bluuebunny/crossref_metadata_2025 huggingface dataset:
Are express saccades generated under natural viewing conditions?
Authors: Schiller Peter H. , Slocum Warren M. , Carvey Christina , Tolias Andreas S.
Published: November 2004

To assess whether express saccades are generated under everyday conditions, we collected eye movement data from Rhesus monkeys engaged in free viewing under a variety of conditions. The durations of the fixation periods that occurred between saccades were calculated. The results show that while short‐duration fixations within the range of express saccades occur quite commonly, the overall distribution is unimodal. This is the case even when all the object elements in the visual scene have the same contrast. The findings suggest that while saccades that fall within the express range occur commonly under natural viewing conditions, bimodal distributions of saccadic latencies are obtainable only under laboratory conditions.
When ‘go’ and ‘nogo’ are equally frequent: ERP components and cortical tomography
Authors: Lavric Aureliu , Pizzagalli Diego A. , Forstmeier Simon
Published: November 2004

In human electrophysiology, a considerable corpus of studies using event‐related potentials have investigated inhibitory processes by employing the ‘go–nogo’ paradigm, which requires responding to one type of event while withholding the response to another type of event. Two event‐related potential waveform features (N2 and P3) have been associated with larger amplitude in nogo trials than in go trials. Traditionally, these differences were thought to reflect response inhibition. Recently, the source localization of N2 to the anterior cingulate cortex, as well as the colocalization of N2 with error‐related negativity, has been interpreted in terms of conflict monitoring. In order to isolate the contribution of inhibitory processes, we matched the frequency of the go and nogo events, thus minimizing differences in response conflict between event types. A data‐driven analytical procedure contrasted go with nogo events across the entire event‐related potential segment and found that N2 reliably differentiated between the two conditions while P3 did not. Tomographical analyses of the N2 difference observed in conditions of equal go and nogo trial frequency localized N2 to the right ventral and dorsolateral prefrontal cortex. Because a growing body of evidence implicates these brain regions in inhibitory processes, we conclude that N2 does, at least in part, reflect inhibition.
Down's syndrome astrocytes have greater antioxidant capacity than euploid astrocytes
Authors: Sebastià Jordi , Cristòfol Rosa , Pertusa Maria , Vílchez David , Torán Núria , Barambio Santiago , Rodríguez‐Farré Eduard , Sanfeliu Coral
Published: November 2004

Down's syndrome (trisomy 21) brain tissue is considered to be susceptible to oxidative injury, mainly because its increased Cu/Zn‐superoxide dismutase (SOD1) activity is not followed by an adaptive rise in hydrogen peroxide metabolizing enzymes.In vitro, trisomic neurons suffer oxidative stress and degenerate. We studied the response of trisomy 21 neuron and astrocyte cultures to hydrogen peroxide injury and found that they were, respectively, more and less vulnerable than their euploid counterparts. Differences were detected 24 h after exposures in the region of 50 µmand 500 µmhydrogen peroxide for neuron and astrocyte cultures, respectively. Cytotoxicity results were paralleled by a decrease in cellular glutathione. In addition, trisomic astrocytes showed a lower basal content of superoxide ion and a higher clearance of hydrogen peroxide from the culture medium. In the presence of hydrogen peroxide, trisomic astrocytes maintained their concentration of intracellular superoxide and hydroperoxides at a lower level than euploid astrocytes. Consistent with these results, trisomic astrocytes in neuron coculture were more neuroprotective than euploid astrocytes against hydrogen peroxide injury. We suggest that SOD1 overexpression has beneficial effects on astrocytes, as it does in other systems with similarly high disposal of hydroperoxides. In addition to a higher enzymatic activity of SOD1, cultures of trisomic astrocytes showed slightly higher glutathione reductase activity than euploid cultures. Thus, trisomy 21 astrocytes showed a greater antioxidant capacity against hydrogen peroxide than euploid astrocytes, and they partially counteracted the oxidative vulnerability of trisomic neurons in culture.
Inactivation and activation of Ras by the neurotrophin receptor p75
Authors: Blöchl Andrea , Blumenstein Lars , Ahmadian Mohammad R.
Published: November 2004

The neurotrophin receptor p75 induces neurotrophic and/or apoptotic signalling pathways and can also cooperate with the neurotrophic Trk receptor tyrosine kinases. Its intracellular part encloses a so‐called ‘death domain’ with a segment similar to the wasp venom mastoparan which binds small GTPases such as Rho. To study possible interactions of p75 and Ras (and Rho) we used wild‐type and mutant genes of p75 stably expressed by MDCK cells which normally have neither Trk nor p75. We found that p75 can directly bind the GTPases Ras and Rho and that the unstimulated p75 inactivates total cellular Ras through a differential influence on the dissociation of GDP and GTP from Ras and an exchange of bound Ras·GDP for free Ras·GTP. These properties of p75 could also be demonstrated in vitro and should therefore be cell type‐independent. Stimulation of p75 with nerve growth factor causes Ras activation via adapter proteins known from Trk signalling and induces rapid outgrowth of cellular processes. Both inactivation and activation of Ras by p75 are controlled by the phosphorylation state of the receptor's two intracellular tyrosines. p75 also influences Rho activation and inactivation, and the combined interactions of the receptor with the two GTPases Ras and Rho can regulate neurite formation in an efficient, synergistic way.
Long‐term effects of striatal lesions on c‐Fos immunoreactivity in the pedunculopontine nucleus
Authors: Mena‐Segovia Juan , Favila Rafael , Giordano Magda
Published: November 2004

The basal ganglia are a group of subcortical nuclei classically thought to be involved in the control of movement, and they have reciprocal connections with the cortex, thalamus and structures in the brainstem. Recent findings suggest that the basal ganglia interact with structures involved in the control of the sleep–waking cycle. The pedunculopontine tegmental nucleus (PPN) maintains a close relationship with the basal ganglia and is intimately involved in the regulation of wakefulness and REM sleep. This study evaluated changes in activity of PPN neurons following striatal kainic acid‐induced lesions. Rats were injected in the anterodorsal striatum with either kainic acid or vehicle and allowed to recover for 7 or 30 days. The results showed an increase in the number of c‐Fos+ cells in the PPN 30 days but not 7 days after the striatal lesion, when motor hyperactivity was no longer detected. In addition, we found a significant correlation between the ventricular brain ratio, as an indicator of lesion size, and the number of c‐Fos+ cells in the PPN. Furthermore, the spatial distribution of cell types suggested that most c‐Fos+ cells in the PPN were not cholinergic. These results provide new insights into the functional relationship between the basal ganglia and the PPN and suggest that the striatum, through its indirect influence on the PPN, may contribute to the regulation of wakefulness and cortical activation.
Evidence for both reaching and grasping activity in the medial parieto‐occipital cortex of the macaque
Authors: Fattori Patrizia , Breveglieri Rossella , Amoroso Katia , Galletti Claudio
Published: November 2004

In humans, the caudal pole of the superior parietal lobule is involved in the control of both reaching and grasping movements, whereas in monkey it is reported to be involved only in the control of reaching. Using single‐unit recordings from trained macaque monkeys, we investigated whether area V6A, a visuomotor area located in the caudal part of the posterior parietal cortex, is involved in both components of prehension, the hand transport towards the visual target and the grip formation to secure the grasp. In Experiment 1, neural activity was recorded in V6A while two monkeys performed two instructed‐delay reaching tasks (reach‐to‐point and reach‐to‐grasp) under controlled conditions in darkness. Fourty‐five of 93 tested neurons (48%) were modulated during reach‐to‐point and 62% (52/84) during reach‐to‐grasp. In 63% of cells (51/81) neural activity was significantly different between reach‐to‐point and reach‐to‐grasp tasks, suggesting that grip formation could influence neural activity. In Experiment 2, two monkeys performed natural reach‐to‐grasp movements in fully lit environment; V6A neural activity and arm–hand movements were recorded by a digital camcorder and analysed frame‐by‐frame using a digital video technique. Thirty of the 58 tested neurons (52%) were modulated during natural prehension; about 30% of these neurons (8/30) were modulated only during the last phase of prehension, i.e. during finger flexion around the object to be grasped. This is the first direct demonstration that both reaching and grasping modulate neural activity in the caudal part of the posterior parietal cortex of the macaque. Our work suggests a strict functional homology between human and monkey superior parietal lobule.
Suppressor of cytokine signalling‐2 and epidermal growth factor regulate neurite outgrowth of cortical neurons
Authors: Goldshmit Yona , Greenhalgh Christopher J. , Turnley Ann M.
Published: November 2004

Factors that regulate neurite outgrowth are important in determining the wiring of the central nervous system. Here we describe that the intracellular regulator of cytokine signalling, suppressor of cytokine signalling‐2 (SOCS2) and epidermal growth factor (EGF), both of which are expressed in the cortical plate during neural development, promote neurite outgrowth of cortical neurons. Cortical neurons derived from transgenic mice that over‐express SOCS2 had an increased rate of neurite outgrowth and an increased length and number of primary neurites compared with wild‐type neurons. EGF produced a similar effect in wild‐type cortical neurons and further enhanced the SOCS2‐induced neurite outgrowth. The mechanism of neurite outgrowth induction by SOCS2 and EGF at least partially overlapped as phosphorylation of the EGF receptor in SOCS2 over‐expressing or EGF‐stimulated neurons was increased on Tyrosine845, the Src binding site and neurite outgrowth in both protocols was blocked by inhibitors of the EGF receptor kinase and Src kinase.
Increased extracellular dopamine concentrations and FosB/ΔFosB expression in striatal brain areas of heterozygous GDNF knockout mice
Authors: Airavaara Mikko , Planken Anu , Gäddnäs Helena , Piepponen Timo Petteri , Saarma Mart , Ahtee Liisa
Published: November 2004

Glial cell line‐derived neurotrophic factor (GDNF) has been shown to be involved in the maintenance of striatal dopaminergic neurons. To study whether reduced levels of endogenous GDNF affect the striatal dopaminergic transmission we estimated the basal extracellular levels of dopamine in vivo, the basal expression of FosB‐related proteins in striatal brain areas as well as the effects of acute and repeated cocaine on locomotor activity and dopamine output in mice lacking one GDNF allele (heterozygous GDNF+/– mice). As expected the striatal GDNF protein content was found to be smaller in the GDNF+/– mice than in their wild‐type littermates. Unexpectedly the extracellular dopamine concentration in the GDNF+/– mice in the dorsal striatum (CPu) was 2.0‐fold, and in the nucleus accumbens (NAc) 1.6‐fold the concentration found in the wild‐type littermates. Also FosB/ΔFosB–like immunoreactivity was found to be elevated in the CPu as well as in the core and in the shell of NAc of the GDNF+/– mice as compared with the wild‐type mice. This suggests chronic postsynaptic activation of these brain areas and is in line with elevated extracellular dopamine concentrations. Cocaine's effects acutely and after repeated treatment on locomotor activity were similar in the GDNF+/– and the wild‐type mice. Neither did cocaine's acute effects on dopamine output differ between the mice of the two strains. Our findings demonstrate that reduced levels of endogenous GDNF induce alterations in dorsal striatal and accumbal dopaminergic transmission, and stress the importance of endogenous GDNF in the regulation of the dopaminergic neurons.
Brief exposure to predator odor and resultant anxiety enhances mesocorticolimbic activity and enkephalin expression in CD‐1 mice
Authors: Hebb Andrea L. O. , Zacharko Robert M. , Gauthier Michelle , Trudel France , Laforest Sylvie , Drolet Guy
Published: November 2004

The present study assessed alterations in mesolimbic enkephalin (ENK) mRNA levels after predator [2,5‐dihydro‐2,4,5‐trimethylethiazoline (TMT)] and non‐predator (butyric acid) odor encounter and/or light–dark (LD) testing in CD‐1 mice immediately, 24, 48 and 168 h after the initial odor encounter and/or LD testing. The nucleus accumbens, ventral tegmental area, basolateral (BLA), central (CEA) and medial amygdaloid nuclei, prelimbic and infralimbic cortex were assessed for fos‐related antigen (FRA) and/or ENK mRNA as well as neuronal activation of ENK neurons (FRA/ENK). Mice exposed to TMT displayed enhanced freezing and spent less time in the light of the immediate LD test relative to saline‐ or butyric acid‐treated mice. Among mice exposed to TMT, LD anxiety‐like behavior was associated with increased FRA in the prelimbic cortex and accumbal shell and decreased ENK‐positive neurons in the accumbal core. Mice displaying high TMT‐induced LD anxiety exhibited increased ENK‐positive neurons in the BLA, CEA and medial amygdaloid nuclei relative to mice that displayed low anxiety‐like behavior in the LD test after TMT exposure. In the BLA and CEA, ‘high‐anxiety’ mice also displayed increased FRA/ENK after TMT exposure and LD testing. In contrast to neural cell counts, the level of ENK transcript was decreased in the BLA and CEA of ‘high‐anxiety’ mice after TMT exposure and LD testing. These data suggest that increased FRA may regulate stressor‐responsive genes and mediate long‐term behavioral changes. Indeed, increased ENK availability in mesolimbic sites may promote behavioral responses that detract from the aversiveness of the stressor experience.
Nitric oxide synthase inhibition prevents neuronal death in the developing visual cortex
Authors: Zhang Yueting , Zhang Jie , Zhao Baolu
Published: November 2004

During postnatal development of the visual cortex of golden hamster, there is a transient increase in both the expression and the activity of nitric oxide synthase (NOS), which coincides temporally with the formation of ipsilateral retino‐collicular and retino‐geniculate projections and the functional differentiation of primary visual cortex, suggesting the involvement of NO in the maturation of the visual cortex. In the present study, an inhibitor of NOS, N‐nitro‐l‐arginine (L‐NNA) was used to block the NOS activity of newborn golden hamster, and effects on development were examined. L‐NNA treatment caused an increase in mortality, and suppression of both body weight gain and nicotinamide adenine dinucleotide phosphate‐diaphorase (NADPH‐d) activity in the early phase of treatment (before postnatal day 14, PD14). The growth of NADPH‐d‐positive neurons in the visual cortex was also suppressed by the treatment. In control animals, significant numbers of apoptotic neurons were detected by terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling assay on PD14, and this apoptosis mainly affected cells in cortical layers II and III. NOS inhibition largely rescued neurons from undergoing apoptosis, indicating that NO may serve as a signal triggering apoptosis and play a role in the maturation of the visual cortex.
Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation in rats
Authors: Milligan E. D. , Zapata V. , Chacur M. , Schoeniger D. , Biedenkapp J. , O'Connor K. A. , Verge G. M. , Chapman G. , Green P. , Foster A. C. , Naeve G. S. , Maier S. F. , Watkins L. R.
Published: November 2004

Recent evidence suggests that spinal cord glia can contribute to enhanced nociceptive responses. However, the signals that cause glial activation are unknown. Fractalkine (CX3C ligand‐1; CX3CL1) is a unique chemokine expressed on the extracellular surface of spinal neurons and spinal sensory afferents. In the dorsal spinal cord, fractalkine receptors are primarily expressed by microglia. As fractalkine can be released from neurons upon strong activation, it has previously been suggested to be a neuron‐to‐glial signal that induces glial activation. The present series of experiments provide an initial investigation of the spinal pain modulatory effects of fractalkine. Intrathecal fractalkine produced dose‐dependent mechanical allodynia and thermal hyperalgesia. In addition, a single injection of fractalkine receptor antagonist (neutralizing antibody against rat CX3C receptor‐1; CX3CR1) delayed the development of mechanical allodynia and/or thermal hyperalgesia in two neuropathic pain models: chronic constriction injury (CCI) and sciatic inflammatory neuropathy. Intriguingly, anti‐CX3CR1 reduced nociceptive responses when administered 5–7 days after CCI, suggesting that prolonged release of fractalkine may contribute to the maintenance of neuropathic pain. Taken together, these initial investigations of spinal fractalkine effects suggest that exogenous and endogenous fractalkine are involved in spinal sensitization, including that induced by peripheral neuropathy.
Identification of three new alternatively spliced variants of the rat mu opioid receptor gene: dissociation of affinity and efficacy
Authors: Pasternak David A. , Pan Ling , Xu Jin , Yu Rui , Xu Ming‐Ming , Pasternak Gavril W. , Pan Ying‐Xian
Published: November 2004

Mu opioid receptors mediate the pharmacological actions of morphine and morphine‐like drugs, such as heroin. The mouse and human Oprm genes undergo splicing. In these present studies, we have identified and characterized three new MOR‐1 splice variants from the rat Oprm gene. Using an RT‐PCR approach, we isolated the new exons 7, 8 and 9 downstream of exon 3. The rat exons 7 and 9 were homologous to the mouse exons 7 and 9 while the rat exon 8 was not. Northern blot analysis with the new exon probes showed distinctive and abundant transcripts of the variants in the rat brain. Full‐length cDNA clones containing the new exons, rMOR‐1C1, rMOR‐1C2 and rMOR‐1D were obtained using an RT‐PCR approach. Each contained the same exons 1, 2 and 3 as the original rMOR‐1, followed by different combinations of the new exons in place of exon 4. In addition, we also isolated another new variant, rMOR‐1A, which contains only exons 1, 2 and 3, and is homologous to the human variant MOR‐1A previously identified. All the variants were highly mu‐selective in binding studies with little difference in affinities for the mu ligands among the variants. However, functional evaluation of assessments of the variants using agonist stimulated [35S]GTPγS binding assays revealed marked differences among the variants, both in terms of potency and efficacy of the drugs. The relative efficacy of a series of mu opioids to each other varied depending upon the variant studied. Efficacy in the [35S]GTPγS assay did not correlate with either receptor binding affinity or with potency. Thus, selectivity of opioid action might be achieved by designing compounds with varying efficacies at different MOR‐1 variants.
Variants of TRP ion channel mRNA present in horseshoe crab ventral eye and brain
Authors: Bandyopadhyay Bidhan C. , Payne Richard
Published: November 2004

Transient receptor potential (TRP) channels mediate light‐induced Ca2+ entry and the electrical response in Drosophila photoreceptors. The role of TRP channels in other invertebrate photoreceptors is unknown, particularly those, exemplified by Limulus ventral eye photoreceptors, in which calcium release from intracellular stores is prominent. We have amplified cDNA encoding three variants of a Limulus TRP channel. LptrpA and LptrpBencode proteins of 896 and 923 amino acids, differing by a 27 amino acid insert within the C‐terminus. LptrpC encodes an alternative 63 amino acid sequence in the pore domain compared with LptrpB. LptrpB and LptrpC are present in ventral eye mRNA, while LptrpA is only present in brain mRNA. In situ hybridization indicates the presence of Lptrp in photoreceptors of the Limulus ventral eye. Some canonical TRP channels can be activated by diacylglycerol analogs. Injection of a diacylglycerol analog, 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG), into Limulus photoreceptors can activate an inward current with electrical characteristics similar to the light‐activated current. However, simultaneous elevation of cytosolic calcium concentration appears to be necessary. Illumination attenuates the response to OAG injections and vice versa. These results provide molecular and pharmacological evidence for a TRP channel in Limulus ventral eye that may contribute to the light‐sensitive conductance.
BUILDING POWER IN THE NEW ECONOMY: THE SOUTH BAY LABOR COUNCIL
Authors: Byrd Barbara , Rhee Nari
Published: November 2004

Confronted with the technological changes and corporate restructuring that is eroding job security for all workers, the once booming economy of Silicon Valley is now undergoing severe growing pains. Moreover, the much vaunted information technology industry is producing a dual economy of high‐wage and low‐wage jobs. Now, with the bursting of the dot.com industry, workers in all sectors are confronting layoffs and lower expectations. In both boom and bust periods, the South Bay American Federation of Labor‐Congress of Industrial Organizations Labor Council has made a tremendous turnaround, made has innovative responses to the “new economy,” and has expanded its capacity to take on issues important to workers and unions. The article offers a detailed account of the labor council's program and explores the environmental and historical context surrounding the revitalization of organized labor in the region. Our findings in San Jose suggest that central labor councils are successful in advancing the needs of workers and labor movement. Today, this experience offers a model for the three‐pronged approach to grassroots movement building: (1) policy research and advocacy, (2) community coalition building, (3) and an aggressive political program that keeps politicians responsive to the needs of workers.
DYNAMIC POLITICAL MOBILIZATION: THE LOS ANGELES COUNTY FEDERATION OF LABOR
Authors: Frank Larry , Wong Kent
Published: November 2004

The Los Angeles County Federation of Labor has attracted national attention as a focal point of the new American labor movement. The emergence of Los Angeles as a union city has been an impressive accomplishment, especially in light of its antiunion history. The growth of labor power in the political arena, the organizing of new workers, the advancement of progressive public policy, and the forging of labor– community alliances, especially with immigrant communities, have all contributed to Los Angeles’ new labor power. Power building in Los Angeles combines the sophisticated political work of the Los Angeles County Federation of Labor and the economic development activism fostered by its allies.
CONFRONTING HOUSTON's DEMOGRAPHIC SHIFT: THE HARRIS COUNTY AFL‐CIO
Authors: Karson Tom
Published: November 2004

Power building involves taking risks. In Houston, the leadership of the Harris County American Federation of Labor‐Congress of Industrial Organizations, recognizing the rapid growth of immigrants in the region, advanced a tangible policy to build worker power through mobilizing workers in these new communities, for many years shunned by unions and central labor councils. The labor council recognizes that the struggle to organize immigrants is difficult and unpredictable. In an antiunion environment, the Harris County labor council had to convince immigrant workers that they would provide resources and support directed to the needs of the diverse communities in the city. By supporting immigrant rights and organizing efforts, the labor council hopes to align the local labor movement with the demographic earthquake shaking their communities. At the same time, the council has managed to deliver to affiliates through mobilizing support for organizing and supporting political candidates favorable to organized labor. This article examines diverse strategies formulated on the basis of the real needs of immigrant workers and assesses the efficacy of these new organizing efforts in building greater labor power.
TAKING BACK AMERICA FOR WORKING PEOPLE: COMMUNITY BY COMMUNITY
Authors: Colburn Bruce
Published: November 2004

Even in an environment hostile to organized labor, unions and workers can advance through taking back power on a local and regional level. While the neoliberal economic agenda of the U.S. and key international organizations do not take into account worker rights, organized labor is winning campaigns on a local level that in the future will lay the groundwork for a stronger labor movement. In the most unfriendly regions that are hostile to worker organizing, local labor councils are waging campaigns to advance labor rights by supporting ongoing worker organizing that will engender power down the road. Through mobilization of members and nonmembers, organized labor is defeating politicians beholden to big businesses and electing labor‐friendly officials on a local and regional level. As workers are displaced by corporate restructuring and shift production, unions must employ regional models of organizing to reach workers in their communities and new workplaces.
Characterization of β-cell function impairment in first-degree relatives of type 2 diabetic subjects: modeling analysis of 24-h triple-meal tests
Authors: Mari Andrea , Gastaldelli Amalia , Natali Andrea , Ostergard Torben , Schmitz Ole , Ferrannini Ele
Published: November 2004

To investigate early secretory defects in prediabetes, we evaluated β-Cell function and insulin sensitivity (M value, by euglycemic clamp) in 26 normotolerant first-degree relatives of type 2 diabetic patients (FDR) and 17 age- and weight-matched control subjects. β-Cell function was assessed by modeling analysis of glucose and C-peptide concentrations measured during 24 h of standardized living conditions. Fasting and total insulin secretion (ISR) were increased in FDR, as was ISR at a reference 5 mM glucose level (ISR5, 107 ± 6 vs. 87 ± 6 pmol· min−1·m−2, P < 0.05). ISR5 was inversely related to M in controls (ISR5 = k/M1.23, ρ = −0.74, P < 0.005) but not in FDR; when M was accounted for (by calculating a compensation index ISR5·M1.23), compensation for insulin resistance was impaired in FDR (10.8 ± 1.0 vs. 13.4 ± 0.6 units, P < 0.05). Potentiation of ISR, expressing relative transient increases in glucose-stimulated ISR during meals, was impaired in FDR (1.29 ± 0.08 vs. 1.62 ± 0.08 during 1st meal, P < 0.02). Moreover, the potentiation time course was related to glucose-dependent insulin-releasing polypeptide (GIP) concentrations in both groups, and the sensitivity of potentiation to GIP derived from this relationship tended to be impaired in FDR. Compensation index, potentiation, and sensitivity to GIP were interrelated parameters ( P < 0.05 or less). β-Cell function parameters were also related to mean 24-h glucose levels ( r2 = 0.63, P < 0.0001, multivariate model). In conclusion, although in absolute terms ISR is increased in insulin-resistant FDR, β-cell function shows a cluster of interrelated abnormalities involving compensation for insulin resistance, potentiation, and sensitivity to GIP, suggesting a β-cell defect in the amplifying pathway of insulin secretion.
Statins Enhance Migratory Capacity by Upregulation of the Telomere Repeat-Binding Factor TRF2 in Endothelial Progenitor Cells
Authors: Spyridopoulos Ioakim , Haendeler Judith , Urbich Carmen , Brummendorf Tim H. , Oh Hidemasa , Schneider Michael D. , Zeiher Andreas M. , Dimmeler Stefanie
Published: November 2004

Background—

Cultivation of endothelial progenitor cells (EPCs) leads to premature replicative senescence, limiting ex vivo expansion for potential clinical cell therapy. Recent studies have linked senescence to the dysfunction of telomeres, the “ends” of chromosomes, via the so-called mitotic clock or culture-induced stress. The purpose of this study was to elucidate a possible role of telomere biology in the functional augmentation of EPCs by statins.

Methods and Results—

Human EPCs were isolated from peripheral blood. Using flow cytometry after fluorescence in situ hybridization with a telomere-specific (C
3
TA
2
)
3
peptide nucleic acid probe (Flow-FISH), we found mean telomere length in untreated EPCs from healthy subjects to range between 8.5±0.2 and 11.1±0.5 kb with no change over 6 days of culture, excluding telomere erosion as one cause for premature senescence. Although mean telomere length did not differ between statin-treated and untreated EPCs, atorvastatin (0.1 μmol/L) and mevastatin (1.0 μmol/L) both led to a more than 3-fold increase in the expression of the telomere capping protein TRF2 (telomere repeat-binding factor), as shown by immunoblotting, whereas quantitative reverse transcription–polymerase chain reaction demonstrated no increase in TRF2 mRNA. Telomere dysfunction of EPCs was also paralleled by a 4-fold increase in the DNA damage checkpoint-kinase 2 (Chk2). Conversely, statin cotreatment or overexpression of TRF2 completely suppressed Chk2 induction. Finally, overexpression of a dominant negative mutant of the TRF2 protein abrogated statin-induced enhancement of migratory activity down to baseline values.

Conclusions—

Ex vivo culturing of EPCs leads to “uncapping” of telomeres, indicated by the loss of TRF2. Statin cotreatment of EPCs prevents impairment of their functional capacity by a TRF2-dependent, posttranscriptional mechanism. This is the first time a beneficial effect of statins on telomere biology has been described.
Transcription Enhancer Factor-1-Related Factor-Transgenic Mice Develop Cardiac Conduction Defects Associated With Altered Connexin Phosphorylation
Authors: Chen Hsiao-Huei , Baty Catherine J. , Maeda Tomoji , Brooks Steven , Baker Linda C. , Ueyama Takahisa , Gursoy Erdal , Saba Samir , Salama Guy , London Barry , Stewart Alexandre F.R.
Published: November 2004

Background—

Conduction system defects and slowed ventricular conduction are common in patients with systolic dysfunction and contribute to arrhythmias and sudden death. In animal models of heart failure, cardiac α
1
-adrenergic signaling is constitutively activated. Here, we report the effects of constitutive activation of α
1
-adrenergic signaling on connexin phosphorylation and cardiac conduction.

Methods and Results—

Transgenic mice were generated with cardiac-specific overexpression of the transcription factor RTEF-1 (transcription enhancer factor-1-related factor), which mediates α
1
-adrenergic signaling in cardiac myocytes. Surface and intracardiac ECGs revealed prolongation of the PR, QRS, and AH intervals and the appearance of progressive atrial arrhythmias in RTEF-1 mice. Optical mapping using voltage-sensitive dye revealed slower conduction velocities across the atrial and ventricular myocardium. Intercellular dye transfer between RTEF-1 transgenic cardiac myocytes confirmed impaired conduction at the cellular level. Conduction defects were correlated with dephosphorylation of connexin40 and connexin43 and upregulation of protein phosphatase 1β (PP1β). Overexpression of PP1β in HeLa cells dephosphorylated cardiac connexin. Confocal microscopy revealed increased levels of dephosphorylated connexin43 at the cardiac gap junctions in RTEF-1 mice, suggesting that defective conduction is a result of impaired gap-junction conductance rather than assembly.

Conclusion—

Constitutive activation of α
1
-adrenergic signaling through the RTEF-1 transcription factor results in chronic elevation of PP1β expression and connexin dephosphorylation. This mechanism may underlie some defects in cardiac conduction.
Prevention of Iatrogenic Atrial Tachycardia After Ablation of Atrial Fibrillation
Authors: Pappone Carlo , Manguso Francesco , Vicedomini Gabriele , Gugliotta Filippo , Santinelli Ornella , Ferro Amedeo , Gulletta Simone , Sala Simone , Sora Nicoleta , Paglino Gabriele , Augello Giuseppe , Agricola Eustachio , Zangrillo Alberto , Alfieri Ottavio , Santinelli Vincenzo
Published: November 2004

Background—

Circumferential pulmonary vein ablation (CPVA) is effective in curing atrial fibrillation (AF), but new-onset left atrial tachycardia (AT) is a potential complication. We evaluated whether a modified CPVA approach including additional ablation lines on posterior wall and the mitral isthmus would reduce the incidence of AT after PV ablation.

Methods and Results—

A total of 560 patients (291 men, 52%; age, 56.5±7.3 years) entered the study; 280 were randomized to CPVA alone (group 1) and 280 to modified CPVA (group 2). The primary end point was freedom from AT after the procedure. In group 1, 28 patients (10%) experienced new-onset AT, and 41 (14.3%) experienced recurrent AF. In group 2, 11 patients (3.9%) experienced AT, and 36 (12.9%) had recurrent AF. Group 1 was more likely to experience AT than group 2 (
P
=0.005). Freedom from AF after ablation was similar in both groups (
P
=0.57). Among those in group 1, gap-related macroreentrant AT was documented in 23 of the 28 patients (82%), and focal AT was found in 5 (18%). In group 2, gap-related macroreentrant AT was found in 8 of the 11 patients (73%), and focal AT was seen in 3 (27%). Two patients in group 1 and 1 patient in group 2 had both AT and AF. The strongest predictor of AT was the presence of gaps (
P
<0.001).

Conclusions—

Modified CPVA is as effective as CPVA in preventing AF but is associated with a lower risk of developing incessant AT.
Evidence for a Heritable Component in Death Resulting From Aortic and Mitral Valve Diseases
Authors: Horne Benjamin D. , Camp Nicola J. , Muhlestein Joseph B. , Cannon-Albright Lisa A.
Published: November 2004

Background—

Cardiac valvular diseases contribute to >42 000 deaths yearly in the United States, but the role of genetics in these deaths is unknown. This study evaluated the familiality of death resulting from aortic, mitral, and all valvular diseases using a population-based genealogy linked to death records.

Methods and Results—

The Utah Population Database contains >2 million individual records with genealogy data and 250 000 linked death certificates. Nonrheumatic aortic (n=932), mitral (n=1165), and all valvular (n=2504) disease deaths and rheumatic heart disease deaths (n=4713) were studied. Familial relative risks (FRRs) were assessed for first- and second-degree relatives. Familiality was also evaluated with the genealogical index of familiality, which considers all relationships in the Utah Population Database. FRRs were increased only for mitral valve death in both first-degree (FRR, 2.55;
P
<0.0001) and second-degree (FRR, 1.67;
P
<0.0001) relatives. Genealogical index of familiality analysis showed significant excess relatedness for all groups (
P
<0.001). Genealogical index of familiality results (
P
<0.001) for early age at death cases showed higher mean relatedness, a common characteristic of heritable disorders. Excess familiality extended to distant relatives for mitral (second-degree relatives) and aortic (beyond second-degree relatives) valve death.

Conclusions—

Deaths resulting from nonrheumatic mitral and aortic diseases clustered among both close and distant relatives, especially among early age at death cases, suggesting a significant genetic component in death resulting from valvular diseases. Future studies should focus on gene discovery.
Epicardial Mapping of Chronic Atrial Fibrillation in Patients
Authors: Sahadevan Jayakumar , Ryu Kyungmoo , Peltz Leora , Khrestian Celeen M. , Stewart Robert W. , Markowitz Alan H. , Waldo Albert L.
Published: November 2004

Background—

The mechanisms of chronic atrial fibrillation (AF) are not well understood. We performed epicardial mapping of chronic AF in patients undergoing open heart surgery to test the hypothesis that chronic AF is due to a left atrial “driver” with a regular, short cycle length, resulting in fibrillatory conduction to the rest of the atria.

Methods and Results—

Nine patients with chronic AF (1 month to >15 years’ duration) were studied at open heart surgery, 8 before and 1 during cardiopulmonary bypass. During AF, atrial electrograms (AEGs) were recorded for 1 to 5 minutes from 404 epicardial electrodes arranged in bipoles along with ECG lead II or ventricular electrogram. Four-second segments of each bipolar AEG were also subjected to fast Fourier transform analysis. Two patterns of atrial activation were present during AF. In pattern 1 (7/9 patients), AEGs from parts of the atria demonstrated a short, regular cycle length with identical beat-to-beat morphology, and the rest of the atria were activated irregularly, and AEGs that demonstrated constant morphology and cycle length were localized to parts of the left atria (5/7), the right atria (1/7), or both atria (1/7). In pattern 2 (2/9 patients), AEGs showed no evidence of regular activation or constant morphology.

Conclusions—

In 9 patients with chronic AF, the commonest recorded AEG pattern showed an area of regular, rapid rhythm, consistent with the possibility that a driver causing fibrillatory conduction is one mechanism of AF in these patients.
Early Life Factors and Blood Pressure at Age 31 Years in the 1966 Northern Finland Birth Cohort
Authors: Järvelin Marjo-Riitta , Sovio Ulla , King Vanessa , Lauren Liisa , Xu Baizhuang , McCarthy Mark I. , Hartikainen Anna-Liisa , Laitinen Jaana , Zitting Paavo , Rantakallio Paula , Elliott Paul
Published: November 2004

Data on the birth weight–blood pressure relationship are inconsistent. Although an inverse association has been suggested in several large studies, interpretation is complicated by publication and other biases. Few data are available on the relationship between other early growth measures and blood pressure. We examined the shape and size of association between determinants of fetal growth, size at birth, growth in infancy, and adult systolic and diastolic blood pressure at 31 years in the prospective northern Finnish 1966 birth cohort of 5960 participants. Birth weight, birth length, gestational age, ponderal index, and birth weight relative to gestational age showed a significant inverse association with blood pressure at age 31. Rapid growth in infancy (“change-up”) was positively associated with blood pressure. Adjusted regression coefficients for birth weight indicated systolic/diastolic blood pressure lower by −1.7 (95% confidence interval [CI], −2.5, −1.0)/−0.7 (95% CI, −1.4, −0.02) mm Hg for 1 kg higher birth weight. The significant inverse association between birth weight and systolic blood pressure persisted without adjustment for adult body mass index for males. Among females, gestational age showed a stronger association with blood pressure than birth weight: gestational age higher by 7 weeks (equivalent to an average of 1 kg higher birth weight) among singletons associated with −2.9 (95% CI, −4.7, −1.1) mm Hg lower systolic blood pressure. Our results support the concept that birth weight, other birth measures, and infant growth are important determinants of blood pressure and hence cardiovascular disease risk in later life.
Some Males are Choosier Than Others: Species Recognition in Blue Waxbills
Authors: Brooks  , Luddem  , Collins  , Winter
Published: November 2004

We investigated whether species specific mating preferences differed between the sexes in three species of blue waxbill (genus Uraeginthus). We compared male preference for conspecific females versus heterospecific blue waxbill females using two-way choice trials. The results were compared with predictions of the strength of species specific mating preferences made on the basis of several different hypotheses. These predictions were made according to the specific behavioural and morphological traits of the three species, their phylogenetic relatedness and relative geographical location. Males did not prefer conspecific females whenever they were given a choice of a larger heterospecific female. Furthermore, males tended to discriminate between females more strongly when there was a large difference in size between the two species of females that they had been presented with. Relating the strength of males preference for conspecific females to the predictions made according to the different hypotheses it appeared that males were discriminating between females on the basis of their size. We compared male mate preferences for conspecifics versus heterospecifics with female mate preferences for conspecifics versus heterospecifics that had been ascertained in a previous study. There were marked differences between preference for conspecifics between the sexes for all three species, suggesting that males and females used different criteria to choose mates when discriminating between related species. Males appeared to use female size whereas females appeared to use the degree of male ornamentation, suggesting that mate preference is under a different selective pressure between the sexes. The results of this study have identified that there is a potential for hybridisation between blue breast females and both red cheek and blue cap males. In the event of a geographical change leading to sympatry between these species the degree of hybridisation will depend on the preference criteria within each species and the differences in morphology between those species. This will ultimately determine how discrimination between heterospecifics will interact with conspecific mate choice.
Phoresy of Rhabditophanes schneideri (Bütschli) (Rhabditida: Alloionematidae) on pseudoscorpions (Arachnida: Pseudoscorpiones)
Authors: Ćurčić Srećko , Sudhaus Walter , Dimitrijević Rajko , Tomić Vladimir , Ćurčić Božidar
Published: November 2004

A total of 227 phoretic J3 dauer juveniles of the nematode Rhabditophanes
schneideri (Bütschli) were observed attached to 63 out of 4845 specimens of
three species of pseudoscorpion from Belgrade, Serbia and Montenegro.
Analysis of the numbers of phoretic dauer larvae on different body regions
revealed that the majority were attached to different pedipalpal and pedal
segments. Only a few nematodes were carried on the prosoma and opisthosoma
and none were observed on the chelicerae.
The ability of rhizosphere bacteria isolated from nematode host and non-host plants to influence the hatch in vitro of the two potato cyst nematode species, Globodera rostochiensis and G. pallida
Authors: Ryan N. Aileen , Jones Peter
Published: November 2004

Seventy bacteria, isolated from the rhizosphere of the potato cyst nematode (PCN) host plant, potato, were cultured in the presence and absence of potato root leachate (PRL) and the resultant culture filtrates were analysed for their ability to affect the hatch in vitro of the two PCN species. Of the isolates tested, nine had a significant effect on PCN hatch. Six affected Globodera pallida hatch and three affected G. rostochiensis hatch. Five of the isolates significantly increased hatch only when cultured in the presence of PRL. Three of the isolates decreased PCN hatch significantly in PRL. Only one isolate increased hatch significantly in the absence of PRL. No isolate affected the hatch of both species. Six of the nine isolates that significantly affected PCN hatch had been pre-selected by culturing on PRL. Bacterial isolates from PCN non-hosts (14 from wheat, 17 from sugar beet) were also tested for hatching activity. The principal effect of the hatch-active isolates from the PCN non-host plants was to increase PCN hatch in the presence of PRL. In contrast to the host bacteria results, the isolates from non-host plants affected only G. rostochiensis hatch (three wheat isolates and four sugar beet isolates significantly increased G. rostochiensis hatch); no such isolate affected G. pallida hatch significantly in the presence of PRL. Ten isolates (32%) from non-host plants had the ability to increase significantly the hatch of PCN in the absence of PRL (eight of these affected G. rostochiensis hatch and four affected G. pallida hatch), compared to only one bacterial isolate (1%) from a host plant. The majority of the isolates from non-hosts produced PCN species-specific effects, as with the bacteria isolated from potatoes, although two wheat isolates increased the hatch of both species significantly in the absence of PRL. Of 20 hatch-active bacterial isolates (from all three plants) identified, 70% were Bacillus spp. Other genera identified were Arthrobacter , Acinetobacter and Staphylococcus .
Heterodera circeae sp. n. and H. scutellariae sp. n. (Tylenchida: Heteroderidae) from Germany, with notes on the goettingiana group
Authors: Subbotin Sergei , Sturhan Dieter
Published: November 2004

Two species of cyst-forming nematodes belonging to the goettingiana group are
described from woodland in Germany. Heterodera circeae sp. n., parasitising
Circaea lutetiana (Onagraceae), most closely resembles H. carotae and H.
cruciferae, from which it differs by larger cysts (430-720 μm) and longer
fenestral length (27-54 μm) and rounded stylet knobs of the second-stage
juveniles. Heterodera scutellariae sp. n., found on the labiate Scutellaria
galericulata (Lamiaceae), is distinguished from the other species of this
group by shorter body (358-437 μm) and tail (41-53 μm) of the second-stage
juveniles. The ITS-rDNA sequences of the new species are very similar and
differ from each other by only a few nucleotides. The phylogenetic position
of the new species within the group is presented based on analyses of
molecular data. A revised diagnosis of the goettingiana group is proposed.
The species of the group have lemon-shaped, ambifenestrate and abullate
(small bullae occasionally present) cysts with egg sac, long vulval slit
(> 35 μm), thin vulval bridge, low semifenestrae (average fenestral
length 30-45 μm), and weak underbridge. Second-stage juveniles are
characterised by body length > 400 μm, tail length > 45 μ m, hyaline
tail portion > 20 μm, stylet length > 20 μm, lateral field with four
incisures and small phasmids. All known species of the goettingiana group
exclusively parasitise dicotyledonous plants.
On the Epistemological Magic of Ethnographic Analysis
Authors: Mort Joel , Slone D. Jason
Published: November 2004

Analyses of religious behavior by cultural (i.e., hermeneutic) scholars of religion are impoverished because the intuitive interpretive method employed in fieldwork analysis fails to fill an explanatory gap in religious studies because of (1) the reliance upon informant (ethnographic) data that itself requires explanation, and because of (2) the rejection of relevant scientific explanatory models required to explain that data. We argue that fieldwork is often necessary for data acquisition but not sufficient for analysis, that stringent methods of evaluation are a necessary component of the analysis of religious behavioral data, and that such tools are currently available to scholars willing to engage methods and theories outside the humanities. Noticing tendencies in ethnographic interpretation, examining fresh interdisciplinary approaches, and revisiting fundamental meta-theoretical issues concerning the nature of explanatory reasoning may help to mitigate the generally ineffective state of scholarship in the field.