bluuebunny/crossref_metadata_2025 huggingface dataset:
Ligand scaffold hopping combining 3D maximal substructure search and molecular similarity
Authors: Quintus Flavien , Sperandio Olivier , Grynberg Julien , Petitjean Michel , Tuffery Pierre
Published: August 2009

Background

Virtual screening methods are now well established as effective to identify hit and lead candidates and are fully integrated in most drug discovery programs. Ligand-based approaches make use of physico-chemical, structural and energetics properties of known active compounds to search large chemical libraries for related and novel chemotypes. While 2D-similarity search tools are known to be fast and efficient, the use of 3D-similarity search methods can be very valuable to many research projects as integration of "3D knowledge" can facilitate the identification of not only related molecules but also of chemicals possessing distant scaffolds as compared to the query and therefore be more inclined to scaffolds hopping. To date, very few methods performing this task are easily available to the scientific community.

Results

We introduce a new approach (LigCSRre) to the 3D ligand similarity search of drug candidates. It combines a 3D maximum common substructure search algorithm independent on atom order with a tunable description of atomic compatibilities to prune the search and increase its physico-chemical relevance. We show, on 47 experimentally validated active compounds across five protein targets having different specificities, that for single compound search, the approach is able to recover on average 52% of the co-actives in the top 1% of the ranked list which is better than gold standards of the field. Moreover, the combination of several runs on a single protein target using different query active compounds shows a remarkable improvement in enrichment. Such Results demonstrate LigCSRre as a valuable tool for ligand-based screening.

Conclusion

LigCSRre constitutes a new efficient and generic approach to the 3D similarity screening of small compounds, whose flexible design opens the door to many enhancements. The program is freely available to the academics for non-profit research at: http://bioserv.rpbs.univ-paris-diderot.fr/LigCSRre.html.
Efficient production of human bivalent and trivalent anti-MUC1 Fab-scFv antibodies in Pichia pastoris
Authors: Schoonooghe Steve , Kaigorodov Vladimir , Zawisza Monika , Dumolyn Caroline , Haustraete Jurgen , Grooten Johan , Mertens Nico
Published: August 2009

Background

Tumour associated antigens on the surface of tumour cells, such as MUC1, are being used as specific antibody targets for immunotherapy of human malignancies. In order to address the poor penetration of full sized monoclonal antibodies in tumours, intermediate sized antibodies are being developed. The cost-effective and efficient production of these molecules is however crucial for their further success as anti-cancer therapeutics. The methylotropicP. pastorisyeast grows in cheap mineral media and is known for its short process times and the efficient production of recombinant antibody fragments like scFvs, bivalent scFvs and Fabs.

Results

Based on the anti-MUC1 PH1 Fab, we have developed bivalent PH1 bibodies and trivalent PH1 tribodies of intermediate molecular mass by adding PH1 scFvs to the C-terminus of the Fab chains using flexible peptide linkers. These recombinant antibody derivatives were efficiently expressed in both mammalian andP. pastoriscells. Stable production in NS0 cells produced 130.5 mg pure bibody and 27 mg pure tribody per litre. This high yield is achieved as a result of the high overall purification efficiency of 77%. Expression and purification of PH1 bibodies and tribodies fromPichiasupernatant yielded predominantly correctly heterodimerised products, free of light chain homodimers. The yeast-produced bi- and tribodies retained the same specific activity as their mammalian-produced counterparts. Additionally, the yields of 36.8 mg pure bibody and 12 mg pure tribody per litre supernatant make the production of these molecules inPichiamore efficient than most other previously described trispecific or trivalent molecules produced inE. coli.

Conclusion

Bi- and tribody molecules are efficiently produced inP. pastoris. Furthermore, the yeast produced molecules retain the same specific affinity for their antigen. These results establish the value ofP. pastorisas an efficient alternative expression system for the production of recombinant multivalent Fab-scFv antibody derivatives.
High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis
Authors: Yeom Chang-Hwan , Lee Gunsup , Park Jin-Hee , Yu Jaelim , Park Seyeon , Yi Sang-Yeop , Lee Hye Ree , Hong Young Seon , Yang Joosung , Lee Sukchan
Published: August 2009

To test the carcinostatic effects of ascorbic acid, we challenged the mice of seven experimental groups with 1.7 × 10-4 mol high dose concentration ascorbic acid after intraperitoneal administrating them with sarcoma S-180 cells. The survival rate was increased by 20% in the group that received high dose concentration ascorbic acid, compared to the control. The highest survival rate was observed in the group in which 1.7 × 10-4 mol ascorbic acid had been continuously injected before and after the induction of cancer cells, rather than just after the induction of cancer cells. The expression of three angiogenesis-related genes was inhibited by 0.3 times in bFGF, 7 times in VEGF and 4 times in MMP2 of the groups with higher survival rates. Biopsy Results, gene expression studies, and wound healing analysis in vivo and in vitro suggested that the carcinostatic effect induced by high dose concentration ascorbic acid occurred through inhibition of angiogenesis.
Use of information entropy measures of sitting postural sway to quantify developmental delay in infants
Authors: Deffeyes Joan E , Harbourne Regina T , DeJong Stacey L , Kyvelidou Anastasia , Stuberg Wayne A , Stergiou Nicholas
Published: August 2009

Background

By quantifying the information entropy of postural sway data, the complexity of the postural movement of different populations can be assessed, giving insight into pathologic motor control functioning.

Methods

In this study, developmental delay of motor control function in infants was assessed by analysis of sitting postural sway data acquired from force plate center of pressure measurements. Two types of entropy measures were used: symbolic entropy, including a new asymmetric symbolic entropy measure, and approximate entropy, a more widely used entropy measure. For each method of analysis, parameters were adjusted to optimize the separation of the results from the infants with delayed development from infants with typical development.

Results

The method that gave the widest separation between the populations was the asymmetric symbolic entropy method, which we developed by modification of the symbolic entropy algorithm. The approximate entropy algorithm also performed well, using parameters optimized for the infant sitting data. The infants with delayed development were found to have less complex patterns of postural sway in the medial-lateral direction, and were found to have different left-right symmetry in their postural sway, as compared to typically developing infants.

Conclusion

The results of this study indicate that optimization of the entropy algorithm for infant sitting postural sway data can greatly improve the ability to separate the infants with developmental delay from typically developing infants.
MicroRNA expression profiling of male breast cancer
Authors: Fassan Matteo , Baffa Raffaele , Palazzo Juan P , Lloyd Joshua , Crosariol Marco , Liu Chang-Gong , Volinia Stefano , Alder Hannes , Rugge Massimo , Croce Carlo M , Rosenberg Anne
Published: August 2009

Introduction

MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. To test the hypothesis that there is a specific miRNA expression signature which characterizes male breast cancers, we performed miRNA microarray analysis in a series of male breast cancers and compared them with cases of male gynecomastia and female breast cancers.

Methods

Paraffin blocks were obtained at the Department of Pathology of Thomas Jefferson University from 28 male patients including 23 breast cancers and five cases of male gynecomastia, and from 10 female ductal breast carcinomas. The RNA harvested was hybridized to miRNA microarrays (~1,100 miRNA probes, including 326 human and 249 mouse miRNA genes, spotted in duplicate). To further support the microarray data, an immunohistochemical analysis for two specific miRNA gene targets (HOXD10 and VEGF) was performed in a small series of male breast carcinoma and gynecomastia samples.

Results

We identified a male breast cancer miRNA signature composed of a large portion of underexpressed miRNAs. In particular, 17 miRNAs with increased expression and 26 miRNAs with decreased expression were identified in male breast cancer compared with gynecomastia. Among these miRNAs, some had well-characterized cancer development association and some showed a deregulation in cancer specimens similar to the one previously observed in the published signatures of female breast cancer. Comparing male with female breast cancer miRNA expression signatures, 17 significantly deregulated miRNAs were observed (four overexpressed and 13 underexpressed in male breast cancers). The HOXD10 and VEGF gene immunohistochemical expression significantly follows the corresponding miRNA deregulation.

Conclusions

Our results suggest that specific miRNAs may be directly involved in male breast cancer development and that they may represent a novel diagnostic tool in the characterization of specific cancer gene targets.
Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells
Authors: Fehm Tanja , Hoffmann Oliver , Aktas Bahriye , Becker Sven , Solomayer Erich F , Wallwiener Diethelm , Kimmig Rainer , Kasimir-Bauer Sabine
Published: August 2009

Introduction

The role of circulating tumor cells (CTCs) in blood of primary breast cancer patients is still under investigation. We evaluated the incidence of CTCs in blood, we evaluated the correlation between CTCs and disseminated tumor cells (DTCs) in the bone marrow (BM), and we characterized CTCs for the expression of HER2, the estrogen receptor (ER) and the progesterone receptor (PR).

Methods

Blood of 431 patients with primary breast cancer were analyzed for EpCAM, MUC1 and HER2 transcripts with the AdnaTest BreastCancer™ (AdnaGen AG, Germany). Expression of the ER and PR was assessed in an additional RT-PCR. BM aspirates from 414 patients were analyzed for DTCs by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3.

Results

DTCs were found in 107/414 patients (24%), CTCs were detected in 58/431 (13%) patients. DTCs were associated with PR status of the primary tumor (P = 0.04) and CTCs significantly correlated with nodal status (P = 0.04), ER (P = 0.05), and PR (P = 0.01). DTCs in the BM weakly correlated with CTCs (P = 0.05) in blood. Interestingly, the spread of CTCs was mostly found in triple-negative tumors (P = 0.01) and CTCs in general were mostly found to be triple-negative regardless of the ER, PR and HER2 status of the primary tumor.

Conclusions

(1) Due to the weak concordance between CTCs and DTCs the clinical relevance may be different. (2) The biology of the primary tumor seems to direct the spread of CTCs. (3) Since the expression profile between CTCs and the primary tumor differs, the consequence for the selection of adjuvant treatment has to be evaluated.
RFX3 governs growth and beating efficiency of motile cilia in mouse and controls the expression of genes involved in human ciliopathies
Authors: El Zein Loubna , Ait-Lounis Aouatef , Morlé Laurette , Thomas Joëlle , Chhin Brigitte , Spassky Nathalie , Reith Walter , Durand Bénédicte
Published: August 2009

Cilia are cellular organelles that play essential physiological and developmental functions in various organisms. They can be classified into two categories, primary cilia and motile cilia, on the basis of their axonemal architecture. Regulatory factor X (RFX) transcription factors have been shown to be involved in the assembly of primary cilia in Caenorhabditis elegans, Drosophila and mice. Here, we have taken advantage of a novel primary-cell culture system derived from mouse brain to show that RFX3 is also necessary for biogenesis of motile cilia. We found that the growth and beating efficiencies of motile cilia are impaired in multiciliated Rfx3–/– cells. RFX3 was required for optimal expression of the FOXJ1 transcription factor, a key player in the differentiation program of motile cilia. Furthermore, we demonstrate for the first time that RFX3 regulates the expression of axonemal dyneins involved in ciliary motility by binding directly to the promoters of their genes. In conclusion, RFX proteins not only regulate genes involved in ciliary assembly, but also genes that are involved in ciliary motility and that are associated with ciliopathies such as primary ciliary dyskinesia in humans.
Simian virus 40 large T antigen targets the microtubule-stabilizing protein TACC2
Authors: Tei Shuchin , Saitoh Noriko , Funahara Tetsushi , Iida Shin-ichi , Nakatsu Yuko , Kinoshita Kayo , Kinoshita Yoshikazu , Saya Hideyuki , Nakao Mitsuyoshi
Published: August 2009

The large T antigens of polyomaviruses target cellular proteins that control fundamental processes, including p53 and the RB family of tumor suppressors. Mechanisms that underlie T-antigen-induced cell transformation need to be fully addressed, because as-yet unidentified target proteins might be involved in the process. In addition, recently identified polyomaviruses are associated with particular human diseases such as aggressive skin cancers. Here, we report that simian virus 40 (SV40) large T antigen interacts with the transforming acidic coiled-coil-containing protein TACC2, which is involved in stabilizing microtubules in mitosis. T antigen directly binds TACC2 and induces microtubule dysfunction, leading to disorganized mitotic spindles, slow progression of mitosis and chromosome missegregation. These mitotic defects are caused by N-terminal-deleted T antigen, which minimally interacts with TACC2, whereas T-antigen-induced microtubule destabilization is suppressed by overexpressing TACC2. Thus, TACC2 might be a key target of T antigen to disrupt microtubule regulation and chromosomal inheritance in the initiation of cell transformation.
Numerical and experimental investigation of the vibration of rotors with loose discs
Authors: Behzad M , Asayesh M
Published: August 2009

In this study, the energy method has been used to develop a finite-element code for studying the effects of loose rotating discs on the rotor—bearing systems’ response. A mathematical model of the loose disc has resulted in terms similar to unbalance and gyroscopic effects in the equation of motion of the system. Results of this study show that rotor response and beating phenomena are a function of measurement location, loose disc mass and inertia, ratio of rotating speed to the speed of loose disc, and clearance between the loose disc and shaft considering constant speed for loose disc and shaft. The developed finite-element model can numerically give the response of rotors with any number of loose discs at any location with isotropic or orthotropic supports. Results of numerical calculation have been verified by experimental tests.
A meshing principle for generating a cylindrical gear using an Archimedes hob with two degrees of freedom
Authors: Zhao Y , Su D , Wei W , Dong X
Published: August 2009

Thorough and systematic investigations are performed into the meshing principium of generating a cylindrical gear by an Archimedes hob based on the two-degree-of-freedom theory of gearing geometry. The numerical examples show the verification and validation of the formulated principium and the developed model. Conclusions suitable for industrial application are reached by means of numerical simulations.
Manufacturing ultra-high-frequency radio frequency identification tag antennas by multilayer printings
Authors: Choi B-O , Kim C H , Kim D S
Published: August 2009

In spite of the advantages of high throughput and a low manufacturing cost conferred by the gravure printing method, it has been shown that antennas printed using the gravure printing method do not offer satisfactory performance because of the limitations of the conductive materials used as ink. In this article, a roll-to-roll gravure-offset printing system is proposed for the manufacturing of printed ultra-high frequency radio frequency identification (RFID) tag antennas. Antennas printed using the multi-layer gravure-offset system are also demonstrated with their performances. The gravure-offset printing system mainly consists of three printing parts, i.e. drying units, vision systems, and register control systems for multi-layer printings. In the identification range test using an RFID reader, compared to the conventional RFID tags with copper-etched antennas, which show the identification range of about 3.2 m on average, the three-layer printed antennas with bonded tag chips exhibit the identification range of about 1.8 m on average (i.e. the performance of about 60 per cent of conventional copper-etched antennas), which implies that the printed antennas could be applicable to real fields.
Design consideration of actuator specifications in a mobile manipulator system
Authors: Lee J-Y , Yu S-N , Choi C-H , Han C-S
Published: August 2009

This article presents a servo motor selection technique for a mobile mine detection system, which is operated in the field condition. As a first step, the mine detection sensor should follow the earth profile while maintaining a constant distance to the earth surface. In order to acquire a reasonable manipulator trajectory and its required torque, a kind of modelling technique is devised to remove the unwanted fluctuations in the earth data. Then, Straete et al.'s normalization method is adopted and is improved to select the adequate actuator for each joint of the manipulator. The improvements are as follows: first, an equivalent output power lines are plotted at the same load curve, which gives another selection criterion. Second, a temperature-based criterion is proposed for the continuous limit, which estimates the steady-state winding temperature of a motor, and can be used to determine a suitable motor and gear ratio. This formulation not only gives the selection of a motor and gear ratio, but also gives the estimated operating temperature.
A note on the inverse dynamic control of parallel manipulators
Authors: Omran A , Elshabasy M
Published: August 2009

This work proposes a simple technique for inverse dynamics control of parallel mani-pulators in a joint space. In this technique, there is no need for forward kinematics, which is exacerbated by no closed-form solution for many parallel manipulators. A set of simulations is introduced to signify the validity of the proposed control technique compared with full joint feedback control.
Hydrogen: A future energy vector for sustainable development
Authors: Mandal T K , Gregory D H
Published: August 2009

The rapid exhaustion of fossil fuel reserves and the adverse effects of climate change have attracted global attention and pose serious threats to mankind. The emergence of new energy technologies based on new materials discovery is crucial if the world is to arrest the adverse effects of climate change and secure the global energy security based on sustainable and renewable energy sources. Hydrogen is thought to be the solution as a clean and renewable future energy vector. The use of hydrogen in a polymer electrolyte membrane fuel cell is likely to be at the centre of power generation for stationary and mobile applications. This review describes the present state of contemporary research on modes of hydrogen generation and storage on the basis of research carried out during the last decade. The article focuses particularly on the key aspects of fuel cells and materials based on the physical and chemical storage of hydrogen. A high storage density together with favourable sorption thermodynamics and kinetics and prolonged cycleability and lifetime are the key requirements for a practical storage material. This review emphasizes both how the engineering of fuel cells and our understanding of solid state hydrogen storages impact on the future of hydrogen storage research and the prospects for the implementation of the hydrogen economy.
How long could we wait for the delivery of the second twin?
Authors: Nkwabong E , Kamgaing Noubi N , Dadje C , Mbu R
Published: August 2009

There is no consensus about the safe time interval between the deliveries of twins. This retrospective study, conducted from 1 January 2000 to 31 December 2004 at the University Teaching Hospital of Yaoundé, Cameroon, was designed to evaluate the safe time interval between deliveries of twins. We analysed 268 twin deliveries. The mean time interval between twin deliveries was 10.0 ± 7.9 minutes. The mean fetal weight of the first twin was 2416 ± 565 g and that of the second was 2395 ± 558 g. However, in 47.7% cases, the second twin was bigger than the first. When the second twin was delivered more than 30 minutes after the first, the mean 5 minute Apgar score was low. Therefore, efforts should be made to deliver the second twin within 30 minutes after the delivery of the first baby.
The incidence, clustering and characteristics of Burkitt lymphoma in the Northwest province of Cameroon
Authors: Wright N J , Hesseling P B , McCormick P , Tchintseme F
Published: August 2009

The epidemiology of Burkitt lymphoma (BL) has never been documented in Cameroon. Data were collected from 16 hospitals, the Delegation of Public Health and the regional pathologist in the Northwest province of Cameroon on all BL cases. The incidence of BL in this region is 5.9/100,000 children aged <15 years/year – the second highest incidence documented to date. Significant clustering was also identified in Ndop, a low-lying region with a high malaria endemicity, at 21.5 cases/100,000 children aged <15 year/year ( P < 0.001).
Life-Threatening Flecainide Intoxication in a Young Child Secondary to Medication Error
Authors: D'Alessandro Lisa CA , Rieder Michael J , Gloor Jane , Freeman David , Buffo-Sequiera Ilan
Published: August 2009

Objective:

To describe a case of life-threatening flecainide intoxication in a toddler, secondary to accidental reversal of syringes used for oral administration.

Case Summary:

A 2-year-old male with a history of a persistent junctional reciprocating tachycardia had been receiving flecainide 4.8 mg/kg/day (1 mL 3 times daily) and nadolol 2 mg/kg/day (5 mL once daily) for 10 months. One morning, 3 hours after the drugs were administered, he became bradycardic (heart rate 50 beats/min) and then presented to the emergency department with vital signs absent. After initial cardiopulmonary resuscitation and epinephrine, he was bradycardic; this was followed by wide-complex tachycardia that converted rapidly to narrow-complex tachycardia after bolus administration of intravenous sodium bicarbonate for suspected flecainide intoxication. Following resuscitation, he remained hemodynamically stable and was discharged in normal sinus rhythm without neurologic sequelae. Drug concentrations obtained at the time of presentation showed a serum concentration of flecainide of 0.668 μg/mL. Drug formulations were also analyzed and found to contain the expected concentration of flecainide.

Discussion:

Literature regarding adverse drug events in the pediatric outpatient population is reviewed, as well as how these risks apply to flecainide, a medication with a low margin of safety. Pediatric experience with flecainide intoxication and sodium bicarbonate administration as an antidote is reviewed. Analysis of the serum drug concentrations demonstrated blood concentrations consistent with syringe reversal, which would have produced a 5-fold flecainide overdose. The Naranjo probability scale indicated a highly probable relationship between flecainide ingestion and the life-threatening event in this case.

Conclusions:

This case of life-threatening flecainide intoxication in a young child, secondary to accidental reversal of medication syringes, underscores the importance of providing parents with accurate dispensing information and labeling medication bottles and syringes in an unambiguous manner.
Endothelin-1 Regulates Oligodendrocyte Development
Authors: Gadea Ana , Aguirre Adan , Haydar Tarik F. , Gallo Vittorio
Published: August 2009

In the postnatal brain, oligodendrocyte progenitor cells (OPCs) arise from the subventricular zone (SVZ) and migrate into the developing white matter, where they differentiate into oligodendrocytes and myelinate axons. The mechanisms regulating OPC migration and differentiation are not fully defined. The present study demonstrates that endothelin-1 (ET-1) is an astrocyte-derived signal that regulates OPC migration and differentiation. OPCsin vivoand in culture express functional ETAand ETBreceptors, which mediate ET-1-induced ERK (extracellular signal-regulated kinase) and CREB (cAMP response element-binding protein) phosphorylation. ET-1 exerts both chemotactic and chemokinetic effects on OPCs to enhance cell migration; it also prevents lineage progression from the O4+to the O1+stage without affecting cell proliferation. Astrocyte-conditioned medium stimulates OPC migration in culture through ET receptor activation, whereas multiphoton time-lapse imaging shows that selective ET receptor antagonists or anti-ET-1 antibodies inhibit OPC migration from the SVZ. Inhibition of ET receptor activity also derepresses OPC differentiation in the corpus callosum in slice cultures. Our findings indicate that ET-1 is a soluble astrocyte-derived signal that regulates OPC migration and differentiation during development.
Overcoming Macrophage-Mediated Axonal Dieback Following CNS Injury
Authors: Busch Sarah A. , Horn Kevin P. , Silver Daniel J. , Silver Jerry
Published: August 2009

Trauma to the adult CNS initiates multiple processes including primary and secondary axotomy, inflammation, and glial scar formation that have devastating effects on neuronal regeneration. After spinal cord injury, the infiltration of phagocytic macrophages coincides with long-distance axonal retraction from the initial site of injury, a deleterious phenomenon known as axonal dieback. We have previously shown that activated macrophages directly induce long-distance retraction of dystrophic axons in anin vitromodel of the glial scar. We hypothesized that treatments that are primarily thought to increase neuronal regeneration following spinal cord injury may in fact derive a portion of their beneficial effects from inhibition of macrophage-mediated axonal retraction. We analyzed the effects of protease inhibition, substrate modification, and neuronal preconditioning on macrophage-axon interactions using our establishedin vitromodel. General inhibition of matrix metalloproteinases and specific inhibition of MMP-9 prevented macrophage-induced axonal retraction despite significant physical interactions between the two cell types, whereas inhibition of MMP-2 had no effect. Chondroitinase ABC-mediated digestion of the aggrecan substrate also prevented macrophage-induced axonal retraction in the presence of extensive macrophage-axon interactions. The use of a conditioning lesion to stimulate intrinsic neuronal growth potential in the absence of substrate modification likewise prevented macrophage-induced axonal retractionin vitroandin vivofollowing spinal cord injury. These data provide valuable insight into the cellular and molecular mechanisms underlying macrophage-mediated axonal retraction and demonstrate modifications that can alleviate the detrimental effects of this unfavorable phenomenon on the postlesion CNS.
Stressed Memories: How Acute Stress Affects Memory Formation in Humans
Authors: Henckens Marloes J. A. G. , Hermans Erno J. , Pu Zhenwei , Joëls Marian , Fernández Guillén
Published: August 2009

Stressful, aversive events are extremely well remembered. Such a declarative memory enhancement is evidently beneficial for survival, but the same mechanism may become maladaptive and culminate in mental diseases such as posttraumatic stress disorder (PTSD). Stress hormones are known to enhance postlearning consolidation of aversive memories but are also thought to have immediate effects on attentional, sensory, and mnemonic processes at memory formation. Despite their significance for our understanding of the etiology of stress-related mental disorders, effects of acute stress at memory formation, and their brain correlates at the system scale, remain elusive. Using an integrated experimental approach, we probed the neural correlates of memory formation while participants underwent a controlled stress induction procedure in a crossover design. Physiological (cortisol level, heart rate, and pupil dilation) and subjective measures confirmed acute stress. Remarkably, reduced hippocampal activation during encoding predicted stress-enhanced memory performance, both within and between participants. Stress, moreover, amplified early visual and inferior temporal responses, suggesting that hypervigilant processing goes along with enhanced inferior temporal information reduction to relay a higher proportion of task-relevant information to the hippocampus. Thus, acute stress affects neural correlates of memory formation in an unexpected manner, the understanding of which may elucidate mechanisms underlying psychological trauma etiology.
Functional Connectivity Delineates Distinct Roles of the Inferior Frontal Cortex and Presupplementary Motor Area in Stop Signal Inhibition
Authors: Duann Jeng-Ren , Ide Jaime S. , Luo Xi , Li Chiang-shan Ray
Published: August 2009

The neural basis of motor response inhibition has drawn considerable attention in recent imaging literature. Many studies have used the go/no-go or stop signal task to examine the neural processes underlying motor response inhibition. In particular, showing greater activity during no-go (stop) compared with go trials and during stop success compared with stop error trials, the right inferior prefrontal cortex (IFC) has been suggested by numerous studies as the cortical area mediating response inhibition. Many of these same studies as well as others have also implicated the presupplementary motor area (preSMA) in this process, in accord with a function of the medial prefrontal cortex in goal-directed action. Here we used connectivity analyses to delineate the roles of IFC and preSMA during stop signal inhibition. Specifically, we hypothesized that, as an integral part of the ventral attention system, the IFC responds to a stop signal and expedites the stop process in the preSMA, the primary site of motor response inhibition. This hypothesis predicted that preSMA and primary motor cortex would show functional interconnectivity via the basal ganglia circuitry to mediate response execution or inhibition, whereas the IFC would influence the basal ganglia circuitry via connectivity with preSMA. The results of Granger causality analyses in 57 participants confirmed this hypothesis. Furthermore, psychophysiological interaction showed that, compared with stop errors, stop successes evoked greater effective connectivity between the IFC and preSMA, providing additional support for this hypothesis. These new findings provided evidence critically differentiating the roles of IFC and preSMA during stop signal inhibition and have important implications for our understanding of the component processes of inhibitory control.
Layer II/III of the Prefrontal Cortex: Inhibition by the Serotonin 5-HT1AReceptor in Development and Stress
Authors: Goodfellow Nathalie M. , Benekareddy Madhurima , Vaidya Vidita A. , Lambe Evelyn K.
Published: August 2009

The modulation of the prefrontal cortex by the neurotransmitter serotonin (5-HT) is thought to play a key role in determining adult anxiety levels. Layer II/III of the prefrontal cortex, which mediates communication across cortical regions, displays a high level of 5-HT1Areceptor binding in normal individuals and a significantly lower level in patients with mood and anxiety disorders. Here, we examine how serotonin modulates pyramidal neurons in layer II/III of the rat prefrontal cortex throughout postnatal development and in adulthood. Using whole cell recordings in brain slices of the rat medial prefrontal cortex, we observed that serotonin directly inhibits layer II/III pyramidal neurons through 5-HT1Areceptors across postnatal development (postnatal days 6–96). In adulthood, a sex difference in these currents emerges, consistent with human imaging studies of 5-HT1Areceptor binding. We examined the effects of early life stress on the 5-HT1Areceptor currents in layer II/III. Surprisingly, animals subjected to early life stress displayed significantly larger 5-HT1A-mediated outward currents throughout the third and fourth postnatal weeks after elevated 5-HT1Aexpression during the second postnatal week. Subsequent exposure to social isolation in adulthood resulted in the almost-complete elimination of 5-HT1Acurrents in layer II/III neurons suggesting an interaction between early life events and adult experiences. These data represent the first examination of functional 5-HT1Areceptors in layer II/III of the prefrontal cortex during normal development as well as after stress.
A New Transgenic Mouse Model of Gerstmann–Sträussler–Scheinker Syndrome Caused by the A117V Mutation ofPRNP
Authors: Yang Wenbin , Cook Julie , Rassbach Benjamin , Lemus Azucena , DeArmond Stephen J. , Mastrianni James A.
Published: August 2009

Gerstmann–Sträussler–Scheinker syndrome (GSS) is a genetic prion disease typified clinically by the development of progressive ataxia and dementia, and histopathologically by the presence of prion protein (PrP) amyloid plaques in the CNS, especially within the cerebellum. Several mutations of the PrP gene (PRNP) are associated with GSS, but only the P102L mutation has been convincingly modeled in transgenic (Tg) mice. To determine whether other mutations carry specific GSS phenotypic information, we constructed Tg mice that express PrP carrying the mouse homolog of the GSS-associated A117V mutation. Tg(A116V) mice express approximately six times the endogenous levels of PrP, develop progressive ataxia by ∼140 d, and die by ∼170 d. Compared with a mouse model of transmissible Creutzfeldt–Jakob disease (CJD), the ataxia of Tg(A116V) mice is more prominent, and the course of disease is more protracted, paralleling that observed in human disease. Neuropathology includes mild scattered vacuolation and prominent, mainly cerebellar localized, thioflavin S-positive PrP plaques comprised of full-length PrPA116V. In some mice, more prominent vacuolation or a noncerebellar distribution of PrP plaques was evident, suggesting some variability in phenotype. The biophysical properties of PrP from Tg(A116V) mice and human GSS(A117V) revealed a similarly low fraction of insoluble PrP and a weakly protease-resistant ∼13 kDa midspan PrP fragment, not observed in CJD. Overall, Tg(A116V) mice recapitulate many clinicopathologic features of GSS(A117V) that are distinct from CJD, supporting PrPA116Vto carry specific phenotypic information. The occasional variation in histopathology they exhibit may shed light on a similar observation in human GSS(A117V).
BC1 Regulation of Metabotropic Glutamate Receptor-Mediated Neuronal Excitability
Authors: Zhong Jun , Chuang Shih-Chieh , Bianchi Riccardo , Zhao Wangfa , Lee Heekyung , Fenton André A. , Wong Robert K. S. , Tiedge Henri
Published: August 2009

Regulatory RNAs have been suggested to contribute to the control of gene expression in eukaryotes. Brain cytoplasmic (BC) RNAs are regulatory RNAs that control translation initiation. We now report that neuronal BC1 RNA plays an instrumental role in the protein-synthesis-dependent implementation of neuronal excitation–repression equilibria. BC1 repression counter-regulates translational stimulation resulting from synaptic activation of group I metabotropic glutamate receptors (mGluRs). Absence of BC1 RNA precipitates plasticity dysregulation in the form of neuronal hyperexcitability, elicited by group I mGluR-stimulated translation and signaled through the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway. Dysregulation of group I mGluR function in the absence of BC1 RNA gives rise to abnormal brain function. Cortical EEG recordings from freely movingBC1−/−animals show that group I mGluR-mediated oscillations in the gamma frequency range are significantly elevated. When subjected to sensory stimulation, these animals display an acute group I mGluR-dependent propensity for convulsive seizures. Inadequate RNA control in neurons is thus causally linked to heightened group I mGluR-stimulated translation, neuronal hyperexcitability, heightened gamma band oscillations, and epileptogenesis. These data highlight the significance of small RNA control in neuronal plasticity.
Membrane-Delimited Coupling of TRPV1 and mGluR5 on Presynaptic Terminals of Nociceptive Neurons
Authors: Kim Yong Ho , Park Chul-Kyu , Back Seung Keun , Lee C. Justin , Hwang Se Jin , Bae Yong Chul , Na Heung Sik , Kim Joong Soo , Jung Sung Jun , Oh Seog Bae
Published: August 2009

Transient receptor potential vanilloid subtype 1 (TRPV1) and metabotropic glutamate receptor 5 (mGluR5) located on peripheral sensory terminals have been shown to play critical roles in the transduction and modulation of pain sensation. To date, however, very little is known regarding the significance of functional expression of mGluR5 and TRPV1 on the central terminals of sensory neurons in the dorsal horn of the spinal cord. Here we show that TRPV1 on central presynaptic terminals is coupled to mGluR5 in a membrane-delimited manner, thereby contributing to the modulation of nociceptive synaptic transmission in the substantia gelatinosa neurons of the spinal cord. Further, our results demonstrate that TRPV1 is involved in the pain behaviors induced by spinal mGluR5 activation, and diacylglycerol produced by the activation of mGluR5 mediates functional coupling of mGluR5 and TRPV1 on the presynaptic terminals. Thus, mGluR5–TRPV1 coupling on the central presynaptic terminals of nociceptive neurons may be an important mechanism underlying central sensitization under pathological pain conditions.
Behavior of Micellar Properties of Zwitterionic Surfactants in the Presence of Glycol Additives: Cyclic Voltammetry, Fluorescence and Viscosity Measurements
Authors: Mahajan R. K. , Shaheen A. , Vohra K. K.
Published: August 2009

Cyclic voltammetry, fluorescence and viscosity measurements were carried out to study the effect of various glycol additives such as EG, DEG, TEG, EGMME and EGMEE on the micellar properties of zwitterionic surfactants, DPS, TPS and HPS. Cyclic voltammetry has been used to determine the diffusion coefficient ‘D’ values by the use of well known Randles-Sevcik equation. The decrease in the ‘D’ values on addition of glycol additives has been explained on the basis of hydration effect and obstruction effect which is more in case of TEG and EGMEE. The destabilization of micelles of zwitterionic surfactants with the addition of glycol additives is explained on the basis of decrease in transfer of free energy (∆Gºt). In case of TEG the change in intensity ratios (∆ I1/I3) determined by fluorescence measurements become more negative with its increasing concentration which indicates that the zwitterionic surfactants are becoming more hydrophobic in its presence. The determination of relative viscosity (ηr) for each system indicates the surfactant-glycol oligomer interaction in the micellar state.
Enaminone Compounds as Corrosion Inhibitors for Austenitic Stainless Steel in Sulphuric Acid Solution. javascript:filterformular(´3´)
Authors: Hosseini S. M. A. , Salari M. , Ghasemi M. , Abaszadeh M.
Published: August 2009

Two newly synthesized Enaminone compounds ethyl-3-[(2-aminoethyl) amino]-2-butenoate (compound I) and ethyl-3-(2-aminoanilino)-2-butenoate (compound II)) in 0.5 M H2SO4 on AISI 316 have been investigated at 20 to 50 ºC using weight loss and potentiostatic polarization techniques. The percentage inhibition efficiencies and surface coverage degrees increase with increasing additive concentration. The inhibition is in both cases of a mixed anodic-cathodic nature. Differences in inhibition efficiency between compound I and II are correlated with their chemical structures. The inhibitors function through adsorption following Temkin isotherm in acid media. Activation energy (E
a) and Gibbs free energy (∆G
ads) for adsorption of inhibitors are calculated. The values of ∆G
ads decreased (attained more negative values) with increasing temperature.
Excess Molar Volumes and Viscosities of Binary Mixture Between n-Butylethanoate and Several Non Polar Hydrocarbons
Authors: Yadava S. S. , Yadav Neetu
Published: August 2009

The densities (ρmix) and viscosities (ηmix) of binary mixtures between n-butylethanoate and several non-polar hydrocarbon solvents viz; cyclohexane, benzene, 1,4-dimethylbenzene and 1,3,5-trimethylbenzene have been measured at 308.15 K for the whole composition range. From the experimental densities values, excess molar volumes(VE) have been estimated. VE values are found to be large positive for mixtures with cyclohexane for entire range of concentration while small positive for benzene and 1,3,5-trimethylbenzene except a negative value at lower concentration of both hydrocarbons and at higher concentration of latter hydrocarbon only. Almost all the VE values are negative for mixtures with 1,4-dimethylbenzene. Deviations in viscosities (Δη) from ideal behaviour have been calculated from the experimental viscosities values. Δη values are large negative for mixtures with cyclohexane. The negative Δη values gradually decreases from benzene, 1,4-dimethylbenzene to 1,3,5-trimethylbenzene respectively. Experimental viscosities values have been analysed on the basis of several viscosities models. The results have been discussed in terms of molecular interactions between unlike molecules.
Hyperthyroid levels of TSH correlate with low bone mineral density: the HUNT 2 study
Authors: Svare Anders , Nilsen Tom Ivar Lund , Bjøro Trine , Forsmo Siri , Schei Berit , Langhammer Arnulf
Published: August 2009

Objective

To study the relationship between TSH and forearm bone mineral density (BMD) in a general female population.

Design

Cross-sectional, population-based study.

Methods

In a substudy of the Nord-Trøndelag Health Study 1995–1997 (HUNT 2), 5778 women without and 944 with self-reported thyroid disease aged ≥40 years had their serum TSH and distal and ultra-distal forearm BMD measured. In range-based categories of TSH, excluding women with previous thyroid disease, a general linear model was used to calculate adjusted mean BMD, and a logistic regression model to compute adjusted odds ratio (OR) for osteopenia and osteoporosis. Corresponding models were used to compare BMD in women with self-reported hypothyroidism or hyperthyroidism to euthyroid women.

Results

In women without self-reported thyroid disease, those with TSH <0.5 mU/l had 10.7 mg/cm2 (95% confidence interval (CI) 0.2–21.1) lower distal and 9.1 mg/cm2 (95% CI −0.7–18.9) lower ultra-distal BMD than women in the reference category (TSH 0.50–1.49 mU/l). No differences were found between the categories with TSH ≥0.50 mU/l. Compared to self-reported euthyroid women, self-reported hyperthyroid women had increased odds for osteoporosis both distally (OR 1.35, 95% CI 1.00–1.82) and ultra-distally (OR 1.48, 95% CI 1.10–1.99).

Conclusion

Women with the lowest TSH (<0.5 mU/l) had lower forearm BMD than the reference category. No differences were observed between the TSH categories ≥0.50 mU/l. The prevalence of osteoporosis was higher in women who reported hyperthyroidism than in women without self-reported thyroid disease.
Clinical outcomes after estimated versus calculated activity of radioiodine for the treatment of hyperthyroidism: systematic review and meta-analysis
Authors: de Rooij A , Vandenbroucke J P , Smit J W A , Stokkel M P M , Dekkers O M
Published: August 2009

Background

Despite the long experience with radioiodine for hyperthyroidism, controversy remains regarding the optimal method to determine the activity that is required to achieve long-term euthyroidism.

Objectives

To compare the effect of estimated versus calculated activity of radioiodine in hyperthyroidism.

Design

Systematic review and meta-analysis.

Methods

We searched the databases Medline, EMBASE, Web of Science, and Cochrane Library for randomized and nonrandomized studies, comparing the effect of activity estimation methods with dosimetry for hyperthyroidism. The main outcome measure was the frequency of treatment success, defined as persistent euthyroidism after radioiodine treatment at the end of follow-up in the dose estimated and calculated dosimetry group. Furthermore, we assessed the cure rates of hyperthyroidism.

Results

Three randomized and five nonrandomized studies, comparing the effect of estimated versus calculated activity of radioiodine on clinical outcomes for the treatment of hyperthyroidism, were included. The weighted mean relative frequency of successful treatment outcome (euthyroidism) was 1.03 (95% confidence interval (CI) 0.91–1.16) for estimated versus calculated activity; the weighted mean relative frequency of cure of hyperthyroidism (eu- or hypothyroidism) was 1.03 (95% CI 0.96–1.10). Subgroup analysis showed a relative frequency of euthyroidism of 1.03 (95% CI 0.84–1.26) for Graves' disease and of 1.05 (95% CI 0.91–1.19) for toxic multinodular goiter.

Conclusion

The two main methods used to determine the activity in the treatment of hyperthyroidism with radioiodine, estimated and calculated, resulted in an equally successful treatment outcome. However, the heterogeneity of the included studies is a strong limitation that prevents a definitive conclusion from this meta-analysis.