bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of Alkyne Monolayers on Hydrogen-Terminated Si(100) Surfaces Investigated by External Reflection Infrared Spectroscopy
Authors: Henriksson Anders , Hoffmann Helmuth
Published: November 2012

Monolayers of terminal alkynes with long hydrocarbon chains CnH2n+1C[CH (n = 10, 13, 16) were prepared on Si(100) substrates via thermally induced hydrosilylation and the surface orientation of the hydrocarbon chains was investigated by external reflection infrared spectroscopy. It was found that under rigorous exclusion of oxygen in the monolayer preparation process, all three compounds yield highly characteristic IR reflection spectra, consisting of upward-pointing v(CH2) absorptions and downward-pointing v(CH3) absorptions, indicative of a highly ordered anisotropic film structure. Via spectral simulations it was found that the methylene backbones (CH2)n in these films adopt a uniform, all-trans conformation with a tilt angle of about 30° toward the surface normal, whereas the chain termini are disordered and give an isotropic film surface composed of randomly oriented CH3 groups. Lower quality films, which are hardly distinguishable from highly ordered films by other methods, but have been shown to exhibit inferior electrical properties, are clearly identified in their infrared (IR) spectra as partly disordered structures. External reflection IR therefore proves to be an exceptionally sensitive tool to detect structural defects in these monolayers.
Automated Cosmic Spike Filter Optimized for Process Raman Spectroscopy
Authors: Mozharov Sergey , Nordon Alison , Littlejohn David , Marquardt Brian
Published: November 2012

Despite the existence of various methods to remove cosmic spikes from Raman data, only a few of them are suitable for process Raman spectroscopy. The disadvantages of these algorithms include increased analysis time, low accuracy of spike detection, or reliance on variable parameters that must be chosen by trial and error in each case. We demonstrate a novel approach to detecting cosmic spikes in process Raman data and validate it using a wide range of experimental data. This new method features a multistage spike recognition algorithm that is based on tracking sharp changes of intensity in the time domain. The algorithm effectively distinguishes cosmic spikes from random spectral noise and abrupt variations of Raman peaks, allowing accurate detection of both high and low intensity cosmic spikes. The procedure is free from variable user-defined parameters and operates reliably in a fully automated manner with a wide range of time-series process Raman data sets containing more than 40 to 50 spectra.
Evaluation of Laser-Induced Breakdown Spectroscopy (LIBS) for Measurement of Silica on Filter Samples of Coal Dust
Authors: Stipe Christopher B. , Miller Arthur L. , Brown Jonathan , Guevara Edward , Cauda Emanuele
Published: November 2012

Airborne silica dust (quartz) is common in coal mines and represents a respiratory hazard that can lead to silicosis, a potentially fatal lung disease. With an eye toward developing a portable monitoring device for rapid analysis of silica dust, laser-induced breakdown spectroscopy (LIBS) was used to quantify quartz in coal dust samples collected on filter media. Pure silica (Min-U-Sil™ 5), Georgia kaolin, and Pittsburgh-4 and Illinois-6 coal dusts were deposited separately and at multiple mass loadings onto 37-mm polyvinylchloride (PVC) filters. LIBS-generated silicon emission was monitored at 288.16 nm, and non-silica contributions to that signal from kaolinite were removed by simultaneously detecting aluminum. Measurements of the four samples were used to calculate limits of detection (LOD) for silicon and aluminum of approximately 0.08 lg/cm2 and 0.05 μg/cm2, respectively (corresponding to 0.16 μg/cm2 and 0. 20 μg/cm2 for silica and kaolinite, respectively). Relative errors of prediction are around 10%. Results demonstrate that LIBS can dependably quantify silica on filter samples of coal dust and confirm that accurate quantification can be achieved for very lightly loaded samples, which supports the potential application of LIBS for rapid, in-field monitoring.
Wavelength Anomalies in Ultraviolet-Visible Spectrophotometry
Authors: Tellinghuisen Joel
Published: November 2012

Spectral scans of atomic line emission sources with a Shimadzu UV2101PC spectrophotometer show that the nominal wavelength depends upon the instrumental slit width, the wavelength sampling interval, and for some slit widths, also on the specified spectral range. The range dependence is manifested as a smoothing that occurs when the range includes >65 sampled wavelengths, and it affects both the wavelength and the line shape. For spectra not subject to this smoothing, the wavelength error looks like a one-sample misassociation of the wavelength and photometric readings. However, the instrument does reliably move to a specified wavelength, independent of the scan parameter settings. These behaviors do not seem to be documented anywhere but have been present in the software for operating this instrument for about two decades.
Analysis and Classification of Heterogeneous Kidney Stones Using Laser-Induced Breakdown Spectroscopy (LIBS)
Authors: Oztoprak Belgin Genc , Gonzalez Jhanis , Yoo Jong , Gulecen Turgay , Mutlu Nazim , Russo Richard E. , Gundogdu Ozcan , Demir Arif
Published: November 2012

Kidney stones were analyzed using laser-induced breakdown spectroscopy (LIBS), utilizing a high resolution multi-channel charge-coupled device (CCD) spectrometer and a nanosecond-pulse Nd: YAG laser. The kidney stones were also characterized using X-ray diffraction (XRD) and X-ray fluorescence (XRF) techniques for comparative analysis. It was found that the ratio of hydrogen (H) to carbon (C) was an important indicator of organic compounds such as uric acid. Advantages of LIBS, especially with regards to amount of sample required and sample preparation as well as the ability to carry out elemental analysis and classification of kidney stones simultaneously, over other analytical techniques such as XRD and XRF are discussed. The common minor elements detected in the kidney stones include P, S, Si, Ti, and Zn. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) of broadband LIBS spectra were employed for classifying different types of kidney stones. The results are beneficial in understanding kidney stone formation processes, which can lead to preventive therapeutic strategies and treatment methods for urological patients.
Fast and Environmentally Friendly Quantitative Analysis of Active Agents in Anti-Diabetic Tablets by an Alternative Laser-Induced Breakdown Spectroscopy (LIBS) Method and Comparison to a Validated Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) Method
Authors: Contreras Victor Ulises , Meneses-Nava Marco A. , Ornelas-Soto Nancy , Barbosa-García Oracio , López-de-Alba Pedro L. , Maldonado José L. , Ramos-Ortiz Gabriel , Acevedo-Aguilar Francisco J. , López-Martínez Leticia
Published: November 2012

Laser-induced breakdown spectroscopy (LIBS) is evaluated as a potential analytic technique for rapid screening and quality control of anti-diabetic tablets. This paper proposes a simple LIBS-based method for the quantitative analysis of two active pharmaceutical ingredients (APIs): metformin (Met) and glybenclamide (Gly). In order to quantify both APIs, chlorine (Cl) concentration was estimated by employing the Cl/Br optical emission ratio, where Br was introduced as internal standard. Calibration curves were prepared, achieving linearity higher than 99%. On the other hand, for comparison to the proposed method, an isocratic reversed-phase high-performance liquid chromatography (RP-HPLC) method was also developed for quantitative determination of the same analytes by ultraviolet (UV) detection. The chromatographic separation was achieved on a Phenomenex Hypersil C18, 250 mm X 4.6 mm, 5 μm column. The mobile phase was K2HPO4/H3PO4-CH3OH and flow rate was 1.0 mL min−1. The method is linear over a range of 10-60 μg mL−1 for Gly and 5-30 μg mL−1 for Met and the correlation coefficients were >0.99. Recoveries were found to be in the range of 95-101%. Furthermore, four different commercial brands of each active agent were evaluated by both proposed LIBS and chromatographic methods and results were compared with each other. The comparison was satisfactorily validated by analysis of variance (ANOVA).
Rapid, Nondestructive Estimation of Surface Polymer Layer Thickness Using Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy and Synthetic Spectra Derived from Optical Principles
Authors: Weinstock B. André , Guiney Linda M. , Loose Christopher
Published: November 2012

We have developed a rapid, nondestructive analytical method that estimates the thickness of a surface polymer layer with high precision but unknown accuracy using a single attenuated total reflection Fourier transform infrared (ATR FT-IR) measurement. Because the method is rapid, nondestructive, and requires no sample preparation, it is ideal as a process analytical technique. Prior to implementation, the ATR FT-IR spectrum of the substrate layer pure component and the ATR FT-IR and real refractive index spectra of the surface layer pure component must be known. From these three input spectra a synthetic mid-infrared spectral matrix of surface layers 0 nm to 10 000 nm thick on substrate is created de novo. A minimum statistical distance match between a process sample's ATR FT-IR spectrum and the synthetic spectral matrix provides the thickness of that sample. We show that this method can be used to successfully estimate the thickness of polysulfobetaine surface modification, a hydrated polymeric surface layer covalently bonded onto a polyetherurethane substrate. A database of 1850 sample spectra was examined. Spectrochemical matrix-effect unknowns, such as the nonuniform and molecularly novel polysulfobetaine-polyetherurethane interface, were found to be minimal. A partial least squares regression analysis of the database spectra versus their thicknesses as calculated by the method described yielded an estimate of precision of ±52 nm.
Nucleic Acid Fluorescent Probes for Biological Sensing
Authors: Su Xin , Xiao Xianjin , Zhang Chen , Zhao Meiping
Published: November 2012

Nucleic acid fluorescent probes are playing increasingly important roles in biological sensing in recent years. In addition to the conventional functions of single-stranded DNA/RNA to hybridize with their complementary strands, affinity nucleic acids (aptamers) with specific target binding properties have also been developed, which has greatly broadened the application of nucleic acid fluorescent probes to the detection of a large variety of analytes, including small molecules, proteins, ions, and even whole cells. Another chemical property of nucleic acids is to act as substrates for various nucleic acid enzymes. This property can be utilized not only to detect those enzymes and screen their inhibitors, but also employed to develop effective signal amplification systems, which implies extensive applications. This review mainly covers the biosensing methods based on the above three types of nucleic acid fluorescent probes. The most widely used intensity-based biosensing assays are covered first, including nucleic acid probe-based signal amplification methods. Then fluorescence lifetime, fluorescence anisotropy, and fluorescence correlation spectroscopy assays are introduced, respectively. As a rapidly developing field, fluorescence imaging approaches are also briefly summarized.
A Conversation with Baldvin Zophoníasson
Authors: Ue Tom , Sterritt David , Brottman Mikita , Gericke Janine
Published: November 2012

Sheffield Doc/Fest 13 – 17 June 2012 A Report by David Sterritt and Mikita Brottman
Attention Influences Single Unit and Local Field Potential Response Latencies in Visual Cortical Area V4
Authors: Sundberg Kristy A. , Mitchell Jude F. , Gawne Timothy J. , Reynolds John H.
Published: November 2012

Many previous studies have demonstrated that changes in selective attention can alter the response magnitude of visual cortical neurons, but there has been little evidence for attention affecting response latency. Small latency differences, though hard to detect, can potentially be of functional importance, and may also give insight into the mechanisms of neuronal computation. We therefore reexamined the effect of attention on the response latency of both single units and the local field potential (LFP) in primate visual cortical area V4. We find that attention does produce small (1–2 ms) but significant reductions in the latency of both the spiking and LFP responses. Though attention, like contrast elevation, reduces response latencies, we find that the two have different effects on the magnitude of the LFP. Contrast elevations increase and attention decreases the magnitude of the initial deflection of the stimulus-evoked LFP. Both contrast elevation and attention increase the magnitude of the spiking response. We speculate that latencies may be reduced at higher contrast because stronger stimulus inputs drive neurons more rapidly to spiking threshold, while attention may reduce latencies by placing neurons in a more depolarized state closer to threshold before stimulus onset.
Differential Reward Coding in the Subdivisions of the Primate Caudate during an Oculomotor Task
Authors: Nakamura Kae , Santos Gustavo S. , Matsuzaki Ryuichi , Nakahara Hiroyuki
Published: November 2012

The basal ganglia play a pivotal role in reward-oriented behavior. The striatum, an input channel of the basal ganglia, is composed of subdivisions that are topographically connected with different cortical and subcortical areas. To test whether reward information is differentially processed in the different parts of the striatum, we compared reward-related neuronal activity along the dorsolateral–ventromedial axis in the caudate nucleus of monkeys performing an asymmetrically rewarded oculomotor task. In a given block, a target in one position was associated with a large reward, whereas the other target was associated with a small reward. The target position–reward value contingency was switched between blocks. We found the following: (1) activity that reflected the block-wise reward contingency emerged before the appearance of a visual target, and it was more prevalent in the dorsal, rather than central and ventral, caudate; (2) activity that was positively related to the reward size of the current trial was evident, especially after reward delivery, and it was more prevalent in the ventral and central, rather than dorsal, caudate; and (3) activity that was modulated by the memory of the outcomes of the previous trials was evident in the dorsal and central caudate. This multiple reward information, together with the target-direction information, was represented primarily by individual caudate neurons, and the different reward information was represented in caudate subpopulations with distinct electrophysiological properties, e.g., baseline firing and spike width. These results suggest parallel processing of different reward information by the basal ganglia subdivisions defined by extrinsic connections and intrinsic properties.
DrosophilaNeuroligin 2 is Required Presynaptically and Postsynaptically for Proper Synaptic Differentiation and Synaptic Transmission
Authors: Chen Yu-Chi , Lin Yong Qi , Banerjee Swati , Venken Koen , Li Jingjun , Ismat Afshan , Chen Kuchuan , Duraine Lita , Bellen Hugo J. , Bhat Manzoor A.
Published: November 2012

Trans-synaptic adhesion between Neurexins (Nrxs) and Neuroligins (Nlgs) is thought to be required for proper synapse organization and modulation, and mutations in several human Nlgs have shown association with autism spectrum disorders. Here we report the generation and phenotypic characterization ofDrosophila neuroligin2 (dnlg2) mutants. Loss ofdnlg2results in reduced bouton numbers, aberrant presynaptic and postsynaptic development at neuromuscular junctions (NMJs), and impaired synaptic transmission. Indnlg2mutants, the evoked responses are decreased in amplitude, whereas the total active zone (AZ) numbers at the NMJ are comparable to wild type, suggesting a decrease in the release probability. Ultrastructurally, the presynaptic AZ number per bouton area and the postsynaptic density area are both increased indnlg2mutants, whereas the subsynaptic reticulum is reduced in volume. We show that both presynaptic and postsynaptic expression of Dnlg2 is required to restore synaptic growth and function indnlg2mutants. Postsynaptic expression of Dnlg2 indnlg2mutants and wild type leads to reduced bouton growth whereas presynaptic and postsynaptic overexpression in wild-type animals results in synaptic overgrowth. Since Nlgs have been shown to bind to Nrxs, we created double mutants. These mutants are viable and display phenotypes that closely resemble those ofdnlg2anddnrxsingle mutants. Our results provide compelling evidence that Dnlg2 functions both presynaptically and postsynaptically together with Neurexin to determine the proper number of boutons as well as the number of AZs and size of synaptic densities during the development of NMJs.
Clustered Fine Compartmentalization of the Mouse Embryonic Cerebellar Cortex and Its Rearrangement into the Postnatal Striped Configuration
Authors: Fujita Hirofumi , Morita Noriyuki , Furuichi Teiichi , Sugihara Izumi
Published: November 2012

Compartmentalization is essential for a brain area to be involved in different functions through topographic afferent and efferent connections that reflect this organization. The adult cerebellar cortex is compartmentalized into longitudinal stripes, in which Purkinje cells (PCs) have compartment-specific molecular expression profiles. How these compartments form during development is generally not understood. To investigate this process, we focused on the late developmental stages of the cerebellar compartmentalization that occur from embryonic day 17.5 (E17.5), when embryonic compartmentalization is evidently observed, to postnatal day 6 (P6), when adult-type compartmentalization begins to be established. The transformation between these compartmentalization patterns was analyzed by mapping expression patterns of several key molecular markers in serial cerebellar sections in the mouse. A complete set of 54 clustered PC subsets, which had different expression profiles of FoxP2, PLCβ4, EphA4, Pcdh10, and a reporter molecule of the 1NM13 transgenic mouse strain, were distinguished in three-dimensional space in the E17.5 cerebellum. Following individual PC subsets during development indicated that these subsets were rearranged from a clustered and multilayered configuration to a flattened, single-layered and striped configuration by means of transverse slide, longitudinal split, or transverse twist spatial transformations during development. The Purkinje cell-free spaces that exist between clusters at E17.5 become granule cell raphes that separate striped compartments at P6. The results indicate that the ∼50 PC clusters of the embryonic cerebellum will ultimately become the longitudinal compartments of the adult cerebellum after undergoing various peri- and postnatal transformations that alter their relative spatial relationships.
Conceptual Object Representations in Human Anterior Temporal Cortex
Authors: Peelen Marius V. , Caramazza Alfonso
Published: November 2012

Interaction with everyday objects requires the representation of conceptual object properties, such as where and how an object is used. What are the neural mechanisms that support this knowledge? While research on semantic dementia has provided evidence for a critical role of the anterior temporal lobes (ATLs) in object knowledge, fMRI studies using univariate analysis have primarily implicated regions outside the ATL. In the present human fMRI study we used multivoxel pattern analysis to test whether activity patterns in ATLs carry information about conceptual object properties. Participants viewed objects that differed on two dimensions: where the object is typically found (in the kitchen or the garage) and how the object is commonly used (with a rotate or a squeeze movement). Anatomical region-of-interest analyses covering the ventral visual stream revealed that information about the location and action dimensions increased from posterior to anterior ventral temporal cortex, peaking in the temporal pole. Whole-brain multivoxel searchlight analysis confirmed these results, revealing highly significant and regionally specific information about the location and action dimensions in the anterior temporal lobes bilaterally. In contrast to conceptual object properties, perceptual and low-level visual properties of the objects were reflected in activity patterns in posterior lateral occipitotemporal cortex and occipital cortex, respectively. These results provide fMRI evidence that object representations in the anterior temporal lobes are abstracted away from perceptual properties, categorizing objects in semantically meaningful groups to support conceptual object knowledge.
Impaired Autophagy in Neurons after Disinhibition of Mammalian Target of Rapamycin and Its Contribution to Epileptogenesis
Authors: McMahon John , Huang Xiaoxing , Yang Jun , Komatsu Masaaki , Yue Zhenyu , Qian Jiang , Zhu Xinjun , Huang Yunfei
Published: November 2012

Certain mutations within the mammalian target of rapamycin (mTOR) pathway, most notably those affecting the tuberous sclerosis complex (TSC), lead to aberrant activation of mTOR and result in a high incidence of epilepsy in humans and animal models. Although hyperactivation of mTOR has been strongly linked to the development of epilepsy and, conversely, inhibition of mTOR by rapamycin treatment is protective against seizures in several models, the downstream epileptic mechanisms have remained elusive. Autophagy, a catabolic process that plays a vital role in cellular homeostasis by mediating the turnover of cytoplasmic constituents, is negatively regulated by mTOR. Here we demonstrate that autophagy is suppressed in brain tissues of forebrain-specific conditional TSC1 and phosphatase and tensin homlog knock-out mice, both of which display aberrant mTOR activation and seizures. In addition, we also discovered that autophagy is suppressed in the brains of human TSC patients. Moreover, conditional deletion ofAtg7, an essential regulator of autophagy, in mouse forebrain neurons is sufficient to promote development of spontaneous seizures. Thus, our study suggests that impaired autophagy contributes to epileptogenesis, which may be of interest as a potential therapeutic target for epilepsy treatment and/or prevention.
Effective Deep Brain Stimulation Suppresses Low-Frequency Network Oscillations in the Basal Ganglia by Regularizing Neural Firing Patterns
Authors: McConnell George C. , So Rosa Q. , Hilliard Justin D. , Lopomo Paola , Grill Warren M.
Published: November 2012

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson's disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90 Hz) improve motor symptoms, while low frequencies (<50 Hz) are either ineffective or exacerbate symptoms. The neuronal basis for these frequency-dependent effects of DBS is unclear. The effects of different frequencies of STN-DBS on behavior and single-unit neuronal activity in the basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high-frequency DBS reversed motor symptoms, and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high-frequency DBS, but not low-frequency DBS, reduced pathological low-frequency oscillations (∼9 Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low-frequency band to the stimulation frequency during high-frequency DBS, but not during low-frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high-frequency DBS is more effective than low-frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low-frequency network oscillations with a regularized pattern of neuronal firing.
Conditional Müller Cell Ablation Causes Independent Neuronal and Vascular Pathologies in a Novel Transgenic Model
Authors: Shen Weiyong , Fruttiger Marcus , Zhu Ling , Chung Sook H. , Barnett Nigel L. , Kirk Joshua K. , Lee SoRa , Coorey Nathan J. , Killingsworth Murray , Sherman Larry S. , Gillies Mark C.
Published: November 2012

Müller cells are the major glia of the retina that serve numerous functions essential to retinal homeostasis, yet the contribution of Müller glial dysfunction to retinal diseases remains largely unknown. We have developed a transgenic model using a portion of the regulatory region of the retinaldehyde binding protein 1 gene for conditional Müller cell ablation and the consequences of primary Müller cell dysfunction have been studied in adult mice. We found that selective ablation of Müller cells led to photoreceptor apoptosis, vascular telangiectasis, blood–retinal barrier breakdown and, later, intraretinal neovascularization. These changes were accompanied by impaired retinal function and an imbalance between vascular endothelial growth factor-A (VEGF-A) and pigment epithelium-derived factor. Intravitreal injection of ciliary neurotrophic factor inhibited photoreceptor injury but had no effect on the vasculopathy. Conversely, inhibition of VEGF-A activity attenuated vascular leak but did not protect photoreceptors. Our findings show that Müller glial deficiency may be an important upstream cause of retinal neuronal and vascular pathologies in retinal diseases. Combined neuroprotective and anti-angiogenic therapies may be required to treat Müller cell deficiency in retinal diseases and in other parts of the CNS associated with glial dysfunction.
Aversive Stimuli Differentially Modulate Real-Time Dopamine Transmission Dynamics within the Nucleus Accumbens Core and Shell
Authors: Badrinarayan Aneesha , Wescott Seth A. , Vander Weele Caitlin M. , Saunders Benjamin T. , Couturier Brenann E. , Maren Stephen , Aragona Brandon J.
Published: November 2012

Although fear directs adaptive behavioral responses, how aversive cues recruit motivational neural circuitry is poorly understood. Specifically, while it is known that dopamine (DA) transmission within the nucleus accumbens (NAc) is imperative for mediating appetitive motivated behaviors, its role in aversive behavior is controversial. It has been proposed that divergent phasic DA transmission following aversive events may correspond to segregated mesolimbic dopamine pathways; however, this prediction has never been tested. Here, we used fast-scan cyclic voltammetry to examine real-time DA transmission within NAc core and shell projection systems in response to a fear-evoking cue. In male Sprague Dawley rats, we first demonstrate that a fear cue results in decreased DA transmission within the NAc core, but increased transmission within the NAc shell. We examined whether these changes in DA transmission could be attributed to modulation of phasic transmission evoked by cue presentation. We found that cue presentation decreased the probability of phasic DA release in the core, while the same cue enhanced the amplitude of release events in the NAc shell. We further characterized the relationship between freezing and both changes in DA as well as local pH. Although we found that both analytes were significantly correlated with freezing in the NAc across the session, changes in DA were not strictly associated with freezing while basic pH shifts in the core more consistently followed behavioral expression. Together, these results provide the first real-time neurochemical evidence that aversive cues differentially modulate distinct DA projection systems.
High-Frequency Hippocampal Oscillations Activated by Optogenetic Stimulation of Transplanted Human ESC-Derived Neurons
Authors: Piña-Crespo Juan C. , Talantova Maria , Cho Eun-Gyung , Soussou Walid , Dolatabadi Nima , Ryan Scott D. , Ambasudhan Rajesh , McKercher Scott , Deisseroth Karl , Lipton Stuart A.
Published: November 2012

After transplantation, individual stem cell-derived neurons can functionally integrate into the host CNS; however, evidence that neurons derived from transplanted human embryonic stem cells (hESCs) can drive endogenous neuronal network activity in CNS tissue is still lacking. Here, using multielectrode array recordings, we report activation of high-frequency oscillations in the β and γ ranges (10–100 Hz) in the host hippocampal network via targeted optogenetic stimulation of transplanted hESC-derived neurons.
Membrane-Proximal Tryptophans of Synaptobrevin II Stabilize Priming of Secretory Vesicles
Authors: Borisovska Maria , Schwarz Yvonne N. , Dhara Madhurima , Yarzagaray Antonio , Hugo Sandra , Narzi Daniele , Siu Shirley W. I. , Kesavan Jaideep , Mohrmann Ralf , Böckmann Rainer A. , Bruns Dieter
Published: November 2012

Trans-solubleN-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) complexes formed between the SNARE motifs of synaptobrevin II, SNAP-25, and syntaxin play an essential role in Ca2+-regulated exocytosis. Apart from the well studied interactions of the SNARE domains, little is known about the functional relevance of other evolutionarily conserved structures in the SNARE proteins. Here, we show that substitution of two highly conserved tryptophan residues within the juxtamembrane domain (JMD) of the vesicular SNARE Synaptobrevin II (SybII) profoundly impairs priming of granules in mouse chromaffin cells without altering catecholamine release from single vesicles. Using molecular dynamic simulations of membrane-embedded SybII, we show that Trp residues of the JMD influence the electrostatic surface potential by controlling the position of neighboring lysine and arginine residues at the membrane–water interface. Our observations indicate a decisive role of the tryptophan moiety of SybII in keeping the vesicles in the release-ready state and support a model wherein tryptophan-mediated protein–lipid interactions assist in bridging the apposing membranes before fusion.
Differential Sulfation Remodelling of Heparan Sulfate by Extracellular 6-O-Sulfatases Regulates Fibroblast Growth Factor-Induced Boundary Formation by Glial Cells: Implications for Glial Cell Transplantation
Authors: Higginson Jennifer R. , Thompson Sophie M. , Santos-Silva Alessandra , Guimond Scott E. , Turnbull Jeremy E. , Barnett Susan C.
Published: November 2012

Previously, it has been shown that rat Schwann cells (SCs), but not olfactory ensheathing cells (OECs), form a boundary with astrocytes, due to a SC-specific secreted factor. Here, we identify highly sulfated heparan sulfates (HSs) and fibroblast growth factors (FGFs) 1 and 9 as possible determinants of boundary formation induced by rat SCs. Disaccharide analysis of HS in SC-conditioned and rat OEC-conditioned media showed that SCs secrete more highly sulfated HS than OECs. The dependence of the boundary-forming activity on high levels of sulfation was confirmed using a panel of semisynthetic modified heparins with variable levels of sulfation. Furthermore, extracellular HS 6-O-endosulfatase enzymes, Sulf 1 and Sulf 2, were expressed at a significantly lower level by SCs compared with OECs, and siRNA reduction of Sulfs in OECs was, in itself, sufficient to induce boundary formation. This demonstrates a key role for remodelling (reduction) of HS 6-O-sulfation by OECs, compared with SCs, to suppress boundary formation. Furthermore, specific anti-FGF1 and anti-FGF9 antibodies disrupted SC–astrocyte boundary formation, supporting a role for an HS sulfation-dependent FGF signaling mechanism via FGF receptors on astrocytes. We propose a model in which FGF1 and FGF9 signaling is differentially modulated by patterns of glial cell HS sulfation, dependent on Sulf 1 and Sulf 2 expression, to control FGF receptor 3-IIIb-mediated astrocytic responses. Moreover, these data suggest manipulation of HS sulfation after CNS injury as a potential novel approach for therapeutic intervention in CNS repair.
Novel H6PDH mutations in two girls with premature adrenarche: ‘apparent’ and ‘true’ CRD can be differentiated by urinary steroid profiling
Authors: Lavery G G , Idkowiak J , Sherlock M , Bujalska I , Ride J P , Saqib K , Hartmann M F , Hughes B , Wudy S A , De Schepper J , Arlt W , Krone N , Shackleton C H , Walker E A , Stewart P M
Published: November 2012

Context

Inactivating mutations in the enzyme hexose-6-phosphate dehydrogenase (H6PDH, encoded by H6PD) cause apparent cortisone reductase deficiency (ACRD). H6PDH generates cofactor NADPH for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by HSD11B1) oxo-reductase activity, converting cortisone to cortisol. Inactivating mutations in HSD11B1 cause true cortisone reductase deficiency (CRD). Both ACRD and CRD present with hypothalamic-pituitary-adrenal (HPA) axis activation and adrenal hyperandrogenism.

Objective

To describe the clinical, biochemical and molecular characteristics of two additional female children with ACRD and to illustrate the diagnostic value of urinary steroid profiling in identifying and differentiating a total of six ACRD and four CRD cases.

Design

Clinical, biochemical and genetic assessment of two female patients presenting during childhood. In addition, results of urinary steroid profiling in a total of ten ACRD/CRD patients were compared to identify distinguishing characteristics.

Results

Case 1 was compound heterozygous for R109AfsX3 and a novel P146L missense mutation in H6PD. Case 2 was compound heterozygous for novel nonsense mutations Q325X and Y446X in H6PD. Mutant expression studies confirmed loss of H6PDH activity in both cases. Urinary steroid metabolite profiling by gas chromatography/mass spectrometry suggested ACRD in both cases. In addition, we were able to establish a steroid metabolite signature differentiating ACRD and CRD, providing a basis for genetic diagnosis and future individualised management.

Conclusions

Steroid profile analysis of a 24-h urine collection provides a diagnostic method for discriminating between ACRD and CRD. This will provide a useful tool in stratifying unresolved adrenal hyperandrogenism in children with premature adrenarche and adult females with polycystic ovary syndrome (PCOS).
STX2171, a 17β-hydroxysteroid dehydrogenase type 3 inhibitor, is efficacious in vivo in a novel hormone-dependent prostate cancer model
Authors: Day Joanna M , Foster Paul A , Tutill Helena J , Schmidlin Fabien , Sharland Christopher M , Hargrave Jonathan D , Vicker Nigel , Potter Barry V L , Reed Michael J , Purohit Atul
Published: November 2012

17β-Hydroxysteroid dehydrogenases (17β-HSDs) catalyse the 17-position reduction/oxidation of steroids. 17β-HSD type 3 (17β-HSD3) catalyses the reduction of the weakly androgenic androstenedione (adione) to testosterone, suggesting that specific inhibitors of 17β-HSD3 may have a role in the treatment of hormone-dependent prostate cancer and benign prostate hyperplasia. STX2171 is a novel selective non-steroidal 17β-HSD3 inhibitor with an IC50of ∼200 nM in a whole-cell assay. It inhibits adione-stimulated proliferation of 17β-HSD3-expressing androgen receptor-positive LNCaP(HSD3) prostate cancer cellsin vitro. An androgen-stimulated LNCaP(HSD3) xenograft proof-of-concept model was developed to study the efficacies of STX2171 and a more established 17β-HSD3 inhibitor, STX1383 (SCH-451659, Schering-Plough),in vivo. Castrated male MF-1 mice were inoculated s.c. with 1×107cells 24 h after an initial daily dose of testosterone propionate (TP) or vehicle. After 4 weeks, tumours had not developed in vehicle-dosed mice, but were present in 50% of those mice given TP. One week after switching the stimulus to adione, mice were dosed additionally with the vehicle or inhibitor for a further 4 weeks. Both TP and adione efficiently stimulated tumour growth and increased plasma testosterone levels; however, in the presence of either 17β-HSD3 inhibitor, adione-dependent tumour growth was significantly inhibited and plasma testosterone levels reduced. Mouse body weights were unaffected. Both inhibitors also significantly lowered plasma testosterone levels in intact mice. In conclusion, STX2171 and STX1383 significantly lower plasma testosterone levels and inhibit androgen-dependent tumour growthin vivo, indicating that 17β-HSD3 inhibitors may have application in the treatment of hormone-dependent prostate cancer.
Structurally similar estradiol analogs uniquely alter the regulation of intracellular signaling pathways
Authors: Yarger James G , Babine Robert E , Bittner Michael , Shanle Erin , Xu Wei , Hershberger Pamela , Nye Steven H
Published: November 2012

Ligand structure can affect the activation of nuclear receptors, such as estrogen receptors (ERs), and their control of signaling pathways for cellular responses including death and differentiation. We hypothesized that distinct biological functions of similar estradiol (E2) analogs could be identified by integrating gene expression patterns obtained from human tumor cell lines with receptor binding and functional data for the purpose of developing compounds for treatment of a variety of diseases. We compared the estrogen receptor subtype selectivity and impact on signaling pathways for three distinct, but structurally similar, analogs of E2. Modifications in the core structure of E2led to pronounced changes in subtype selectivity for estrogen receptors, ER-α or ER-β, along with varying degrees of ER dimerization and activation. While all three E2analogs are predominantly ER-β agonists, the cell growth inhibitory activity commonly associated with this class of compounds was detected for only two of the analogs and might be explained by a ligand-specific pattern of gene transcription. Microarray studies using three different human tumor cell lines demonstrated that the analogs distinctly affect the transcription of genes in signaling pathways for chromosome replication, cell death, and oligodendrocyte progenitor cell differentiation. That the E2analogs could lower tumor cell viability and stimulate neuronal differentiation confirmed that gene expression data could accurately distinguish biological activity of the E2analogs. The findings reported here confirm that cellular responses can be regulated by making key structural alterations to the core structure of endogenous ER ligands.
Karyological studies in Brazilian species of Lippia L. (Verbenaceae)
Authors: Sousa Saulo M. , Torres Giovana A. , Viccini Lyderson F.
Published: November 2012

The genus Lippia (Verbenaceae) comprise around 160 species spread out mainly in South and Central Americas with few African species, some of them with potential medicinal use. Brazil is one the most important centers of diversity with approximately 75% of the species described so far. Innumerous species are endemic and poorly studied especially at a cytological level. Here, chromosomal length, karyomorphology and chromosome asymmetry of twelve Brazilian species of Lippia were evaluated [L. alba (Miller) N.E.Brown, L. diamantinensis Glaz., L. florida Cham., L. hermanioides Cham., L. lacunosa Mart. & Schauer, L. lupulina Cham., L. pohliana Schauer, L. pseudothea (St. Hil) Schauer, L. rosella Moldenke, L. rotundifolia Cham., L. rubella Moldenke and L. sidoides Cham.]. The analysis suggested that the genus has a variable chromosome number (from 2n = 20 to 2n = 56) originated by dysploidy and polyploidy. This is the first description of chromosome morphology for 11 of the 12 Lippia species studied.
Competição assimétrica e o incremento diamétrico de árvores individuais de Cedrela odorata L. na Amazônia ocidental
Authors: Cunha Thiago Augusto da , Finger César Augusto Guimarães
Published: November 2012

Um modelo de crescimento dependente e independente da distância foi ajustado para avaliar como variáveis de competição explicam a variação do crescimento periódico em diâmetro de 132 árvores de cedro (Cedrela odorata). Utilizando a abordagem de crescimento potencial relativo (PRI), estimou-se o incremento relativo em diâmetro (IRd) a partir do produto do crescimento máximo em diâmetro (incremento potencial) e da função modificada (porção do crescimento reduzido). A significância do modelo do crescimento reduzido ajustado demonstrou influência da competição assimétrica sobre o crescimento em diâmetro, explicando 71% do total da variação e também revelou que a resposta à competição não foi constante, mas variou entre as diferentes classes de tamanho dos indivíduos arbóreos.
Os custos de produção e a rentabilidade da soja nos municípios de Santarém e Belterra, estado do Pará
Authors: Oliveira Cyntia Meireles de , Santana Antônio Cordeiro de , Homma Alfredo Kingo Oyama
Published: November 2012

O artigo teve por objetivo analisar os custos de produção da soja, nos municípios de Santarém e Belterra, considerando que, este é um critério competitivo básico para determinar a eficiência operacional, bem como para a formação de vantagens competitivas sustentáveis. Para tanto, a análise foi realizada a partir da percepção de 20 produtores sobre os conceitos e aplicação dos custos fixos e variáveis, utilizados nas decisões de produzir. Entre os produtores, 18 utilizam tecnologia mecânica e de insumos modernos, porém não empregam práticas conservacionistas. Também não computam grande parte dos custos fixos para determinar o lucro, um indicador de desempenho competitivo. As unidades de produção com produtividade de até 2.400 kg ha-1 (40 sacas de 60 kg ha-1) estão tendo prejuízo. Por outro lado, os agricultores que utilizam tecnologias conservacionistas, como o plantio direto, estão gerando lucro. Finalmente, conclui-se que, 80% dos sistemas de produção de grãos que utilizam tecnologia tradicional não são sustentáveis na região estudada e têm maiores custos de produção.
Avaliação de risco ambiental por contaminação metálica e material orgânico em sedimentos da bacia do Rio Aurá, Região Metropolitana de Belém - PA
Authors: Siqueira Gilmar W. , Aprile Fabio
Published: November 2012

A bacia do Rio Aurá está situada na região metropolitana de Belém, entre os municípios de Belém e Ananindeua, onde a taxa populacional tem aumentado sem qualquer medida de controle social ou ambiental. A região é intensamente explorada, sendo que os principais problemas ambientais são o desmatamento, erosão, inundação, poluição e contaminação das águas, especialmente por metais pesados e compostos orgânicos. O comportamento geoquímico dos elementos Al, Fe, Mn, Cr, Ni e Cu e os teores de compostos orgânicos foram avaliados em 30 pontos de amostragem no período entre 2008 e 2010 nos sedimentos fluviais. O aterro sanitário não controlado localizado nas proximidades da bacia do Rio Aurá é responsável, em parte, pela contaminação dos sedimentos. O estresse ambiental é resultado das atividades antrópicas locais, que contribuem no transporte de material clástico contendo metais para o rio. As variáveis estudadas foram classificadas segundo mecanismos de transporte e fonte (autóctone ou alóctone). Os resultados demonstraram que a principal contribuição de íons Al e Fe foi o aterro sanitário; Mn e Ni vieram principalmente dos solos adjacentes; Cr foi modificado (III/VI) por processo alobioquímico e Cu por processo bioinduzido.
Brachyuran crustaceans from the bycatch of prawn fisheries at the mouth of the Amazon river
Authors: Lima Jô de Farias , Silva Thibério Carvalho da , Silva Luis Mauricio Abdon da , Garcia Jamile da Silva
Published: November 2012

The present paper is a pioneering study on the Brachyura bycatch associated with the artisan prawn fisheries at the mouth of the Amazon River. The study was conducted at four collection sites distributed along the mouth of the Amazon River between the months of January/2009 and January/2010. The animals were caught using handcrafted traps called "matapi", which are used by prawn fisherman in the region. Twenty matapis were used at each collection site. A total of 145 specimens were captured and six species were identified, all belonging to the Trichodactylidae family - Sylviocarcinus maldonadoensis, S. pictus, S. devillei, Valdivia serrata, Dilocarcinus septemdentatus and D. pagei. The most representative species, S. maldonadoensis, S. pictus and S. devillei were classified as regular. Regarding the composition of the capture, there were three specimens of D. pagei , only one male specimen of D. septemdentatus, forty-eight specimens of S. maldonadoensis, sixty-eight specimens of S. pictus, twenty-two specimens of S. devillei and three specimens of V. serrata. In all months, the brachyuran fauna showed a considerably lower biomass when compared to the prawns, representing only 5% of the catch, in a ratio of 1:0.06. For most species, the number of males was always higher than the number of females in almost all collection months.
Fauna parasitária de tambaqui Colossoma macropomum (Characidae) cultivado em tanque-rede no estado do Amapá, Amazônia oriental
Authors: Santos Evandro Freitas , Tavares-Dias Marcos , Pinheiro Douglas Anadias , Neves Ligia Rigôr , Marinho Renata das Graças Barbosa , Dias Márcia Kelly Reis
Published: November 2012

O objetivo principal deste trabalho foi estudar a parasitofauna e a relação hospedeiro- parasito em tambaqui Colossoma macropomum cultivados em tanques-rede no Rio Matapi, município de Santana, estado do Amapá, região da Amazônia oriental, Brasil. Foram examinados 60 tambaquis, dos quais 96,7% estavam parasitados por protozoários Ichthyophthirius multifiliis (Ciliophora) e Piscinoodinium pillulare (Dinoflagellida), monogenoideas Mymarotheciun boegeri e Anacanthorus spathulatus (Dactylogyridae) e sanguessugas Glossiiphonidae gen. sp. (Hirudinea). Os maiores níveis de parasitismo foram causados por protozoários I. multifiliis e P. pillulare e os menores por sanguessugas Glossiiphonidae gen. sp. Porém, os índices de infestação não tiveram efeitos na saúde dos peixes hospedeiros, uma vez que o fator de condição relativo (Kn) não foi estatisticamente (p<0,05) correlacionado com a intensidade desses parasitos. Este foi o primeiro relato da ocorrência de I. multifiliis e P. pillulare em C. macropomum cultivados em tanques-rede na Amazônia brasileira.
Essential oils of the Sextonia rubra (Mez ) van der Werff (Lauraceae)
Authors: Alcântara Joelma Moreira , Yamaguchi Klenicy Kazumi , Veiga Junior Valdir Florêncio da
Published: November 2012

The essential oils of the leaves and branches of Sextonia rubra were obtained by hydrodistillation and analyzed by GC-FID and GC-MS. In the leaves were identified as the major constituents α-pinene (21.7%), β-pinene (15.4%), α-copaene (12.5%) and germacrene D (12.1%). In the branches essential oil, α-copaene (22.9%), β-selinene (7.9%) and β-elemene (7.2%) were identified as the most abundant constituents. This paper describes for the first time the composition of these essential oils.