bluuebunny/crossref_metadata_2025 huggingface dataset:
Isokinetic eccentric exercise can induce skeletal muscle injury within the physiologic excursion of muscle-tendon unit: a rabbit model
Authors: Tsuang Yang-Hwei , Lam Shui-Ling , Wu Lien-Chen , Chiang Chang-Jung , Chen Li-Ting , Chen Pei-Yu , Sun Jui-Sheng , Wang Chien-Che
Published: August 2007

Background and Purpose

Intensive eccentric exercise can cause muscle damage. We simulated an animal model of isokinetic eccentric exercise by repetitively stretching stimulated triceps surae muscle-tendon units to determine if such exercise affects the mechanical properties of the unit within its physiologic excursion.

Methods

Biomechanical parameters of the muscle-tendon unit were monitored during isokinetic eccentric loading in 12 rabbits. In each animal, one limb (control group) was stretched until failure. The other limb (study group) was first subjected to isokinetic and eccentric cyclic loading at the rate of 10.0 cm/min to 112% (group I) or 120% (group II) of its initial length for 1 hour and then stretched to failure. Load-deformation curves and biomechanical parameters were compared between the study and control groups.

Results

When the muscle-tendon unit received eccentric cyclic loading to 112%, changes in all biomechanical parameters – except for the slope of the load-deformation curve – were not significant. In contrast, most parameters, including the slope of the load-deformation curve, peak load, deformation at peak load, total energy absorption, and energy absorption before peak load, significantly decreased after isokinetic eccentric cyclic loading to 120%.

Conclusion

We found a threshold for eccentrically induced injury of the rabbit triceps surae muscle at between 12% and 20% strain, which is within the physiologic excursion of the muscle-tendon units. Our study provided evidence that eccentric exercise may induce changes in the biomechanical properties of skeletal muscles, even within the physiologic range of the excursion of the muscle-tendon unit.
Androgens and Glucuronidated Androgen Metabolites Are Associated with Metabolic Risk Factors in Men
Authors: Vandenput Liesbeth , Mellström Dan , Lorentzon Mattias , Swanson Charlotte , Karlsson Magnus K. , Brandberg John , Lönn Lars , Orwoll Eric , Smith Ulf , Labrie Fernand , Ljunggren Östen , Tivesten Åsa , Ohlsson Claes
Published: August 2007

Context: Androgens are associated with metabolic risk factors in men. However, the independent impact of androgens and androgen metabolites on metabolic risk factors in men is unclear.

Objective: Our objective was to determine the predictive value of serum levels of androgens and glucuronidated androgen metabolites for metabolic risk factors.

Design and Study Subjects: We conducted a population-based study of two Swedish cohorts (1068 young adult and 1001 elderly men).

Main Outcome Measures: We measured correlation of serum dihydrotestosterone (DHT), testosterone (T), and glucuronidated androgen metabolites with fat mass, fat distribution, serum lipids, and insulin resistance.

Results: Both DHT and T were negatively associated with different measures of fat mass in both cohorts (P < 0.001). Further statistical analysis indicated that DHT, but not T, was independently negatively associated with different measures of fat mass and insulin resistance (P < 0.001). The glucuronidated androgen metabolite androstane-3α,17β-diol-17glucuronide (17G) was independently positively associated with fat mass (P < 0.001). Most importantly, the 17G to DHT ratio was strongly correlated, not only with fat mass but also with central fat distribution, intrahepatic fat, disturbed lipid profile, insulin resistance, and diabetes, explaining a substantial part of the total variance in total body fat (12% in young adult men, 15% in elderly men), the homeostasis model assessment index (10%), and high-density lipoprotein cholesterol (7%).

Conclusion: Our findings demonstrate that 17-glucuronidation of the DHT metabolite androstane-3α,17β-diol is strongly associated with several metabolic risk factors in men. Future longitudinal studies are required to determine the possible impact of the 17G to DHT ratio as a metabolic risk factor in men.
Cell-surface transglutaminase undergoes internalization and lysosomal degradation: an essential role for LRP1
Authors: Zemskov Evgeny A. , Mikhailenko Irina , Strickland Dudley K. , Belkin Alexey M.
Published: August 2007

Tissue transglutaminase functions as a protein crosslinking enzyme and an integrin-binding adhesion co-receptor for fibronectin on the cell surface. These activities of transglutaminase and the involvement of this protein in cell-matrix adhesion, integrin-mediated signaling, cell migration and matrix organization suggest a precise and efficient control of its cell-surface expression. We report a novel mechanism of regulation of surface transglutaminase through internalization and subsequent lysosomal degradation. Constitutive endocytosis of cell-surface transglutaminase depends on plasma membrane cholesterol and the activity of dynamin-2, and involves both clathrin-coated pits and lipid rafts or caveolae. Furthermore, the key matrix ligands of transglutaminase, fibronectin and platelet-derived growth factor, promote its endocytosis from the cell surface. Our results also indicate that transglutaminase interacts in vitro and on the cell surface with the major endocytic receptor, low-density lipoprotein receptor-related protein 1, and demonstrate the requirement for this receptor in the endocytosis of transglutaminase. Finally, a deficiency of this endocytic receptor or blockade of endo-lysosomal function upregulate transglutaminase expression on the cell surface, leading to increased cell adhesion and matrix crosslinking. These findings characterize a previously unknown pathway of transglutaminase internalization and degradation that might be crucial for regulation of its adhesive and signaling functions on the cell surface and reveal a novel functional link between cell-matrix adhesion and endocytosis.
Evolution of the eukaryotic membrane-trafficking system: origin, tempo and mode
Authors: Dacks Joel B. , Field Mark C.
Published: August 2007

The emergence of an endomembrane system was a crucial stage in the prokaryote-to-eukaryote evolutionary transition. Recent genomic and molecular evolutionary analyses have provided insight into how this critical system arrived at its modern configuration. The apparent relative absence of prokaryotic antecedents for the endomembrane machinery contrasts with the situation for mitochondria, plastids and the nucleus. Overall, the evidence suggests an autogenous origin for the eukaryotic membrane-trafficking machinery. The emerging picture is that early eukaryotic ancestors had a complex endomembrane system, which implies that this cellular system evolved relatively rapidly after the proto-eukaryote diverged away from the other prokaryotic lines. Many of the components of the trafficking system are the result of gene duplications that have produced proteins that have similar functions but differ in their subcellular location. A proto-eukaryote possessing a very simple trafficking system could thus have evolved to near modern complexity in the last common eukaryotic ancestor (LCEA) via paralogous gene family expansion of the proteins encoding organelle identity. The descendents of this common ancestor have undergone further modification of the trafficking machinery; unicellular simplicity and multicellular complexity are the prevailing trend, but there are some remarkable counter-examples.
Poliovirus infection blocks ERGIC-to-Golgi trafficking and induces microtubule-dependent disruption of the Golgi complex
Authors: Beske Oren , Reichelt Mike , Taylor Matthew P. , Kirkegaard Karla , Andino Raul
Published: August 2007

Cells infected with poliovirus exhibit a rapid inhibition of protein secretion and disruption of the Golgi complex. Neither the precise step at which the virus inhibits protein secretion nor the fate of the Golgi complex during infection has been determined. We find that transport-vesicle exit from the endoplasmic reticulum (ER) and trafficking to the ER-Golgi intermediate compartment (ERGIC) are unaffected in the poliovirus-infected cell. By contrast, poliovirus infection blocks transport from the ERGIC to the Golgi complex. Poliovirus infection also induces fragmentation of the Golgi complex resulting in diffuse distribution of both large and small vesicles throughout the cell. Pre-treatment with nocodazole prevents complete fragmentation, indicating that microtubules are required for poliovirus-induced Golgi dispersion. However, virally induced inhibition of the secretory pathway is not affected by nocodazole, and Golgi dispersion was found to occur during infection with mutant viruses with reduce ability to inhibit protein secretion. We conclude that the dispersion of the Golgi complex is not in itself the cause of inhibition of traffic between the ERGIC and the Golgi. Instead, these phenomena are independent effects of poliovirus infection on the host secretory complex.
UK national audit of sexual health care for people with HIV infection: case-notes audit
Authors: Carne Chris , McClean Hugo , Bunting Paul , Wilkins Ed , Tucker Linda , Baguley Steve , Daniels David ,   The National Audit Group of the British Association for Sexual Health and HIV
Published: August 2007

The case-notes of 3210 patients with HIV infection were audited. A sexual history was documented within four weeks before or after initial HIV diagnosis in 69% of cases (regional range 45–84%), and in the six months before attendance during the audit interval in 34% (12–53%). An offer of tests for sexually transmitted infections was documented within four weeks before or after HIV diagnosis in 58% (30–83%), and in the prior six months in 28% (14–47%). Syphilis serology was offered in the previous three months to 45% (14–100%) of cases resident in syphilis outbreak areas and to 25% (7–62%) of other cases. Hepatitis B testing was performed for 98% (95–100%) of cases and for hepatitis C, for 91% (79–100%). Cervical cytology results in the past year were documented for 73% (43–94%) of eligible women. Considerable inter-regional variation in performance exists. Interventions are needed to improve the sexual health care of people with HIV infection.
Management of HIV infection in adolescents attending inner London HIV services
Authors: Ferrand R A , Miller R F , Jungmann E A
Published: August 2007

Increasing numbers of HIV-infected children are now reaching adulthood and young people account for 10% of new HIV diagnosis in the UK each year. This audit of young people attending specialist and generic HIV services in Inner London in 2006 ( n=39) highlights the complex medical and psychosocial needs of this patient group: 63% were diagnosed with HIV because of poor health, 39% had received more than three antiretroviral regimens, 21% had resistance to two antiretroviral classes and 32% had significant mental health problems. In addition, 45% reported to be sexually active with poor uptake of contraception other than condoms and frequent non-disclosure of their HIV status to a sexual partner.
How much do blood exposures contribute to HIV prevalence in female sex workers in sub-Saharan Africa, Thailand and India?
Authors: Gisselquist David
Published: August 2007

Female sex workers (FSWs) are subject to frequent invasive procedures in health care and cosmetic services. When infection control is deficient, these procedures not only put FSWs at risk to acquire HIV, but are also risks for FSWs to transmit HIV to the general population. Direct information about blood exposures other than injection drug use as risks for HIV infection in FSWs has been too limited to test the hypothesis that unsterile health-care procedures have infected large numbers of FSWs in sub-Saharan Africa and Asia. However, indirect evidence suggests that blood exposures might account for an important proportion of their HIV infections. This indirect evidence includes: higher prevalence of hepatitis C infection among sex workers than among other women; continuing HIV acquisition among FSWs despite high rates of condom use and surprisingly high ratios of incidence of HIV compared with incidence of syphilis, gonorrhoea and chlamydia.
Partnerships and the role of financial advisors: private control over public policy?
Authors: Shaoul Jean , Stafford Anne , Stapleton Pamela
Published: August 2007

English

This article shows how the use of private sector advisors, predominantly from the Big Four accounting firms, to develop and manage the government's Public–Private Partnerships policy, has led to the privatisation of policy formulation and implementation. Financial advisors develop the policy and appraisal procedures, appraise individual projects, and advise both public and private sector clients. In some cases, the firms also have an equity stake and/or are key subcontractors. They prepare evaluative reports on the same policies in which they have a vested interest. Such conflicts of interest raise questions about who controls policy and the implications for democracy.
Differential ability and attainment in language and arithmetic of Dutch primary school pupils
Authors: Mooij Ton , Driessen Geert
Published: August 2007

Background. In preschool and primary education, pupils differ in many abilities and competences (giftedness). Yet mainstream educational practice seems rather homogeneous in providing age‐based or grade–class subject matter approaches.

Aims. To clarify whether pupils scoring initially at high ability level do develop and attain differently at school with respect to language and arithmetic compared with those displaying other initial ability levels. To investigate whether specific individual, family, or educational variables covary with the attainment of these different types of pupils in school.

Samples. Data from the large‐scale PRIMA cohort study including a total of 8,258 Grades 2 and 4 pupils from 438 primary schools in The Netherlands.

Methods. Secondary analyses were carried out to construct gain scores for both language and arithmetic proficiency and a number of behavioural, attitudinal, family, and educational characteristics. The pupils were grouped into four different ability categories (highly able, able, above average, average or below average). Further analyses used Pearson correlations and analyses of variance both between‐ and within‐ability categories. Cross‐validation was done by introducing a cohort of younger pupils in preschool and grouping both cohorts into decile groups based on initial ability in language and arithmetic.

Results. Highly able pupils generally decreased in attainment in both language and arithmetic, whereas pupils in average and below‐average groups improved their language and arithmetic scores. Only with highly able pupils were some educational characteristics correlated with the pupils' development in achievement, behaviour, and attitudes.

Conclusions. Preschool and primary education should better match pupils' differences in abilities and competences from their start in preschool to improve their functioning, learning processes, and outcomes. Recommendations for educational improvement strategies are presented at the end of the article.
YKL-40 Protein Expression in the Early Developing Human Musculoskeletal System
Authors: Johansen Julia S. , Høyer Poul E. , Larsen Lars A. , Price Paul A. , Møllgård Kjeld
Published: August 2007

YKL-40 is a growth factor for chondrocytes and fibroblasts. The aim was to evaluate YKL-40 expression in the musculoskeletal system during early human development. We studied sections from 15 human embryos [weeks 5.5-8; 7- to 31-mm crown-rump length (CRL)] and 68 fetuses (weeks 9-14; 33- to 105-mm CRL) for YKL-40 protein expression by immunohistochemistry. YKL-40 mRNA expression was evaluated in two human embryos (days 41 and 51). Initially YKL-40 is expressed in all germ layers: ecto-, meso-, and endoderm. YKL-40 mRNA and protein expression are found in tissues of the ecto-, meso-, and endoderm, and YKL-40 protein expression is present during development of cartilage, bone, joints, and muscles. At the cellular level, YKL-40 protein expression is high in tissues characterized by rapid proliferation, marked differentiation, and undergoing morphogenetic changes. Examples of rapid cell proliferation include the chondrogenic inner layer of perichondrium and the osteogenic inner layer of periosteum. Differences in YKL-40 expression during differentiation are found in the chondrogenic and osteogenic cell lineages. The initial shaping of cartilage and bone models and joints is concomitant with a strong outline of YKL-40-positive cells. This indicates that YKL-40 is associated with cell proliferation, differentiation, and tissue morphogenesis during development of the human musculoskeletal system.
Disorganized Microtubules Underlie the Formation of Retraction Bulbs and the Failure of Axonal Regeneration
Authors: Ertürk Ali , Hellal Farida , Enes Joana , Bradke Frank
Published: August 2007

Axons in the CNS do not regrow after injury, whereas lesioned axons in the peripheral nervous system (PNS) regenerate. Lesioned CNS axons form characteristic swellings at their tips known as retraction bulbs, which are the nongrowing counterparts of growth cones. Although much progress has been made in identifying intracellular and molecular mechanisms that regulate growth cone locomotion and axonal elongation, a comprehensive understanding of how retraction bulbs form and why they are unable to grow is still elusive. Here we report the analysis of the morphological and intracellular responses of injured axons in the CNS compared with those in the PNS. We show that retraction bulbs of injured CNS axons increase in size over time, whereas growth cones of injured PNS axons remain constant. Retraction bulbs contain a disorganized microtubule network, whereas growth cones possess the typical bundling of microtubules. Usingin vivoimaging, we find that pharmacological disruption of microtubules in growth cones transforms them into retraction bulb-like structures whose growth is inhibited. Correspondingly, microtubule destabilization of sensory neurons in cell culture induces retraction bulb formation. Conversely, microtubule stabilization prevents the formation of retraction bulbs and decreases axonal degenerationin vivo. Finally, microtubule stabilization enhances the growth capacity of CNS neurons cultured on myelin. Thus, the stability and organization of microtubules define the fate of lesioned axonal stumps to become either advancing growth cones or nongrowing retraction bulbs. Our data pinpoint microtubules as a key regulatory target for axonal regeneration.
Functional Organization of Presynaptic Metabotropic Glutamate Receptors in Vagal Brainstem Circuits
Authors: Browning Kirsteen N. , Travagli R. Alberto
Published: August 2007

We demonstrated previously that, by suppressing cAMP levels, metabotropic glutamate receptors (mGluRs) play a crucial role in opioid receptor trafficking on GABAergic nerve terminals within gastric brainstem vagal circuits. Using whole-cell patch-clamp recordings, we aimed to correlate the influence of sensory vagal afferent fibers with the functional organization of mGluRs on the synaptic connections between the nucleus tractus solitarius and dorsal motor nucleus of the vagus. Group II mGluRs were identified on both excitatory and inhibitory synapses; the receptor-selective agonist APDC [(2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate] induced a concentration-dependent decrease in glutamatergic and GABAergic synaptic transmission (EC50, ∼20 μmfor both). The group II mGluRs were activated tonically on GABAergic, but not glutamatergic synapses, as the receptor-selective antagonist (2S)-α-ethylglutamic acid (EGLU; 200 μm) modulated GABA currents only. After selective vagal deafferentation, EGLU was without effect, suggesting that vagal afferent (sensory) fibers are the source of this tonic input. Conversely, group III mGluRs, although not activated tonically, were present on excitatory, but not inhibitory, synapses; in fact, the receptor-selective agonistl-AP-4 [l-(+)-2-amino-4-phosphonbutyric acid] induced a concentration-dependent decrease in glutamatergic synaptic transmission (EC50, ∼2 μm) but had no effect on GABAergic synaptic transmission. Together with our previous results on receptor trafficking, these data suggest that visceral information plays a fundamental role in shaping the response of homeostatic brainstem circuits that receive inputs from higher integrative neuronal centers.
High-Resolution Maps of Real and Illusory Tactile Activation in Primary Somatosensory Cortex in Individual Monkeys with Functional Magnetic Resonance Imaging and Optical Imaging
Authors: Chen Li M. , Turner Gregory H. , Friedman Robert M. , Zhang Na , Gore John C. , Roe Anna W. , Avison Malcolm J.
Published: August 2007

Although blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to explore human brain function, questions remain regarding the ultimate spatial resolution of positive BOLD fMRI, and indeed the extent to which functional maps revealed by positive BOLD correlate spatially with maps obtained with other high-spatial-resolution mapping techniques commonly used in animals, such as optical imaging of intrinsic signal (OIS) and single-unit electrophysiology. Here, we demonstrate that the positive BOLD signal at 9.4T can reveal the fine topography of individual fingerpads in single-condition activation maps in nonhuman primates. These digit maps are similar to maps obtained from the same animal using intrinsic optical imaging. Furthermore, BOLD fMRI reliably resolved submillimeter spatial shifts in activation in area 3b previously identified with OIS (Chen et al., 2003) as neural correlates of the “funneling illusion.” These data demonstrate that at high field, high-spatial-resolution topographic maps can be achieved using the positive BOLD signal, weakening previous notions regarding the spatial specificity of the positive BOLD signal.
Dendritic Spikes in Apical Dendrites of Neocortical Layer 2/3 Pyramidal Neurons
Authors: Larkum Matthew Evan , Waters Jack , Sakmann Bert , Helmchen Fritjof
Published: August 2007

Layer 2/3 (L2/3) pyramidal neurons are the most abundant cells of the neocortex. Despite their key position in the cortical microcircuit, synaptic integration in dendrites of L2/3 neurons is far less understood than in L5 pyramidal cell dendrites, mainly because of the difficulties in obtaining electrical recordings from thin dendrites. Here we directly measured passive and active properties of the apical dendrites of L2/3 neurons in rat brain slices using dual dendritic–somatic patch-clamp recordings and calcium imaging. Unlike L5 cells, L2/3 dendrites displayed little sag in response to long current pulses, which suggests a low density ofIhin the dendrites and soma. This was also consistent with a slight increase in input resistance with distance from the soma. Brief current injections into the apical dendrite evoked relatively short (half-width 2–4 ms) dendritic spikes that were isolated from the soma for near-threshold currents at sites beyond the middle of the apical dendrite. Regenerative dendritic potentials and large concomitant calcium transients were also elicited by trains of somatic action potentials (APs) above a critical frequency (130 Hz), which was slightly higher than in L5 neurons. Initiation of dendritic spikes was facilitated by backpropagating somatic APs and could cause an additional AP at the soma. As in L5 neurons, we found that distal dendritic calcium transients are sensitive to a long-lasting block by GABAergic inhibition. We conclude that L2/3 pyramidal neurons can generate dendritic spikes, sharing with L5 pyramidal neurons fundamental properties of dendritic excitability and control by inhibition.
Requirement for Slit-1 and Robo-2 in Zonal Segregation of Olfactory Sensory Neuron Axons in the Main Olfactory Bulb
Authors: Cho Jin Hyung , Lépine Manon , Andrews William , Parnavelas John , Cloutier Jean-François
Published: August 2007

The formation of precise stereotypic connections in sensory systems is critical for the ability to detect and process signals from the environment. In the olfactory system, olfactory sensory neurons (OSNs) project axons to spatially defined glomeruli within the olfactory bulb (OB). A spatial relationship exists between the location of OSNs within the olfactory epithelium (OE) and their glomerular targets along the dorsoventral axis in the OB. The molecular mechanisms underlying the zonal segregation of OSN axons along the dorsoventral axis of the OB are poorly understood. Usingrobo-2−/−(roundabout) andslit-1−/−mice, we examined the role of the Slit family of axon guidance cues in the targeting of OSN axons during development. We show that a subset of OSN axons that normally project to the dorsal region of the OB mistarget and form glomeruli in the ventral region inrobo-2−/−andslit-1−/−mice. In addition, we show that the Slit receptor, Robo-2, is expressed in OSNs in a high dorsomedial to low ventrolateral gradient across the OE and that Slit-1 and Slit-3 are expressed in the ventral region of the OB. These results indicate that the dorsal-to-ventral segregation of OSN axons are not solely defined by the location of OSNs within the OE but also relies on axon guidance cues.
Dark Rearing Rescues P23H Rhodopsin-Induced Retinal Degeneration in a TransgenicXenopus laevisModel of Retinitis Pigmentosa: A Chromophore-Dependent Mechanism Characterized by Production of N-Terminally Truncated Mutant Rhodopsin
Authors: Tam Beatrice M. , Moritz Orson L.
Published: August 2007

To elucidate the molecular mechanisms underlying the light-sensitive retinal degeneration caused by the rhodopsin mutation P23H, which causes retinitis pigmentosa (RP) in humans, we expressedXenopus laevis, bovine, human, and murine forms of P23H rhodopsin in transgenicX. laevisrod photoreceptors. All P23H rhodopsins caused aggressive retinal degeneration associated with low expression levels and retention of P23H rhodopsin in the endoplasmic reticulum (ER), suggesting involvement of protein misfolding and ER stress. However, light sensitivity varied dramatically between these RP models, with complete or partial rescue by dark rearing in the case of bovine and human P23H rhodopsin, and no rescue forX. laevisP23H rhodopsin. Rescue by dark rearing required an intact 11-cis-retinal chromophore binding site within the mutant protein and was associated with truncation of the P23H rhodopsin N terminus. This yielded an abundant nontoxic ∼27 kDa form that escaped the ER and was transported to the rod outer segment. The truncated protein was produced in the greatest quantities in dark-reared retinas expressing bovine P23H rhodopsin and was not observed withX. laevisP23H rhodopsin. These results are consistent with a mechanism involving enhanced protein folding in the presence of 11-cis-retinal chromophore, with ER exit assisted by proteolytic truncation of the N terminus. This study provides a molecular mechanism for light sensitivity observed in other transgenic models of RP and for phenotypic variation among RP patients.
Astroglial Glutamate–Glutamine Shuttle Is Involved in Central Sensitization of Nociceptive Neurons in Rat Medullary Dorsal Horn
Authors: Chiang Chen-Yu , Wang Jing , Xie Yu-Feng , Zhang Sun , Hu James W. , Dostrovsky Jonathan O. , Sessle Barry J.
Published: August 2007

Growing evidence suggests that astroglia are involved in pain states, but no studies have tested their possible involvement in modulating the activity of nociceptive neurons per se. This study has demonstrated that the central sensitization induced in functionally identified nociceptive neurons in trigeminal subnucleus caudalis (the medullary dorsal horn) by application of an inflammatory irritant to the rat's tooth pulp can be significantly attenuated by continuous intrathecal superfusion of methionine sulfoximine (MSO; 0.1 mm), an inhibitor of the astroglial enzyme glutamine synthetase that is involved in the glutamate–glutamine shuttle. Simultaneous superfusion of MSO and glutamine (0.25 mm) restored the irritant-induced central sensitization. In control experiments, superfusion of either MSO or glutamine alone, or vehicle, did not produce any significant changes in neuronal properties. These findings suggest that the astroglial glutamate–glutamine shuttle is essential for the initiation of inflammation-induced central sensitization but that inhibition of astroglial function may not affect normal nociceptive processing.
Immunotherapy Targeting Pathological Tau Conformers in a Tangle Mouse Model Reduces Brain Pathology with Associated Functional Improvements
Authors: Asuni Ayodeji A. , Boutajangout Allal , Quartermain David , Sigurdsson Einar M.
Published: August 2007

Immunotherapies for various neurodegenerative diseases have recently emerged as a promising approach for clearing pathological protein conformers in these disorders. This type of treatment has not been assessed in models that develop neuronal tau aggregates as observed in frontotemporal dementia and Alzheimer's disease. Here, we present that active immunization with a phosphorylated tau epitope, in P301L tangle model mice, reduces aggregated tau in the brain and slows progression of the tangle-related behavioral phenotype. Females had more tau pathology than males but were also more receptive to the immunotherapy. The tau antibodies generated in these animals recognized pathological tau on brain sections. Performance on behavioral assays that require extensive motor coordination correlated with tau pathology in corresponding brain areas, and antibody levels against the immunogen correlated inversely with tau pathology. Interestingly, age-dependent autoantibodies that recognized recombinant tau protein but not the immunogen were detected in the P301L mice. To confirm that anti-tau antibodies could enter the brain and bind to pathological tau, FITC-tagged antibodies purified from a P301L mouse, with a high antibody titer against the immunogen, were injected into the carotid artery of P301L mice. These antibodies were subsequently detected within the brain and colocalized with PHF1 and MC1 antibodies that recognize pathological tau. Currently, no treatment is available for clearing tau aggregates. Our present findings may lead to a novel therapy targeting one of the major hallmarks of Alzheimer's disease and frontotemporal dementia.
Actin Polymerization and ERK Phosphorylation Are Required for Arc/Arg3.1 mRNA Targeting to Activated Synaptic Sites on Dendrites
Authors: Huang Fen , Chotiner Jennifer K. , Steward Oswald
Published: August 2007

The mRNA for the immediate early geneArc/Arg3.1is induced by strong synaptic activation and is rapidly transported into dendrites, where it localizes at active synaptic sites. NMDA receptor activation is critical for mRNA localization at active synapses, but downstream events that mediate localization are not known. The patterns of synaptic activity that induce mRNA localization also trigger a dramatic polymerization of actin in the activated dendritic lamina and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) throughout the postsynaptic cytoplasm. The local polymerization of actin in the activated dendritic lamina is of particular interest because it occurs in the same dendritic domains in which newly synthesized Arc/Arg3.1 mRNA localizes. Here, we explore the role of activity-induced alterations in the actin network and mitogen-activated protein (MAP) kinase activation in Arc/Arg3.1 mRNA localization. We show that actin polymerization induced by high-frequency stimulation is blocked by local inhibition of Rho kinase, and Arc/Arg3.1 mRNA localization is abrogated in the region of Rho kinase blockade. Local application of latrunculin B, which binds to actin monomers and inhibits actin polymerization, also blocked the targeting of Arc/Arg3.1 mRNA to activated synaptic sites. Local application of the MAP kinase kinase inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-amino-phenylthio]butadiene) blocked ERK phosphorylation, and also blocked Arc/Arg3.1 mRNA localization. Our results indicate that the reorganization of the actin cytoskeletal network in conjunction with MAP kinase activation is required for targeting newly synthesized Arc/Arg3.1 mRNA to activated synaptic sites.
Different Species of α-Synuclein Oligomers Induce Calcium Influx and Seeding
Authors: Danzer Karin M. , Haasen Dorothea , Karow Anne R. , Moussaud Simon , Habeck Matthias , Giese Armin , Kretzschmar Hans , Hengerer Bastian , Kostka Marcus
Published: August 2007

Aggregation of α-synuclein (α-syn) has been linked to the pathogenesis of Parkinson's disease (PD) and other neurodegenerative diseases. Increasing evidence suggests that prefibrillar oligomers and protofibrils, rather than mature fibrils of α-syn, are the pathogenic species in PD. Despite extensive effort on studying oligomerization of α-syn, no studies have compared different oligomer species directly on a single-particle level and investigated their biological effects on cells. In this study, we applied a novel highly sensitive single molecule detection system that allowed a direct comparison of different oligomer types. Furthermore, we studied biological effects of different oligomer types on cells. For this purpose, we developed new oligomerization protocols, that enabled the use of these different oligomers in cell culture. We found that all of our three aggregation protocols resulted in heterogeneous populations of oligomers. Some types of oligomers induced cell death via disruption of cellular ion homeostasis by a presumably pore-forming mechanism. Other oligomer types could directly enter the cell resulting in increased α-syn aggregation. Based on our results, we propose that under various physiological conditions, heterogeneous populations of oligomeric forms will coexist in an equilibrium. These different oligomer types lead directly or indirectly to cell damage. Our data indicate that inhibition of early α-syn aggregation events would consequently prevent all α-syn oligomer related toxicities. This has important implications for the development of disease-modifying drugs for the treatment of PD and other synucleinopathies.
Design and construction of the New Sheppey Crossing, UK
Authors: Clough R. , Parsons J.
Published: August 2007

The £100 million A249 Iwade bypass to Queenborough improvement scheme includes a new road bridge over the Swale and the construction of road links on either side, improving transport links between the Isle of Sheppey and mainland Kent. The Highways Agency awarded a 30-year design, build, finance and operate contract to Sheppey Route Limited in February 2004. Sheppey Route Limited's contractor, Carillion, has designed and constructed the 5·6 km long A249 Iwade bypass to Queenborough improvement. The bridge and road project were completed during summer 2006. The existing A249 crosses the Swale via a vertical lifting bridge and there are long delays to traffic when it is raised to allow shipping through. The new Swale Crossing is a vital part of the scheme and will provide major benefits by reducing congestion and improving journey times on the route because it is high enough for ships to pass underneath. This paper describes the design, fabrication, erection and construction of the new Swale High-level Crossing.
The repair and strengthening of Burnton railway viaduct, UK
Authors: McQueen W. , Goodall M. , Bell G.
Published: August 2007

Burnton railway viaduct in Ayrshire, Scotland, carries the freight-only, single-track Waterside branch line from Dalrymple Junction to Chalmerston coal yard over the Purclewan Burn and the B742. The striking grade ‘B’ listed structure was constructed in 1889, is curved in plan and comprises 16 masonry arch spans. A permanent speed restriction of 5 miles/h had been imposed on the line and the structure was being constantly monitored in real time using accelerometers attached to the arch intrados and the vertical face of the spandrel walls. In 2001 the structure began to exhibit an increase in ‘liveliness' during the passage of the trains. This movement was investigated by Railtrack engineering staff as a matter of urgency. As part of their commitment to maintain the safe and efficient operation of the railway, Railtrack (succeeded by Network Rail) commissioned John Mowlem Ltd (now Carillion JM Ltd), through its alliance contract, to investigate the problem and prepare a cost-effective solution in accordance with the line classification. In turn, Carillion appointed Scott Wilson Scotland Ltd (SWSL) as its designer. Initially, SWSL and Carillion undertook a joint investigation of the viaduct, which was quickly followed by an assessment of the structure. This confirmed that there was a need to undertake a comprehensive programme of strengthening and refurbishment. This paper describes the techniques adopted to stabilise the viaduct and the methods of construction.
REGIONAL EXTENT OF AN ECOSYSTEM ENGINEER: EARTHWORM INVASION IN NORTHERN HARDWOOD FORESTS
Authors: Holdsworth Andrew R. , Frelich Lee E. , Reich Peter B.
Published: August 2007

The invasion of exotic earthworms into northern temperate and boreal forests previously devoid of earthworms is an important driver of ecosystem change. Earthworm invasion can cause significant changes in soil structure and communities, nutrient cycles, and the diversity and abundance of herbaceous plants. However, the regional extent and patterns of this invasion are poorly known. We conducted a regional survey in the Chippewa and Chequamegon National Forests, in Minnesota and Wisconsin, USA, respectively, to measure the extent and patterns of earthworm invasion and their relationship to potential earthworm introduction sites. We sampled earthworms, soils, and vegetation in 20 mature, sugar maple‐dominated forest stands in each national forest and analyzed the relationship between the presence of five earthworm taxonomic groups, habitat variables, and distance to the nearest potential introduction site. Earthworm invasion was extensive but incomplete in the two national forests. Four of the six earthworm taxonomic groups occurred in 55–95% of transects; however 20% of all transects were invaded by only one taxonomic group that has relatively minor ecological effects. Earthworm taxonomic groups exhibited a similar sequence of invasion found in other studies:Dendrobaena>Aporrectodea=Lumbricusjuveniles >L. rubellus>L. terrestris.Distance to the nearest road was the best predictor of earthworm invasion in Wisconsin while distance to the nearest cabin was the best predictor in Minnesota. These data allow us to make preliminary assessments of landscape patterns of earthworm invasion. As an example, we estimate that 82% of upland mesic hardwood stands in the Wisconsin region are likely invaded by most taxonomic groups while only 3% are unlikely to be invaded at present. Distance to roads and cabins provides a coarse‐scale predictor of earthworm invasion to focus stand‐level assessments that will help forest managers better understand current and potential forest conditions and identify uninvaded areas that could serve as important refugia for plant species threatened by earthworm invasion.
INTERRELATIONSHIPS AMONG SHRUB ENCROACHMENT, LAND MANAGEMENT, AND LITTER DECOMPOSITION IN A SEMIDESERT GRASSLAND
Authors: Throop Heather L. , Archer Steven R.
Published: August 2007

Encroachment of woody plants into grasslands, and subsequent brush management, are among the most prominent changes to occur in arid and semiarid systems over the past century. Despite the resulting widespread changes in landcover, substantial uncertainty about the biogeochemical impacts of woody proliferation and brush management exists. We explored the role of shrub encroachment and brush management on leaf litter decomposition in a semidesert grassland where velvet mesquite (Prosopis velutina) abundance has increased over the past 100 years. This change in physiognomy may affect decomposition directly, through altered litter quality or quantity, and indirectly through altered canopy structure. To assess the direct and indirect impacts of shrubs on decomposition, we quantified changes in mass, nitrogen, and carbon in litterbags deployed under mesquite canopies and in intercanopy zones. Litterbags contained foliage from mesquite and Lehmann lovegrass (Eragrostis lehmanniana), a widespread, nonnative grass in southern Arizona. To explore short‐ and long‐term influences of brush management on the initial stages of decomposition, litterbags were deployed at sites where mesquite canopies were removed three weeks, 45 years, or 70 years prior to study initiation.

Mesquite litter decomposed more rapidly than lovegrass, but negative indirect influences of mesquite canopies counteracted positive direct effects. Decomposition was positively correlated with soil infiltration into litterbags, which varied with microsite placement, and was lowest under canopies. Low under‐canopy decomposition was ostensibly due to decreased soil movement associated with high under‐canopy herbaceous biomass. Decomposition rates where canopies were removed three weeks prior to study initiation were comparable to those beneath intact canopies, suggesting that decomposition was driven by mesquite legacy effects on herbaceous cover‐soil movement linkages. Decomposition rates where shrubs were removed 45 and 70 years prior to study initiation were comparable to intercanopy rates, suggesting that legacy effects persist less than 45 years.

Accurate decomposition modeling has proved challenging in arid and semiarid systems but is critical to understanding biogeochemical responses to woody encroachment and brush management. Predicting brush‐management effects on decomposition will require information on shrub–grass interactions and herbaceous biomass influences on soil movement at decadal timescales. Inclusion of microsite factors controlling soil accumulation on litter would improve the predictive capability of decomposition models.
WILLOW ON YELLOWSTONE'S NORTHERN RANGE: EVIDENCE FOR A TROPHIC CASCADE?
Authors: Beyer Hawthorne L. , Merrill Evelyn H. , Varley Nathan , Boyce Mark S.
Published: August 2007

Reintroduction of wolves (Canis lupus) to Yellowstone National Park in 1995–1996 has been argued to promote a trophic cascade by altering elk (Cervus elaphus) density, habitat‐selection patterns, and behavior that, in turn, could lead to changes within the plant communities used by elk. We sampled two species of willow (Salix boothii and S. geyeriana) on the northern winter range to determine whether (1) there was quantitative evidence of increased willow growth following wolf reintroduction, (2) browsing by elk affected willow growth, and (3) any increase in growth observed was greater than that expected by climatic and hydrological factors alone, thereby indicating a trophic cascade caused by wolves. Using stem sectioning techniques to quantify historical growth patterns we found an approximately twofold increase in stem growth‐ring area following wolf reintroduction for both species of willow. This increase could not be explained by climate and hydrological factors alone; the presence of wolves on the landscape was a significant predictor of stem growth above and beyond these abiotic factors. Growth‐ring area was positively correlated with the previous year's ring area and negatively correlated with the percentage of twigs browsed from the stem during the winter preceding growth, indicating that elk browse impeded stem growth. Our results are consistent with the hypothesis of a behaviorally mediated trophic cascade on Yellowstone's northern winter range following wolf reintroduction. We suggest that the community‐altering effects of wolf restoration are an endorsement of ecological‐process management in Yellowstone National Park.
THE IMPORTANCE OF PROTECTED AREAS FOR THE FOREST AND ENDEMIC AVIFAUNA OF SULAWESI (INDONESIA)
Authors: Lee Tien Ming , Sodhi Navjot S. , Prawiradilaga Dewi M.
Published: August 2007

Protected areas are critical for the conservation of residual tropical forest biodiversity, yet many of these are being deforested by humans both within and outside of their administrative boundaries. Therefore, it is critical to document the significance of protected areas for conserving tropical biodiversity, particularly in mega‐diverse Southeast Asia. We evaluated the importance of protected areas (national parks [NP], nature reserves [NR], and wildlife reserves [WR]) in preserving avifaunal diversity, particularly the endemic and forest species, on the island of Sulawesi. This island has one of the highest numbers of endemic avifauna genera (12) globally and is also experiencing heavy deforestation. Rarefaction analyses and species estimators showed that parks and reserves consistently recorded higher number of forest, endemic, and endemic forest bird species, in addition to larger population densities, than in their surrounding human‐modified areas across eight protected areas (Gunung Manembo‐nembo WR, Tangkoko‐Batu Angus and Dua Saudara NR, Gunung Ambang NR, Bogani Nani Wartabone NP, Gunung Tinombala NR, Gunung Sojol NR, Lore Lindu NP, and Rawa Aopa Watumohai NP). This implies that protecting natural forests must remain as one of the fundamental conservation strategies in Sulawesi. Two small reserves (Gunung Manembo‐nembo WR and Tangkoko‐Batu Angus and Dua Saudara NR), however, had high number of forest and endemic bird species both within and outside their boundaries, suggesting the importance of buffer areas for augmenting small reserves so as to improve their conservation value. Ordination analyses revealed the differential response of bird species to different environmental factors (e.g., native tree cover), highlighting the significance of forested habitats with dense native vegetation cover for effective conservation of forest dependent and endemic avifauna. In addition, the distinctiveness in bird species composition among protected areas highlights the importance of establishing a reserve network across major altitudinal zones so as to achieve maximum complementarity for the conservation of Sulawesi's unique avifauna.
A CROSS‐REGIONAL ASSESSMENT OF THE FACTORS AFFECTING ECOLITERACY: IMPLICATIONS FOR POLICY AND PRACTICE
Authors: Pilgrim Sarah , Smith David , Pretty Jules
Published: August 2007

The value of accumulated ecological knowledge, termed ecoliteracy, is vital to both human and ecosystem health. Maintenance of this knowledge is essential for continued support of local conservation efforts and the capacity of communities to self‐ or co‐manage their local resources sustainably. Most previous studies have been qualitative and small scale, documenting ecoliteracy in geographically isolated locations. In this study, we take a different approach, focusing on (1) the primary factors affecting individual levels of ecoliteracy, (2) whether these factors shift with economic development, and (3) if different knowledge protection strategies are required for the future. We compared non‐resource‐dependent communities in the United Kingdom with resource‐dependent communities in India and Indonesia (n = 1250 interviews). We found that UK residents with the highest levels of ecoliteracy visited the countryside frequently, lived and grew up in rural areas, and acquired their knowledge from informal word‐of‐mouth sources, such as parents and friends, rather than television and schooling. The ecoliteracy of resource‐dependent community members, however, varied with wealth status and gender. The least wealthy families depended most on local resources for their livelihoods and had the highest levels of ecoliteracy. Gender roles affected both the level and content of an individual's ecoliteracy. The importance of reciprocal oral transfer of this knowledge in addition to direct experience to the maintenance of ecoliteracy was apparent at all sites. Lessons learned may contribute to new local resource management strategies for combined ecoliteracy conservation. Without novel policies, local community management capacity is likely to be depleted in the future.