bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogeography of the flag cabrilla Epinephelus labriformis (Serranidae): implications for the biogeography of the Tropical Eastern Pacific and the early stages of speciation in a marine shore fish
Authors: Craig Matthew T. , Hastings Philip A. , Pondella Daniel J. , Ross Robertson D. , Rosales‐Casián Jorge A.
Published: April 2006

Aim  To examine the role of previously described biogeographical boundaries in shaping phylogeographical relationships within and among two putative eastern Pacific sibling species, the flag cabrilla, Epinephelus labriformis and the Clipperton grouper, Epinephelus clippertonensis (Serranidae).

Location  Tropical Eastern Pacific (TEP).

Methods  Sequence data from the mitochondrial cytochrome b gene were obtained from samples throughout the range of the species. Coalescence analysis, mismatch distributions and an analysis of molecular variance (amova) were used to infer population differentiation.

Results  Overall, 49 haplotypes were found among 304 specimens, and there was significant structure corresponding to geographical locality (amova, Φct = 0.198, P < 0.001; Φst = 0.207, P < 0.001; Fst = 0.169, P < 0.001; Fct = 0.151, P = 0.036). Coalescence analysis indicates a population expansion at Clipperton Atoll during the mid‐Pleistocene.

Main conclusions  Our results suggest that previously described barriers to dispersal along the mainland of the TEP may not impinge on the dispersal ability of marine species, such as these groupers, that have long‐lived pelagic larvae. In contrast, gene flow between mainland and island populations of the readily distinguishable morphospecies E. labriformis and E. clippertonensis is restricted. The low level of genetic differentiation between the two species indicates that changes in external colour patterns may evolve more rapidly than genetic markers commonly used to delimit species boundaries. Thus a combination of colour differences and a lack of reciprocal monophyly may act as good indicators of incipient speciation in the marine environment.
Cell wall assembly in Bacillus subtilis: how spirals and spaces challenge paradigms
Authors: Bhavsar Amit P. , Brown Eric D.
Published: April 2006

Although the bacterial cell wall has been the subject of decades of investigation, recent studies continue to generate novel and controversial models of its synthesis and assembly. Here we compare and contrast the transcompartmental biosyntheses of peptidoglycan and teichoic acid in Bacillus subtilis. In addition, the current paradigms of B. subtilis wall assembly and structure are distinguished from emerging models of murein insertion and organization. We discuss evidence for the directed, cytoskeleton‐dependent insertion of nascent peptidoglycan and the existence of a periplasmic compartment. Furthermore, we summarize the challenges these findings represent to the existing paradigm of murein insertion. Finally, motivated by these new developments, we discuss outstanding issues that remain to be addressed and suggest research directions that may contribute to a better understanding of cell wall assembly in B. subtilis.
Tumour vascularity is of prognostic significance in adult, but not paediatric astrocytomas
Authors: Birlik B. , Canda S. , Ozer E.
Published: April 2006

Astrocytomas are the commonest type of brain tumours in adults and children. Although the most reliable prognostic indicators have been shown consistently to be patient age and tumour histological grade, biological progression in these tumours is inevitable and the overall prognosis has remained poor. Due to the evidence that vascular changes are important histological features of astrocytomas, the aim of this study was to investigate prognostic significance of tumour vascularity in paediatric and adult astrocytomas. Study population consisted of 70 patients (45 adult and 25 children) with histologically proven diagnosis of astrocytoma with no history of previous therapy. Histological quantification of tumour vascularity was performed using three different methods: microvessel density, vascular grading and Chalkley counting. Histological classification and grading were also assessed using the World Health Organization system. In contrast to the results in paediatric astrocytomas, tumour vascularity in adult tumours correlated significantly with postoperative survival by univariate analysis (P < 0.05). Microvessel density appeared to be an independent indicator of prognosis by multivariate analysis (P = 0.001). Likewise, patients with microvessel density of 70 or greater had significantly shorter survival than the remaining group (P < 0.001). Patient age and tumour histological grade were also correlated with survival. We conclude that histological quantification of tumour vascularity is a significant prognosticator in adult astrocytomas, but not in children. Our data do not support the validity of applications of antiangiogenic agents in paediatric astrocytic tumours, particularly pilocytic astrocytomas.
No evidence for a substantial involvement of primary motor hand area in handedness judgements: a transcranial magnetic stimulation study
Authors: Sauner Dieter , Bestmann Sven , Siebner Hartwig R. , Rothwell John C.
Published: April 2006

Twelve right‐handed volunteers were asked to judge the laterality of a hand stimulus by pressing a button with one of their toes. Judgements were based on two‐dimensional drawings of the back or palm of a right or left hand at various orientations. Suprathreshold single‐pulse transcranial magnetic stimulation (TMS) was given to the left primary motor hand area (M1‐HAND) at 0, 200, 400, 600, 800 or 1000 ms after stimulus onset to probe the functional involvement of the dominant left M1 at various stages of handedness recognition. We found that mean reaction times and error rates increased with angle of rotation depending on the actual biomechanical constraints of the hand but suprathreshold TMS had no influence on task performance regardless of the timing of TMS. However, the excitability of the corticomotor output from the left M1‐HAND was modulated during the reaction. Judging left hand drawings was associated with an attenuation of motor‐evoked potentials 300–100 ms before the response, whereas judging right hand drawings facilitated the motor‐evoked potentials only immediately before the response. These effects were the same for pictures of backs and palms and were independent of the angle of rotation. The failure of TMS to affect task performance suggests that there is no time window during which the M1‐HAND makes a critical contribution to mental rotation of the hand. The modulation of motor‐evoked potentials according to the laterality of the stimulus indicates a secondary effect of the task on corticomotor excitability that is not directly related to mental rotation itself.
Rapid‐rate transcranial magnetic stimulation of animal auditory cortex impairs short‐term but not long‐term memory formation
Authors: Wang Hong , Wang Xu , Wetzel Wolfram , Scheich Henning
Published: April 2006

Bilateral rapid‐rate transcranial magnetic stimulation (rTMS) of gerbil auditory cortex with a miniature coil device was used to study short‐term and long‐term effects on discrimination learning of frequency‐modulated tones. We found previously that directional discrimination of frequency modulation (rising vs. falling) relies on auditory cortex processing and that formation of its memory depends on local protein synthesis. Here we show that, during training over 5 days, certain rTMS regimes contingent on training had differential effects on the time course of learning. When rTMS was applied several times per day, i.e. four blocks of 5 min rTMS each followed 5 min later by a 3‐min training block and 15‐min intervals between these blocks (experiment A), animals reached a high discrimination performance more slowly over 5 days than did controls. When rTMS preceded only the first two of four training blocks (experiment B), or when prolonged rTMS (20 min) preceded only the first block, or when blocks of experiment A had longer intervals (experiments C and D), no significant day‐to‐day effects were found. However, in experiment A, and to some extent in experiment B, rTMS reduced the within‐session discrimination performance. Nevertheless the animals learned, as demonstrated by a higher performance the next day. Thus, our results indicate that rTMS treatments accumulate over a day but not strongly over successive days. We suggest that rTMS of sensory cortex, as used in our study, affects short‐term memory but not long‐term memory formation.
Cardiovascular metabolic syndrome – an interplay of, obesity, inflammation, diabetes and coronary heart disease
Authors: Rana J. S. , Nieuwdorp M. , Jukema J. W. , Kastelein J. J. P.
Published: April 2006

Cardiovascular disease is currently one of the biggest causes of morbidity and mortality facing humanity. Such a paradigm shift of disease pattern over the last century has only worsened due to the alarming global prevalence of obesity and type 2 diabetes. In recent years there is increasing focus on inflammation as one of the key players in the patho‐physiology of these disorders. In addition to these overt risk factors new research is unraveling the significance of a constellation of early metabolic abnormalities that include weight gain, insulin resistance, prehypertension and a specific pattern of dyslipidaemia. There exists a complex interrelationship of these various metabolic disorders and their effect on cardiovascular system. Simplified explanation can be that inflammation increases insulin resistance, which in turn leads to obesity while perpetuating diabetes, high blood pressure, prothrombotic state and dyslipidaemia. While inflammation and insulin resistance have direct adverse effects on cardiac muscle, these metabolic abnormalities as a whole cause causes cardiovascular complications; warranting a multi pronged therapeutic and preventive approach for the ‘Cardiovascular Metabolic Syndrome’ as an entity.
The influence of physical activity on abdominal fat: a systematic review of the literature
Authors: Kay S. J. , Fiatarone Singh M. A.
Published: April 2006

The relationship between excess abdominal adipose tissue, metabolic and cardiovascular health risk has stimulated interest in the efficacy of physical activity in specifically perturbing this adipose depot. The evolution of imaging techniques has enabled more direct measurement of changes in abdominal and visceral fat. The purpose of this summary was to systematically review the relationship between physical activity and abdominal fat. Methods: Database searches were performed on MEDLINE, CINAHL, SPORT DISCUS and PUBMED, from 1985 to 2005 with keywords ‘exercise’, ‘abdominal fat’ and ‘visceral fat’. Results: Nineteen randomized controlled trials (RCTs) and eight non‐randomized controlled trials were selected. In RCTs using imaging techniques to measure change in abdominal fat in overweight or obese subjects, seven out of 10 studies (including three trials with type 2 diabetics) reported significant reductions compared with controls. Reductions in visceral and total abdominal fat may occur in the absence of changes in body mass and waist circumference. Waist‐to‐hip ratio is not a sensitive measure of change in regional adiposity in exercise studies. No studies fulfil the Consolidated Standards of Reporting Trials (CONSORT) statement's criteria for the highest quality of randomized trial; however, many studies were in progress or published before the opportunity to comply with these recommendations. Therefore, limited evidence from a number of studies suggests a beneficial influence of physical activity on reduction in abdominal and visceral fat in overweight and obese subjects when imaging techniques are used to quantify changes in abdominal adiposity. More rigorous studies are needed to confirm these observations.
Buying Influence: Aid Fungibility in a Strategic Perspective
Authors: Hagen Rune Jansen
Published: April 2006

I study equilibria of non‐cooperative games between an aid donor and a recipient when there is conflict over the allocation of their combined budgets. The general conclusion is that a donor's influence over outcomes is increasing in the share of the available resources it controls; if this share is large enough, aid fungibility is not important as the donor achieves its most preferred allocation. The game‐theoretic approach to fungibility is contrasted with the traditional non‐strategic approach. I argue that the former is superior as it derives final allocations instead of assuming them, making analysis of the sources of influence over outcomes possible.
Dopamine transporter immunoreactivity in peripheral blood mononuclear cells in amyotrophic lateral sclerosis
Authors: Buttarelli F. R. , Circella A. , Pellicano C. , Pontieri F. E.
Published: April 2006

Amyotrophic lateral sclerosis (ALS) is a chronic progressive neuromuscular disorder of unknown etiology, characterized by weakness, muscle wasting, fasciculations, and increased reflexes, with conserved intellect and higher functions. The neuropathology of ALS is mostly confined to damage of the motor neurons in the cerebral cortex, some motor nuclei of the brainstem, and anterior horns of the spinal cord. However, there is evidence for the involvement of other neuronal systems in the disease. In particular, damage of the dopamine neurons has been shown by neurochemical and imaging studies in the brain and spinal cord of ALS patients. Recent reports suggest that peripheral blood mononuclear cells (PBMC) may represent a useful in vivo model to study neurochemical alterations that occur in neurodegenerative disorders. Here we demonstrate the significant reduction of dopamine transporter immunoreactivity in PBMC of patients affected by ALS with respect to healthy subjects. These results extend our knowledge of damage of the dopamine system in ALS to peripheral cells. Thus, the original concept of ALS as an isolated degeneration of motor neurons seems to extend to a more widespread understanding of the disease with involvement of other neuronal systems in the central as well as peripheral nervous system.
An epidemiology study of patients with uremic pruritus
Authors: Mistik S , Utas S , Ferahbas A , Tokgoz B , Unsal G , Sahan H , Ozturk A , Utas C
Published: April 2006

Background  Pruritus is a common problem in continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis patients. There are few studies on the clinical characteristics of uremic itch, the cause of which is still unknown.

Objectives  The aim of this study was to define the prevalence and clinical characteristics of pruritus in CAPD and haemodialysis patients.

Methods  A questionnaire was used to evaluate pruritus in 52 CAPD and 289 haemodialysis patients in two dialysis units. The relationship of various factors and medical parameters to itch was examined.

Results  Of the 341 patients, 177 (51.9%) had pruritus at the time of examination, 97 (28.4%) had pruritus in the past. Pruritus was present in 145 (50.2%) of the haemodialysis patients and 32 (61.5%) of the CAPD patients. Men, patients with liver disease, and patients with pruritus before starting dialysis treatment were more likely to have uremic pruritus.

Conclusions  This study showed us that uremic pruritus was observed more in men than women. The high prevalence of uremic pruritus in our study does not support the decrease of pruritus due to an improvement in the management of dialysis patients.
Isolation and characterization of microsatellite loci from mangrove red snapper Lutjanus argentimaculatus
Authors: ZHANG JUNBIN , CAI ZEPING , HUANG HUI
Published: April 2006

Lutjanus argentimaculatus, also called mangrove red snapper, is a commercially important fish in East Asia. A proper understanding of population structure is primarily linked with the management of genetic resources in exploiting marine fisheries. Herein, seven microsatellite loci, which showed high polymorphism (observed heterozygosity per locus ranging from 0.3571 to 0.7857 and expected heterozygosity per locus ranging from 0.6236 to 0.8821), were isolated and characterized from L. argentimaculatus. Cross‐species amplifications also indicate that primers designed for these loci may be useful for further studies about other closely phylogenetic species of the family Lutjanidae.
Ethanol and Sucrose Seeking and Consumption Following Repeated Administration of the GABAB Agonist Baclofen in Rats
Authors: Czachowski Cristine L. , Legg Brooke H. , Stansfield Kirstie H.
Published: April 2006

Background: Baclofen, a GABAB agonist, has been found to decrease alcohol craving in humans and to nonselectively decrease ethanol intake in some rodent models. This experiment assessed the effects of repeated administration of baclofen on reinforcer seeking and consumption using the sipper tube appetitive/consummatory model of ethanol access.

Methods: Subjects were divided into 2 groups and trained to make 30 lever press responses that resulted in access to either 10% ethanol or 2% sucrose in a sipper tube‐drinking spout for 20 minutes. Three doses of baclofen were tested (0.3, 1.0, and 3.0 mg/kg) and each drug treatment was assessed using the following schedule: Monday, saline; Tuesday to Thursday, baclofen; and Friday, saline.

Results: The low dose of baclofen had no effect on the seeking or intake of either sucrose or ethanol, and the 1.0 mg/kg dose also had no effect on the appetitive, seeking response. However, the 1.0 mg/kg dose significantly decreased sucrose intake (from an average of 0.56 to 0.41 g/kg) and significantly increased ethanol intake (from an average of 0.77 to 1.00 g/kg). Similarly, the high dose (3.0 mg/kg) decreased sucrose intake and had a tendency to increase ethanol intake while decreasing both sucrose seeking and ethanol seeking.

Conclusions: Overall, baclofen treatment affected reinforcer intake at doses that had no effect on reinforcer seeking, and effective doses decreased both sucrose seeking and ethanol seeking. Moreover, the effects on reinforcer intake were disparate, in that baclofen increased ethanol drinking and decreased sucrose drinking. The nonspecific effects of baclofen suggest that the GABAB system may be involved in general consummatory or drinking behaviors and does not appear to specifically regulate ethanol‐motivated responding.
Rheologic behavior of sickle and normal red blood cell mixtures in sickle plasma: implications for transfusion therapy
Authors: Alexy Tamas , Pais Eszter , Armstrong Jonathan K. , Meiselman Herbert J. , Johnson Cage S. , Fisher Timothy C.
Published: April 2006

BACKGROUND:  Guidelines for transfusion in sickle cell disease usually define an upper hematocrit (Hct) limit of 0.30 to 0.35 to avoid blood hyperviscosity. In vitro viscosity studies of normal (AA) and sickle (SS) red blood cell (RBC) mixtures in buffer appear to confirm that this Hct limit is optimal for oxygen delivery to vascular beds as judged by the ratio of Hct to viscosity, with this ratio often termed “oxygen or RBC transport effectiveness.” In the absence of plasma, however, effects due to RBC‐RBC interactions mediated by plasma proteins cannot be assessed.

STUDY DESIGNS AND METHODS:  To investigate the optimal Hct‐to‐viscosity ratio of RBCs in plasma, the rheologic effects of Hct (0.20‐0.40), the proportion of SS RBCs (0‐100%), and shear rate (1‐1000/sec) for mixtures of oxygenated and deoxygenated SS and AA RBCs were evaluated in sickle plasma at 37°C.

RESULTS:  RBC suspension viscosity was shear‐dependent (i.e., viscosity decreased with increasing shear rate) and increased with Hct and proportion of SS RBCs. An “optimal” Hct level (defined as a maximal of the Hct‐to‐viscosity ratio) was seen only at shear rates above 50/sec. At lower shear rates (e.g., 5/sec), where plasma‐mediated RBC‐RBC interactions predominate, any increment in Hct was offset by a proportionally greater increase in viscosity, thus leading to a lower Hct‐to‐viscosity ratio.

CONCLUSION:  These results indicate the importance of plasma‐mediated RBC interactions and suggest that the benefits of transfusion may vary depending on local flow rates (i.e., shear rates) and organ‐specific hemodynamics.
Na+ Current in Human Ventricle: Implications for Sodium Loading and Homeostasis
Authors: MAKIELSKI JONATHAN C. , FARLEY AMANDA L.
Published: April 2006

The Na current (INa) in human ventricle is carried through a specific isoform of the voltage gated Na channel in heart. The pore forming α‐subunit is encoded by the gene SCN5A. Up to four β‐subunits may be associated, and the larger macromolecular complex may include attachments to cytoskeleton and scaffolding proteins, all of which may affect the gating kinetics of the current. INa underlies initiation and propagation of action potentials in the heart and plays a prominent role in cardiac electrophysiology and arrhythmia. In addition, INa also loads the ventricular cell with Na+ ions and plays an important role in intracellular Na homeostasis. This review considers the structure and function of the human cardiac Na channel that carries INa with a particular consideration of the implications of alterations in INa in acquired cardiac diseases such as hypertrophy, failure, and ischemia, which affect Na loading.
Molecular Control of Cardiac Sodium Homeostasis in Health and Disease
Authors: HILGEMANN DONALD W. , YARADANAKUL ALP , WANG YONG , FUSTER DANIEL
Published: April 2006

Introduction: Cardiac myocytes utilize three high‐capacity Na transport processes whose precise function can determine myocyte fate and the triggering of arrhythmias in pathological settings. We present recent results on the regulation of all three transporters that may be important for an understanding of cardiac function during ischemia/reperfusion episodes.

Methods and Results: Refined ion selective electrode (ISE) techniques and giant patch methods were used to analyze the function of cardiac Na/K pumps, Na/Ca exchange (NCX1), and Na/H exchange (NHE1) in excised cardiac patches and intact myocytes. To consider results cohesively, simulations were developed that account for electroneutrality of the cytoplasm, ion homeostasis, water homeostasis (i.e., cell volume), and cytoplasmic pH. The Na/K pump determines the average life‐time of Na ions (3–10 minutes) as well as K ions (>30 minutes) in the cytoplasm. The long time course of K homeostasis can determine the time course of myocyte volume changes after ion homeostasis is perturbed. In excised patches, cardiac Na/K pumps turn on slowly (−30 seconds) with millimolar ATP dependence, when activated for the first time. In steady state, however, pumps are fully active with <0.2 mM ATP and are nearly unaffected by high ADP (2 mM) and Pi (10 mM) concentrations as may occur in ischemia. NCX1s appear to operate with slippage that contributes to background Na influx and inward current in heart. Thus, myocyte Na levels may be regulated by the inactivation reactions of the exchanger which are both Na‐ and proton‐dependent. NHE1 also undergo strong Na‐dependent inactivation, whereby a brief rise of cytoplasmic Na can cause inactivation that persists for many minutes after cytoplasmic Na is removed. This mechanism is blocked by pertussis toxin, suggesting involvement of a Na‐dependent G‐protein. Given that maximal NCX1‐ and NHE1‐mediated ion fluxes are much greater than maximal Na/K pump‐mediated Na extrusion in myocytes, the Na‐dependent inactivation mechanisms of NCX1 and NHE1 may be important determinants of cardiac Na homeostasis.

Conclusions: Na/K pumps appear to be optimized to continue operation when energy reserves are compromised. Both NCX1 and NHE1 activities are regulated by accumulation of cytoplasmic Na. These principles may importantly control cardiac cytoplasmic Na and promote myocyte survival during ischemia/reperfusion episodes by preventing Ca overload.
The Application of Geographic Information Systems and Spatial Analysis to Assess Dumped and Subsequently Scattered Human Remains*
Authors: Manhein Mary H. , Listi Ginesse A. , Leitner Michael
Published: April 2006

ABSTRACT: This study utilizes geographic information systems (GIS) and spatial analysis (SA) technology to address the problems associated with prediction of location and effective recovery of dumped and scattered human remains in Louisiana. The goals are to determine if a selective bias exists in Louisiana as to where and when human remains are dumped and to assess whether or not geographically specific patterns exist in the dispersal of human remains. We hypothesized that a positive relationship exists between postmortem interval (PMI) and dispersal distance, and that there are negative relationships between PMI and dispersal direction and between dispersal direction and distance. Our results indicate that, in Louisiana, remains are more often dumped in rural areas away from a structure, and are found within ¼ mile of the nearest road. For Louisiana, no seasonal bias was found in the analysis of when remains are dumped. Furthermore, with the exception of the relationship between PMI and the shortest distance remains were dispersed, no geographically specific patterns were detected in the analyses of dispersal distance, dispersal direction, and PMI.
Sacroiliac Joint Bridging: Simple and Reliable Criteria for Sexing the Skeleton
Authors: Dar Gali , Hershkovitz Israel
Published: April 2006

ABSTRACT: Vital to the study of past populations and an important phase in executing a forensic anthropological examination is the determination of skeleton sex. The aim of this study is to present an easy and reliable criterion for sexing the skeleton. The ilium and sacrum of 2845 skeletons were examined for new bone formation and for bridging/fusion in/across the sacroiliac joint. Sacroiliac joint bridging (SIB) was present in 12.27% of the males and 1.83% of the females. In 97% of the males bridging was extra‐articular, whereas in all females bridging was intra‐articular. In addition, computed tomograghy images of 81 in vivo individuals were examined for the same phenomenon. SIB was present in 34.2% of the males and 4.6% of the females. Bony spurs present on the ilium for a preliminary partial or full extra‐articular bridging of the sacroiliac joint indicate a male skeleton. SIB presents an easy technique for sexing skeletons (especially in elderly individuals where the phenomenon of SIB becomes very common), as no prior knowledge, training, or equipment is required to apply the criterion.
Intracellular Salmonella enterica Redirect Exocytic Transport Processes in a Salmonella Pathogenicity Island 2‐Dependent Manner
Authors: Kuhle Volker , Abrahams Garth L. , Hensel Michael
Published: April 2006

During intracellular life, Salmonella enterica proliferate within a specialized membrane compartment, the Salmonella‐containing vacuole (SCV), and interfere with the microtubule cytoskeleton and cellular transport. To characterize the interaction of intracellular Salmonella with host cell transport processes, we utilized various model systems to follow microtubule‐dependent transport. The vesicular stomatitis virus glycoprotein (VSVG) is a commonly used marker to follow protein transport from the Golgi to the plasma membrane. Using a VSVG‐GFP fusion protein, we observed that virulent intracellular Salmonella alter exocytotic transport and recruit exocytotic transport vesicles to the SCV. This virulence function was dependent on the function of the type III secretion system encoded by Salmonella Pathogenicity Island 2 (SPI2) and more specifically on a subset of SPI2 effector proteins. Furthermore, the Golgi to plasma membrane traffic of the shingolipid C5‐ceramide was redirected to the SCV by virulent Salmonella. We propose that Salmonella modulates the biogenesis of the SCV by deviating this compartment from the default endocytic pathway to an organelle that interacts with the exocytic pathway. This observation might reveal a novel element of the intracellular survival and replication strategy of Salmonella.
Root resorption associated with an impacted mesiodens: a surgical and endodontic approach to treatment
Authors: Zmener Osvaldo
Published: April 2006

Abstract –  This article describes a case of root resorption of a maxillary non‐vital immature incisor associated with an impacted and angulated mesiodens. The impacted tooth was surgically removed and the compromised incisor was subsequently endodontically treated. Over a period of 27 months the tooth was medicated with repeated applications of calcium hydroxide. Radiographically after 18 months, an incomplete hard tissue barrier was observed with full apical closure at the conclusion of 27 months of treatment. Once the patient was comfortable after surgical removal of the mesiodens, the tooth was asymptomatic and remained so for the duration of the treatment and after definitive restorative work had been completed.
SHP‐1 dephosphorylates 3BP2 and potentially downregulates 3BP2‐mediated T cell antigen receptor signaling
Authors: Yu Zhenbao , Maoui Meryem , Zhao Zhizhuang J. , Li Yang , Shen Shi‐Hsiang
Published: April 2006

Src homology 2 (SH2) domain‐containing protein tyrosine phosphatase‐1 (SHP‐1) is a critical inhibitory regulator in T cell‐receptor (TCR) signaling. However, the exact molecular mechanism underlying this is poorly defined, largely because the physiological substrates for SHP‐1 in T cells remain elusive. In this study, we showed that adaptor protein 3BP2 serves as a binding protein and a physiological substrate of SHP‐1. 3BP2 is phosphorylated on tyrosyl residue 448 in response to TCR activation, and the phosphorylation is required for T cell signalling, as indicated by transcriptional activation of nuclear factor activated in T cells (NFAT). Concurrently, phosphorylation of Tyr566 at the C‐terminus of SHP‐1 causes specific recruitment of 3BP2 to the phosphatase through the SH2 domain of the adaptor protein. This leads to efficient dephosphorylation of 3BP2 and thereby termination of T cell signaling. The study thus defines a novel function of the C‐terminal segment of SHP‐1 and reveals a new mechanism by which T cell signaling is regulated.
The SK channel blocker apamin inhibits slow afterhyperpolarization currents in rat gonadotropin‐releasing hormone neurones
Authors: Kato Masakatsu , Tanaka Nobuyuki , Usui Sumiko , Sakuma Yasuo
Published: April 2006

Gonadotropin‐releasing hormone (GnRH) neurones play an essential role in the hypothalamo‐pituitary‐gonadal axis. As for other neurones, the discharge pattern of action potentials is important for GnRH neurones to properly function. In the case of a luteinizing hormone (LH) surge, for example, GnRH neurones are likely to continuously fire for more than an hour. For this type of firing, GnRH neurones must have a certain intrinsic property. To address this issue, we investigated the voltage‐gated Ca2+ currents and Ca2+‐activated voltage‐independent K+ currents underlying afterhyperpolarization, because they affect cell excitability. Dispersed GnRH neurones from adult GnRH‐EGFP (enhanced green fluorescent protein) transgenic rats were cultured overnight and then used for an electrophysiological experiment involving the perforated patch‐clamp configuration. The GnRH neurones showed five subtypes of voltage‐gated Ca2+ currents, i.e. the T‐, L‐, N‐, P/Q‐ and R‐types. The GnRH neurones also showed a slow afterhyperpolarization current (IsAHP), but not a medium one. It is reported that the SK channel blocker apamin (10 pm–100 nm) blocks a medium afterhyperpolarization current but not an IsAHP. In contrast to previous reports, the IsAHP observed in rat GnRH neurones was potently blocked by apamin. In addition, the GnRH neurones expressed transcripts for SK1–3 channels. The results indicate that rat GnRH neurones express all five subtypes of voltage‐gated Ca2+ channels and exhibit an apamin‐sensitive IsAHP, which may allow continuous firing in response to a relatively strong depolarizing input.
Differential Targeting of Gßγ-Subunit Signaling with Small Molecules
Authors: Bonacci Tabetha M. , Mathews Jennifer L. , Yuan Chujun , Lehmann David M. , Malik Sundeep , Wu Dianqing , Font Jose L. , Bidlack Jean M. , Smrcka Alan V.
Published: April 2006

G protein βγ subunits have potential as a target for therapeutic treatment of a number of diseases. We performed virtual docking of a small-molecule library to a site on Gβγ subunits that mediates protein interactions. We hypothesized that differential targeting of this surface could allow for selective modulation of Gβγ subunit functions. Several compounds bound to Gβγ subunits with affinities from 0.1 to 60 μM and selectively modulated functional Gβγ-protein-protein interactions in vitro, chemotactic peptide signaling pathways in HL-60 leukocytes, and opioid receptor–dependent analgesia in vivo. These data demonstrate an approach for modulation of G protein–coupled receptor signaling that may represent an important therapeutic strategy.
A KNOT-THEORETIC EQUIVALENT OF THE KERVAIRE CONJECTURE
Authors: GONZÁLEZ-ACUÑA FRANCISCO , RAMÍREZ ARTURO
Published: April 2006

Kervaire's conjecture is equivalent to the following one: If F is a compact orientable nonseparating surface properly embedded in a knot exterior E then π1(E/F) ≈ Z.
EXTRASPECIAL 2-GROUPS AND IMAGES OF BRAID GROUP REPRESENTATIONS
Authors: FRANKO JENNIFER M. , ROWELL ERIC C. , WANG ZHENGHAN
Published: April 2006

We investigate a family of (reducible) representations of the braid groups [Formula: see text] corresponding to a specific solution to the Yang–Baxter equation. The images of [Formula: see text] under these representations are finite groups, and we identify them precisely as extensions of extra-special 2-groups. The decompositions of the representations into their irreducible constituents are determined, which allows us to relate them to the well-known Jones representations of [Formula: see text] factoring over Temperley–Lieb algebras and the corresponding link invariants.
Na+-K+-2Cl−cotransporters and Cl−channels regulate citric acid cough in guinea pigs
Authors: Mazzone Stuart B. , McGovern Alice E.
Published: April 2006

Loop diuretics have been shown to inhibit cough and other airway defensive reflexes via poorly defined mechanisms. We test the hypothesis that the furosemide-sensitive Na+-K+-2Cl−cotransporter (NKCC1) is expressed by sensory nerve fibers innervating the airways where it plays an important role in regulating sensory neural activity. NKCC1 immunoreactivity was present on the cell membranes of most nodose and jugular ganglia neurons projecting to the trachea, and it was present on the peripheral terminals of putative mechanosensory nerve fibers in the airways. In urethane-anesthetized, spontaneously breathing guinea pigs, bolus application of citric acid (1 mM to 2 M) to an isolated and perfused segment of the tracheal mucosa evoked coughing and respiratory slowing. Removal of Cl−from the tracheal perfusate evoked spontaneous coughing and significantly potentiated cough and respiratory slowing reflexes evoked by citric acid. The NKCC1 inhibitor furosemide (10–100 μM) significantly reduced both the number of coughs evoked by citric acid and the degree of acid-evoked respiratory slowing ( P < 0.05). Localized tracheal pretreatment with the Cl−channel inhibitors DIDS or niflumic acid (100 μM) also significantly reduced cough, whereas the GABAAreceptor agonist muscimol potentiated acid-evoked responses. These data suggest that vagal sensory neurons may accumulate Cl−due to the expression of the furosemide-sensitive Cl−transporter, NKCC1. Efflux of intracellular Cl−, in part through calcium-activated Cl−channels, may play an important role in regulating airway afferent neuron activity.
Seasonal Variation of Bell’s Palsy in Athens, Greece – A Hospital-Based Retrospective Evaluation over Fifteen Years
Authors: Spengos Konstantinos , Sameli Sofia , Stouraitis Georgios , Kolias Angelos , Koulouri Olymbia , Kokkinos Zacharias , Makrylou Irini , Tsivgoulis Athanassios , Tsivgoulis Georgios , Vassilopoulos Demitris
Published: April 2006

Epidemiological data on the incidence of Bell’s palsy (BP) are conflicting. The aim of this retrospective study was to evaluate the variation of cases of BP acutely presented in the emergency room of our department over a 15-year period (January 1990 to December 2004). We examined the monthly and seasonal distribution of BPs among 36,312 patients who came to our emergency services and compared it with the assumed equal distribution of cases over the year (null hypothesis) using χ2 techniques. During the observation period 1,252 of all patients (3.45%) presented due to BP. A decline during the summer was observed, in contrast to a peak documented during the autumn and winter. January and July were the months with the highest and lowest frequency of BP, respectively. Statistical analysis revealed a significantly different seasonal (χ2 = 10.569; d.f. = 3; p = 0.014) and monthly (χ2 = 25.445; d.f. = 11; p = 0.008) pattern of BP cases. The distribution of cases of BP shows a significant variation with a decline during the summer and an increase during the colder period of the year. A similar pattern has been described for reactivated herpetic ocular infections. Since a similar pathogenetic mechanism is regarded as the main cause of BP, the chronobiological aspects and the influence of meteorological factors on the reactivation of latent infections deserves further prospective evaluation.
Proteinuria in Diabetic Patients – Is It Always Diabetic Nephropathy?
Authors: Bergner Raoul , Lenz Tomas , Henrich Dirk M. , Hoffmann Martin , Uppenkamp Michael
Published: April 2006

Background: Diabetic nephropathy (dNP) is a consequence of type 1 and type 2 diabetes, typically occurring between 5 and 15 years after diabetes has been diagnosed. The coincidence of dNP and diabetic retinopathy (dRP) is well known. In this study we correlated the histological findings of the kidney biopsy with the clinically expected diagnosis of dNP. Patients and Methods: Over a 4-year period with a total of 326 kidney biopsies, 85 biopsies were performed on patients with diabetes. In all of these patients we had information about duration of diabetes and ophthalmological status. Additionally, data about proteinuria, urine sediment and autoantibodies were available. The nephrologist had to give the suspected diagnosis before the biopsy was performed, using the clinical data available. Results: In 57 patients (67%) dNP was predicted clinically before biopsy. In 28 patients we expected a different kind of kidney disease. Only 43 patients had dNP histologically. In 16 out of 19 patients with dRP we also found dNP. 26 patients with dNP did not have dRP. So dRP was very specific but not sensitive to predict dNP. On the other hand, all patients without dRP but acanthocytes in urine sediment had non-diabetic kidney disease (NDKD). In the case of patients with neither dRP nor acanthocytes, it was very difficult to distinguish between dNP and NDKD. Acanthocytes and antineutrophil cytoplasmatic antibodies with positive antibodies for proteinase 3 or myeloperoxidase were found only in NDKD, but ANAs were detected in a wide titer range in dNP and NDKD. The known duration of the diabetes ranged from 1 to 40 years. There were no additional parameters to differentiate this group. Conclusions: Diabetic patients with dRP and proteinuria frequently have dNP. In patients without typical retinal findings dNP is less likely, thus a kidney biopsy is necessary to confirm the diagnosis. Additional knowledge about urine sediment and autoantibodies is helpful, but is not sufficient to differentiate NDKD from dNP in the majority of patients.
Prior Events Predict Cerebrovascular and Coronary Outcomes in the PROGRESS Trial
Authors: Arima Hisatomi , Tzourio Christophe , Butcher Ken , Anderson Craig , Bousser Marie-Germaine , Lees Kennedy R. , Reid John L. , Omae Teruo , Woodward Mark , MacMahon Stephen , Chalmers John
Published: April 2006

Background and Purpose—

The relationship between baseline and recurrent vascular events may be important in the targeting of secondary prevention strategies. We examined the relationship between initial event and various types of further vascular outcomes and associated effects of blood pressure (BP)–lowering.

Methods—

Subsidiary analyses of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial that established the benefits of BP–lowering in 6105 patients (mean age 64 years, 30% female) with cerebrovascular disease, randomly assigned to either active treatment (perindopril for all, plus indapamide in those with neither an indication for, nor a contraindication to, a diuretic) or placebo(s).

Results—

Stroke subtypes and coronary events were associated with 1.5- to 6.6-fold greater risk of recurrence of the same event (hazard ratios, 1.51 to 6.64;
P
=0.1 for large artery infarction,
P
<0.0001 for other events). However, 46% to 92% of further vascular outcomes were not of the same type. Active treatment produced comparable reductions in the risk of vascular outcomes among patients with a broad range of vascular events at entry (relative risk reduction, 25%;
P
<0.0001 for ischemic stroke; 42%,
P
=0.0006 for hemorrhagic stroke; 17%,
P
=0.3 for coronary events;
P
homogeneity=0.4).

Conclusions—

Patients with previous vascular events are at high risk of recurrences of the same event. However, because they are also at risk of other vascular outcomes, a broad range of secondary prevention strategies is necessary for their treatment. BP–lowering is likely to be one of the most effective and generalizable strategies across a variety of major vascular events including stroke and myocardial infarction.
Occupational pesticide intoxications among farmers in Bolivia: a cross-sectional study
Authors: Jørs Erik , Morant Rafael Cervantes , Aguilar Guido Condarco , Huici Omar , Lander Flemming , Bælum Jesper , Konradsen Flemming
Published: April 2006

Background

Pesticide use and its consequences are of concern in Bolivia due to an intensive and increasing use.

Methods

To assess the magnitude and reasons for occupational pesticide intoxication, a cross-sectional study with interviews and blood-tests was performed among 201 volunteer farmers from 48 villages in the temperate and subtropical valleys in the eastern part of the Andes Mountains in Bolivia. Of these 171 male farmers using pesticides in their agricultural production were used in the statistical analysis, including linear- and logistic regression analysis.

Results

This study documented a frequent use of the most toxic pesticides among farmers who have had almost no instructions in how to use pesticides and protect themselves against the dangers of intoxication, reflected in the hazardous practices used when handling pesticides. Symptoms of intoxications were common in connection with spraying operations. The risk of experiencing symptoms and the serum cholinesterase activity were influenced by whether or not organophosphates were used and the number of times sprayed. The experience of symptoms was moreover influenced by the hygienic and personal protective measures taken during spraying operations while this had no influence on the serum cholinesterase level.

Conclusion

The study showed that occupational pesticide intoxications were common among farmers and did depend on multiple factors. Pesticide use is probably one of the largest toxicological problems in Bolivia, and a coordinated action by authorities, society and international bodies is needed to limit the number of intoxications and the environmental pollution.
DAX-1 Expression Is Regulated during Mammary Epithelial Cell Differentiation
Authors: Helguero Luisa A. , Hedengran Faulds Malin , Förster Carola , Gustafsson Jan-Åke , Haldosén Lars-Arne
Published: April 2006

In recent studies, we have found that DAX-1 (dosage-sensitive sex reversal/adrenal hypoplasia congenita critical region on the X chromosome) is expressed in the mouse mammary epithelial cell line HC11. In this study, we focused on the regulation of DAX-1 expression and subcellular localization throughout mouse mammary epithelial cell differentiation and its hormonal regulation in the mouse mammary gland. Proliferating HC11 cells grown in epidermal growth factor (EGF)-containing medium, expressed very low levels of DAX-1 as detected by Western blotting and quantitative real-time PCR, whereas, upon EGF withdrawal and induction of differentiation, DAX-1 expression increased. Inhibition of MAPK pathway with PD 098059 resulted in increased DAX-1 levels even in the presence of EGF. Using confocal microscopy, we showed that DAX-1 cytoplasmic levels increased as cells differentiated. DAX-1 staining was nuclear in luminal cells of mouse mammary glands from 3-month-old virgin mice. A nucleo-cytoplasmic pattern was observed in pseudopregnant mice and a cytoplasmic pattern was found in mammary glands from 6-d lactating mice. The influence of DAX-1 on transcriptional activity of endogenously expressed estrogen receptors α (ERα) and β (ERβ) in HC11 mammary epithelial cells was evaluated with an estrogen response element-luciferase reporter assay and by quantitative real-time PCR of the ER-regulated gene receptor-interacting protein 140 kDa. Cotransfection of HC11 cells with human DAX-1 inhibited estrogen response element-reporter and receptor-interacting protein 140 kDa expression induced by 17β-estradiol, the ERα-selective agonist 4,4′,4′-(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol, or the ERβ-selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile. In summary, DAX-1 expression increased upon differentiation induced by EGF withdrawal, and DAX-1 decreased response to estrogens in HC11 cells. Further studies are needed to determine whether DAX-1 is also important in regulation of differentiation of HC11 cells.
Osteoblasts Provide a Suitable Microenvironment for the Action of Receptor Activator of Nuclear Factor-κB Ligand
Authors: Yamamoto Yohei , Udagawa Nobuyuki , Matsuura Sachiko , Nakamichi Yuko , Horiuchi Hiroshi , Hosoya Akihiro , Nakamura Midori , Ozawa Hidehiro , Takaoka Kunio , Penninger Josef M. , Noguchi Toshihide , Takahashi Naoyuki
Published: April 2006

Deficiency of osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor-κB ligand (RANKL), in mice induces osteoporosis caused by enhanced bone resorption. Serum concentrations of RANKL are extremely high in OPG-deficient (OPG−/−) mice, suggesting that circulating RANKL is involved in osteoclastogenesis. RANKL−/− mice exhibit osteopetrosis, with the absence of osteoclasts. We examined the requirements for osteoclastogenesis using OPG−/− mice, RANKL−/− mice, and a system involving bone morphogenetic protein 2 (BMP-2)-induced ectopic bone formation. When collagen disks containing BMP-2 (BMP-2-disks) or vehicle were implanted into OPG−/− mice, osteoclast-like cells (OCLs) and alkaline phosphatase-positive OCLs appeared in BMP-2-disks but not the control disks. F4/80-positive osteoclast precursors were similarly distributed in both BMP-2- and control disks. Cells expressing RANKL were detected in the BMP-2-disks, and the addition of OPG to the disk inhibited OCL formation. Muscle cells in culture differentiated into alkaline phosphatase-positive cells in the presence of BMP-2 and accordingly expressed RANKL mRNA in response to PTH. This suggests that RANKL expressed by osteoblasts is a requirement for osteoclastogenesis. We then examined how osteoblasts are involved in osteoclastogenesis other than RANKL expression, using RANKL−/− mice. BMP-2- and control disks were implanted into RANKL−/− mice, which were injected with RANKL for 7 d. Many OCLs were observed in the BMP-2-disks and bone tissues but not the control disks. These results suggest that osteoblasts also play important roles in osteoclastogenesis through offering the critical microenvironment for the action of RANKL.