bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 68
Authors: Volpi N , Magi S , Greco G , Ulivelli M , Alessandrini C , Giannini F
Published: October 2010

Colchicine is an anti‐inflammatory drug commonly used for the treatment of gouty arthritis, Behçet's disease and amyloidosis. Reported side effects, such as blood dyscrasias and gastroenteritis, are probably ascribed to its antimitotic properties. Colchicine‐induced myopathy with vacuolar changes and frequently associated sensory‐motor axonal neuropathy have also been described. A 52‐yr‐old woman, previously treated for gouty arthritis, persisted in self‐administering colchicine intermittently for three years, in order to reduce body weight by inducing diarrhea. The patient had weakness and hypotrophy in upper and lower girdles and proximal muscles, “stocking and glove” hypoesthesia and loss of deep tendon reflexes in lower limbs. EMG examination showed a neurogenic/myogenic mixed pattern and nerve conduction studies were consistent with sensory‐motor axonal polyneuropathy. Muscle biopsy showed a vacuolar myopathy, with autophagic vacuoles and associated neurogenic changes. A moderate loss of myelinated fibers and some degenerating axons were observed in sural nerve biopsy. There were neither demyelinating changes nor autophagic vacuoles within axons. Muscle and nerve findings were thus suggestive of colchicine neuromyopathy. The drug was withdrawn and clinical‐electrophysiological data improved. Colchicine muscular toxicity is presumably due to inhibition of tubulin monomer polymerization. The microtubular network destabilization might cause cytoplasmic deposits of autophagic debris in skeletal muscle. We thus evaluated number, density and spatial array of microtubules in myelinated and unmyelinated axons by transmission electron microscopy. Quantitative ultrastructural analysis was carried out on high magnification photographs in our patient biopsy and in control nerves (normal and with axonal loss). Decrease of microtubular density and increase of tangentially oriented microtubules were observed both in myelinated and unmyelinated axons. No neural deposits of tubulin‐like material, as described in some cases of colchicine myopathy, were found. As in experimental vincristine neuropathy, cytoskeletal damage induced by colchicine seems related to effects of primary microtubular disarray on axonal transport and caliber, rather than to the extent of axonal loss.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 71
Authors: Donzelli E , Carfì M , Miloso M , Strada A , Galbiati S , Cavaletti G , Tredici G
Published: October 2010

Platinum compounds are very effective anti‐cancer agents and act forming adducts with DNA and cytoplasmic proteins. Their main dose‐limiting side effect is peripheral neurotoxicity. Cisplatin neurotoxicity has been studied in many in vitro and in vivo models but little information is available for oxaliplatin. In this study we evaluated and compared the effect of cisplatin and oxaliplatin (a gift from Debiopharm S.A., Lausanne, Switzerland) in an in vitro model of neurotoxicity using the human neuroblastoma SH‐SY5Y cells, which may be considered as neuroblasts. Both platinum compounds are toxic and induce cellular death by apoptosis. Oxaliplatin is less neurotoxic than cisplatin. Concentrations of oxaliplatin 3–4 times higher than those of cisplatin are necessary to induce the same percentage of cellular death. We analyzed the activation/inactivation of specific molecules involved in the apoptotic transduction pathway. After exposure to both cisplatin and oxaliplatin the anti‐apoptotic protein Bcl‐2 was significantly reduced and thus could not exert its anti‐apoptotic action. Conversely, the pro‐apoptotic proteins p53, caspase 3, and caspase 7 were activated. In our experiments in SH‐SY5Y cells treated with cisplatin or oxaliplatin, the amount of p53 protein was markedly increased. In treated cultures, both caspase 3 and 7 were cleaved with the appearance of their active fragments which induced PARP cleavage. Our results suggest that neurotoxicity of cisplatin and oxaliplatin share a similar pathway. Neurotoxicity induced by platinum compounds is due not only to DNA damage but also to the activation of specific molecular pathways committing cells to apoptosis.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 78
Authors: Osio M , Zampini L , Muscia F , Valsecchi L , Nascimbene C , Mariani C , Cargnel A
Published: October 2010

Introduction: Acetyl‐L‐Carnitine (ALC) is a safe and well‐tolerated drug in the treatment of peripheral neuropathy in HIV infected patients. Its efficacy is focused on its role in modulating TNF‐alpha expression and on the restoration of endogenous acetylcarnitine. Peripheral nervous system is frequently involved during HIV infection and distal sensitive polyneuropathy is one of the most common neurological complications (up to 30% of AIDS patients). Etiology is still unknown. One of the pathogenetic hypotheses is the role of proinflammatory cytokines (TNF‐alpha) in causing neuropathic pain. Method: Twenty HIV‐ positive patients affected by neuropathic pain with EMG‐evidence of axonal alterations were enrolled; we excluded patients with mini‐mental test score < 24, acute CMV infection, chronic demyelinating neuropathies. All patients were treated with ALC at the dose of 1 gram t.i.d. for 4 weeks. A visual analogue scale (VAS) was used to evaluate characteristics of patient's pain before, during, and after treatment. EMG and neurographic assessment was performed before and after treatment. To evaluate changes in VAS score we used non‐parametric Friedman's test (F). Wilcoxon's test (W) was performed to timing the appearance of pain improvement, and to evaluate neurophysiological data. Results: The changes in VAS score were statistically significant during ALC treatment (mean score: before 6.7 ± 2.1 – after treatment 5.0 ± 2.1)(F = P < 0.001). The appearance of therapeutic effect was reached during the first week (W = P < 0.03) and during the fourth week (W = P < 0.05) of treatment. Analysis of neurophysiological data showed a statistically significant improvement of peroneal nerve motor parameters: reduced motor distal latency (W = P < 0.02), increased amplitude of the compound motor action potential at distal (W = P < 0.02) and proximal (W = P < 0.05) site of stimulation. Conclusions: Our data show the efficacy of ALC in the treatment of neuropathic pain, confirming previous results. Moreover, the analgesic effects appear during the first week of treatment according with pre‐clinical data in different experimental models of pain. Among mechanisms for ALC efficacy in patients with HIV‐related polyneuropathy, there is a neurotrophic effect as evidenced from patch‐skin biopsy evaluation.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 80
Authors: Passadore P , Polo A , Cerini R , Menestrina F , Raimondi Basso , De Grandis D
Published: October 2010

We report two cases of focal inflammatory neuropathy of median nerve with sensory symptoms only in the first patient and motor and sensory disturbances in the second one. In both patients we found at MNR an important segmentary increase of nerve caliber. Surgery excluded nerve tumor and biopsy showed only edema and lymphocytic infiltration sparing nerve fibers. Steroid therapy was successful with rapid disappearance of sensory symptoms and motor deficit. The presence of severe sensory and motor conduction block without signs of axonal damage represent a peculiar neurophysiological aspect in chronic inflammatory focal neuritis; treatment with high‐dose of i.v. corticosteroids is frequently helpful.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 82
Authors: Polo A , Sorarù G
Published: October 2010

A 69‐year‐old right‐handed man was recently referred to our institution with a two‐month history of diplopia and ptosis in his left eye: the ocular symptoms typically fluctuates during the day, being least severe in the morning and worsening as the day progress or while reading or driving. Neostigmine injection produced a clear improvement of weakness. The serum concentration of anti‐AChR antibody was elevated > 8.4 nmol/L (NV < 0.4); a chest CT scan was unremarkable with no evidence of mediastinal mass. The clinical picture and laboratory tests support the diagnosis of ocular myasthenia. His past medical history was insignificant until the age of 59. At that time, he complained with a diffuse, slightly asymmetrical muscle weakness both in the upper and lower limbs and sensory symptoms of glove and stocking distribution (numbness). A progressive course over months was seen with hand and anterior leg muscles hypertrophy becoming evident. Strength was decreased distally greater than proximally in the upper and lower extremities. Deep tendon reflexes were absent. The cerebrospinal fluid demonstrated a protein level of 72 mg/dl (NV < 45 mg/dl). Nerve conduction study showed a multifocal sensory‐motor polyneuropathy with both conduction block/temporal dispersion of the C‐MAP and slowing of the velocity. A diagnosis of chronic inflammatory polyneuropathy (CIDP) was considered and the patient was treated with steroids, plasmapheresis and azathiaprine: after a slight improvement, the condition has been stabilized. Both MG and CIDP have been individually associated with disorders of presumed autoimmune pathogenesis. Their concurrence is rarely found (less than 10 cases to the best of our knowledge): although the existence of this syndrome can be strongly supported by the clinical, electrophysiological and laboratory data, a common basic abnormality of immune regulation is still unknown.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 85
Authors: Donadio V , Montagna P , Provini F , Vetrugno R , Di Stasi V , Baruzzi A , Liguori R
Published: October 2010

The aim of this study is to report changes in muscle sympathetic activity (MSA) and other cardiovascular variables during central apnea occurring during a relaxed wakefulness. We describe a 47‐year‐old man with a five‐year history of apnea. Polysomnographic recording showed repeated central apnea, without an obstructive peripheral component, during sleep or relaxed wakefulness. Neuromuscular disease was excluded by EMG investigation. During relaxed wake, MSA was evaluated by a microneurographic recording from the left peroneal nerve in association with blood pressure (BP), heart rate (HR), thoracoabdominal respiration and sympathetic skin response (SSR). Microneurographic polygraphic recording was performed during normal respiration (5 minutes) and during repeated apnea episodes (4 consecutive episodes with mean duration of 26.2 s; range 18–45). During normal respiration, MSA was 39.5 burst/min and 64.7 bursts/100 heartbeats, the heart rate was 61.1 beat/min. During the apnea episodes, both MSA (29% and 27%: 50.9 burst/min e 82.1 bursts/100 heartbeats respectively; mean values) and HR (1%: 61.9 beat/min; mean values) increased. The maximum MSA and HR increase was reached at the end of apnea and was followed by a BP increase. Spontaneous SSR were absent during apnea episodes whereas sporadic responses were recorded after the apnea episodes when the breathing acts were wide and prolonged. In conclusion, central apnea caused an increase in MSA and minor increase in HR leading to a BP increase following the apnea episode.
Ultrastructural identification of peripheral myelin proteins by a pre‐embedding immunogold labeling method
Authors: Canron Marie‐Hélène , Bouillot Sandrine , Favereaux Alexandre , Petry Klaus G. , Vital Anne
Published: October 2010

Abstract Ultrastructural immunolabeling of peripheral nervous system components is an important tool to study the relation between structure and function. Owing to the scarcity of certain antigens and the dense structure of the peripheral nerve, a pre‐embedding technique is likely appropriate. After several investigations on procedures for pre‐embedding immunolabeling, we propose a method that offers a good compromise between detection of antigenic sites and preservation of morphology at the ultrastructural level, and that is easy to use and suitable for investigations on peripheral nerve biopsies from humans. Pre‐fixation by immersion in paraformaldehyde/glutaraldehyde is necessary to stabilize the ultrastructure. Then, ultrasmall gold particles with silver enhancement are advised. Antibodies against myelin protein zero and myelin basic protein were chosen for demonstration. The same technique was applied to localize a 35 kDa myelin protein.
Repair of ventral root avulsion using autologous nerve grafts in cats
Authors: Holtzer Carlo A. J. , Marani Enrico , Van Dijk Gert J. , Thomeer Ralph T. W. M.
Published: October 2010

Abstract This study focuses on the capacity of motor axons to elongate from the spinal cord through an autologous nerve graft into a spinal nerve. Applying a ventral surgical approach, C7 ventral roots were avulsed from the cord in 12 cats. Autologous saphenous nerve grafts were implanted into the cord at the ventral root outlet site and coaptated to the spinal nerve. Outgrowth of axons was studied at survival times 7, 14, 30, 60 and 120 days, respectively. The results showed horseradish peroxidase positive motoneurons in the C7 ventral horn after retrograde labeling, as well as neurofilament and acetylcholinesterase positive axons in the entire trajectory from spinal cord to spinal nerve. Neurotization of the C7 spinal nerve started between 14 and 30 days after graft implantation. In addition electrophysiology provided evidence that outgrowing axons had re‐established functional contact with the spinodeltoid muscle at 120 days after implantation.
Modeling the response of a fast ion loss detector using orbit tracing techniques in a neutral beam prompt-loss study on the DIII-D tokamak
Authors: Pace D. C. , Fisher R. K. , García-Muñoz M. , Darrow D. S. , Heidbrink W. W. , Muscatello C. M. , Nazikian R. , Van Zeeland M. A. , Zhu Y. B.
Published: October 2010

A numerical model describing the expected measurements of neutral beam prompt-losses by a newly commissioned fast ion loss detector (FILD) in DIII-D is presented. This model incorporates the well understood neutral beam deposition profiles from all eight DIII-D beamlines to construct a prompt-loss source distribution. The full range of detectable ion orbit phase space available to the FILD is used to calculate ion trajectories that overlap with neutral beam injection footprints. Weight functions are applied to account for the level of overlap between these detectable orbits and the spatial and velocity (pitch) properties of ionized beam neutrals. An experimental comparison is performed by firing each neutral beam individually in the presence of a ramping plasma current. Fast ion losses determined from the model are in agreement with measured losses.
Phase coexistence near a morphotropic phase boundary in Sm-doped BiFeO3 films
Authors: Emery S. B. , Cheng C.-J. , Kan D. , Rueckert F. J. , Alpay S. P. , Nagarajan V. , Takeuchi I. , Wells B. O.
Published: October 2010

We have investigated heteroepitaxial films of Sm-doped BiFeO3 with a Sm-concentration near a morphotropic phase boundary. Our high-resolution synchrotron x-ray diffraction, carried out in a temperature range of 25 to 700 °C, reveals substantial phase coexistence as one changes temperature to crossover from a low-temperature PbZrO3-like phase to a high-temperature orthorhombic phase. We also examine changes due to strain for films exhibiting anisotropic misfit between film and substrate. Additionally, thicker films exhibit a substantial volume collapse associated with the structural transition that is suppressed in thinner films.
Hydrogen induced passivation of Si interfaces by Al2O3 films and SiO2/Al2O3 stacks
Authors: Dingemans G. , Beyer W. , van de Sanden M. C. M. , Kessels W. M. M.
Published: October 2010

The role of hydrogen in Si surface passivation is experimentally identified for Al2O3 (capping) films synthesized by atomic layer deposition. By using stacks of SiO2 and deuterated Al2O3, we demonstrate that hydrogen is transported from Al2O3 to the underlying SiO2 already at relatively low annealing temperatures of 400 °C. This leads to a high level of chemical passivation of the interface. Moreover, the thermal stability of the passivation up to 800 °C was significantly improved by applying a thin Al2O3 capping film on the SiO2. The hydrogen released from the Al2O3 film favorably influences the passivation of Si interface defects.
Surface enhanced resonance Raman and luminescence on plasmon active nanostructured cavities
Authors: Lordan Frances , Rice James H. , Jose Bincy , Forster Robert J. , Keyes Tia E.
Published: October 2010

Presented here are studies of the impact of excitation angle on surface enhanced Raman and luminescence spectroscopy of dye immobilized on a plasmon active nanocavity array support. Results show that both Raman and luminescence intensities depend on the angle of incidence consistent with the presence of cavity supported plasmon modes. Dependence of scattering or emission intensity with excitation angle occurs over the window of observation.
Random breakup of microdroplets for single-cell encapsulation
Authors: Um Eujin , Lee Seung-Goo , Park Je-Kyun
Published: October 2010

Microfluidic droplet-based technology enables encapsulation of cells in the isolated aqueous chambers surrounded by immiscible fluid but single-cell encapsulation efficiency is usually less than 30%. In this letter, we introduce a simple microgroove structure to break droplets into random sizes which further allows collecting of single-cell [Escherichia coli (E. coli)] containing droplets by their size differences. Pinched-flow separation method is integrated to sort out droplets of certain sizes which have high probability of containing one cell. Consequently, we were able to obtain more than 50% of droplets having single E. coli inside, keeping the proportion of multiple-cell containing droplets less than 16%.
Perfluorinated compounds in marine surface waters: data from the Baltic Sea and methodological challenges for future studies
Authors: Kirchgeorg Torben , Weinberg Ingo , Dreyer Annekatrin , Ebinghaus Ralf
Published: October 2010

Environmental context.Perfluorinated compounds are man-made chemicals of emerging environmental concern because of their global distribution in water, air and biota. We investigate the distribution of these chemicals in surface water of the Baltic Sea, a unique ecosystem and the world’s largest body of brackish water. The observed contamination was of the same order of magnitude as classical persistent organic pollutants in the world’s oceans, and decreased with lower population density in the Baltic Sea catchments.
Abstract.Poly- and perfluorinated compounds (PFCs) are chemicals of emerging environmental concern. Except for very few coastal sites, PFC contamination of the Baltic Sea has not been investigated. In order to assess the PFC contamination of Baltic Sea water and evaluate the spatial distribution of PFCs, 74 surface water samples from the entire Baltic Sea were taken during two sampling campaigns in the summer of 2008 and analysed for PFCs. Of 40 analysed PFCs, 13 were detected at concentrations below 1 ng L–1, which indicates a rather low PFC contamination of Baltic Sea surface water. Usually, PFOA was the analyte observed in highest concentrations followed by PFNA, PFBS, and PFOS. PFC concentrations decreased from the Kattegat to the Bothnian Bay and the Gulf of Finland, reflecting the decreasing population density and thus the potential contamination in corresponding catchments or the decreasing influence of potentially contaminated North Sea water.
Biogeochemistry and cyanobacterial blooms: investigating the relationship in a shallow, polymictic, temperate lake
Authors: Grace Michael R. , Scicluna Todd R. , Vithana Chamindra L. , Symes Peter , Lansdown Katrina P.
Published: October 2010

Environmental context.Effective mitigation of algal blooms, and their associated detrimental impacts on flora and fauna, requires an understanding of the factors leading to bloom development, including nutrients, light and hydrodynamics. We investigated a shallow, freshwater lake and demonstrate that there is sufficient bioavailable phosphorus to annually generate a large algal biomass. Extensive, seasonal phosphorus release from sediments is controlled by the interactions of the biogeochemical cycles of nitrogen, carbon, oxygen, iron and sulfur. Abstract.The shallow, polymictic Ornamental Lake in the Royal Botanic Gardens, Melbourne, Australia, has suffered significant blooms of toxic Anabaena then Microcystis species every summer over the last decade. Although the hydrodynamic conditions of the water column are conducive for algal growth, the prolific growth is controlled by the bioavailable phosphorus concentration. Springtime phosphorus fluxes of 0.1–0.2 mmol m–2 day–1 from the sediment contribute to bloom development. These rates are also observed in anoxic sediment core incubations. Diel stratification, combined with high oxygen consumption associated with organic carbon loading, favour P release. Release rates may be amplified by the effects of sulfate reduction on P sorption onto FeIII (oxyhydroxide) surfaces. Sulfate concentrations are at the threshold where methanogenesis is inhibited in anoxic conditions. Effective bloom mitigation will require a >100-fold reduction in P concentrations, which may be achieved through macrophyte planting and inducing greater water flow through the lake system.
Kinetics of fiber solidification
Authors: Mercader C. , Lucas A. , Derré A. , Zakri C. , Moisan S. , Maugey M. , Poulin P.
Published: October 2010

Many synthetic or natural fibers are produced via the transformation of a liquid solution into a solid filament, which allows the wet processing of high molecular weight polymers, proteins, or inorganic particles. Synthetic wet-spun fibers are used in our everyday life from clothing to composite reinforcement applications. Spun fibers are also common in nature. Silk solidification results from the coagulation of protein solutions. The chemical phenomena involved in the formation of all these classes of fibers can be quite different but they all share the same fundamental transformation from a liquid to a solid state. The solidification process is critical because it governs the production rate and the strength that fibers can sustain to be drawn and wound. An approach is proposed in this work to investigate the kinetics of fiber solidification. This approach consists in circulating solidifying fibers in the extensional flow of a surrounding liquid. Such as polymers in extensional flows, the fibers break if resultant drag forces exceed the fiber tensile strength. The solidification kinetics of nanotube composite fibers serves as a validation example of this approach. The method could be extended to other systems and advance thereby the science and technology of fiber and textile materials. It is also a way to directly visualize the scission of chain-like systems in extensional flows.
Electrical transport along bacterial nanowires from
Shewanella oneidensis
MR-1
Authors: El-Naggar Mohamed Y. , Wanger Greg , Leung Kar Man , Yuzvinsky Thomas D. , Southam Gordon , Yang Jun , Lau Woon Ming , Nealson Kenneth H. , Gorby Yuri A.
Published: October 2010

Bacterial nanowires are extracellular appendages that have been suggested as pathways for electron transport in phylogenetically diverse microorganisms, including dissimilatory metal-reducing bacteria and photosynthetic cyanobacteria. However, there has been no evidence presented to demonstrate electron transport along the length of bacterial nanowires. Here we report electron transport measurements along individually addressed bacterial nanowires derived from electron-acceptor–limited cultures of the dissimilatory metal-reducing bacterium
Shewanella oneidensis
MR-1. Transport along the bacterial nanowires was independently evaluated by two techniques: (
i
) nanofabricated electrodes patterned on top of individual nanowires, and (
ii
) conducting probe atomic force microscopy at various points along a single nanowire bridging a metallic electrode and the conductive atomic force microscopy tip. The
S. oneidensis
MR-1 nanowires were found to be electrically conductive along micrometer-length scales with electron transport rates up to 10
9
/s at 100 mV of applied bias and a measured resistivity on the order of 1 Ω·cm. Mutants deficient in genes for
c
-type decaheme cytochromes MtrC and OmcA produce appendages that are morphologically consistent with bacterial nanowires, but were found to be nonconductive. The measurements reported here allow for bacterial nanowires to serve as a viable microbial strategy for extracellular electron transport.
Light at night increases body mass by shifting the time of food intake
Authors: Fonken Laura K. , Workman Joanna L. , Walton James C. , Weil Zachary M. , Morris John S. , Haim Abraham , Nelson Randy J.
Published: October 2010

The global increase in the prevalence of obesity and metabolic disorders coincides with the increase of exposure to light at night (LAN) and shift work. Circadian regulation of energy homeostasis is controlled by an endogenous biological clock that is synchronized by light information. To promote optimal adaptive functioning, the circadian clock prepares individuals for predictable events such as food availability and sleep, and disruption of clock function causes circadian and metabolic disturbances. To determine whether a causal relationship exists between nighttime light exposure and obesity, we examined the effects of LAN on body mass in male mice. Mice housed in either bright (LL) or dim (DM) LAN have significantly increased body mass and reduced glucose tolerance compared with mice in a standard (LD) light/dark cycle, despite equivalent levels of caloric intake and total daily activity output. Furthermore, the timing of food consumption by DM and LL mice differs from that in LD mice. Nocturnal rodents typically eat substantially more food at night; however, DM mice consume 55.5% of their food during the light phase, as compared with 36.5% in LD mice. Restricting food consumption to the active phase in DM mice prevents body mass gain. These results suggest that low levels of light at night disrupt the timing of food intake and other metabolic signals, leading to excess weight gain. These data are relevant to the coincidence between increasing use of light at night and obesity in humans.
Syk is a dual-specificity kinase that self-regulates the signal output from the B-cell antigen receptor
Authors: Heizmann Beate , Reth Michael , Infantino Simona
Published: October 2010

Upon B-cell activation, the signaling subunits Ig-α and Ig-β of the B-cell antigen receptor become phosphorylated not only on tyrosines but also on serine residues. Using a specific antibody, we show that serine 197 (S197) in the cytoplasmic tail of Ig-α is phosphorylated upon B-cell antigen receptor activation, and that this modification inhibits the signal output of the B-cell antigen receptor. Surprisingly, we found that the well-known protein tyrosine kinase Syk (spleen tyrosine kinase) phosphorylates S197 on Ig-α, thus not only activating but also inhibiting signaling from the B-cell antigen receptor. This finding identifies Syk as a dual-specificity kinase and establishes a previously unexplored paradigm for the self-regulation of biological signaling processes.
Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins
Authors: Coelho Vania , Krysov Sergey , Ghaemmaghami Amir M. , Emara Mohamed , Potter Kathleen N. , Johnson Peter , Packham Graham , Martinez-Pomares Luisa , Stevenson Freda K.
Published: October 2010

Surface Ig (sIg) of follicular lymphoma (FL) is vital for tumor cell survival. We found previously that the Ig in FL is unusual, because the variable region genes carry sequence motifs for
N
-glycan addition. These are introduced by somatic mutation and are tumor specific. Unexpectedly, added glycans terminate at high mannose, suggesting a potentially important interaction of FL cells with mannose-binding lectins of the innate immune system. We have now identified mannosylated IgM at the surface of primary lymphoma cells. Recombinant lectin domains of the mannose receptor (MR) or DC-SIGN bind mannosylated Igs in vitro and bind to FL cells, signaling sIgM-associated increases in intracellular Ca
2+
. Lectins also bind to normal B cells but fail to signal. In contrast, anti-Ig signaled similarly in both FL and normal B cells. Mannosylation patterns were mimicked by FL Ig-derived single-chain Fvs (scFv), providing probes for potential receptors. Mannosylated scFv bound specifically to the lectin domains of the MR and DC-SIGN and blocked signaling. Mannosylated scFv also bound to DC-SIGN on the surface of dendritic cells. This unique lymphoma-specific interaction of sIg with lectins of innate immunity reveals a potential route for microenvironmental support of tumor cells, mediated via the key B-cell receptor.
Dual selection mechanisms drive efficient single-gene reverse genetics for rotavirus
Authors: Trask Shane D. , Taraporewala Zenobia F. , Boehme Karl W. , Dermody Terence S. , Patton John T.
Published: October 2010

Current methods for engineering the segmented double-stranded RNA genome of rotavirus (RV) are limited by inefficient recovery of the recombinant virus. In an effort to expand the utility of RV reverse genetics, we developed a method to recover recombinant viruses in which independent selection strategies are used to engineer single-gene replacements. We coupled a mutant SA11 RV encoding a temperature-sensitive (
ts
) defect in the NSP2 protein with RNAi-mediated degradation of NSP2 mRNAs to isolate a virus containing a single recombinant gene that evades both selection mechanisms. Recovery is rapid and simple; after two rounds of selective passage the recombinant virus reaches titers of ≥10
4
pfu/mL. We used this reverse genetics method to generate a panel of viruses with chimeric NSP2 genes. For one of the chimeric viruses, the introduced NSP2 sequence was obtained from a pathogenic, noncultivated human RV isolate, demonstrating that this reverse genetics system can be used to study the molecular biology of circulating RVs. Combining characterized RV
ts
mutants and validated siRNA targets should permit the extension of this “two-hit” reverse genetics methodology to other RV genes. Furthermore, application of a dual selection strategy to previously reported reverse genetics methods for RV may enhance the efficiency of recombinant virus recovery.
Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain
Authors: Liu Ke , Chen Chen , Guo Yahong , Lam Robert , Bian Chuanbing , Xu Chao , Zhao Dorothy Y. , Jin Jing , MacKenzie Farrell , Pawson Tony , Min Jinrong
Published: October 2010

Arginine methylation modulates diverse cellular processes and represents a molecular signature of germ-line-specific Piwi family proteins. A subset of Tudor domains recognize arginine methylation modifications, but the binding mechanism has been lacking. Here we establish that, like other germ-line Tudor proteins, the ancestral staphylococcal nuclease domain-containing 1 (SND1) polypeptide is expressed and associates with PIWIL1/Miwi in germ cells. We find that human SND1 binds PIWIL1 in an arginine methylation-dependent manner with a preference for symmetrically dimethylated arginine. The entire Tudor domain and a bifurcated SN domain are required for this binding activity, whereas the canonical Tudor domain alone is insufficient for methylarginine ligand binding. Crystal structures show that the intact SND1 extended Tudor domain forms a wide and negatively charged binding groove, which can accommodate distinct symmetrically dimethylated arginine peptides from PIWIL1 in different orientations. This analysis explains how SND1 preferentially recognizes symmetrical dimethylarginine via an aromatic cage and conserved hydrogen bonds, and provides a general paradigm for the binding mechanisms of methylarginine-containing peptides by extended Tudor domains.
Kinetics of G-protein–coupled receptor endosomal trafficking pathways revealed by single quantum dots
Authors: Fichter Katye M. , Flajolet Marc , Greengard Paul , Vu Tania Q.
Published: October 2010

G-protein–coupled receptors (GPCRs) are the largest protein superfamily in the human genome; they comprise 30% of current drug targets and regulate diverse cellular signaling responses. The role of endosomal trafficking in GPCR signaling regulation is gaining substantial consideration. However, this process remains difficult to study due to the inability to distinguish among many individual receptors, simultaneously trafficking within multiple endosomal pathways. Here we show accurate measurement of the internalization and endosomal trafficking of single groups of serotonin (5-hydroxytryptamine, 5-HT) receptors using single quantum dot (QD) probes and quantitative colocalization. We demonstrate that the presence of a QD tag does not interfere with 5-HT receptor internalization or endosomal recycling. Direct measurements show simultaneous trafficking of the 5-HT1A receptor in two distinct endosomal recycling pathways. Single-molecule imaging of endosomal trafficking will significantly impact the understanding of cellular signaling and provide powerful tools to elucidate the actions of GPCR-targeted therapeutics.
Constitutively active H-ras accelerates multiple forms of plasticity in developing visual cortex
Authors: Kaneko Megumi , Cheetham Claire E. , Lee Yong-Seok , Silva Alcino J. , Stryker Michael P. , Fox Kevin
Published: October 2010

Experience-dependent cortical plasticity has been studied by using loss-of-function methods. Here, we take the complementary approach of using a genetic gain-of-function that enhances plasticity. We show that a constitutively active form of H-ras (H-ras
G12V
), expressed presynaptically at excitatory synapses in mice, accelerates and enhances multiple, mechanistically distinct forms of plasticity in the developing visual cortex. In vivo, H-ras
G12V
not only increased the rate of ocular dominance change in response to monocular deprivation (MD), but also accelerated recovery from deprivation by reverse occlusion. In vitro, H-ras
G12V
expression decreased baseline presynaptic release probability and enhanced presynaptically expressed long-term potentiation (LTP). H-ras
G12V
expression also accelerated the increase following MD in the frequency of miniature excitatory potentials, mirroring accelerated plasticity in vivo. These findings demonstrate accelerated neocortical plasticity, which offers an avenue toward future therapies for many neurological and neuropsychiatric disorders.
Virtual Instruction: A Qualitative Research Laboratory Course
Authors: Stadtlander Lee M. , Giles Martha J.
Published: October 2010

Online graduate programs in psychology are becoming common; however, a concern has been whether instructors in the programs provide adequate research mentoring. One issue surrounding research mentoring is the absence of research laboratories in the virtual university. Students attending online universities often do research without peer or lab support and without previous experience in supervised research projects. This article describes a virtual qualitative research lab course at an online university that both mentored students and collected data through a virtual qualitative lab on a national scale. The authors also address logistics, problems and issues that arose, and suggestions for future courses.
An Integrative Undergraduate Capstone Course on the Unconscious
Authors: Boysen Guy A.
Published: October 2010

Theories and research related to the unconscious can be found in every area of psychology, but there is no course devoted to the topic in the undergraduate curriculum. A capstone course on the unconscious is described. The course integrates topics across the major fields of psychology. Themes in the course include the existence of mental processes that individuals are not aware of, do not have access to, and are not able to control, and how these processes lead to efficiency and confabulation. Course topics related to these themes are organized into subsections including why psychology needs the unconscious, psychodynamic theories, the modern unconscious, and consciousness and free will. Suggestions are made for course readings, assignments, and activities.
For Better or for Worse: Using an Objective Program Assessment Measure to Enhance an Undergraduate Psychology Program
Authors: Dolinsky Beverly , Kelley John M.
Published: October 2010

We describe how an objective form of measurement can be used to promote curriculum review, resulting in enhancements to curriculum and pedagogy. During a 4-year period, senior psychology majors took the ETS Major Field Test, and we systematically compared these results to SAT scores, grade point averages, and credits completed. Although diligent, honest, and sometimes frustrating analysis of the comparative results of our students' performance was necessary, the positive outcomes included a more structured curriculum within the psychology major, increased collaboration among faculty, and enhanced student learning experiences.
The Pleasures and Lessons of Academic Mythbusting: An Interview with Scott Lilienfeld
Authors: Zinn Tracy E.
Published: October 2010

Scott O. Lilienfeld is a professor of psychology at Emory University, in Atlanta, Georgia. Dr. Lilienfeld is founder and editor of the journal, Scientific Review of Mental Health Practice, and is past president of the Society for a Science of Clinical Psychology. He has been a member of 11 journal editorial boards, including the Journal of Abnormal Psychology and Clinical Psychology Review. Dr. Lilienfeld has published more than 200 articles, book chapters, and books on personality disorders, personality assessment, anxiety disorders, psychiatric classification and diagnosis, pseudoscience in psychology, and evidence-based practices in clinical psychology. His most recent book, coauthored with Steven Jay Lynn, John Ruscio, and Barry Beyerstein, is 50 Great Myths of Popular Psychology: Shattering Widespread Misconceptions About Human Behavior (Wiley-Blackwell, 2010).

Tracy E. Zinn is an associate professor of psychology at James Madison University. She earned a PhD in industrial/organizational psychology from Auburn University in 2002. In 2005, Tracy received the Early Career Award from the Society for the Teaching of Psychology. She has published several articles and book chapters on the topic of effective teaching practices. Tracy currently serves as the program coordinator for the APS-STP Teaching Institute at the Association for Psychological Sciences annual convention.
Functional central spindle assembly requires de novo microtubule generation in the interchromosomal region during anaphase
Authors: Uehara Ryota , Goshima Gohta
Published: October 2010

The central spindle forms between segregating chromosomes during anaphase and is required for cytokinesis. Although anaphase-specific bundling and stabilization of interpolar microtubules (MTs) contribute to formation of the central spindle, it remains largely unknown how these MTs are prepared. Using live imaging of MT plus ends and an MT depolymerization and regrowth assay, we show that de novo MT generation in the interchromosomal region during anaphase is important for central spindle formation in human cells. Generation of interchromosomal MTs and subsequent formation of the central spindle occur independently of preanaphase MTs or centrosomal MT nucleation but require augmin, a protein complex implicated in nucleation of noncentrosomal MTs during preanaphase. MTs generated in a hepatoma up-regulated protein (HURP)–dependent manner during anaphase also contribute to central spindle formation redundantly with preanaphase MTs. Based on these results, a new model for central spindle assembly is proposed.
The innate immune system in host mice targets cells with allogenic mitochondrial DNA
Authors: Ishikawa Kaori , Toyama-Sorimachi Noriko , Nakada Kazuto , Morimoto Mami , Imanishi Hirotake , Yoshizaki Mariko , Sasawatari Shigemi , Niikura Mamoru , Takenaga Keizo , Yonekawa Hiromichi , Hayashi Jun-Ichi
Published: October 2010

Mitochondrial DNA (mtDNA) has been proposed to be involved in respiratory function, and mtDNA mutations have been associated with aging, tumors, and various disorders, but the effects of mtDNA imported into transplants from different individuals or aged subjects have been unclear. We examined this issue by generating trans-mitochondrial tumor cells and embryonic stem cells that shared the syngenic C57BL/6 (B6) strain–derived nuclear DNA background but possessed mtDNA derived from allogenic mouse strains. We demonstrate that transplants with mtDNA from the NZB/B1NJ strain were rejected from the host B6 mice, not by the acquired immune system but by the innate immune system. This rejection was caused partly by NK cells and involved a MyD88-dependent pathway. These results introduce novel roles of mtDNA and innate immunity in tumor immunology and transplantation medicine.
Tim3 binding to galectin-9 stimulates antimicrobial immunity
Authors: Jayaraman Pushpa , Sada-Ovalle Isabel , Beladi Sarah , Anderson Ana C. , Dardalhon Valerie , Hotta Chie , Kuchroo Vijay K. , Behar Samuel M.
Published: October 2010

T cell immunoglobulin and mucin domain 3 (Tim3) is a negative regulatory molecule that inhibits effector TH1-type responses. Such inhibitory signals prevent unintended tissue inflammation, but can be detrimental if they lead to premature T cell exhaustion. Although the role of Tim3 in autoimmunity has been extensively studied, whether Tim3 regulates antimicrobial immunity has not been explored. Here, we show that Tim3 expressed on TH1 cells interacts with its ligand, galectin-9 (Gal9), which is expressed by Mycobacterium tuberculosis–infected macrophages to restrict intracellular bacterial growth. Tim3–Gal9 interaction leads to macrophage activation and stimulates bactericidal activity by inducing caspase-1–dependent IL-1β secretion. We propose that the TH1 cell surface molecule Tim3 has evolved to inhibit growth of intracellular pathogens via its ligand Gal9, which in turn inhibits expansion of effector TH1 cells to prevent further tissue inflammation.
Voltage-dependent inactivation gating at the selectivity filter of the MthK K+ channel
Authors: Thomson Andrew S. , Rothberg Brad S.
Published: October 2010

Voltage-dependent K+ channels can undergo a gating process known as C-type inactivation, which involves entry into a nonconducting state through conformational changes near the channel’s selectivity filter. C-type inactivation may involve movements of transmembrane voltage sensor domains, although the mechanisms underlying this form of inactivation may be heterogeneous and are often unclear. Here, we report on a form of voltage-dependent inactivation gating observed in MthK, a prokaryotic K+ channel that lacks a canonical voltage sensor and may thus provide a reduced system to inform on mechanism. In single-channel recordings, we observe that Po decreases with depolarization, with a half-maximal voltage of 96 ± 3 mV. This gating is kinetically distinct from blockade by internal Ca2+ or Ba2+, suggesting that it may arise from an intrinsic inactivation mechanism. Inactivation gating was shifted toward more positive voltages by increasing external [K+] (47 mV per 10-fold increase in [K+]), suggesting that K+ binding at the extracellular side of the channel stabilizes the open-conductive state. The open-conductive state was stabilized by other external cations, and selectivity of the stabilizing site followed the sequence: K+ ≈ Rb+ > Cs+ > Na+ > Li+ ≈ NMG+. Selectivity of the stabilizing site is weaker than that of sites that determine permeability of these ions, suggesting that the site may lie toward the external end of the MthK selectivity filter. We could describe MthK gating over a wide range of positive voltages and external [K+] using kinetic schemes in which the open-conductive state is stabilized by K+ binding to a site that is not deep within the electric field, with the voltage dependence of inactivation arising from both voltage-dependent K+ dissociation and transitions between nonconducting (inactivated) states. These results provide a quantitative working hypothesis for voltage-dependent, K+-sensitive inactivation gating, a property that may be common to other K+ channels.
On dynamical Teichmüller spaces
Authors: Cabrera Carlos , Makienko Peter
Published: October 2010

Following ideas from a preprint of the second author (see Automorphisms of a rational function with disconnected Julia set, Orsay, Preprint, 03 1992), we investigate relations of dynamical Teichmüller spaces with dynamical objects. We also establish some connections with the theory of deformations of inverse limits and laminations in holomorphic dynamics (see J. Diff. Geom. 47 (1997), 17–94).
Reduction of Corky Root Infections on Greenhouse Tomato Crops by Soil Solarization in South Italy
Authors: Vitale A. , Castello I. , Cascone G. , D'Emilio A. , Mazzarella R. , Polizzi G.
Published: October 2010

Five greenhouse experiments were conducted in southeastern Sicily (Italy) from 2000 to 2009 to evaluate the effectiveness of soil solarization in reducing natural infections of tomato corky root caused by Pyrenochaeta lycopersici. Tests were performed with clear, traditional, and innovative plastic films and fumigant applications. In all the trials, soil solarization was effective in controlling corky root disease relative to an untreated control. Although inducing different thermal regimes in the soil, the use of different greenhouse covering and mulching films for solarization proved effective in reducing corky root severity relative to the untreated control. Solarization reduced infections caused by P. lycopersici comparable with methyl bromide fumigation and greater than metham sodium and metham potassium. Among the tested films, green coextruded film may be most attractive because it can be left on after solarization as mulch.