bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of poly(A) binding protein function in translation: Characterization of the Paip2 homolog, Paip2B
Authors: Berlanga Juan José , Baass Alexis , Sonenberg Nahum
Published: June 2006

The 5′ cap and 3′ poly(A) tail of eukaryotic mRNAs act synergistically to enhance translation. This synergy is mediated via interactions between eIF4G (a component of the eIF4F cap binding complex) and poly(A) binding protein (PABP). Paip2 (PABP-interacting protein 2) binds PABP and inhibits translation both in vitro and in vivo by decreasing the affinity of PABP for polyadenylated RNA. Here, we describe the functional characteristics of Paip2B, a Paip2 homolog. A full-length brain cDNA of Paip2B encodes a protein that shares 59% identity and 80% similarity with Paip2 (Paip2A), with the highest conservation in the two PABP binding domains. Paip2B acts in a manner similar to Paip2A to inhibit translation of capped and polyadenylated mRNAs both in vitro and in vivo by displacing PABP from the poly(A) tail. Also, similar to Paip2A, Paip2B does not affect the translation mediated by the internal ribosome entry site (IRES) of hepatitis C virus (HCV). However, Paip2A and Paip2B differ with respect to both mRNA and protein distribution in different tissues and cell lines. Paip2A is more highly ubiquitinated than is Paip2B and is degraded more rapidly by the proteasome. Paip2 protein degradation may constitute a primary mechanism by which cells regulate PABP activity in translation.
Acid Suppressive Therapy Use on an Inpatient Internal Medicine Service
Authors: Pham Co QD , Regal Randolph E , Bostwick Thomas R , Knauf Kara S
Published: June 2006

Background:

Use of acid suppressant medications has increased in both frequency and breadth in recent years. Data have indicated that questionable use of acid suppressants for non-accepted indications is common.

Objective:

To assess the indications and prevalence of acid suppressants used by inpatients on admission and at discharge.

Methods:

A retrospective chart review of 213 patients admitted to the University of Michigan Hospital non-critical care general medical service was conducted. Relevant medical history, acid suppressant drug used, and indications were collected from both inpatient medical records and discharge medication lists.

Results:

Of the 213 patients reviewed, 29% were taking acid suppressants prior to admission, with 33% being proton pump inhibitors (PPIs). Once patients were admitted, acid suppressant use increased to 71% (152 of 213), with 84% PPIs, 11% histamine2-receptor antagonists, and 5% combination therapy. Based upon our criteria, only 10% (15 of 152) of those on acid suppressants were found to have an acceptable indication. In patients where any history of gastroesophageal reflux disorder (GERD) was deemed as an acceptable indication (32 other patients), 31% (47 of 152) had an acceptable indication. For the 137 patients with non-accepted indications, 29% had no discernable indication and 38% were prescribed acid suppressants for corticosteroid-associated or stress ulcer prophylaxis. A history of gastrointestinal bleeds or peptic ulcer disease of more than 3 months since initial diagnosis or documented exacerbation of symptoms comprised 8% of the population. The aforementioned group of GERD patients made up 23% of this group. Compared to the 29% of patients taking acid suppressants prior to admission, 54% (115 of 213) of patients were prescribed acid suppressants at discharge. If only recent exacerbations of GERD were deemed as long-term indications, 10% (12 of 115) of these patients were found to have accepted indications. If all GERDs were acceptable long-term indications, 27% (31 of 115) would have met criteria for acceptable outpatient use.

Conclusions:

There is considerable excess usage of acid suppressants in both the inpatient and outpatient settings.
Does Celecoxib Potentiate the Anticoagulant Effect of Warfarin? A Randomized, Double-Blind, Controlled Trial
Authors: Dentali Francesco , Douketis James D , Woods Karen , Thabane Lehana , Foster Gary , Holbrook Anne , Crowther Mark
Published: June 2006

Background:

The management of patients who are receiving warfarin therapy and have musculoskeletal problems that require treatment with a nonsteroidal antiinflammatory drug (NSAID) is problematic because NSAID use may increase the risk for bleeding. Cyclooxygenase-2 selective NSAIDs such as celecoxib may be less likely to promote gastrointestinal bleeding; however, there are concerns that they could potentiate the anticoagulation effect of warfarin.

Objective:

To determine whether celecoxib potentiates the anticoagulant effect of warfarin, as measured by the international normalized ratio (INR).

Methods:

We performed a randomized, controlled, crossover trial to assess the effect on INR of celecoxib versus codeine (control treatment) in 15 patients who were receiving warfarin therapy and required analgesic treatment for osteoarthritis. During Phase 1 of the study, patients were randomly allocated to receive celecoxib 200 mg/day or codeine phosphate 7–15 mg 3–4 times daily for 5 weeks. During Phase 2 of the study, patients stopped the first study medication and started the other study medication; there was no drug-free interval between phases. Weekly INR testing was performed during the 10 week study period. Adopting the intent-to-treat principle, we used generalized estimating equations to analyze the data.

Results:

There was no significant difference in the mean INR values during each 5 week treatment period when patients received either celecoxib or codeine. There was, therefore, insufficient evidence to reject the hypothesis that these 2 treatments had an equal effect on the INR (mean difference [95% CI] 0.10 [-0.04 to 0.24]; p=0.16) based on mean imputation. This finding was confirmed after we repeated the analysis with multiple imputations (mean difference [95% CI] 0.093 [-0.16 to 0.35]; p = 0.47).

Conclusions:

Our results suggest that treatment with celecoxib does not potentiate the INR when taken with warfarin. Larger randomized trials are warranted to address the effects of coadministered warfarin and celecoxib on clinical outcomes.
Drug Dosage Adjustments According to Renal Function at Hospital Discharge
Authors: van Dijk Elisabeth A , Drabbe Nathalie RG , Kruijtbosch Martine , De Smet Peter AGM
Published: June 2006

Background:

Adequate dosing of medication in renal impairment to prevent hospitalizations and adverse reactions is a growing concern in the aging society. There are several dosing guidelines available, but structural use is uncommon.

Objective:

To perform a retrospective analysis of the incidence of required versus implemented dosage adjustments according to guidelines in patients with renal insufficiency at discharge and evaluate specific determinants responsible for the percentage of overlooked dosage adjustments.

Methods:

Medication and laboratory data were collected from patients at discharge during February and November 2004. For patients with a calculated creatinine clearance less than 51 mL/min/1.73 m2, the necessity for dosage adjustments was evaluated by pharmacists. All data were collected for further research and subsequent statistical analysis.

Results:

At discharge, 237 of 647 (36.6%) patients had a calculated creatinine clearance less than 51 mL/min/1.73 m2. Dosage adjustment based on renal function was necessary in 411 of 1718 (23.9%) of prescriptions. These adjustments were performed in 242 (58.9%) prescriptions and not performed in 169 (41.1%) cases. The risk of not adjusting the dosage was significantly associated with serum creatinine levels greater than 1.71 mg/dL and creatinine clearance less than 35 mL/min/1.73 m2 (p <0.05). The risk of not adjusting the dosage was also significantly associated with drugs producing severe consequences when dosing guidelines were overlooked (p < 0.05).

Conclusions:

In patients with a calculated creatinine clearance less than 51 mL/min/1.73 m2, dosing according to their renal function can be improved. Because of the need and the association found in this study, an alert system could help prescribers and pharmacists to adapt drug dosage in patients with renal impairment.
Warning Signs for Suicide: Theory, Research, and Clinical Applications
Authors: Rudd M. David , Berman Alan L. , Joiner Thomas E. , Nock Matthew K. , Silverman Morton M. , Mandrusiak Michael , Van Orden Kimberly , Witte Tracy
Published: June 2006

The current article addresses the issue of warning signs for suicide, attempting to differentiate the construct from risk factors. In accordance with the characteristic features discussed, a consensus set of warning signs identified by the American Association of Suicidology working group are presented, along with a discussion of relevant clinical and research applications.
Warning Signs for Suicide on the Internet: A Descriptive Study
Authors: Mandrusiak Michael , Rudd M. David , Joiner Thomas E. , Berman Alan L. , Van Orden Kimberly A. , Witte Tracy
Published: June 2006

The issue of suicide warning signs on the Internet is considered. In addition to reviewing some of the relevant conceptual issues about warning signs, a random sample of Internet sites was selected and reviewed. Warning signs were grouped and agreement across sites was examined, with results confirming broad disparity in what is presented to the public. The implications of a lack of consensus on warning signs for suicide are discussed.
A Test of the Effectiveness of a List of Suicide Warning Signs for the Public
Authors: Van Orden Kimberly A. , Joiner Thomas E. , Hollar Daniel , Rudd M. David , Mandrusiak Michael , Silverman Morton M.
Published: June 2006

In this study we examined the effect that reading a list of warning signs for suicide has on beliefs about suicide, including the belief that one can recognize a suicidal crisis. All participants read two sets of warning signs (with only the experimental group reading the suicide warning signs) and then answered questions concerning beliefs related to three health problems. Results indicate that participants who read the suicide warning signs reported greater abilities to recognize if someone is suicidal but did not report stronger beliefs that suicidal individuals are partly to blame, nor did they report lower likelihoods of befriending suicidal individuals. Results suggest that reading the list of warning signs may be effective in increasing the public's ability to recognize suicidal crises without creating or magnifying stigmatizing beliefs about suicidal individuals.
The Emotional Impact and Ease of Recall of Warning Signs for Suicide: A Controlled Study
Authors: Rudd M. David , Mandrusiak Michael , Joiner Thomas E. , Berman Alan L. , Van Orden Kimberly A. , Hollar Daniel
Published: June 2006

In light of concerns about potential iatrogenic effects of information about suicide, in the current study we examined the emotional impact of reading a list of warning signs for suicide in comparison to comparable lists for heart attacks and diabetes. All participants read two sets of warning signs, with the experimental group reading the suicide warning signs. Results confirm no difference in emotional impact across groups, along with providing evidence that warning signs for suicide are as easy to recall after exposure as warning signs for heart attack. Implications for pubic health campaigns are discussed.
Imminent Suicide: The Illusion of Short‐Term Prediction
Authors: Simon Robert I.
Published: June 2006

The concept of imminent suicide is examined. A search of National Electronic Library for Mental Health, the Cochrane Library, PubMed, OVID and MD Consult databases was conducted using the terms “suicide, imminent.” The termimminentfrequently appears in the mental health literature, finding common usage among clinicians. It is also a legal term of art embedded in civil commitment statutes; duty to warn and protect statutes and case law, usually under the rubric of dangerousness; and in seclusion and restraint policies. Managed care admission protocols may contain imminence criteria for patients at risk for suicide before approving insurance benefits, yet no suicide risk factors exist for the short‐term prediction of suicide.
The Hospital Management of Fatal Self‐Poisoning in Industrialized Countries: An Opportunity for Suicide Prevention?
Authors: Kapur Navneet , Turnbull Pauline , Hawton Keith , Simkin Sue , Mackway‐Jones Kevin , Gunnell David
Published: June 2006

Suicide by self‐poisoning is a prevalent cause of death worldwide. A substantial proportion of individuals who poison themselves come into contact with medical services before they die. Our focus in the current study was the medical management of drug self‐poisoning in industrialized countries and its possible contribution to suicide prevention. We reviewed the literature to determine the proportion of self‐poisoning suicides who reach hospital alive, the sociodemographic and clinical characteristics of in‐hospital overdose deaths, the in‐hospital management this group of patients receives, and whether there are specific aspects of pre‐hospital care and in‐hospital management that have the potential to improve survival. Between 11% and 28% of individuals who died following deliberate ingestion of drugs reached hospital alive. The substances which were most frequently implicated in death were paracetamol (acetaminophen) and paracetamol compounds, tricyclic antidepressants, and benzodiazepines. Most patients received fairly intensive treatment, yet death may have been preventable in a small proportion of cases. Only one intervention (the administration of acetylcysteine) was shown to reduce mortality and this was in a highly selected group of patients (those who had ingested paracetamol and developed fulminant hepatic failure). It is possible that other interventions such as better airway management, the prompt administration of activated charcoal, and improved pre‐hospital care may improve outcomes but their potential contribution to suicide prevention needs to be investigated in future studies.
Suicidal and Deliberate Self‐Harm Ideation Among Patients with Physical Illness: The Role of Coping Styles
Authors: Marusic Andrej , Goodwin Renee D.
Published: June 2006

The relationship between coping styles and suicidal ideation (SI) or deliberate self‐harm (DSH) ideation among patients with physical illness was examined. Four hundred fifteen adult male medical inpatients completed the Coping Styles Questionnaire. Patients with and without SI, and with and without DSH, were compared on coping styles. Sixteen percent of patients (n = 67) had SI and 18.3% (n = 76) had DSH. SI was associated with higher scores on emotional coping and lower scores on rational and detachment coping styles, compared with those without SI. DSH, compared with those without DSH, was associated with significantly higher scores on avoidance coping strategies. These data suggest coping styles among medical patients with and without SI or DSH may differ. The mechanism of this link is not entirely clear, but it may be that coping styles reflect one possible pathway of the association between poor physical health and SI and DSH. Replication of these results in a longitudinal study is needed. If replicated, incorporation of these data into the development of intervention strategies focused on improving coping strategies may be worthwhile.
Gender in Suicide Attempt Rates and Childhood Sexual Abuse Rates: Is There an Interaction?
Authors: Roy Alec , Janal Malvin
Published: June 2006

Two competing explanations for higher rates of attempted suicide in women than men were compared. Because childhood sexual abuse is more prevalent in girls than boys, one explanation of higher rates of suicide attempts in women is that it is a direct result of the higher incidence of sexual abuse in girls. Alternatively, higher rates of suicide attempts might result from gender differences in the impact of childhood sexual abuse on suicidal behavior. To compare these theories, data from 1,889 abstinent, substance‐dependent patients who completed the Childhood Trauma Questionnaire (CTQ) and who were interviewed about suicide attempts was examined. Scores on each scale of the CTQ were examined as a function of gender and attempter status. Results showed higher rates of suicide attempts in women than in men, higher CTQ scores in women than men, and a higher CTQ score in attempters than nonattempters. However, logistic regression indicated that gender and abuse did not interact to determine attempter status. Thus, the data support the first hypothesis that the greater frequency of suicide attempts in women may be partly attributed to the higher prevalence of childhood sexual abuse in girls. The generalizability of these results to the general population and to other diagnostic groups requires further study.
Variation in Functioning, Psychosocial Characteristics, and Six‐Month Outcomes Among Suicidal Youth in Comprehensive Community Mental Health Services
Authors: Mandell David S. , Walrath Christine M. , Goldston David B.
Published: June 2006

In this study we compared the psychosocial (n = 7,896) and clinical (n = 4,664) characteristics and 6‐month functional outcomes (n = 2,594) of suicidal and nonsuicidal youth. Repeat and previous attempters were more likely than first‐time and never attempters to experience psychosocial problems and to be functionally impaired in a variety of domains. Differences in functional impairment persisted at 6 months. Among those who were not severely functionally impaired at baseline, repeat attempters were more likely to be severely impaired at 6 months. Subgroups of suicide attempters may present to treatment differently, have a different expression of problems over time, and have different treatment needs.
Layer Acquisition by Cortical GABAergic Interneurons Is Independent of Reelin Signaling
Authors: Pla Ramón , Borrell Víctor , Flames Nuria , Marín Oscar
Published: June 2006

Functioning of the cerebral cortex requires the coordinated assembly of circuits involving glutamatergic projection neurons and GABAergic interneurons. Despite their segregated origin in different regions of the telencephalon, projection neurons and interneurons born synchronically end up adopting the same cortical layer, suggesting that layer acquisition is highly coordinated for both neuronal types. The radial migration and laminar arrangement of projection neurons depends on Reelin, a secreted glycoprotein expressed near the pial surface during embryogenesis. In contrast, the mechanisms controlling layer acquisition by cortical interneurons remain essentially unknown. Here, we have used an ultrasound-guided transplantation approach to analyze the mechanisms underlying the acquisition of laminar locations by cortical interneurons. We found that layer acquisition by cortical GABAergic interneurons does not directly depend on Reelin signaling. Moreover, interneurons invade their target layers well after synchronically generated projection neurons reach their final destination. These results suggest a model in which cues provided by projection neurons guide cortical interneurons to their appropriate layer, and reveal that, at least for some neuronal types, long-range radial migration does not directly require Reelin.
Identification of an Endoplasmic Reticulum-Retention Motif in an Intracellular Loop of the Kainate Receptor Subunit KA2
Authors: Nasu-Nishimura Yukiko , Hurtado David , Braud Stephanie , Tang Tina Tze-Tsang , Isaac John T. R. , Roche Katherine W.
Published: June 2006

Neuronal kainate receptors are typically heteromeric complexes composed of GluR5–7 and KA1–2 subunits. Although GluR5–7 can exist as functional homomeric channels, the KA subunits cannot. KA2 is widely expressed in the CNS, and KA2/GluR6 heteromers are the most prevalent subunit composition in brain. Previous work has identified endoplasmic reticulum (ER)-retention motifs in the C terminus of KA2, which prevent surface expression of KA2 homomers. However, we find that, when these motifs are mutated, only a small fraction of KA2 is surface expressed. We now identify an additional ER retention motif in the intracellular loop region of KA2, which, when mutated together with the C-terminal motifs, significantly increases the level of KA2 surface expression. However, electrophysiological analysis of surface-expressed KA2 homomers indicates that they do not form functional ion channels. In heterologous cells, a large fraction of KA2 remains intracellular even when the trafficking motifs are mutated or when GluR6 is coexpressed. Therefore, we analyzed the trafficking of endogenous KA2in vivo. We find that native KA2 surface expression is dramatically reduced in GluR6 knock-out mice compared with wild-type mice. In contrast, KA2 trafficking was unaffected in the GluR5 knock-out. Thus, our study demonstrates that trafficking motifs in both the intracellular loop and C terminus regulate KA2 surface expression; however, in neurons, GluR6 oligomerization is required for egress of KA2 from the ER and transport to the cell surface. The combination of these mechanisms likely prevents surface expression of nonfunctional KA2 homomers and ensures a high level of GluR6/KA2 heteromeric kainate receptors.
Brief Bursts of Parallel Fiber Activity Trigger Calcium Signals in Bergmann Glia
Authors: Beierlein Michael , Regehr Wade G.
Published: June 2006

Changes in synaptic strength during ongoing activity are often mediated by neuromodulators. At the synapse between cerebellar granule cell parallel fibers (PFs) and Purkinje cells (PCs), brief bursts of stimuli can evoke endocannabinoid release from PCs and GABA release from interneurons that both inhibit transmission by activating presynaptic G-protein-coupled receptors. Studies in several brain regions suggest that synaptic activity can also evoke calcium signals in astrocytes, thereby causing them to release a transmitter, which acts presynaptically to regulate neurotransmitter release. In the cerebellum, Bergmann glia cells (BGs) are intimately associated with PF synapses. However, the mechanisms leading to calcium signals in BGs under physiological conditions and the role of BGs in regulating ongoing synaptic transmission are poorly understood. We found that brief bursts of PF activity evoke calcium signals in BGs that are triggered by the activation of metabotropic glutamate receptor 1 and purinergic receptors and mediated by calcium release from IP3-sensitive internal stores. We found no evidence for modulation of release from PFs mediated by BGs, even when endocannabinoid- and GABA-mediated presynaptic modulation was prominent. Thus, despite the fact that PF activation can reliably evoke calcium transients within BGs, it appears that BGs do not regulate synaptic transmission on the time scale of seconds to tens of seconds. Instead, endocannabinoid release from PCs and GABA release from molecular layer interneurons provide the primary means of feedback that dynamically regulate release from PF synapses.
Deletion of the Ubiquitin Ligase CHIP Leads to the Accumulation, But Not the Aggregation, of Both Endogenous Phospho- and Caspase-3-Cleaved Tau Species
Authors: Dickey Chad A. , Yue Mei , Lin Wen-Lang , Dickson Dennis W. , Dunmore Judith H. , Lee Wing C. , Zehr Cynthia , West Gemma , Cao Songsong , Clark Amber M. K. , Caldwell Guy A. , Caldwell Kim A. , Eckman Christopher , Patterson Cam , Hutton Michael , Petrucelli Leonard
Published: June 2006

Accumulation of the microtubule-associated protein tau into neurofibrillary lesions is a pathological consequence of several neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Hereditary mutations in theMAPTgene were shown to promote the formation of structurally distinct tau aggregates in patients that had a parkinsonian-like clinical presentation. Whether tau aggregates themselves or the soluble intermediate species that precede their aggregation are neurotoxic entities in these disorders has yet to be resolved; however, recentin vivoevidence supports the latter. We hypothesized that depletion of CHIP, a tau ubiquitin ligase, would lead to an increase in abnormal tau. Here, we show that deletion of CHIP in mice leads to the accumulation of non-aggregated, ubiquitin-negative, hyperphosphorylated tau species. CHIP−/−mice also have increased neuronal caspase-3 levels and activity, as well as caspase-cleaved tau immunoreactivity. Overexpression of mutant (P301L) human tau in CHIP−/−mice is insufficient to promote either argyrophilic or “pre-tangle” structures, despite marked phospho-tau accumulation throughout the brain. These observations are supported in postdevelopmental studies using RNA interference forCHIP(chn-1) inCaenorhabditis elegansand cell culture systems. Our results demonstrate that CHIP is a primary component in the ubiquitin-dependent degradation of tau. We also show that hyperphosphorylation and caspase-3 cleavage of tau both occur before aggregate formation. Based on these findings, we propose that polyubiquitination of tau by CHIP may facilitate the formation of insoluble filamentous tau lesions.
Actions and Consequences in Bimanual Interaction Are Represented in Different Coordinate Systems
Authors: Bays Paul M. , Wolpert Daniel M.
Published: June 2006

Moving one part of the body can generate interaction forces that tend to destabilize other parts of the body. However, stability is maintained by mechanisms that predict and actively oppose these interaction forces. When our body or environment changes, these anticipatory mechanisms adapt so as to continue to produce accurate predictions. In this study, we examine the acquisition of a novel predictive coordination between the arms, in a situation in which a force is produced on one hand as a consequence of the action of the other hand. Specifically, a force was applied to the left hand that depended on the velocity of the right hand. With practice, subjects learned to stabilize the perturbed left arm during right-arm movements by predicting and actively opposing the externally applied forces. After adaptation, we examined how learning generalized to a new joint configuration of the right or left arm to investigate the coordinate systems in which the internal transformation from movement to force is represented. This revealed a dissociation between the representation of the action of the right arm and the representation of its consequence, that is the force on the left arm. The movement is represented in extrinsic coordinates related to the velocity of the hand, whereas the force resulting from the movement is represented in a joint-based intrinsic coordinate system.
Main Determinants of Presynaptic Ca2+Dynamics at Individual Mossy Fiber–CA3 Pyramidal Cell Synapses
Authors: Scott Ricardo , Rusakov Dmitri A.
Published: June 2006

Synaptic transmission between hippocampal mossy fibers (MFs) and CA3 pyramidal cells exhibits remarkable use-dependent plasticity. The underlying presynaptic mechanisms, however, remain poorly understood. Here, we have used fluorescent Ca2+indicators Fluo-4, Fluo-5F, and Oregon Green BAPTA-1 to investigate Ca2+dynamics in individual giant MF boutons (MFBs) in area CA3 traced from the somata of granule cells held in whole-cell mode. In an individual MFB, a single action potential induces a brief peak of free Ca2+(estimated in the range of 8–9 μm) followed by an elevation to ∼320 nm, which slowly decays to its resting level of ∼110 nm. Changes in the somatic membrane potential influence presynaptic Ca2+entry at proximal MFBs in the hilus. This influence decays with distance along the axon, with a length constant of ∼200 μm. In giant MFBs in CA3, progressive saturation of endogenous Ca2+buffers during repetitive spiking amplifies rapid Ca2+peaks and the residual Ca2+severalfold, suggesting a causal link to synaptic facilitation. We find that internal Ca2+stores contribute to maintaining the low resting Ca2+providing ∼22% of the buffering/extrusion capacity of giant MFBs. Rapid Ca2+release from stores represents up to 20% of the presynaptic Ca2+transient evoked by a brief train of action potentials. The results identify the main components of presynaptic Ca2+dynamics at this important cortical synapse.
Mitochondrial Trafficking to Synapses in Cultured Primary Cortical Neurons
Authors: Chang Diane T. W. , Honick Anthony S. , Reynolds Ian J.
Published: June 2006

Functional synapses require mitochondria to supply ATP and regulate local [Ca2+]ifor neurotransmission. Mitochondria are thought to be transported to specific cellular regions of increased need such as synapses. However, little is known about how this occurs, including the spatiotemporal distribution of mitochondria relative to presynaptic and postsynaptic sites, whether mitochondria are dynamically recruited to synapses, and how synaptic activity affects these trafficking patterns. We used primary cortical neurons in culture that form synaptic connections and show spontaneous synaptic activity under normal conditions. Neurons were cotransfected with a mitochondrially targeted cyan fluorescent protein and an enhanced yellow fluorescent protein-tagged synaptophysin or postsynaptic density-95 plasmid to label presynaptic or postsynaptic structures, respectively. Fluorescence microscopy revealed longer dendritic mitochondria that occupied a greater fraction of neuronal process length than axonal mitochondria. Mitochondria were significantly more likely to be localized at synaptic sites. Although this localization was unchanged by inhibition of synaptic activity by tetrodotoxin, it increased in dendritic synapses and decreased in axonal synapses during overactivity by veratridine. Mitochondrial movement and recruitment to synapses also differed between axons and dendrites under basal conditions and when synaptic activity was altered. Additionally, we show that movement of dendritic mitochondria can be selectively impaired by glutamate and zinc. We conclude that mitochondrial trafficking to synapses is dynamic in neurons and is modulated by changes in synaptic activity. Furthermore, mitochondrial morphology and distribution may be optimized differentially to best serve the synaptic distributions in axons and dendrites. Last, selective cessation of mitochondrial movement in dendrites suggests early postsynaptic dysfunction in neuronal injury and degeneration.
N-Cadherin Transsynaptically Regulates Short-Term Plasticity at Glutamatergic Synapses in Embryonic Stem Cell-Derived Neurons
Authors: Jüngling Kay , Eulenburg Volker , Moore Robert , Kemler Rolf , Lessmann Volkmar , Gottmann Kurt
Published: June 2006

The cell adhesion molecule N-cadherin has been proposed to regulate synapse formation in mammalian central neurons. This is based on its synaptic localization enabling alignment of presynaptic and postsynaptic specializations by an adhesion mechanism. However, a potential role of N-cadherin in regulating synaptic transmission has remained elusive. In this paper, a functional analysis of N-cadherin knock-out synapses was enabled byin vitroneuronal differentiation of mouse embryonic stem cells circumventing the early embryonic lethality of mice genetically null for N-cadherin. In ourin vitrosystem, initial synapse formation was not altered in the absence of N-cadherin, which might be attributable to compensatory mechanisms. Here, we demonstrate that N-cadherin is required for regulating presynaptic function at glutamatergic synapses. An impairment in the availability of vesicles for exocytosis became apparent selectively during high activity. Short-term plasticity was strongly altered with synaptic depression enhanced in the absence of N-cadherin. Most intriguingly, facilitation was converted to depression under specific stimulation conditions. This indicates an important role of N-cadherin in the control of short-term plasticity.

To analyze, whether N-cadherin regulates presynaptic function by a transsynaptic mechanism, we studied chimeric cultures consisting of wild-type neocortical neurons and ES cell-derived neurons. With N-cadherin absent only postsynaptically, we observed a similar increase in short-term synaptic depression as found in its complete absence. This indicates a retrograde control of short-term plasticity by N-cadherin. In summary, our results revealed an unexpected involvement of a synaptic adhesion molecule in the regulation of short-term plasticity at glutamatergic synapses.
On the Role of the Pontine Brainstem in Vocal Pattern Generation: A Telemetric Single-Unit Recording Study in the Squirrel Monkey
Authors: Hage Steffen R. , Jürgens Uwe
Published: June 2006

In a recent study, we localized a discrete area in the ventrolateral pontine brainstem of squirrel monkeys, which seems to play a role in vocal pattern generation of frequency-modulated vocalizations. The present study compares the neuronal activity of this area with that of three motoneuron pools involved in phonation, namely the trigeminal motor nucleus, facial nucleus, and nucleus ambiguus. The experiments were performed in freely moving squirrel monkeys (Saimiri sciureus) during spontaneous vocal communication, using a telemetric single-unit recording technique. We found vocalization-related activity in all motoneuron pools recorded. Each of them, however, showed a specific profile of activity properties with respect to call types uttered, syllable structure, and pre-onset time. Different activity profiles were also found for neurons showing purely vocalization-correlated activity, vocalization- and mastication-correlated activity, and vocalization- and respiration-correlated activity. By comparing the activity properties of the proposed vocal pattern generator with the three motoneuron pools, we show that the pontine vocalization area is, in fact, able to control each of the three motoneuron pools during frequency-modulated vocalizations. The present study thus supports the existence of a vocal pattern generator for frequency-modulated call types in the ventrolateral pontine brainstem.
The management of menstrual disorders in early reproductive life
Authors: Hickey Martha , Lester Sari
Published: June 2006

Gynaecological disorders in adolescence are relatively uncommon, but may present diagnostic and management challenges for the obstetrician and gynaecologist. This review describes the normal patterns of sex steroid and gynaecological development during puberty and discusses the common and uncommon menstrual disorders that may arise in early reproductive life, giving guidance on their investigation and management. Some of the rarer but important conditions that the gynaecologist should be aware of are briefly mentioned.
Diabetes in pregnancy
Authors: Black Rebecca S. , Gillmer Michael DG
Published: June 2006

Diabetes is the most common medical disorder of pregnancy and the incidence of type 2 diabetes is increasing. Although pregnancy outcomes have improved for both mother and baby over past decades, much needs to be done to reach the aspiration of similar outcomes to nondiabetic pregnancies, which many believe to be a realistic goal. Improvements can be achieved through better multidisciplinary management, although the best approach to gestational diabetes remains controversial.
Cytokines in health and disease
Authors: Cheong Ying C. , Ledger William L.
Published: June 2006

Cytokines are proteins important in cell‐cell signalling. They are involved in many physiological processes such as ovulation, menstruation and pregnancy. Equally, they play an important role in conditions such as preterm labour, pre‐eclampsia, endometriosis and adhesion formation and reformation. Research into cytokines in normal reproductive processes as well as diseases is of paramount importance as the potential health and therapeutic benefits are large.
Growth and Maturity of Hatchery and Wild Lean Lake Trout during Population Recovery in Michigan Waters of Lake Superior
Authors: Sitar Shawn P. , He Ji X.
Published: June 2006

The recovery of populations of wild lake troutSalvelinus namaycushin Lake Superior was the first success among Great Lakes—wide rehabilitation efforts for this species. Knowledge of changes in major demographic factors (e.g., growth and maturity schedules) is very important for enhancing our understanding of stock status during the recovery process, particularly for a fish population with a relatively long life span, such as lake trout in Lake Superior. We separated the recovery time line into three periods—hatchery dominant (1970–1979), transitional (1980–1985), and wild dominant (1986–2003)—and compared growth and sexual maturity (1) between hatchery‐ and wild‐origin lake trout within each period and (2) among the three periods for a given origin. In all three periods, the lengths at old ages (age >6) were similar between wild and hatchery lake trout, but wild fish had smaller lengths at ages 4–6 and at maturity than did hatchery fish. Consequently, wild lake trout had a lower wounding rate by sea lampreyPetromyzon marinusand higher survival than did hatchery lake trout at a given maturity level. Across the three periods, both wild and hatchery lake trout showed significant declines in mean length at old ages and length at 50% maturity, while declines in length at young ages were not significant. Those temporal declines corresponded with the increase in wild lake trout abundance to historic high levels and the lower abundance of major prey fishes. Our estimates of age at 50% maturity also increased over time, but excessive variance in age determinations precluded statistical significance. The observed dynamics of lake trout growth and maturation in the context of population recovery and food web changes are valuable for studying the population dynamics of harvested fish populations.
Using Otolith Microstructure to Determine Natal Origin of Lake Ontario Chinook Salmon
Authors: Smith Nathan G. , Sullivan Patrick J. , Rudstam Lars G.
Published: June 2006

Stocking of hatchery‐reared Chinook salmon Oncorhynchus tshawytscha in Lake Ontario has led to the development of a sport fishery that provides high economic returns to local communities. However, increased natural or “wild” production resulting from the naturalization of hatchery Chinook salmon to the system could result in changing salmonine dynamics that would require alteration of management practices in Lake Ontario. Using young‐of‐the‐year (age‐0) Chinook salmon of known origin—from hatchery and wild sources—we established a baseline for separating these two groups using otolith microstructure. Hatchery‐reared Chinook salmon hatch earlier than wild Chinook salmon, and back‐calculated hatch dates from otoliths correctly classified 97% of fish of known origin. A second protocol developed for determining the origin of Chinook salmon used the daily growth characteristics in the vicinity of 300 μm from the center of the otolith. Measuring the width of 20‐d growth from 300 μm inward toward the origin correctly classified 100% of known hatchery fish and 89% of known wild fish. These measurements were used to determine the origin of Chinook salmon smolts caught in the nearshore of Lake Ontario adjacent to the Salmon River, New York, in 2000 and 2001. In both years, the nearshore population was dominated by naturally produced fish (85% to 89%). These results indicate that natural reproduction of Chinook salmon may play a larger role in Lake Ontario than previously thought.
Hybridization and Cytonuclear Associations among Native Westslope Cutthroat Trout, Introduced Rainbow Trout, and Their Hybrids within the Stehekin River Drainage, North Cascades National Park
Authors: Ostberg Carl O. , Rodriguez Rusty J.
Published: June 2006

Historic introductions of nonnative rainbow troutOncorhynchus mykissinto the native habitats of cutthroat troutO. clarkiihave impacted cutthroat trout populations through introgressive hybridization, creating challenges and concerns for cutthroat trout conservation. We examined the effects of rainbow trout introductions on the native westslope cutthroat troutO. c. lewisiiwithin the Stehekin River drainage, North Cascades National Park, Washington, by analyzing 1,763 salmonid DNA samples from 18 locations with nine diagnostic nuclear DNA markers and one diagnostic mitochondrial DNA (mtDNA) marker. Pure westslope cutthroat trout populations only occurred above upstream migration barriers in the Stehekin River and Park Creek. Two categories of rainbow trout admixture were observed: (1) less than 10% within the Stehekin River drainage above the Bridge Creek confluence and the middle and upper Bridge Creek drainage and (2) greater than 30% within the Stehekin River below the Bridge Creek confluence and in lower Bridge Creek. Hybrid indices and multilocus genotypes revealed an absence of rainbow trout and reduced hybrid diversity within the Stehekin River above the Bridge Creek confluence relative to hybrid diversity in the Stehekin River below the confluence and within lower Bridge Creek. Cytonuclear disequilibrium statistics revealed assortative mating between westslope cutthroat and rainbow trout but not among hybrids within the same locations. This suggests that a randomly mating hybrid swarm does not currently exist. However, continual migration of parental genotypes into the study location could also create significant cytonuclear disequilibria. The Stehekin River represents a novel and unique example of a dynamic hybridization zone where the invasion of rainbow trout alleles into the Stehekin River westslope cutthroat trout population above the Bridge Creek confluence appears to be impeded, suggesting that divergent ecological or evolutionary mechanisms promote the population structure within the Stehekin River drainage, depending upon location.
A Histologic Evaluation of Various Stages of Palatal Healing Following Subepithelial Connective Tissue Grafting Procedures: A Comparison of Eight Cases
Authors: Soileau Kristi M. , Brannon Robert B.
Published: June 2006

Background: It is often necessary to procure tissue from the same area of the palate in cases where connective autogenous grafting procedures are warranted due to limitations caused by anatomical features. The purpose of this study was to determine whether the length of time between a first procurement and a second would have any bearing on the quality of tissue available for recipient sites.

Methods: Eight patients requiring more than one grafting procedure underwent surgery at baseline and again at various intervals ranging from 6 weeks to 11 months. Specimens were taken from the palate and evaluated microscopically, and photographs were taken for purposes of visual comparison.

Results: The 6.9‐ to 7.7‐week specimens exhibited complete reepithelialization. The lamina propriae were composed of a cellular proliferation of fibroblasts with loosely arranged collagen deposition and an occasional thin vascular channel. However, remodeling of the wound appeared complete in the specimens removed at the 9‐week interval and beyond. The lamina propria was, in general, composed of thick, dense, interlacing bundles of collagen. Small‐caliber blood vessels were interspersed throughout the fibrous element.

Conclusion: Reharvesting of tissue performed earlier than at 9 weeks may result in poorer autogenous graft quality due to indications that remodeling of the connective tissue is still progressing and not as mature as specimens noted at weeks 9 to 47.
Anorganic Bovine Matrix/P‐15 “Flow” in the Treatment of Periodontal Defects: Case Series With 12 Months of Follow‐Up
Authors: Barros Raquel R.M. , Novaes Arthur B. , Roriz Virgílio M. , Oliveira Rafael R. , Grisi Márcio F.M. , Souza Sérgio L.S. , Taba Mário , Palioto Daniela B.
Published: June 2006

Background: Nowadays there is a trend in developing biologic modalities that may enhance wound healing of specific sites. In this regard, a cell‐binding activity of type I collagen provided by a synthetic peptide (P‐15) was incorporated in a scaffold (anorganic bovine matrix [ABM]) to facilitate the attachment, migration, and differentiation of cells. This case series describes a surgical protocol for the placement of ABM/P‐15 “flow” during regenerative procedures.

Methods: Wide periodontal defects were treated with sulcular incisions preserving the papillae, full‐thickness flap reflection, granulation tissue debridement, mechanical and chemical root surface treatment, placement of the ABM/P‐15 “flow,” and wound‐closure sutures. Weekly, and then monthly, deplaquing was performed until the 12‐month postoperative recall, in which the clinical parameters were reevaluated.

Results: Significant clinical changes, including probing depth reduction and relative clinical attachment level gain, were achieved after the 12‐month period. The radiographs demonstrated increase in radiopacity when compared to those taken initially, suggesting hard tissue improvements.

Conclusions: The topography of the defects described here could be understood as a challenge for regeneration, once the previous breakdown of the supporting tissues had diminished the source of cells for the healing process and reduced the number of residual walls to retain the graft material. Thus, it seems that the ABM/P‐15 “flow” contributed to the clinical success achieved. Based on this result, ABM/P‐15 “flow” could be a useful and beneficial material for the treatment of periodontal defects.
Periodontal Assessment by Right‐ and Left‐Handed Examiners: Is There a Difference?
Authors: Khan Saba M. , Blanchard Steven B. , Dowsett Sherie A. , Eckert George J. , Kowolik Michael J.
Published: June 2006

Background: Multiple factors that influence the precision of periodontal probing measurements have been identified. These factors can be categorized as being dependent upon host‐related, probe‐related, or examiner‐related variables. However, the potential influence of examiner handedness (right or left) on the measurement of periodontal probing depths (PDs) has not been addressed. The purpose of this study was to determine whether the measurements of PDs in the right and left quadrants are influenced by the handedness of the examiner.

Methods: Eight systemically healthy adult subjects with varying degrees of attachment loss and a minimum of 20 teeth were examined by five right‐handed and five left‐handed clinicians. The 10 clinicians were trained and calibrated for reproducible probe placement and angulation. PDs were measured using a conventional periodontal probe at six sites per tooth. Mean PD measurements were compared between right‐ and left‐handed examiners using analysis of variance (ANOVA) with a random patient effect to correlate participant data and a random effect for the examiner.

Results: There was no statistical difference in the measurement of PDs between right‐ and left‐handed examiners at various locations in the mouth (P >0.17 in all cases). Only three individual sites showed a statistically significantly different mean PD between right‐ and left‐handed examiners (unadjusted P <0.05; differences at or near 0.5 mm). Overall, right‐handed examiners tended to record slightly higher PD measurements than left‐handed examiners, but this difference did not reach statistical significance.

Conclusions: The handedness of the periodontal examiner does not appear to influence the recorded measurement of probing depths. This finding is relevant to those conducting clinical research involving assessment of periodontal status.