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Human peripheral blood mononuclear cells: ; Inhibition of biotin transport by reversible competition with pantothenic acid is quantitatively minor.

A transporter present in intestinal cells and in choriocarcinoma cells has been shown to transport both pantothenic acid and biotin at similar transporter affinities. However, the concentration of pantothenic acid in most foods and biological fluids is approximately 200 times the concentration of biotin; theoretically, pantothenic acid might substantially reduce biotin transport via competition. In the present study, we sought to determine whether pantothenic acid reduces biotin transport by the biotin transporter in peripheral blood mononuclear cells (PBMC). PBMC were isolated from human blood by gradient centrifugation. Incubations with [(3)H]biotin and pantothenic acid were conducted at physiologic concentrations. Intracellular [(3)H]biotin was quantified after washing by liquid scintillation counting. Pantothenic acid at 10 to 1,000 nmol/L reduced biotin (475 pmol/L) uptake by less than 12% (P < 0.05). Based on Lineweaver-Burk plots, the competition was reversible. Several structural analogs of pantothenic acid at 1,000 nmol/L reduced biotin transport by only 7 to 15% (P = 0.13). No pattern of molecular structure required for recognition by the transporter was apparent. Extracellular pantothenic acid did not affect biotin efflux from [(3)H]biotin-loaded PBMC (P > 0.05), suggesting that countertransport of extracellular pantothenic acid and intracellular biotin does not increase biotin efflux from PBMC. We conclude that the physiologic effects of pantothenic acid on the transport of biotin in PBMC are likely to be quantitatively minor.

Journal Article↗

Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments.

Pattern recognition by Toll-like receptors (TLRs) is known to be important for the induction of dendritic cell (DC) maturation. DCs, in turn, are critically important in the initiation of T cell responses. However, most viruses do not infect DCs. This recognition system poses a biological problem in ensuring that most viral infections be detected by pattern recognition receptors. Furthermore, it is unknown what, if any, is the contribution of TLRs expressed by cells that are infected by a virus, versus TLRs expressed by DCs, in the initiation of antiviral adaptive immunity. Here we address these issues using a physiologically relevant model of mucosal infection with herpes simplex virus type 2. We demonstrate that innate immune recognition of viral infection occurs in two distinct stages, one at the level of the infected epithelial cells and the other at the level of the noninfected DCs. Importantly, both TLR-mediated recognition events are required for the induction of effector T cells. Our results demonstrate that virally infected tissues instruct DCs to initiate the appropriate class of effector T cell responses and reveal the critical importance of the stromal cells in detecting infectious agents through their own pattern recognition receptors.

Adaptor Proteins, Signal Transducing↗

Trend recognition in clinical signals using template-based methods.

The recognition of clinically significant trends in monitored signals plays an important role in many medical diagnostic applications. A template-based system technique to identify characteristic patterns in time-series data is described, based on fuzzy logic. Fuzzy set theory allows the creation of fuzzy templates from linguistic rules. The resulting fuzzy template system can accommodate multiple time signals, relative or absolute trends, and automatically generates a normalised "goodness of fit" score. The template approach was originally developed for monitoring during anaesthesia but has the potential to be useful in other domains that require temporal pattern recognition.

Artificial Intelligence↗

APOE-dependent PET patterns of brain activation in Alzheimer disease.

Using H2(15)O PET, the authors imaged 13 patients with Alzheimer disease (AD) while performing a serial nonverbal recognition memory task. Patterns of brain activation differed as a function of APOE genotype: epsilon4 carriers exhibited lower activation in the left lingual gyrus and higher activation in left cuneus, precuneus, parahippocampal, and right precentral gyrus. The APOE genotype seems to play a role in cerebral physiologic activity even after onset of clinical manifestations of AD.

Age of Onset↗

The functional emergence of prefrontally-guided working memory systems in four- to eight-year-old children.

The neural processes that underlie the functional emergence of human cognitive functions, particularly those associated with the prefrontal cortex (PFC), are of growing interest to developmental psychologists and neuroscientists. Specifically, working memory functions have been correlated with PFC activity in nonhuman primates and adult humans but have not been extensively studied in children. We examined the developmental emergence of functions involved in working memory through the use of the Cambridge Neuropsychological Test Automated Battery (CANTAB), a computerized battery of nonverbal visually-presented neuropsychological tests designed to dissociate frontal from temporal lobe behavioral functions. Participants were normal children, aged 4-8 (n = 181) and a small group of young adults (n = 24) who completed measures of Spatial Memory Span, Spatial Working Memory, the Tower of London planning task, Visual Pattern and Spatial Recognition tasks, and a Set-Shifting task. Findings indicate a general age-related progression in ability levels on frontal lobe tasks, with 4-year-olds performing worse than 5- to 7-year-olds on all measures. Eight-year-olds are superior to younger children in their ability to solve complex problems but have not yet reached adult levels of performance on the most difficult items of the Tower of London and Spatial Working Memory tasks. We conclude that the development of working memory functions proceeds dimensionally, starting with refinement of basic perceptual and sensorimotor functions and culminating with the physiological maturation of widespread neural networks that integrate complex processing demands inherent to working memory tasks.

Adolescent↗

Visual resolution, contrast sensitivity, and the cortical magnification factor.

This study shows that photopic contrast sensitivity and resolution can be predicted by means of simple functions derived by using the cortical magnification factor M as a scale factor of mapping from the visual field into the striate cortex. We measured the minimum contrast required for discriminating the direction of movement or orientation of sinusoidal gratings, or for detecting them in central and peripheral vision. No qualitative differences were found between central and peripheral vision, and almost all quantitative differences observed could be removed by means of a size compensation derived from M. The results indicated specifically that (1) visual patterns can be made equally visible if they are scaled so that their calculated cortical representations become equivalent; (2) contrast sensitivity follows the same power function of the cortical area stimulated by a grating at any eccentricity; (3) area and squared spatial frequency are reciprocally related as determinants of contrast sensitivity; and (4) acuity and resolution are directly proportional to M, and the minimum angle of resolution is directly proportional to M-1. The power law of spatial summation expressed in (2) and (3) suggests the existence of a central integrator that pools the activity of cortical neurons. This summation mechanism makes the number of potentially activated visual cells the most important determinant of visibility and contrast sensitivity. The functional homogeneity of image processing across the visual field observed here agrees with the assumed anatomical and physiological uniformity of the visual cortex.

Brain Mapping↗

Consequence of functional Nod2 and Tlr4 mutations on gene transcription in Crohn's disease patients.

The concept that mutations in germ-line encoded pattern recognition receptors with immune activating functions are associated with an increased incidence in Crohn's disease (CD) is gaining acceptance. Whether these mutations have similar or distinct effects on cellular physiology remains obscure. The incidence of three single nucleotide polymorphisms (SNPs) within the Nod2 gene and one functional SNP within both the Tlr4 and Tlr5 gene in a Dutch cohort of 637 patients with inflammatory bowel disease and 127 controls was investigated. The functional consequence of mutant NOD2 and TLR4 was investigated by comparing gene expression profiles after stimulation of monocyte-derived dendritic cells (DCs) from homozygous TLR4- and NOD2-mutant patients with lipopolysaccharides and peptidoglycan, respectively. We observed that the R702W and 1007fs Nod2 alleles and the A299G Tlr4 alleles were significantly more prevalent in patients with CD as compared to healthy controls or patients with ulcerative colitis. The phenotype of TLR4- and NOD2-mutant DCs is distinct, but a large number of genes are up- or down-regulated concordantly. These data provide a concept for the genetic basis of CD; mutations in innate immunity cause similar effects on gene transcription and finally result in comparable clinical disease presentation.

Adult↗

A left-prefrontal lateralized, sympathetic mechanism directs attention towards social threat in humans: evidence from repetitive transcranial magnetic stimulation.

The prioritized processing of threat is suggested to be motivated by anxiety, regulated by the parasympatheticus, and biased to the right hemisphere. However, according to an anterior dimensional model of negative affect this is unlikely to be true when threat is of social origin. Social threat is communicated by the angry facial expression, and recent research indicates that prioritized processing of angry faces is motivated by anger. Anger is a sympathetically dominated emotion, and for its expression and experience, neuroimaging data have demonstrated anterior lateralization to the left hemisphere. To scrutinize the above diverging statements, suprathreshold low-frequency repetitive transcranial magnetic stimulation (rTMS) was applied over the right and the left prefrontal cortex (PFC) of ten healthy subjects during 15min continuously, and the subsequent effects on sympathetic and parasympathetic activity of the heart, and selective attention to angry facial expressions were investigated. Combined rTMS-neuroimaging studies have shown contralateral excitation after unilateral supratheshold low-frequency rTMS, hence the strengthening of contralaterally mediated emotion functions. The earlier reported increases in selective attention to angry facial expressions after right-PFC rTMS were found to be accompanied by and significantly associated with elevations in sympathetic activity. Our data suggest that a left-PFC lateralized, sympathetic mechanism directs attention towards the angry facial expression.

Adolescent↗

Effects of negative ions on interpersonal attraction: evidence for intensification.

In Study 1, female subjects received information suggesting either that a stranger (a female accomplice) shared their attitudes and evaluated them positively or that a stranger did not share their attitudes and evaluated them negatively. These procedures took place in the presence of a low (ambient) or high level of negative ions. On the basis of previous research, it was predicted that a high level of negative ions would intensify subjects' reactions to the stranger, thus enhancing their evaluations of her when she seemed to share their attitudes and to like them, but reducing these evaluations when she did not share their attitudes and disliked them. Results offered support for these predictions. In Study 2, female subjects performed two tasks (letter and digit copying) in the presence of a low or high concentration of negative ions. Their blood pressure and pulse were measured at several points during the experiment. Results indicated that on various trials both systolic and diastolic blood pressure were higher in the high-ions than in the low-ions condition. In addition, subjects reported higher levels of subjective arousal and made significantly more errors on the letter-copying task in the presence of a high concentration of negative ions. Together, the results of these studies were interpreted as offering support for the view that high concentrations of negative ions can increase both physiological and psychological (subjective) arousal.

Arousal↗

The rise and fall of priming: how visual exposure shapes cortical representations of objects.

How does the amount of time for which we see an object influence the nature and content of its cortical representation? To address this question, we varied the duration of initial exposure to visual objects and then measured functional magnetic resonance imaging (fMRI) signal and behavioral performance during a subsequent repeated presentation of these objects. We report a novel 'rise-and-fall' pattern relating exposure duration and the corresponding magnitude of fMRI cortical signal. Compared with novel objects, repeated objects elicited maximal cortical response reduction when initially presented for 250 ms. Counter-intuitively, initially seeing an object for a longer duration significantly reduced the magnitude of this effect. This 'rise-and-fall' pattern was also evident for the corresponding behavioral priming. To account for these findings, we propose that the earlier interval of an exposure to a visual stimulus results in a fine-tuning of the cortical response, while additional exposure promotes selection of a subset of key features for continued representation. These two independent mechanisms complement each other in shaping object representations with experience.

Adaptation, Physiological↗

Pattern identification and perceived stimulus quality as a function of stimulation waveform on a fingertip-scanned electrotactile display.

The effect of stimulation waveform on pattern perception was investigated on a 49-point fingertip-scanned electrotactile (electrocutaneous) display. Waveform variables burst frequency (F), number of pulses per burst (NPB), and pulse repetition rate (PRR) were varied in a factorial design. Contrast reduction was used to limit performance of perceiving a 1-tactor gap defined within a 3 x 3 tactor outline square. All three variables accounted for significant variations in performance with higher levels of F and NPB and lower levels of PRR, leading to better performance. In addition, we collected qualitative data on each waveform, and the qualitative differences were related to performance (e.g., waveforms perceived as having a more localized sensation were correlated with better pattern identification performance than those waveforms perceived as more broad). We also investigated the effect of stimulation contrast on pattern perception.

Adult↗

Pattern identification as a function of stimulation current on a fingertip-scanned electrotactile display.

Two studies were conducted to determine the effect of stimulation current on pattern perception on a 49-point fingertip-scanned electrotactile (electrocutaneous) display. Performance increased monotonically from near chance levels at the lowest sub-threshold current levels tested to approximately 90% at the highest comfortable current levels. This suggests the existence of a tradeoff between spatial performance and usable "gray scale" range in electrotactile presentation of graphical information.

Adult↗

Adaptive two-pass median filter based on support vector machines for image restoration.

In this letter, a novel adaptive filter, the adaptive two-pass median (ATM) filter based on support vector machines (SVMs), is proposed to preserve more image details while effectively suppressing impulse noise for image restoration. The proposed filter is composed of a noise decision maker and two-pass median filters. Our new approach basically uses an SVM impulse detector to judge whether the input pixel is noise. If a pixel is detected as a corrupted pixel, the noise-free reduction median filter will be triggered to replace it. Otherwise, it remains unchanged. Then, to improve the quality of the restored image, a decision impulse filter is put to work in the second-pass filtering procedure. As for the noise suppressing both fixed-valued and random-valued impulses without degrading the quality of the fine details, the results of our extensive experiments demonstrate that the proposed filter outperforms earlier median-based filters in the literature. Our new filter also provides excellent robustness at various percentages of impulse noise.

Adaptation, Physiological↗

Fundamentals of pacemakers ECG interpretation - part 2.

BACKGROUND: Modern pacemakers incorporate arrhythmia-response algorithms, ventricular pacing minimization protocols, and safety mechanisms that generate ECG patterns indistinguishable from pathological AV block, sensing malfunction, or device-mediated tachycardia. Failure to recognize these algorithm-driven signatures leads to unnecessary interventions, misdiagnosis, and inappropriate device reprogramming. This manuscript is the second in a two-part series on pacemaker ECG interpretation. METHODS: We conducted a narrative review of peer-reviewed literature and device-specific documentation on algorithm-driven ECG behavior, synthesizing evidence across arrhythmia recognition, upper rate physiology, ventricular pacing minimization, mode switching, safety mechanisms, and hysteresis algorithms. RESULTS: Pacemaker-mediated tachycardia produces regular paced wide-complex tachycardia locked at the upper tracking rate, initiated by any event with retrograde VA conduction. Ventricular tachycardia is identified by QRS morphology diverging from the known paced pattern, absent pacing spikes, and AV dissociation. Upper rate Wenckebach behavior mimics Mobitz type I AV block; 2:1 upper rate response mimics second-degree AV block. Ventricular pacing minimization algorithms produce isolated nonconducted P waves and prolonged AV intervals that simulate pathological conduction disease. Mode switching causes abrupt rate drops misidentified as output failure. Ventricular safety pacing generates a conspicuously short, fixed AV interval. Three discrete pacing artifacts reflect AV-sequential cardiac resynchronization therapy (CRT), ventricular safety pacing in CRT, or His-bundle pacing with backup RV output. Rate and AV hysteresis produce pauses and wandering AV intervals mimicking oversensing or Wenckebach periodicity. CONCLUSIONS: Recognizing algorithm-driven ECG patterns requires knowledge of device timing intervals and refractory periods, which lets clinicians distinguish programmed behavior from true malfunction or cardiac arrhythmia.

Humans↗

Detecting instabilities of cardiac rhythm.

Diminished beat-to-beat variations in cardiac cycle lengths (CLs) are associated with poor prognosis after acute myocardial infarction and in patients with heart failure. Short-long-short sequences of cardiac cycles, or ultra-short rhythm instabilities, precede initiation of ventricular tachyarrhythmias in some patients. However, little is known about clinical or prognostic significance of abrupt short-term instabilities in CL (AICL) that occur minutes to hours before the event, in part because appropriate analytical methods are lacking. Although various techniques have been used to analyze CL changes, methods for analysis of AICL are limited. We compared performance of time domain, spectral, nonlinear, and pattern recognition techniques with respect to the detection and quantification of AICL. Because of high intra- and inter-subject variability of CL, pattern recognition techniques compared favorably to other studied methods. In continuous ambulatory ECG recordings, AICL occurred hours before spontaneous initiation of sustained atrial and ventricular arrhythmias in different patient populations. AICL were also found prior to the onset of spontaneous ventricular arrhythmias in a mouse model of congestive heart failure. To quantify AICL, we used the number of unstable orthogonal projection coefficients; this number gradually increased hours before the event. Removal of ectopic beats reduced but did not eliminate AICL. To illustrate potential physiological effects and temporal evolution of AICL, we used a simple, continuous, two-dimensional model of cardiac tissue governed by the Morris-Lecar equations. Computer simulations in this model showed that AICL may lead to gradual accumulation of spatial irregularities of the propagation wavefront giving rise to the initiation of reentry. Time-frequency analysis of the most significant eigenvectors of cardiac rhythm in subjects undergoing head-up tilt showed that AICL could indicate instabilities and unsuccessful adaptation of autonomic nervous system activity to physiological stimuli.

Animals↗

Identification and differential vulnerability of a neural network in sleep deprivation.

The study aimed to identify task-related brain activation networks whose change in expression exhibits subject differences as a function of differential susceptibility to sleep deprivation. Brain activity during a non-verbal recognition memory task was investigated in an event-related functional MRI paradigm both prior to and after 48 h of sleep deprivation. Nineteen healthy subjects participated. Regional covariance analysis was applied to data. An activation network pattern was identified whose expression decreased from pre- to post-sleep deprivation in 15 out 19 subjects (P < 0.05). Differential decrease in expression correlated with worsening performance in recognition accuracy (P < 0.05). Sites of de-activation were found in the posterior cerebellum, right fusiform gyrus and precuneus, and left lingual and inferior temporal gyri; increased activation was found in the bilateral insula, claustrum and right putamen. A network whose expression decreased after sleep deprivation and correlated with memory performance was identified. We conclude that this activation network plays a role in cognitive function during sleep deprivation.

Adaptation, Physiological↗