bluuebunny/crossref_metadata_2025 huggingface dataset:
A Conditioned Stressful Environment Causes Short-Term Metaplastic-Like Changes in the Rat Nucleus Accumbens
Authors: Hugues Sandrine , Kessal Karima , Hunt Mark J. , Garcia René
Published: May 2006

Stress-related alterations to the induction of hippocampal synaptic plasticity have been implicated in certain forms of psychiatric disorders. However, relatively little is known about such changes in other psychiatric disorders-related structures. We tested this possibility in one of such structures, the nucleus accumbens, during re-exposure of rats to a conditioned stressful environment, in which they had previously received shock. In both control rats (no shock) and shocked rats previously submitted to an extensive pre-exposure to the to-be-conditioned contextual cues (latent inhibition), high- and low-frequency stimulation of fimbriaaccumbens pathway induced, in the nucleus accumbens, similar pattern of increases and decreases in synaptic efficacy, respectively. However, in non-pre-exposed shocked rats, re-exposure to the conditioned contextual cues evoked high levels of freezing, which was accompanied by a blockade of the induction of enhancement, but a facilitation of the depression, of synaptic efficacy. In addition, contextual conditioning did not alter the baseline transmission whatever the stimulus intensity and was ineffective on the induction of fimbriaaccumbens synaptic plasticity following complete extinction of freezing response to the conditioned contextual cues. These data support the idea according to which stress may be involved in certain forms of psychiatric disorders via induction of metaplastic changes in circuits including the hippocampus and hippocampal limbic target structures such as the nucleus accumbens.
Scene Segmentation and Attention in Primate Cortical Areas V1 and V2
Authors: Marcus Daniel S. , Van Essen David C.
Published: May 2006

The responses of many neurons in primary visual cortex are modulated by stimuli outside the classical receptive field in ways that may contribute to integrative processes like scene segmentation. To explore this issue, single-unit neuronal responses were recorded in monkey cortical areas V1 and V2 to visual stimuli containing either a figure or a background pattern over the receptive field. Figures were defined either by orientation contrast or by illusory contours. In all conditions, the stimulation over the RF and its nearby surround was identical. Both figure types enhanced the average population response in V1 and V2. For orientation contrast figures, enhancement averaged 50% in V2 and 30% in V1; for illusory contour figures, the enhancement averaged 24% in V2 and 18% in V1. These differences were statistically significant for figure type but not for visual area. In V2, the latency of enhancement to illusory contour-defined figures was longer than that to orientation-defined figures. Neuronal responses were recorded while the monkey performed a directed-attention task. Enhancement to both figure types was observed even when attention was directed away from the figure. Attention slightly enhanced responses in V2, independent of figure type, but did not affect responses in V1. There was no discernible effect of attention on background firing rate in either V1 or V2. These results suggest that scene segmentation is a distributed process, in which neuronal signals at successive stages of the visual hierarchy and over time increasingly reflect the global structure of the image. This process occurs independent of directed visual attention.
A Functional-Anatomical Model for Lipreading
Authors: Paulesu E. , Perani D. , Blasi V. , Silani G. , Borghese N. A. , De Giovanni U. , Sensolo S. , Fazio F.
Published: May 2006

Regional cerebral blood flow (rCBF) PET scans were used to study the physiological bases of lipreading, a natural skill of extracting language from mouth movements, which contributes to speech perception in everyday life. Viewing connected mouth movements that could not be lexically identified and that evoke perception of isolated speech sounds (nonlexical lipreading) was associated with bilateral activation of the auditory association cortex around Wernicke's area, of left dorsal premotor cortex, and left opercular-premotor division of the left inferior frontal gyrus (Broca's area). The supplementary motor area was active as well. These areas have all been implicated in phonological processing, speech and mouth motor planning, and execution. In addition, nonlexical lipreading also differentially activated visual motion areas. Lexical access through lipreading was associated with a similar pattern of activation and with additional foci in ventral- and dorsolateral prefrontal cortex bilaterally and in left inferior parietal cortex. Linear regression analysis of cerebral blood flow and proficiency for lexical lipreading further clarified the role of these areas in gaining access to language through lipreading. The results suggest cortical activation circuits for lipreading from action representations that may differentiate lexical access from nonlexical processes.
Quantitative Relationship Between Kv4.2 mRNA and A-Type K+ Current in Rat Striatal Cholinergic Interneurons During Development
Authors: Hattori Satoko , Murakami Fujio , Song Wen-Jie
Published: May 2006

Channel density is a fundamental factor in determining neuronal firing and is primarily regulated during development through transcriptional and translational regulation. In adult rats, striatal cholinergic interneurons have a prominent A-type current and co-express Kv4.1 and Kv4.2 mRNAs. There is evidence that Kv4.2 plays a primary role in producing the current in adult neurons. The contribution of Kv4.2 and Kv4.1 to the A-type current in cholinergic interneurons during development, however, is not known. Here, using patch-clamp recording and semi-quantitative single-cell reverse transcription-polymerase chain reaction (RT-PCR) techniques, we have examined the postnatal development of A-type current and the expression of Kv4.2 and Kv4.1 in rat striatal cholinergic interneurons. A-type current was detectable at birth, and its amplitude was up-regulated with age, reaching a plateau at about 3 wk after birth. At all ages, the current inactivated with two time constants: one ranging from 15 to 27 ms and the other ranging from 99 to 142 ms. Kv4.2 mRNA was detectable at birth, and the expression level increased exponentially with age, reaching a plateau by 3 wk postnatal. In contrast, Kv4.1 mRNA was not detectable during the first week after birth, and the expression level did not show a clear tendency with age. Taken together, our results suggest that Kv4.2 plays an essential role in producing the A-type current in striatal cholinergic interneurons during the entire course of postnatal development.
Somatosympathetic Reflexes From the Low Back in the Anesthetized Cat
Authors: Kang Y. M. , Kenney M. J. , Spratt K. F. , Pickar J. G.
Published: May 2006

In the appendicular skeleton, substantial evidence demonstrates that somatosensory input from deep tissues including limb muscles and joints elicits somatosympathetic reflexes. Much less is known about the presence and organization of these reflexes from the axial skeleton. We determined if mechanical loading of the lumbar spine and lumbar paraspinal muscle irritation reflexively affects postganglionic sympathetic nerve discharge (SND) to the spleen and kidney. In 27 α-chloralose-anesthetized cats, the L2–4 multifidus muscles were injected with the inflammatory irritant mustard oil (20%, 60 μl total) and a vertebral load (100% body weight) was applied dorsal-ventral at the L3 spinous process. Mustard oil injection alone without vertebral loading ( n = 7) increased mean splenic SND (60%), renal SND (30%), and heart rate (HR; 52 bpm). Mustard oil injection accompanied by the vertebral load ( n = 7) increased mean splenic SND (55%), renal SND (16%), and HR (27 bpm). Blood pressure changes were biphasic and could not account for these changes. When the vertebral load accompanied mustard oil, the increases in splenic SND, renal SND, and HR remained elevated in a pattern significantly different from when the vertebral load was absent. Vehicle injection combined with the mechanical load ( n = 3) did not change any of the autonomic responses. Similarly, mustard oil injection combined with a mechanical load did not change these responses when either the medial branches of the dorsal rami from T11–L5 had been cut ( n = 4) or when the spinal cord had been transected between the second and third cervical vertebrae ( n = 6). The results indicate that inflammatory stimulation of multifidus muscle in the low back evokes a somatosympathetic reflex integrated supraspinally in the upper cervical spinal cord or higher. The reflex's afferent arm travels in the medial branch of the dorsal ramus, and its efferent arm can affect sympathetic outflow to the spleen and the kidney as well as HR and BP. A static mechanical load applied to the lumbar spine accompanying the inflammatory stimulus appears to sustain the inflammatory-induced reflex activity.
Effects of Partial Lidocaine Inactivation of the Paramedian Pontine Reticular Formation on Saccades of Macaques
Authors: Barton Ellen J. , Nelson Jon S. , Gandhi Neeraj J. , Sparks David L.
Published: May 2006

To investigate the brain stem control of saccadic eye movements, the paramedian pontine reticular formation (PPRF) in rhesus monkeys was temporarily and partially inactivated with the local anesthetic lidocaine. The influence on ipsilesional, contralesional, and upward saccades was examined. While the effects of the inactivation on contralesional and upward saccades were inconsistent and small, consistent and marked modifications were observed for ipsilesional movements. For ipsilesional, horizontal saccades, all lidocaine injections caused a decrease in peak velocity and a proportional increase in duration, which substantially altered the shape of the velocity profile. The rise in duration usually fell short of preventing hypometric saccades at the peak of the effect. However, as the lidocaine effect dissipated, the amplitude often returned to control, even though the velocity and duration remained compromised. For ipsilesional, oblique saccades, the effect of lidocaine on the horizontal component was similar to that for horizontal saccades. The vertical component of oblique saccades was also influenced, albeit to a much lesser extent: the duration of the vertical component typically increased, while the vertical peak velocity either decreased or exhibited no significant change. These results were compared with simulations of three prominent models for cross-coupling oblique saccades. In general, these results of the temporary inactivation of PPRF are consistent with the predictions of local feedback models for saccadic control.
Drawing Sequences of Segments in 3D: Kinetic Influences on Arm Configuration
Authors: Breteler Mary D. Klein , Hondzinski Jan M. , Flanders Martha
Published: May 2006

Complex movements are generally thought to consist of a series of simpler elements. If this is so, how does the sensorimotor system assemble the pieces? This study recorded and evaluated sequences of arm movements to various targets placed in three-dimensional (3D) space. Subjects performed sequences consisting of single, double, or triple segments with the same first target but with different second targets. The data analysis focused on the first movement segment and evaluated hand path curvature, the hand's final approach to the first target, and the whole arm postures at the beginning and end. Although some idiosyncratic differences in approach were observed, only the final arm posture depended, in a consistent way, on which particular movement was to follow as the second segment. This provided evidence for “coarticulation” of the two segments, only at the level of arm posture, and simulations revealed that this anticipatory modification improved the energetic efficiency of the second segment. Data from movements through five consecutive triple segments (i.e., 5 triangles) were assessed to determine whether kinematic constraints, such as Donders' law, apply to repetitive drawing movements. Although such constraints could prevent the accumulation of changes in arm posture, this was not observed. Instead, in most cases, the elbow was a little bit higher at the end of each triangle than at the beginning. Taken together, the results suggest that coarticulation may facilitate the joining of two segments and the efficiency of the second movement, but does not extend over the drawing of several segments.
Neuromuscular Modulation inAplysia. I. Dynamic Model
Authors: Brezina Vladimir , Orekhova Irina V. , Weiss Klaudiusz R.
Published: May 2006

Many physiological systems are regulated by complex networks of modulatory actions. Here we use mathematical modeling and complementary experiments to study the dynamic behavior of such a network in the accessory radula closer (ARC) neuromuscular system of Aplysia. The ARC muscle participates in several types of rhythmic consummatory feeding behavior. The muscle's motor neurons release acetylcholine to produce basal contractions, but also modulatory peptide cotransmitters that, through multiple cellular effects, shape the contractions to meet behavioral demands. We construct a dynamic model of the modulatory network and examine its operation as the motor neurons fire in realistic patterns that change gradually over an hour-long meal and abruptly with switches between the different feeding behaviors. The modulatory effects have very disparate dynamical time scales. Some react to the motor neuron firing only over many cycles of the behavior, but one key effect is fast enough to respond to each individual cycle. Switches between the behaviors are therefore followed by rapid relaxations along some modulatory dimensions but not others. The trajectory of the modulatory state is a transient throughout the meal, ranging widely over regions of the modulatory space not accessible in the steady state. There is a pronounced history-dependency: the modulatory state associated with a cycle of a particular behavior depends on when that cycle occurs and what behaviors preceded it. On average, nevertheless, each behavior is associated with a different modulatory state. In the following companion study, we add a model of the neuromuscular transform to reconstruct and evaluate the actual modulated contraction shapes.
Human Amylin Actions on Rat Cholinergic Basal Forebrain Neurons: Antagonism of Beta-Amyloid Effects
Authors: Jhamandas Jack H. , Harris Kim H. , Cho Caroline , Fu Wen , MacTavish David
Published: May 2006

Human amylin (hAmylin), a 37-amino acid pancreatic peptide, and amyloid β protein (Aβ), a 39–43 amino acid peptide, abundantly deposited in the brains of Alzheimer's patients, induce neurotoxicity in hippocampal and cortical cultures. Although the mechanism of this neurotoxicity is unknown, both peptides are capable of modulating ion channel function that may result in a disruption of cellular homeostasis. In this study, we examined the effects of hAmylin on whole cell currents in chemically identified neurons from the rat basal forebrain and the interactions of hAmylin-induced responses with those of Aβ. Whole cell patch-clamp recordings were performed on enzymatically dissociated neurons of the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus. Bath application of hAmylin (1 nM to 5 μM) resulted in a dose-dependent reduction in whole cell currents in a voltage range between -30 and +30 mV. Single-cell RT-PCR analysis reveal that all DBB neurons responding to hAmylin or Aβ were cholinergic. Using specific ion channel blockers, we identified hAmylin and Aβ effects on whole cell currents to be mediated, in part, by calcium-dependent conductances. Human amylin also depressed the transient outward ( IA) and the delayed rectifier ( IK) potassium currents. The hAmylin effects on whole cell currents could be occluded by Aβ and vice versa. Human amylin and Aβ responses could be blocked with AC187 (50 nM to 1μM), a specific antagonist for the amylin receptor. The present study indicates that hAmylin, like Aβ, is capable of modulating ion channel function in cholinergic basal forebrain neurons. Furthermore, the two peptides may share a common mechanism of action. The ability of an amylin antagonist to block the responses evoked by hAmylin and Aβ may provide a novel therapeutic approach for Alzheimer's disease.
Sequential Activity of Simultaneously Recorded Neurons in the Superior Colliculus During Curved Saccades
Authors: Port Nicholas L. , Wurtz Robert H.
Published: May 2006

The visual world presents multiple potential targets that can be brought to the fovea by saccadic eye movements. These targets produce activity at multiple sites on a movement map in the superior colliculus (SC), an area of the brain related to saccade generation. The saccade made must result from competition between the populations of neurons representing these many saccadic goals, and in the present experiments we used multiple moveable microelectrodes to follow this competition. We recorded simultaneously from two sites on the SC map where each site was related to a different saccade target. The two targets appeared in rapid sequence, and the monkey was rewarded for making a saccade toward the one appearing first. Our study concentrated on trials in which the monkey made strongly curved saccades that were directed first toward one target and then toward the other. These curved saccades activated both sites on the SC map as they veered from one target to the other. The major finding was that the strongly curved saccades were preceded by sequential activity in the two neurons as indicated by three observations: the firing rate for the neuron related to the first target reached its peak earlier than did the rate of the neuron for the second target; the timing of the peak activity of the two neurons was related to the beginning and end of the saccade curvature; a weighted vector-average model based on the activity of the two neurons predicted the timing of saccade curvature. Straight averaging saccades ended between the targets so that they did not go to either target, and they were accompanied by simultaneous rather than sequential activation of the two neurons. Thus when multiple populations of neurons are active on the SC movement map, the resulting saccade is determined by the relative timing of the activity in the populations as well as their magnitude. In contrast, SC activity at the two sites did not predict the final direction of the saccade, and several control experiments found insufficient activity at other sites on the SC map to account for that final direction. We conclude that the SC neuronal activity predicts the timing of the saccade curvature, but not the final direction of the trajectory. These observations are consistent with SC activity being critical in selecting the goal of the saccade, but not in determining the exact trajectory.
Enhanced Responses of the Chorda Tympani Nerve to Sugars in the Ventromedial Hypothalamic Obese Rat
Authors: Shimizu Yasutake , Yamazaki Mifumi , Nakanishi Keiji , Sakurai Maki , Sanada Atsushi , Takewaki Tadashi , Tonosaki Keiichi
Published: May 2006

Sweet taste sensitivity in obese rats with lesions of the ventromedial hypothalamus (VMH) was studied by examining chorda tympani nerve responses to various taste stimuli including sugars. In the early progressive phase of obesity (2 wk after creating VMH lesions), there was no significant difference in the nerve responses to any taste stimulus between sham-operated and VMH-lesioned rats. In contrast, in the late phase of obesity (15–18 wk after VMH lesions), the magnitude of responses to sugars (except for fructose) was prominently greater than that in age-matched controls. High-fat diet-induced obese rats and streptozotocin-diabetic rats also showed greater chorda tympani nerve responses to sugars as was observed in VMH-lesioned obese rats, indicating that VMH lesions might not be specifically related to the enhanced gustatory neural responses to sugars. Although it has been demonstrated that the enhanced responses of the chorda tympani nerve to sugars in genetically diabetic db/db mice is largely attributable to the lack of the direct suppressive effect of leptin on the taste receptor cells, plasma leptin levels were not correlated with the changes in chorda tympani responsiveness to sugars in these models of obesity and diabetes. Accordingly, our results suggest that some chronic factors, including high blood glucose, inefficiency of insulin action, or leptin resistance may be related to the enhancement of chorda tympani nerve responses to sugars.
The Physical and Psychological Measurement of Gambling Environments
Authors: Finlay Karen , Kanetkar Vinay , Londerville Jane , Marmurek Harvey H. C.
Published: May 2006

This research examined the influence of the physical design of gambling venues on emotion. Two competing casino designs were identified. According to Kranes's playground model, casinos should include environmental elements designed to induce pleasure, legibility, and restoration. In contrast, Friedman proposed a set of design principles focusing on the machines as the dominant feature of the décor. Three exemplars of each design were identified. Measures of emotional reactions to the casinos were collected from 22 people who had gambled in all six casinos. Kranes-type casinos yielded significantly higher ratings than did Friedman-type casinos on pleasure and restoration (relief from environmental stress). Future research should focus on design variations that can be built into a Friedman-type setting to enhance restoration.
Overlapping Mental Representations of Self, Ingroup, and Outgroup: Unraveling Self-Stereotyping and Self-Anchoring
Authors: Otten Sabine , Epstude Kai
Published: May 2006

Smith and collaborators presented strong response time evidence for overlapping mental representations of the self and relevant ingroups, and they interpreted their findings as reflecting that people define themselves in terms of their ingroups. Besides on inferences from ingroup to self (self-stereotyping) however, self-ingroup overlap could also be based on inferences from the self to the ingroup (self-anchoring). The present research tackled this interpretational ambiguity and empirically distinguished self-anchoring versus self-stereotyping as processes possibly under-lying self-ingroup overlap. Results from three studies revealed stronger evidence for inferences from self to ingroup (selfanchoring) than the other way round (self-stereotyping).
A Strategy for Assessing the Impact of Time-Varying Family Risk Factors on High School Dropout
Authors: Randolph Karen A. , Fraser Mark W. , Orthner Dennis K.
Published: May 2006

Human behavior is dynamic, influenced by changing situations over time. Yet the impact of the dynamic nature of important explanatory variables on outcomes has only recently begun to be estimated in developmental models. Using a risk factor perspective, this article demonstrates the potential benefits of regressing time-varying outcome measures on time-varying explanatory measures in longitudinal models. The authors apply event history analysis techniques to demonstrate a methodological strategy that accounts for changes over time in two family risk factors for high school graduation. In a sample of 686 low-income youth attending school in an urban district, the authors found that maternal employment status and income are significant predictors of high school graduation only when conceptualized and measured as time-varying influences. The implications for policy and practice and, from a methodological perspective, for the use of time-varying explanatory variables in event models are discussed.
Knee Angular Impulse as a Predictor of Patellofemoral Pain in Runners
Authors: Stefanyshyn Darren J. , Stergiou Pro , Lun Victor M. Y. , Meeuwisse Willem H. , Worobets Jay T.
Published: May 2006

Background

Identification of mechanical factors associated with patellofemoral pain, the most prevalent running injury, is necessary to help in injury prevention, but unfortunately they remain elusive.

Hypothesis

Runners who develop patellofemoral pain have increased knee joint angular impulse in the frontal plane.

Study Design

Case control study; Level of evidence, 3.

Methods

A retrospective study compared knee abduction impulses of 20 patellofemoral pain patients with those of 20 asymptomatic patients. A second prospective study quantified knee angular impulses during the stance phase of running of 80 runners at the beginning of the summer running season. Epidemiologic data were then collected, recording the type and severity of injury of these runners during a 6-month running period.

Results

The patellofemoral pain patients in the retrospective study had significantly higher (P =. 026) knee abduction impulses (17.0 ± 8.5 Nms) than did the asymptomatic patients (12.5 ± 5.5 Nms). Six patients developed patellofemoral pain during the prospective study. The prospective data showed that patients who developed patellofemoral pain had significantly higher (P =. 042) knee abduction impulses (9.2 ± 3.7 Nms) than did matched patients who remained uninjured (4.7 ± 3.5 Nms).

Conclusion

The data indicate that increased knee abduction impulses should be deemed risk factors that play a role in the development of patellofemoral pain in runners.

Clinical Relevance

Footwear and running style can influence knee angular impulse, and the appropriate manipulation of these variables may play a preventive role for patients who are predisposed to patellofemoral pain.
A novel fibrinogen variant (fibrinogen Seoul II; AαGln328Pro) characterized by impaired fibrin α-chain cross-linking
Authors: Park Rojin , Doh Hyun-Ju , An Seong-Soo A. , Choi Jong-Rak , Chung Kwang-Hoe , Song Kyung-Soon
Published: May 2006

We report a novel fibrinogen variant (fibrinogen Seoul II), which has a heterozygous point mutation from CAA to CCA leading to AαGln328Pro. The mutation site is among several glutamine residues that serve as α-chain cross-linking acceptor sites. Fibrinogen Seoul II was found in a 51-year-old male patient and his family in Seoul, Korea. The patient was diagnosed with myocardial infarction at age 43. Eight years later he was admitted to the emergency room due to recurrence of the disease, where he expired under treatment with tissue plasminogen activator (t-PA). Fibrin polymerization curves, made using purified fibrinogen from the patient's relatives, showed a decreased final turbidity, suggesting Seoul II fibrin clots are composed of thinner fibers. This supposition was verified using scanning electron microscopy. Alpha-polymer formation by the mutant fibrinogen upon thrombin treatment in the presence of factor XIII and calcium was distinctly impaired. This result confirms that the residue Aα328 plays a pivotal role in α-chain cross-linking.
Genome-wide detection and analysis of homologous recombination among sequenced strains of Escherichia coli
Authors: Mau Bob , Glasner Jeremy D , Darling Aaron E , Perna Nicole T
Published: May 2006

Background

Comparisons of complete bacterial genomes reveal evidence of lateral transfer of DNA across otherwise clonally diverging lineages. Some lateral transfer events result in acquisition of novel genomic segments and are easily detected through genome comparison. Other more subtle lateral transfers involve homologous recombination events that result in substitution of alleles within conserved genomic regions. This type of event is observed infrequently among distantly related organisms. It is reported to be more common within species, but the frequency has been difficult to quantify since the sequences under comparison tend to have relatively few polymorphic sites.

Results

Here we report a genome-wide assessment of homologous recombination among a collection of six complete Escherichia coli and Shigella flexneri genome sequences. We construct a whole-genome multiple alignment and identify clusters of polymorphic sites that exhibit atypical patterns of nucleotide substitution using a random walk-based method. The analysis reveals one large segment (approximately 100 kb) and 186 smaller clusters of single base pair differences that suggest lateral exchange between lineages. These clusters include portions of 10% of the 3,100 genes conserved in six genomes. Statistical analysis of the functional roles of these genes reveals that several classes of genes are over-represented, including those involved in recombination, transport and motility.

Conclusion

We demonstrate that intraspecific recombination in E. coli is much more common than previously appreciated and may show a bias for certain types of genes. The described method provides high-specificity, conservative inference of past recombination events.
Melatonin modulates 900 MHz microwave-induced lipid peroxidation changes in rat brain
Authors: Köylü Halis , Mollaoglu Hakan , Ozguner Fehmi , Nazýroölu Mustafa , Delibap Namýk
Published: May 2006

Microwaves (MW) from cellular phones may affect biological systems by increasing free radicals, which may enhance lipid peroxidation levels of the brain, thus leading to oxidative damage. Melatonin is synthesized in and secreted by the pineal gland at night and exhibits anti-oxidant properties. Several studies suggest that supplementation with anti-oxidant can influence MW-induced brain damage. The present study was designed to determine the effects of MW on the brain lipid peroxidation system, and the possible protective effects of melatonin on brain degeneration induced by MW.

Twenty-eight Sprague-Dawley male rats were randomly divided into three groups as follows: (1) sham-operated control group (N-8); (2) study 900-MHz MW-exposed group (N-8); and (3) 900-MHz MW-exposed-melatonin (100 mg/kg sc before daily MW exposure treated group) (N-10). Cortex brain and hippocampus tissues were removed to study the levels of lipid peroxidation as malonyl dialdehyde. The levels of lipid peroxidation in the brain cortex and hippocampus increased in the MW group compared with the control group, although the levels in the hippocampus were decreased by MW-melatonin administration. The brain cortex lipid peroxidation levels were unaffected by melatonin treatment.

We conclude that melatonin may prevent MW-induced oxidative changes in the hippocampus by strengthening the anti-oxidant defense system, by reducing oxidative stress products.
C-Terminal Amino Acid Alteration rather than Late Termination Causes Complete Deficiency of Thyroxine-Binding Globulin CD-NeuIsenburg
Authors: Moeller Lars C. , Fingerhut Anja , Lahner Harald , Grasberger Helmut , Weimer Bernd , Happ Joachim , Mann Klaus , Janssen Onno E.
Published: May 2006

Context: T4-binding globulin (TBG) is the main transport protein for T4 in blood and a member of the superfamily of serine proteinase inhibitors. So far, 14 mutations leading to familial complete TBG deficiency have been reported. Eleven of these are caused by mutations leading to truncation of the molecule, and three are caused by single amino acid substitutions.

Objective: We report and study the complete deficiency TBG variant found in a patient from NeuIsenburg, Germany (TBG-CDNI).

Methods: Direct DNA sequencing was used to identify the TBG-CDNI mutation in the propositus, which was confirmed by allele-specific amplification. Site-directed mutagenesis and expression in Xenopus oocytes was used to study the secretion defect of TBG-CDNI and several variants by Western blot and T4-binding assay.

Results: The deletion of two nucleotides in codon 384 (1211_1212delTC) causes a frameshift altering the last 11 residues, introduces a new glycosylation site, and elongates the molecule by seven new amino acids. In contrast to normal TBG, TBG-CDNI was not secreted by Xenopus oocytes. Elongation of normal TBG by seven alanines did not affect its secretion or binding properties. On the other hand, neither disruption of its new glycosylation site nor termination of TBG-CDNI at the normal length repaired its secretion defect.

Conclusions: In this first late termination variant of complete TBG deficiency, alteration of β-strand 5B, located in the core of the molecule, rather than elongation of the molecule or introduction of a new glycosylation site, suffices to disrupt secretion of TBG-CDNI.
The Multiple-Family ELSP with Safety Stocks
Authors: Karalli Serge M. , Flowers A. Dale
Published: May 2006

The multiple-family economic lot scheduling problem with safety stocks (MFELSP-SS) with normally distributed, time-stationary demand is considered in a manufacturing setting where the relevant costs include family setup costs, item setup costs, and inventory holding costs for both cycle and safety stocks. A family is a subset of the items that share a common family setup with its associated setup cost and setup time. Each item within the family may have its own setup time and setup cost. The families form a partition of the set of items manufactured on a single facility. The safety stock level for any item is a function of the time interval between production runs for the item, the service level specified, and the variance of its demand. We consider safety stocks explicitly in the formulation, as their holding costs vary nontrivially with the model’s decision variables. The MFELSP-SS differs from multilevel inventory models with family setups in that the former assumes noninstantaneous inventory replenishment and considers the cost of holding safety stocks; the latter assumes instantaneous replenishment and does not directly assess the impact of safety stock levels on the total cost. An efficient solution procedure is developed for this model. Properties of the nonconvex feasible space are identified and used in the solution approach. The solution to the mathematical model comprises the basic period length, the family multipliers, and the item multipliers that give the lowest total cost of setups and carrying inventory. The family multipliers and item multipliers are restricted to integer powers of two.
Conditioned Withdrawal Drives Heroin Consumption and Decreases Reward Sensitivity
Authors: Kenny Paul J. , Chen Scott A. , Kitamura Osamu , Markou Athina , Koob George F.
Published: May 2006

Aspects of drug withdrawal may become conditioned to previously neutral environmental stimuli via classical conditioning processes. Nevertheless, the significance of conditioned withdrawal effects in motivating drug intake remains largely unexplored. Here, we investigated the effects of conditioned withdrawal in modulating heroin consumption and brain reward sensitivity in rats. Rats intravenously self-administered heroin (20 μg/infusion) during 0 h (control), 1 h (nondependent), or 23 h (dependent) sessions and had daily intracranial self-stimulation (ICSS) thresholds assessed. ICSS thresholds remained stable and unaltered in control rats. In nondependent rats, heroin self-administration induced a transient activation of reward systems, reflected in lowering of ICSS thresholds. In dependent rats, heroin intake escalated across sessions and was associated with a gradual decrease in reward sensitivity, reflected in progressively elevated ICSS thresholds. Thus, as dependence develops, heroin may be consumed not only for its acute reward-facilitating effects, but also to counter persistent deficits in reward sensitivity. In nondependent rats, the opioid receptor antagonist naloxone (30 μg/kg) increased heroin consumption and reversed heroin-induced lowering of ICSS thresholds, effects resistant to classical conditioning. In contrast, in dependent rats naloxone (30 μg/kg) increased heroin consumption and also elevated ICSS thresholds above their already elevated baseline levels (i.e., precipitated withdrawal). Most importantly, stimuli repeatedly paired with naloxone-precipitated withdrawal provoked heroin consumption and elevated ICSS thresholds in dependent rats. Thus, conditioned stimuli predicting the onset of heroin withdrawal, and hence the reward deficits coupled with this state, may play a critical role in provoking craving and relapse in human opiate addicts.
Root Cementum Modulates Periodontal Regeneration in Class III Furcation Defects Treated by the Guided Tissue Regeneration Technique: A Histometric Study in Dogs
Authors: Gonçalves Patricia F. , Gurgel Bruno C.V. , Pimentel Suzana P. , Sallum Enilson A. , Sallum Antonio W. , Casati Márcio Z. , Nociti Francisco H.
Published: May 2006

Background: Because the possibility of root cementum preservation as an alternative approach for the treatment of periodontal disease has been demonstrated, this study aimed to histometrically evaluate the effect of root cementum on periodontal regeneration.

Methods: Bilateral Class III furcation defects were created in dogs, and each dog was randomly assigned to receive one of the following treatments: control (group A): scaling and root planing with the removal of root cementum; or test (group B): removal of soft microbial deposits by polishing the root surface with rubber cups and polishing paste, aiming at maximum cementum preservation. Guided tissue regeneration (GTR) was applied to both groups.

Results: Four months after treatment, a superior length of new cementum (3.59 ± 1.67 mm versus 6.20 ± 2.26 mm; P = 0.008) and new bone (1.86 ± 1.76 mm versus 4.62 ± 3.01 mm; P = 0.002) and less soft tissue along the root surface (2.77 ± 0.79 mm versus 1.10 ± 1.48 mm; P = 0.020) was observed for group B. Additionally, group B presented a larger area of new bone (P = 0.004) and a smaller area of soft tissue (P = 0.008).

Conclusion: Within the limits of this study, root cementum may modulate the healing pattern obtained by guided tissue regeneration in Class III furcation defects.
The Widening Gap in Mortality by Educational Level in the Russian Federation, 1980–2001
Authors: Murphy Michael , Bobak Martin , Nicholson Amanda , Rose Richard , Marmot Michael
Published: May 2006

Objectives. We examined trends in the relation between educational level and adult mortality in the Russian Federation in the period 1989 through 2001.

Methods. We used a convenience cohort based on survey respondents’ information about age, survival status, and educational level of close relatives, and applied modified indirect demographic techniques to stratify mortality rates by educational level in the study period. A random sample of 7172 respondents (response rate=61%) provided full information on 10440 relatives.

Results. The mortality advantage of better-educated men and women in 1980 increased substantially by 2001. In 1980, life expectancy at age 20 for university-educated men was 3 years greater than for men with elementary education only, but was 11 years greater by 2001, reflecting not only declining life expectancy in less-educated men but also an improvement among better-educated men. Similar patterns were seen in women.

Conclusions. The well-documented mortality increases seen in Russia after 1990 have predominantly affected less-educated men and women, whereas the mortality of persons with university education has improved, resulting in a sharp increase in educational-level mortality differentials.
Comparison of the response to infliximab or etanercept monotherapy with the response to cotherapy with methotrexate or another disease‐modifying antirheumatic drug in patients with rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register
Authors: Hyrich Kimme L. , Symmons Deborah P. M. , Watson Kath D. , Silman Alan J. ,   British Society for Rheumatology Biologics Register
Published: May 2006

Objective

To compare outcome at 6 months in unselected “real‐world” patients with rheumatoid arthritis treated with etanercept or infliximab as either monotherapy, cotherapy with methotrexate (MTX), or cotherapy with another disease‐modifying antirheumatic drug (DMARD).

Methods

A total of 2,711 subjects starting treatment with their first biologic agent (1,453 infliximab and 1,258 etanercept) were followed up for 6 months. Outcome was assessed using the European League Against Rheumatism (EULAR) response criteria. Ordinal regression was used to model the response in the MTX and other DMARD cotherapy groups relative to the monotherapy group separately for the 2 anti–tumor necrosis factor α agents, after adjusting for baseline differences.

Results

Etanercept‐treated patients had an increased likelihood of achieving a higher EULAR response category with cotherapy with MTX (odds ratio [OR] 2.0, 95% confidence interval [95% CI] 1.5–2.7) and with another DMARD (OR 1.2, 95% CI 0.9–1.6) as compared with monotherapy. For infliximab‐treated patients, the likelihoods were 1.4 (95% CI 0.9–2.0) for MTX and 1.3 (95% CI 0.8–2.1) for other DMARDs versus monotherapy. Cotherapy with MTX or another DMARD produced significantly higher rates of remission with etanercept (12% and 11%, respectively) as compared with etanercept monotherapy (5%). Infliximab‐treated patients showed similar remission rates in the MTX and other DMARD cotherapy groups (8% and 5%, respectively) as in the monotherapy group (7%).

Conclusion

In this study of real‐world patients, the use of MTX and, to a lesser extent, other DMARDs as cotherapy with etanercept was associated with a higher likelihood of response. Although the infliximab guidelines suggest that MTX be used as cotherapy, in clinical practice, both monotherapy and cotherapy with DMARDs other than MTX are used. These data suggest that either of the latter strategies may be useful in patients who are intolerant to MTX.
Gene profiling of scleroderma skin reveals robust signatures of disease that are imperfectly reflected in the transcript profiles of explanted fibroblasts
Authors: Gardner Humphrey , Shearstone Jeffrey R. , Bandaru Raj , Crowell Tom , Lynes Matthew , Trojanowska Maria , Pannu Jaspreet , Smith Edwin , Jablonska Stefania , Blaszczyk Maria , Tan Filemon K. , Mayes Maureen D.
Published: May 2006

Objective

To determine whether biopsy specimens obtained from systemic sclerosis (SSc) lesions show a distinctive gene profile, whether that gene profile is maintained in fibroblasts cultured from SSc skin biopsy specimens, and whether results from tissue obtained from multiple clinical centers can be combined to yield useful observations in this rare disease.

Methods

Biopsy samples and passaged fibroblasts were stored in RNAlater solution prior to processing for RNA. RNA from SSc and control skin biopsy specimens, as well as SSc and control explanted passage 4 fibroblasts, from 9 patients and 9 controls was hybridized to Affymetrix HG‐U133A arrays. Data were analyzed using the BRB ArrayTools system. When appropriate, findings were followed up with immunohistochemical analysis or TaqMan studies.

Results

Biopsy samples obtained from patients with SSc had a robust and distinctive gene profile, with ∼1,800 qualifiers distinguishing normal skin from SSc skin at a significant level. The SSc phenotype was the major driver of sample clusters, independent of origin. Alterations in transforming growth factor β and Wnt pathways, extracellular matrix proteins, and the CCN family were prominent. Explanted fibroblasts from SSc biopsy samples showed a far smaller subset of changes that were relatively variable between samples, suggesting that either nonfibroblast cell types or other aspects of the dermal milieu are required for full expression of the SSc phenotype.

Conclusion

SSc has a distinct gene profile that is not confounded by geographic location, indicating that extended multicenter studies may be worthwhile to identify distinct subsets of disease by transcript profiling. Explanted SSc fibroblasts show an incomplete reflection of the SSc phenotype.
African‐American men with nonpalpable prostate cancer exhibit greater tumor volume than matched white men
Authors: Sanchez‐Ortiz Ricardo F. , Troncoso Patricia , Babaian Richard J. , Lloreta Josep , Johnston Dennis A. , Pettaway Curtis A.
Published: May 2006

BACKGROUND

Although prostate cancer (PC) mortality disproportionately affects African‐American (AA) men, limited data exist comparing the pathologic characteristics of white and AA patients with nonpalpable PC (clinical stage T1c).

METHODS

The authors reviewed the radical prostatectomy (RP) specimens from 37 consecutive AA men with clinical stage T1c PC and 35 white men who were matched for age, clinical stage, serum prostate‐specific antigen (PSA) level, year of surgery, prostate weight, and prostate biopsy strategy. Pathologic characteristics were compared after mapping tumor foci and calculating tumor volumes by using computer software.

RESULTS

For AA men, the median age (57.7 years), mean serum PSA level (9.3 ng/mL), mean prostate weight (43 g), and biopsy strategy (73% sextant) were matched with the cohort of 35 white men (median age, 57.1 years; mean PSA, 9.3 ng/mL;, mean prostate weight, 43 g; biopsy strategy, 66% sextant). Despite similar biopsy characteristics between the 2 groups (Gleason score ≥7 in 43% of AA men vs. 37% of white men), AA men exhibited significantly higher prostatectomy Gleason scores (≥7 in 76% of AA men vs. 34% of white men; P = .01). AA men also had a higher mean tumor volume (1.82 cm3 vs. 0.72 cm3; P = .001) and had 2.8 times more tumor per ng/mL of serum PSA (0.22 cm3 per ng/mL vs. 0.079 cm3 per ng/mL; P = .001).

CONCLUSIONS

Compared with a cohort of white men with similar clinical features at the time of biopsy, AA men with nonpalpable PC had higher prostatectomy Gleason scores, greater cancer volume, and greater tumor volume per ng/mL of serum PSA. These data provide additional support for the concept of early PC detection using a serum PSA threshold of 2.5 ng/mL for biopsy among AA men. Cancer 2006. © 2006 American Cancer Society.
Topography and connections of the telencephalon in a chondrostean, Acipenser baeri: An experimental study
Authors: Huesa Gema , Anadón Ramón , Yáñez Julián
Published: May 2006

Sturgeons belong to an ancient group of the extant actinopterygian fishes. Accordingly, the study of their brain connections is important to understand brain evolution in the line leading to teleosts. We examined the topography and connections of the various telencephalic regions of the Siberian sturgeon (Acipenser baeri). The telencephalic regions were characterized on the basis of acetylcholinesterase histochemistry and calbindin‐D28k and calretinin immunohistochemistry. The telencephalic connections were investigated by using the fluorescent dye DiI (1,1′‐dioctadecyl 3,3,3′,3′‐tetramethylindocarbocyanine perchlorate) in fixed brains. Application of DiI to different areas of the pallial (dorsal) regions of the telencephalic lobes showed that they have mostly intratelencephalic connections. A posterior pallial region is characterized by its similar hodology to that of the posterior zone of the teleosts dorsal telencephalon and those described in other ancient groups. Extratelencephalic connections of the pallium are scarce, although a few afferent and efferent connections with the diencephalon, mesencephalon, and rostral rhombencephalon were observed. DiI application to subpallial regions showed both intratelencephalic connections and connections with different brain regions. Afferents to the subpallium originate from the olfactory bulbs, preoptic area, thalamus, posterior tuberculum, hypothalamus, secondary gustatory nucleus, and raphe nuclei. Some of these connections are quite similar to those described for other vertebrates. J. Comp. Neurol. 497:519–541, 2006. © 2006 Wiley‐Liss, Inc.