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PubMed1981

Within-day physiologic variation of leukocyte types in healthy subjects as assayed by two automated leukocyte differential analyzers.

The physiologic within-day (700-2200 h) variation of leukocyte-type concentrations in blood as determined for 21 healthy young adults is reported. All blood specimens were obtained in duplicate such that the within-batch analytic variation, as well as the pertinent biologic sources of variation, was able to be determined. All specimens were analyzed on each of two automated leukocyte differential systems: Hemalog-D Differential System and the Hematrak-240 Analyzer. On the basis of a comparison of the performances of the two analyzers, it was decided to report the neutrophil and the lymphocyte values as measured on both systems, the monocyte values as measured on teh Hematrak only, and the eosinophil and basophil values as measured on the Hemalog-D only. The intrasubject within-day physiologic variations for the cell on the Hemalog-D and Hematrak, respectively, in terms of coefficient of variation wee as follows: neutrophils 19.4% and 19.6%; lymphocytes, 13.8% and 17.5%. For monocytes, as measured on the Hematrak, it was 13.4%. For eosinophils and basophils, as measured on the Hemalog-D, it was 27.2% and 8.3%, respectively. There was a consistent group-specific diurnal variance that amounted to more than 40% of the total within-day variance, both for lymphocytes and for eosinophils. The within-day physiologic variation of the cell type concentrations for eight of the volunteers was compared with that of the plasma cortisol concentrations, as determined on specimens derived from the same veni-puncture sessions. The decrease in plasma cortisol values was in most instances associated with decreases in eosinophils and increases in neutrophils. For total leukocytes and neutrophils, the mean concentration for smokers was significantly higher than that for nonsmokers.

Adult↗

PubMed1989

Event-related potentials and visual spatial attention: influence of a cholinergic drug.

The effects of two dosages (200 mg, 600 mg, placebo) of a cholinergic nootropic (WEB 1881 FU) were investigated in a visual spatial attention task. Event-related brain potentials (ERPs) were used as a physiological measure of attention as they have previously been shown to be sensitive to allocation of attention to points in space. The typical enhancement of several peaks of the visual ERP due to attention was found in the present experiment. No systematic effect of the medication was revealed, suggesting that the effects of WEB 1881 FU do not extend to early perceptual processes.

Adult↗

PubMed1991

Failure of object recognition due to a breakdown of figure-ground discrimination in a patient with normal acuity.

We report the case of a 71-year-old woman with partial cortical blindness attributable to cortical degeneration. Her visual acuity and colour perception were satisfactory but she was almost totally unable to recognize objects or people by sight. Investigations revealed a hitherto unreported dissociation between relatively well preserved shape discrimination and gravely impaired figure-ground discrimination. Thus, she was able to discriminate between a square and an oblong matched for total surface but she was unable to detect a simple shape against a pattern background. In a series of experiments it was shown that she could identify single printed capital letters of the alphabet relatively satisfactorily. She had no difficulty in identifying single, simple geometric shapes. By contrast, she was unable to discriminate configurations of two or three overlapping or concentric, simple, shapes. Strikingly she appeared to be "blind" to subjective contours and she was unable to perceive visual illusions normally. These deficits are interpreted to reflect a failure to achieve primitive organization of visual information rather than higher level perceptual impairments. The results are discussed in the context of physiological and computational models of early visual information processing.

Aged↗

PubMed2005

Metabolomics in human nutrition: opportunities and challenges.

Metabolomics has been widely adopted in pharmacology and toxicology but is relatively new in human nutrition. The ultimate goal, to understand the effects of exogenous compounds on human metabolic regulation, is similar in all 3 fields. However, the application of metabolomics to nutritional research will be met with unique challenges. Little is known of the extent to which changes in the nutrient content of the human diet elicit changes in metabolic profiles. Moreover, the metabolomic signal from nutrients absorbed from the diet must compete with the myriad of nonnutrient signals that are absorbed, metabolized, and secreted in both urine and saliva. The large-bowel microflora also produces significant metabolic signals that can contribute to and alter the metabolome of biofluids in human nutrition. Notwithstanding these possible confounding effects, every reason exists to be optimistic about the potential of metabolomics for the assessment of various biofluids in nutrition research. This potential lies both in metabolic profiling through the use of pattern-recognition statistics on assigned and unassigned metabolite signals and in the collection of comprehensive data sets of identified metabolites; both objectives have the potential to distinguish between different dietary treatments, which would not have been targeted with conventional techniques. The latter objective sets out a well-recognized challenge to modern biology: the development of libraries of small molecules to aid in metabolite identification. The purpose of the present review was to highlight some early challenges that need to be addressed if metabolomics is to realize its great potential in human nutrition.

Diet↗

PubMed2005

User stress detection in human-computer interactions.

The emerging research area of Affective Computing seeks to advance the field of Human-Computer Interaction (HCI) by enabling computers to interact with users in ways appropriate to their affective states. Affect recognition, including the use of psychophysiologcal measures (e.g. heart rate), facial expressions, speech recognition etc. to derive an assessment of user affective state based on factors from the current task context, is an important foundation required for the development of Affective Computing. Our research focuses on the use of three physiological signals: Blood Volume Pulse (BVP), Galvanic Skin Response (GSR) and Pupil Diameter (PD), to automatically monitor the level of stress in computer users. This paper reports on the hardware and software instrumentation development and signal processing approach used to detect the stress level of a subject interacting with a computer, within the framework of a specific experimental task, which is called the 'Stroop Test'. For this experiment, a computer game was implemented and adapted to make the subject experience the Stroop Effect, evoked by the mismatch between the font color and the meaning of a certain word (name of a color) displayed, while his/her BVP, GSR and PD signals were continuously recorded. Several data processing techniques were applied to extract effective attributes of the stress level of the subjects throughout the experiment. Current results indicate that there exists interesting similarity among changes in those three signals and the shift in the emotional states when stress stimuli are applied to the interaction environment.

Adult↗

PubMedDate not supplied

Clinical trial of time-resolved scanning optical mammography at 4 wavelengths between 683 and 975 nm.

The first time-resolved optical mammograph operating beyond 900 nm (683, 785, 913, and 975 nm) is presently being used in a clinical trial to test the diagnostic potential of the technique in detecting and characterizing breast lesions. Between November 2001 and October 2002, 101 patients with malignant and benign lesions were analyzed retrospectively. Scattering plots, as derived from a homogeneous model, and late gated intensity images, to monitor spatial changes in the absorption properties, are routinely used. The intensity images available at four wavelengths provide sensitivity to the main tissue constituents (oxy- and deoxyhemoglobin, water, and lipids), in agreement with expected tissue composition and physiology, while the scattering plots mirror structural changes. Briefly, tumors are usually identified due to the strong blood absorption at short wavelengths, cysts to the low scattering, and fibroadenomas to low absorption at 913 nm and high at 975 nm, even though the optical features of fibroadenomas seem not to be uniquely defined. The effectiveness of the technique in localizing and discriminating different lesion types is analyzed as a function of various parameters (lesion size, compressed breast thickness, and breast parenchymal pattern). .

Algorithms↗

PubMed1991

A model for contrast discrimination with incremental and decremental test patches.

Whittle [Vision Research, 26, 1677 (1986)] has shown that the metric of contrast W = delta L/Lmin (delta L = difference in luminance between test patch and background, Lmin = the smaller of the luminance of the background or test patch) is able to provide a unifying description of the pattern of contrast discrimination thresholds for pairs of test patches set against a common background. In particular the metric W unifies the pattern of discrimination thresholds for both increment and decrement pairs. We argue that while W provides a good mathematical description of Whittle's data it is functionally implausible since it implies that the component of the stimulus which sets the adaptational level for increments is different from that which sets the adaptational level for decrements. We argue that the metric G = ln(L/Lb) (L = test patch luminance, Lb = background luminance) is physiologically more plausible than W and show that G can provide at least as good a fit as W to Whittle's data when incorporated in a transfer function of the form RG = kG1-n, with n set to 0.69. The fit to the data can be improved still further if a parameter representing the non-linearity in the gain-luminance function at low luminances is included in the RG equation. The theoretical implications for retinal gain mechanisms are discussed.

Contrast Sensitivity↗

PubMed2003

New models of intravital microscopy for analysis of chemokine receptor-mediated leukocyte vascular recognition.

Chemokines control selective targeting of circulating leukocytes to the microvasculature by triggering inside-out signal transduction pathways leading to integrin-dependent adhesion. Presently, a few examples of presentation of chemokines by the inner surface of blood vessels responsible for triggering leukocyte arrest are available. A complete pattern of chemokine expression and presentation by the endothelium in different tissues and in homeostatic versus inflammatory conditions is still lacking. This review describes a novel intravital microscopy model allowing visualization of cerebral vessels through the skull, and analysis of the interactions between different leukocyte subpopulations and the endothelium in brain superficial microvasculature of mice. It has been recently shown that inflamed brain endothelium expresses a combination of adhesion ligands and activating factor(s) for G(i)-linked receptors that together mediate lymphocyte recruitment, and that the combination of molecules involved in this central nervous system (CNS) venule adhesion cascade strongly favors the arrest of activated versus nai;ve T cells. However, the identification of the chemokine(s) expressed by the endothelium leading to integrin activation and arrest still remains to be determined. The new approach presented here to study the brain microcirculation may provide an useful tool for further investigations of physiologic and pathologic events that occur in the CNS.

Animals↗

PubMed2006

TLRs in the Gut I. The role of TLRs/Nods in intestinal development and homeostasis.

The innate immune system includes microbial pattern recognition receptors that detect bacteria and viral products at the cell surface, in vesicles, and within the cytoplasm. Transmembrane signaling occurs through Toll-like receptors (TLRs). Cytoplasmic receptors are generally members of the nucleotide-binding domain (NOD)-leucine-rich repeat (LRR) family (CATERPILLER family). They influence the effects of other family members and of TLRs. Most NOD-LRR members enhance signal transduction, but Monarch-1 counterbalances TLR activity. NOD-LRR family members also act within the adaptive immune system. The class II transactivator regulates major histocompatibility complex class II expression. In the intestine, it is developmentally regulated, and its expression depends on weaning and, independently, on age.

Animals↗

PubMed2006

Soluble fibrin inhibits monocyte adherence and cytotoxicity against tumor cells: implications for cancer metastasis.

BACKGROUND: Soluble fibrin (sFn) is a marker for disseminated intravascular coagulation and may have prognostic significance, especially in metastasis. However, a role for sFn in the etiology of metastatic cancer growth has not been extensively studied. We have reported that sFn cross-linked platelet binding to tumor cells via the major platelet fibrin receptor alphaIIb beta3, and tumor cell CD54 (ICAM-1), which is the receptor for two of the leukocyte beta2 integrins (alphaL beta2 and aM beta2). We hypothesized that sFn may also affect leukocyte adherence, recognition, and killing of tumor cells. Furthermore, in a rat experimental metastasis model sFn pre-treatment of tumor cells enhanced metastasis by over 60% compared to untreated cells. Other studies have shown that fibrin(ogen) binds to the monocyte integrin alphaM beta2. This study therefore sought to investigate the effect of sFn on beta2 integrin mediated monocyte adherence and killing of tumor cells. METHODS: The role of sFn in monocyte adherence and cytotoxicity against tumor cells was initially studied using static microplate adherence and cytotoxicity assays, and under physiologically relevant flow conditions in a microscope perfusion incubator system. Blocking studies were performed using monoclonal antibodies specific for beta2 integrins and CD54, and specific peptides which inhibit sFn binding to these receptors. RESULTS: Enhancement of monocyte/tumor cell adherence was observed when only one cell type was bound to sFn, but profound inhibition was observed when sFn was bound to both monocytes and tumor cells. This effect was also reflected in the pattern of monocyte cytotoxicity. Studies using monoclonal blocking antibodies and specific blocking peptides (which did not affect normal coagulation) showed that the predominant mechanism of fibrin inhibition is via its binding to alphaM beta2 on monocytes, and to CD54 on both leukocytes and tumor cells. CONCLUSION: sFn inhibits monocyte adherence and cytotoxicity of tumor cells by blocking alphaL beta2 and alphaM beta2 binding to tumor cell CD54. These results demonstrate that sFn is immunosuppressive and may be directly involved in the etiology of metastasis. Use of specific peptides also inhibited this effect without affecting coagulation, suggesting their possible use as novel therapeutic agents in cancer metastasis.

Journal Article↗

PubMed1996

Dynamic synapse: a new concept of neural representation and computation.

Presynaptic mechanisms influencing the probability of neurotransmitter release from an axon terminal, such as facilitation, augmentation, and presynaptic feedback inhibition, are fundamental features of biological neurons and are cardinal physiological properties of synaptic connections in the hippocampus. The consequence of these presynaptic mechanisms is that the probability of release becomes a function of the temporal pattern of action potential occurrence, and hence, the strength of a given synapse varies upon the arrival of each action potential invading the terminal region. From the perspective of neural information processing, the capability of dynamically tuning the synaptic strength as a function of the level of neuronal activation gives rise to a significant representational and processing power of temporal spike patterns at the synaptic level. Furthermore, there is an exponential growth in such computational power when the specific dynamics of presynaptic mechanisms varies quantitatively across axon terminals of a single neuron, a recently established characteristic of hippocampal synapses. During learning, alterations in the presynaptic mechanisms lead to different pattern transformation functions, whereas changes in the postsynaptic mechanisms determine how the synaptic signals are to be combined. We demonstrate the computational capability of dynamic synapses by performing speech recognition from unprocessed, noisy raw waveforms of words spoken by multiple speakers with a simple neural network consisting of a small number of neurons connected with synapses incorporating dynamically determined probability of release. The dynamics included in the model are consistent with available experimental data on hippocampal neurons in that parameter values were chosen so as to be consistent with time constants of facilitative and inhibitory processes governing the dynamics of hippocampal synaptic transmission studied using nonlinear systems analytic procedures.

Acoustic Stimulation↗

PubMed1982

The oblique effects of pattern and flicker sensitivity: implications for mixed physiological input.

The inferior contrast sensitivity for oblique gratings has been previously demonstrated at high spatial frequencies with an absolute criterion. In this study contrast sensitivity at oblique and main axis orientations was obtained under separate pattern and flicker threshold criteria across a range of both spatial and temporal frequencies. The anisotropy of contrast sensitivity was not observed at low spatial frequencies under any stimulus or criterion conditions. At high spatial frequencies the anisotropy was observed for both pattern and flicker thresholds, although the flicker anisotropy was less pronounced. If, as previously suggested, this anisotropy is mediated by X cells, then these psychophysical findings suggest a mixed model in which both pattern and flicker systems receive input from both X and Y-cell pathways.

Adult↗

PubMedDate not supplied

Calcium oscillations encoding neuron-to-astrocyte communication.

The observation that the excitatory neurotransmitter glutamate released from presynaptic terminals can activate, beside the post-synaptic neuron, the glial cell astrocyte, stimulated glial cell research like no other event since the recognition in the 1980s that astrocytes can express on their membrane many receptors for classical neurotransmitters. The properties and the functional role(s) of such a neuron-to-astrocyte signaling have now become the focus of intense research in neurobiology. Indeed, a growing body of evidence has recently highlighted the ability of astrocytes to work as sophisticated detectors of synaptic activity: by changing the frequency of [Ca(2+)](i) oscillations evoked by the synaptic release of glutamate, these cells display the remarkable capacity to discriminate between different levels and patterns of synaptic activity. Furthermore, the observation that astrocytes increase the frequency of [Ca(2+)](i) oscillations in response to repetitive episodes of high neuronal activity challenges the common concept that memory function in the brain is an exclusive property of neuronal cells. Glutamate-mediated [Ca(2+)](i) elevations can also trigger in astrocytes the release of glutamate that can ultimately affect neuronal transmission. Given the wide role played by glutamate in brain physiology, our view on how the brain operates needs now to be revised taking into account the bi-directional, glutamatergic communication between neurons and astrocytes.

Animals↗

PubMed2006

Objective detection of evoked potentials using a bootstrap technique.

Evoked potentials are usually evaluated subjectively, by visual inspection, and considerable differences between interpretations can occur. Objective, automated methods are normally based on calculating one (or more) parameters from the data, but only some of these techniques can provide statistical significance (p-values) for the presence of a response. In this work, we propose a bootstrap technique to provide such p-values, which can be applied to a wide variety of parameters. The bootstrap method is based on randomly resampling (with replacement) the original data and gives an estimate of the probability that the response obtained is due to random variation in the data rather than a physiological response. The method is illustrated using auditory brainstem responses (ABRs) to detecting hearing thresholds. The flexibility of the approach is illustrated, showing how it can be used with different parameters, numbers of stimuli and with user-defined false-positive rates. The bootstrap method provides a new, simple and yet powerful means of detecting evoked potentials, which is very flexible and readily adapted to a wide variety of signal parameters.

Adolescent↗

PubMed1986

In vitro binding of LexA repressor to DNA: evidence for the involvement of the amino-terminal domain.

Both the amino-terminal and the carboxy-terminal domain of the LexA repressor have been purified using the LexA protein autodigestion reaction at alkaline pH, which leads to the same specific products as the physiological RecA-catalyzed proteolysis of repressor. We show by circular dichroism (c.d) that, upon non-specific binding to DNA, the purified amino-terminal domain induces a very similar if not identical conformational change of the DNA as does the entire repressor. The positive c.d. signal increases approximately 3-fold if the DNA lattice is fully saturated with protein. Further, the amino-terminal domain of the LexA protein binds specifically to the operator of the recA gene, producing qualitatively the same effects on the methylation pattern of the guanine bases by dimethylsulfate as the entire repressor, consisting of a methylation inhibition effect at four distal operator guanines and a slight enhancement at the central bases. The spacing between these contacts suggests that LexA does not bind to the operator along the same face of the DNA helix. As shown by c.d. studies the amino-terminal domain harbours a substantial amount of residues in alpha-helical conformation, a prerequisite for DNA recognition via a helix--turn--helix structural motif as proposed for many other regulatory proteins.

Bacterial Proteins↗

PubMed2004

Low-dose hyper-radiosensitivity: a consequence of ineffective cell cycle arrest of radiation-damaged G2-phase cells.

This review highlights the phenomenon of low-dose hyper- radiosensitivity (HRS), an effect in which cells die from excessive sensitivity to small single doses of ionizing radiation but become more resistant (per unit dose) to larger single doses. Established and new data pertaining to HRS are discussed with respect to its possible underlying molecular mechanisms. To explain HRS, a three-component model is proposed that consists of damage recognition, signal transduction and damage repair. The foundation of the model is a rapidly occurring dose-dependent pre-mitotic cell cycle checkpoint that is specific to cells irradiated in the G2phase. This checkpoint exhibits a dose expression profile that is identical to the cell survival pattern that characterizes HRS and is probably the key control element of low-dose radiosensitivity. This premise is strengthened by the recent observation coupling low- dose radiosensitivity of G2-phase cells directly to HRS. The putative role of known damage response factors such as ATM, PARP, H2AX, 53BP1 and HDAC4 is also included within the framework of the HRS model.

Adaptation, Physiological↗

PubMed1994

Differential recognition by conglutinin and mannan-binding protein of N-glycans presented on neoglycolipids and glycoproteins with special reference to complement glycoprotein C3 and ribonuclease B.

Conglutinin and mannan-binding protein are serum proteins that have similar carbohydrate binding specificities toward high mannose-type oligosaccharides, and yet only conglutinin binds the complement glycoprotein iC3b, which contains oligosaccharides of this type. In the present study, the interactions of conglutinin and mannan-binding protein were evaluated with the complement glycoprotein C3, including various physiologically derived fragments of this glycoprotein, and neoglycolipids prepared from oligosaccharides released from C3 and its isolated alpha and beta chains. Several conclusions can be drawn. First, the interaction of conglutinin is profoundly influenced by the state of the protein moiety of the alpha chain in the vicinity of the glycosylation site Asn-917. Second, the binding to the C3-derived glycoprotein iC3b appears to be exclusively mediated through the Man8 or Man9 oligosaccharide on the alpha chain; there is no evidence for other N-linked oligosaccharides on C3 that are uniquely bound by conglutinin. Third, although conglutinin shows a more restricted binding relative to mannan-binding protein toward the oligosaccharides free of protein, it has a broader binding pattern toward the oligosaccharides as presented on C3-derived glycoproteins. From these and additional observations with RNase B, which contains high mannose-type oligosaccharides at Asn-34, it is clear that the protein moieties of these glycoproteins markedly influence the presentation of the oligosaccharides such that biological specificity is mediated by the commonly occurring high mannose-type oligosaccharides in the context of specific carrier proteins.

Blood Proteins↗

PubMed2005

Ecological adaptation and species recognition drives vocal evolution in neotropical suboscine birds.

Given that evolutionary divergence in mating signals leads to reproductive isolation in numerous animal taxa, understanding what drives signal divergence is fundamental to our understanding of speciation. Mating signals are thought to diverge via several processes, including (1) as a by-product of morphological adaptation, (2) through direct adaptation to the signaling environment, or (3) to facilitate species recognition. According to the first two hypotheses, birdsongs diversify in different foraging niches and habitats as a product of selection for optimal morphology and efficient sound transmission, respectively. According to the third hypothesis, they diversify as a result of selection against maladaptive hybridization. In this study I test all three hypotheses by examining the influence of morphology, acoustic environment, and the presence of closely related congeners on song structure in 163 species of antbird (Thamnophilidae). Unlike oscine passerines, these Neotropical suboscines make ideal subjects because they develop their songs without learning. In other words, patterns of vocal divergence are not complicated by cultural evolution. In support of the morphological adaptation hypothesis, body mass correlates with the acoustic frequency of songs, and bill size with temporal patterning. These relationships were robust, even when controlling for phylogenetic inertia using independent contrasts, suggesting that there has been correlated evolution between morphological and acoustic traits. The results also support the acoustic adaptation hypothesis: birds which habitually sing in the understory and canopy produce higher-pitched songs than those that sing in the midstory, suggesting that song structure is related to the sound transmission properties of different habitat strata. Finally, the songs of sympatric pairs of closely related species are more divergent than those of allopatric pairs, as predicted by the species recognition hypothesis. To my knowledge, these data provide the first direct evidence that species recognition and ecological adaptation operate in tandem, and that the interplay between these factors drives the evolution of mating signals in suboscine birds.

Acoustics↗