrast thresholds using the Visual Evoked Potential (VEP). Our previous work [2] suggests that spatial summation in the VEP is nonlinear and that it occurs preferentially for collinear configurations. Traditional probability summation models predict that areal summation will improve threshold independent of stimulus configuration. Contrast thresholds were derived from VEP contrast response functions for either circular or elongated Gabor patches with aspect ratios up to 6:1. The carrier orientation was either the same as the patch envelope orientation (collinear) or orthogonal to it. Response amplitudes were larger and contrast sensitivity was higher for collinear configurations. The results are consistent with nonlinear, configuration dependent summation that is more extensive along the axis of orientation.

Contrast Sensitivity↗

Non-malignant FDG uptake in infradiaphragmatic adipose tissue: a new site of physiological tracer biodistribution characterised by PET/CT.

The purpose of this study was to characterise a benign pattern of infradiaphragmatic 18F-fluorodeoxyglucose (FDG) uptake in cancer patients using PET/CT. Infradiaphragmatic foci of FDG uptake, localised by PET/CT in regions of normal fat tissues, were demonstrated, in conjunction with fatty uptake in the neck and shoulders, in 9 of 1,241 (0.7%) patients. The imaging and clinical characteristics of this pattern and its possible clinical significance were assessed. PET/CT precisely localised infradiaphragmatic fat uptake (IDFU) within normal retroperitoneal fatty tissue of the perirenal space (nine patients) and in the paracolic or parahepatic space (four patients). Perirenal uptake was bilateral in five patients and focal in six. Paracolic and parahepatic uptake was bilateral in three patients and linear in all four patients. There was no evidence of malignancy at any of the sites during a follow-up period of 9-21 months. IDFU was significantly more prevalent in young patients assessed for monitoring response to therapy, and was always associated with the benign supradiaphragmatic uptake pattern, although its prevalence was significantly lower. There were no significant differences between the clinical characteristics of these two patterns of benign fatty FDG uptake. It is concluded that PET/CT allows for precise identification of increased FDG uptake in abdominal fatty tissue and further exclusion of disease at such sites. This benign uptake may represent increased glucose consumption in activated brown adipose tissue, similar to the mechanism suggested for supradiaphragmatic uptake. Recognition of this benign IDFU pattern is important for correct interpretation of abdominal PET findings in cancer patients.

Abdominal Neoplasms↗

Identification and utilization of arbitrary correlations in models of recombination signal sequences.

BACKGROUND: A significant challenge in bioinformatics is to develop methods for detecting and modeling patterns in variable DNA sequence sites, such as protein-binding sites in regulatory DNA. Current approaches sometimes perform poorly when positions in the site do not independently affect protein binding. We developed a statistical technique for modeling the correlation structure in variable DNA sequence sites. The method places no restrictions on the number of correlated positions or on their spatial relationship within the site. No prior empirical evidence for the correlation structure is necessary. RESULTS: We applied our method to the recombination signal sequences (RSS) that direct assembly of B-cell and T-cell antigen-receptor genes via V(D)J recombination. The technique is based on model selection by cross-validation and produces models that allow computation of an information score for any signal-length sequence. We also modeled RSS using order zero and order one Markov chains. The scores from all models are highly correlated with measured recombination efficiencies, but the models arising from our technique are better than the Markov models at discriminating RSS from non-RSS. CONCLUSIONS: Our model-development procedure produces models that estimate well the recombinogenic potential of RSS and are better at RSS recognition than the order zero and order one Markov models. Our models are, therefore, valuable for studying the regulation of both physiologic and aberrant V(D)J recombination. The approach could be equally powerful for the study of promoter and enhancer elements, splice sites, and other DNA regulatory sites that are highly variable at the level of individual nucleotide positions.

Animals↗

Childhood derivatives of inhibition and lack of inhibition to the unfamiliar.

Behavioral and physiological assessments of 41 7 1/2-year-old children who had been selected to be inhibited or uninhibited at 21 months and observed again at 4 and 5 1/2 years revealed that each of the 2 original behavioral profiles predicted theoretically reasonable derivatives. A majority of the formerly shy, timid children became quiet and socially avoidant in unfamiliar social situations, while a majority of the formerly sociable children became talkative and interactive with peers and adults. Absolute heart-rate and cortisol level at 7 1/2 years were not as discriminating of the 2 behavioral groups as they had been 2 years earlier.

Arousal↗

Kinetics of the inhibition of axonal defasciculation and arborization mediated by carbohydrate markers in the embryonic leech.

We studied carbohydrate interactions that mediate the targeting of sensory afferents in the synaptic neuropil of segmental central nervous system (CNS) ganglia in the embryonic leech. First, we determined the rate of sensory afferent development in vivo, and then we devised a culture system that permits the normal patterning of their projections in the CNS and PNS to proceed at 92% the normal rate. Using this in vitro system, we analyzed the mannose-specific recognition that mediates the defasciculation and arborization of sensory afferents in the CNS neuropil after they have tracked through peripheral nerves as a tight axon bundle. Sensory afferent defasciculation and arborization in the neuropil were inhibited by culturing embryos in Fab fragments directed against the mannose-containing surface epitope of sensory afferents. We demonstrate that the rate at which separately extending axons or their branches are lost from the neuropil can be modeled by a first-order decay process. These kinetic studies indicate that the loss of each separately extending axon or branch is an independent event. This suggests that sensory afferent projections extend autonomously across the target region in the search of their appropriate postsynaptic partners.

Animals↗

Affective response to color-slide stimuli in subjects with physical anhedonia: a three-systems analysis.

Emotion-provoking visual stimuli were presented to college undergraduates identified as anhedonic or normal, based on their scores on the Physical Anhedonia Scale (Chapman, Chapman, & Raulin, 1976). The affective stimuli (35 mm color slides) were chosen to elicit a wide range of both positive and negative emotion, with emotional response assessed through affective judgments, viewing time, and monitoring of a variety of physiological systems (heart rate, skin conductance, and facial musculature). The experiment was successful in demonstrating differential emotional response in the two subject groups; anhedonic subjects reported a less positive response than control subjects to positive and neutral stimuli and showed no association between heart rate and the emotion content of the slides. Paradoxically, activity in the muscles of facial expression was greater in anhedonic than control subjects during the presentation of both positive and negative slides. No between-group differences were noted in the viewing-time measure. The results are discussed in the context of Lang's bioinformational theory of human emotion (Lang, 1984, 1985).

Adult↗

Associations between the neuroendocrine and immune systems.

Organisms respond to infection with complex adaptations involving bidirectional communication between the immune and neuroendocrine systems. The idea of intercellular communication between the neuroendocrine and immune systems via common signal molecules has provided a conceptual framework for such crosstalk. The studies to date show that cells of the immune system contain receptors for neuroendocrine hormones and can also be considered a source of pituitary and hypothalamic peptides. The structure and pattern of synthesis of these peptides by leukocytes appear similar to neuroendocrine hormones, although some differences exist. Once secreted, these peptide hormones may function as endogenous regulators of the immune system as well as conveyors of information from the immune to the neuroendocrine system. The plasma hormone concentrations contributed by lymphocytes usually do not reach the levels required when the pituitary gland is the source, but because immune cells are mobile, they have the potential to locally deposit the hormone at the target site. Likewise, other studies show that cells of the neuroendocrine system contain receptors for cytokines and can also be considered a source of cytokines, particularly interleukin-1 (IL-1) and IL-6. In the pituitary IL-1 beta coexists with thyroid stimulating hormone in a subpopulation of thyrotropes, suggesting it may have a role as a pituitary paracrine factor. The cytokines, including IL-1, IL-2, IL-6, interferon-gamma, and tumor necrosis factor, exert profound effects on hypothalamic pituitary axes. It is our hypothesis that the relay of information to the neuroendocrine system represents a sensory function for the immune system wherein leukocytes recognize stimuli that are not recognizable by the central and peripheral nervous systems (i.e., bacteria, tumors, viruses, and antigens). The recognition of such noncognitive stimuli by immunocytes is then converted into information and a physiological change occurs. Future studies into the physiological role that cytokines and neuroendocrine hormones have in these systems will be of considerable interest for both immunologists and endocrinologists.

Animals↗

Economic analysis of eating and physical activity: a next step for research and policy change.

Poor nutrition and physical inactivity are among the leading causes of morbidity and mortality in the United States, and widespread behavior modification is needed to improve health now and in the future. There is growing evidence that modifications in the physical environment and in social policies will be required to accomplish this goal. There is also growing recognition that economic factors have contributed to current eating and physical activity patterns, and that economic factors need to be considered when developing strategies for improving these behaviors. Identifying where economic and public health priorities converge could suggest new avenues for sustainable policy changes, which will, in turn, promote healthy choices on both an individual and population-wide level. To review the effect that economics has on eating and physical activity behaviors, the Partnership to Promote Healthy Eating and Active Living convened an Economic Analysis Forum. Two working groups were formed-one focusing on eating behaviors and one on physical activity, and both with equal representation from health-related and economic disciplines. The groups examined how economics has contributed to present eating and physical activity patterns and how economics could be used to develop interventions to improve these patterns. This article describes the challenges the groups faced in their work, the way in which the public health and economic approaches were integrated, and the questions left unanswered.

Cost-Benefit Analysis↗

Penguins use the two-voice system to recognize each other.

The sound-producing structure in birds is the syrinx, which is usually a two-part organ located at the junction of the bronchi. As each branch of the syrinx produces sound independently, many birds have two acoustic sources. Thirty years ago, we had anatomical, physiological and acoustical evidence of this two-voice phenomenon but no function was known. In songbirds, often these two voices with their respective harmonics are not activated simultaneously but they are obvious in large penguins and generate a beat pattern which varies between individuals. The emperor penguin breeds during the Antarctic winter, incubating and carrying its egg on its feet. Without the topographical cue of a nest, birds identify each other only by vocal means when switching duties during incubation or chick rearing. To test whether the two-voice system contains the identity code, we played back the modified call of their mate to both adults and also the modified call of their parents to chicks. Both the adults and the chicks replied to controls (two voices) but not to modified signals (one voice being experimentally suppressed). Our experiments demonstrate that the beat generated by the interaction of these two fundamental frequencies conveys information about individual identity and also propagates well through obstacles, being robust to sound degradation through the medium of bodies in a penguin colony. The two-voice structure is also clear in the call of other birds such as the king penguin, another non-nesting species, but not in the 14 other nesting penguins. We concluded that the two-voice phenomenon functions as an individual recognition system in species using few if any landmarks to meet. In penguins, this coding process, increasing the call complexity and resisting sound degradation, has evolved in parallel with the loss of territoriality.

Animals↗

Cellular glycoconjugates and their potential endogenous receptors in the cerebral microvasculature of man: a glycohistochemical study.

Protein-carbohydrate interactions are supposed to play a pivotal role in mediation of recognitive interactions, relevant to cellular interactions and transport. The brain microvasculature is the site of numerous cell-cell and cell-matrix recognitive interactions. Assuming carbohydrate-protein interactions play important physiological roles here, then specific carbohydrate-binding proteins should be prominent components of this microvasculature, in addition to the wealth of endogenous glycoconjugates reported by other authors. Human brain and brain tumor microvessels were analyzed histochemically for expression of endogenous sugar-binding proteins using a panel of biotin-conjugated, chemically glycosylated probes with specificities for alpha-/beta-D-galactosides and -D-glucosides, alpha-L-fucosides, alpha-D-mannosides, and beta-D-xylosides, and for expression of endogenous glycoconjugates using a panel of biotin-conjugated plant lectins with specificities for fucoside, galactoside, mannoside and glucoside moieties. Wax-embedded aldehyde- or Bouin-fixed tissues or acetone-fixed frozen sections were examined. Blood-brain barrier function was checked by ascertaining immunohistochemically the extravasation of serum albumin in these tissues. Microvessels in normal human brain tissues (with intact blood-brain barrier) contained abundant endogenous sugar-binding proteins with specificities for beta-galactosides, alpha-mannosides and beta-xylosides, and lesser amounts of proteins binding alpha-galactosides, alpha-fucosides and glucosides. Endogenous glycoconjugates bearing beta-galactoside, alpha-D-mannoside/alpha-D-glucoside or alpha-L-fucoside moieties were also abundant. In brain tumors (with defective blood brain barrier) the microvessels contained altered patterns of endogenous sugar-binding proteins, particularly noticeable in glioblastomas, in which there were notable alterations in galactoside-binding proteins in the microvessels.

Adult↗

Localization of epileptic foci.

This chapter is devoted to the contribution of long-term EEG and behavioral monitoring to the localization of epileptic foci. Combined EEG and video monitoring may clarify the clinical seizure pattern reported by history; it may confirm or invalidate its localizing significance. It may also reveal unsuspected multiple clinical seizure patterns which may or may not correspond to multiple areas of seizure onset. The localizing evidence derived from interictal EEG abnormality provides valuable additional diagnostic information, identifying a likely area of seizure onset. Automatic spike recognition may improve the quality of the information provided by interictal activity by providing otherwise unavailable quantitative information. The main application of EEG monitoring is for detecting the region of seizure onset. This is important for the identification of seizure type, the differentiation between epileptic and non-epileptic seizures and the preoperative localization of seizure onset. Reliable localization in patients with partial seizures depends upon demonstration of a precise focal or regional onset of the ictal EEG changes occurring prior to or simultaneously with clinical seizure manifestations. Use of intracranial electrodes is indicated when monitoring with extracranial electrodes has not provided unequivocal localization of seizure onset. Automatic seizure recognition and phase analysis may again increase the yield of monitoring in localizing epileptogenic foci.

Automation↗

Lentiviral vectors and antiretroviral intrinsic immunity.

Multicellular organisms have evolved under relentless attacks from pathogens, and as a consequence have spiked their genomes with numerous genes that serve to thwart these threats, notably through the building of the innate and adaptive arms of the immune system. The innate immune system is by far the most ancient, being found as widely as in plants and Drosophila, while adaptive immunity arose with the emergence of cartilaginous fishes. Innate immunity enters rapidly into the game during the course of an infection and generally involves the recognition by specific cellular receptors of common pathogen-associated patterns to elicit broad defensive responses, mediated in humans by interferons, macrophages, and natural killer cells, amongst others. When innate immunity fails to eradicate the infection quickly, adaptive immune responses enter into play, to generate exquisitely specific defenses to virtually any pathogen, thanks to a quasi-infinite repertoire of nonself receptors and effectors. A specific form of innate immunity, coined "intrinsic immunity," completes this protection by providing a constant, always-on, line of defense, generally through intracellular obstacles to the replication of pathogens. This component of the immune system has gained much attention as it was discovered that it is a cornerstone of the resistance of mammals against retroviruses. One of these newly discovered intracellular molecular weapons, the APOBEC family of proteins, is active against several classes of retroelements. We present here the current state of knowledge on this rapidly evolving field and discuss implications for gene therapy.

APOBEC-3G Deaminase↗

The mouse homolog of the orphan nuclear receptor tailless is expressed in the developing forebrain.

The Drosophila tailless gene is a member of the orphan nuclear receptor subfamily. In Drosophila, the tailless gene is required for pattern formation in embryonic poles. During development, tailless is activated in the termini of the embryo in response to the torso receptor tyrosine kinase signal transduction cascade. Recessive mutations of tailless result in abnormalities in anterior portions of the head and in all structures posterior to the eighth abdominal segment. Localised expression of tailless is required in combination with a second terminal gene, huckebein, to control the expression of downstream genes. We have isolated a mouse homolog of the Drosophila tailless gene, which shows considerable homology in the DNA-binding domain suggesting that the respective proteins bind similar recognition sequences. Although the ligand-binding domain shows features in common with the tailless ligand domain, it also shares conserved amino acid stretches with other orphan nuclear receptors, the human ovalbumin upstream binding protein transcription factors (hCOUP-TF I and II). We have analysed the expression of taillees in mice, and show that it is specifically localised to the developing forebrain from day 8 p.c. and in dorsal midbrain from day 8.75 p.c. To define the anterior and posterior boundaries of expression, we compared the expression pattern of tailless to those of other forebrain markers, including distal-less (Dlx1), brain factor 1 (BF1), and the orthodenticle genes (Otx1 and Otx2). In addition to the developing forebrain, these genes show dynamic patterns of expression in two structures whose development requires inductive signals from the forebrain: the eye and the nose. These results suggest that the mouse taillees gene may be required to pattern anterior brain differentiation.

Animals↗

Illusory contours do not pass through the "blind spot".

Our visual percepts are not fully determined by the physical stimulus input. That is why we perceive crisp bounding contours even in the absence of luminance-defined borders in visual illusions such as the Kanizsa figure. It is important to understand which neural processes are involved in creating these artificial visual experiences because this might tell us how we perceive coherent objects in natural scenes, which are characterized by mutual overlap. We have already shown using functional magnetic resonance imaging [Maertens, M., & Pollmann, S. fMRI reveals a common neural substrate of illusory and real contours in v1 after perceptual learning. Journal of Cognitive Neuroscience, 17, 1553-1564, 2005] that neurons in the primary visual cortex (V1) respond to these stimuli. Here we provide support for the hypothesis that V1 is obligatory for the discrimination of the curvature of illusory contours. We presented illusory contours across the portion of the visual field corresponding to the physiological "blind spot." Four observers were extensively trained and asked to discriminate fine curvature differences in these illusory contours. A distinct performance drop (increased errors and response latencies) was observed when illusory contours traversed the blind spot compared to when they were presented in the "normal" contralateral visual field at the same eccentricity. We attribute this specific performance deficit to the failure to build up a representation of the illusory contour in the absence of a cortical representation of the "blind spot" within V1. The current results substantiate the assumption that neural activity in area V1 is closely related to our phenomenal experience of illusory contours in particular, and to the construction of our subjective percepts in general.

Adult↗

Nucleic acid is a novel ligand for innate, immune pattern recognition collectins surfactant proteins A and D and mannose-binding lectin.

Collectins are a family of innate immune proteins that contain fibrillar collagen-like regions and globular carbohydrate recognition domains (CRDs). The CRDs of these proteins recognize various microbial surface-specific carbohydrate patterns, particularly hexoses. We hypothesized that collectins, such as pulmonary surfactant proteins (SPs) SP-A and SP-D and serum protein mannose-binding lectin, could recognize nucleic acids, pentose-based anionic phosphate polymers. Here we show that collectins bind DNA from a variety of origins, including bacteria, mice, and synthetic oligonucleotides. Pentoses, such as arabinose, ribose, and deoxyribose, inhibit the interaction between SP-D and mannan, one of the well-studied hexose ligands for SP-D, and biologically relevant d-forms of the pentoses are better competitors than the l-forms. In addition, DNA and RNA polymer-related compounds, such as nucleotide diphosphates and triphosphates, also inhibit the carbohydrate binding ability of SP-D, or approximately 60 kDa trimeric recombinant fragments of SP-D that are composed of the alpha-helical coiled-coil neck region and three CRDs (SP-D(n/CRD)) or SP-D(n/CRD) with eight GXY repeats (SPD(GXY)(8)(n/CRD)). Direct binding and competition studies suggest that collectins bind nucleic acid via their CRDs as well as by their collagen-like regions, and that SP-D binds DNA more effectively than do SP-A and mannose-binding lectin at physiological salt conditions. Furthermore, the SP-D(GXY)(8)(n/CRD) fragments co-localize with DNA, and the protein competes the interaction between propidium iodide, a DNA-binding dye, and apoptotic cells. In conclusion, we show that collectins are a new class of proteins that bind free DNA and the DNA present on apoptotic cells by both their globular CRDs and collagen-like regions. Collectins may therefore play an important role in decreasing the inflammation caused by DNA in lungs and other tissues.

Animals↗

Patterns of attractor dimensions of sleep EEG.

Low dimensional chaos is a property of many physiological oscillatory systems including the brain. Time series of sleep EEG records have been analyzed in the framework of recent developments in nonlinear dynamics. One of the characteristics of a chaotic time series is its attractor dimension. The running attractor dimension of a chaotic time series may reflect changes in states more accurately than manually scored records. In the present study the attractor dimensions of consecutive EEG segments of five sleep records were analyzed. The block of the EEG segment (window) was shifted by various lengths along the entire sleep data of each subject thus producing a running attractor dimension curve for each record. The attractor dimension values for different sleep stages were significantly different. The pattern of the running attractor dimension closely matched the scored hypnograms in these five sleep records.

Adolescent↗