bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring a Local Linear Model Tree Approach to Car‐Following
Authors: Aghabayk Kayvan , Forouzideh Nafiseh , Young William
Published: March 2013

Because car‐following (CF) models are fundamental to replicating traffic flow they have received considerable attention over the last 50 years. They are in a continuous state of improvement due to their significant role in traffic microsimulations, intelligent transportation systems, and safety engineering models. This article uses the local linear model tree (LOLIMOT) approach to model driver's CF behavior to incorporate human perceptual imperfections into a CF model. This model defines some localities in the input space. These localities are fuzzy and have overlaps with each other. Specific models for each of the localities are then defined and combined in a fuzzy manner to predict the final output. The model was developed using real world dynamic data sets. Three different data sets were used for training, testing, and validating the model. The performance of the model was compared to a number of existing CF models. The results showed very close agreement between the real data and the LOLIMOT outputs.
BRG1 promotes survival of UV‐irradiated melanoma cells by cooperating with MITF to activate the melanoma inhibitor of apoptosis gene
Authors: Saladi Srinivas V. , Wong Philip G. , Trivedi Archit R. , Marathe Himangi G. , Keenen Bridget , Aras Shweta , Liew Zi‐Qi , Setaluri Vijayasaradhi , de la Serna Ivana L.
Published: March 2013

Microphthalmia‐associated transcription factor (MITF) is a survival factor in melanocytes and melanoma cells. MITF regulates expression of antiapoptotic genes and promotes lineage‐specific survival in response to ultraviolet (UV) radiation and to chemotherapeutics. SWI/SNF chromatin‐remodeling enzymes interact with MITF to regulate MITF target gene expression. We determined that the catalytic subunit, BRG1, of the SWI/SNF complex protects melanoma cells against UV‐induced death. BRG1 prevents apoptosis in UV‐irradiated melanoma cells by activating expression of the melanoma inhibitor of apoptosis (ML‐IAP). Down‐regulation of ML‐IAP compromises BRG1‐mediated survival of melanoma cells in response to UV radiation. BRG1 regulates ML‐IAP expression by cooperating with MITF to promote transcriptionally permissive chromatin structure on the ML‐IAP promoter. The alternative catalytic subunit, BRM, and the BRG1‐associated factor, BAF180, were found to be dispensable for elevated expression of ML‐IAP in melanoma cells. Thus, we illuminate a lineage‐specific mechanism by which a specific SWI/SNF subunit, BRG1, modulates the cellular response to DNA damage by regulating an antiapoptotic gene and implicate this subunit of the SWI/SNF complex in mediating the prosurvival function of MITF.
Reduction of clubroot (Plasmodiophora brassicae) formation in Arabidopsis thaliana after treatment with prohexadione‐calcium, an inhibitor of oxoglutaric acid‐dependent dioxygenases
Authors: Päsold S. , Ludwig‐Müller J.
Published: March 2013

Recently, flavonoids were shown to modulate the outcome of clubroot development in Arabidopsis thaliana after infection with the obligate biotrophic pathogen Plasmodiophora brassicae. Therefore, the development of clubroot disease was investigated in Arabidopsis after treatment with prohexadione‐calcium (ProCa), an inhibitor of ascorbic acid/2‐oxoglutaric acid‐dependent dioxygenases such as flavanone‐3‐hydroxylase. The treatment resulted in a reduction of the flavonols quercetin and kaempferol in clubroots, whereas the precursor naringenin highly accumulated. The root system of ProCa‐treated plants was better developed although galls were still visible. Thus, ProCa treatment resulted in reduced gall size. Flavonoids are thought to inhibit polar auxin transport by modulating auxin efflux carriers. It was investigated whether the auxin response might change as a consequence of the accumulation of naringenin in ProCa‐treated plants. In the areas of gall development an auxin response was indicated by the auxin‐responsive promoter DR5 coupled to the reporter β‐glucuronidase (GUS), whereas very little staining was found in healthy root parts. No differences in GUS activity were found between P. brassicae‐infected and ProCa‐treated plants, and plants only infected with P. brassicae, indicating that the effect of ProCa treatment on clubroot reduction is not via changes in auxin responses. As ProCa is also an inhibitor of late steps in gibberellin biosynthesis, a specific gibberellin biosynthesis inhibitor, chlormequatchloride (CCC), was tested on club development. However, CCC did not reduce disease symptoms, indicating that the observed reduced gall development was not because of gibberellin biosynthesis inhibition by ProCa.
Multiple Antigen Peptide Containing B and T Cell Epitopes of F1 Antigen of Yersinia pestis Showed Enhanced Th1 Immune Response in Murine Model
Authors: Ali R. , Naqvi R. A. , Kumar S. , Bhat A. A. , Rao D. N.
Published: March 2013

Yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. Apart from humoral response, cell‐mediated protection plays a major role in combating the disease. Fraction 1 capsular antigen (F1‐Ag) of Y. pestis has long been exploited as a vaccine candidate. In this study, F1‐multiple antigenic peptide (F1‐MAP or MAP)‐specific cell‐mediated and cytokine responses were studied in murine model. MAP consisting of three B and one T cell epitopes of F1‐antigen with one palmitoyl residue was synthesized using Fmoc chemistry. Mice were immunized with different formulations of MAP in poly DL‐lactide‐co‐glycolide (PLGA) microspheres. F1‐MAP with CpG oligodeoxynucleotide (CpG‐ODN) as an adjuvant showed enhanced in vitro T cell proliferation and Th1 (IL‐2, IFN‐γ and TNF‐α) and Th17 (IL‐17A) cytokine secretion. Similar formulation also showed significantly higher numbers of cytokine (IL‐2, IFN‐γ)‐secreting cells. Moreover, F1‐MAP with CpG formulation showed significantly high (P < 0.001) percentage of CD4+ IFN‐γ+ cells as compared to CD8+ IFN‐γ+ cells, and also more (CD4‐ IFN‐γ)+ cells secrete perforin and granzyme as compared to (CD8‐ IFN‐γ)+ showing Th1 response. Thus, the study highlights the importance of Th1 cytokine and existence of CD4+ and CD8+ immune response. This study proposes a new perspective for the development of vaccination strategies for Y. pestis that trigger T cell immune response.
An Arabidopsis ATPase gene involved in nematode‐induced syncytium development and abiotic stress responses
Authors: Ali Muhammad Amjad , Plattner Stephan , Radakovic Zoran , Wieczorek Krzysztof , Elashry Abdelnaser , Grundler Florian M.W. , Ammelburg Moritz , Siddique Shahid , Bohlmann Holger
Published: March 2013

The beet cyst nematode Heterodera schachtii induces syncytia in the roots of Arabidopsis thaliana, which are its only nutrient source. One gene, At1g64110, that is strongly up‐regulated in syncytia as shown by RT‐PCR, quantitative RT‐PCR, in situ RT‐PCR and promoter::GUS lines, encodes an AAA+‐type ATPase. Expression of two related genes in syncytia, At4g28000 and At5g52882, was not detected or not different from control root segments. Using amiRNA lines and T‐DNA mutants, we show that At1g64110 is important for syncytium and nematode development. At1g64110 was also inducible by wounding, jasmonic acid, salicylic acid, heat and cold, as well as drought, sodium chloride, abscisic acid and mannitol, indicating involvement of this gene in abiotic stress responses. We confirmed this using two T‐DNA mutants that were more sensitive to abscisic acid and sodium chloride during seed germination and root growth. These mutants also developed significantly smaller roots in response to abscisic acid and sodium chloride. An in silico analysis showed that ATPase At1g64110 (and also At4g28000 and At5g52882) belong to the ‘meiotic clade’ of AAA proteins that includes proteins such as Vps4, katanin, spastin and MSP1.
Microtubules and biotic interactions
Authors: Hardham Adrienne R.
Published: March 2013

Plant microtubules undergo extensive reorganization in response to symbiotic and pathogenic organisms. During the development of successful symbioses with rhizobia and mycorrhizal fungi, novel microtubule arrays facilitate the progression of infection threads and hyphae, respectively, from the plant surface through epidermal and cortical cells. During viral and nematode infections, plant microtubules appear to be commandeered by the pathogen. Viruses use plant microtubules for intra and intercellular movement, as well as for interhost transmission. Nematodes manipulate spindle and phragmoplast microtubules to enhance mitosis and partial cytokinesis during the development of syncytia and giant cells. Pathogenic bacteria, fungi and oomycetes induce a range of alterations to microtubule arrays and dynamics. In many situations, the pathogen, or the elicitor or effector proteins derived from them, induce depolymerization of plant cortical microtubule arrays. In some cases, microtubule disruption is associated with the plant defence response and resistance. In other cases, microtubule depolymerization increases plant susceptibility to the invading pathogen. The reasons for this apparent inconsistency may depend on a number of factors, in particular on the identity of the organism orchestrating the microtubule changes. Overall, the weight of evidence indicates that microtubules play an important role in both the establishment of functional symbioses and in defence against invading pathogens. Research is beginning to unravel details about the nature of both the chemical and the mechanical signals to which the plant microtubule arrays respond during biotic interactions.
IMAGING DIAGNOSIS—MAGNETIC RESONANCE IMAGING FEATURES OF A CEREBRAL HEMANGIOBLASTOMA IN A DOG
Authors: Liebel Francois‐Xavier , Summers Brian A. , Lowrie Mark , Smith Peter , Garosi Laurent
Published: March 2013

The magnetic resonance (MR) imaging features of a cerebral hemangioblastoma in a 9‐year‐old dog are described. Imaging revealed a well‐defined contrast‐enhancing lesion of the rostral forebrain that appeared extraparenchymal. Histopathology of the excised mass showed clusters of small blood vessels interspersed with interstitial cells staining positive for neuronal specific enolase, features consistent with a cerebral hemangioblastoma; the mass also appeared intraparenchymal after further immunohistochemistry study. This neoplasm should be considered a rare differential diagnosis for intracranial masses in dogs.
STUDENT PERFORMANCE AND COURSE EVALUATIONS BEFORE AND AFTER USE OF THE CLASSROOM PERFORMANCE SYSTEM™ IN A THIRD‐YEAR VETERINARY RADIOLOGY COURSE
Authors: Hecht Silke , Adams W. H. , Cunningham M. A. , Lane I. F. , Howell N. E.
Published: March 2013

Effective teaching of veterinary radiology can be challenging in a traditional classroom environment. Audience response systems, colloquially known as “clickers,” provide a means of encouraging student interaction. The purpose of this study was to compare student performance and course evaluations before and after using the Classroom Performance System™ in the third‐year (fifth semester) didactic radiology course at the University of Tennessee College of Veterinary Medicine. Overall student performance was assessed by comparing median numeric final course grades (%) between years without and with use of the Classroom Performance System™. Grades of students were determined for individual instructors’ sections. Student evaluations of the radiology course were compared for the years available (2007–2010). Student interactions were also evaluated subjectively by instructors who used the Classroom Performance System™. There was a significant difference (p = 0.009) between the median student grade before (2005 – 2008, median 82.2%; interquartile range 77.6–85.7%; range 61.9–95.5%) and after use of the classroom performance system (2009–2010, median 83.6%; interquartile range 79.9–87.9%; range 68.2–93.2%). There was no statistically significant difference in median student grades for individual instructors over the study period. The radiology course student evaluation scores were significantly higher in years where the Classroom Performance System™ was used in comparison to previous years (P = 0.019). Subjectively, students appeared more involved when using clickers. Findings indicated that the Classroom Performance System™ may be a useful tool for enhancing veterinary radiology education.
USING MACHINE LEARNING TO CLASSIFY IMAGE FEATURES FROM CANINE PELVIC RADIOGRAPHS: EVALUATION OF PARTIAL LEAST SQUARES DISCRIMINANT ANALYSIS AND ARTIFICIAL NEURAL NETWORK MODELS
Authors: McEvoy Fintan J. , Amigo José M.
Published: March 2013

As the number of images per study increases in the field of veterinary radiology, there is a growing need for computer‐assisted diagnosis techniques. The purpose of this study was to evaluate two machine learning statistical models for automatically identifying image regions that contain the canine hip joint on ventrodorsal pelvis radiographs. A training set of images (120 of the hip and 80 from other regions) was used to train a linear partial least squares discriminant analysis (PLS‐DA) model and a nonlinear artificial neural network (ANN) model to classify hip images. Performance of the models was assessed using a separate test image set (36 containing hips and 20 from other areas). Partial least squares discriminant analysis model achieved a classification error, sensitivity, and specificity of 6.7%, 100%, and 89%, respectively. The corresponding values for the ANN model were 8.9%, 86%, and 100%. Findings indicated that statistical classification of veterinary images is feasible and has the potential for grouping and classifying images or image features, especially when a large number of well‐classified images are available for model training.
COMPARISON BETWEEN CRANIAL THORACIC INTERVERTEBRAL DISC HERNIATIONS IN GERMAN SHEPHERD DOGS AND OTHER LARGE BREED DOGS
Authors: Gaitero Luis , Nykamp Stephanie , Daniel Rob , Monteith Gabrielle
Published: March 2013

Cranial thoracic intervertebral disc herniations have been reported to be rare in dogs due to the presence of the intercapital ligament, however some studies have proposed they may not be uncommon in German Shepherd dogs. The purpose of this retrospective study was to compare cranial thoracic intervertebral disc herniations in German Shepherd dogs and other large breed dogs (control group). Medical records at the Ontario Veterinary College were searched for German Shepherd dogs and other large breed dogs that had magnetic resonance imaging studies including the T1‐T9 region. For each dog and each disc space from T1‐T9, three variables (compression, disc degeneration, and herniation) were recorded and graded based on review of sagittal T2‐weighted images. Twenty‐three German Shepherd dogs and 47 other large breed dogs met inclusion criteria. The German Shepherd dog group had higher scores than the control group for compression (P= 0.0099) and herniation (P< 0.001), but not disc degeneration (P= 0.97). In the German Shepherd dog group, intervertebral discs T2‐T3 and T4‐T5 had an increased risk for compression and T3‐T4 had an increased risk for compression and herniation. Findings from this study indicated that German Shepherd dogs may be more likely than other large breed dogs to have spinal cord compression due to cranial thoracic disc herniations. Imaging of the cranial thoracic spine, including T2‐T3, is recommended for German Shepherd dogs with T3‐L3 neurological signs.
OPTIMIZING A PROTOCOL FOR1H‐MAGNETIC RESONANCE SPECTROSCOPY OF THE CANINE BRAIN AT 3T
Authors: Ober Christopher P. , Warrington Christopher D. , Feeney Daniel A. , Jessen Carl R. , Steward Susan
Published: March 2013

Intracranial diseases are common in dogs and improved noninvasive diagnostic tests are needed. Magnetic resonance (MR) spectroscopy is a technique used in conjunction with conventionalMRimaging to characterize focal and diffuse pathology, especially in the brain. As with conventional MR imaging, there are numerous technical factors that must be considered to optimize image quality. This study was performed to develop an MR spectroscopy protocol for routine use in dogs undergoingMRimaging of the brain. Fifteen canine cadavers were used for protocol development. Technical factors evaluated included use of single‐voxel or multivoxel acquisitions, manual placement of saturation bands, echo time (TE), phase‐ and frequency‐encoding matrix size, radiofrequency coil, and placement of the volume of interest relative to the calvaria. Spectrum quality was found to be best when utilizing a multivoxel acquisition with the volume of interest placed entirely within the brain parenchyma without use of manually placed saturation bands,TE= 144 ms, and a quadrature extremity radiofrequency coil. An 18 × 18 phase‐ and frequency‐encoding matrix size also proved optimal for image quality, specificity of voxel placement, and imaging time.
CLINICAL AND ULTRASONOGRAPHIC CHARACTERISTICS OF SALIVARY MUCOCELES IN 13 DOGS
Authors: Torad Faisal A. , Hassan Elham A.
Published: March 2013

Salivary mucocele is one of the causes of submandibular swelling in dogs and is due to a collection of mucoid saliva that has leaked from a damaged salivary gland. The purpose of this case series report was to describe the clinical and ultrasonographic characteristics of confirmed salivary mucoceles in 13 dogs admitted to theFaculty ofVeterinaryMedicine atCairoUniversity. The final diagnosis of salivary mucocele was based on aspirate cytology for all dogs and additional surgical excision for seven dogs. For dogs admitted from 2 weeks to 1 month from the onset of clinical signs, the cervical mucocele appeared as a round echogenic structure with a large volume of central anechoic content. The wall was a clearly identified hyperechoic structure surrounding the gland. For dogs admitted between 1 to 2 months from the onset of clinical signs, the volume of anechoic material appeared less than that seen in the acute cases. The overall appearance of the salivary mucocele was heterogenous. For dogs admitted after 2 months from the onset of clinical signs, the salivary mucocele appeared grainy or mottled, with a heterogenous appearance and a further decrease in anechoic content. For one dog that presented after 3 months from the onset of clinical signs, the salivary mucocele was hard on palpation and appeared hyperechoic with distal acoustic shadowing. Findings from this study indicated that ultrasonographic characteristics of salivary mucoceles in dogs vary depending on the chronological stage of the disease.
CONTRAST‐ENHANCED ULTRASONOGRAPHIC CHARACTERISTICS OF ADRENAL GLANDS IN DOGS WITH PITUITARY‐DEPENDENT HYPERADRENOCORTICISM
Authors: Bargellini Paolo , Orlandi Riccardo , Paloni Chiara , Rubini Giuseppe , Fonti Paolo , Peterson Mark E. , Boiti Cristiano
Published: March 2013

A noninvasive method for quantifying adrenal gland vascular patterns could be helpful for improving detection of adrenal gland disease in dogs. The purpose of this retrospective study was to compare the contrast‐enhanced ultrasound (CEUS) characteristics of adrenal glands in 18 dogs with pituitary‐dependent hyperadrenocorticism (PDH) vs. four clinically healthy dogs. Each dog received a bolus of the contrast agent (SonoVue®, 0.03 ml/kg of body weight) into the cephalic vein, immediately followed by a 5 ml saline flush. Dynamic contrast enhancement was analyzed using time–intensity curves in two regions of interest drawn manually in the caudal part of the adrenal cortex and medulla, respectively. In healthy dogs, contrast enhancement distribution was homogeneous and exhibited increased intensity from the medulla to the cortex. In the washout phase, there was a gradual and homogeneous decrease of enhancement of the adrenal gland. For all dogs with PDH, there was rapid, chaotic, and simultaneous contrast enhancement in both the medulla and cortex. Three distinct perfusion patterns were observed. Peak perfusion intensity was approximately twice as high (P< 0.05) in dogs with PDH compared with that of healthy dogs (28.90 ± 10.36 vs. 48.47 ± 15.28, respectively). In dogs with PDH, adrenal blood flow and blood volume values were approximately two‐ to fourfold (P< 0.05) greater than those of controls. Findings from the present study support the use of CEUS as a clinical tool for characterizing canine adrenal gland disease based on changes in vascular patterns.
Cellular effects of acute direct current stimulation: somatic and synaptic terminal effects
Authors: Rahman Asif , Reato Davide , Arlotti Mattia , Gasca Fernando , Datta Abhishek , Parra Lucas C. , Bikson Marom
Published: March 2013

Key points

The diversity of cellular targets of direct current stimulation (DCS), including somas, dendrites and axon terminals, determine the modulation of synaptic efficacy.

Axon terminals of cortical pyramidal neurons are two–three times more susceptible to polarization than somas.

DCS in humans results in current flow dominantly parallel to the cortical surface, which in animal models of cortical stimulation results in synaptic pathway‐specific modulation of neuronal excitability.

These results suggest that somatic polarization together with axon terminal polarization may be important for synaptic pathway‐specific modulation of DCS, which underlies modulation of neuronal excitability during transcranial DCS.

Abstract  Transcranial direct current stimulation (tDCS) is a non‐invasive brain stimulation technique to modulate cortical excitability. Although increased/decreased excitability under the anode/cathode electrode is nominally associated with membrane depolarization/hyperpolarization, which cellular compartments (somas, dendrites, axons and their terminals) mediate changes in cortical excitability remains unaddressed. Here we consider the acute effects of DCS on excitatory synaptic efficacy. Using multi‐scale computational models and rat cortical brain slices, we show the following. (1) Typical tDCS montages produce predominantly tangential (relative to the cortical surface) direction currents (4–12 times radial direction currents), even directly under electrodes. (2) Radial current flow (parallel to the somatodendritic axis) modulates synaptic efficacy consistent with somatic polarization, with depolarization facilitating synaptic efficacy. (3) Tangential current flow (perpendicular to the somatodendritic axis) modulates synaptic efficacy acutely (during stimulation) in an afferent pathway‐specific manner that is consistent with terminal polarization, with hyperpolarization facilitating synaptic efficacy. (4) Maximal polarization during uniform DCS is expected at distal (the branch length is more than three times the membrane length constant) synaptic terminals, independent of and two–three times more susceptible than pyramidal neuron somas. We conclude that during acute DCS the cellular targets responsible for modulation of synaptic efficacy are concurrently somata and axon terminals, with the direction of cortical current flow determining the relative influence.
Masking of sounds by a background noise – cochlear mechanical correlates
Authors: Recio‐Spinoso Alberto , Cooper Nigel P.
Published: March 2013

Key points

Basilar membrane responses to tone and noise stimuli presented simultaneously were measured in chinchillas and a gerbil. Overall responses increase monotonically with stimulus level in a compressive manner.

Response components elicited by the weaker stimulus, whether tone or noise, were reduced by the stronger one. That is, the suppressor stimulus could be either the tone or the noise. Suppression by noise stimuli occurred only when the tone frequency was in the non‐linear region of the basilar membrane recording site.

Basilar membrane responses to click and noise stimuli were also recorded in some experiments. The click response component was suppressed by the noise.

Mutual suppression, meaning the simultaneous suppression of the tone and noise response components, was also observed under certain stimulus conditions.

Detection thresholds of the tone stimuli increased in a near‐linear fashion with noise level increments.

Abstract In the search for cochlear correlates of auditory masking by noise stimuli, we recorded basilar membrane (BM) vibrations evoked by either tone or click signals in the presence of varying levels of background noise. The BM vibrations were recorded from basal regions in healthy cochleae of anaesthetized chinchilla and gerbil. Non‐linear interactions that could underpin various aspects of psychophysical masking data, including both compression and suppression at the BM level, were observed. The suppression effects, whereby the amplitude of the responses to each stimulus component could be reduced, depended on the relative intensities of the noise and the tones or clicks. Only stimulus components whose frequencies fell inside the non‐linear region of the recording site, i.e. around its characteristic frequency (CF), were affected by presentation of the ‘suppressing’ stimulus (which could be either the tone or the noise). Mutual suppression, the simultaneous reduction of the responses to both tones and noise components, was observed under some conditions, but overall reductions of BM vibration were rarely observed. Moderate‐ to high‐intensity tones suppressed BM responses to low‐intensity Gaussian stimuli, including both broadband and narrowband noise. Suppression effects were larger for spectral components of the noise response that were closer to the CF. In this regime, the tone and noise stimuli became thesuppressorandprobesignals, respectively. This study provides the first detailed observations of cochlear mechanical correlates of the masking effects of noise. Mechanical detection thresholds for tone signals, which were arbitrarily defined using three criteria, are shown to increase in almost direct proportion to the noise level for low and moderately high noise levels, in a manner that resembles the findings of numerous psychophysical observations.
Differential presynaptic control of the synaptic effectiveness of cutaneous afferents evidenced by effects produced by acute nerve section
Authors: Rudomin P. , Jiménez I. , Chávez D.
Published: March 2013

Key points

We investigated, in the anaesthetized cat, the effects of acute section of the saphenous and superficial peroneal nerves on the synaptic effectiveness of the sural nerve afferents.

We found that acute section of these nerves produced a long‐lasting increase of the sural‐evoked field potentials. At the same time, sural afferents ending within Rexed's laminae III–IV showed a reduced tonic primary afferent depolarization, while sural afferents projecting deeper into the dorsal horn (Rexed's laminae V–VI) instead showed increased tonic primary afferent depolarization.

It is suggested that a differential control of the synaptic effectiveness of the low‐threshold cutaneous afferents according to their sites of termination within the dorsal horn provides means for a selective processing of sensory information in response to tactile and nociceptive stimulation or during the execution of different motor tasks.

Abstract  In the anaesthetized cat, the acute section of the saphenous (Saph) and/or the superficial peroneal (SP) nerves was found to produce a long‐lasting increase of the field potentials generated in the dorsal horn by stimulation of the medial branch of the sural (mSU) nerve. This facilitation was associated with changes in the level of the tonic primary afferent depolarization (PAD) of the mSU intraspinal terminals. The mSU afferent fibres projecting into Rexed's laminae III–IV were subjected to a tonic PAD that was reduced by the acute section of the SP and/or the Saph nerves. The mSU afferents projecting deeper into the dorsal horn (Rexed's laminae V–VI) were instead subjected to a tonic PAD that was increased after Saph and SP acute nerve section. A differential control of the synaptic effectiveness of the low‐threshold cutaneous afferents according to their sites of termination within the dorsal horn is envisaged as a mechanism that allows selective processing of sensory information in response to tactile and nociceptive stimulation or during the execution of different motor tasks.
Manganese‐52 positron emission tomography tracer characterization and initial results in phantoms and in vivo
Authors: Topping Geoffrey J. , Schaffer Paul , Hoehr Cornelia , Ruth Thomas J. , Sossi Vesna
Published: March 2013

Purpose:

Manganese(II) is employed as a contrast agent with magnetic resonance imaging (MRI) for study of neuronal activation in rats and mice. However, at the concentrations required for MRI, Mn may induce pharmacological or toxic effects. Positron emission tomography (PET) imaging of52MnCl2 at tracer doses has the potential to allow similar Mn studies as manganese‐enhanced MRI while providing quantitative results and avoiding toxic effects. In this work, 52MnCl2 is produced and characterized as a PET tracer in phantoms and in rats.

Methods:

52MnCl2 was produced by proton irradiation of natural Cr foil and separated by column chromatography. Images were acquired on a Siemens Focus 120 small animal PET scanner. Phantom images were acquired to assess uniformity, resolution, cascade background correction, and count rate linearity. Images of rats were also acquired after systemic and intracerebroventricular (ICV) administration of 52MnCl2 to investigate Mn(II) distribution in vivo.

Results:

Irradiation yield was 74.6 ± 8.5 kBq/μA min 52Mn at end of bombardment with initial specific activity of at least 3.5 MBq/nmol. 52Mn PET images show similar uniformity and resolution to 18F. 18F based detector efficiency normalization is adequate for 52Mn imaging. Subtraction of a rescaled random events distribution from sinogram data is effective for cascade correction of 52Mn PET data. After systemic injection, 52Mn appears in structures throughout the body of rats, including bones, liver, intestines, and the pituitary gland, but does not appear detectably throughout the brain. After ICV injection, 52Mn remains in the brain and spinal cord.

Conclusions:

52Mn is a promising tracer for small animal PET imaging, yielding image quality comparable to 18F. Potential applications include studies similar to Mn‐enhanced neuronal MRI, and in other organ systems including bones, spinal cord, and the digestive tract.
Determination of gonad doses during robotic stereotactic radiosurgery for various tumor sitesa)
Authors: Zorlu Faruk , Dugel Gozde , Ozyigit Gokhan , Hurmuz Pervin , Cengiz Mustafa , Yildiz Ferah , Akyol Fadil , Gurkaynak Murat
Published: March 2013

Purpose:

The authors evaluated the absorbed dose received by the gonads during robotic stereotactic radiosurgery (SRS) for the treatment of different tumor localizations.

Methods:

The authors measured the gonad doses during the treatment of head and neck, thoracic, abdominal, or pelvic tumors in both RANDO phantom and actual patients. The computerized tomography images were transferred to the treatment planning system. The contours of tumor and critical organs were delineated on each slice, and treatment plans were generated. Measurements for gonad doses were taken from the geometric projection of the ovary onto the skin for female patients, and from the scrotal skin for male patients by attaching films and Thermoluminescent dosimeters (TLDs). SRS was delivered with CyberKnife (Accuray Inc., Sunnyvale, CA).

Results:

The median gonadal doses with TLD and film dosimeter in actual patients were 0.19 Gy (range, 0.035–2.71 Gy) and 0.34 Gy (range, 0.066–3.18 Gy), respectively. In the RANDO phantom, the median ovarian doses with TLD and film dosimeter were 0.08 Gy (range, 0.03–0.159 Gy) and 0.05 Gy (range, 0.015–0.13 Gy), respectively. In the RANDO phantom, the median testicular doses with TLD and film dosimeter were 0.134 Gy (range 0.056–1.97 Gy) and 0.306 Gy (range, 0.065–2.25 Gy).

Conclusions:

Gonad doses are below sterility threshold in robotic SRS for different tumor localizations. However, particular attention should be given to gonads during robotic SRS for pelvic tumors.
Bayesian tracking of multiple acoustic sources in an uncertain ocean environment
Authors: Dosso Stan E. , Wilmut Michael J.
Published: March 2013

This letter develops a Bayesian approach to matched-field tracking of multiple acoustic sources in a poorly-known environment. Markov-chain Monte Carlo methods explicitly sample the posterior probability density over source locations and environmental parameters, while analytic maximum-likelihood solutions for complex source strengths and noise variance in terms of the explicit parameters allow these parameters to be sampled efficiently. This produces a time-ordered sequence of joint marginal probability distributions over source range and depth, from which optimal track estimates and uncertainties are extracted. Synthetic examples consider tracking a submerged source in the presence of a louder shallow interferer in an unknown environment.
Inner speech captures the perception of external speech
Authors: Scott Mark , Yeung H. Henny , Gick Bryan , Werker Janet F.
Published: March 2013

Talking silently to ourselves occupies much of our mental lives, yet the mechanisms underlying this experience remain unclear. The following experiments provide behavioral evidence that the auditory content of inner speech is provided by corollary discharge. Corollary discharge is the motor system's prediction of the sensory consequences of its actions. This prediction can bias perception of other sensations, pushing percepts to match with prediction. The two experiments below show this bias induced by inner speech, demonstrating that inner speech causes external sounds to be heard as similar to the imagined speech, and that this bias operates on subphonemic content.
The Emergence of the Conserved AAA+ ATPases Pontin and Reptin on the Signaling Landscape
Meeting Information:
The First International Workshop on Pontin (RUVBL1) and Reptin (RUVBL2) took place at the European Institute for Chemistry and Biology in Pessac, France, 16 to 19 October 2012.
Authors: Rosenbaum Jean , Baek Sung Hee , Dutta Anindya , Houry Walid A. , Huber Otmar , Hupp Ted R. , Matias Pedro M.
Published: March 2013

The AAA+ ATPases Pontin and Reptin play a diverse role in cell biology and signaling.
Science Signaling
Podcast: 12 March 2013
Authors: Altan-Bonnet Grégoire , VanHook Annalisa M.
Published: March 2013

Variability in receptor protein abundance affects the sensitivity of T cells to the cytokines IL-2 and IL-7.
Bees Get That Caffeine "Buzz"
Authors: Vignieri Sacha
Published: March 2013

Caffeine at concentrations found in flowers helps individual honeybees remember where to find associated nectar.
Glial Death Star
Authors: VanHook Annalisa M.
Published: March 2013

The lipocalin lcn2 is secreted from reactive astrocytes and induces neuronal cell death.
VEGFR Internalization Promotes Sprouting
Authors: Gough Nancy R.
Published: March 2013

Vascular endothelial growth factor receptor is stable at the surface of center vessels and rapidly endocytosed, degraded, and synthesized at sites of endothelial sprouting.
Targeting Mycobacterium tuberculosis and Other Microbial Pathogens Using Improved Synthetic Antibacterial Peptides
Authors: Ramón-García Santiago , Mikut Ralf , Ng Carol , Ruden Serge , Volkmer Rudolf , Reischl Markus , Hilpert Kai , Thompson Charles J.
Published: March 2013

The lack of effective therapies for treating tuberculosis (TB) is a global health problem. While
Mycobacterium tuberculosis
is notoriously resistant to most available antibiotics, we identified synthetic short cationic antimicrobial peptides that were active at low micromolar concentrations (less than 10 μM). These small peptides (averaging 10 amino acids) had remarkably broad spectra of antimicrobial activities against both bacterial and fungal pathogens and an indication of low cytotoxicity. In addition, their antimicrobial activities displayed various degrees of species specificity that were not related to taxonomy. For example,
Candida albicans
and
Staphylococcus aureus
were the best surrogates to predict peptide activity against
M. tuberculosis
, while
Mycobacterium smegmatis
was a poor surrogate. Principle component analysis of activity spectrum profiles identified unique features associated with activity against
M. tuberculosis
that reflect their distinctive amino acid composition; active peptides were more hydrophobic and cationic, reflecting increased tryptophan with compensating decreases in valine and other uncharged amino acids and increased lysine. These studies provide foundations for development of cationic antimicrobial peptides as potential new therapeutic agents for TB treatment.
Novel 16S rRNA Methyltransferase RmtH Produced by Klebsiella pneumoniae Associated with War-Related Trauma
Authors: O'Hara Jessica A. , McGann Patrick , Snesrud Erik C. , Clifford Robert J. , Waterman Paige E. , Lesho Emil P. , Doi Yohei
Published: March 2013

Klebsiella pneumoniae
strain MRSN2404 was isolated from the chronic wound of a soldier who had been wounded in Iraq in 2006. The strain displayed very high MICs of all aminoglycosides, including arbekacin. A gene encoding a novel 16S rRNA methyltransferase, now designated RmtH, was identified. RmtH had 64% identity with RmtB1 and RmtB2.
rmtH
was bracketed by two copies of IS
CR2
, which may have played a role in its mobilization.
Activity of Halogeno-Thiazolides against Cryptosporidium parvum in Experimentally Infected Immunosuppressed Gerbils (Meriones unguiculatus)
Authors: Gargala Gilles , François Arnaud , Favennec Loïc , Rossignol Jean-François
Published: March 2013

Nitazoxanide and three halogeno-thiazolides, RM-4850, RM-4865, and RM-5038, were tested against
Cryptosporidium parvum
in experimentally infected immunosuppressed Mongolian gerbils. Daily 400-mg/kg doses of the four test drugs for 5 to 8 consecutive days produced similar reductions of oocyst shedding. Using early-infected gerbils, a shorter 4-day treatment with RM-5038 reduced oocyst shedding by 95%, compared to 47% for nitazoxanide (
P
= 0.02), suggesting that RM-5038 is more effective than nitazoxanide under the experimental conditions used.
TEM-187, a New Extended-Spectrum β-Lactamase with Weak Activity in a Proteus mirabilis Clinical Strain
Authors: Corvec Stéphane , Beyrouthy Racha , Crémet Lise , Aubin Guillaume Ghislain , Robin Frédéric , Bonnet Richard , Reynaud Alain
Published: March 2013

A
Proteus mirabilis
clinical strain (7001324) was isolated from urine sample of a patient hospitalized in a long-term-care facility. PCR and cloning experiments performed with this strain identified a novel TEM-type β-lactamase (TEM-187) differing by four amino acid substitutions (Leu21Phe, Arg164His, Ala184Val, and Thr265Met) from TEM-1. This characterization provides further evidence for the diversity of extended-spectrum β-lactamases (ESBL) produced by
P. mirabilis
and for their potential spread to other
Enterobacteriaceae
due to a lack of sensitive detection methods used in daily practice.
Early
In Vitro
and
In Vivo
Development of High-Level Daptomycin Resistance Is Common in Mitis Group Streptococci after Exposure to Daptomycin
Authors: García-de-la-Mària Cristina , Pericas Juan M. , del Río Ana , Castañeda Ximena , Vila-Farrés Xavier , Armero Yolanda , Espinal Paula A. , Cervera Carlos , Soy Dolors , Falces Carlos , Ninot Salvador , Almela Manel , Mestres Carlos A. , Gatell Jose M. , Vila Jordi , Moreno Asuncion , Marco Francesc , Miró Jose M.
Published: March 2013

The development of high-level daptomycin resistance (HLDR; MIC of ≥256 mg/liter) after exposure to daptomycin has recently been reported in viridans group streptococcus (VGS) isolates. Our study objectives were as follows: to know whether
in vitro
development of HLDR after exposure to daptomycin was common among clinical isolates of VGS and
Streptococcus bovis
; to determine whether HLDR also developed during the administration of daptomycin to treat experimental endocarditis caused by the daptomycin-susceptible, penicillin-resistant
Streptococcus mitis
strain
S. mitis
351; and to establish whether combination with gentamicin prevented the development of HLDR
in vitro
and
in vivo. In vitro
studies were performed with 114 VGS strains (mitis group, 92; anginosus group, 10; mutans group, 8; and salivarius group, 4) and 54
Streptococcus bovis
strains isolated from 168 consecutive patients with infective endocarditis diagnosed between 1995 and 2010. HLDR was only observed after 24 h of exposure to daptomycin in 27% of the mitis group, including 27% of
S. mitis
isolates, 47% of
S. oralis
isolates, and 13% of
S. sanguis
isolates. In our experimental model, HLDR was detected in 7/11 (63%) and 8/12 (67%) isolates recovered from vegetations after 48 h of daptomycin administered at 6 mg/kg of body weight/24 h and 10 mg/kg/24 h, respectively.
In vitro
, time-kill experiments showed that daptomycin plus gentamicin was bactericidal against
S. mitis
351 at tested concentrations of 0.5 and 1 times the MIC and prevented the development of HLDR.
In vivo
, the addition of gentamicin at 1 mg/kg/8 h to both daptomycin arms prevented HLDR in 21 out of 23 (91%) rabbits. Daptomycin plus gentamicin was at least as effective as vancomycin plus gentamicin. In conclusion, HLDR develops rapidly and frequently
in vitro
and
in vivo
among mitis group streptococci. Combining daptomycin with gentamicin enhanced its activity and prevented the development of HLDR in most cases.
Activities of First-Choice Antimicrobials against Gamma Interferon-Treated Chlamydia trachomatis Differ in Hypoxia
Authors: Shima Kensuke , Klinger Matthias , Solbach Werner , Rupp Jan
Published: March 2013

Gamma interferon (IFN-γ)-mediated host responses play a central role in resolving genital
Chlamydia trachomatis
infections but may also result in persistence of the pathogen, which shows reduced susceptibility to antimicrobials. The antichlamydial function of IFN-γ is oxygen dependent, and the efficacy of antimicrobials against
C. trachomatis
is reduced in a low-oxygen environment. In this study, we show that the antichlamydial efficacies of azithromycin and doxycycline differ in IFN-γ-treated cells under hypoxia.
Pharmacokinetic Interaction between Telaprevir and Methadone
Authors: van Heeswijk Rolf , Verboven Peter , Vandevoorde Ann , Vinck Petra , Snoeys Jan , Boogaerts Griet , De Paepe Els , Van Solingen-Ristea Rodica , Witek James , Garg Varun
Published: March 2013

Hepatitis C virus (HCV) antibody is present in most patients enrolled in methadone maintenance programs. Therefore, interactions between the HCV protease inhibitor telaprevir and methadone were investigated. The pharmacokinetics of
R-
and
S
-methadone were measured after administration of methadone alone and after 7 days of telaprevir (750 mg every 8 h [q8h]) coadministration in HCV-negative subjects on stable, individualized methadone therapy. Unbound
R
-methadone was measured in predose plasma samples before and during telaprevir coadministration. Safety and symptoms of opioid withdrawal were evaluated throughout the study. In total, 18 subjects were enrolled; 2 discontinued prior to receiving telaprevir. The minimum plasma concentration in the dosing interval (
C
min
), the maximum plasma concentration (
C
max
), and the area under the plasma concentration-time curve from h 0 (time of administration) to 24 h postdose (AUC
0–24
) for
R
-methadone were reduced by 31%, 29%, and 29%, respectively, in the presence of telaprevir. The AUC
0–24
ratio of
S
-methadone/
R
-methadone was not altered. The median unbound percentage of
R
-methadone increased by 26% in the presence of telaprevir. The
R
-methadone median (absolute) unbound
C
min
values in the absence (10.63 ng/ml) and presence (10.45 ng/ml) of telaprevir were similar. There were no symptoms of opioid withdrawal and no discontinuations due to adverse events. In summary, exposure to total
R
-methadone was reduced by approximately 30% in the presence of telaprevir, while the exposure to unbound
R
-methadone was unchanged. No symptoms of opioid withdrawal were observed. These results suggest that dose adjustment of methadone is not required when initiating telaprevir treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT00933283.)
Interaction of Leptospira interrogans with Human Proteolytic Systems Enhances Dissemination through Endothelial Cells and Protease Levels
Authors: Vieira Monica L. , Alvarez-Flores Miryam P. , Kirchgatter Karin , Romero Eliete C. , Alves Ivy J. , de Morais Zenaide M. , Vasconcellos Silvio A. , Chudzinski-Tavassi Ana M. , Nascimento Ana L. T. O.
Published: March 2013

We have recently reported the ability of
Leptospira
to capture plasminogen (PLG) and generate plasmin (PLA) bound on the microbial surface in the presence of exogenous activators. In this work, we examined the effects of leptospiral PLG binding for active penetration through the endothelial cell barrier and activation. The results indicate that leptospires with PLG association or PLA activation have enhanced migration activity through human umbilical vein endothelial cell (HUVEC) monolayers compared with untreated bacteria.
Leptospira
cells coated with PLG were capable of stimulating the expression of PLG activators by HUVECs. Moreover, leptospires endowed with PLG or PLA promoted transcriptional upregulation matrix metalloprotease 9 (MMP-9). Serum samples from patients with confirmed leptospirosis showed higher levels of PLG activators and total MMP-9 than serum samples from normal (healthy) subjects. The highest level of PLG activators and total MMP-9 was detected with microscopic agglutination test (MAT)-negative serum samples, suggesting that this proteolytic activity stimulation occurs at the early stage of the disease. Furthermore, a gelatin zymography profile obtained for MMPs with serum samples from patients with leptospirosis appears to be specific to leptospiral infection because serum samples from patients with unrelated infectious diseases produced no similar degradation bands. Altogether, the data suggest that the
Leptospira
-associated PLG or PLA might represent a mechanism that contributes to bacterial penetration of endothelial cells through an activation cascade of events that enhances the proteolytic capability of the organism. To our knowledge, this is the first proteolytic activity associated with leptospiral pathogenesis described to date.