bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute study of interaction among cadmium, calcium, and zinc transport along the rat nephron in vivo
Authors: Barbier O. , Jacquillet G. , Tauc M. , Poujeol P. , Cougnon M.
Published: July 2004

This study investigates the effect in rats of acute CdCl2(5 μM) intoxication on renal function and characterizes the transport of Ca2+, Cd2+, and Zn2+in the proximal tubule (PT), loop of Henle (LH), and terminal segments of the nephron (DT) using whole kidney clearance and nephron microinjection techniques. Acute Cd2+injection resulted in renal losses of Na+, K+, Ca2+, Mg2+, PO4−2, and water, but the glomerular filtration rate remained stable.45Ca microinjections showed that Ca2+permeability in the DT was strongly inhibited by Cd2+(20 μM), Gd3+(100 μM), and La3+(1 mM), whereas nifedipine (20 μM) had no effect.109Cd and65Zn2+microinjections showed that each segment of nephron was permeable to these metals. In the PT, 95% of injected amounts of109Cd were taken up.109Cd fluxes were inhibited by Gd3+(90 μM), Co2+(100 μM), and Fe2+(100 μM) in all nephron segments. Bumetanide (50 μM) only inhibited109Cd fluxes in LH; Zn2+(50 and 500 μM) inhibited transport of109Cd in DT. In conclusion, these results indicate that 1) the renal effects of acute Cd2+intoxication are suggestive of proximal tubulopathy; 2) Cd2+inhibits Ca2+reabsorption possibly through the epithelial Ca2+channel in the DT, and this blockade could account for the hypercalciuria associated with Cd2+intoxication; 3) the PT is the major site of Cd2+reabsorption; 4) the paracellular pathway and DMT1 could be involved in Cd2+reabsorption along the LH; 5) DMT1 may be one of the major transporters of Cd2+in the DT; and 6) Zn2+is taken up along each part of the nephron and its transport in the terminal segments could occur via DMT1.
ACAT inhibition reverses LCAT deficiency and improves plasma HDL in chronic renal failure
Authors: Vaziri N. D. , Liang K.
Published: July 2004

Chronic renal failure (CRF) is associated with increased risk of arteriosclerotic cardiovascular disease and profound alteration of plasma lipid profile. Uremic dyslipidemia is marked by increased plasma concentration of ApoB-containing lipoproteins and impaired high-density lipoprotein (HDL)-mediated reverse cholesterol transport. These abnormalities are, in part, due to acquired LCAT deficiency and upregulation of hepatic acyl-CoA:cholesterol acyltransferase (ACAT). ACAT catalyzes intracellular esterification of cholesterol, thereby promoting hepatic production of ApoB-containing lipoproteins and constraining HDL-mediated cholesterol uptake in the peripheral tissues. In view of the above considerations, we tested the hypothesis that pharmacological inhibition of ACAT may ameliorate CRF-induced dyslipidemia. 5/6 Nephrectomized rats were treated with either ACAT inhibitor IC-976 (30 mg·kg−1·day−1) or placebo for 6 wk. Sham-operated rats served as controls. Key cholesterol-regulating enzymes, plasma lipids, and creatinine clearance were measured. The untreated CRF rats exhibited increased plasma low-density lipoprotein (LDL) and very LDL (VLDL) cholesterol, unchanged plasma HDL cholesterol, elevated total cholesterol-to-HDL cholesterol ratio, reduced liver microsomal free cholesterol, and diminished creatinine clearance. This was accompanied by reduced plasma LCAT, increased hepatic ACAT-2 mRNA, ACAT-2 protein and ACAT activity, and unchanged hepatic HMG-CoA reductase and cholesterol 7α-hydroxylase. ACAT inhibitor raised plasma HDL cholesterol, lowered LDL and VLDL cholesterol, and normalized total cholesterol-to-HDL cholesterol ratio without changing total cholesterol concentration (hence, a shift from ApoB-containing lipoproteins to HDL). This was accompanied by normalizations of hepatic ACAT activity and plasma LCAT. In conclusion, inhibition of ACAT reversed LCAT deficiency and improved plasma HDL level in CRF rats. Future studies are needed to explore the efficacy of ACAT inhibition in humans with CRF.
Apical potassium channels in the rat connecting tubule
Authors: Frindt Gustavo , Palmer Lawrence G.
Published: July 2004

Apical membrane K channels in the rat connecting tubule (CNT) were studied using the patch-clamp technique. Tubules were isolated from the cortical labyrinth of the kidney and split open to provide access to the apical membrane. Cell-attached patches were formed on presumed principal and/or connecting tubule cells. The major channel type observed had a single-channel conductance of 52 pS, high open probability and kinetics that were only weakly dependent on voltage. These correspond closely to the “SK”-type channels in the cortical collecting duct, identified with the ROMK (Kir1.1) gene product. A second channel type, which was less frequently observed, mediated larger currents and was strongly activated by depolarization of the apical membrane voltage. These were identified as BK or maxi-K channels. The density of active SK channels revealed a high degree of clustering. Although heterogeneity of tubules or of cell types within a tubule could not be excluded, the major factor underlying the distribution appeared to be the presence of channel clusters on the membrane of individual cells. The overall density of channels was higher than that previously found in the cortical collecting tubule (CCT). In contrast to results in the CCT, we did not detect an increase in the overall density of SK channels in the apical membrane after feeding the animals a high-K diet. However, the activity of amiloride-sensitive Na channels was undetectable under control conditions but was increased after both 1 day (90 ± 24 pA/cell) or 7 days (385 ± 82 pA/cell) of K loading. Thus one important factor leading to an increased K secretion in the CNT in response to increased dietary K is an increased apical Na conductance, leading to depolarization of the apical membrane voltage and an increased driving force for K movement out into the tubular lumen.
PPAR-α ligand ameliorates acute renal failure by reducing cisplatin-induced increased expression of renal endonuclease G
Authors: Li Shenyang , Bhatt Renu , Megyesi Judit , Gokden Neriman , Shah Sudhir V. , Portilla Didier
Published: July 2004

Cisplatin injury to the kidney is characterized, in part, by inhibition of substrate oxidation, inflammation, and tubular cell death in the form of apoptosis and necrosis. Recently, we demonstrated that cisplatin-induced inhibition of substrate oxidation can be reversed by the administration of peroxisome proliferator-activated receptor-α (PPAR-α) ligands, resulting in amelioration of renal function. We therefore hypothesize that by improving fatty acid oxidation in vivo might protect renal function by reducing both apoptosis and necrosis in cisplatin-treated mice. Mice subjected to a single intraperitoneal injection of cisplatin developed acute renal failure (ARF) at days 3 and 4. At day 4 after cisplatin injection mRNA, protein levels and enzyme activity of proapoptotic renal endonuclease G (Endo G) were increased compared with saline-treated mice. In situ hybridization and immunohistochemical studies localized the increased expression of Endo G mRNA to the cytosolic compartment and Endo G protein to the nuclear compartment of proximal tubules in cisplatin-treated mice. Pretreatment of PPAR-α wild-type mice with PPAR-α ligand WY-14643 reduced significantly cisplatin-induced increased protein expression and enzyme activity of Endo G and prevented the nuclear translocation of mitochondrial Endo G. Morphological examination of tubular injury in the PPAR-α wild-type mice that received PPAR-α ligand and cisplatin did show significant amelioration of acute tubular necrosis, as well as a significant reduction in the number of apoptotic cells in the proximal tubule when compared with the cisplatin-treated group. In contrast, in PPAR-α-null mice treated with the ligand and cisplatin, Endo G protein expression was not reduced and this was accompanied by lack of protection of kidney function. We conclude that PPAR-α ligand protects against cisplatin-induced renal injury via a PPAR-α-dependent mechanism by reducing the expression and enzyme activity of proximal tubule Endo G, which results in amelioration of both proximal tubule cell apoptosis and necrosis.
Effects of Chronic Dorsal Column Lesions on Pelvic Viscerosomatic Convergent Medullary Reticular Formation Neurons
Authors: Hubscher Charles H. , Johnson Richard D.
Published: July 2004

Single medullary reticular formation (MRF) neurons receive multiple somatovisceral convergent inputs originating from many different spinal and cranial nerves, including the pelvic nerve (PN), dorsal nerve of the penis (DNP), and the abdominal branches of the vagus. In a previous study, the input to MRF from the male genitalia was shown to be eliminated with chronic 30-day dorsal hemisection at the T8 spinal level. In this study, the effect of a smaller chronic lesion [dorsal column lesion (DCx)] on MRF neuronal responses was examined. Responses to bilateral electrical stimulation of the DNP remained. MRF neuronal responses to non-noxious (touch/stroke) levels of penile stimulation, however, were eliminated; only responses to noxious pinch remained. No differences were found for the number of neurons responding to noxious distention of the colon between the DCx and control groups. Although no differences were found across these groups for the percent MRF responses to vagal stimulation, the mean response latency for the DCx group was twice the sham-DCx/intact control group. Taken together, these results indicate that the MRF receives at least some of its input from the male genitalia via pathways located within the dorsal columns at the mid-thoracic spinal level.
Gamma Oscillation Maintains Stimulus Structure-Dependent Synchronization in Cat Visual Cortex
Authors: Samonds Jason M. , Bonds A. B.
Published: July 2004

Visual cortical cells demonstrate both oscillation and synchronization, although the underlying causes and functional significance of these behaviors remain uncertain. We simultaneously recorded single-unit activity with microelectrode arrays in supragranular layers of area 17 of cats paralyzed and anesthetized with propofol and N2O. Rate-normalized autocorrelograms of 24 cells reveal bursting (100%) and gamma oscillation (63%). Renewal density analysis, used to explore the source of oscillation, suggests a contribution from extrinsic influences such as feedback. However, a bursting refractory period, presumably membrane-based, could also encourage oscillatory firing. When we investigated the source of synchronization for 60 cell pairs we found only moderate correlation of synchrony with bursts and oscillation. We did, nonetheless, discover a possible functional role for oscillation. In all cases of cross-correlograms that exhibited oscillation, the strength of the synchrony was maintained throughout the stimulation period. When no oscillation was apparent, 75% of the cell pairs showed decay in their synchronization. The synchrony between cells is strongly dependent on similar response onset latencies. We therefore propose that structured input, which yields tight organization of latency, is a more likely candidate for the source of synchronization than oscillation. The reliable synchrony at response onset could be driven by spatial and temporal correlation of the stimulus that is preserved through the earlier stages of the visual system. Oscillation then contributes to maintenance of the synchrony to enhance reliable transmission of the information for higher cognitive processing.
Learning to Control Arm Stiffness Under Static Conditions
Authors: Darainy Mohammad , Malfait Nicole , Gribble Paul L. , Towhidkhah Farzad , Ostry David J.
Published: July 2004

We used a robotic device to test the idea that impedance control involves a process of learning or adaptation that is acquired over time and permits the voluntary control of the pattern of stiffness at the hand. The tests were conducted in statics. Subjects were trained over the course of 3 successive days to resist the effects of one of three different kinds of mechanical loads: single axis loads acting in the lateral direction, single axis loads acting in the forward/backward direction, and isotropic loads that perturbed the limb in eight directions about a circle. We found that subjects in contact with single axis loads voluntarily modified their hand stiffness orientation such that changes to the direction of maximum stiffness mirrored the direction of applied load. In the case of isotropic loads, a uniform increase in endpoint stiffness was observed. Using a physiologically realistic model of two-joint arm movement, the experimentally determined pattern of impedance change could be replicated by assuming that coactivation of elbow and double joint muscles was independent of coactivation of muscles at the shoulder. Moreover, using this pattern of coactivation control we were able to replicate an asymmetric pattern of rotation of the stiffness ellipse that was observed empirically. These findings are consistent with the idea that arm stiffness is controlled through the use of at least two independent co-contraction commands.
Timing and Laminar Profile of Eye-Position Effects on Auditory Responses in Primate Auditory Cortex
Authors: Fu Kai-Ming G. , Shah Ankoor S. , O'Connell Monica N. , McGinnis Tammy , Eckholdt Haftan , Lakatos Peter , Smiley John , Schroeder Charles E.
Published: July 2004

We examined effects of eye position on auditory cortical responses in macaques. Laminar current-source density (CSD) and multiunit activity (MUA) profiles were sampled with linear array multielectrodes. Eye position significantly modulated auditory-evoked CSD amplitude in 24/29 penetrations (83%), across A1 and belt regions; 4/24 cases also showed significant MUA AM. Eye-position effects occurred mainly in the supragranular laminae and lagged the co-located auditory response by, on average, 38 ms. Effects in A1 and belt regions were indistinguishable in amplitude, laminar profile, and latency. The timing and laminar profile of the eye-position effects suggest that they are not combined with auditory signals at a subcortical stage of the lemniscal auditory pathways and simply “fed-forward” into cortex. Rather, these effects may be conveyed to auditory cortex by feedback projections from parietal or frontal cortices, or alternatively, they may be conveyed by nonclassical feedforward projections through auditory koniocellular (calbindin positive) neurons.
Comparison of Preperfusion and Postperfusion Magnetic Resonance Angiography in Acute Stroke
Authors: Pedraza Salvador , Silva Yolanda , Mendez José , Inaraja Luis , Vera Joana , Serena Joaquín , Dávalos Antoni
Published: July 2004

Background and Purpose—

The multimodal magnetic resonance imaging study in acute stroke includes perfusion-weighted imaging (PWI) after administration of contrast and magnetic resonance angiography (MRA). However, MRA may overestimate the degree of vessel obstruction caused by limitations to detect low flow states. Our aim was to determine the usefulness of a new fast imaging protocol combining classical MRA, PWI, and postperfusion MRA to improve the diagnostic management in acute ischemic stroke.

Methods—

We studied 31 patients with a middle cerebral artery (MCA) infarction within the first 12 hours from the onset of symptoms. All patients had an MCA stenosis or occlusion. The study protocol included a preperfusion MRA and a postperfusion MRA. Modified thrombolysis in myocardial infarction (TIMI) classification was used to assess the patency of vessels.

Results—

In 17 patients (group A, 55%), preperfusion MRA and postperfusion MRA accorded in the estimation of vascular status, whereas in 14 patients (group B, 45%) postperfusion MRA showed a better vascular flow than preperfusion MRA. The improvement in the depiction of flow was from a complete occlusion (TIMI I) to a partial occlusion (TIMI II) in 9 patients and from TIMI II to normal patency (TIMI III) in 5 patients. Thirty-six percent of the patients with suspected internal carotid artery occlusion in the preperfusion MRA showed flow in the intracranial internal carotid artery in the postperfusion MRA.

Conclusions—

Postperfusion contrast-enhanced MRA can demonstrate arterial segments with low flow and avoid overestimation of vascular obstruction.
Declining Mortality From Subarachnoid Hemorrhage
Authors: Stegmayr Birgitta , Eriksson Marie , Asplund Kjell
Published: July 2004

Background and Purpose—

Northern Sweden has one of the highest incidence rates of subarachnoid hemorrhage (SAH) among the populations covered by the WHO MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Project, approximately twice as high as in the other populations in Europe. In this study, trends in incidence, 28-day case fatality (CF), and mortality in SAH were followed over a 16-year period.

Methods—

Since 1985, all SAHs in northern Sweden among patients 25 to 74 years old have been validated using strict MONICA criteria. From 1985 through 2000, 392 men and 592 women had SAH. During 3 years, 1997 to 1999, SAH among those aged 75 and older were also included.

Results—

The total incidence among those 25 years and older was 13.3 per 100 000 in men and 24.4 per 100 000 in women. During the 16 years of observation, age standardized incidence in the group aged 25 to 74 years decreased significantly in men (
P
for trend <0.0001) but remained essentially unchanged in women (
P
for trend=0.64). The 28-day CF for all years was 36.5% in men, with no significant trend (
P
=0.7). In women, average CF was 35%, with a significant decline (
P
=0.003). The annual mortality decreased significantly in both sexes (by 3.87 [95% CI±2.75 percentage points] in men and 3.97 [95% CI±2.29] in women).

Conclusions—

The decline in SAH mortality has different explanations in men (declining incidence) and in women (declining CF).
Modulation of Motor Excitability during Speech Perception: The Role of Broca's Area
Authors: Watkins Kate , Paus Tomáš
Published: July 2004

Studies in both human and nonhuman primates indicate that motor and premotor cortical regions participate in auditory and visual perception of actions. Previous studies, using transcranial magnetic stimulation (TMS), showed that perceiving visual and auditory speech increased the excitability of the orofacial motor system during speech perception. Such studies, however, cannot tell us which brain regions mediate this effect. In this study, we used the technique of combining positron emission tomography with TMS to identify the brain regions that modulate the excitability of the motor system during speech perception. Our results show that during auditory speech perception, there is increased excitability of motor system underlying speech production and that this increase is significantly correlated with activity in the posterior part of the left inferior frontal gyrus (Broca's area). We propose that this area “primes” the motor system in response to heard speech even when no speech output is required and, as such, operates at the interface of perception and action.
Timing of Target Discrimination in Human Frontal Eye Fields
Authors: O'Shea Jacinta , Muggleton Neil G. , Cowey Alan , Walsh Vincent
Published: July 2004

Frontal eye field (FEF) neurons discharge in response to behaviorally relevant stimuli that are potential targets for saccades. Distinct visual and motor processes have been dissociated in the FEF of macaque monkeys, but little is known about the visual processing capacity of FEF in humans. We used double-pulse transcranial magnetic stimulation [(d)TMS] to investigate the timing of target discrimination during visual conjunction search. We applied dual TMS pulses separated by 40 msec over the right FEF and vertex. These were applied in five timing conditions to sample separate time windows within the first 200 msec of visual processing. (d)TMS impaired search performance, reflected in reduced d′ scores. This effect was limited to a time window between 40 and 80 msec after search array onset. These parameters correspond with single-cell activity in FEF that predicts monkeys' behavioral reports on hit, miss, false alarm, and correct rejection trials. Our findings demonstrate a crucial early role for human FEF in visual target discrimination that is independent of saccade programming.
Optimizing a Linear Algorithm for Real-Time Robotic Control using Chronic Cortical Ensemble Recordings in Monkeys
Authors: Wessberg Johan , Nicolelis Miguel A. L.
Published: July 2004

Previous work in our laboratory has demonstrated that a simple linear model can be used to translate cortical neuronal activity into real-time motor control commands that allow a robot arm to mimic the intended hand movements of trained primates. Here, we describe the results of a comprehensive analysis of the contribution of single cortical neurons to this linear model. Key to the operation of this model was the observation that a large percentage of cortical neurons located in both frontal and parietal cortical areas are tuned for hand position. In most neurons, hand position tuning was time-dependent, varying continuously during a 1-sec period before hand movement onset. The relevance of this physiological finding was demonstrated by showing that maximum contribution of individual neurons to the linear model was only achieved when optimal parameters for the impulse response functions describing time-varying neuronal position tuning were selected. Optimal parameters included impulse response functions with 1.0-to 1.4-sec time length and 50-to 100-msec bins. Although reliable generalization and long-term predictions (60–90 min) could be achieved after 10-min training sessions, we noticed that the model performance degraded over long periods. Part of this degradation was accounted by the observation that neuronal position tuning varied significantly throughout the duration (60–90 min) of a recording session. Altogether, these results indicate that the experimental paradigm described here may be useful not only to investigate aspects of neural population coding, but it may also provide a test bed for the development of clinically useful cortical prosthetic devices aimed at restoring motor functions in severely paralyzed patients.
How Would You Feel versus How Do You Think She Would Feel? A Neuroimaging Study of Perspective-Taking with Social Emotions
Authors: Ruby Perrine , Decety Jean
Published: July 2004

Perspective-taking is a complex cognitive process involved in social cognition. This positron emission tomography (PET) study investigated by means of a factorial design the interaction between the emotional and the perspective factors. Participants were asked to adopt either their own (first person) perspective or the (third person) perspective of their mothers in response to situations involving social emotions or to neutral situations. The main effect of third-person versus first-person perspective resulted in hemodynamic increase in the medial part of the superior frontal gyrus, the left superior temporal sulcus, the left temporal pole, the posterior cingulate gyrus, and the right inferior parietal lobe. A cluster in the postcentral gyrus was detected in the reverse comparison. The amygdala was selectively activated when subjects were processing social emotions, both related to self and other. Interaction effects were identified in the left temporal pole and in the right postcentral gyrus. These results support our prediction that the frontopolar, the somatosensory cortex, and the right inferior parietal lobe are crucial in the process of self/ other distinction. In addition, this study provides important building blocks in our understanding of social emotion processing and human empathy.
The Influence of Semantic and Syntactic Context Constraints on Lexical Selection and Integration in Spoken-Word Comprehension as Revealed by ERPs
Authors: Brink Daniëlle van den , Hagoort Peter
Published: July 2004

An event-related brain potential experiment was carried out to investigate the influence of semantic and syntactic context constraints on lexical selection and integration in spoken-word comprehension. Subjects were presented with constraining spoken sentences that contained a critical word that was either (a) congruent, (b) semantically and syntactically incongruent, but beginning with the same initial phonemes as the congruent critical word, or (c) semantically and syntactically incongruent, beginning with phonemes that differed from the congruent critical word. Relative to the congruent condition, an N200 effect reflecting difficulty in the lexical selection process was obtained in the semantically and syntactically incongruent condition where word onset differed from that of the congruent critical word. Both incongruent conditions elicited a large N400 followed by a left anterior negativity (LAN) time-locked to the moment of word category violation and a P600 effect. These results would best fit within a cascaded model of spoken-word processing, proclaiming an optimal use of contextual information during spoken-word identification by allowing for semantic and syntactic processing to take place in parallel after bottom-up activation of a set of candidates, and lexical integration to proceed with a limited number of candidates that still match the acoustic input.
Cue Validity and Object-Based Attention
Authors: He Xun , Fan Silu , Zhou Ke , Chen Lin
Published: July 2004

In a previous study, Egly, Driver, and Rafal (1994) observed both space-and object-based components of visual selective attention. However, the mechanisms underlying these two components and the relationship between them are not well understood. In the present research, with a similar paradigm, these issues were addressed by manipulating cue validity. Behavioral results indicated the presence of both space-and object-based components under high cue validity, similar to the results of Egly et al.'s study. In addition, under low cue validity, the space-based component was absent, whereas the object-based component was maintained. Further event-related potential results demonstrated an object-based effect at a sensory level over the posterior areas of brain, and a space-based effect over the anterior region. The present data suggest that the space-and object-based components reflect mainly voluntary and reflexive mechanisms, respectively.
Reaching Out to See: Arm Position Can Attenuate Human Visual Loss
Authors: Schendel Krista , Robertson Lynn C.
Published: July 2004

Electrophysiological recordings in monkeys have now revealed several brain regions that contain bimodal visuotactile neurons capable of responding to either tactile or visual stimuli placed on or near the hands, arms, and face. These cells have now been found in frontal, parietal, and subcortical areas of the monkey brain, suggesting a cortical network of neurons that preferentially represent near peripersonal space. The degree to which the visual responses of such cells rely on input from the primary visual cortex and the extent to which they may contribute to visual perception is not completely understood. Nonetheless, recent neuropsychological studies suggest that a similar representation of near space may be bimodally coded in humans as well. Given the accumulating evidence for specialized processing of visual stimuli placed near the hands and arms, we hypothesized that arm position may be capable of modulating human visual ability. Here we report the case of WM, who lost his ability to see in his left visual hemifield after sustaining damage to his right primary visual cortex. Interestingly, the placement of WM's left arm into his “blind” field resulted in significantly better detection of left visual field stimuli compared to when his hand was placed in his lap at midline. Moreover, we found this attenuation to be confined to stimuli presented within reaching distance (unless a tool that extended WM's reach was held while he performed the test). These findings are highly consistent with the characteristics of the bimodal visuo-tactile neurons that have been described in monkeys. Thus, it seems that arm position can modulate human visual ability, even after damage to the primary visual cortex. This study provides an exciting bridge between monkey neurophysiology and human visual capacity while also offering a novel approach for improving visual defects acquired via cortical injury.
Musical Training Enhances Automatic Encoding of Melodic Contour and Interval Structure
Authors: Fujioka Takako , Trainor Laurel J. , Ross Bernhard , Kakigi Ryusuke , Pantev Christo
Published: July 2004

In music, melodic information is thought to be encoded in two forms, a contour code (up/down pattern of pitch changes) and an interval code (pitch distances between successive notes). A recent study recording the mismatch negativity (MMN) evoked by pitch contour and interval deviations in simple melodies demonstrated that people with no formal music education process both contour and interval information in the auditory cortex automatically. However, it is still unclear whether musical experience enhances both strategies of melodic encoding. We designed stimuli to examine contour and interval information separately. In the contour condition there were eight different standard melodies (presented on 80% of trials), each consisting of five notes all ascending in pitch, and the corresponding deviant melodies (20%) were altered to descending on their final note. The interval condition used one five-note standard melody transposed to eight keys from trial to trial, and on deviant trials the last note was raised by one whole tone without changing the pitch contour. There was also a control condition, in which a standard tone (990.7 Hz) and a deviant tone (1111.0 Hz) were presented. The magnetic counterpart of the MMN (MMNm) from musicians and nonmusicians was obtained as the difference between the dipole moment in response to the standard and deviant trials recorded by magnetoencephalography. Significantly larger MMNm was present in musicians in both contour and interval conditions than in nonmusicians, whereas MMNm in the control condition was similar for both groups. The interval MMNm was larger than the contour MMNm in musicians. No hemispheric difference was found in either group. The results suggest that musical training enhances the ability to automatically register abstract changes in the relative pitch structure of melodies.
Behavioral and Neuroimaging Evidence for a Contribution of Color and Texture Information to Scene Classification in a Patient with Visual Form Agnosia
Authors: Steeves Jennifer K. E. , Humphrey G. Keith , Culham Jody C. , Menon Ravi S. , Milner A. David , Goodale Melvyn A.
Published: July 2004

A common notion is that object perception is a necessary precursor to scene perception. Behavioral evidence suggests, however, that scene perception can operate independently of object perception. Further, neuroimaging has revealed a specialized human cortical area for viewing scenes that is anatomically distinct from areas activated by viewing objects. Here we show that an individual with visual form agnosia, D.F., who has a profound deficit in object recognition but spared color and visual texture perception, could still classify scenes and that she was fastest when the scenes were presented in the appropriate color. When scenes were presented as black-and-white images, she made a large number of errors in classification. Functional magnetic resonance imaging revealed selective activation in the parahippocampal place area (PPA) when D.F. viewed scenes. Unlike control observers, D.F. demonstrated higher activation in the PPA for scenes presented in the appropriate color than for black-and-white versions. The results demonstrate that an individual with profound form vision deficits can still use visual texture and color to classify scenes—and that this intact ability is reflected in differential activation of the PPA with colored versions of scenes.
Prefrontal Cortex Activity Associated with Source Monitoring in a Working Memory Task
Authors: Mitchell Karen J. , Johnson Marcia K. , Raye Carol L. , Greene Erich J.
Published: July 2004

Using functional magnetic resonance imaging (fMRI), we investigated prefrontal cortex (PFC) activity during remembering specific source information (format, location judgments) versus remembering that could be based on undifferentiated information, such as familiarity (old/new recognition [ON], recency judgments). A working memory (WM) paradigm with an immediate test yielded greater activation in the lateral PFC for format and location source memory (SM) tasks than ON recognition; this SM-related activity was left lateralized. The same regions of PFC were recruited in Experiment 2 when information was tested immediately and after a filled delay. Substituting recency for location judgments (Experiment 3) resulted in an overall shift in task context that produced greater right PFC activity associated with ON and recency tasks compared to the format task, in addition to left SM-related activity. These data extend to WM previous findings from long-term memory (LTM) indicating that the left and right PFC may be differentially involved in memory attributions depending on the specificity of information evaluated. The findings also provide evidence for the continuity of evaluative processes recruited in WM and LTM.
fMRI Evidence for Separable and Lateralized Prefrontal Memory Monitoring Processes
Authors: Dobbins Ian G. , Simons Jon S. , Schacter Daniel L.
Published: July 2004

Source memory research suggests that attempting to remember specific contextual aspects surrounding prior stimulus encounters results in greater left prefrontal cortex (PFC) activity than simple item-based old/new recognition judgments. Here, we tested a complementary hypothesis that predicts increases in the right PFC with tasks requiring close monitoring of item familiarity. More specifically, we compared a judgment of frequency (JOF) task to an item memory task, in which the former required estimating the number of previous picture encounters and the latter required discriminating old from new exemplars of previously seen items. In comparison to standard old/new recognition, both source memory and the JOF task examined here require more precise mnemonic judgments. However, in contrast to source memory, cognitive models suggest the JOF task relies heavily upon item familiarity, not specific contextual recollections. Event-related fMRI demonstrated greater recruitment of right, not left, dorso-lateral and frontopolar PFC regions during the JOF compared to item memory task. These data suggest a role for right PFC in the close monitoring of the familiarity of objects, which becomes critical when contextual recollection is ineffective in satisfying a memory demand.
Haloperidol Impairs Learning and Error-related Negativity in Humans
Authors: Zirnheld Patrick J. , Carroll Christine A. , Kieffaber Paul D. , O'Donnell Brian F. , Shekhar Anantha , Hetrick William P.
Published: July 2004

Humans are able to monitor their actions for behavioral conflicts and performance errors. Growing evidence suggests that the error-related negativity (ERN) of the event-related cortical brain potential (ERP) may index the functioning of this response monitoring system and that the ERN may depend on dopaminergic mechanisms. We examined the role of dopamine in ERN and behavioral indices of learning by administering either 3 mg of the dopamine antagonist (DA) haloperidol (n = 17); 25 mg of diphenhydramine (n = 16), which has a similar CNS profile but without DA properties; or placebo (n = 18) in a randomized, double-blind manner to healthy volunteers. Three hours after drug administration, participants performed a go/no-go Continuous Performance Task, the Eriksen Flanker Task, and a learning-dependent Time Estimation Task. Haloperidol significantly attenuated ERN amplitudes recorded during the flanker task, impaired learning of time intervals, and tended to cause more errors of commission, compared to placebo, which did not significantly differ from diphenhydramine. Drugs had no significant effects on the stimulus-locked P1 and N2 ERPs or on behavioral response latencies, but tended to affect post-error reaction time (RT) latencies in opposite ways (haloperidol decreased and diphenhydramine increased RTs). These findings support the hypothesis that the DA system is involved in learning and the generation of the ERN.
Dichoptic Visual Masking Reveals that Early Binocular Neurons Exhibit Weak Interocular Suppression: Implications for Binocular Vision and Visual Awareness
Authors: Macknik Stephen L. , Martinez-Conde Susana
Published: July 2004

Visual masking effects are illusions in which a target is rendered invisible by a mask, which can either overlap or not overlap the target spatially and/or temporally. These illusions provide a powerful tool to study visibility and consciousness, object grouping, brightness perception, and much more. As such, the physiological mechanisms underlying the perception of masking are critically important to our understanding of visibility. Several models that require cortical circuits have been proposed previously to explain the mysterious spatial and timing effects associated with visual masking. Here we describe single-unit physiological experiments from the awake monkey that show that visual masking occurs in at least two separate and independent circuits, one that is binocular and one that is monocular (possibly even subcortical), without feedback from higher-level visual brain areas. These and other results together fail to support models of masking that require circuits found only in the cortex, but support our proposed model that suggests that simple ubiquitous lateral inhibition may itself be the fundamental mechanism that explains visual masking across multiple levels in the brain. We also show that area V1 neurons are dichoptic in terms of excitation, but monoptic in terms of inhibition. That is, responses within area V1 binocular neurons reveal that excitation to monocular targets is inhibited strongly only by masks presented to the same eye, and not by masks presented to the opposite eye. These results lead us to redefine the model for the first stage of binocular processing in the visual system, and may be crucial to interpreting the effects of other similar binocular and dichoptic stimulation paradigms, such as the binocular rivalry family of illusions.
Orientalism and the Modern Myth of "Hinduism"
Authors: King Richard
Published: July 2004

Is there really a single ancient religion designated by the catch-all term 'Hinduism' or is the term merely a fairly recent social construction of Western origin? This paper examines the role played by Orientalist scholars in the construction of Western notions of Indian religion by an examination of the origins of the concept of 'Hinduism'. It is argued that the notion of 'Hinduism' as a single world religion is a nineteenth century construction, largely dependent upon the Christian presuppositions of the early Western Orientalists. However, exclusive emphasis upon the role of Western Orientalists constitutes a failure to acknowledge the role played by key indigenous informants (mostly from the brāhmana castes) in the construction of modern notions of 'the Hindu religion'. To ignore the indigenous dimension of the invention of 'Hinduism' is to erase the colonial subject from history and perpetuate the myth of the passive Oriental. The paper concludes with a discussion of the accuracy and continual usefulness of the term 'Hinduism'.
Opposites Attract: the Body and Cognition in a Debate over Baptism
Authors: Vial Theodore
Published: July 2004

Analysis of a change in a historical rite of passage, the baptism ceremony in Zurich in the 1860s, shows the relative strengths and weaknesses of recent developments in the field of ritual studies. Those who argue that ritualized action is an embodied negotiation of power relations are helpful in understanding why various groups in society fought either for or against the ritual change. But the weak structural component of these theories and an inadequate model of human action make them unable to account for speech acts in ritual, or for the change in the Zurich ritual. Cognitive theories of ritual are far more successful in explaining the force of specific structural changes. Far from being incompatible, these different approaches to ritual, if based on an adequate model of human agency, are complementary and necessary for an adequate account of the historical ritual change examined.
Women's History and Ottoman Sharia Court Records: Shifting Perspectives in Social History
Authors: Agmon Iris
Published: July 2004

This paper revisits some methodological and conceptual aspects of scholarly works on the social history of Middle Eastern women based on Ottoman court records that were published in the last three decades. It discusses the main approaches employed by historians in the field for analyzing court records, and the circumstances that shaped these patterns. It shows that, during the 1970s and 1980s, this body of scholarly works on women's history, as part of Middle Eastern social history, adhered to historiographical approaches that did not follow the "cultural turn" characterizing West European and North American historiography. This situation, however, has recently changed.
Families on the Move: The Changing Role of Afghan Refugee Women in Iran
Authors: Hoodfar Homa
Published: July 2004

In their attempts to "modernize" and bring about socio-economic change, Afghan governments have been preoccupied with restructuring the institutions of marriage and family, and women's role within them, since the 1880s. Serious commitment to introduce legal reform and democratize the family and gender roles cost King Amanullah his throne (1919–1929). From 1930 to 1976 the government attempted a gradual approach introducing reforms piecemeal which had little impact beyond the capital and major cities. After the coup d'état in 1973 and the installation of socialism, the regime introduced a new family decree (known as Number 7) in October 1978 and aggressively pursued women's education and the reform of family laws. This policy incensed the conservative communities and tribal societies, who rebelled against the government; the ensuing Russian occupation brought about the resistance movements and subsequent civil war that has wreaked havoc on Afghanistan for more than two decades. Many conservatives who had tried to resist the intended changes regarding family law and education for girls and "protect" their women, who represented the males honor, decided to leave the country with their families. More than six million Afghans moved to neighboring countries, mostly to Iran and Pakistan. Examining data collected among Afghan refugees in Iran from 1999 to 2002, this paper argues that, ironically, living in exile has brought about the very changes resistance to which had forced them into the refugee situation. Forced to cope with a crisis situation, they developed economic and social survival strategies that altered women's role. Moreover, that exposure to an Islamic society very different from their own brought about structural and ideological changes in the family and in gender roles which legal reforms in Afghanistan had failed to induce. Given the considerable size of the refugee population in Iran (but also in Pakistan and elsewhere) and the destruction of the old fabric(s) of Afghan society, this paper argues that these changes may be irreversible.
Interleukin-15 enhances immune reconstitution after allogeneic bone marrow transplantation
Authors: Alpdogan Onder , Eng Jeffrey M. , Muriglan Stephanie J. , Willis Lucy M. , Hubbard Vanessa M. , Tjoe Kartono H. , Terwey Theis H. , Kochman Adam , van den Brink Marcel R. M.
Published: July 2004

Interleukin-15 (IL-15) is a γ-common cytokine that plays an important role in the development, survival, and proliferation of natural killer (NK), NK T, and CD8+ T-cells. We administered IL-15 to recipients of an allogeneic bone marrow transplantation (allo BMT) to determine its effects on immune reconstitution. Posttransplantation IL-15 administration significantly increased donor-derived CD8+ T (mostly CD122+CD44+CD8+ T-cells), NK, and NK T-cells at day +28 in young and old recipients of allo BMT. This was associated with enhanced T-cell and NK-cell function. IL-15 stimulated homeostatic proliferation of donor CD8+ T-cells in recipients of carboxyfluorescein diacetate succinimidyl ester–labeled donor T-cell infusions. Posttransplantation IL-15 administration also resulted in a decrease in apoptotic CD8+ T-cells, an increase in Bcl-2–expressing CD8+ T-cells, and an increase in the fraction of Ki67+ proliferative NK and CD8+ T-cells in recipients of allo BMT. IL-15 did not exacerbate graft-versus-host disease (GVHD) in recipients of T-cell–depleted BMT but could aggravate GVHD in some cases in recipients of a T-cell–repleted BMT. Finally, we found that IL-15 administration could enhance graft-versus-leukemia activity. In conclusion, IL-15 can be administered safely to recipients of a T-cell–depleted allo BMT to enhance CD8+ T, NK, and NK T-cell reconstitution.
Surface fucosylation of human cord blood cells augments binding to P-selectin and E-selectin and enhances engraftment in bone marrow
Authors: Xia Lijun , McDaniel J. Michael , Yago Tadayuki , Doeden Andrea , McEver Rodger P.
Published: July 2004

Murine hematopoietic stem and progenitor cells (HSPCs) home to bone marrow in part by rolling on P-selectin and E-selectin expressed on endothelial cells. Human adult CD34+ cells, which are enriched in HSPCs, roll on endothelial selectins in bone marrow vessels of nonobese diabetic/severe combined immune deficiency (NOD/SCID) mice. Many human umbilical cord blood (CB) CD34+ cells do not roll in these vessels, in part because of an uncharacterized defect in binding to P-selectin. Selectin ligands must be α1-3 fucosylated to form glycan determinants such as sialyl Lewis x (sLex). We found that inadequate α1-3 fucosylation of CB CD34+ cells, particularly CD34+CD38–/low cells that are highly enriched in HSPCs, caused them to bind poorly to E-selectin as well as to P-selectin. Treatment of CB CD34+ cells with guanosine diphosphate (GDP) fucose and exogenous α1-3 fucosyltransferase VI increased cell-surface sLex determinants, augmented binding to fluid-phase P- and E-selectin, and improved cell rolling on P- and E-selectin under flow. Similar treatment of CB mononuclear cells enhanced engraftment of human hematopoietic cells in bone marrows of irradiated NOD/SCID mice. These observations suggest that α1-3 fucosylation of CB cells might be a simple and effective method to improve hematopoietic cell homing to and engraftment in bone marrows of patients receiving CB transplants.