bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a cis‐acting element required for dendritic targeting of activity‐regulated cytoskeleton‐associated protein mRNA
Authors: Kobayashi Hiroaki , Yamamoto Sachiya , Maruo Tomohiko , Murakami Fujio
Published: December 2005

The mRNA encoding activity‐regulated cytoskeleton‐associated protein (Arc) is known to be targeted to dendritic regions that have received strong synaptic inputs. However, the cis‐acting elements in Arc mRNA that mediate dendritic targeting have not been identified. To identify the dendritic targeting element (DTE) in rat Arc mRNA, we expressed reporter mRNAs containing various regions of Arc in primary hippocampal neurones and analysed their subcellular distribution by in situ hybridization. Here, we report that the 3′‐untranslated region of rat Arc mRNA contains a 350‐nucleotide DTE with strong dendritic targeting activity and another 370‐nucleotide sequence with weaker dendritic targeting activity. The 350‐nucleotide DTE does not share any obvious sequence similarity with other known DTEs previously reported.
Bi‐directional regulation of postsynaptic cortactin distribution by BDNF and NMDA receptor activity
Authors: Iki Junko , Inoue Akihiro , Bito Haruhiko , Okabe Shigeo
Published: December 2005

Cortactin is an F‐actin‐associated protein which interacts with the postsynaptic scaffolding protein Shank at the SH3 domain and is localized within the dendritic spine in the mouse neuron. Green fluorescent protein (GFP)‐based time‐lapse imaging revealed cortactin redistribution from dendritic cytoplasm to postsynaptic sites by application of brain‐derived neurotrophic factor (BDNF). This response was mediated by mitogen‐activated protein (MAP) kinase activation and was dependent on the C‐terminal SH3 domain. In contrast, activation of N‐methyl‐d‐aspartate (NMDA) receptors induced loss of cortactin from postsynaptic sites. This NMDA‐dependent redistribution was blocked by an Src family kinase inhibitor. Conversely, increasing Src family kinase activity induced cortactin phosphorylation and loss of cortactin from the postsynaptic sites. Finally, blocking of endogenous BDNF reduced the amount of cortactin at the postsynaptic sites and an NMDA receptor antagonist prevented this reduction. These results indicate the importance of counterbalance between BDNF and NMDA receptor‐mediated signalling in the reorganization of the postsynaptic actin cytoskeleton during neuronal development.
Dopamine regulates melanopsin mRNA expression in intrinsically photosensitive retinal ganglion cells
Authors: Sakamoto Katsuhiko , Liu Cuimei , Kasamatsu Manami , Pozdeyev Nikita V. , Iuvone P. Michael , Tosini Gianluca
Published: December 2005

In mammals a subpopulation of retinal ganglion cells are intrinsically photosensitive (ipRGCs), express the photopigment melanopsin, and play an important role in the regulation of the nonimage‐forming visual system. We have recently reported that melanopsin mRNA and protein levels in the rat retina are under photic and circadian control. The aim of the present work was to investigate the mechanisms that control melanopsin expression in the rat retina. We discovered that dopamine (DA) is involved in the regulation of melanopsin mRNA, possibly via dopamine D2 receptors that are located on these ipRGCs. Interestingly, we also discovered that pituitary adenylate cyclase‐activating peptide (PACAP) mRNA levels are affected by DA. Dopamine synthesis and release in the retina are regulated by the rod and the cone photoreceptors via retinal circuitry; our new data indicate that DA controls melanopsin expression, indicating that classical photoreceptors may modulate the transcription of this new photopigment. Our study also suggests that DA may have an important role in mediating the light signals that are used for circadian entrainment and for other responses that are mediated by the nonimage‐forming visual system.
Influence of photoperiodic history on clock genes and the circadian pacemaker in the rat retina
Authors: Rohleder Nils , Langer Christina , Maus Christian , Spiwoks‐Becker Isabella , Emser Angela , Engel Lydia , Spessert Rainer
Published: December 2005

The influence of seasonal lighting conditions on expression of clock genes and the circadian pacemaker was investigated in the rat retina. For this purpose, the 24‐h profiles of nine clock genes (bmal1, clock, per1, per2, per3, dec1, dec2, cry1 and cry 2) and the arylalkylamine N‐acetyltransferase gene as an indicator of the circadian pacemaker output were compared between light–dark periods of 8 : 16 and 16 : 8 h. The photoperiod influenced the daily patterns of the amount of transcript for per1, per3, dec2 and arylalkylamine N‐acetyltransferase. This indicates that photoperiodic information modulates clock gene expression in addition to the circadian pacemaker of the retina. Under constant darkness, photoperiod‐dependent changes in the daily profile of the level of transcript persisted for the arylalkylamine N‐acetyltransferase gene but not for any of the clock genes. Hence, quantitative expression of each clock gene is influenced by the photoperiod only under the acute light–dark cycle, whereas the pacemaker is capable of storing photoperiodic information from past cycles.
Increased mRNA levels of tyrosine hydroxylase and dopamine transporter in the VTA of male rats after chronic food restriction
Authors: Lindblom Jonas , Johansson Andreas , Holmgren Andreas , Grandin Elisabeth , Nedergård Carina , Fredriksson Robert , Schiöth Helgi B.
Published: December 2005

Dieting as a strategy to reduce body weight often fails as it causes food cravings leading to bingeing and weight regain. Evidence from several lines of research suggests the presence of shared elements for neural regulation of food and drug craving. We quantified the expression of eight genes involved in dopamine signalling in brain regions related to the mesolimbic and nigrostriatal dopamine system in male rats subjected to chronic food restriction using quantitative real‐time polymerase chain reaction. Food restriction strongly increased mRNA levels of tyrosine hydroxylase and the dopamine transporter in the ventral tegmental area. Quantitative autoradiography indicated that the dopamine transporter was also upregulated at the protein level in the shell of the nucleus accumbens. However, these effects were not observed after acute food deprivation. We suggest that the results reflect a sensitization of the mesolimbic dopamine pathway characterized by increased clearance of extracellular dopamine in the nucleus accumbens shell. Such sensitization of the mesolimbic dopamine system may be one of the underlying causes for the food cravings that interfere with dietary compliance.
Deep biosphere‐related bacteria within the subsurface of tidal flat sediments
Authors: Wilms Reinhard , Köpke Beate , Sass Henrik , Chang Tae Soo , Cypionka Heribert , Engelen Bert
Published: December 2005

Biogeochemical and microbiological processes in the upper sediment layers of tidal flats were analysed in many investigations, while deeper zones remained largely unexplored. Therefore, denaturant gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene fragments along the depth profile of up to 5.5 m‐long sediment cores was performed in comparison with lithological and geochemical parameters. The investigation revealed that different compartments of the sediment columns were characterized by specific microbial communities. These compartments were analysed by sequencing of 113 DGGE bands. The upper layers down to 160–200 cm were dominated by gamma‐ and delta‐Proteobacteria representing more than 60% of the total number of phylotypes. Underneath, a striking shift in community composition was observed, as the Proteobacteria were replaced by Chloroflexi with more than 60% of all sequences. As sulfate was still available as an electron acceptor in these layers, the abundance of Chloroflexi might be promoted by the electron donor or the quality of the carbon source. The dominance of this group, previously known as green non‐sulfur bacteria, indicates the presence of a typical deep‐biosphere microbial community in relatively young subsurface sediments. Thus, tidal flats might offer a convenient possibility to study and understand certain aspects of the deep biosphere in general.
Denaturing gradient electrophoresis (DGE) and single‐strand conformation polymorphism (SSCP) molecular fingerprintings revisited by simulation and used as a tool to measure microbial diversity
Authors: Loisel Patrice , Harmand Jérôme , Zemb Olivier , Latrille Eric , Lobry Claude , Delgenès Jean‐Philippe , Godon Jean‐Jacques
Published: December 2005

The exact extent of microbial diversity remains unknowable. Nevertheless, fingerprinting patterns [denaturing gradient electrophoresis (DGE), single‐strand conformation polymorphism (SSCP)] provide an image of a microbial ecosystem and contain diversity data. We generated numerical simulation fingerprinting patterns based on three types of distribution (uniform, geometric and lognormal) with a range of units from 10 to 500 000. First, simulated patterns containing a diversity of around 1000 units or more gave patterns similar to those obtained in experiments. Second, the number of bands or peaks saturated quickly to about 35 and were unrelated to the degree of diversity. Finally, assuming lognormal distribution, we used an estimator of diversity on in silico and experimental fingerprinting patterns. Results on in silico patterns corresponded to the simulation inputs. Diversity results in experimental patterns were in the same range as those obtained from the same DNA sample in molecular inventories. Thus, fingerprinting patterns contain extractable data about diversity although not on the basis of a number of bands or peaks, as is generally assumed to be the case.
Minocycline exerts inhibitory effects on multiple mitogen‐activated protein kinases and IκBα degradation in a stimulus‐specific manner in microglia
Authors: Nikodemova Maria , Duncan Ian D. , Watters Jyoti J.
Published: December 2005

CNS inflammation mediated by microglial activation can result in neuronal and glial cell death in a variety of neurodegenerative and demyelinating diseases. Minocycline, a second‐generation tetracycline, has profound anti‐inflammatory properties in the CNS mediated, in part, by inhibition of microglia. MAPK and nuclear factor‐κB (NF‐κB) activation are hallmarks of activated microglia and they are critical for the expression of many inflammatory mediators. In the present study, we investigated minocycline effects on activation of p38, c‐Jun‐N‐terminal activated protein kinase (JNK) 1/2 and extracellular signal regulated kinase (ERK) 1/2 MAPKs and inhibitor α of NF‐κB (IκBα) degradation in BV‐2 and primary microglial cells. Our results demonstrate that minocycline has the ability to inhibit all MAPKs but these effects strongly depend on the stimulus used for MAPK activation. Minocycline significantly decreased activation of all lipopolysaccharide‐stimulated MAPKs but it was without effect on MAPKs activated by H2O2. Minocycline inhibited JNK1/2 and ERK1/2 but not p38 when stimulated by 2′,3′‐O‐(4‐benzoylbenzoyl)‐adenosine 5′‐triphosphate, indicating that minocycline affects only certain upstream signaling target(s) that are stimulus‐specific. Our data also suggest that protein kinase C (PKC) inhibition may be partially involved in the minocycline mechanism of MAPK inhibition. In addition, minocycline attenuated lipopolysaccharide‐stimulated degradation of IκBα implying a possible inhibitory role on NF‐κB transcriptional activity.
Regulation of phosphorylation of the GluR1 AMPA receptor by dopamine D2 receptors
Authors: Håkansson Kerstin , Galdi Stacey , Hendrick Joseph , Snyder Gretchen , Greengard Paul , Fisone Gilberto
Published: December 2005

In the striatum, stimulation of dopamine D2 receptors results in attenuation of glutamate responses. This effect is exerted in large part via negative regulation of AMPA glutamate receptors. Phosphorylation of the GluR1 subunit of the AMPA receptor has been proposed to play a critical role in the modulation of glutamate transmission, in striatal medium spiny neurons. Here, we have examined the effects of blockade of dopamine D2‐like receptors on the phosphorylation of GluR1 at the cAMP‐dependent protein kinase (PKA) site, Ser845, and at the protein kinase C and calcium/calmodulin‐dependent protein kinase II site, Ser831. Administration of haloperidol, an antipsychotic drug with dopamine D2 receptor antagonistic properties, increases the phosphorylation of GluR1 at Ser845, without affecting phosphorylation at Ser831. The same effect is observed using eticlopride, a selective dopamine D2 receptor antagonist. In contrast, administration of the dopamine D2‐like agonist, quinpirole, decreases GluR1 phosphorylation at Ser845. The increase in Ser845 phosphorylation produced by haloperidol is abolished in dopamine‐ and cAMP‐regulated phosphoprotein of 32 kDa (DARPP‐32) knockout mice, or in mice in which the PKA phosphorylation site on DARPP‐32 (i.e. Thr34) has been mutated (Thr34 → Ala mutant mice), and requires tonic activation of adenosine A2A receptors. These results demonstrate that dopamine D2 antagonists increase GluR1 phosphorylation at Ser845 by removing the inhibitory tone exerted by dopamine D2 receptors on the PKA/DARPP‐32 cascade.
Deformation and fluid flow during orogeny at the palaeo‐Pacific active margin of Gondwana: the Early Palaeozoic Robertson Bay accretionary complex (north Victoria Land, Antarctica)
Authors: ROSSETTI F. , TECCE F. , ALDEGA L. , BRILLI M. , FACCENNA C.
Published: December 2005

Structural investigations, integrated with X‐ray diffraction, fluid inclusion microthermometry and oxygen‐stable isotope analyses are used to reconstruct the deformation history and the palaeo‐fluid circulation during formation of the low‐grade, turbidite‐dominated Early Palaeozoic Robertson Bay accretionary complex of north Victoria Land (Antarctica). Evidence for progressive deformation is elucidated by analysing the textural fabric of chronologically distinct, thrust‐related quartz vein generations, incrementally developed during progressive shortening and thickening of the Robertson Bay accretionary complex. Our data attest that orogenic deformation was mainly controlled by dissolution–precipitation creep, modulated by stress‐ and strain‐rate‐dependent fluid pressure cycling, associated with local and regional permeability variations induced by the distribution and evolution of the fracture network during regional thrusting. Fracture‐related fluid pathways constituted efficient conduits for episodic fluid flow. The dominant migrating fluid was pre‐to‐syn‐folding and associated with the migration of warm (160–200 °C) nitrogen‐ and carbonic (CO2 and CH4)‐bearing fluids. Both fluid advection and diffusive mass transfer are recognized as operative mechanisms for fluid–rock interaction and vein formation during continuous shortening. In particular, fluid–rock interaction was the consequence of dissolution–precipitation creep assisted by tectonically driven cooling fluids moving through the rock section as a result of seismic pumping. The most likely source of the migrating fluids would be the frontal part of the growing accretionary complex, where fluids from the deep levels in the hinterland are driven trough channelization operated by the thrust‐related fracture (fault) systems.
Influenza and Pneumococcal Vaccination in Older Veterans: Results from the Behavioral Risk Factor Surveillance System
Authors: Chi Ru‐Chien , Reiber Gayle E. , Neuzil Kathleen M.
Published: December 2005

OBJECTIVES: To compare influenza and pneumococcal vaccination rates of older veterans with those of nonveterans and to compare vaccination rates of veterans who receive care at U.S. Department of Veterans Affairs (VA) medical centers with those of veterans who do not.

DESIGN: Cross‐sectional population‐based study.

SETTING: United States and territories.

PARTICIPANTS: Persons aged 65 and older who participated in the 2003 Behavioral Risk Factor Surveillance System.

MEASUREMENTS: Telephone survey of sociodemographics factors, including veteran status and VA care, health and behavioral characteristics, and influenza and pneumococcal vaccine use.

RESULTS: Thirty percent of adults aged 65 and older were veterans, and 21% of veterans reported receiving care at VA health facilities. Veterans, especially VA users, were older and described poorer self‐perceived health than nonveterans. Influenza and pneumococcal vaccination rates were higher for veterans than for nonveterans (74% vs 68% and 68% vs 63%, respectively, P<.001 for both) and for VA users than non‐VA users (80% vs 72% and 81% vs 64%, respectively, P<.001 for both). For veterans, VA care was independently associated with influenza (odds ratio (OR)=1.8, 95% confidence interval (CI)=1.5–2.2) and pneumococcal (OR=2.4, 95% CI=2.0–2.9) vaccine use after adjusting for sociodemographics factors, perceived health status, diabetes mellitus, asthma, and smoking. Current smoking and black race were independent predictors of low influenza vaccine uptake.

CONCLUSION: VA care was associated with improved influenza and pneumococcal vaccine coverage, although vaccination rates for all elderly veterans fell short of Healthy People 2010 goals. Increased efforts to reach undervaccinated groups, particularly blacks and smokers, are warranted.
Therapeutic Exercise and Depressive Symptoms After Stroke
Authors: Lai Sue‐Min , Studenski Stephanie , Richards Lorie , Perera Subashan , Reker Dean , Rigler Sally , Duncan Pamela W.
Published: December 2005

OBJECTIVES: To examine the effect of exercise on depressive symptoms and the effect of baseline depressive symptoms on the benefits from exercise in stroke survivors who have completed acute rehabilitation.

DESIGN: Planned secondary analysis of the data from a 9‐month randomized, controlled trial.

SETTING: Participant homes.

PARTICIPANTS: One hundred stroke survivors who had completed acute rehabilitation.

INTERVENTION: A progressive, structured, 3‐month physical exercise program.

MEASUREMENTS: Demographics, stroke characteristics, impairments, functional limitations, the Geriatric Depression Scale, the Stroke Impact Scale, and the Medical Outcomes Study 36‐Item Short Form.

RESULTS: Baseline rates of depressive symptoms and other stroke sequelae were similar between the two arms. Ninety‐three participants were assessed immediately after the intervention (3 months after enrollment), and 80 were assessed 9 months after enrollment. Six (14%) of the exercise group and 16 (35.6%) of the usual‐care group had depressive symptoms at 3 months (P=.03). At 9 months, three (7.5%) of the exercisers had significant depressive symptoms compared with 10 (25%) who received usual care (P=.07). Participants with and without baseline depressive symptoms had equivalent treatment‐related gains in impairments and functional limitations, but only participants with depressive symptoms had improved quality of life.

CONCLUSION: Exercise may help reduce poststroke depressive symptoms. Depressive symptoms do not limit gains in physical function due to exercise. Exercise may contribute to improved quality of life in those with poststroke depressive symptoms.
Soft tissue myxoma: report of an unusual case located on the gingiva
Authors: Perrotti Vittoria , Rubini Corrado , Fioroni Massimiliano , Piattelli Adriano
Published: December 2005

Background: Soft tissue myxoma of the oral cavity is rare. Only three cases of myxoma of gingiva have been reported in the literature. We present a case of soft tissue myxoma arising from the left maxillary adherent gingiva in a 42‐year‐old female patient.

Methods: Histological examination showed spindle‐shaped cells in a myxoid stroma. Immunohistochemical stains with S‐100 protein were negative, while those with vimentin were positive.

Results: Clinical examination revealed a soft tissue mass, with tense elastic consistency on palpation. The overlying mucosa was normal and healthy. A clinical diagnosis of fibroma was given. Histological examination showed spindle‐shaped and stellate cells, arranged in a myxoid fibrous stroma, with collagen fibres distributed uniformly. Scattered islands or strands of inactive odontogenic epithelium were present. On the basis of the histological and immunohistochemical findings, the final diagnosis was soft tissue myxoma.

Conclusions: Further studies are necessary to clarify the origin and histogenesis of this lesion.
A review of the effects of stannous fluoride on gingivitis
Authors: Paraskevas S. , Van Der Weijden G. A.
Published: December 2005

Aim: To review the literature on the effects of stannous fluoride on gingivitis.

Material and Methods: The Medline and cochrane central register of controlled trials were searched up to August 2005 to identify appropriate studies. The primary outcome measure was gingivitis.

Results: Independent screening of titles and abstracts of 542 papers resulted in 36 publications (inter‐reviewer ê score of 0.76), out of which 15 papers finally fulfilled the criteria of eligibility. For SnF2dentifrices, a statistically significant reduction in gingivitis was noted in comparison with control (weighted mean difference (WMD) of 0.15 (gingival index) and 0.21 (gingivitis severity index) (test for heterogeneity p<0.00001, I2=91.1% and p=0.03, I2=80.1%, respectively)). With regard to plaque reduction inconsistent results existed. On using the plaque index no differences were found, whereas meta‐analysis of the Turesky index provided a WMD of 0.31 (p=0.01, test for heterogeneity p<0.0001, I2=91.7%). Because of insufficient data, a meta‐analysis for SnF2mouth rinse and dentifrice/mouthrinse formulations was not performed.

Conclusions: The use of SnF2 dentifrices results in gingivitis and plaque reduction when compared with a conventional dentifrice. The precise magnitude of this effect was difficult to assess because of a high level of heterogeneity in study outcomes.
The effect of wear on ultrasonic scaler tip displacement amplitude
Authors: Lea Simon C. , Landini Gabriel , Walmsley A. Damien
Published: December 2005

Aim: During clinical usage, scaler tips may become worn and reduced in length. It is unknown what effect wear has on the magnitude of scaler tip vibrations when they are utilized under typical clinical loads. The aim of this investigation was to assess the effect of simulated wear on ultrasonic scaler tip displacement amplitude, using a scanning laser vibrometer.

Materials and Methods: A Cavitron SPS (Dentsply) ultrasonic generator and three scaler insert designs (FSI‐100, FSI‐1000 and FSI‐SLI‐10S) were selected for the investigation. Tip vibration displacement amplitude was assessed unloaded and then contacting against tooth surfaces with loads of 0.5 and 1.0 N. Tips were then ground down by 1 mm and then 2 mm and scans were repeated.

Results: For all tips, load and length were found to be significant variables (p<0.0001). The scaler tips showed a fall in displacement amplitude with a reduction in tip length. However, all scaler tips showed variability in the amount oscillation that occurred. This was most pronounced with FSI‐SLI‐10S.

Conclusions: This investigation demonstrated that tip wear could affect the performance of dental ultrasonic scaler inserts by reducing their vibration displacement amplitude. Clinicians should be aware of this variability, which may be significant enough to affect clinical procedures.
Oral malodor‐related parameters in the Chinese general population
Authors: Liu Xue Nan , Shinada Kayoko , Chen Xiao Chi , Zhang Bo Xue , Yaegaki Ken , Kawaguchi Yoko
Published: December 2005

Objectives: To estimate the prevalence of halitosis in the Chinese population and to assess the relationships between halitosis and oral health, social and behavioural factors.

Methods: The correlation between the incidence of oral malodor and oral health was surveyed in a sample of 2000 individuals (1000 males and 1000 females) aged 15–64 years residing in urban and rural areas. Malodor was measured with both organoleptic measurements and with a portable sulphide monitor. Assessment of oral health included decayed, missing and filled teeth (DMFT), periodontal status, dental plaque, and tongue coating. Behavioural and social factors related with oral health or halitosis were also investigated.

Results: The prevalence of halitosis was 27.5% according to the organoleptic score. The level of volatile sulphur compounds (VSCs) in mouth air was significantly lower in males and in some of the age groups after lunch. Age and location of residence (rural or urban areas) did not influence the VSCs concentration in mouth air. The amount of tongue coating played the most important role in increasing VSCs concentration in mouth air, followed by periodontal status and plaque index values. DMFT, social, and behavioural factors did not contribute to halitosis.

Conclusions: Tongue coating score, modified sulcus bleeding index and calculus index were factors significantly related to oral malodor in this study.
Cynical hostility as a determinant of toothbrushing frequency and oral hygiene
Authors: Mettovaara Hanna‐Leena , Suominen‐Taipale Anna‐Liisa , Uutela Antti K. , Martelin Tuija P. , Knuuttila Matti L.E.
Published: December 2005

Aim:

Our aim was to investigate whether cynical hostility, self‐reported toothbrushing frequency and objectively assessed levels of oral hygiene were associated.

Material and Methods: The present study sample consisted of 4156 30–64‐year‐old dentate Finns. The questionnaire and the home interview included information about socioeconomic and sociodemographic factors and behavioural variables, such as toothbrushing frequency, dental attendance, smoking and cynical hostility. The level of oral hygiene was assessed during a clinical oral examination. The χ2 test and ordinal logistic regression analyses were used.

Results: After controlling for sociodemographic and socioeconomic factors, smoking habits and reported dental attendance, the subjects belonging to the lowest cynical hostility level were found to brush their teeth significantly more often and to have better oral hygiene compared with those belonging the highest cynical hostility level. Toothbrushing frequency was adjusted when oral hygiene was used as the outcome variable. The association of cynical hostility with toothbrushing frequency and the oral hygiene seems to be partly dependent on the level of education.

Conclusions: Cynical hostility is a psychosocial risk marker for the frequency and quality of toothbrushing and it could be a connecting trait between general health behaviour and oral health behaviour.
Autogenous bone graft in conjunction with enamel matrix derivative in the treatment of deep periodontal intra‐osseous defects: a report of 13 consecutively treated patients
Authors: Trombelli Leonardo , Annunziata Marco , Belardo Salvatore , Farina Roberto , Scabbia Alessandro , Guida Luigi
Published: December 2005

Aim: The purpose of the present study was to investigate the effectiveness of a regenerative procedure based on supra‐crestal soft tissue preservation in association with combined autogenous bone (AB) graft/enamel matrix derivative (EMD) application in the treatment of deep periodontal intra‐osseous defects.

Methods: Thirteen consecutively treated patients, seven females and six males, aged 30–65 years, three smokers, were included. A total of 15 deep, one‐ to two‐wall intra‐osseous defects were selected. Immediately before surgery and 6 months after surgery, pocket probing depth (PPD), clinical attachment level (CAL), and gingival recession (REC) were recorded.

Results: PPD amounted to 9.4±1.8 mm before surgery, and decreased to 4.7±1.2 mm post‐surgery (p<0.0000). CAL varied from 10.5±2.0 mm pre‐surgery to 6.2±1.7 mm post‐surgery (p<0.0000), with CAL gain averaging 4.3±1.4 mm. Fourteen (93.3%) defects presented CAL gain 3 mm. REC change was 0.4±0.7 mm.

Conclusions: Results from the present study indicated that a regenerative procedure based on supra‐crestal soft tissue preservation and combined AB/EMD treatment leads to a clinically and statistically significant improvement of soft tissue conditions of deep periodontal intra‐osseous defects.
Psychiatric endophenotypes and the development of valid animal models
Authors: Gould T. D. , Gottesman I. I.
Published: December 2005

Endophenotypes are quantifiable components in the genes‐to‐behaviors pathways, distinct from psychiatric symptoms, which make genetic and biological studies of etiologies for disease categories more manageable. The endophenotype concept has emerged as a strategic tool in neuropsychiatric research. This emergence is due to many factors, including the modest reproducibility of results from studies directed toward etiologies and appreciation for the complex relationships between genes and behavior. Disease heterogeneity is often guaranteed, rather than simplified, through the current diagnostic system; inherent benefits of endophenotypes include more specific disease concepts and process definitions. Endophenotypes can be neurophysiological, biochemical, endocrine, neuroanatomical, cognitive or neuropsychological. Heritability and stability (state independence) represent key components of any useful endophenotype. Importantly, they characterize an approach that reduces the complexity of symptoms and multifaceted behaviors, resulting in units of analysis that are more amenable to being modeled in animals. We discuss the benefits of more direct interpretation of clinical endophenotypes by basic behavioral scientists. With the advent of important findings regarding the genes that predispose to psychiatric illness, we are at an important crossroads where, without anthropomorphizing, animal models may provide homologous components of psychiatric illness, rather than simply equating to similar (loosely analogized) behaviors, validators of the efficacy of current medications or models of symptoms. We conclude that there exists a need for increased collaboration between clinicians and basic scientists, the result of which should be to improve diagnosis, classification and treatment on one end and to increase the construct relevance of model organisms on the other.
Imaging the Neonatal Brain: Novel Techniques
Authors: Whitby E. H. , Griffiths P. D. , Paley M. N.
Published: December 2005

Magnetic resonance (MR) imaging of the neonate can be a difficult procedure especially when most imaging departments are geographically distant to neonatal intensive care units. These vulnerable neonates are often notable to be imaged by MR as they are too sick to transport. MR scanners are expensive pieces of equipment in specialist centres and this limits their availability. Low field strength scanners have a small capital cost and small running costs. This has allowed them to be developed for dedicated neonatal imaging in a few centres. Experience using these scanners is limited but they provide additional information over and above ultrasound imaging and are an ideal method to increase the availability of MR. MR compatible incubators that double as transport incubators reduce the amount of handling the vulnerable neonate is exposed to and maintains the environmental conditions required for the neonate. This makes access to distant MR scanners possible. Fast imaging sequences reduce the overall scanning time and reduce the need for sedation or anaesthesia. These methods allow the vulnerable neonate to be imaged safely whilst providing essential imaging information for optimal clinical management.
Cellular Analysis of Disorazole C1and Structure–Activity Relationship of Analogs of the Natural Product
Authors: Wipf Peter , Graham Thomas H. , Vogt Andreas , Sikorski Rachel P. , Ducruet Alexander P. , Lazo John S.
Published: December 2005

Structure–activity analyses of synthetic disorazole C1and eight of its analogs indicate that the presence of a vinyl oxirane moiety or a tetraene sequence is not necessary for potent cytotoxic and antimitotic properties. Using an automated multiparameter fluorescence‐based cellular assay to simultaneously probe the effects of disorazole analogs on cellular microtubules, mitotic arrest, and cytotoxicity, we found that disorazole C1enhanced the mitotic index and chromatin condensation and arrested cells in the G2/M phase of the cell cycle. All structural analogs and synthesis precursors of disorazole C1were at least two orders of magnitude less potent than the parent compound, thus indicating that both the functional group array and the three‐dimensional conformation of the parent compound are critical for interaction with the biological target. We conclude that disorazole C1is a potent inducer of mitotic arrest and hypothesize that this biological activity may be mediated by microtubule perturbation.
Restoration of Degraded Tropical Forest Landscapes
Authors: Lamb David , Erskine Peter D. , Parrotta John A.
Published: December 2005

The current scale of deforestation in tropical regions and the large areas of degraded lands now present underscore the urgent need for interventions to restore biodiversity, ecological functioning, and the supply of goods and ecological services previously used by poor rural communities. Traditional timber plantations have supplied some goods but have made only minor contributions to fulfilling most of these other objectives. New approaches to reforestation are now emerging, with potential for both overcoming forest degradation and addressing rural poverty.
Neural Systems Responding to Degrees of Uncertainty in Human Decision-Making
Authors: Hsu Ming , Bhatt Meghana , Adolphs Ralph , Tranel Daniel , Camerer Colin F.
Published: December 2005

Much is known about how people make decisions under varying levels of probability (risk). Less is known about the neural basis of decision-making when probabilities are uncertain because of missing information (ambiguity). In decision theory, ambiguity about probabilities should not affect choices. Using functional brain imaging, we show that the level of ambiguity in choices correlates positively with activation in the amygdala and orbitofrontal cortex, and negatively with a striatal system. Moreover, striatal activity correlates positively with expected reward. Neurological subjects with orbitofrontal lesions were insensitive to the level of ambiguity and risk in behavioral choices. These data suggest a general neural circuit responding to degrees of uncertainty, contrary to decision theory.
A Systems Model of Signaling Identifies a Molecular Basis Set for Cytokine-Induced Apoptosis
Authors: Janes Kevin A. , Albeck John G. , Gaudet Suzanne , Sorger Peter K. , Lauffenburger Douglas A. , Yaffe Michael B.
Published: December 2005

Signal transduction pathways control cellular responses to stimuli, but it is unclear how molecular information is processed as a network. We constructed a systems model of 7980 intracellular signaling events that directly links measurements to 1440 response outputs associated with apoptosis. The model accurately predicted multiple time-dependent apoptotic responses induced by a combination of the death-inducing cytokine tumor necrosis factor with the prosurvival factors epidermal growth factor and insulin. By capturing the role of unsuspected autocrine circuits activated by transforming growth factor–α and interleukin-1α, the model revealed new molecular mechanisms connecting signaling to apoptosis. The model derived two groupings of intracellular signals that constitute fundamental dimensions (molecular “basis axes”) within the apoptotic signaling network. Projection along these axes captures the entire measured apoptotic network, suggesting that cell survival is determined by signaling through this canonical basis set.
Response to Comment on "How Science Survived: Medieval Manuscripts' `Demography' and Classic Texts' Extinction"
Authors: Cisne John L.
Published: December 2005

Declercq's rejection of an otherwise well-supported model is based on demonstrably too narrow an interpretation of the use of Bede's
De Temporum Ratione
and on questionable appreciation of predictive modeling as a complementary alternative to traditional deductive methods. Additional evidence on library holdings further supports previous conclusions regarding the survival of medieval manuscripts.
The Chemistry of Deformation: How Solutes Soften Pure Metals
Authors: Trinkle Dallas R. , Woodward Christopher
Published: December 2005

Solutes have been added to strengthen elemental metals, generating usable materials for millennia; in the 1960s, solutes were found to also soften metals. Despite the empirical correlation between the “electron number” of the solute and the change in strength of the material to which it is added, the mechanism responsible for softening is poorly understood. Using state-of-the-art quantum-mechanical methods, we studied the direct interaction of transition-metal solutes with dislocations in molybdenum. The interaction increases dramatically with increasing electron number and strongly influences the mechanisms responsible for plasticity in these materials. Our quantitative model explains solution softening of metals by using changes in energy and stress scales of plasticity from solutes.
On the Origins of Novelty and Variation
Authors: Charlesworth Brian
Published: December 2005

The Plausibility of Life
. Resolving Darwin's Dilemma.
By Marc W. Kirschner and John C. Gerhart
. Yale University Press, New Haven, CT, 2005. 330 pp. $30, £18.95. ISBN 0-300-10865-6.

The authors hold that the accumulation of small genetic mutations over time does not explain the variety and complexity of life. Instead, they propose "facilitated variation" to account for the conversion of random genetic change into complex innovations.
Rapid Chiral Assembly of Rigid DNA Building Blocks for Molecular Nanofabrication
Authors: Goodman R. P. , Schaap I. A. T. , Tardin C. F. , Erben C. M. , Berry R. M. , Schmidt C. F. , Turberfield A. J.
Published: December 2005

Practical components for three-dimensional molecular nanofabrication must be simple to produce, stereopure, rigid, and adaptable. We report a family of DNA tetrahedra, less than 10 nanometers on a side, that can self-assemble in seconds with near-quantitative yield of one diastereomer. They can be connected by programmable DNA linkers. Their triangulated architecture confers structural stability; by compressing a DNA tetrahedron with an atomic force microscope, we have measured the axial compressibility of DNA and observed the buckling of the double helix under high loads.
Differential Subcellular Localization of Members of the
Toxoplasma gondii
Small Heat Shock Protein Family
Authors: de Miguel N. , Echeverria P. C. , Angel S. O.
Published: December 2005

The results of this study describe the identification and characterization of the
Toxoplasma gondii
α-crystallin/small heat shock protein (sHsp) family. By database (
www.toxodb.org
) search, five parasite sHsps (Hsp20, Hsp21, Hsp28, Hsp29, and the previously characterized Hsp30/Bag1) were identified. As expected, they share the homologous α-crystallin domain, which is the key characteristic of sHsps. However, the N-terminal segment of each protein contains unique characteristics in size and sequence. Most
T. gondii
sHsps are constitutively expressed in tachyzoites and fully differentiated bradyzoites, with the exception of Hsp30/Bag1. Interestingly, by subcellular localization we observed that
T. gondii
sHsps are located in different compartments. Hsp20 is located at the apical end of the cell, Hsp28 is located inside the mitochondrion, Hsp29 showed a membrane-associated labeling, and Hsp21 appeared throughout the cytosol of the parasites. These particular differences in the immunostaining patterns suggest that their targets and functions might be different.
Envoy, a PAS/LOV Domain Protein of
Hypocrea jecorina
(Anamorph
Trichoderma reesei
), Modulates Cellulase Gene Transcription in Response to Light
Authors: Schmoll Monika , Franchi Lisa , Kubicek Christian P.
Published: December 2005

Envoy, a PAS/LOV domain protein with similarity to the
Neurospora
light regulator Vivid, which has been cloned due to its lack of expression in a cellulase-negative mutant, links cellulase induction by cellulose to light signaling in
Hypocrea jecorina
. Despite their similarity,
env1
could not compensate for the lack of
vvd
function. Besides the effect of light on sporulation, we observed a reduced growth rate in constant light. An
env1
PAS−
mutant of
H. jecorina
grows significantly slower in the presence of light but remains unaffected in darkness compared to the wild-type strain QM9414.
env1
rapidly responds to a light pulse, with this response being different upon growth on glucose or glycerol, and it encodes a regulator essential for
H. jecorina
light tolerance. The induction of cellulase transcription in
H. jecorina
by cellulose is enhanced by light in the wild-type strain QM9414 compared to that in constant darkness, whereas a delayed induction in light and only a transient up-regulation in constant darkness of
cbh1
was observed in the
env1
PAS−
mutant. However, light does not lead to cellulase expression in the absence of an inducer. We conclude that Envoy connects the light response to carbon source signaling and thus that light must be considered an additional external factor influencing gene expression analysis in this fungus.
Regulation and Recovery of Functions of
Saccharomyces cerevisiae
Chaperone BiP/Kar2p after Thermal Insult
Authors: Seppä Laura , Makarow Marja
Published: December 2005

We described earlier a novel mode of regulation of Hsp104, a cytosolic chaperone directly involved in the refolding of heat-denatured proteins, and designated it delayed upregulation, or DUR. When
Saccharomyces cerevisiae
cells grown at the physiological temperature of 24°C, preconditioned at 37°C, and treated briefly at 50°C were shifted back to 24°C, Hsp104 expression was strongly induced after 2.5 h of recovery and returned back to normal after 5 h. Here we show that the endoplasmic reticulum (ER) chaperones BiP/Kar2p and Lhs1p and the mitochondrial chaperone Hsp78 were also upregulated at the physiological temperature during recovery from thermal insult. The heat shock element (HSE) in the
KAR2
promoter was found to be sufficient to drive DUR. The unfolded protein element could also evoke DUR, albeit weakly, in the absence of a functional HSE. BiP/Kar2p functions in ER translocation and assists protein folding. Here we found that the synthesis of new BiP/Kar2p molecules was negligible for more than an hour after the shift of the cells from 50°C to 24°C. Concomitantly, ER translocation was blocked, suggesting that preexisting BiP/Kar2p molecules or other necessary proteins were not functioning. Translocation resumed concomitantly with enhanced synthesis of BiP/Kar2p after 3 h of recovery, after which ER exit and protein secretion also resumed. For a unicellular organism like
S. cerevisiae
, conformational repair of denatured proteins is the sole survival strategy. Chaperones that refold proteins in the cytosol, ER, and mitochondria of
S. cerevisiae
appear to be subject to DUR to ensure survival after thermal insults.
The Polybasic Juxtamembrane Region of Sso1p Is Required for SNARE Function In Vivo
Authors: Van Komen Jeffrey S. , Bai Xiaoyang , Rodkey Travis L. , Schaub Johanna , McNew James A.
Published: December 2005

Exocytosis
in
Saccharomyces cerevisiae
requires the specific interaction
between the plasma membrane t-SNARE complex (Sso1/2p;Sec9p)and a vesicular v-SNARE (Snc1/2p). While SNARE proteins drive membrane
fusion, many aspects of SNARE assembly and regulation are ill defined.
Plasma membrane syntaxin homologs (including Sso1p) contain a highly
charged juxtamembrane region between the transmembrane helix and the“
SNARE domain” or core complex domain. We examined this
region in vitro and in vivo by targeted sequence modification,
including insertions and replacements. These modified Sso1 proteins
were expressed as the sole copy of Sso in
S. cerevisiae
and
examined for viability. We found that mutant Sso1 proteins with
insertions or duplications show limited function, whereas replacement
of as few as three amino acids preceding the transmembrane domain
resulted in a nonfunctional SNARE in vivo. Viability is also maintained
when two proline residues are inserted in the juxtamembrane of Sso1p,
suggesting that helical continuity between the transmembrane domain and
the core coiled-coil domain is not absolutely required. Analysis of
these mutations in vitro utilizing a reconstituted fusion assay
illustrates that the mutant Sso1 proteins are only moderately impaired
in fusion. These results suggest that the sequence of the juxtamembrane
region of Sso1p is vital for function in vivo, independent of the
ability of these proteins to direct membrane
fusion.
An
Ustilago maydis
Septin Is Required for Filamentous Growth in Culture and for Full Symptom Development on Maize
Authors: Boyce Kylie J. , Chang Howard , D'Souza Cletus A. , Kronstad James W.
Published: December 2005

During maize infection, the fungal pathogen
Ustilago maydis
undergoes a dimorphic transition from budding, yeast-like cells to a filamentous dikaryon that proliferates in the host. This transition is regulated by mating and environmental signals. Septation is likely to be important in the growth of the infectious dikaryon because of the need to maintain specific cellular compartments during dikaryotic growth. Recently, we found that the transcript level for a septin gene was influenced by the conserved cyclic AMP (cAMP)/protein kinase A signaling pathway that participates in regulating dimorphism in
U. maydis
. In this study, we describe the detailed analysis of the function of this septin gene, designated
sep3
, in the growth, development, and pathogenesis of
U. maydis
. We show that
sep3
is required for normal cellular morphology and the division of budding haploid cells. The gene is also required for lipid-induced filamentous growth in culture but not during the formation of mating filaments on agar medium or in planta. Strains with a deletion in
sep3
have a reduction in symptom development in maize, with filamentous cells in planta displaying morphological defects. In addition,
sep3
influences the differentiation of hyphae into teliospores and the germination of these teliospores to produce the meiotic haploid progeny that complete the disease life cycle. Finally, the deletion of
sep3
was found to influence the multiple budding phenotype of a mutant with a defect in the regulatory subunit of protein kinase A. This result is consistent with a link between
sep3
and the control of morphogenesis by cAMP signaling. Overall, this study highlights the importance of regulating septation and changes in morphology during phytopathogenesis.